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Withdrawal/Redaction Sheet Clinton Library DOCUMENT NO. SUBJECT/TITLE DATE RESTRICTION AND TYPE 001. note re: FDA Reform [partial] (1 page) 07/12/1996 b(6) COLLECTION: Clinton Presidential Records Domestic Policy Council Elizabeth Drye OA/Box Number: 10452 FOLDER TITLE: FDA Reform 1996 [2] 2014-0046-S rc1402 RESTRICTION CODES Presidential Records Act - - |44 U.S.C. 2204(a)| Freedom of Information Act - 15 U.S.C. 552(b)] P1 National Security Classified Information [(a)(1) of the PRA] b(1) National security classified information |(b)(1) of the FOIA] P2 Relating to the appointment to Federal office |(a)(2) of the PRA] b(2) Release would disclose internal personnel rules and practices of P3 Release would violate a Federal statute [(a)(3) of the PRAJ an agency [(b)(2) of the FOIA] P4 Release would disclose trade secrets or confidential commercial or b(3) Release would violate a Federal statute [(b)(3) of the FOIA] financial information [(a)(4) of the PRA] b(4) Release would disclose trade secrets or confidential or financial P5 Release would disclose confidential advice between the President information [(b)(4) of the FOIA] and his advisors, or between such advisors [a)(5) of the PRA| b(6) Release would constitute a clearly unwarranted invasion of P6 Release would constitute a clearly unwarranted invasion of personal privacy |(b)(6) of the FOIA] personal privacy [(a)(6) of the PRA] b(7) Release would disclose information compiled for law enforcement purposes |(b)(7) of the FOIA] C. Closed in accordance with restrictions contained in donor's deed b(8) Release would disclose information concerning the regulation of of gift. financial institutions [(b)(8) of the FOIA] PRM. Personal record misfile defined in accordance with 44 U.S.C. b(9) Release would disclose geological or geophysical information 2201(3). concerning wells |(b)(9) of the FOIA] RR. Document will be reviewed upon request. Creation of Food Safety Panel Criticized http://www.nytimes.com/yr/mo/day/politics/farm-bill-meat-exclusive.html Page 1 Forget bookmarks. The New York Times Build your library. CLICK HERE TO CREATE YOUR CUSTOM START PAGE. Home Sections Contents Search Forums Help April 1, 1996 Creation of Food Safety Panel Criticized Related Articles Political Points: A Guide to Web Resources Politics Index By MARIAN BURROS A little-noted amendment to the farm bill approved by the Congress last week is causing an uproar among consumer groups and even some producers of meat and poultry. But the framers of the amendment, Republican staff members of the House Agriculture Committee, say they cannot understand what all the furor is about. The amendment creates a Safe Meat and Poultry Inspection Panel, with broad powers to review the decisions by the Department of Agriculture's Food Safety and Inspection Service on such matters as inspection procedures, food safety standards and practices in meat and poultry plants as well as work rules and labor relations. Backers say the review panel would improve food safety by requiring more scientists to be involved in the decisions. Opponents say the panel's mandate will be too comprehensive. "We would grind to a halt," said Mike Taylor, acting under secretary for food safety and inspection services. "An incredible array of almost all the decisions we make would be put through this committee." The creation of the panel comes at a time when the Agriculture Department is about to replace the current system of visual inspections of meat and poultry with a more scientific approach that includes microbial testing and performance standards. While the industry does not agree with all provisions of the new system, called Hazard Analysis Critical Control Point, most in the industry are eager for it to begin. Faced with an avalanche of reports of tainted meat and poultry that have caused thousands of cases of illness and hundreds of deaths each year, the industry sees the new system as a way to improve the public's perception of its products. The reports of the spread of what is known as mad cow disease in Britain have heightened their interest. Carol Tucker Foreman, assistant secretary of agriculture for food and consumer services in the Carter administration who now works as a consultant on food issues, said the amendment was being treated as though it were an honest contribution to the safety process, but "it is not." "It's intention," Mrs. Foreman said, "is to stop the implementation of performance standards and microbial testing." The department's scientific methods seem to be under attack, she said, adding, "Some members of Congress didn't like USDA's science about harmful bacteria, so they are going to set up a panel to try to get the science they do like." William O'Conner, the policy director of the House Agriculture Committee, which added the amendment, said the panel was "not designed to slow down the process" and was only advisory. Besides, O'Conner said, "the HACCP rule is purported to be science-based, but it seemed clear that some of the regulatory decisions have no scientific validity. The regulations should never have gotten to this stage." Creation of Food Safety Panel Criticized http://www.nytimes.com/yr/mo/day/politics/farm-bill-meat-exclusive.html Page 2 O'Conner said the review panel was necessary because the inspection service devised its new system without consulting its existing advisory panel, the National Advisory Committee for Microbiological Criteria for Meat and Poultry. Taylor said, however, that was not true and provided documentation of the committee's meetings. "HACCP is based on the recommendations of that committee," he said. At the largest producer of beef and pork in the world, IBP of Dakota City, Neb., officials say they have serious concerns about the review panel. "It adds another layer of bureaucracy and potentially would delay innovations aimed at enhancing food safety regulations," said Gary Mickelson, an IBP spokesman. The amendment would require the secretary of agriculture to submit formal regulations and informal directives to the review panel and respond in writing in the Federal Register to any panel report. The secretary would then have to allow an additional 90 days for public comment. If the secretary ignored a panel report, Mrs. Foreman said, the Agriculture Department could face a reduction in appropriations. This system would make speedy decisions impossible, Taylor said. It would also hamper actions like the agency's recent directive to the beef industry for increased surveillance of cattle before slaughter because of an increase in what is known as mad cow disease in Britain and concern about a possible human form of the disease. "We're dealing with an emergency situation," Taylor said. "With the panel in place, instead of being able to issue directions we'd be subject to the panel review process." Unlike outside advisory panels at other agencies that are convened at the discretion of the agency head, the Agriculture review panel would decide which Food Safety and Inspection Service decisions it wanted to examine. In addition, it could meet in secret. "Outside scientists can be quite useful," Taylor said, "but I don't know of any other advisory panel that decides how a department does business." The amendment would also require the Agriculture Department to pay the travel and per diem costs for the seven-member panel out of the existing budget at a time when the inspection service is seeking additional money to run its food safety program. At least five of the panel members would have to be food, meat and poultry scientists. "Why would you create a panel for a human health program and require that a majority of them be experts on animal health?" Mrs. Foreman asked. Taylor said: "The provisions of the amendment are so poorly thought through that it has given food, meat and poultry scientists a charge that is so broad it is beyond their expertise. It is severe overkill." Among the decisions the panel could examine under the amendment are work rules and labor relations, but O'Conner said the panel would not be involved in such work rules as whether plant workers could have "two or three bathroom visits." The amendment was added to the farm bill at the House-Senate conference, an occasional way of passing controversial legislation without attracting attention or opposition. "An ordinary bill becomes law by holding hearings," Mrs. Foreman said, "but there were no hearings. Now it is a typical congressional mess because they decided they wanted to slip something in under the cover of night. We're going to end up in court for years." O'Conner disagreed. "I don't consider that much of a criticism," he said. President Clinton is expected to sign the bill, but a senior administrative official said: "The administration has serious concerns about the effect the amendment would have in delaying modernization of food safety inspection." Critic Calls Anti-Smoking Drive Off Course http://www.nytimes.com/yr/mo/dav/news/national/teen-smokers.html Page 1 The New York Times Home Sections Contents Search Forums Help April 1, 1996 Critic Calls Anti-Smoking Drive Off Course By BARNABY J. FEDER c HICAGO -- Everyone from President Clinton to tobacco companies is preaching these days that teen-agers should be kept from smoking, and that has some anti-tobacco advocates worried. "The anti-tobacco movement has careened off on this narrow path because they know it's noncontroversial," said Stanton Glantz, a cardiology professor at the University of California in San Francisco. "But it's probably counterproductive. A kid-centered program is doomed to fail." Glantz fears the focus on trying to stop the 3 million teen-agers under the age of 18 who become smokers each year is diverting too much attention from the nation's 40 million adult smokers. He argues that any letup in the pressure on adult smokers to quit or at least cut back will end up reinforcing the industry's message that smoking is a pleasure to be enjoyed by adults. The result: naturally rebellious teen-agers will be seduced into becoming the tobacco companies' next generation of customers at the same time the industry is claiming public relations credit for saying "kids shouldn't smoke." Glantz's views, which were spelled out in a recent editorial published by the American Journal of Public Health, angered some anti-tobacco advocates. Many were even more upset when he attacked plans announced last month by the Robert Wood Johnson Foundation and other groups to finance a new clearinghouse called the National Center for Tobacco-Free Kids, calling it "a total waste of money." The bigger danger as they see it is that Glantz is sowing doubt and sapping momentum among groups that need all the unity they can get to battle the $45 billion tobacco industry. "You don't need to have someone saying you should focus on something else just when you are about to achieve some of your goals," said Bill Godshall, who is head of SmokeFree Pennsylvania, in Pittsburgh, and a firm believer that a direct attack on teen-age access to cigarettes could have a big impact. The squabbling among the anti-smoking forces has been largely confined to private conversations and E-mail on Scarcnet, an electronic bulletin board used by anti-tobacco groups. But it underscores the diversity among anti-tobacco groups and experts that often undercuts their efforts to counter the money and lobbying skills of the tobacco companies. The divisiveness showed up this year in Kentucky when the state passed a law aimed at reducing teen-age smoking, with the support of the tobacco industry, retailers and tobacco growers. The law included penalties for teen-age smokers and money for inspections of retail establishments. The bill was endorsed by the Kentucky Medical Association on the grounds, as an association spokesman put it, "It was the best you could expect from a tobacco state." Other members of the state's coalition of anti-tobacco groups were furious at the Kentucky Medical Association. They thought group's endorsement undercut their chances, however remote, of forcing the Legislature to turn out a stronger law, such as one that would ban cigarette vending machines. Critic Calls Anti-Smoking Drive Off Course http://www.nytimes.com/yr/mo/dav/news/national/teen-smokers.html Page 2 "The argument over the focus on kids is fairly new but there is always a split of one kind or another," said Phillip Wilbur, a spokesman for the Advocacy Institute, a Washington lobbying group. The most common disputes, like those in Kentucky, are over tactics and which changes to emphasize. But tobacco critics are also at odds over fundamental goals. Although many health experts see cigarettes as socially tolerable for adults if smoking is more strictly regulated, like alcohol, others active in the anti-tobacco effort want total prohibition. "There are some real zealots," said Dr. Kenneth Warner of the Michigan School of Public Health, who favors toleration. "They're a minority but they are vocal and visible." The tobacco companies, which typically refer to critics as the "anti-tobacco industry," maintain that prohibition is the goal of all of their important critics, whether stated openly or not. Walker Merryman, the chief spokesman for the Tobacco Institute, the Washington-based trade group, said, "If someone in the industry came to me and said we have to open a dialogue with these people, I don't know who I'd speak with." The toughest question for tobacco critics may be one that is rarely openly discussed: Should they encourage tobacco companies to produce and market safer cigarettes? Some health experts argue that such products would be beneficial to society because 46 million Americans are addicted smokers. Others say that such products would make it harder to combat smoking. So far, the tobacco critics have been spared an all-out civil war because no company has successfully introduced an obviously safer product. The closest test came in 1988 when R.J. Reynolds Tobacco Co. tried to market a smokeless cigarette called Premier. The company and most tobacco critics presumed it was healthier because of low-tar levels and virtually no secondhand exposure to smoke, although Reynolds refrained from making any explicit health claims. A few industry critics expressed interest in the potential benefits, but they were drowned out by attacks on the company. As it turned out, though, there was little chance for debate because Premier was quickly pulled from the market after being rejected by smokers. "There was only one politically correct side in the tobacco-control movement when Premier came out," Warner said. "I don't think that would be true now." For now, there is plenty to disagree over concerning teen-age smoking, an issue ushered onto center stage by Congress' passage in 1992 of the Synar Amendment. That measure, named after former Rep. Mike Synar, D-Okla., required states to clamp down on teen-age access to cigarettes or lose federal grants for programs to fight drugs. Final regulations spelling out how states should prove they were complying were published in February. By then, however, the spotlight had shifted to the Food and Drug Administration's proposal to attack teen-age smoking with nationwide restrictions on the sale, distribution and marketing of cigarettes. Glantz and some supporters argue that preoccupation with the FDA rule and other so-called youth-access measures has made it easier for the industry to divert broad, aggressive anti-tobacco advertising campaigns in states like California and Massachusetts toward less effective youth-oriented advertising. Glantz says the switch is at least partly to blame for a slowing in the decline of adult smoking and a rise in teen-age smoking in California. The same preoccupation, he said, diverted the attention of most tobacco control groups from the Occupational Safety and Health Administration's proposal for a nationwide ban on smoking in public workplaces. Restrictions exist in many municipalities, including New York City. They are cited by Glantz as a means of reducing the number of smoking workers by 25 percent (others say evidence of the impact of these measures is mixed) and cutting second-hand exposure. The outlook is now bleak for the OSHA proposal. While most tobacco-control groups kept their attention on the Food Critic Calls Anti-Smoking Drive Off Course http://www.nytimes.com/yr/mo/day/news/national/teen-smokers.html Page 3 and Drug Administration, the tobacco industry managed to get the ban proposed by OSHA merged into a far broader group of proposed regulations, which are now stalled by widespread criticism. "When you reframe the goal from a smoke-free society to not wanting kids to smoke, it really narrows what you can do about issues like second-hand smoke," said Robin Hobart, associate director of Americans for Non-Smoker Rights in Berkeley, Calif. But others say the focus on youth can help draw attention to the whole range of tobacco control issues. "One of the ways you get adults concerned is by focusing on kids," said Dr. David Burns of the University of California at San Diego. "There's a lot more people involved in smoking control in 1996 than in 1993 because we have a theme that a lot of people can identify with." Home I Sections I Contents I Search I Forums I Help Copyright 1996 The New York Times Company FDA Reform 3/22/96- - FOA D -Wed- night mer w/Hill staff - they ro Set Jerry jemb kleps Manda better understanding w/staff, Put in what FDA's proposed fix would be. Dave - Gave them marhed upbill. - Bill this Pracy sally Jemas Kassebann - Mikersh, Dodd, Welstone, Kameds - agreed to meet with - to have fursher discussors about Siparmsan fix to her bill V Devices - # of was - comparies can mahe changes w/out coming to us " Dence changes which affect 2 officace std. - # drugs of ways. clerice Device area- change defn. of stel 1/3 { duries never come to FDA 98% go Through 510 (k) - "as good as 3 Deadlines w/out resources - how That currerfends w/ PDUFA Induary will 50g more if Devoccements are unified Members are may. Mondey EXECUTIVE OFFICE OF THE PRESIDENT 19-Mar-1996 06:38pm TO: Elizabeth E. Drye FROM: Jeremy D. Benami Domestic Policy Council SUBJECT: Schall letter Thoughts on the Schall response: Dear Ellen: Thank you SO much for your letter and for your offer to pull together some leaders of non-profits to meet with the President. I am sorry it has taken me a little while to get back to you. I am very interested in continuing the dialogue on how best to involve the President and the Administration in the consideration of the role of non-profits in these turbulent times. There are some discussions going on among White House staff on this very topic, and I will certainly keep your offer in mind as these proceed. Also, if we decide to sponsor a meeting here in Washington, I may be back in touch with you for ideas regarding possible attendees and the agenda. Once again, I enjoyed my visit in New York immensely and I appreciate your offer of assistance. Sincerely, File I=1dpc\data\ Schall. Itr In early January, the local Million Denver Is Proving Fertile Ground Man March organizing committee decided to hold the black men's con- ference at the Macedonia Baptist For Theme of Million Man March Church. Four firebombings in the previous two weeks served to sweil the crowd when the conference was Haynor may ideas be some for AI held on Jan. 27. By JAMES BROOKE "We expected only. 400 people," DENVER, March 24 - After a 3. "Our youths are killing each oth- recalled Mr. Simmons, executive di- year-old boy was killed in a drive-by er," Mr. Muhammad told a rapt au- rector of the organizing committee. shooting in December, 100 black dience at a predominantly black high "We had 1,100 people Inside - and men fanned out through a black school here last month. "You can't 200 people trying to get in." neighborhood here. They knocked on blame that on the white man. You Mr. Simmons, a former mayoral doors until leads resulted in three better take responsibility, black aide for gang liaison, recalled the arrests several days later. man." angry words Inside the packed After rival gangs firebombed four Mr. Rogers sounded a similar church. "We gave them an edict," he houses in the same northeast Denver theme in a recent interview. "We said, referring to the gangs. "We will here neighborhood in January, more than have to go forward to a basic set of help you get a job, but our babies' 1,000 men turned out for a five-hour values: hard work, family responsi- lives are not negotiable." protest rally, the All Black Men Con- bility, social responsibility,' he said. Everyone agrees on what hap- ference. The firebombings stopped. "There is a movement taking place pened afterward. Gang-related fire- It has been nearly six months in northeast Denver that says, 'It's bombings stopped in Denver's black since the Million Man March, the time to wake up. neighborhoods. gathering of hundreds of thousands In Denver, there is no white politi- of black men in October in Washing- cal power structure to blame. In- Not everyone agrees on why. "We had a task force out - the ton organized by the Nation of Islam stead, there is a nascent black busi- gangs felt the pressure on the and its leader, Louis Farrakhan. Far ness class to emulate. street," Police Chief David Michaud from fading away, the march's mes- Although blacks account for only 5 said in an interview. The anti-arson sages of moral renewal and personal percent of the two million people who task force conducted hundreds of in- responsibility have found particular- live in the Denver metropolitan area, terviews and arrested two teen- ly fertile ground among the 100,000 the city's Mayor, Wellington E. agers. They were charged with the blacks in the Denver area, the larg- Webb, is black, as is the president of Jan. 25 bombing, a fire that caused est such community in the Rocky Mountain West. Denver's black the school board, Aaron Gray. Hardly ghettos, Denver's black $25,000 in damage, leaving a family neighborhoods seem changed by the neighborhoods include low-rise hous- with five children homeless. event, in ways tangible and intangi- ble. ing projects, working-class bunga- Community leaders argued that lows and suburban ranch homes. public pressure had curbed the "Men are getting more involved on their blocks; traditionally, it was Bolstering a black middle class, gangs. there are about 4,000 black-owned Mr. Simmons, who received tele- only the women," said Alvertis Sim- businesses in greater Denver. phoned death threats from the gangs mons, who is organizing a local fol- "Denver has so many good things before the conference, said, "I want low-up rally to the Million Man going for it - we've elected a black them to have in the back of their March to be held here next month. Mayor and re-elected a black May- minds, 'If I firebomb that house the Recalling his efforts to set up anti- crime groups three years ago, he or," said the Rev. James Peters, neighbors will see me and put me said: "Before, there were hardly pastor of the New Hope Baptist away for 30 years.' any men in the neighborhood watch Church. "The gangs are not repre- groups. Last week, I heard of a black sentative of black people in Denver. Next month, Denver's rally for You've had retired people from the "people of color" will keep pressure man setting up one on his block." The march has inspired a similar military, working two jobs and buy- on the gangs, predicted Chet Whye ing nice homes here." Jr., the local director of the National level of activity in other black neigh- But, as the 63-year-old pastor Rainbow Coalition, which is helping borhoods around the nation. From spoke one recent Saturday, police oragnize the rally. New York to Los Angeles, black men officers stationed in his vestibule "There is a different attitude now are becoming more involved. handed out basketball tickets to men that people are coming out," said Mr. At Northeast High School in Kan- who turned in handguns, no questions Whye, who moved here from Balti- sas City, Mo., for example, several asked. more 10 years ago. "The atmosphere dozen are volunteering as tutors, "Denver's like a comfort zone," has sparked some people to make counselors and cafeteria monitors in warned Mr. Muhammad, who was real changes in their lives." a program to provide a positive male sent here last year from Los Angeles by Mr. Farrakhan. "A lot of black image for teen-agers. In Chicago, a similar mentor program has attract- people, and a lot of white people, come here to get away from urban ed about 100 black men, many of problems." whom took part in the Washington But he noted that the Crips and the march in October. And in Detroit Bloods, two national street gangs, and Los Angeles, agencies that help had recruited here and warned that THE NEW YORK TIMES "Denver could end up like L.A." Continued on Page A12. Column 1 Two-thirds of the area's homicides MONDAY, MARCH 25, 1996 have occurred in Denver's urban Continued from Page Al core even though it has only a fifth of the greater metropolitan area's pop- in the adoption of black children are ulation. But the surge in youth vio- reporting a surge of interest. lence was driven home this winter About 350 communities now have when the Denver Fire Department Million Man March organizing com- announced that there were 51 fire- mittees, said Benjamin F. Chavis Jr., bombings in the city in 1995, up from national director of the Million Man 39 the previous year. March Organizing Committee, which Of the firebombings, 13 are be- is based in Washington. lieved to be gang-related. Arrests In Atlanta, he said, march organ- were made in only one of the 13 izers have registered 28,000 people to cases. More than two-thirds of the vote and have directed a campaign firebombings occurred in the last six that increased deposits in black- months of 1995. owned banks by $2 million, Mr. Cha- "Getting leads from the communi- vis said in a telephone interview ty is like pulling teeth," Lieut. Joe He said Denver was "typical of Sarconi, chief of the department's what is happening in numerous Arson Bureau, said in an interview. areas around the country." "The community is terribly intimi- In political discourse here, there dated by these gang members." has been an overwhelming shift to Although no one has been killed in the march's themes. Prominent the firebombings, Lieutenant Sar- blacks as diverse as Jamal Muham- coni said that was only a matter of mad, a local Nation of Islam minis- luck. "These are more indiscrimi- ter, and Joe Rogers, a Republican nate than drive-by shootings," he lawyer who became the first black to said. "The potential to kill groups of run for Congress in Colorado, both people is greater." emphasize responsibility. "The bodies were often slashed From One Serbian Militia Chief, But in a move that probably meant with knife marks and were black and death for Mr. Obradovic, he was re- blue," he said. "The young women leased in a prisoner exchange. He A Trail of Plunder and Slaughter were wrapped in blankets that were has since disappeared. tied at each end. These female Mr. Lukic, witnesses said, began to drive his captives to the center of the corpses were always naked. We bur- By CHRIS HEDGES AI bridge. Women and men said they led several children, including two had turned their heads as Mr. Lukic boys 18 months old. We found one VISEGRAD, Bosnia and Herzego- of the 14,500 Muslims who lived in and his men taunted their victims, man crucified to the back of a door. vina, March 21 - For the thousands Visegrad before the war, 3,000 are who were made to stand on the walls Once we picked up a garbage bag of Muslims who fled from this town now missing or dead. The others are of the bridge, before pushing them filled with 12 human heads." in eastern Bosnia, and for the Serbs scattered around Bosnia, many liv- into the water and opening fire with By the autumn, with Visegrad who remained, the war has bound ing in poverty in overcrowded nearly emptied of Muslims, the kill- automatic weapons. this generation and the next to a rooms. Most shudder when they Muslims in Visegrad were desper- ings subsided but did not end. Serbian militia leader named Milan speak of this bridge. And even the ate to leave. But the city officials Those who survived the Serbian Lukic. Serbs in the town speak of what refused to give them papers to leave capture In July 1995 of the United Witnesses and survivors say Mr. until they had stripped them of their Nations "safe areas" of Srebrenica Lukic, 29, killed scores of Muslims in happened in hushed and enigmatic this region from 1992 to 1995. He has sentences. property and wealth. and Zepa say they saw Mr. Lukic not been indicted by the United Na- "I read again Ivo Andric's novel On June 7. 1992, Hasan Ajanovic with the Bosnian Serb troops. Mr. was picked up with five friends and Lukic, they said, took away 65 Vise- tions' war crimes tribunal in The during the war," said Boshko Polic, driven to the river by Mr. Lukic and grad natives who had moved to the Hague, and the Serbs in Visegrad 68, the retired principle of the Ivo Andric High School, now taken over two other men, including Mr. Vasilje- United Nations "protected" en- say they do not know his where- abouts. by Serbian families displaced from vic, the former waiter. One of the claves. Sarajevo. "I would look up from the victims, Meho Djafic, had worked for Beyond Visegrad, his name and pages and see what he was describ- 20 years in the Panos restaurant with story are largely unknown. But de- ing around me." Mr. Vasiljevic. Capture, Killing, tailed accounts collected over the last two weeks from witnesses, In April 1992, when the conflict "Lukic told us to wade out into the between the Bosnian Serbs and Mus- water," he said, Interviewed by tele- Then a Coca-Cola many of them now dispersed around Bosnia, provide a picture of slaugh- lims began, Mr. Lukic returned from phone from a Western European Serbia to his hometown. He gathered country that he asked not be Identi- Jasmin Kulovac, a young Muslim ter, pillage and abuse condoned by together a group of men, including fied. "I did not hear the first shot, 1 fighter from Zepa who now lives in the local authorities and Serbian suspect because Lukic's gun had a Sarajevo, tried to escape from Zepa commanders from Belgrade. his brother Milos, his cousin Sredoje silencer. But I heard the screams through the woods toward Montene- Mr. Lukic (pronounced LOO-kich) and a waiter, Mitar Vasiljevic. Mr. is emblematic of dozens of Serbian Lukic, who often went barefoot, and then the other shots. Meho's gro after the enclave was captured militia leaders who rose to promi- named the group the Wolves. He set body fell on top of me. I lay with my in July. But he was arrested with nence in the war in Bosnia, who used about pillaging and looting Muslim face in the sand until night. I swam eight companions on Aug. 4 by the homes, witnesses said. across the river and escaped. The Serbian police along the border near the call for an ethnically pure Serbi- The Uzice Corps, the Yugoslav water stank of death." Zemlica. an state to drive tens of thousands of Army unit that moved into Visegrad Killings were occurring each day. The Serbs drove the men to Vise- Muslim families from their homes grad and turned them over to Mr. and eventually turned their weapons On the afternoon of July 19, 1992, Lukic. Mr. Kulovac said he had seen and kill thousands of others. over to the Bosnian Serbs, did noth- Milos Lukic kicked down the door one companion gunned down along The legacy he and others left of ing to intervene, survivors said. where Hasena Muharemovic lived the banks of the Drina and heard hatred, loss and pain - is something The plunder quickly turned to kill- with her sister, mother, invalid fa- shots that he suspects indicated the no peace agreement seems likely to ing. On May 18 Mr. Lukic burst into ther and two small girls, Mrs. Mu- Dzemo Zukic's home and shot his killing of the others. erase. It helps explain why Muslims, haremovic said. Her husband had "Lukic took me to the middle of Croats and Serbs refuse to return to wife, Bakha, in the back, according to been abducted and had disappeared Visegrad to have a Coke afterward," homes controlled by other ethnic neighbors who saw the shooting. He drove the terrified husband away in two weeks earlier. She swept up Ner- he said. "As we sat in the cafe, the groups, as called for in the peace mina, 6, and her older girl and hid. agreement reached last year in Day- the family car, a red Volkswagen other Serbs spat at me. He walked Passat. Mr. Zukic was never seen around the town like a god." ton, Ohio. And It fuels the yearning for vengeance that could in time again. But the car became a harbin- Mrs. Muharemovic, who lives in a unleash another conflict. ger of death. Mother and Sister tiny Sarajevo apartment with her "The sight of the Passat sent ter- daughters, is gaunt and nervous. "Every child from Visegrad, even ror into our hearts," said Hajdra Are Shot on Bridge "I do not sleep much," she said. "I those too young to remember, knows the name Milan Lukic," said Meh- Karahodsic, whose husband was tak- But her mother, Ramiza, and her am plagued by the same dream. My met Prtkovic, the leader of the dis- en away by Mr. Lukic and who now sister, Asima, were driven to the room is filled with water. 1 am fight- placed Muslims from Visegrad who lives in Gorazde. "We all prayed that center of the bridge. Mrs. Muhare- ing to get to the surface. I see the now lives in the isolated Muslim It would not stop in front of our movic crept from her hiding place bodies of my mother and my sister enclave of Gorazde. "Our communi- homes." and saw her mother and sister sit- swirling past me in the current. I ty will never forget. We will never Survivors said the killings quickly ting astride the wall. burst to the surface." allow our children to forget." became frenzied and common. On "Milan Lukic and his brother shot Her voice went low and hoarse. In Visegrad there is a graceful one occasion, witnesses said, Mr. Lu- them in the stomach," she said. "I can always see It above me," 400-year-old bridge, hewn of large "When they fell in the water, the men she said. "The bridge. The bridge. kic tied a man with a rope to his car off-white stones, that spans the em- and dragged him through the streets leaned over and laughed." The bridge." erald-green waters of the Drina Riv- until he died. That night she huddled in an aban- er The Nobel laureate Ivo Andric They said that on at least two doned house with her daughters. At centered his novel 'The Bridge on occasions, Mr. Lukic herded large dawn she went to see her father. groups of Muslims into houses and "My father told me to take the Continued on Page A8, Column 1 set the buildings on fire. Zahra Tur- girls and run away, that if we stayed jacanin, her face and arms badly we would all be killed," she said. "I Continued from Page Al marred by the flames, escaped from cannot go, he said. I will stay until one burning house on June 27 and they come for me. "Nermina," he said THE NEW YORK TIMES the Drina" around the purnice struc- raced screaming through the streets. to my daughter, 'come kiss your ture, which he could see from his Townspeople said she was the only grandfather goodbye for the last MONDAY, MARCH 25, 1996 window as a boy. survivor of 71 people inside. She now time.' Then we fled." The book chronicles, over 350 lives in France. The mother and two girls were years, the surbulent and often violent "We watched all these things," picked up by Serbs and taken for two history of Visegrad and Bosnia. And said Fadila Mujakic, 46, who now months to a house with six other as the novel points out, the bridge has lives in Gorazde. "But when we saw served as a kind of public theater in poor Zahra yelling in terror and pain, women, Mrs. Muharemovic said. But times of war and upheaval. Brigands we knew Visegrad had descended she would not talk about the experi- into some kind of hell. I gathered my ence. and criminals were once impaled family, and we snuck out that same In September the mother and her and executed on its stone flanks. Mr. night." daughters where sent to work on a Andric wrote in the book, "In all farm with dozens of other captives. tales about personal, family or public "Lukic would come to stuff pieces events, the words 'on the bridge' could always be heard." Captured Serb of pork in our mouths," she said. (Pork is forbidden under Islamic di- Testifies on Lukic etary rules.) "He beat people with A Long History metal rods and took many away." On Aug. 5, 1994, a United Nations In October 1995 Mrs. Muharemo- policeman, Sgt. T. Cameron, inter- Of Major Killers vic and her daughters were freed in a viewed a captured Serbian soldier prisoner exchange. The steep wooded hillsides that from Visegrad, and gathered the The killings here, witnesses said, plunge to the river have for centuries only known Serbian testimony of Mr. filled the waters of the river with Lukic's actions. also produced killers of appalling magnitude. Mr. Lukic, along with his The soldier, Milomir Obradovic, bloated and mangled bodies. Mesud Cocalic lived about 12 miles group of some 15 well-armed com- told how fleeing Muslims were hauled off buses, lined up and shot by down river from Visegrad in the vil- panions, was the latest, according to Mr. Lukic and his companions. He lage of Slap, which did not fall to the more than two dozen survivors and identified the sites of two mass Serbs until last summer. He said he witnesses. According to their ac- graves, but neither have yet been and a group of neighbors had buried counts, he too used the bridge as a investigated He said Mr. Lukic and 180 bodies they had retrieved from prop to extinguish a Muslim commu- his followers raped young girls held the water. The men identified 82 of nity that had been here for centuries. captive at the Vilina Vlas spa outside the bodies and wrote out detailed Visegrad. And he said Jasna Ahmed- descriptions of the others. spahic, a young woman, jumped to her death from a window of the spa after being raped for four days. AMENDMENT NO Calendar No Purpose: To reduce overly burdensome, bureaucratic, and unnecessary requirements. IN THE SENATE OF THE UNITED STATES-- 104th Cong., 2d Sess. An Amendment to the amendment offered by Mrs. Kassebaum to S. 1477 To amend the Federal Food, Drug, and Cosmetic Act and Public Health Service Act to improve the regulation of food, drugs, devices, and biological products, and for other purposes. Referred to the Committee on and ordered to be printed Ordered to lie on the table and to be printed AMENDMENTS intended to be proposed by Mr. Kennedy 1 On page XX, strike lines XX-XX and replace with: 2 "(ii) requests for meetings and the scheduling of meetings relating to 3 reviews of protocols and relating to review of applications or submissions 4 (including petitions or notifications) for product approval or clearance; 5 and"; 5 line 22 through P. 22 6 On page XX, strike lines XX through ** and replace with: 7 "(2)(A) A clinical investigation of a new drug (including a biological 8 product) may begin thirty days after the date the Secretary receives from 9 the sponsor a notification containing information about the drug and the 10 clinical investigation unless, prior to the thirtieth day, the Secretary 1 informs the sponsor that the investigation may not begin and specifies the 2 basis for the decision. Within an additional twenty days, the Secretary 3 shall specify in writing the deficiencies and the information needed in 4 order for the clinical investigation to commence. 24 line \ through 24 24 25 strike page linez 5 On page **, strike lines ** through XX and replace with: 6 "(3)(A) The Secretary may place a clinical hold on any ongoing 7 clinical investigation if the Secretary determines that such action is 8 necessary for the protection of human subjects or for other reasons set 9 forth by the Secretary in regulations. 10 "(B) If the Secretary places a clinical hold on an ongoing 11 investigation, the Secretary shall immediately advise the sponsor of such 12 investigation in writing of such action, and provide such sponsor an 13 opportunity to confer within ten working days of receipt of such 14 communication to discuss the basis for the clinical hold. Within ten 15 working days of such conference, the Secretary shall provide to the 16 sponsor a written list of conditions for the withdrawal of the clinical hold. 17 Any written request from the sponsor requesting that a clinical hold be 18 withdrawn shall receive a decision in writing and specifying the reasons 19 therefor, within twenty working days of the receipt of the request." 16 / 10 20 On page **, strike lines ** through line ** and replace with: 21 "(b) REVIEW BY SCIENTIFIC REVIEW GROUP 1 "(1) In General The product sponsor or applicant shall have a right 2 to request an evaluation by an appropriate scientific review group 3 established under section 904 of any significant scientific decisions made 4 by the Secretary under this Act. In addition, a product sponsor or 5 applicant shall have a right to request an evaluation by an appropriate 6 scientific review group established under section 904 of any significant 7 scientific issue under this Act appealed by such person under subsection 8 (a) that has been pending before the Secretary, without final resolution, for 9 more than 180 days." Administration Marries Policy Initiatives to Political Message CLINTON, From A1 wanted to expand benefits to people exposed to Agent, Orange in Vietnam, the White House quickly approved the proposal and Clinton scheduled a speech to announce the move. The real-world impact of these initia- tives-a sample of more than a dozen examples so far this year-varies widely. Six weeks after Clinton unveiled the education tax-credit proposal, for in- stance, the administration has yet to send a bill to Capitol Hill to implement the idea, and aides say they have yet to make some basic decisions about how the tax credit would work. Even so, Clinton weaves mentions of the plan in- to almost every campaign speech. The Agent Orange decision, by con- trast, quickly disappeared from view BY RUTH after a round of headlines the day it President Clinton, with daughter Chelsea, left, and wife Hillary, leaves for was announced. The administration of- Camp David. Clinton uses agenda-setting power to "define himself." fered no precise cost estimates. But medical experts say the decision to new rules requiring women to provide by juveniles was largely a presidential compensate every Vietnam veteran more information about who fathered restatment of something the Bureau of who gets prostate cancer could eventu- their children before receiving welfare Alcohol, Tobacco and Firearms an- ally cost the federal government far benefits. The move, White House offi- nounced more than two years ago. more than $1 billion, although the big cials said, would help show Clinton as a But sometimes Clinton's pronounce- bills won't come due until many years tough-minded innovator, and help blunt ments involve important policy. The from now as veterans grow older. the GOP charge that by vetoing two Agriculture Department had been The VA made its decision despite a Republican bills Clinton had reneged working for years on a compromise lack of scientific evidence showing any- on his 1992 promise to "end welfare as plan for more rigorous meat inspec- thing more than a possible link be- we know it." tions. The final announcement was has- tween Agent Orange exposure and In March, Clinton announced that tened by several days last week, ad- prostate cancer, which more than 10 Housing and Urban Development De- ministration officials said, in time for percent of all males will get regardless partment aid to local housing authori- Clinton's weekly radio address, domi- of whether they served in Vietnam. ties would be weighted in favor of pro- nating the Sunday papers a week ago. The presidential campaign of former jects that evict tenants accused of a The relationship between the execu- Senate majority leader Robert J. Dole single crime, even if the tenants have tive branch and Clinton's political ad- accuses Clinton of politicizing the gov- yet to be convicted. HUD and Justice visers works in both directions. Some- ernment and campaigning at taxpayer Department officials helped draft the times the campaign takes advantage of expense. But White House aides are initiative, which a spokesman for the an idea the bureaucracy had been unapologetic about their determination American Civil Liberties Union called working on. Other times, the political to merge government policy and cam- "political grandstanding at the expense team orders the bureaucracy to work paign message, and claim they are of the poor." on a proposal that Clinton campaign practicing sensible incumbency politics. The next day, Clinton announced consultant Dick Morris or some other Poor coordination between the that the Food and Drug Administration adviser believes will prove popular. White House and the reelection cam- was streamlining rules to bring anti- In the Agent Orange decision last paign contributed significantly to Presi- cancer drugs to market. Clinton said it May, Clinton seized upon a policy deci- dent George Bush's defeat in 1992 by was an example of how the administra- sion that as a practical matter had al- making him vulnerable to the charge tion's "reinventing government" cam- ready been made. Congress in 1991 that he had no message or philosophy, paign was helping individuals. But it al- passed legislation requiring the gov- Clinton aides contend. They are eager SO responded to Republican complaints ernment to give the benefit of the not to let Dole benefit the same way that the FDA is too slow and bureau- doubt to veterans in cases where the they did. cratic. scientific evidence is murky about "We are determined to speak with In April, Clinton answered consumer whether Agent Orange causes a partic- one voice and not have a disconnect," fears that gasoline prices were rising ular health problem. A scientific panel said White House senior adviser too high by ordering the Energy De- found there was "suggestive" but in- George Stephanopoulos. partment to sell some of the strategic conclusive evidence of a link between New examples keep springing forth, petroleum reserve. The next day, he prostate cancer and exposure to the answered ranchers' fears that beef sometimes two or three a week. herbicide and recommended the dis- This spring, with campaign polling prices were falling too low by enlisting ease be added to a list of others for showing that people want to get tough the Agriculture Department to speed which Vietnam veterans receive bene- on wayward youths, the White House up school lunch program purchases. fits. ordered the Justice Department to de- Sometimes, the effort to put Clinton Once the panel made its decision, velop guidelines to be mailed to locali- forward with a campaign message of according to interviews with officials at ties to encourage them to impose night the day involves initiatives that amount the White House and Department of to little. Last week's announcement of curfews. The Education Department Veterans Affairs, there was no serious put together a similar manual on how a program to track guns used in crimes discussion of the considerable costs in schools can stop truancy. Last month, the Heath and Human Services Department came up with THE WASHINGTON POST `A16 SUNDAY, JULY 14, 1996 PHOTOCOPY PRESERVATION future years or any possibility that Clinton might not approve. Instead, according to officials there was considerable discussion of how Clinton should announce the decision. Some thought a Memorial Day address would be appropriate, but others THE WASHINGTON POST thought that would look too political. A16 SUNDAY, JULY 14 1996 Clinton made his announcement the day after the holiday surroundeduby veterans. The education tax credit by con- trast, was conceived at the White House Clinton, according to an alde was eager for "a big idea on education that would help "define what the sec- ond term would be about,' and had long been intrigued by a Georgia pro- gramito subsidize the first two:years of college. The problem was meshing it with the realities of budgeting. Economic adviser Laura D' Andrea Tyson and one other deputies, Clinton campaign vet eran Gene Sperling, supervised a pro- cess of extended wrangling among the White House and Departments of Edu- cation and Treasury over how big to make the credit, and how to pay for it. Aides said the scope and cost of Clin- ton's was scaled back as it went through the policy process. And some questions, such as whether the tax credit should be paid to the college or to the individual student, ar unan swered White House press secretary Mi- chael McCurry said Clinton agrees that the tax credit proposal is in part politi- cal, but that it is appropriate for a pres- ident to offer new policies in ancelec tion year to highlight what he would do in a second term. But Christina Martin, a spokes vom an for Dole, said Clinton is the powers of incumbency on several fronts to unfair advantage. "Whether it's travel, events staging, war rooms in the White House, or taxpayer fund ed policy experts being used for Bill Clinton's political gain, it is abusive and wrong, Martin said. Mary Matalin, a veteran of Bush's campaign, said if Clinton thought the tax credit or other proposals were good ideas, he should have pushed them when Democrats had control of Congressitwo years ago. But Martha Joynt Kumar, a Towson State University political scientist said Clinton is shrewdly using the agenda- setting powers of the presidency. By announcing even a modest propo sale "He can immediately get on the news; and that public exposure gives him a chance "to define himself PHOTOCOPY PRESERVATION Staff writers Bill McAllister and Rick Weiss contributed to this report. THE WASHINGTON POST SUNDAY, 4. 1996 A 11 Congress May End Funding for Agriculture's Pesticide Testing Program Associated Press thresholds set by the Environmental Pro budget," said Jay J. Vroom, the group's The Environmental Protection Agency residues were found, although only two ap- tection Agency. president. advises the Agriculture Department on ples had that many pesticides. The Agriculture Department's Pesticide About 39 percent of the nearly 7,600 Conversely, the House decided that if which pesticides to examine. Because of a Activist organizations such as the Envi- Data Program, created in 1991 to test pro- samples tested in 1994 had no detectable pesticide were so low, the program 1993 report by the National Academy of ronmental Working Group also say the pro- duce in the wake of theiscare over the pesti- residues, even though scientists can meas wasn needed. After all, the Food and Scientists, the government has been look gram should be kept, especially because of cide Alar in apples, faces possible extinction. ure down to the tiniest part Just under 2 Drug Administration already enforces pes, The House passed a spending bill for the ing more closely at the special impact of growing concern over exposure to multiple percent of imported produce and just over ticide laws testing 10,000 food samples a Agriculture Department in June that cut pesticides in the diets of infants and chil- residues. 1 percent of U.S. grown produce had resi- year. out the $11.5 million needed to the dren. Although the allowed pesticide levels dues that would violate standards The EPA says the data help it do a bet The agency is also beginning the difficult may be too high by their reckoning, the program in l 997. The Senate bill, awaiting The data hasibeen our friend," said Den- of calculating the health risk from nis Stolte, pesticide specialist with the task of looking at total exposure from all group says, at least there would be knowl- final,passage, restores the money. Negotia- pesticides edge of the situation. tors will have to decide the program's fu- American Farm Bureau Federation. The The fruits and vegetables are taken from pesticides rather than regulating each pes- With a little bit more refinement, and a ture. American Crop Protection Association, warehouses and tested after they been ticide as though it were the only one being little bit harder looking by this program, The arguments for ending the program which represents pesticide makers agreed. peeled; scrubbed and otherwise prepared used. About 36 percent of the samples had you could really get a pretty good picture look like those for keeping it. To the extent this information is valu- for consumption: Without the data the traces of more than one pesticide of what pesticides are on these fruits and Farm groups and pesticide makers want able in reassuring public confidence in the EPA has to assume that the maximum al- Compared with previous years samples, vegetables when people eat them," said it because it shows the food supply/has very safety of the food supply ACPA would be lowable levels set for crops ready to har there were more multiple residues, and Richard Wiles, the group's pesticide spe- low levels of pesticides well below sad to see this program removed from the vest rather than are in the food. 1994 was the time that as many as 10 cialist PHOTOCOPY PRESERVATION 07-29-96 10:24AM FROM 00 HF-1 FB-8 TO 94567028 P002/004 House 19 SEC. 23. ENVIRONMENTAL IMPACT REVIEW. 20 Chapter VII is amended by adding at the end the 21 following: 22 "SUBCHAPTER D-ENVIRONMENTAL IMPACT REVIEW 23 "SEC. 741. ENVIRONMENTAL IMPACT REVIEW. 24 "No action by the Secretary proposed to be taken 25 pursuant to this Act shall require the preparation of an 1 environmental assessment or environmental impact state- 2 ment under the National Environmental Policy Act of 3 1969 unless the Secretary finds that because of extraor- 4 dinary circumstances the proposed action may have a sig- 5 nificant effect, either directly or cumulatively, on the 6 human environment." 07-29-96 10:24AM FROM 0C/HF-1/FB-8 TO 94567028 P003/004 Senate 4 SEC. 406. ENVIRONMENTAL IMPACT REVIEW. 5 Chapter VII (21 U.S.C. 371 et seq.), as amended by 6 section 405, is further amended by adding at the end thereof 7. the following new section: 8 "SEC. 745. ENVIRONMENTAL IMPACT REVIEW. 9 "Notwithstanding any other provision of law, no ac- 10 tion by the Secretary pursuant to this Act shall be subject 11 to an environmental assessment, an environmental impact 12 statement, or other environmental consideration unless the 13 director of the office responsible for the action demonstrates, 14 in writing- 15 "(1) that there is a reasonable probability that 16 the environmental impact of the action is sufficiently 17 substantial and within the factors that the Secretary 18 is authorized to consider under this Act; and 19 "(2) that consideration of the environmental im- 20 pact will directly affect the decision on the action.". By regulation - proposed nub they we visals reduced # of env. analysis NERA 07-29-96 10:24AM FROM 00/HR-1/FB-8 TO 94567028 P004/004 4 SEC. 406. ENVIRONMENTAL IMPACT REVIEW. 5 Chapter VII (21 U.S.C. 371 et seq.), as amended by 6 section 405, is further amended by adding at the end thereof 7 the following new section: 8 "SEC. 745. ENVIRONMENTAL IMPACT REVIEW. 9 "Notwithstanding any other provision of law, no ac- 10 tion by the Secretary pursuant to this Act shall be subject 11 to an environmental assessment, an environmental impact 12 statement, or other environmental consideration unless the 13 director of the office responsible for the action demonstrates, Aufos burden 14 in writing shows "(1) there is U. reasonable probability that the environmental impact of the action is sufficiently was burden why. as 18 17 tojustify such an assessment, substantial and within the factors that the Secretary is authorized to consider under this Act; and 19 "(2) that consideration of the environmental im- 20 pact will directly affect the decision on the action.". Possible EXECUTIVE OFFICE OF THE PRESIDENT 02-Aug-1996 10:38am TO: Jonathan Winer TO: Sally Katzen TO: Elizabeth E. Drye TO: John F. Morrall, III TO: Michael A. Fitzpatrick FROM: Daniel J. Chenok Office of Mgmt and Budget, OIRA SUBJECT: DELAY OF MARKUP ON FDA REFORM BILLS SEEN AS IMPROVING PROSPE DELAY OF MARKUP ON FDA REFORM BILLS SEEN AS IMPROVING PROSPECTS FOR The House Commerce Committee's decision to delay its scheduled markup of Food and Drug Administration reform legislation in favor of continued negotiations with the Clinton administration actually improves the prospects for congressional action, a drug industry source told BNA Aug. 1. The House Commerce Health and Environment Subcommittee had been expected to consider three FDA reform bills (HR 3199, 3200, 3201) beginning Aug. 1, but announced July 30 that markup would be postponed to allow discussions to proceed through August. According to the source, both Republican and Democratic staffers have represented the postponement as a positive step, not a reason for disappointment. If the negotiations had broken off for subcommittee markup there would have been more confrontation, rather than less, brought about by amendments being offered on controversial issues, the source said. It appears that reform bills will be brought to the House floor in September under suspension of the rules, the source added, which means the leadership considers them to be non-controversial and few amendments will be allowed. Roles Of Bliley, Greenwood Moreover, the bills currently have approximately 208 cosponsors from both parties, SO passage by the House seems assured. The source credited Rep. Jim Greenwood (R-Pa), head of the Republican task force appointed by Commerce Committee Chairman Thomas Bliley Jr. (R-Va), with garnering ``90 percent' of the cosponsors for the bills. Greenwood initially took the lead on meeting with FDA Commissioner David Kessler and his staff as well as industry, patient, and medical groups to reach agreement on controversial issues before proceeding to mark up. Bliley and his staff have moved to the forefront now, however, since Health and Human Services Secretary Donna E. Shalala asked that meetings be held prior to mark up to work out differences between Congress and the administration. The drug industry source said Bliley wanted one more ``legislative success' before the end of this congressional session. Bliley's involvement again underscores the probability of the bills will pass in September because THE WHITE HOUSE WASHINGTON Elizabeth, This was givento Chris by Genentech He is inlerested in your Views -- they believe it's a sign of movement & hope we can help to push through an acceptable agreement. -Sandy SENT BY:GENENTECH, INC. ; 8- 8-96 ; 9:49AM ; GENENTECH-WASH: DC- 2024566487;; # 2/ 2 DISSEMINATION OF INFORMATION CURRENT LAW 1) Only when fundamentally consistent with approved label MACK/FRIST/DODD 1) Only independent journals and texts 2) Only information that is scientifically reliable 3) All information reviewed by FDA for balance 4) Disclaimers 5) Obligation to update by companies 6) Secretary has no authority with respect to cost and cost effectiveness of drug claims FDA POSITION 1) Dissemination only after a company has filed a supplement 2) Unclear position on other issues "A THIRD WAY" 1) Limit journals to those approved by the Secretary 2) Create three categories of FDA reviewable documents. Those which relate to: a) filed supplemental applications; b) those consistent with recommendations of federal health agencies; and c) those consistent with medical practice guidelines. These determinations to be made by the Secretary. 3) Limit application of a pending "Guidance document", negotiated rule making, and authority for the FDA to regulate false and misleading claims pending a final rule. THE WHITE HOUSE WASHINGTON August 6, 1996 MEMORANDUM FOR THE PRESIDENT FROM: Elizabeth Drye, 848 DPC SUBJECT: Update on FDA Reform Legislation Many biotechnology, pharmaceutical, and medical device companies would like to see FDA reform legislation pass this year. California biotechnology leaders may raise the issue with you. Senator Kassebaum has moved a bill out of the Labor Committee with some Democratic support. The House Commerce Committee has held hearings on three separate bills addressing FDA's regulation of food, drugs, and medical devices. As you know, FDA has already made substantial changes under Vice President Gore's National Performance Review to speed drug and device approval times, provide patients earlier access to new drugs for cancer and other life-threatening diseases, and ease regulatory burdens for manufactures. In November of 1995 FDA announced and biotechnology leaders applauded a package of six reforms that help the biotechnology industry. FDA has also proposed a third-party review pilot to test private review of low-risk medical devices. Democrats have been divided on pending legislation. Senators Dodd, Harkin and Mikulski voted to report Senator Kassebaum's bill out of Committee while noting the need for improvements. Senator Kennedy, however, wrote a scathing op-ed calling the Senate bill a "prescription for disaster." FDA has testified that numerous provisions in both the House and Senate bills undermine safety and efficacy standards. HHS and FDA staff, in consultation with White House staff, have been working with both House and Senate Committee members and staff toward developing legislation the Administration can support. We have sought to be responsive to industry's concerns while preserving safety and efficacy standards. Key remaining issues include provisions establishing expansive private review of medical devices, unrealistic review deadlines with "hammers" that kick products into private review, and rules governing the distribution of promotional material for "off-label" drug uses (uses for which a drug is not explicitly approved). We are working to reach agreement on an FDA reform bill that does not undermine safety and efficacy. Given the limited number of legislative days remaining, this Congress is not likely to pass legislation unless Democrats, Republicans, and the Administration achieve consensus soon on outstanding issues. THE NEW YORK TIMES FRIDAY, MAY 24, 1996 Senators Offer Bipartisan Plan To Cut Taxes in Washington By MICHAEL JANOFSKY would cost $700 million to $800 mil- WASHINGTON, May 23 - In an lion a year for up to six years. effort to reverse years of population The proposed tax cuts have be- and economic decline in the District come the latest in a series of efforts of Columbia, two Senators said today to restore the District's economy. that they would introduce a bill on Congress last year created a finan- Friday that would substantially cut cial control board to help the city the Federal taxes paid by District curb spending. The White House has residents. appointed a task force to work with The measure, co-sponsored by city agencies to solve problems. And Connie Mack, a Florida Republican, Mayor Marion S. Barry Jr. has be- and Joseph 1. Lieberman, a Connecti- gun work on a four-year plan to cut, Democrat, is almost identical to reduce the size of city government a House bill introduced last month by by 25 percent. the District's representative, Elea- But the tax cuts would appear to be nor Holmes Norton, a Democrat, the most dramatic of the initiatives. which she said was the only viable Stressing the bipartisan nature of way of saving the city from ruin. their efforts, Mr. Kemp nodded to- The House and Senate bills would ward Ms. Norton and said: "We've both create a flat Federal income tax joined together in a bleeding heart rate for District residents of 15 per- issue to save the nation's capital. cent, down from as high as 39.6 per- This is an urgent plea to the White cent. Standard deductions would rise House and leaders of the House and to $15,000 for single filers, $25,000 for Senate. Do it now. People in this city head of household filers and $30,000 desperately need urgent action." for married couples. Those figures were $3,900, $5,750 and $6,550, respec- tively, last year. The Senate bill would eliminate capital gains taxes for any business investment in the city, while the House bill would do so only for in- vestments by District residents. The Senate bill would also provide a $5,000 tax credit for first-time home buyers in the District. Ms. Norton's Corrections bill has no such incentive. Describing the tax cuts as "the An article on April 16 about at- who died in March, was a graduate best way to help" the nation's capi- tempts to improve the safety record of Bates College, not Colby College, tal, Mr. Mack said today that he of the taxi fleet in Nairobi, Kenya, which was Mr. Gurney's alma ma- expected both bills to pass this year. misstated the etymology of the Ki- ter. And if that happened, Mr. Lieberman swahili colloquialism for the mini- said, "I bet you a lot of money Presi- vans that make up the bulk of the An article on Saturday about a dent Clinton signs it." fleet. Matatu, literally meaning resolution by the Association of Jus- "High taxes are driving people out threes, derives from the fare of 30 tices of the Supreme Court of the of the District of Columbia," Mr. cents (mateni matatu, or three 10- State of New York, criticizing Gov. Mack said at a news conference, cent pieces) originally charged by George E. Pataki's proposal to elim- where the Senators were joined by Ms. Norton and Jack Kemp, the Sec- drivers, not from the practice of inate parole for violent felons, mis- retary of Housing and Urban Devel- people banding together to operate stated the authorship of the resolu- the taxis. This correction was de- tion. It was drawn up-by the associa- opment in the Bush Administration. layed for consultation with authori- tion's executive committee, not by Mr. Kemp has been a strong support- Justice Burton B. Roberts of the er of using tax breaks to attract ties on Kiswahili. Bronx. residents and businesses to citles. The lawmakers and Mr. Kemp A headline on Wednesday with the An obituary on Saturday about said that if the cuts helped Washing- continuation of a front-page article Sam Lopata, who designed a number ton's economy, Federal and state tax about the erosion of consensus of New York restaurants, gave an breaks could be used to resuscitate among the nation's governors on re- incorrect date for the opening of one other urban areas losing population shaping the Federal-state health of them. The restaurant, Joanna, for the same reasons - crime, poor program for the poor referred incor- was opened in 1980, not 1978. schools and inefficient city services. rectly to that program. It is Medic- It is not clear, however, whether aid, not Medicare. A Critic's Notebook yesterday the Clinton Administration supports about television news reports tied to the idea of Federal tax cuts for Dis- An obituary yesterday about Ed- prime-time shows misidentified the trict residents or of having the cuts ward J. Gurney, the former Senator weatherman on WNYW, the Fox- be a model for use across the coun- from Florida, misstated Edmund S. owned station in New York. He is try. In an interview after Ms. Norton Muskie's alma mater. Mr. Muskie, Nick Gregory, not Nick Gomez. proposed her bill, Alice M. Rivlin, the director of the Office of Management and Budget, said the measure was "more a dramatization of the prob- lem than a real solution." Also, at a time when Congress and the White House are straining to balance the budget in seven years; the lawmakers said that neither the House nor Senate had analyzed how much the tax cuts would cost the Federal Government. Mr. Kemp estimated the cuts Senator D'Amato, a Republican, Continued From Page B1 Senator Christopher Dodd, Demo- Pataki Outlaws crat of Connecticut, and Representa- allergies, bronchial disorders and tive Bill Frist, Republican of Tennes- asthma that contain ephedra - in- see, have introduced legislation that Herbal Stimulant cluding Primatene and Sudafed - would reclassify as a drug any herb will not be affected. or dietary supplement like ephedra Besides Herbal Ecstacy, the prod- that advertises itself as a euphoria- Used by Youths ucts bear such names as Euphoria, producing or awareness-heightening Brain Wash and Buzz Tablets. product. Such products would then In a related action, the Commis- come under stricter regulation by By CLIFFORD KRAUSS sioner of Agriculture and Markets, the Federal Drug Administration. Donald R. Davidsen, issued a recall Concern over ephedra intensified Gov. George E. Pataki has announced an of six carbonated beverages that last month when a Florida coroner immediate statewide ban on the sale of so- contain ephedra. called Herbal Ecstacy and other herbal The ban will be enforced by local ruled that Peter Schlendorf, a 20- products containing the stimulant ephedra, and state public health officials, who year-old college student from North- which has been blamed for 15 deaths nation- will do spot checks of stores that port, L.I., had died from taking dou- wide. have sold the products and will inves- ble the recommended dose of Ulti- Typically sold in health food and novelty tigate complaints. Merchants violat- mate Xphoria, one of the 20 products shops in the form of pills, powders and ing the ban will face fines of $2,000 banned yesterday by Mr. Pataki. sodas, the stimulants have become increas- and prison terms of up to one year. Since 1993, according to the F.D.A., ingly popular among middle-class youths The state's action does not target about 400 people have reported ad- seeking alternatives to the kick received possession of ephedra, meaning that verse reactions to ephedra-based from illegal drugs. But while the stimulants there would be little to stop New products, ranging from dizziness to have been promoted as safe natural-food York residents from buying such strokes, and 15 people have died. supplements by about 100 companies, the herbal products in New Jersey or In an interview, New York State's Food and Drug Administration issued a Connecticut. Health Commissioner, Barbara A. warning to consumers last month that the But Richard Curtis, an expert on DeBuono, predicted that many stimulants can be dangerous when taken in narcotics at John Jay College of states, including Connecticut and excess, especially to people with high blood Criminal Justice, said he thought New Jersey, would follow New pressure, heart disease and diabetes. Governor Pataki's action would be York's lead. But she said there was "We're not going to let our kids be exploit- largely effective in stemming the no need for a complete ban on ephe- ed for a cheap profit," Governor Pataki said market. "I can't imagine there will dra-based products that serve medi- at a news conference in Manhattan yester- cal functions. be much of a big black market," he day to announce the ban, which state health said, "because if you want to go that Speaking of several prescription laws allow him to impose without legislative and over-the-counter medications far, you might as well buy real Ec- action. "Obviously the best solution would that include ephedra, she said, stasy, the illegal narcotic kind." be a Federal role, but we can't sit back and Companies can appeal the banning "There is nothing about the way wait and let our young people die." of their products at a hearing in those products are marketed, adver- tised or sold that has indicated to us The Governor's action came two days Albany on June 4. after his ally, Senator Alfonse M. D'Amato, Konstantine Theoharis, the execu- a threat to the public's health, since introduced legislation to increase Federal tive media coordinator of Global they are properly labeled and there are appropriate warnings for ad- controls on ephedra-based products. World Media Corporation, the pro- verse health affects." Under the Governor's order, the State ducer of Herbal Ecstacy, said he Health Department has issued a ban on the thought there was a good chance that sale of 20 specific ephedra-based products the ban on his product could be re- that are explicitly marketed for people look- versed. ing for a drug high or that do not include "Politicians and bureaucracies directions on appropriate dosage. Prescrip- usually overreact," Mr. Theoharis tion and over-the-counter medications for said. "We feel there is tons of misin- THE NEW YORK TIMES formation out there and once we Continued on Page B6 have a fair chance to represent our- FRIDAY, MAY 24, 1996 selves our products will be shown to be harmless and beneficial." He added, "Our products are an alternative to chemically toxic legal and illegal drugs available to any- body." Few people in the East Village, a center of ephedra sales in the city, had heard of the ban yesterday, and most sellers and buyers reacted with little emotion. Armida Barth, owner of Lady in the Moon shop at 111 St. Mark's Place, said that she had stopped sell- ing ephedra products three months ago when she learned of the dangers. "The only reason why I sold it is because I'm against kids using drugs," she said. Larry Carter, a manager at Love Saves the Day, at 119 Second Avenue, where a sign in the window pro- claims "Herbal Ecstacy Sold Here," said, "We're not going to cry if we have to take it off the shelves." But he noted that sales had increased in recent months. In the last nine months, the store's biweekly orders of 10-packs of Herbal Ecstacy pills increased more than three-fold to 860 packages from 150. While other restrictions have been imposed in Ohio and Florida, the Federal and state governments have for the most part been slow to regu- late ephedra because it is considered a safe food supplement when taken according to directions. While techni- cally classified as a natural herb and not a drug, ephedra can induce a euphoric feeling or heart palpitations when taken in-excessive doses. JUL-29-1996 13:53 TO:DEBBIE FINE FROM: DADE, J. P. 1/6 EXECUTIVE OFFICE OF THE PRESIDENT LRM NO: 5218 OFFICE OF MANAGEMENT AND BUDGET Washington, D.C. 20503-0001 FILE NO: 1746 SPECIAL 7/29/96 LEGISLATIVE REFERRAL MEMORANDUM Total Page(s): 6 TO: Legislative Liaison Officer - See Distribution below: FROM: Janet FORSGREN (for) Assistant Director for Legislative Reference OMB CONTACT: Robert PELLICCI 395-4871 Logislative Assistant's Line: 395-7362 C=US, A=TELEMAIL, P=GOV+EOP, O=OMB, OU1=LRD, S=PELLICCI, G=ROBERT. I=J [email protected] SUBJECT: HHS Drafting Service RE: HR3199, Drug and Biological Products Reform Act of 1996 DEADLINE: 10:00 a.m. Wednesday, July 31,1996 In accordance with OMB Circular A-19, OMB requests the views of your agency on the above subject before advising on its relationship to the program of the President. Please advise us if this item will affect direct spending or receipts for purposes of the "Pay-As-You-Go" provisions of Title XIII of the Omnibus Budget Reconciliation Act of 1990. COMMENTS: The attached language may be added to pending legislation that would reform the operations of the FDA. House Committee markup could occur this week. Please expedite your views on the attached language affecting the regulation of human tissue. DISTRIBUTION LIST: AGENCIES: 61-JUSTICE - Andrew Fois - 2025142141 76-National Economic Council - Sonyia Matthews - 2024562174 EOP: Nancy-Ann Min Chris Jennings Greg Simon Jennifer Klein Elizabeth Drye Michael Fitzpatrick Barry Clendenin Richard Turman Jim Esquea Jonathan Winer Allison Eydt Elena Kagan Bob Damus Janet Forsgren JUL-29-1996 13:53 TO:DEBBIE FINE FROM:DADE, J. P. 2/6 RESPONSE TO LRM NO: 5218 LEGISLATIVE REFERRAL FILE NO: 1746 MEMORANDUM If your response to this request for views is short (e.g., concur/no comment). we prefer that you respond by e-mail or by faxing us this response sheet. If the response is short and you prefer to call, please call the branch-wide line shown below (NOT the analyst's line) 10 leave a message with a legislative assistant. You may also respond by: (1) calling the analyst/attorney's direct line (you will be connected to voice mail if the analyst does not answer); or (2) sending US 8 memo or letter Please include the LRM number shown above, and the subject shown below. TO: Robert PELLICCI 395-4871 Office of Management and Budget Fax Number: 395-6148 Branch-Wide Line (to reach legislative assistant): 395-7362 FROM: (Date) (Name) (Agency) (Telephone) SUBJECT: HHS Drafting Service RE: HR3199, Drug and Biological Products Reform Act of 1996 The following is the response of our agency 10 your request for views on the above-captioned subject: Concur No Objection No Comment See proposed edits on pages Other: FAX RETURN of pages, attached to this response sheet P.3/6 JUL-29-1996 13:53 TO:DEBBIE FINE FROM: DADE, J. VA 002 301 443 0739 FDA GEN COUNSEL 07/24/88 18:57 002 07/24/88 WED 14:53 FAX REGULATION OF HUMAN TISSUE- (1) REQUIREMENT OF Part F of Title III of the Public Health Service ACT (42 U.S.C. 262 et seq.) is amended by inserting after section 352 the following new section: "Section 352A REQUIREMENTS FOR HUMAN TISSUE (a) IN GENERAL Facilities and persons that engage in the recovery, processing, storage, or distribution of human tissue: (1) shall annually register with the Secretary and provide the Secretary 2 list of all human tissues that are recovered, processed, stored, or distributed to/from such facility, except that the Secretary may exempt facilities or persons from such requirements on the grounds that they are not necessary to protect the public health; (2) shall at the time of registration provide a list of all contractors or agents of the tissue establishment who engage in the recovery, processing, storage, or distribution of human tissue; and (3) shall comply with good tissue practices including, but not limited to, practices that address: (A) quarantine; recordkeeping the recovery, processing, storage, and distribution of tissue; validation of manufacturing facilities and equipment; quality control; packaging and labeling; adverse experience reports, complaint files and failure investigations; personnel qualification and training: and tissue tracking procedures to identify tissue from donor to recipient and from recipient to donor; and (B) donor screening and infectious disease testing (4) are subject to inspection by individuals authorized by the Secretary; (5) shall comply with regulations regarding labeling, advertising and promotion, which may be promulgated by the Secretary. (b) REGULATIONS The Secretary may promulgate regulations for implementation of this section. Such regulations may include provisions for certification of facilities that engage in the recovery, processing, storage, or distribution of human rissue. 1 JUL-29-1996 13:53 TO:DEBBIE FINE FROM: DADE, J. P. 4/6 003 301 413 0738 FDA GEN COUNSEL 07/24/98 16:58 003 07/24/96 WED 14:38 FAI (c) FINDING OF INTERSTATE COMMERCE Congress finds that human tissue that is recovered, processed, distributed, or stored in the United States for medical use is in, or otherwise directly affects, interstate commerce. (d) DEFINITION - (1) HUMAN TISSUE - The term "human tissue" means any tissue (an aggregate of similar cells together with their intercellular substance, or acellular integuments that have a particular structure and function) derived from a human body which: (A) is intended for administration to another human for the diagnosis. cure. mitigation, treatment, or prevention of any condition or disease; (B) is intended only to replace or repair comparable bodily tissue and does not act through a systemic mechanism; (C) is recovered, processed, stored, or distributed by methods which do not change tissue function or characteristics or propagate the tissue's cells; (D) may include the addition of substances that are safe under conditions of intended use and not intended to contribute to or provide a therapeutic effect to the recipient; and (E) includes demineralized bone, heart valves, and dura mater. (2) Such term does not include: (A) human material regulated or classified as a drug, medical device or biological product except as specified in (d)(1)(8) : (B) vascularized human organs, such as heart, liver, kidneys, lungs, Intestines, or panoreas; (C) blood, blood products, bone marrow, stem cells, somatic cell therapy, gene therapy, or human milk; (D) tissue that is combined with a drug, device, biologic, or another tissue; and (e) TISSUE SPECIFIC REVIEW For specific human dssue as the Secretary deems appropriate and for which she has 2 JUL-29-1996 13:53 TO:DEBBIE FINE FROM:DADE, J. P. 5/6 1 07/24/98 16:58 FDA GEN COUNSEL F.L 004 201 443 0738 07/24/98 WED 14:38 FAX 004 identified 8 public health concern related to clinical safety or effectiveness, the Secretary may conduct a review of existing data on clinical use, indications, outcomes, sufety, and effectiveness of such tissue and may, as part of, or following, such review: (1) promulgate regulations controlling such tissue including, but not limited to, requirements for special labeling or reclassification (under reclassification subsection) of such tissue; and (2) set such other limitations as the Secretary may require to protect the public health. (f) CLASSIFICATION AND RECLASSIFICATION (1) the Secretary may classify or reclassify 1 human tissue as a drug, biological product or medical device, if the Secretary determines that such classification or reclassification is needed to protect the public health or, during the tissue specific review of subsection (e), the Secretary determines that premarket study of effectiveness is warranted; and (2) the Secretary may reclassify a human drug, biological product or medical device as a human tissue, if the Secretary determines that such previous classification is unnecessary to protect the public health (g) RECALL, RETENTION, AND DESTRUCTION AUTHORITY- If the Secretary finds that a facility or human tissue violates any provision in this section or any regulations promulgated thereunder, the Secretary may issue an order that such facility coase distribution of human tissue or that such human tissue be retained, recalled. of destroyed. After receipt of such an order, the person in possession of the human tissue shall not distribute or dispose of the human tissue in any manner except consistent with the provisions of the order. Persons subject to the order who wish to challenge the order, shall, within 5 days of receipt of such order, request an opportunity for an informal hearing to be held within 30 days. (2) INTERIM REGULATIONS - The requirements set forth in the interim regulations promulgated by the Secretary in December, 1993 shall remain in effect until new regulations that supersede these regulations are in effect. (3) ADULTERATION PROVISION Section 501 (21 U.S.C. 351) is amended as follows: (A) in the first sentence by changing "drug or device" io "drug device, or human tissue." 3 JUL-29-1996 13:53 TO:DEBBIE FINE FROM: DADE, J. P. 6/6 07/24/96 16:59 301 443 0738 FDA GEN COUNSEL 005 07/24/96 WED 15:38 FAX 002 (B) by inserting at the end thereof the following new subsection: "0) If it is human tissue and it is recovered, processed, stored, or distributed by a facility that does not comply with good tissue practices consistent with section 352(a) of the Public Health Service Act." (4) MISBRANDING PROVISIONS - section SOZ (21 U.S.C. 352) is amended as follows: (A) by renaming the section "Misbranded Drugs, Devices, and Human Tissue" (B) in the first sentence by adding "(a)" before "A drug or device." (C) by redesignating subsections (a) through (t) as paragraphs (1) through (20). (D) by adding at the end thereof the following new subsection: "(b) Human tissue shall be deemed to be misbranded if its labeling is false or misleading in any particular or if its labeling, advertising, or promotion does not comply with regulations promulgated under section 352A(a) (5). (5) PROHIBITED ACTS. Section 301 (21 U.S.C. 331) is amended by inserting the following new subsection: "(v) The adulteration or misbranding of any human tissue. (6) SEIZURE. -- (A) Section 304 (a)(2)(D) (21 U.S.C. 334 (a) ) is amended by inserting "or human tissue" after "device." (B) Section 304(d)(1) is amended by deleting the "or" before "cosmetic" and inserting", or human tissue" after "cosmetic" in the first sentence. 4 JUL-29-1996 13:53 TO:204 - C. JENNINGS FROM:DADE J. P. 1/6 EXECUTIVE OFFICE OF THE PRESIDENT LRM NO: 5218 OFFICE OF MANAGEMENT AND BUDGET Washington, D.C. 20503-0001 FILE NO: 1746 SPECIAL 7/29/96 LEGISLATIVE REFERRAL MEMORANDUM Total Page(s): 6 TO: Legislative Liaison Officer Sce Distribution below: FROM: Janet FORSGREN (for) Assistant Director for Legislative Reference OMB CONTACT: Robert PELLICCI 395-4871 Logislative Assistant's Line: 395-7362 C=US, A=TELEMAIL, P=GOV+EOP, O=OMB, OU1=LRD, S=PELLICCI, G=ROBERT, I=J [email protected] SUBJECT: HHS Drafting Service RE: HR3199, Drug and Biological Products Reform Act of 1996 DEADLINE: 10:00 a.m. Wednesday, July 31, 1996 In accordance with OMB Circular A-19, OMB requests the views of your agency on the above subject before advising on its relationship to the program of the President. Please advise us if this item will affect direct spending or receipts for purposes of the "Pay-As-You-Go" provisions of Title XIII of the Omnibus Budget Reconciliation Act of 1990. COMMENTS: The attached language may be added 10 pending legislation that would reform the operations of the FDA. House Committee markup could occur this week. Please expedite your views on the attached language affecting the regulation of human tissue. DISTRIBUTION LIST: AGENCIES: 61-JUSTICE- Andrew Fois - 2025142141 76-National Economic Council - Sonyia Matthews - 2024562174 EOP: Nancy-Ann Min Chris Jennings Greg Simon Jennifer Klein Elizabeth Drye Michael Fitzpatrick Barry Clendenin Richard Turman Jim Esquea Jonathan Winer Allison Eydt Elena Kagan Bob Damus Janet Forsgren JUL-29-1996 13:53 TO:204 - C. JENNINGS FROM:DADE. J. P. 2/6 RESPONSE TO LRM NO: 5218 LEGISLATIVE REFERRAL FILE NO: 1746 MEMORANDUM If your response to this request for views is short (e.g., concur/no comment). we prefer that you respond by e-mail or by faxing us this response sheet. If the response is short and you prefer to call, please call the branch-wide line shown below (NOT the analyst's line) to leave 8 message with a legislative assistant. You may also respond by: (1) calling the analyst/attorney's direct line (you will be connected to voice mail if the analyst does not answer); or (2) sending us a memo or letter Please include the LRM number shown above, and the subject shown below. TO: Robert PELLICCI 395-4871 Office of Management and Budget Fax Number: 395-6148 Branch-Wide Line (to reach legislative assistant): 395-7362 FROM: (Date) (Name) (Agency) (Telephone) SUBJECT: HHS Drafting Service RE: HR3199, Drug and Biological Products Reform Act of 1996 The following is the response of our agency to your request for views on the above-captioned subject: Concur No Objection No Comment See proposed edits on pages Other: FAX RETURN of pages, attached to this response sheet P. 3/6 JUL-29-1996 13:53 TO:204 - C. JENNINGS FROM:DADE. J. 002 301 443 0739 FDA GEN COUNSEL 002 07/24/96 18:57 07/24/86 WED 14:53 FAX REGULATION OF HUMAN TISSUE (1) REQUIREMENT of Part F of Title III of the Public Health Service Act (42 U.S.C. 262 et seq.) is amended by inserting after section 352 the following new section: "Section 352A REQUIREMENTS FOR HUMAN TISSUE (a) IN GENERAL - Facilities and persons that engage in the recovery. processing, storage, or distribution of human tissue: (1) shall annually register with the Secretary and provide the Secretary a list of all human tissues that are recovered, processed, stored, or distributed to/from such facility, except that the Secretary may exempt facilities or persons from such requirements on the grounds that they are not necessary to protect the public health: (2) shall at the time of registration provide s list of all contractors or agents of the tissue establishment who engage: in the recovery, processing, storage, or distribution of human tissue; and (3) shall comply with good tissue practices including, but not limited to, practices that address: (A) quarantine; recordkeeping the recovery, processing, storage, and distribution of tissue; validation of manufacturing facilities and equipment; quality control; packaging and labeling; adverse experience reports; complaint files and failure investigations; personnel qualification and training and tissue tracking procedures to identify tissue from donor to recipient and from recipient to donor; and (B) donor screening and infectious disease testing. (4) are subject to inspection by individuals authorized by the Secretary; (5) shall comply with regulations regarding labeling, advertising and promotion, which may be promulgated by the Secretary. (b) REGULATIONS The Secretary may promulgate regulations for implementation of this section. Such regulations may include provisions for certification of facilities that engage in the recovery, processing, storage, or distribution of human tissue. 1 JUL-29-1996 13:53 TO:204 - C. JENNINGS FROM:DADE, J. P. 4/6 2 003 07/24/96 15:58 TJ01 4d3 0738 FDA GEN COUNSEL 003 07/24/95 WED 14:58 FAI (c) FINDING OF INTERSTATE COMMERCE Congress finds that human tissue that is recovered, processed, distributed, or stored in the United States for medical use is in, or otherwise directly affects, interstate commerce. (d) DEFINITION - (1) HUMAN TISSUE The term "human tissue" means any tissue (an aggregate of similar cells together with their intercellular substance, or acellular integuments that have a particular structure and function) derived from a human body which: (A) is intended for administration to another human for the diagnosis. cure, mitígation, treatment, or prevention of any condition or disease; (B) is intended only to replace or repair comparable bodily tissue and does not act through a systemic mechanism; (C) is recovered, processed, stored, or distributed by methods which do not change tissue function or characteristics or propagate the tissue's cells; (D) may include the addition of substances that are safe under conditions of intended use and not intended to contribute to or provide a therapeutic effect to the recipient; and (E) includes demineralized bons, heart valves, and dura mater. (2) Such term does not include: (A) human material regulated or classified as a drug, medical device or biological product except as specified in (d)(1)(8) : (B) vascularized human organs, such as heart, liver, kidneys, lungs, Intestines, or pancreas; (C) blood, blood products, bone marrow, stem cells, somatic cell therapy, gene therapy, or human milk; (D) tissue that is combined with a drug, device, biologic, or another tissue; and (e) TISSUE SPECIFIC REVIEW For specific human tissue as the Secretary deems appropriate and for which she has 2 JUL-29-1996 13:53 TO:204 - C. JENNINGS FROM:DADE J. P. 5/6 07/24/96 16:38 FDA GEN COUNSEL 004 301 443 0739 07/24/96 WED 14:38 FAI @ 004 identified 1 public health concern related to clinical safety or effectiveness, the Secretary may conduct a review of existing data on clinical use, indications, outcomes, safety, and effectiveness of such tissue and may, as part of, or following, such review: (1) promulgate regulations controlling such tissue including, but not limited to, requirements for special labeling or reclassification (under recisssification subsection) of such tissue; and (2) set such other limitations as the Secretary may require to protect the public health. (f) CLASSIFICATION AND RECLASSIFICATION (1) the Secretary may classify or reclassify a human tissue as a drug, biological product or medical device, if the Secretary determines that such classification or reclassification is needed to protect the public health or, during the tissue specific review of subsection (e), the Secretary determines that premarket study of effectiveness is warranted; and (2) the Secretary may reclassify a human drug, biological product or medical device as a human tissue, if the Secretary determines that such previous classification is unnecessary to protect the public health. (B) RECALL, RETENTION, AND DESTRUCTION AUTHORITY If the Secretary finds that & facility or human tissue violates any provision in this section or any regulations promulgated thereunder, the Secretary may issue an order that such facility cease distribution of human tissue or that such human tissue be retained, recalled, or destroyed. After receipt of such an order, the person in possession of the human tissue shall not distribute or dispose of the human tissue in any manner except consistent with the provisions of the order. Persons subject to the order who wish to challenge the order, shall, within 5 days of receipt of such order, request an opportunity for an informal hearing to be held within 30 days. (2) INTERIM REGULATIONS - The requirements set forth in the interim regulations promulgated by the Secretary in December, 1993 shall remain in effect until new regulations that supersede these regulations are in effect. (3) ADULTERATION PROVISION Section 501 (21 U.S.C. 351) is amended as follows: (A) in the first sentence by changing "drug or device" to "drug, device, or human tissue." 3 JUL-29-1996 13:53 TO:204 - C. JENNINGS FROM:DADE, J. P. 6/6 07/24/96 16:59 301 443 0739 FDA GEN COUNSEL 005 07/24/96 WED 15:35 FAX 002 (B) by inserting at the end thereof the following new subsection: "0) If it is human tissue and it is recovered, processed, stored, or distributed by a facility that does not comply with good tissue practices consistent with section 352(a) of the Public Health Service Act." (4) MISBRANDING PROVISIONS - section 50Z (z1 U.S.C. 352) is amended as follows: (A) by renaming the section "Misbranded Drugs, Devices, and Human Tissue" (B) in the first sentence by adding "(a)" before "A drug or device." (C) by redesignating subsections (a) through (t) as paragraphs (1) through (20). (D) by adding at the end thereof the following new subsection: "(b) Human tissue shall be deemed to be misbranded if its labeling is false or misleading in any particular or If its labeling, advertising, or promotion does not comply with regulations promulgated under section 352A(a) (5). (5) PROHIBITED ACTS. - Section 301 (21 U.S.C. 331) is amended by inserting the following new subsection: "(v) The adulteration or misbranding of any human tissue. (6) SEIZURE. -- (A) Section 304 (a)(2)(D) (21 U.S.C. 334 (a) ) is amended by inserting "or human tissue" after "device." (B) Section 304(d)(1) is amended by deleting the "or" before "cosmetic" and inserting", or human tissue" after "cosmetic" in the first sentence. 4 SERVICES. DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service Food and Drug Administration RockVille MD 20857 STATEMENT BY WILLIAM B. SCHULTZ DEPUTY COMMISSIONER FOR POLICY FOOD AND DRUG ADMINISTRATION PUBLIC HEALTH SERVICE DEPARTMENT OF HEALTH AND HUMAN SERVICES BEFORE THE COMMITTEE ON LABOR AND HUMAN RESOURCES UNITED STATES SENATE FEBRUARY 22, 1996 FOR RELEASE ONLY UPON DELIVERY INTRODUCTION Madam Chairman and Members of the Committee. I appreciate the opportunity to testify on the important issue of promotion of unapproved uses of prescription drugs and medical devices. My name is William B. Schultz. I am the Deputy Commissioner for Policy at the Food and Drug Administration. FDA SUPPORTS THE DISSEMINATION OF INFORMATION TO PHYSICIANS Madam Chairman, I am here today to talk about uses that do not appear in a product's FDA-approved labeling and are not approved by the Agency. Such uses commonly are referred to as "off label, " "unapproved," "unlabeled," or "extra-label" uses. The Food and Drug Administration recognizes that, in certain circumstances, off label uses of approved products are appropriate, rational, and accepted medical practice. FDA knows that there are important off label uses of approved drugs. In this context, it is important that physicians have access to accurate information about drugs. But we also know that allowing the promotion of these kinds of uses can have negative public health consequences -- including exposing patients to unnecessary risks and destroying the incentive for companies to conduct the necessary research to demonstrate that products are safe and effective for these uses. Striking the proper balance between the need to regulate the promotion of unapproved uses for drugs and devices and the need for reliable scientific data and information on unapproved uses of approved products is a difficult and controversial challenge. FDA'S REGULATORY AUTHORITY I would like to start today by explaining how, in passing and amending the Federal Food, Drug, and Cosmetic Act (FDC Act), Congress struck that balance and what, as a result of Congressional decisions, FDA can and cannot do with respect to off label uses. The legislative history of the Federal Food, Drug, and Cosmetic Act indicates that Congress did not intend FDA to interfere with the practice of medicine. Thus, once a drug is approved for marketing, FDA does not generally regulate how, and for what uses, physicians prescribe that drug. A physician may prescribe a drug for uses or in treatment regimens or patient populations that are not listed in the FDA-approved labeling. Generally, FDA does not prohibit the dissemination of information to health care professionals. Physicians access information about off label uses through compendia, journal articles, continuing medical education programs, symposia, and professional meetings. Physicians also have access to a number of databases that provide information about off label uses. For example, the National Cancer Institute's Physician Data Query (PDQ) system is an excellent source for oncologists to obtain - 2 - information about current oncologic therapies. The National Library of Medicine (NLM) offers a Medical Literature Analysis and Retrieval System (MEDLARS), which is a computerized system of databases and databanks pertinent to biomedical research and patient care. NLM currently offers free access to three databases relating to AIDS. FDA does not regulate a physician's access to any of these types of independent off label use information -- no matter how preliminary it may be. In addition, FDA does not prohibit a manufacturer from providing a physician information about off label uses if the physician requests that information. Recently, the Agency announced a proposed change to its policy with respect to the dissemination of reference texts (medical textbooks and compendia). Drug companies may distribute independent reference texts even if they contain certain information about off label uses of approved drugs, as long as the texts do not have a significant focus on an off label use of the manufacturer supporting dissemination of the text. FDA recognizes that all of these sources of information can be very important to good medical practice. Although the FDC Act does not authorize FDA to regulate the practice of medicine, it specifically directs FDA to regulate the promotion of drugs and devices. Promotional materials are unlawful if they promote an unapproved use for the product; contain claims relating to the dosing, safety or effectiveness of the product that are inconsistent with the approved labeling; or - 3 - if they lack a fair and balanced presentation of information, i.e., of benefits and risks. Although submission of an article for publication in a journal is not promotional, the use of such an article to sell a drug or device is promotional. Under current law, if a company wants to promote a use of a drug or device it can do so by submitting an efficacy supplement and getting that use onto the label. As I will explain later in my testimony, getting a use onto the label has benefits beyond being allowed to promote. For example, it ensures reimbursement from third party payors, it helps to get that use included in formularies, and it gives the medical community more complete information about the product. As I will further explain later in my testimony, the requirements for efficacy supplements are often significantly simpler than the requirements for applying for permission to market a product in the first place. Moreover, the Agency is considering a number of measures that will make the supplement process a more effective tool for getting additional uses on the label of drug and device products. S. 1447 The Food and Drug Administration Performance and Accountability Act of 1995, S. 1447, bypasses the current approach. It would permit drug and device companies to use journal articles, textbook chapters, continuing medical education program materials, and compendial information relating to uses - 4 - recognized for purposes of third party coverage or reimbursement that discuss off label uses to promote the sale of their products for those uses. The bill also would permit drug companies to use summaries of journal articles, textbook chapters, CME program materials, or information relating to uses recognized for purposes of third party coverage or reimbursement to promote the sale of their products for off label uses. Device companies could distribute oral and written information about off label uses that are part of an "exchange" among health care practitioners, health care reimbursement officials, and the industry, that is exchanged for "educational or scientific purposes," or that is presented at CME programs, seminars, workshops, or demonstrations for devices to promote the sale of their products for those uses. We recognize that the purpose of the bill is to enhance dissemination of information and not to facilitate or encourage promotion of off label uses. But we strongly believe that if the bill is enacted, that will be its effect. Drug and device manufacturers market their products principally by sending sales representatives, referred to as detail men and women, out to talk one on one with physicians who might prescribe their products. A detailer's job is to convince those physicians to use and prescribe their products. They do this by providing information that purports to describe the usefulness of their products in the patient population. Written materials such as journal articles - 5 - that discuss favorable studies of these products are powerful tools in the hands of a detailer. If the bill is enacted, drug and device companies will be free to use these materials to promote off label uses. Pursuant to the bill, after a company receives FDA approval of a drug or device for one use, it would be permitted to promote that product, through these other means, for other uses. The material that companies could distribute often would be very preliminary, based on poorly designed or wholly uncontrolled studies. Companies could promote the use of a product even when the evidence merely suggests or can be interpreted as suggesting that a product may work for a specific use. Effectiveness would not have to be demonstrated. Thus, if drug X is approved for cancer patients, and there is some preliminary data that suggests it is beneficial for patients with crippling arthritis, the drug's manufacturer would be permitted to promote the drug and encourage its use for arthritis on the basis of this preliminary or unsubstantiated data. This promotion would be permitted even though the data have not been reviewed by independent scientific FDA experts. In addition, the clinical information that appears in the materials that the bill allows manufacturers to distribute has not been validated in any way. For example, neither peer reviewers nor textbook editors review the data underlying a study - 6 - described in a journal article or textbook chapter. In fact, peer reviewers and editors do not even see that data. FDA has serious concerns regarding the promotion of indications that have not been reviewed and approved by the Agency. Because promotional activities of drug companies and others are substantially motivated by profit and market expansion, the widespread promotion of prescription drugs and devices for uses that have not been determined to be safe and effective could be detrimental to the health and safety of the public. Permitting companies to promote drugs and devices for off label uses could have a number of devastating consequences for the quality of medical care in this country. PROBLEMS WITH PERMITTING PROMOTION OF OFF LABEL USES The fundamental problem with permitting the promotion of off label uses is that not all off label uses are safe and effective. The only way to know which ones are safe and effective is to collect and analyze the data supporting a finding of safety and efficacy. Because the data on off label uses have not been collected and analyzed, their promotion raises a number of serious concerns. Undercutting the Efficacy Standard Permitting the promotion of off label uses based on studies reported in journal articles or other texts that clearly are an - 7 - inadequate basis for approval by FDA would undercut the efficacy standard. A fundamental precept of drug and device regulation in this country is that these products must be proven safe and effective before they can be sold. The requirement that these products must be proven effective, on the basis of well-controlled clinical studies, was first adopted by Congress in 1962. Congress specifically added the concept of effectiveness to the definition of "new drug" in order to ensure that the efficacy requirement would apply not only to initial claims made for a drug, but also to claims made after the initial new drug application had been approved. 108 Cong. Rec. S22044-46 (daily ed. October 3, 1962) i S. Rep. No. 1744, 87th Cong., 2d Sess. Part 2 at 267, 271 (1962) ("On what logical basis can one possibly argue that the initial claim for a drug should be supported by "substantial evidence" but that successive claims should not be so supported?" 108 Cong. Rec. at S22045.) The addition of the "efficacy standard" revolutionalized drug development and approval, not only in the United States, but worldwide, as well. Essentially, a manufacturer cannot just say that a product works for a particular disease or condition, it must prove that the product works for that disease or condition. The only way manufacturers can prove efficacy is by submitting data from well-controlled clinical trials for evaluation by - 8 - independent experts at FDA. Anecdotal reports and poorly controlled observations do not suffice because those kinds of reports may be wrong or may not be an adequate basis for conclusion. We know this because we have had experience with this type of information. Many drugs approved before 1962 turned out not to work when, after 1962, they had to be (and were) studied. Even when such reports suggest efficacy, they fail to provide important guidance in areas critical to the effective use of a therapy such as dosage and patient selection and management. The solid foundation that is laid down by the efficacy standard is one of the main reasons that there is a strong sense of confidence in the drug products that are on the U.S. market today. Because the standard requires well-controlled clinical trials, once FDA has made a determination of effectiveness, there can be a high degree of confidence that the drug will work. Thus, when a manufacturer claims that a product is safe and effective for a particular disease or condition, doctors can be confident that the product is in fact safe and effective for that disease or condition. Patients, in turn, can have confidence in the quality of the products they are receiving. Eliminating the need for well-controlled studies would be a major setback for the first-rate medical care that the health care system in this country provides. Consider some of the - 9 - additional uses that FDA has approved on the basis of such studies -- for example, timolol, propranolol, metoprolol, and atenolol to improve the survival of heart attack patients, taxol for breast cancer, and interferon-alpha 2b for chronic hepatitis B and C. Without the requirement to submit clinical studies to prove that drugs are effective for their intended uses, it is far less likely that we would know that these drugs will work to decrease mortality in heart attack patients, to delay or prevent breast cancer recurrence, or to treat chronic hepatitis B and C. In the absence of the efficacy requirement, the market will be filled with drugs that manufacturers claim work and that physicians use because of a belief that they work, but for which there is relatively little evidence. Disincentive to Conduct Studies One of the most serious consequences of allowing companies to freely promote off label uses is that companies would have no incentive to conduct or fund the necessary scientific research and to present data to FDA to verify the safety and efficacy of those off label uses. In fact, because the Agency might determine that the new use is not supported by the evidence, there would be an incentive to avoid FDA review. To use the example of the cancer drug that may be useful for crippling arthritis, why would the drug company undergo the expense of actually studying whether the drug works for arthritis if it could promote the drug for arthritis based on preliminary - 10 - evidence, particularly since a thorough study might fail to establish efficacy for arthritis? In a world where off label uses can be widely promoted, manufacturers would have an incentive to do the minimal amount of studies necessary to obtain approval for the first, narrowest/easiest indication and then heavily promote the product for other broader (and possibly more speculative) uses. For example, interferon-alpha 2b was approved for use in hairy cell leukemia, of which there are approximately 300-400 cases per year. It subsequently was approved to treat chronic hepatitis B and C, of which there are tens of thousands of cases per year. If S. 1477 had been in effect, the manufacturer of interferon- alpha 2b could have sought approval for hairy cell leukemia and then just promoted for chronic hepatitis B and C -- the much broader use -- based on preliminary data. Interferon-alpha 2b is just one of many examples of a second, very different use being significantly broader than the original use for which a drug was approved. Under the approach taken in the bill, we might never learn whether interferon alpha actually works to treat hepatitis B -- yet the manufacturer could promote its use. This is precisely the scenario that Congress sought to prevent when it added the effectiveness requirement to the definition of a new drug. A group of Senators, lead by Senator Kefauver, argued that unless - 11 - the effectiveness requirement was added to the definition of drugs, "the expectation would be that the initial claim would tend to be quite limited, which of course, would expedite approval of the new drug application. Thereafter, 'the sky would be the limit' and extreme claims of any kind could be made," subject only to FDA's enforcement authority. 108 Cong. Rec. at S22046. Because the incentive to conduct research on uses of drugs and devices will decrease, the end result will be that the dissemination of off label information pursuant to this bill will actually reduce the amount of information that health care providers receive about drugs and devices. Safety Issues Widespread promotion of unapproved uses also raises significant safety concerns. Even under the current law, which prohibits the promotion of off label uses, we know of a number of instances where physicians have used drugs for off label uses that have resulted in disastrous consequences. For example, the drugs encainide and flecainide were approved for life-threatening and symptomatic arrhythmias, which are abnormal rhythms of the heart. In the late 1980's, physicians began to prescribe these two drugs for heart attack victims who were experiencing ventricular premature complexes - 12 - (VPCs), a type of asymptomatic or minimally symptomatic arrhythmia. (Asymptomatic arrhythmias are arrhythmias that can be detected by tests, but which the patients do not feel.) This off label use, which was supported by published peer-reviewed journal articles, was intended to prevent the well-documented increased mortality of heart attack victims who have a high level of VPCs by suppressing those VPCs. The use was logical and became so widespread that the National Institutes of Health decided to study the effectiveness of encainide and flecainide in these patients. To the surprise of almost everybody, that study demonstrated not only that the drugs were ineffective in reducing the risk of death but that the drugs were actually harmful in patients for whom it was being prescribed off label -- that is the death rate among those receiving the drug was more than twice the rate of those receiving a placebo. If these unapproved uses had been heavily promoted by drug companies, it is estimated that thousands more unnecessary deaths would have occurred. Another example relates to the widespread off label use of a class of drugs called calcium channel blockers (CCBs). These drugs are effective for patients suffering from angina, which is chest pain caused by insufficient oxygen to the heart muscle. CCBs have no established role in patients who have had a heart attack but have no symptoms. These patients do, however, benefit from another class of drugs, beta-blockers, which are known to reduce mortality by 25-30% after heart attacks. Nevertheless, - 13 - CCBs are widely used in this patient population and there are publications that could be interpreted as supporting this use. Because CCBs and beta-blockers generally should not be used simultaneously, patients are receiving CCBs in lieu of clearly life-saving beta blockers. Many, probably thousands, of lives are lost each year because a drug of no known benefit is being used for an unapproved use in place of a drug with known value. Widespread promotion of this use would make the problem even worse. Yet another example of a case where the distribution of published articles on off label use could have resulted in very serious harm to the public involves the fentanyl transdermal system (Duragesic). Approved for use in chronic pain in patients requiring opioids, the fentanyl patch was not approved for acute post-operative pain because of concern that it would cause respiratory depression (a serious condition in which less air reaches the lungs) in those patients not used to the effect of opioids. A number of publications prior to the time of approval, however, described the drug as safe and effective for post- operative pain. After approval, reports to FDA and the literature documented life-threatening respiratory depression in post-operative patients given the patches. Extensive promotion of this off label use could have been disastrous. There are many other claims that could be promoted through - 14 - peer-reviewed journal articles describing off label uses that could be detrimental to a large number of patients if they were heavily promoted. FDA fears that problems illustrated by these examples would be multiplied if manufacturers were given free rein to promote unapproved uses. Unbalanced View Another significant problem with permitting companies to promote unapproved uses by distributing the type of information described in the bill is that physicians may not receive a balanced view of the available information. It is well documented that there is publication bias. Studies with favorable results have a greater likelihood of getting published; studies with less favorable results less often get published. More importantly, even if less favorable or contradictory results have been published, companies have no incentive to distribute articles, textbook chapters, or other information recommending against a particular use. Because the bill permits companies to distribute certain chapters of textbooks or mere summaries of journal articles, chapters, and CME materials, with no obligation for balance or comprehensiveness, physicians may see only one side of an off label use story. The current law governing promotion requires balance. Changing the law to allow the distribution of journal articles and other similar materials that discuss off label uses will - 15 - allow drug detail men and women to provide materials that describe favorable study results of their product for a particular use, but without providing copies of materials that go the other way. I would like to illustrate with an example. Human growth hormone currently is indicated for use only in children who are short because they lack sufficient growth hormone and children who are short because of kidney problems. Its use in children who are short, but have no growth hormone deficiency or underlying kidney problem, is an off label use of uncertain value and safety. We identified four journal articles that discuss this off label use -- two more or less supported the off label use and two did not. If a physician receives information about this off label use from a detail person, it is possible that he or she will receive only the two favorable articles. On the other hand, if the physician were conducting his or her own research into the subject, he or she would likely locate both the pro and con articles. Given the approximately $20,000 per year price tag of human growth hormone, the pain a child must endure because of multiple drug injections each week, and the potential adverse effects that growth hormone may cause (such as diabetes and possibly tumor growth), it is important that physicians see all pieces of the scientific puzzle until the answer is clear. - 16 - By using this example, I am not targeting a specific drug or drug company. I am merely trying to illustrate what the bill would permit and why FDA has serious concerns. What makes this situation even more troubling is that when we have evidence that a particular use is unsafe or ineffective, federal confidentiality laws frequently prohibit FDA from disseminating that information. Thus, there are off label uses about which positive studies appear in the literature and negative data are contained in our files. However, depending on its source, FDA may be unable to use that information to ensure that the medical community has all of the available facts on which to base treatment decisions. Even under current law, physicians have access to positive articles about off label uses and FDA may be unable to counter those positive articles with any negative information that might be in our files. However, under current law, company detail men and women cannot use those articles to promote potentially dangerous off label uses. The Bill's Requirements Are Not Substitutes for FDA Review The bill imposes very few requirements on the off label use information that companies could disseminate. Basically, the unapproved use must appear in a peer-reviewed journal article, a chapter from a recognized text, text from an approved CME - 17 - program, information relating to a use recognized under Federal law for purposes of third party coverage or reimbursement, or a summary of one of the above. For devices, the information may also be from oral and written information that is part of an "exchange" among health care practitioners, health care reimbursement officials, and the industry, is exchanged for educational or scientific purposes, or is presented at CME programs, seminars, workshops, or demonstrations. None of these sources has procedures that confirm the validity of the data and information contained therein. The purpose of the "peer review" process, for example, is to determine if an article is worthy of publication. At its best, peer review can ensure that the reader is provided with enough detail and clarity to make a general judgment about the strengths and weaknesses of the study. However, there are no generally accepted standards for what constitutes "peer review. " Essentially, anyone can establish a "peer review" journal; the rigor of the review varies considerably. Regardless of the rigor, there are severe limitations inherent in the peer review process that make it inappropriate to rely solely on a peer-reviewed journal article for efficacy determinations. For example, peer reviewers almost never receive the study protocol. They cannot tell what the initial hypothesis was or whether the final analysis represents the planned analysis - 18 - or an analysis crafted with the results in hand. Peer reviewers do not have access to the underlying data. The peer reviewers must rely on the data and facts as they are presented by the author. FDA, on the other hand, does have access to the data and can verify the critical statistical outcomes and the conclusions of a study. Moreover, peer reviewers do not necessarily have the time or the expertise in all aspects of the subject matter to adequately review the information. In fact, a survey reveals that a peer reviewer spends on average less than three hours reviewing a prospective article. The peer review process cannot guarantee the correctness or authenticity of the article, nor can it detect fraudulent or flawed research. The data and information supporting off label uses that appear in reference textbook chapters, which could highlight off label uses of particular drugs or devices, CME materials, and materials related to third party coverage and reimbursement are even less likely to be validated than that in peer-reviewed journals. In fact, we have no reason to believe that such data have been reviewed or validated at all. Textbook editors do not review the data underlying information about off label uses that appear in those books. The recognition of suggested uses in texts or treatment guidelines for purposes of third-party reimbursement serve different societal purposes. The decision to include such uses is not based on the standards used by FDA to substantiate safety and efficacy. FDA has serious concerns about - 19 - a provision that allows companies to use these types of unproven/unvalidated information for promotional purposes. There are many instances when uncontrolled studies have supported a use and subsequent well-controlled studies have failed to show effectiveness. Moreover, the literature is laden with studies that report preliminary findings -- e.g., studies that involve a small number of patients and case reports or are not properly controlled. Although the studies or reports may be scientifically accurate, they are not sufficient to show safety and efficacy. Thus, companies should not be allowed to use these less rigorous studies to promote off label uses of approved products. GETTING SUPPORTED OFF LABEL USES ON THE LABEL As you know, a drug is approved for its initial indications via a new drug application, which includes data on the drug's safety and efficacy. A subsequent indication is added via a supplemental new drug application, which usually needs to present only efficacy information to support that new use. After review and approval by FDA, the new use is added to the approved labeling and can be promoted by the drug's manufacturer. There are several good reasons for drug companies to submit these "efficacy supplements": - 20 - - Approval usually ensures that third-party payers will reimburse for the use, as insurance companies virtually always pay for approved uses of drugs and devices. - As health maintenance organizations continue to grow in size and number, a sponsor's ability to get their drug included in the HMO's drug formulary will be significantly enhanced. - The physician, via the approved labeling, is given more complete information about the drug's uses, contraindications, adverse effects, and other important information about the manufacturer's product. - Drug companies can present the FDA findings to drug approval bodies in other countries, thus enhancing their ability to gain approval (and reimbursement) for uses in other markets. - And, of course, the manufacturer can promote the use, whether through the use of journal articles or other means. Unfortunately, in many instances these incentives have been insufficient to persuade drug sponsors to submit efficacy supplements. There appear to be two reasons for their reluctance. First, they fear they will be expected to spend millions of additional dollars conducting new clinical studies to convince FDA reviewers that the new use should be approved. And - 21 - second, they have often complained that efficacy supplements are given low priority by FDA, resulting in delays of years in getting new indications approved. These concerns -- or at least the perception -- have been valid in the past, and we at FDA must address them. We have been working on ideas for encouraging and expediting efficacy supplements for unapproved uses and for otherwise addressing industry concerns. We are doing a number of things and have several ideas for additional progress in this area. Let me summarize them for you: Expediting Review of Efficacy Supplements As you know from yesterday's testimony, the Prescription Drug User Fee Act of 1992 (PDUFA) is helping resolve the problem of timely reviews for drugs and biologics. Under PDUFA, by 1997, the Agency will make approval decisions on all new drug and biologic applications (NDAs, PLAs, and ELAs) within 12 months and within 6 months for priority drugs and biologics. These time frames apply to efficacy supplements as well. The approval times for NDAs, PLAs, ELAs, and efficacy supplements have decreased significantly, and the backlog of pending applications has also decreased markedly. In fact, for NDAS, PLAs, ELAs, and efficacy supplements, the Agency has exceeded the interim goals established by Congress. For applications submitted in FY 1994, the Agency reviewed and acted upon 96% of the NDAs, PLAs and ELAs - 22 - and 73% of efficacy supplements on time. [The interim goal for all of these was 55%.] With adequate resources, we are confident that we can make the same progress for medical devices. We should, however, be able to exceed the PDUFA targets. I believe we should try to reduce the 6-12 month timeframes. To do so, we will need to give supplements a greater priority than they have had in the past, and we are committed to that. Fewer Data Are Needed Than Commonly Believed In addition to assuring companies that we can and will expedite their supplemental applications, we also need to address the industry perception that many efficacy supplements do not warrant the expense associated with getting them approved. Companies fear that they must conduct multiple and expensive new clinical trials and collect and analyze thousands of pages of medical data, with no assurances of approval. We need to more clearly explain that in the vast majority of cases this is just not so. Some off label uses could be approved by FDA if the sponsor would simply compile the existing literature and submit it to us. Others may need only limited data or data about the studies, such as protocols, data tapes, or verification of endpoints, all of which is already in existence but simply needs to be found and copied. In any event, because FDA has already learned much about the drug's actions and effects in humans from the original application and has considerable experience relevant - 23 - to safety, the data required for second and subsequent indications is often far less than for the original indication. It is, in sum, Madam Chairman, a much simpler process than generally believed and we must convince sponsors of that. To that end, we intend to draft a new policy statement articulating the data needs of the Agency for efficacy supplements for new indications. Pediatric Labeling We are already demonstrating how limited data can get more uses on the label in the pediatric area. We have recently promulgated new regulations that provide, in certain cases, for pediatric uses to be included on the approved labeling without new clinical studies. Pursuant to these regulations, when there is sufficient basis to conclude that the course of the disease and the effects of the drug are sufficiently similar in children and adults, drug firms can rely on existing studies in adults, extrapolate the data to children, and get those uses on the label with relative ease. The only new data that will ordinarily be needed are information about the drug's course throughout the body (e.g., blood and tissue levels) that will allow the proper dosage to be established for the use of that drug in children. Seek Out the Most Appropriate Off Label Uses As I said earlier, many off label uses are quite appropriate, and some may even be the treatment of choice. - 24 - Although off label use is seen in all medical specialties, it seems to be most widespread in certain areas, such as oncology and pediatrics. Beginning with those specialties, we will work with practitioners and their specialty associations to identify the off label uses that are most appropriate. We will then present those findings to the sponsors of those drugs and urge them to work with us to get the indications in the labeling. In many, if not most, cases that will entail only the compilation of existing information, not the design and conduct of new clinical studies. We have not done enough to reach out to the medical profession and to drug sponsors on this issue, but we believe we can get the majority of the most appropriate current off label uses in the labeling through this process. The best way to get information to physicians about the best uses of the drug and device armamentarium, Madam Chairman, is to have it in the product's labeling. Our collective goal ought to be to get this done. CONCLUSION Public confidence in drug and device therapy has been built on the recognized rigor of FDA's approval process. It is important that we not change a system that has the respect and confidence of the health care community and the public. FDA recognizes that there are important lifesaving off label uses. FDA believes, however, that the best way to address any concerns - 25 - that the information about those uses is not reaching medical practitioners is to get those uses in the labeling. We believe that the risks of allowing drug companies to distribute journal articles and other information about off label uses far outweigh any benefits. I would be happy to answer any questions. - 26 - ORGANIZATIONS & INDIVIDUALS ENDORSING THE ACCESS TO MEDICAL TREATMENT ACT HR 2019/S 1035 American Academy of Anti-Aging Medicine American Academy of Environmental Medicine American Academy of Pain Management American College for Advancement in Medicine American Herbalist Guild American Holistic Centers American Holistic Medical Association American Holistic Health Association American Massage Therapists Association American Preventive Medical Association American Academy of Metabolic Medicine American Association of Naturopathic Physicians American Association of Acupuncture & Oriental Medicine Association of Applied Psychophysiology & Biofeedback Calello Martinez P.C. Cancer Control Society Cancer Awareness Coalition Center for Mind-Body Medicine Center for Natural and Traditional Medicine Citizens for Health Citizens for Nutrition Choice Council for Responsible Nutrition Direct Access for A.I.D.S. Research Direct Action for Treatment Access Dr. Mohammed Ranavaya, of Academy of Disability Evaluating Physicians * Ed Hudgins of Cato Institute * Great Lakes Association of Clinical Medicine Healing Alternatives Foundation H.I.V. Complimentary Therapy Center Institute for Naturopathic Medicine Institute of Pain Management International Academy of Compounding Pharmacists International Association of Cancer Victors & Friends International Oxidative Medical Association Lyme Disease Foundation National Center for Homeopathy National Council for Improved Health National Nutritional Foods Association Mr. Duke Pearson and Ms. Sandy Shaw People Against Cancer Physician's Committee for Responsible Nutrition Physician's Association for Anthroposophical Medicine Pure Food Campaign Southwest College of Naturopathic Medicine & Health Sciences Traditional Acupuncture Associates Traditional Acupuncture Institute Utah Natural Products Association Vegetarian Awareness Network * - Signifies a personal endorsement and is not intended to convey endorsement by the Association July 29, 1996 Prepared by the American Preventive Medical Association 459 Walker Road Great Falls, Virginia 22066 703-759-0662 Fax 703-759-6711 CEI COMPETITIVE ENTERPRISE INSTITUTE CARDIAC AND CANCER SPECIALISTS ON THE NEED FOR FDA REFORM Polls Show Need for Access to Unapproved Therapies Cardiology and oncology are two medical specialties whose members understand the need for new, life-saving drugs and devices. They know, on a first-hand basis, that such technologies can frequently mean the difference between life and death for many patients. What do cardiologists and oncologists think of FDA and of access to new therapies? In the past year, CEI commissioned two polls to examine the views of these specialists. The first, a poll of oncologists, was released in August, 1995. It involved a total of 160 telephone interviews with randomly selected hospital-based oncologists. Its margin of error was ±5.1% at the 95th percentile confidence level--that is, similar results would have been obtained in 19 out of 20 cases. The second poll, of 216 randomly selected cardiologists and cardiac surgeons, was released last week on July 24, 1996. Its margin of error is ±4.8 percent at the same high confidence level. Both polls demonstrate highly negative views of FDA on such issues as whether the agency is too slow in approving new drugs and devices, whether the public understands the human cost of FDA delays, and whether FDA delays impair the ability of these specialists to give the best possible care to patients. Both polls also demonstrate overwhelming opposition to FDA's policy of restricting information about off-label use. Majorities of both specialties support allowing physicians to use unapproved drugs and devices, provided those products carried a warning about their unapproved status (Question 8). Both specialties believed they could rely on published research, on foreign governments' approvals, and on their colleagues' opinions to determine whether such therapies were suitable for their patients (Question 9). Cardiologists and oncologists agree that FDA regulation has prevented them from giving their patients the best possible care. Something is wrong when an agency charged with protecting public health is viewed this negatively by physicians fighting for their patients' lives. The Access to Medical Treatment Act (S. 1035), on which the Senate Labor and Human Resources Committee is holding hearings today, is an important step toward giving doctors the freedom to treat their patients to the best of their abilities. Sam Kazman July 30, 1996 1001 Connecticut Avenue, N.W. Suite 1250 Washington, D.C. 20036 Phone: (202) 331-1010 Fax: (202) 331-0640 E-mail: [email protected] Web site: http://www.cei.org Summary of Poll Results 1. On balance, do FDA regulations help or prevent you from using promising new drugs or medical devices in the treatment of your patients? Would that be strongly or just somewhat? Cardiologists Oncologists TOTAL HELP 42% 44% Strongly help 20% 8% Somewhat help 22% 36% TOTAL PREVENT 46% 43% Somewhat prevent 33% 35% Strongly prevent 13% 8% Neither 7% 14% Don't know/Refused 5% - 2. The FDA is too slow in approving new drugs and medical devices. Cardiologists Oncologists TOTAL AGREE 65% 77% Strongly agree 30% 31% Somewhat agree 35% 46% TOTAL DISAGREE 30% 20% Somewhat disagree 18% 14% Strongly disagree 12% 6% Neither 3% 2% Don't know/Refused 2% 1% 2 3. The additional time it takes for the FDA to approve drugs and medical devices costs lives by forcing people to go without potentially beneficial therapies. Cardiologists Oncologists TOTAL AGREE 57% 47% Strongly agree 17% 11% Somewhat agree 40% 36% TOTAL DISAGREE 37% 48% Somewhat disagree 21% 34% Strongly disagree 16% 14% Neither 5% 4% Don't know/Refused 2% 1% 4. In your opinion, to what extent does the general public understand the "human cost" of the FDA approval process, that is, that some people may suffer or die waiting for the FDA to act? Do they Cardiologists Oncologists TOTAL UNDERSTAND HUMAN COST 24% 19% Completely understand 4% 1% Somewhat understand 20% 18% TOTAL DON'T UNDERSTAND HUMAN COST 63% 74% Understand only a little 33% 51% Don't understand at all 30% 23% Refused/Disagreed with statement/Don't know 12% 9% 5. If a drug or medical device has already been approved for one use by the FDA, should the FDA restrict information about off-label uses, that is, other unapproved uses of that drug or device? Cardiologists Oncologists YES 21% 16% NO 67% 76% Sometimes 5% 4% Don't know 5% 1% Refused 2% 3% 3 6. To what extent does this FDA policy of limiting information make it more difficult for you to learn about new uses for drugs or devices? Cardiologists Oncologists TOTAL MORE DIFFICULT 60% 60% Much more difficult 13% 17% Somewhat more difficult 47% 43% TOTAL LESS DIFFICULT 28% 28% Somewhat less difficult 14% 22% Much less difficult 14% 6% No impact 7% - Don't know 4% 8% Refused 1% 5% 7. Would you say the FDA's approval process has hurt your ability to treat your patients with the best possible care frequently, some of the time, at least once, or never? Cardiologists Oncologists TOTAL HURT ABILITY 71% 63% TO TREAT Frequently 7% 11% Some of the time 45% 37% At least once 19% 15% NEVER 28% 36% Refused 1% 1% 8. What would your position be on a proposal to change FDA law so that unapproved drugs or devices could be made available to physicians as long as they carried a warning about their unapproved status? Would you strongly favor, somewhat favor, somewhat oppose, or strongly oppose such a proposal? Cardiologists Oncologists TOTAL FAVOR 53% 61% Strongly favor 21% 24% Somewhat favor 31% 37% TOTAL OPPOSE 44% 37% Somewhat oppose 24% 24% Strongly oppose 20% 13% Don't know/refused 3% 2% 4 9. Assume for a moment that a system was in place where unapproved drugs or devices were available to you for treating patients. Which of the following would be the most important factor in your decision to use such an unapproved drug or device? Cardiologists Oncologists Whether persuasive published research exists 47% 59% about the drug or device Whether the drug or device has received approval 25% 29% in other medically advanced countries Whether the drug or device was well-regarded by 19% 10% physician colleagues Don't know/Refused 10% 2% 10. And finally, how many years have you been in practice? Cardiologists Oncologists 5 years or less 7% 14% 5-8 years 7% 14% 8-12 years 14% 14% 12-15 years 17% 11% More than 15 years 56% 47% 11. Gender Cardiologists Oncologists Male 94% 89% Female 6% 11% 5 CEI COMPETITIVE ENTERPRISE INSTITUTE For Immediate Release: Contact: Greg Smith (202) 331-1010 PHYSICIAN ACCESS TO UNAPPROVED THERAPIES SUPPORTED BY NEW LEGAL STUDY AND BY TWO NATIONAL POLLS OF MEDICAL SPECIALISTS WASHINGTON, DC July 30, 1996-A public interest group today announced the release of a new legal study on giving physicians access to drugs and devices that have not been approved by FDA. On Tuesday, July 30, the Senate Labor & Human Resources Committee holds hearings on the Access to Medical Treatment Act (S. 1035), a bill which increases physician access to such therapies. The CEI study, Breaking the FDA's Drug Approval Monopoly--Implications for Tort Law and Consumer Welfare, is written by George Mason Law Professor Michael I. Krauss. It concludes that FDA's current command-and-control approach to therapeutic approval cannot be justified by the "market failure" arguments that are usually offered to support it. Physician access to unapproved therapies would serve the interests of patients who frequently suffer under FDA delays, and would ultimately force FDA itself to earn its credibility. A CEI poll of cardiologists, released on July 24, demonstrates that support for this approach is far wider than commonly assumed. A majority of the over 200 cardiologists polled (53%) supported physician access to properly labeled unapproved therapies, while 44% opposed it. Similarly, a 1995 CEI poll of cancer specialists found 61% favoring this approach. Both groups stated that "persuasive published research" would be the single most important factor in their deciding whether to use such therapies. CEI General Counsel Sam Kazman stated: "Physician access to unapproved therapies is often derided as opening the door to snake oil. The fact that such an approach is favored not only by the public, but by majorities of these two life-saving specialties indicates that FDA is far more of a health problem than its supporters will admit." Under CEI's proposal, FDA would continue to evaluate new therapies, but it would not have the power to veto unapproved therapies, which would be available under medical supervision and with clear warning of their unapproved status. CEI is a non-profit, non-partisan public policy group dedicated to free markets and limited government. For more information, or a copy of the study or the polls, call Greg Smith at (202) 331-1010. 1001 Connecticut Avenue, N.W. Suite 1250 Washington, D.C. 20036 Phone: (202) 331-1010 Fax: (202) 331-0640 E-mail: [email protected] Web site: http://www.cei.org THE FEDERATION OF STATE MEDICAL BOARDS OF THE UNITED STATES, INC. 400 FULLER WISER ROAD. SUITE 300 EULESS. TEXAS 76039-3855 817 868-4000 FAX 817 868-4099 PRESIDENT ROBERT E. PORTER. MD ONE MEDICAL CENTER DR. STATEMENT OF THE LEBANON. NH 03756 FEDERATION OF STATE MEDICAL BOARDS PRESIDENT ELECT JAMES E. WEST. MD 901 EAST LEIGHTON AVENUE. SUITE 702 OF THE UNITED STATES, INC. ANNISTON. AL 36207 VICE PRESIDENT ON SUSAN M. SPAULDING P.O. BOX 222 MONTPELIER. VT 05601 TREASURER S.1035, ACCESS TO MEDICAL TREATMENT ACT BRUCE H. HASENKAMP JD 900 HYDE ST.. SUITE 1208 SAN FRANCISCO. CA 94109 TO THE IMMEDIATE PAST PRESIDENT GERALD J BECHAMPS. MD P.O. BOX 2698 WINCHESTER. VA 22601 COMMITTEE ON LABOR AND HUMAN RESOURCES DIRECTORS UNITED STATES SENATE LEROY B BUCKLER. MD 640 SOUTH STATE ST DOVER. DE 19901 WILLIAM H. FLEMING. III. MD JULY 30, 1996 7777 SW FREEWAY. SUITE 1004 HOUSTON TX 77074 JOHN T. HINTON. DO. MPH 655 EDEN PARK DR. CINCINNATI OH 45202 PHILIP M. MARGOLIS. MD 900 WALL ST. ANN ARBOR. MI 48105 DINESH PATEL. MD 15 PARKMAN ST. SUITE 510 BOSTON, MA 02114 ALAN E. SCHUMACHER. MD 3020 CHILDREN'S WAY / MC 5008 SAN DIEGO. CA 92123 GEORGE J VAN KOMEN. MD 745 EAST 300 SOUTH SALT LAKE CITY. UT 84102 RAY Q BUMGARNER JD 77 SOUTH HIGH ST. 17th FLOOR COLUMBUS. OH 43266 JAMES R. WINN. MD EXECUTIVE VICE PRESIDENT DALE L. AUSTIN. BSN. MA DEPUTY EXECUTIVE VICE PRESIDENT CAROL CLOTHIER. BA ASSISTANT VICE PRESIDENT P/R. PUBLICATIONS. EDUCATION [. KATHRYN HILL. MEd ASSISTANT VICE PRESIDENT EXAM/BADB SVCS. DIV. The Federation of State Medical Boards is pleased to provide comments about S.1035, The Access to Medical Treatment Act. The Federation is a national organization, the members of which are the state medical boards empowered to license and discipline physicians in the United States. The mission of the state medical boards is to protect the public from unqualified practitioners of medical services, through enforcement of standards established by state laws. The Federation assists boards with this mission, acting as a clearinghouse for the latest information on licensure and discipline, and assists in the credentialling process through maintenance of a comprehensive database of board actions involving physician disciplinary matters, that is available for query by state boards and other credentialling agencies. The evaluation of a medical practitioner is best performed at a level of government that allows regulators to take advantage of professional and personal relationships with individuals whose judgment they trust. Since being established in the late nineteenth century in response to a number of incidents in which patients were harmed, state medical licensure boards have evolved into sophisticated regulatory agencies dedicated to ensuring that the public is protected from unfit and/or unqualified practitioners. During the last century each state has enacted and amended its own version of a medical practice act. While the specifics of each medical practice act differ, each prescribes through statute and implementing regulation the process by which the initial granting of a license and the monitoring of the privilege to practice medicine shall be accomplished. Today, there are 54 allopathic and 16 osteopathic state medical boards which have the authority to license physicians, to regulate the practice of medicine within the state, and to discipline those who violate the relevant medical practice act. In particular, state medical boards: Establish academic and clinical skill standards for all license applicants; Establish rules and regulations promoting the safe and effective practice of medicine; Require periodic re-registration of medical licensees in order to review the qualifications of licensees on a regular basis; (the frequency of re-registration required varies from state to state); Investigate and adjudicate allegations of physician misconduct; Take appropriate disciplinary actions against any physician who is found to have violated the state medical practice act. The action taken may involve sanctions that range from license revocation to reprimands and fines. These central functions of state medical boards serve to accomplish the primary purpose of medical licensure; protecting the public from sub-standard medical care. The member Federation boards recognize that patients have a right to participate with their physicians and other health care practitioners in the decisions to pursue a particular therapy as long as risks, benefits, costs, and alternatives are discussed between practitioners and patients before a particular course of treatment is begun. A number of our boards have had to discipline practitioners for providing treatment without adequate disclosure to the patient. For that reason the Federation is supportive of several provisions in S.1035 that recognize the need for full disclosure prior to treatment. Unfortunately, other provisions in the bill seriously undermine the ability of state licensing boards to take actions against physicians who may jeopardize public health. S.1035 grants every patient a right to be treated by a health care practitioner with any medical treatment that such individual desires (including one not approved, certified, or licensed by the Secretary of Health and Human Services), provided: a) that such practitioner has personally examined the individual and agrees to treat such individual, and b) the administration of such treatment does not violate licensing laws. The Federation has grave concerns about this central provision and does not believe that the limitations (e.g. requiring a personal examination and prohibiting treatment that violates licensing laws) provide adequate safeguards for patients. First, although the bill requires a personal examination of a patient by a practitioner, it does not specify the nature of the examination; whether it may be perfunctory, or must be exhaustive, nor whether it shall include particular attention to the patient's mental and emotional state if a treatment involving products that have not been approved by FDA is being recommended. Second, The bill prohibits the administration of any treatment that violates licensing laws. For the most part, licensing laws do not contain prescriptive lists of dos and don'ts for practitioners to follow. State licensing laws are designed to give boards wide latitude in making determinations whether a particular practitioner is practicing competently. A practitioner contemplating the use of an unapproved therapy will not be able to find in statute a definitive answer to the question of whether its use violates his or her state licensure law. In fact, a practitioner is not likely to find out if use of an unapproved product violates state licensure law until a board makes a determination after the treatment has been provided. For this reason, the Federation does not believe that the limitation in the bill indicating that a procedure must not violate licensing laws will be effective in preventing a practitioner from engaging in activities specifically authorized by this new legislation but not explicitly prohibited under a state licensure statute. Further, the protocol that must be followed by a practitioner who provides an unapproved therapy is inadequate and provides only illusory protection for the patient. The first element of this protocol is that the practitioner must determine that there is no reasonable basis to conclude that the treatment poses an unreasonable and significant risk of danger to a patient. This stands the Hippocratic Oath on its head. "First, do no harm" has been transformed to, "Do no harm that is unreasonable and poses a significant risk of danger." It will be very difficult for state licensure boards to accept this standard. Many boards will find it contradictory with standards they have developed over years of experience in dealing with both responsible and irresponsible practitioners. 2 The legislation also require that a practitioner who provides a treatment that involves a product not approved by FDA provide the patient with written notice of the product's lack of approval, the treatment's anticipated benefits, foreseeable side effects, and the results of past treatments. While this appears to be a fairly complete list of information that will allow a patient to make an informed decision, in most cases, the information will not be very useful and could be misleading. Information about the risks, benefits, contraindications, and side effects of treatments that have not been subjected to clinical studies is anecdotal possibly misleading and not reliable. As suggested at the outset, the concept of providing extensive information to a patient so that he or she can make an informed decision about therapy is laudable. Application of that concept to therapies for which there is little or no verifiable clinical data is useless in most cases and fraudulent in others. The Federation also believes that other provisions in the bill need significant revision. Many of the definitions are imprecise. For instance, the definition of a health care practitioner is someone "who is legally authorized to provide health services in the State in which the services are provided." In order to make it clear that an individual may only provide those health services for which he or she is licensed, the definition should reference licensure for a specific type of practitioner. Similarly, Section 8 of the bill requires that a health care practitioner who discovers that a treatment was a danger to the individual receiving such treatment must immediately report to the Secretary of HHS. Unfortunately, this section does not go on to require the practitioner to immediately cease using the treatment until further investigation or study about the treatment has been conducted. It appears that the practitioner's obligation is met by filing a report, despite the apparent danger of the treatment. In summary, the Federation of State Medical Boards is very concerned that S.1035 if enacted would interfere with state medical boards' ability to make appropriate decisions about the competency of physicians. Our member boards are constantly balancing the right of individuals to make informed choices about their health care and the boards' obligation to protect vulnerable people who may not be fully informed about the benefits and risks of different therapies from being exploited or harmed by licensees of the state. If S.1035 is enacted, the public will no longer be confident that licensure is an indication that the safety of the individual being treated by the licensees is of paramount importance. 3 CEL HEALTH CARE REFORM PROJECT COMPETITIVE ENTERPRISE INSTITUTE BREAKING THE FDA'S DRUG APPROVAL MONOPOLY IMPLICATIONS FOR TORT LAW AND CONSUMER WELFARE MICHAEL I. KRAUSS July 1996 ISSN#1085-9055 BREAKING THE FDA'S DRUG APPROVAL MONOPOLY IMPLICATIONS FOR TORT LAW AND CONSUMER WELFARE Michael I. Krauss EXECUTIVE SUMMARY The Food and Drug Administration's monopoly over approving new medical therapies is pre- mised on the idea that information markets fail. In fact, competitive forces produce information much more readily than is commonly believed through advertising, testing publications, and companies' reputations for quality. This holds important implications for FDA reform. The common law inspires confidence in information produced without the need for heavy- handed regulations. Tort and product-liability law can and do result in increased informational output from manufacturer to physician and consumer precisely in those instances where such output might otherwise be insufficient. The market failure argument supposes that private corporations have insufficient incentives to produce information, but that government incentives to inform consumers are somehow not distorted. But FDA is subject to its own set of perverse incentives. For the agency, the political consequences of mistakenly approving a bad drug or device are far worse than those of mistakenly delaying or disap- proving a needed therapy. As a result, FDA is inherently overcautious - an approach which serves its interests but not those of the public. The path to reform can be found in a gap in FDA's current monopoly. Under existing law, manufacturers may not market drugs or devices that have not received FDA approval. But if a drug or device is approved by the agency as safe and effective for one purpose, then doctors are free to pre- scribe it for other purposes as well. Despite its efforts to suppress these "off-label" uses, FDA has not stemmed the tide. Off-label prescriptions have proliferated despite tort law's implicit bias in favor of FDA-approved uses. A proposal by the Competitive Enterprise Institute suggests a way to preserve FDA's evaluative functions while expanding therapeutic choice. Under this proposal, FDA would function not as a veto agency, but as an evaluation agency. Rather than being banned across the board, unapproved therapies would be available under medical supervision and with clear warning of their unapproved status. That is, "off-label manufacturing" would be permitted, much as "off-label prescribing" is presently allowed. FDA would lose its veto power over new therapies, but it would continue to act as a state-funded evaluator of therapies. Manufacturers might still choose to seek FDA approval if that approval was sufficiently valued by the public and by physicians. Moreover, under this proposal FDA approval would confer a shield against design defect liability. But patients and their doctors would be free to go beyond the circle of government approved therapies. The arena of initial therapeutic evaluation would itself expand to encompass such private entities as testing laboratories and medical journals, so that FDA itself would be subject to competition in producing credible, and timely, evaluations of new drugs and devices. FDA's legal control over medicine has never been all-encompassing, but its exercise of that power has had deadly consequences. The "off-label" use gap in FDA's power has mitigated its poten- tially disastrous effects, and contains the kernel of a regulatory approach that would be far safer and more effective than our current system. BREAKING THE FDA'S DRUG APPROVAL MONOPOLY IMPLICATIONS FOR TORT LAW AND CONSUMER WELFARE by Michael I. Krauss¹ INTRODUCTION Origins and Characteristics of the FDA's "Certification Monopoly" In the 1970s, a configuration of geo-political factors resulted in a serious but temporary tightening of oil supplies. Several sets of sweeping federal fuel economy regulations were enacted. The institutionalization of this expanded federal mandate led to the production and sale of relatively dangerous and unattractive automobiles.² In a similar way, federal drug regulation has been driven by reactions to sensational occurrences. For ethical drugs as for cars, the belief that markets (tempered by common law) Federal drug can provide safe and effective products has been a notable casualty of federal regulation has regulation. been driven by The first statute regulating pharmaceutical products in the United reactions to States was the Pure Food and Drug Act of 1906,³ which established federal sensational offenses for adulteration and mislabeling of ingredients in food and drugs.⁴ The statute was apparently Congress' response to the "literary emergency" occurrences. generated by Upton Sinclair's The Jungle, a turn-of-the-century Soylent Green portraying a world in which all medicines were deleterious, all milk tainted and all sausages once human. Both before and after the 1906 bill's passage, non-narcotic drugs were as freely available as newspapers (as they remain in many countries today⁵). No government approval was required before drugs were manufactured or marketed, nor was a physician's prescrip- tion legally required (though doctors' advice was relied on by many, with prescriptions accounting for almost one third of all drugs consumed).⁶ Patent medicines of dubious effectiveness were available on the market in 1906. Amendments to the 1906 law in 1912 criminalized false and misleading claims of a medication's efficacy. It is worthwhile noting that, federal criminal law aside, even at this early stage of its development⁷ the common law already provided recourse to those injured by negligently mislabeled or poorly manufactured drugs.⁸ Economic analysis suggests that Krauss: Loosening the FDA's Drug Certification Monopoly Page 1 market forces will tend to provide correct incentives for manufacturers to design and produce safe drugs if tort remedies are available in such cases.⁹ Of course, tort law has little effect on insolvent tortfeasors, and in any case the national ruckus generated by The Jungle provided an impetus for federal officials anxious to be seen "doing something" about drug problems. Perhaps not surprisingly, criminal enforcement also presented difficulties (insolvent producers are often "fly-by-night" and hard to locate; criminal intent is more difficult to prove than tortious negligence; etc.). All of these factors curtailed enforcement of the 1906 Act 10 Federal drug regulation was of little consequence until a tragedy in 1937. In attempting to formulate a liquid form of sulfanilamide (a sulfa drug) one Samuel E. Massengill, a Tennessean doing business as the Massengill Company, marketed a syrup that employed diethylene glycol as its solvent. One hundred seven children died after ingesting this poisonous concoction.¹¹ Though Massengill was of course found liable in tort for his gross negli- gence, 12 the political temptation to provide additional "protection" to voters proved irresistible for the Roosevelt administration, which was enjoying the huge expansion of federal jurisdiction produced by the "switch in time that Federal drug saved nine. "13 The President signed the Food, Drug and Cosmetic Act of 1938, which for the first time required firms to submit New Drug Applica- regulation was of tions (NDA's) to the FDA before introducing pharmaceuticals into interstate little conse- commerce. Each NDA enumerated the proposed uses of a drug and demonstrated that tests "proved" it safe¹⁴ at recommended dosages. NDA's quence until a were approved after 60 days unless the FDA determined before that period tragedy in 1937. that they did not reveal sufficient safety testing. [The 1938 act contained another, seemingly innocuous, provision allowing discretionary exemptions from labelling requirements. This provision was subsequently interpreted by the FDA to greatly expand its authority (and physicians' income) by creating a category of "ethical drugs," that could henceforth be sold only by prescrip- tion. FDA safety evaluations obviously caused delays in the marketing of new drugs. But lag times were relatively short: by the end of the 1950's record levels of new drugs were being marketed with mean regulatory delays of seven months. The 1938 act is most renowned, however, for the delay it occasioned in the introduction of the German sedative Thalidomide in 1960. While an FDA reviewer investigated reports (published in Europe for years¹⁶) that Thalidomide caused peripheral nerve damage, news of a different side effect, deformities in the fetuses of pregnant users of the sedative, led to its withdrawal from markets worldwide in 1961. 17 The 1938 act had indirectly prevented any Thalidomide tragedies in the United States. Congress nonetheless sprang to action to dramatically expand federal powers. In 1962 a hastily drafted Food and Drug Act required that drugs henceforth be found safe and effective by the FDA before they could be marketed. 18 Whereas under the 1938 act NDAs were approved Page 2 Krauss: Loosening the FDA's Drug Certification Monopoly unless the FDA denied them, after 1962 disapproval was the default position: for an NDA to be approved the FDA must affirmatively conclude that a new drug is safe and effective. 19 While the 1938 bill allowed firms to test the safety of their own products (subject to documenting their tests for FDA review), after 1962 all human testing of new drugs had to be pre-cleared by the agency. The FDA acquired, additionally, the power to pre-approve all drug advertising and all labels, and set out "good manufacturing practices" regulations. As others have noted,²⁰ the combined effect of the 1938 and 1962 legislation was to fundamentally alter the nature of American pharmaceuti- cal production and distribution. Whereas the 1906 act had essentially sought to make markets work better through the prohibition of false claims and information,²¹ after 1962 the judgment about what was desirable or undesir- able was to be made by a central regulatory authority rather than by the choices of suppliers, physicians, and patients. As might be expected, one effect of the FDA's post-1962 "certifica- FDA safety tion monopoly" is a much more lengthy "drug lag." By 1967, average post- test review times for an NDA had increased from seven to thirty months. 22 evaluations Largely because of agency involvement in testing, total pre-authorization obviously caused development time for a new drug (which had averaged from 4 to 6 years before 1962) increased to over 16 years by 1990. 23 Only one out of 5,000 new delays in the drugs now completes this process successfully, at an average manufacturer's marketing of new cost of $200 million.²⁴ Economic theory leads to the prediction that these substantial increases in the cost of developing a drug for the US market affect drugs. both the number of new drugs developed (at the margin, otherwise market- able drugs will now be unprofitable ex ante to a manufacturer)²⁵ and the market price of developed drugs during what remains of their patent monopoly.²⁶ Both these forecasts have been amply documented in practice.² Also increasingly chronicled is the net cost in lost lives of not approving effective drugs quickly, as the following section relates. THE RATIONALE FOR THE FDA CERTIFICATION MONOPOLY: ANALYSIS AND CRITIQUE The 1938 and 1962 amendments came during "New Deal" and "Great Society" administrations, when confidence in government as an efficient provider and allocator of goods and services was high. General preference for government over markets is typically accounted for in "wel- fare economics" by the existence of "market failures." In the case of drugs, the lay version of the "market failure" argument is that the profit motive leads manufacturers to produce too many drugs too quickly, that these drugs would consequently either be poorly manufactured, 28 designed²⁹ or marketed,³⁰ and that consumers would suffer losses that could be avoided if manufacturers Krauss: Loosening the FDA's Drug Certification Monopoly Page 3 were forced through regulatory hoops. Several "consumer watchdog" groups embrace this market failure theory wholeheartedly. Dr. Sidney Wolfe of Public Citizen, for example, recently warned Congress not to privatize any FDA functions because drug manufacturers "mak[e] decisions based more on who fills their pocketbook than what is best for the public health."3¹ In economic theory, the "market failure" popularly attributed to pharmaceutical manufactures' profit motive is ascribed to "imperfect infor- mation." The theoretical argument goes roughly as follows: Private choice of goods and services maximizes global satisfaction only if consumers perfectly know what they want and flawlessly calculate whether products offered for sale will give them what they want. These conditions imply an elimination of all risk; A risk-free universe exists nowhere, of course, and is especially absent where disease is concerned. Consumers of drugs in fact have doubts both about what ails them and about the effects of proposed remedies for that ailment; By 1967, average Producers of a remedy can of course provide useful information on the latter subject to consumers, but (as statements like Dr. Wolfe's above post-test review indicate) informational asymmetry is held to encourage false or biased reports; times for an NDA Furthermore, information is a "public good:" once originated, it can be had increased reproduced or broadcast. Since others can copy costly-to-produce infor- mation, the argument goes, insufficient quantities of data about pharma- from seven to ceuticals are likely to be produced by the private market. Notably, it is thirty months. held to be unlikely that disinterested third parties would spring up to provide correct evaluations of a drug's safety and effectiveness; Thus, concludes the argument, government must fill the gap created by informational market failure. This government can do by testing and certifying drugs, and by requiring exceptional quality before authorizing drug marketing. There are many difficulties with the market failure rationale for a government drug certification monopoly. Some can be usefully sketched here: The market failure argument explains little because it explains too much. Virtually all consumer goods and services are purchased by buyers with incomplete information. How long will that pair of panty hose last, and will its chemical formulation provoke allergic reactions? Will this champagne bottle explode in my face, scarring me for life? Is the doctor operating on me this morning recovering from last night's party? Will the university I just applied to have an excellent reputation when I graduate four years from now? On all these issues, should I trust the information I receive from the not disinterested department store, bottler, surgeon or law school? Consumer information is never perfect, and ignorance (i.e., risk) therefore inevitably influences all choices relevant to our well-being. But few are confident enough in government's ability to discover and process information to argue for the replacement of market allocation and Page 4 Krauss: Loosening the FDA's Drug Certification Monopoly consumer choice by regulatory agencies merely because information is imperfect.³² The major premise of the market failure argument, that information is a "public good" underproduced by markets and therefore efficiently provided only by government, is flawed. Competitive forces privatize information much more readily than is commonly believed by welfare economists.33 Competitors with better products profit by pointing out imperfections in their rivals' merchandise. Testing publications from Consumer Reports to Car and Driver find markets for information, ranging from open evaluation to formal certification of products. 34 The value of these publications (and for that matter, the value of pharmaceu- tical manufacturers' products) derives from the reputation for quality they acquire. In fact the "good will" value of brand names, trademarks, and other intellectual property, which both product manufacturers and con- sumer publications ferociously protect,35 is largely a function of this reputational effect. Commercial activity (whether by automobile manu- facturers or drug producers) consists not of one-shot events but rather of a series of repeat dealings; only myopic producers generate false product The market information if it is likely that the misinformation will become known. Admittedly, fly-by-night operators by definition don't feel reputational risk: but that is precisely why the market values their products less than it failure argument does those of a Proctor & Gamble or a Merck. That is why the used car explains little sold through classified ads costs less than the same car sold by a reputable dealer. In the absence of any federal regulation, market prices for because it products already compensate ex ante for informational imperfections. explains too Of course, reputational markets are not perfect. Most notably, "agency problems" incite misbehavior. Managers may, for example, deceive drug much. Virtually (or car, or pantyhose, or surgery, or law school) "purchasers" because by all consumer the time the misinformation is discovered the manager will have comfort- ably retired, personally reaping the short term gain while the corporation goods and is left with the long-term pain. While agency problems do exist (in government³⁶ as well as in private industry), it is important to note that tort services are pur- and contract law create powerful incentives for private firms³ to monitor managerial behavior. The common law inspires confidence in informa- chased by buyers tion produced without the need for heavy-handed regulations. with incomplete For example, incorrect information dispensed by manufacturers typi- information. cally constitutes a "breach of express warrant," giving rise to strict liability suits by consumers injured as a consequence. Poor manufac- turing techniques, shoddy design work, inadequate warnings or careless preparation (whether by a too-hasty marketer of a drug with side-effects or by a partying surgeon) result in tort or products liability. This liability is designed to fully compensate wrongfully harmed victims, thereby forcing wrongdoers to internalize the cost of their misbehavior. Some believe that tort law undercompensates plaintiffs, while others feel that tort recovery is too generous. Depending on who is right, tort should be made more plaintiff- or defendant-friendly. But that is a question of tort law, not of government regulation.³⁹ If the amount manufacturers (or service providers) must pay injured parties in tort suits is greater than the long term gain they derive from deceiving their clientele (and such gain should not be easily assumed: reputational costs make it problematic, as seen above), information will be improved. This will occur precisely in cases where we want to modify the manufacturer's (or service provider's) behavior. 40 Tort and product liability law can and do result in increased Krauss: Loosening the FDA's Drug Certification Monopoly Page 5 informational output from manufacturer to consumer precisely in those instances where such output might otherwise be insufficient.⁴¹ The market failure argument supposes (incorrectly, as seen immediately above) that private corporations' incentives to produce information are insufficient. It also believes that government incentives to inform consumers arenot distorted. But this benign view of government has been challenged by political theorists ever since the Federalist Papers. Schol- ars who monitor civil servants know that "agency problems" are notori- ously likely to reduce bureaucrats' efficiency. 42 "Public Choice" analysis teaches that we should expect government agencies to be overcautious in approving new drugs. The loved ones of those who have died because a non-approved (or non-developed) drug they have never heard of might have saved them had it been developed and marketed are unlikely to protest to their elected representative. On the other hand, every crippled victim of a defective drug is visible to journalists and to politicians, lawyers and judges. Every new drug is therefore potentially another Thalidomide to bureaucrats. As Sam Kazman has written, "From the FDA commissioner to the bureau heads to the individual NDA reviewers, the message is clear: if you approve a drug with Drug lag's unanticipated side effects, both you and the agency will face the heat of newspaper headlines, television coverage and congressional hear- victims and their ings. On the other hand, if the FDA insists on more and more data from a manufacturer, and finally approves a drug which should have families will been on the market months or years before, there is no such price to pay. Drug lag's victims and their families will hardly be complain- hardly be ing, because they won't know what hit them They only know that there is nothing their doctors can do for them. From the standpoint complaining, of politics, they are invisible."44 because they As between what might be called "Type 1" certification error (a drug won't know what is approved that turns out to cause more harm than good) and "Type 2" hit them. certification error (a drug is not approved, but that drug would have caused more good than harm), the above analysis indicates that market forces (tempered by contract and tort remedies) tend to minimize the sum of these two errors: anything less would reduce profits. Government regulation, in contrast, is acutely sensitive to Type 1 error but relatively unfeeling to Type 2 error. In sum, Public Choice theory leads us to predict that government monopoly over drug certification would exacerbate, not solve, informational failure. Theory has been borne out by practice, as is revealed by recent illustrations of the informational failure resulting from the FDA's certifica- tion monopoly: The cardiopump is standard equipment in ambulances in many coun- tries. But it is not available in the United States. Initial tests in the US in 1992 showed that, though not universally effective, use of a cardiopump led to a survival rate 35% greater among unconscious heart attack victims. However the FDA ordered in 1993 that tests on the pump cease because unconscious patients could not give "informed consent" before the device was "tested" on them The cardiopump may help many people: one Page 6 Krauss: Loosening the FDA's Drug Certification Monopoly estimate is that up to 7,000 Americans could be saved each year through its use.45 We will never know who these "missing dead" are, of course. A 42-month delay in making Interleukin-2 available to patients with kidney cancer cost nearly one hundred unidentified deaths per month.⁴⁶ Delays in the approval of the emergency blood-clotting drug TPA are estimated to have resulted in more than 100,000 preventable heart-attack deaths.⁴⁷ The FDA took seven years before approving tacrine (or THA), which would have greatly improved (and in some cases saved⁴⁸) the lives of thousands of Alzheimers patients.4 Wyoming physician Michael Werner had the knowledge and wealth needed to visit Japan in 1993 for experimental treatment for his rare form of brain cancer. The treatment has not been approved by the FDA for use in the US. According to Dr. Werner, 120 patients with brain tumors like his had been treated in Japan with a 52% five-year survival ratio. In the US 90% of patients with Dr. Werner's disease die within twelve months; only 1% survive five years.5 FDA regulations require that the clinical studies needed to obtain Government approval of a new drug or medical device be "randomized" and "concur- rent;" i.e., new devices or drugs must be blind-tested against placebos or monopoly over FDA-approved products. This poses ethical problems if the new device or drug is so superior to existing technology that the "placebo" half of the drug certification "double-blind" cohort is virtually condemned to death. However, the would exacer- FDA tolerates this state of affairs and tends to intervene only when real victims are publicly identified. For example, the agency ordered hospitals bate, not solve, to stop using specialized baby ventilators (irreplaceable in saving very sick infants because they provide uniquely tiny breaths of air) because informational hospitals refused to "blind-test" them (and thereby condemn 50% of air- deprived "neonates"). Dr. Martin Kessler of Georgetown University failure. Medical Center estimates that scores of babies died as a result. Subse- quent to the FDA decision, protests from doctors who pointed to specific infant deaths were aired on the television show "20/20." Only then did the agency allow use of the ventilators.⁵¹ The pre-market approval process for new medical devices, required since 1976,52 averaged 840 days during the first six months of fiscal 1994 compared to 420 days in 1990. If manufacturers wish to improve devices already on the market before 1976, they must file a notification (or "510(k)") application with the agency.53 Although the FDA is legally obliged to rule on 510(k) applications within 90 days, in fact the average review time has increased from 98 days in 1990 to 213 days in 1994. 54 These expensive delays, obviously a product of the agency's zealous desire to control for Type 1 error, result at the margin in decisions not to introduce new or improved devices. These and other illustrations of FDA behavior⁵⁵ are not mere techni- cal failings that could be addressed through more careful oversight. 56 Rather, they are the inevitable result of the institutional incentives of public regula- tors. The more complete the government's monopoly, the more pernicious Krauss: Loosening the FDA's Drug Certification Monopoly Page 7 these results are. Fortunately, however, the FDA's monopoly has never been complete. THE GAP IN THE FDA'S CERTIFICATION MONOPOLY: OFF-LABEL PRESCRIPTIONS The FDA's certification monopoly for drugs and new devices has hastened the death of thousands of Americans. But, as seen in Section 1 above, the use of ethical drugs and devices in America pre-dates mandatory pre-certification rules. This chronology has left "gaps" in the FDA's certification monopoly: pockets of market-oriented behavior that have not yet been stifled by the agency. One important breach of the monopoly results from "off-label prescriptions." Physicians may not prescribe, nor may manufacturers market, drugs or devices that have not received FDA approval.57 Both doctors and pharmaceutical companies have been found "per se negligent" in tort if they defy the FDA's power in this area.⁵⁸ But if a drug or device is approved by the agency as safe and effective for a one purpose, no FDA regulations prevent doctors from prescribing the approved drug or device Fortunately, the for any other purpose. Thus, doctors, hospitals and researchers may discover FDA's monopoly that a drug approved, labeled and marketed for treatment of one kind of cancer is effective at treating other diseases. They write up these discoveries has never been in refereed medical journals and other publications. Physicians read or hear complete. about these other uses and then prescribe the drug for an "off-label" use. Under common law, an "off-label prescription" is not "per se" negligent. Tort law will, of course, sanction independently negligent prescriptions (if a doctor has misread the journal literature, if he has neglected to prescribe the correct dose, etc.). The FDA has had mixed success in its sporadic efforts to suppress off-label prescriptions. 60 In 1979 the agency attempted to prevent a physician from prescribing a drug that had been approved as a medication for lead poisoning for a patient with arteriosclerosis. The Fifth Circuit Court of Appeals rejected the FDA's claim that the physician had "misbranded" (falsely claimed that the agency had approved the proposed use of) the drug by prescribing it or by advertising the new therapy.61 FDA power has been more successfully invoked against manufacturers, however. Pharmaceutical companies routinely publicized (to doctors and to the general public) the results of new research on their already-approved drugs, thereby alerting physicians (the vast majority of whom do not subscribe to, say, the New England Journal of Medicine) to new ways to help their patients. In 1991 FDA Commissioner Kessler successfully cracked down on this "misbrand- ing."⁶² Page 8 Krauss: Loosening the FDA's Drug Certification Monopoly These efforts to extend the FDA's certification monopoly to off-label prescriptions have cost lives and money, in several ways. For example, many insurers, following Medicare's lead, 63 deny or limit drug cost reimbursement for off-label use. Nearly 25% of oncologists surveyed by the Government Accounting Office in 1991 reported varying from their preferred treatment because of anticipated denial of Medicare reimbursement.64 But because Medicare reimbursement for costly hospital stays is fixed, hospitalization is used to work around the out-patient system. Five of every eight surveyed oncologists admitted patients to hospitals solely to ensure reimbursement for drug therapy that would be denied to an out-patient. 65 However, case law has limited state governments' (and, to a much lesser degree, private) health insurers' discretion to rely exclusively on FDA approved use in determining coverage, however.66 More direct illustrations of health risks created by the FDA's crack- down on manufacturers' "misbranding" include one case involving an "over- the-counter" drug. Influential studies suggest that the risk of heart attacks for males over 50 is cut in half by taking one aspirin every other day. According to a 1988 article in the New England Journal of Medicine, Widespread widespread publicity of the aspirin treatment could save from 10,000 to 100,000 American lives each year.⁶⁷ Yet the FDA has prohibited aspirin publicity of the manufacturers from distributing such notices, and since aspirin is no longer aspirin treatment patented no company has the incentive to spend the millions of dollars for clinical trials and other tests necessary to lead the agency to authorize could save from publicity for this "new use."68 Even when drug patents are effective, unless 10,000 to a manufacturer is willing to submit an NDA supplement for an unapproved use it has little incentive to generate information on its safety and effective- 100,000 Ameri- ness. Nor may manufacturers even distribute reprints of peer-reviewed can lives each journals or textbooks in which off-label uses are documented, even though drug producers are an efficient clearing house for such material.⁶⁹ year. Yet the FDA has prohibited Despite its efforts, the FDA has not stemmed the tide of off-label prescriptions. According to one officer of the American Medical Associa- this. tion, off-label uses may presently account for 60 percent of all prescription drug use today.⁷⁰ A recent study by the Government Accounting Office found off-label prescribing to be the rule for many types of therapy.⁷¹ Common law suits recognize this common practice, and there is no require- ment that physicians inform patients that they are prescribing a medication for a non-FDA-approved use.⁷² It is interesting to note that off-label prescriptions have proliferated despite tort law's implicit bias in favor of FDA-approved uses. A physician has a qualified tort immunity in that he is never negligent merely for prescribing a drug for a purpose approved by the FDA (though he still must transmit appropriate warnings, check for possible drug allergies, etc.). 73 If, on the other hand, a doctor prescribes an drug "off-label," there is no such immunity.74 Common-law negligence principles apply; i.e., a doctor will be Krauss: Loosening the FDA's Drug Certification Monopoly Page 9 liable to an injured patient if the current state of research or customary medical practice impugn the off-label use.⁷⁵ Obviously, many more would die (and the clamor about FDA- induced "drug lag" would be more intense) if off-label prescriptions were suppressed. In an important sense, the medical profession has reduced public pressure on the FDA by privately performing research and issuing recom- mendations that manufacturers find too costly due to agency regulations. Just as obviously, private research and recommendations only deal with already-approved drugs and devices, for despite the gap in the agency's certification monopoly the FDA retains legal control over the approval of a drug or device for its "first" approved use. The proliferation of beneficial off- label prescriptions demonstrates the illogical character of this monopoly, though: why should FDA approval be a sine qua non to "first use" when, once approved, the drug can be put to any number of other non-approved uses, A recommenda- subject only to the general rules of tort liability? tion initially The intolerable features of the status quo make it worthwhile to formulated by the elaborate on a recommendation initially formulated by the Competitive Competitive Enterprise Institute. 76 This proposal, properly developed, could preserve all FDA evaluative functions while saving hundreds of thousands of lives. It Enterprise consists of terminating the FDA's unsound "first use" monopoly by permit- Institute could ting "off-label manufacturing," much as "off-label prescribing" is presently allowed. This proposal would resolve asymmetries of incentives and result preserve all FDA in consideration of both "Type 1" and "Type 2" certification errors. The evaluative proposal is clarified and defended in the remainder of this paper. functions while LOOSENING THE CERTIFICATION MONOPOLY: saving hundreds FROM OFF-LABEL PRESCRIPTION of thousands of TO "OFF-LABEL MANUFACTURING" lives. To recap this paper's findings: FDA authority has expanded piecemeal in reaction to scattered occur- rences. The result of this expansion is that the agency has metamorphosed from a guardian against consumer fraud to a prime determinant of the production of ethical drugs and medical devices; The FDA's present role cannot be justified by economic or political theory. The agency's skewed informational incentives, which contrast with those of manufacturers and physicians, have had the effect of aggravating illnesses and accelerating deaths; The FDA has attempted to suppress what remains of the private selection of ethical drug use. Despite all its efforts, a significant proportion of medications are used in non-FDA-approved ways. If private defiance of FDA hegemony had not been allowed, the perverse effects of the agency's disincentives would have been far more severe. Page 10 Krauss: Loosening the FDA's Drug Certification Monopoly What measures can be taken to reconcile economic and political theory with FDA practice? The outright abolition of the agency, or even its reinstatement as a "consumer protection" department devoted to policing and prosecuting fraudulent claims about drugs, are likely nonviable solu- tions. A significant segment of the public is probably convinced that the agency should retain a role in the ex ante evaluation of drug safety and efficacy. On the other hand, the phenomenon of off-label prescriptions demonstrates that the FDA has never exercised hegemony over the therapeu- tic use of medication; practitioners (controlled by common-law tort, not by federal regulation) do "end-runs" around the FDA with quite desirable effects. Once this is grasped, it becomes apparent that the FDA's social function would not change if practitioners could recommend non-approved drugs as easily as they can now recommend non-approved uses of drugs. Just as any doctor may today legally write "off-label" prescriptions of drugs In at least two or devices, it could be lawful to manufacture drugs and devices "off-label." areas this plan The FDA would, under this proposal, remain accessible as a state-funded monitor of safety and efficacy. enhances the value of FDA Note that this proposal does not create a windfall gain for manufac- turers of dangerous drugs. By analogy to physicians writing "off-label certification. prescriptions," manufacturers producing "off-label drugs" would not benefit from tort immunity. 77 They would be liable for design defects in these drugs, while (as is the case for "on-label" prescriptions today) producers of FDA- approved drugs would be immune to design defect liability.⁷⁸ All producers of drugs would of course still be liable for manufacturing defects and failures to warn⁷⁹ (e.g., if a batch of the drug is contaminated, or if a label incorrectly indicates the appropriate dosage, etc.) just as physicians are liable for negligently mis/prescribing approved drugs under current law. But liability for design defect⁸⁰ (marketing a drug that should never have been put on the market) would be precluded only if the FDA has approved a drug. This is not, therefore, a revolutionary proposal to sterilize the FDA. In fact, in at least two areas this plan enhances the value of FDA certification. As just stated, it provides "on-label" manufacturers with a "design defect shield" they presently lack, courtesy of agency approval.81 Second, while physicians are presently not compelled by statute or common law to inform patients that they are writing "off-label" prescriptions,⁸² this proposal would assuage nervous consumers and increase FDA visibility by requiring doctors to obtain "informed consent" from patients if an ethical drug they recom- mend is not approved by the agency. What effect would this modification of the FDA's authority have on the allocation and distribution of ethical drugs? The remainder of this paper will explore this question Socratically, by answering a series of hypothetical Krauss: Loosening the FDA's Drug Certification Monopoly Page 11 criticisms dealing with the interface between tort liability and drug produc- tion and use decisions. Critique #1: "Without an FDA right to reject market decisions to commence production of a drug, manufacturers would massively produce "snake-oil" cures harming millions." Readers who have followed the analysis in this paper will hopefully recognize that this critique is unfounded. Manufacturers interested in maintaining a presence in the market and in enhancing their brand image will not market "snake oil." Excellent quality automobiles, croissants and knives are produced despite the absence of mandatory pre-market govern- ment approval, even though defective versions of any these products are extremely detrimental to our health. In rebuttal, it might be contended that government pre-approval of drugs The label "FDA is more prized by the public than pre-certification of the neighborhood baker or cutler. This argument fails to recognize that all certifications tend inspected and to become valuable over time. It may well be the FDA's structural obsession with avoiding Type 1 headlines that instills misplaced public approved," if confidence.⁸³ If the public retains this confidence, manufacturers will make the investment needed to obtain FDA approval, which they could truly esteemed by then recoup by exacting a premium in the marketplace. Over time, market the public, would valuation of FDA approval would stabilize (formally stated, a demand function for the agency's services would emerge). The label "FDA add more than inspected and approved," if truly esteemed by the public, would add more than enough value to a drug or device to ensure the agency's survival even enough value to a in the absence of a statutory monopoly. The government could then engage in informed cost-benefit analysis of the FDA's policies, including drug or device to its fixation with Type 1 errors. ensure the Critique #2: "Without mandatory FDA approval, manufacturers would agency's survival refuse to produce most drugs or devices because of their fear of product even in the liability." absence of a Both economic theory and present-day practice tell us that this is not so. Manufacturers produce motorcycles and ladders despite the absence of statutory pre-market government approval. They are held liable when their product monopoly. is defectively designed.⁸⁴ Conversely, FDA approval does not presently immunize manufacturers of pharmaceuticals (as distinguished from Class III medical devices from product liability.86 This proposal's proposed immunization of manufacturers (against design defect liability only) for FDA-approved drugs might therefore increase the availability of ethical drugs.⁸⁷ At the very least, it is clear that the elimination of the agency's certification monopoly would not remove ethical drugs from the market. It was observed above that manufacturers now decline to develop certain drugs because pre-approval expenses render such development unprofit- able. If Critique #2 is to be accepted, this would imply that manufacturers will refuse to produce drugs with or without agency oversight. This is a non sequitur. It is clear that the elimination of the agency's certification monopoly would not remove ethical drugs from the market. Page 12 Krauss: Loosening the FDA's Drug Certification Monopoly Critique #3: "Doctors would never prescribe non-FDA approved drugs or devices, for fear of malpractice liability." The prevailing "gap" in the FDA's certification monopoly dulls this criticism. Fear of malpractice liability has not precluded off-label prescriptions, despite the loss of tort protection that derives from FDA use approval. Doctors are clearly willing to be held to common law negli- gence standards⁸⁸ when prescribing drugs for off-label uses. They would arguably agree to be held to the same standards when prescribing off-label drugs. Indeed, common law tort has evolved to the point that a physician's decision not to prescribe a drug for a widely accredited "off-label" use could well constitute malpractice. In this way again has the private sector mitigated the effects of the FDA's disdain for "Type 2" error. Legislation permitting prescription of off-label drugs would further palliate this problem. One might wonder how doctors would learn of "off-label manufactured drugs." After all, off-label uses of FDA-approved drugs are presently Doctors are described in medical journals, which can be admitted into evidence at a malpractice trial; how would "off-label drugs" be introduced? The clearly willing to procedure would likely be very similar. Journals and other producers of knowledge about the safety (and efficacy) of drugs would find it in their be held to interest to produce information on manufacturers' products. The same common law reputational pressures that encourage the New England Journal of Medi- cine to refrain from publishing unscientific drivel on new uses will negligence promote accuracy on the part of private reviewers of new drugs.⁸⁹ Note that these new drugs would likely fill very urgent medical needs; the standards when relative tort protection of FDA certification means that physicians would likely need good reasons⁹⁰ for utilizing non-FDA approved drugs or prescribing drugs devices if there exist FDA-certified alternative treatments. for off-label uses. It is important to see that agencies already provide informational services in fields where government has not snatched a legal monopoly. They would Private firms regularly evaluate and certify design and production param- arguably agree to eters (or "standards"⁹") for goods and services as diverse as bricks and law schools. Reliance on these evaluations and certifications, even when they be held to the lack mandatory legal authority,⁹² is an important element of malpractice defense for (in the above examples) architects and guidance counsellors. same standards Unlike government agencies like the FDA, private firms cannot be politically constrained to accredit (or to refuse to accredit) new products when prescribing or designs.93 But (also unlike government agencies) if a sufficient number of knowledgeable parties belittle a certifying agency's inefficiency or off-label drugs. corruption the creation of a rival agency is permissible.94 Competing agencies exist in many fields,95 some of them well known to physicians.⁹⁶ Critique #4: "Private firms will not be willing to certify drugs and devices, because (unlike the FDA)⁹⁷ they will be liable for the unexpected side effects of drugs they have 'approved'." This is another baseless critique. It begs two important questions: - As regards reasonably foreseeableside effects (for example, Thalido- mide-type side effects that were clearly discernable through testing), the critique impliedly assumes that such calamities will occur frequently as a result of private drug certification; i.e., that market incentives will not lead Krauss: Loosening the FDA's Drug Certification Monopoly Page 13 private certifying agencies to discover and prevent drug tragedies. The burden of much of this paper has been to challenge that assumption. Markets (supplemented by tort law) do provide strong incentives for certifying agencies to do their jobs well; - As regards unknowable future side effects, it is not clear why a non- negligent certifier should be liable for results it could not have reasonably prevented. Manufacturers of ethical drugs are most certainly not liable for such side effects today,⁹⁸ and there is no reason why a certifying agency would assume presently non-existent liability in their place.99 More fundamentally, this paper's critique of the "informational market failure" argument emphasizes that profits can be earned from certification even if there is a risk of liability. Some firms (like Underwriters' Laboratories) charge manufacturers directly for their services. Others (like Consumers Union, publisher of Consumer Reports) earn money solely from the public sale of evaluative information. Both types of companies devote considerable resources to protecting their intellectual property, which of course enables them to privatize the information they produce. 100 Still other companies (like Hearst, publisher of Good House- keeping, whose "Seal of Approval" is affixed to products) earn money from subscribers (purchasers of their evaluative information) and from manufacturers. Although payment of fees might blur the distinction The UL model between publicity and certification, both protection of trademark value has particular and tort liability¹⁰¹ furnish incentives to accurately assess products. relevance for the It seems likely that insurance companies would have a comparative advantage in competing as quality certifiers. Liability insurance compa- ethical drug nies already have a vital incentive to accurately evaluate products whose quality is likely to affect their exposure. One of America's most venerable industry under private certifiers, Underwriters' Laboratories, is in fact a cooperative venture of insurance companies that presumably lower total risk (thereby this proposal. increasing their profit)¹⁰ by assuring that only certified products are produced or used by their clients. Since UL certification incurs the venture's liability to consumers injured by a defectively designed product that never should have been certified,¹⁰³ and since insurance companies are typically vent, UL accreditation can be seen as a kind of surety bond paid for by manufacturers, assuring purchasers¹⁰⁴ that a product design is effective. 105 The UL model has particular relevance for the ethical drug industry under this proposal. Drug manufacturers could offer to "hold harmless" (i.e., to indemnify, as if they had issued a surety bond to) any physician found liable for prescribing a (non-government-approved) drug they produced, just as, analogously, Ford Motor Company contractually holds harmless independent dealers for liability they incur as a result of selling a defective new (non-government-approved) Ford. In both cases, of course, manufacturers either self-insure or purchase their own insurance against concomitant risks. 106 Drug manufacturers deciding to forego FDA certification could, by risking their capital ("self-insurance") or by pur- chasing liability insurance, produce quality guarantees for products in which they already have an interest and an expertise. Poor certification practices for ethical drugs would obviously directly cut into the profits of these "insurers," who in fact are serving as a bond for the quality of their pharmaceuticals. Good certification practices, accomplished through the establishment of reputable independent agencies (such as Underwriters' Laboratories), maximize insurers' and manufacturers' profits. Both tort Page 14 Krauss: Loosening the FDA's Drug Certification Monopoly liability and self-interested monitoring by insurers will hold cooperative certifying agencies in check. CONCLUSION The FDA's legal control over medicine has never been all-encom- passing. What monopoly the agency does possess was acquired episodically and accidentally. The agency's power over drug certification is not justified by economic or political realities, and its exercise has had deadly conse- quences. However, a gap in the FDA's power, resulting from the ad hoc process through which its jurisdiction was granted, has mitigated its poten- tially disastrous effects. This current process itself contains the kernel of a safer and more effective drug regulation policy. This paper argues that the FDA's authority should be modified by allowing doctors to prescribe non-approved drugs and devices just as they Since this today promote non-approved uses. Indeed, the FDA itself has recently proposal in no presented a (very diluted) version of this proposal¹⁰ in an effort to calm hostile critics on both sides of the aisle¹⁰⁸ in Congress. way eliminates the FDA, Although the relaxation of the agency's monopoly that this paper proposes would not substantially alter the FDA's everyday work, it would consumers who have far-reaching and beneficial effects. It might well lead to the establish- remain troubled ment of a drug certification industry likely be composed of different types of competitive firms, as is the case in other fields. Non-profits (like Consumers by non-FDA- Union), for-profits (like Hearst Publications) and insurers' cooperatives (like approved Underwriters' Laboratories) could be expected to enter the drug certification industry. To compete successfully, these firms would have to convince products will be producers, consumers and doctors that their evaluation process is of high able to insist on quality. Physicians and manufacturers would not decline to make and use privately certified products under these new ground rules, while risks of FDA certifica- liability will be transferred (via insurance and bonding mechanisms) to tion. efficient risk bearers. Of course, no private evaluation industry will be viable if consumers balk at non-FDA certified drugs. Since this proposal in no way eliminates the agency, consumers who remain troubled by non-FDA-approved products will be able to insist on FDA certification. If consumers remain unconvinced that the market has provided efficient substitutes for the agency, drug manufacturers will continue to submit their products to the FDA for pre- market approval. On the other hand, if the FDA becomes perceived as an inefficient agency focused exclusively on the elimination of Type 1 testing errors (at the cost of an inefficiently high number of Type 2 errors), the agency's "market share" of certifications will decline. Sick people will increasingly opt to consume privately certified ethical drugs. If this happens, an FDA that wishes to prosper sans certification monopoly can be expected to put patients' best interests at heart by balancing Type 1 and Type 2 errors Krauss: Loosening the FDA's Drug Certification Monopoly Page 15 instead of responding to bureaucratic pressures at the cost of thousands of lives. At that point consumers will finally benefit from an FDA which will put their interests first. ABOUT THE AUTHOR Michael I. Krauss is a professor of law at George Mason University School of Law in Arlington, Virginia. He is a graduate of Carleton University, and received his degrees in law from the Université de Sherbrooke and Yale University. He has published numerous law review articles on issues of tort law, market processes and comparative law. His writings have also appeared in publications ranging from the Wall Street Journal to Reason magazine and Policy Review. In 1994 he received George Mason University's first "Teacher of the Year" award for excellence in teaching. A slightly different version of this monograph will shortly be published in the George Mason University Law Review. Page 16 Krauss: Loosening the FDA's Drug Certification Monopoly END NOTES 1 Professor of Law, George Mason University, 3401 North Fairfax Drive, Arlington, Virginia USA 22201. Internet: [email protected]. Assistance from the Law and Economics Center of George Mason University and from the Competitive Enterprise Institute is gratefully acknowledged. Thanks to Richard Jacobus and to Sam Kazman for their useful comments, and to Kenneth Rossman for valuable research assistance. Any remaining errors are, of course, solely the author's responsibility. ²See Competitive Enterprise Institute V. NHTSA, 956 F.2d 321 (D.C. Cir. 1992) (holding NHTSA must consider reduced safety effects when determining fuel efficiency standards). See also Crandall & J.D. Graham, "The Effect of Fuel Economy Standards on Automobile Safety," 32J. L. & Econ. 97 (1989). ³Federal Food and Drugs Act of 1906, ch. 3915, 34 Stat. 768. 4See Peter Temin, Taking Your Medicine: Drug Regulation in the United States, Harvard U. Press, 1980, for a good history of drug regulation. ⁵See S. Peltzman, The Health Effects of Mandatory Prescriptions, 30 J.L. & Econ. 207 (1987). ⁶Federal regulations did not determine which drugs would be controlled by the prescription process until 1951. Humphrey-Durham Act, ch. 578, 65 Stat. 648 (1951). In fact, until that time drug manufacturers decided on their own how to label and sell their drugs, subject to state laws. See DeFreese V. United States, 270 F.2d 730 (5th Cir. 1959), cert. denied, 362 U.S. 944 (1960). 7 Notably, the requirement of privity for successful products liability lawsuits was in the process of being relaxed at this time. See, e.g., Macpherson v. Buick, 111 N.E. 1050 (1916). ⁸See, e.g., Thomas V. Winchester, 6N.Y. 397 (1906) (liability for manufacturer of incorrectly labelled drug, even if no privity is involved); Osborne v. McMasters (1906) (liability of druggist for mislabeling a poisonous drug); Macpherson V. Buick, 111 N.E., 1050 (1916) (liability for manufacturer of misrepre- sented vehicle). Contrary to popular belief, even early products liability law didn't preclude recovery from a defendant manufacturer whose misrepresented product caused injury. ⁹See M. Polinsky, An Introduction to Law and Economics, 1983, ch. 4. Assume, for example, that one million "units" (of an ethical drug) currently sell for $5 each, but that for $1 per unit more the manufacturer could add a safety device that would reduce total consumer injuries by two million dollars (for instance, manufacturers could substitute a hypo-allergenic substance for an ingredient that randomly affects a very tiny number of users). Assume that if the drug is not improved consumers cannot cheaply avoid these injuries at any cost less than five million dollars (because, say, no consumer knows whether they are allergic to the substance). The drug manufacturer should realize that it can maximize profits by choosing this new ingredient and selling the improved drug at a price above $6. If the manufacturer fails to realize this, tort law will "help" it figure this out. When sued by a consumer who suffers an allergic reaction to the non-improved drug, the manufacturer will be found to have marketed a negligently designed drug (under comment k, §402A, Restatement on Torts (2nd)), since it could have improved the drug for less ($1 million) than the damages the unimproved drug caused ($2 million). Internalizing these damages, the firm will realize that it is cheaper for it to add the safety device to the drug. ¹⁰Drug regulation was originally the responsibility of the Bureau of Chemistry in the Department of Agriculture. See Federal Food and Drugs Act of 1906, ch. 3915, 34 Stat. 768. The Bureau became the Food, Drug and Insecticide Administration in 1927. That name was shortened to the Food and Drug Administration in 1930. McNary-Mapes Amendment, ch. 874, 46 Stat. 1019 (1930). "The syrup had already been marketed in pill form, and Mr. Massengill decided to produce it as a syrup by liquefying it with diethylene glycol. For further discussion of the relationship between the Elixir Sulfanilamide tragedy and the 1938 Act, see David F. Cavers, Food, Drug and Cosmetic Act of 1938: Its Legislative History and Its Substantive Provisions, 6 Law & Contemp. Probs. 2. Krauss: Loosening the FDA's Drug Certification Monopoly Page 17 ¹²Tort liability was rendered difficult by the fact that Mr. Massengill apparently owned assets only in Tennessee, which had a very short statute of limitations for wrongful death suits. Ultimately, Massengill was found liable under Tennessee law by applying the statutes of limitations of the states where the injury occurred. See, e.g., Wilson V. Massengill, 124 F.2d 666 (C.C.A.6 (Tenn.), Jan. 9, 1942, cert. denied, Massengill v. Wilson, 316 U.S. 686. In addition, Massengill was fined $26,100 under the 1906 Act for misbranding violations under the 1906 Act. ¹³The phrase refers to Justice Roberts' vote in West Coast Hotel v. Parrish, 300 U.S. 379 (1937), reversing a series of cases which held unconstitutional various components of "New Deal" legislation. These cases displeased President Roosevelt, prompting his threat to increase the number of Supreme Court Justices until he obtained a majority which would validate to his platform. See The Oxford Dictionary of American Legal Quotations 393 (Fred R. Shapiro ed., 1993); Gerald Gunther, Constitutional Law 457 (12th ed., 1991). No one is certain who authored the phrase. See Michael Ariens, A Thrice-Told Tale, or Felix the Cat, 107 Harv. L. Rev. 620, 623 n.11 (1994). ¹⁴It is important to note that the safety of a new drug had to be established. The effectiveness of the drug was not the FDA's concern, however. Presumably, market forces were still relied on to distinguish effective from ineffective medications. ¹⁵See Temin, supra note 4, pp. 46-51; Peltzman, supra note 5. ¹⁶Chemie Grünenthal, the producer of Thalidomide, had been alerted to the drug's neurological hazards by many European physicians. But the firm, in a move that did not serve its long-term commercial interests, constantly dissimulated the problem. W. S. Ross, The Life/Death Ratio 22 (1977) ¹⁷It should be noted that there is no reason to believe that the FDA ever suspected that Thalidomide had any teratogenic effect. The delay in US approval for the drug was entirely due to the above-mentioned adverse neurological reactions, whose theoretical link to birth deformities is still unclear. See Ross, supra note 16, at 39. ¹⁸For a summary of the modifications to Food and Drug law in 1962, see H. Grabowski and J. Vernon, The Regulation of Pharmaceuticals, American Enterprise Institute, 1983, p. 2-4. ¹⁹The agency was required to render decisions within 180 days, but no sanctions were provided for longer deliberation time. See Pub. L. 87-781, Title I, Part A, 76 Stat. 781-83, 784, 785 (codified in relevant part at 21 U.S.C. § 355(c)). 20Grabowski and Vernon, supra note 18, p. 5. ²¹In other words, the 1906 bill recognized the primacy of the market in the production and distribution of medicines, and saw a purely informational role for government. Of course, it is not clear that government is even efficient in evaluating information accurately. See on this point M. Krauss, "Regulation V. Markets in the Development of Standards," 3 S. Cal. Interdisciplinary L. J. 781 (1994) ²²S. Peltzman, Regulation of Pharmaceutical Innovation, American Enterprise Institute, 1974, p. 18. ²³Grabowski, supra note 18, p. 30; K. Kaitin, Written Testimony Before House Subcommittee on oversight and Investigations, Tufts Center for the Study of Drug Development, May 25, 1995. The process for new drug approval begins with preclinical testing of a compound in a laboratory and on animals. This stage takes on average 3.5 years to satisfy the FDA. If successful, researchers then file an IDA (Investigational New Drug Application) with the agency. This requires a three-stage clinical testing procedure on human subjects, monitored constantly by the agency: Phase 1 determines safety and dosage on a small group of volunteers, over about one year. Phase 2 measures the effectiveness of the drug on hundreds of volunteers, over about two years. Phase 3 confirms the efficacy of the drug in double-blind tests involving hundreds if not thousands of volunteers and control groups, lasting on average three years. See 21 C.F.R. $312.21 ²⁴San Francisco Chronicle, Oct.26, 1992, p. A1. 25The pharmaceutical industry introduced an average of more than three times as many drugs (54 to 16) before Page 18 Krauss: Loosening the FDA's Drug Certification Monopoly 1962 as after. See H. Grabowski, "The Prescription for High Drug Prices: Factors Contributing to Rising Prescription Drug Prices," (December 1992) Consumers' Research 10. 26If fewer drugs are available, lessened competition will increase prices. ²⁷See K. Kaitin et al., "The drug lag: An update of new drug introductions in the United States and in the United Kingdom, 1977-87," 46-2 Clinical Pharmacology & Therapeutics 121 (1989). ²⁸For example, using poor sterilization processes. ²⁹For example, with insufficient care given to allergic or other abreactions, or to drug interaction effects. ³⁰For example, firms might exaggerate a drug's therapeutic effects, or not draft labels that would alert users to abreactions or optimal dosage. 31 FDA to leave firms to devices," Washington Times, 4-7-95, p. A6. ³²Some readers might have the following reaction to the above examples: "Yes, we almost always have incomplete information, but in the case of ethical drugs imperfect information is especially severe, and its consequences can be especially bad." Later in this paper I try to show that government monopoly over drug certification is, neither in theory nor in practice, the best way to combat this informational problem. At this point my modest claim is that informational problems are endemic to daily life in a free society. ³³See M. Krauss, "Property, Monopoly, and Intellectual Rights," 12 Hamline L. Rev. 305 (1989) for an in- depth discussion of this point. See also Krauss, supra note 21. The privatization of information will not be possible, of course, if legislation prevents it (say, by denying copyright or patent protection to information producers). 34 The burgeoning growth of private on-line information systems (e.g., America Online, LEXIS-NEXIS, etc.) and the anticipated streamlining of Internet services will likely make the diffusion of such information much less costly. Once dangerous side effects emerge in users of a particular product, the "Net" may allow extremely rapid dissemination of this information. Arguably, news of Thalidomide's neurological side-effects would become much more difficult to hide today. ³⁵See infra, note 100. 36 Janet Novack has repeatedly detailed FDA corruption scandals in articles written for Forbes magazine. See, e.g., Oct. 16, 19989, p. 10; April 29, 1991, p. 34. ³⁷Unfortunately, tort law provides less incentive to monitor negligent government workers, since their managers (unlike corporate owners) have no direct ownership claims which allow them to directly profit from good monitoring. Tort law's inability to adequately motivate government officials is a contempo- rary justification for sovereign immunity (excluding tort liability to limit drains on tax dollars). ³⁸See, e.g., Seely V. White Motor Co. 63 Cal.2d 9 (1965) (Privity between consumer and manufacturer is not required for manufacturer to be sued for breach of express warranty.) 39 See M. Krauss, "Tort Law and Private Ordering", 53 St. Louis U. L. J. 423 (1992). 40If it would have cost moree ante to modify the manufacturer's behavior than would be saved through such a change, then of course the modification is not socially beneficial. See R. Coase, "The Problem of Social Cost," 3 J. of L. & Econ. 1 (1960), and supra note 9. 41 Again, a strong argument can be made that the consumer is presently paying for more information than she wants because tort law is skewed to over-compensating victims. Any reader who has seen the labels on new ladders will understand this point. 42 "Public Choice" vision of government and bureaucracy largely based on these agency problems garnered a Nobel prize for one of my George Mason colleagues. See J. Buchanan, with G. Tullock, The Calculus of Consent, 1961. ⁴³During the Thalidomide episode the regulatory authority and one of its employees was praised by both the President and Congress for the purely negative action of delaying (not disapproving) endorsement of Thalidomide. The employee and the FDA had never been praised forapproving a drug, or for expediting approval or, in fact, for any positive decision. Krauss: Loosening the FDA's Drug Certification Monopoly Page 19 ⁴⁴See S. Kazman, "Deadly Overcaution: FDA's Drug Approval Process," 1J. of Regulation & Social Costs 35 (1990), 41. ⁴⁵See, "Feel a Heart Attack Coming? Go to France," Wall Street Journal, August 2, 1994, p. A14. In April, 1995 the Journal of the American Medical Association published a study questioning the claimed superior efficacy of the cardiopump: see Schwab et al., "A Randomized Clinical Trial of Active Compression-Decompression CPR V. Standard CPR in Out-of-Hospital Cardiac Arrests in Two Cities," JAMA 1995: 273:1261-1268. However neither this nor any other study has found any added risk from cardiopumps, and the article underlined the need for further research, which hospitals would presumably be free to conduct were it not for the FDA prohibition. An editorial in the same issue of the AMAJournal expressed "astonish and dismay at the FDA's policy on research of emergency devices. A 1993 Congressional report, "Less than the Sum of its Parts," found that 26 US-made life-sustaining cardiovascular products were not available in this country, but have been approved and are in widespread use overseas. Less Than the Sum of its Parts: Reforms Needed in the Organization, management, and Resources of the Food and Drug Administrations Center for Devices and Radiological Health (Comm. Print 103-N) 103d Cong., 1st Sess. (1993). Competitive Enterprise Institute, "Consumer Advocacy Group Attacks FDA For Slow Approval of Cancer Treatment" (press release, May 14, 1992). 47 Investor's Business Daily, May 3, 1994, p.1. 48 An Alzheimers patient whose symptoms are controlled is less likely to wander off from home, etc. 49 Baltimore Sun, May 10, 1994, p. 1. Dr. Went to Japan for Treatment He Couldn't Receive in America," Minneapolis Star Tribune, June 26, 1994, p. 12A. ⁵¹See 20/20, August 12, 1994, transcript, p. 7. ⁵²See Medical Device Amendments to the Food and Drug Act, 21 USC § 360 et seq. (90 U.S. Stat. 539). ⁵³Referring to section 510(k) of the Act. ⁵⁴Testimony of Mr. Robert O'Holla, Vice-President for Regulatory Affairs, Johnson & Johnson. Medical Device User Fee Act of 1994: Hearings on H.R. 4728 Before the Subcomm. on Health and the Environment of the House of Representatives Committee on Energy and Commerce, 103d Congress, 2d Session (1994). ⁵⁵See, for other examples, J. DiMasiet al., "New Drug Development in the United States from 1963 to 1992," Clin. Pharm. Therap., pp. 609-622. ⁵⁶uch is the recurrent claim of FDA Chairman David Kessler. See, e.g., "Statement Before the Subcom- mittee on Human Resources and Intergovernmental Relations, Committee on Government Operations." Council on Competitiveness and FDA Plans to Alter the Drug Approval Process at FDA: Hearings Before the Subcomm. on Human Resources and Intergovernmental Relations of the House of Represen- tatives Comm. on Government Operations, 102d Congress, 2d Session 47-145, 226-357 (March 19, 1992). ⁵⁷Except for those drugs and devices which are "grandfathered" by the 1976 amendments. ⁵⁸See Stanton by Brooks V. Astra Pharmaceutical Products Inc., 718 F.2d 553 (3d Cir. 1983); Orthopedic Equipment Co. V. Eutsler, 276 F.2d 455, 460-61 (4th Cir. 1960). 59 See Richard M. Cooper, Unapproved Uses of Drugs: An Analysis and Some Proposals, 49 Food & Drug L.J. 533 (1994); William L. Christopher, Drug Prescription: Filling the Regulatory Vacuum, 48 Food & Drug L.J. 247 (1993), for examples of this process involving journals, textbooks, and even the Internet. ⁶⁰In a position paper over twenty years ago, the FDA admitted that "Once the new drug is in a local pharmacy the physician may, as part of the practice of medicine, lawfully vary the conditions of use from those approved on the package insert without informing or obtaining the approval of the Food and Drug Administration." 37 Federal Register 16,503 (1972). This acknowledgment by the FDA was in fact Page 20 Krauss: Loosening the FDA's Drug Certification Monopoly part of a proposal to curb off-label uses, if necessary by revoking approval of any drug used "too often" in an off-label fashion. The 1972 proposal was abandoned, however, and in 1982 the FDA issued a bulletin formally emphasizing that it condoned off-label use as "accepted medical practice." 12 FDA DRUG BULLETIN, April 1982, at 4. The 1982 bulletin was seen by some as an abdication by the FDA of its desire to control off-label use. See, e.g., American Medical Association, 1991 Drug Evaluations Manual 13. But see infra, note 62 where more recent efforts to discourage off-label prescriptions are detailed. United States V. Evers, 643 F.2d 1043 (5th Cir. 1981). ⁶²See T. Randall, "FDA Scrutinizes 'Off-Label' Promotions," 266 JAMA 11 (1991). See also 21 C.F.R. §§310.3(h)(4), 312.7(a), 314.70(b)(3) (1994). ⁶See 54 Fed. Reg. 4302, 4306, 4316 (1989) (providing reimbursement only for "safe and effective" drug use, and defining FDA approved uses as "safe and effective." ⁶⁴United States Government Accounting Office, Off-Label Drugs: Reimbursement Policies Constrain Physicians in their Choice of Cancer Therapies, GAO/PEMD-91-14, (1991) at 35. 65 See supra note 64, at 37. ⁶⁶In Weaver v. Reagan, 886 F.2d 194 (8th Cir. 1989), Missouri defended its refusal to provide Medicaid coverage to certain AIDS patients on the grounds that their preferred therapy, AZT, had only been approved by the FDA for patients with a different HIV profile than the plaintiffs'. The Eighth Circuit reasoned that Medicaid was required to provide "medically necessary" care, and that the distinction between "medically necessary" and "experimental" care should be established by the medical commu- nity, not by the FDA approvals. In Pirozzi v. Blue Cross-Blue Shield, 741 F.Supp. 586 (E.D. 1990), a district court enjoined an insurer from denying reimbursement for a new cancer therapy known as high dose chemotherapy-autologous bone marrow transplant (HDCT-ABMT), a therapy in which standard cancer drugs are used at levels far higher than approved by the FDA. The grounds for the injunction were narrow: the court held that the insurer's contract with the plaintiff did not disclose that the insurers could refuse to reimburse a non-FDA-approved use. ⁶⁷See D. Thompson, "Aspirin: the Cardiologist's Dream?" 131 Time 56 (Feb. 8, 1988). 68 This is one area where, because of legislation, there is indeed an informational "market failure." See supra note 33 and accompanying text. 69 According to one critic, this new FDA interpretation has actually intimidated textbook publishers, who now fear that including the latest information on drug use may result in restrictions on the sale of their textbooks. See J. Bovard, "FDA's pharmaceutical hide-and-seek," Washington Times, April 9, 1995, p. B4. ⁷⁰See J. Calfee, "The Leverage Principle in FDA's Regulation of Information" in R. Helms, ed., Competitive Strategies in the Pharmaceutical Industry, American Enterprise Institute, 1995. S. Lane, "Medical Precautions," Washington Times, April 9, 1995, p. B4. ⁷United States Government Accounting Office, Off-Label Drugs: Reimbursement Policies Constrain Physicians in their Choice of Cancer Therapies, GAO/PEMD-91-14, at 3. The report notes that off-label use of three drugs, ifosamide, interferon and mitoxantrone, constituted 85% of total prescriptions. Id. at 22. ⁷²No appellate cases have been found holding that a doctor's failure to disclose that a frequently prescribed drug therapy was "off-label" violated the rigorous "informed consent" requirements of tort law. "The Food and Drug act has generally been seen as preempting state tort law liability holdings in such cases. See, e.g., Slater V. Optical Radiation Corp., 961 F.2d 1330 (7th Cir., 1992); Evraets V. Intermedics Intraocular, 34 Cal.Rptr. 2d 852 (1995). The Supreme Court recently granted a certiorari petition in a case in which the Eleventh Circuit had ruled that the "grandfathering" of a medical device (under the Medical Device Amendments to the Food, Drug and Cosmetic Act) precluded any state-based products Krauss: Loosening the FDA's Drug Certification Monopoly Page 21 liability suit. See Medtronic, Inc. V. Lohr, cert. granted, Jan. 19, 1996. The issues posed in Lohr to the Supreme Court are not relevant to the qualified tort immunity discussed in this paragraph. 74 Mulder V. Parke Davis, 181 N.W.2d 882 (Minn., 1970) is occasionally cited as contrary authority. In Mulder, the Minnesota court held (at 887) that when the drug manufacturers' warnings and contraindications have been clearly communicated to the physician, who then deviates from them, prima facie evidence of negligence has been established, requiring the physician to explain his deviation. Mulder clearly rejects any "per se" rule for off-label prescriptions, as it does not preclude a demonstration by the defendant physician of the reasonableness of his use of the drug, given current medical practice. See, e.g., Lhotka V. Larson, 238 N.W.2D 870 (Minn. 1976). ⁷⁵See, e.g., Salgo v. Leland Stanford Jr. Univ. Board of Trustees, 317 P.2d 170 (CA, 1957) (finding, at 180, that drug manufacturers' recommendations are always conservative and are quickly outdated, and after a drug has been available for a period of time physicians rely on their own experience concerning its use in actual practice); Craft V. Peebles, 893 P.2d 138 (HI, 1995) (holding that manufacturers' instructions about use and dosage, which are presumably those approved by the FDA, do not establish the standard of medical care as a matter of law). ⁷⁶See Competitive Enterprise Institute, "The Food and Drug Administration: A Modest Proposal" (press release, January 6, 1995); see also Kazman, supra note 44, at 51-52. ⁷⁷See supra note 74 and accompanying text. ⁷⁸The situation is analogous in that, under present law, a doctor prescribing a drug for an "on-label" (i.e. FDA approved) use could not successfully be sued on the grounds that the drug was inappropriate for that use. However an "off-label" prescriber is vulnerable to this type of lawsuit. 79I.e., when the drug as sold is not identical to the drug as advertised. ⁸⁰See comment k, §402A Restatement (Second) of Torts: k. Unavoidably unsafe products. There are some products which, in the present state of human knowledge, are quite incapable of being made safe for their intended and ordinary use. These are especially common in the field of drugs. An outstanding example is the vaccine for the Pasteur treatment of rabies, which not uncommonly leads to very serious and damaging consequences when it is injected. Since the disease itself invariably leads to a dreadful death, both the marketing and use of the vaccine are fully justified, notwithstanding the unavoidable high degree of risk which they involve. Such a product, properly prepared, and accompanied by proper directions and warning, is not defective, nor is it unreasonably dangerous. The same is true of many other drugs, vaccines, and the like, many of which for this very reason cannot legally be sold except to physicians, or under the prescription of a physician. It is also true in particular of many new or experimental drugs as to which, because of lack of time and opportunity for sufficient medical experience, there can be no assurance of safety, or perhaps even of purity of ingredients, but such experience as there is justifies the marketing and use of the drug notwithstanding a medically recognizable risk. The seller of such products, again with the qualification that they are properly prepared and marketed, and proper warning is given, where the situation calls for it, is not to be held to strict liability for unfortunate consequences attending their use, merely because he has undertaken to supply the public with an apparently useful and desirable product, attended with a known but apparently reasonable risk. Restatement (Second) of Torts § 402A, comment k. 81 Absolute design defect immunity for FDA approved drugs is not presently enjoyed by manufacturers: indeed, in only five states (Arizona, New Jersey, Ohio, Oregon and Utah) does FDA approval currently preclude punitive damages for faulty design. See Viscusi, Rowland, Dorman & Walsh, "Deterring Inefficient Pharmaceutical Litigation: an Economic Rationale for the FDA Regulatory Compliance Defense," 24 Seton Hall L. Rev. 1437 (1994). It follows that in an important way this proposal would increase the present value of FDA approval. It is thus incorrect to think that implementation of the proposal contained in this paper would "emasculate" the agency. However, just as some doctors currently Page 22 Krauss: Loosening the FDA's Drug Certification Monopoly prescribe "off-label" despite the lack of tort immunity, some manufacturers would, for reasons explicated below, produce non-approved drugs despite the risk of liability for design defect. This would eliminate the noxious drug lag described above. ⁸²See supra note 75. ⁸³Reputable certifications are relied on in many areas unrelated to drugs. Well-heeled consumers (of products as diverse as shotguns, wallets and four-wheel-drive vehicles) prize the knowledge that a product has achieved "appointment to Her Majesty the Queen," who therefore acts as a certifier of exceptional quality control throughout the British Commonwealth. In the food industry, registration with the Pennsylvania Department of Agriculture was likely a sign of high quality a generation ago. Perhaps the governmental nature of the certifier led to insufficient cultivation, and thus a slow deterioration, of its "brand name." But private food certifiers continue to thrive. For example, consumers of Kosher food products are often fussy about the identity of the agency which has certified that a product complies with Jewish dietary rules. "Star K," "Circle U" and "MK" logos on products are brand marks of three of many competing rabbinical inspection boards, which contract with manufacturers to inspect and certify their manufactur- ing and packaging facilities. These marks add value to food for consumers of Kosher goods who trust the agency owning the relevant trademark. If (as has occasionally happened in the past) it is revealed that a certification board has erroneously (or even intentionally, as a result of corruption) certified a non- Kosher product, the commercial effect on the board is devastating. Many experts in Tort law, including this author, feel that manufacturers are presently being held liable even if their motorcycle or ladder was properly designed and manufactured. See Krauss, supra note 39. Again, this is a problem that substantive tort reform can handle. Mandatory government certification is not needed. See Michael V. Shiley, Inc., 46 F.3d 1316 (3d Cir. 1995) (ruling that the 1976 amendments to the Food and Drug act preempt state actions for negligence, strict liability and implied warranty for Class III medical devices, the only devices subject to formal pre-market FDA approval). ⁸Numerous cases have held that FDA approval does not preempt state products liability. See, e.g., MacDonald v. Ortho Pharm. Corp., 475 N.E.2d 65, cert. denied, 474 U.S. 920 (1985) (holding state not preempted from imposing higher duty of warning); Allen v. G.D. Searle & Co., 708 F. Supp. 1142 (D. Or. 1989) (holding state law claim of defective labelling for IUD was not preempted because the device was classified as a prescription drug). ⁸⁷For example, Bendectin, the most effective anti-nausea drug for pregnant women, was withdrawn from the market after many successful (but expensive) product liability defenses against claims that it induced birth defects. Had these suits been "demurrable" (i.e., seen as ill-founded on the basis of a preliminary motion) on the grounds that Bendectin had been tested and found safe by the FDA, the drug would most certainly still be marketed. ⁸E.g., allowing doctors to defend themselves by citing medical studies showing the utility of the drug, etc. ⁸⁹In a recent survey, the Competitive Enterprise Institute asked oncologists how they would obtain reliable information about drugs that had not obtained FDA approval: 59% of respondents stated that they would rely on studies published by refereed journals. CEI, "A National Survey of Oncologists Regarding the Food and Drug Administration," p. 5 (Aug. 1995). ⁹⁰E.g., superior effectiveness, enhanced safety, much lower price (due to the high costs of FDA certification) for low-income patients, etc. ⁹See Krauss, supra note 21. ⁹²See, e.g., In the Matter of Analysis of Wash Trucking, 521 A.2d 883 (N.J.Super., 1987) (confirming the voluntary nature of Underwriters' Laboratories). ⁹See, e.g., Roofire Alarm Co. V. Underwriters' Laboratories, 188 F. Supp. 753 (E.D. Tenn., 1959) [UL cannot be forced to change its standards as to fire warning devices, as it is a private entity. Consolidated Krauss: Loosening the FDA's Drug Certification Monopoly Page 23 Metal Products V. American Petroleum Institute, 846 F. 2D 284 (5th Cir., 1988) [Trade association that evaluates products and issues private "licenses" does not violate § 1 of Sherman Act when it fails to favorably evaluate a product.] 94Of course, it is conceivable that private certification firms may be bribed or otherwise corrupted; but this is a risk that has also afflicted the FDA. See, e.g., Novack, supra note 36. If a private firm is corrupted it loses most or all of its goodwill, while a government monopolist does not have this fear. The likelihood of corruption is thus lower for private certifiers than for the FDA. 95 For example, for metal gasoline containers standards have been privately proclaimed by Underwriters' Laboratories (Standard #30 for Metal Safety Cans), by the National Fire Prevention Association (NFPA Flammable and Combustible Liquids Code #30-77), and by Factory Mutual Insurance (Standard for Safety Containers and Filling Supply and Disposal Containers #FM 6051). ⁹⁶Medical malpractice trials are replete with expert testimony from various hospital and physicians' associations, which have adopted competing standards for surgical techniques. ⁹⁷See Sun Up Foods, Inc. v. Florida Dept. of Citrus, (M.D. Fla., Dec. 31, 1991) (holding FDA's sovereign immunity bars suits for damaging business through manner of enforcement); Giles v. Villanileea, No. C 93-2461 BAC (N.D. Cal. Dec. 14, 1993); Daley v. Weinburger, 400 F. Supp. 1288 (E.D.N.Y. 1975) (denying injunction request because of the FDA's sovereign immunity). 98 Comment k, § 402A, Restatement (second) of Torts. This comment applies to prescription drugs, so in fact a negligence rule applies to manufacturers of FDA approved drugs. See, e.g., Carmichael V. Reitz, 95 Cal. Rptr. 381 (Cal. App., 1971). Strict liability is also held inapplicable to medical devices, whether approved by the FDA or grandfathered. See, e.g., Phillips v. Baxter Healthcare, 1993 WL 524688 (Cal. App. 2 Dist.) (1993). ⁹⁹See, e.g., Yassin V. Certified Grocers of Illinois, 502 N.E.2d 315 (III. App., 1986) at 331 (refusing to hold Underwriters' Laboratories to a "strict liability" standard under § 402A of the Restatement (Second) of Torts, as UL is a testing facility and not a manufacturer). 100 Their efforts are not always successful. In Consumers Union of the United States V. General Signal Corp., 730 F.2d 47 (2nd Cir., 1984), the Union (publisher of Consumer Reports) sued to prevent a manufacturer from using that magazine's research findings about Regina vacuum cleaners in its advertising. A majority of the court opined that quoting Consumer Reports' ratings of a product constituted "fair use" under 17 U.S.C. § 107. Oakes, J., in dissent (ibid, at 47), correctly observed that the majority's opinion prevented Consumers Union from maximizing profits by deciding what mix of endorsement revenues and newsstand sales is optimal. Buyers informed about Regina's high CR rating directly from the manufacturer have less of a need to purchase the CR "vacuum cleaner" issue to see "who won." In practice, of course, the Union can refuse to evaluate products manufactured by corporations which violate its prohibition of citations. Even in Second Circuit states there is a strong economic incentive to refrain from using CR's name. See also Toman v. Underwriters' Laboratories, 707 F.2d 620 (5th Cir., 1983) (Underwriters' Laboratories may sue manufacturer and distributor of hair dryer if they place laboratory approval marks on their product without authorization). 101 See, e.g. Hanberry v. Hearst Corp., 81 Cal. Rptr. 519 (Cal. App., 1969) (recognizing the possible liability for negligent issuance of "Good Housekeeping Seal of Approval" for a dangerous product). Acceptance of an advertisement by a magazine does not constitute an endorsement (see, e.g., Walters V. Seventeen Magazine, 241 Cal. Rptr. 101 (Cal. App. 1987)), but Good Housekeeping purports to evaluate, not just advertise, products which gain its seal of approval. 102 Insurance companies derive profits in two ways: by investing the premiums they receive, and by accurately gauging their risk exposure. High absolute risks are more variable; it follows that if insurance companies can lower their risk they can (by definition) more accurately gauge their exposure. Risk is lowered in three ways: intrinsically through the aggregation of identical risks into pools (via the "law of large Page 24 Krauss: Loosening the FDA's Drug Certification Monopoly numbers"); through production of more accurate information about the extent of risk; and through reinsurance (by which insurance companies "contract out" the aggregation of some risks). Certification agencies test products and thereby produce new information about their risk potential. Insurance companies are "natural" certifiers of risk, and therefore of quality. Note that managed care providers are typically insurers in this sense. ¹⁰³See Restatement of Torts, § 324A. See: United States Lighting Service V. Llerrad Corp., 800 F.Supp. 1513 (N.D.Ohio, E.D., 1992) (UL can be considered a "product endorser," and is liable when it fails to exercise reasonable care when performing its testing procedures, or if inaccurately communicating its testing results). See also Toman v. Underwriters' Laboratories, 532 F. Supp. 1017 (D. Mass. 1982) (reversed on other grounds, 707 F.2d 620). 104 The reputational effect of UL certification is significant. See, e.g., Brazos Graphics v. Arvin Industries, 574 S.W.2d 240 (Tex App., 1978) (evidence of UL approval of an electric heater admissible in defense against claim that the heater was defectively designed). ¹⁰⁵Robert Cooter has produced analogous and interesting work on insurers' purchase and sale of tort claims. Robert Cooter, Towards a Market in Unmatured Tort Claims, 75 Va. L. Rev. 383 (1989). 106 See Frank H. Easterbrook, Limited Liability and the Corporation, 52 Chi. L. Rev. 89 (1985) (discussing reasons why corporations insure, despite the portfolio diversification of their owners and their presumed resulting risk neutrality). 107 On April 6, 1995 the agency, in a package of reforms announced at the White House, announced that for a two-year trial period it would contract out testing of low-risk devices (like laboratory cholesterol tests and electronic stethoscopes) to private certification firms, but only if those firms are accredited by the agency. The agency reserved the right to nullify private certifications in any case. See Washington Times, April 7, 1995, p. A6. Note that no drugs (and no devices affected by long time lags, such as pacemakers) are affected by the FDA's offer. Note also that the FDA accreditation requirement would have the effect of exporting many of the bureaucratic pressures afflicting the agency, and would preclude free competitive entry into a nascent "certification industry." 108 Senator Barbara Mikulski (D-MD) insisted that the FDA have a "passion for change" if it did not wish to be "rolled right over" by Congress. Ibid. Krauss: Loosening the FDA's Drug Certification Monopoly Page 25 The Competitive Enterprise Institute The Competitive Enterprise Institute is a public policy organization committed to advancing the principles of free enterprise and limited government. Founded in 1984 by Fred Smith, Jr., CEI promotes classical liberal ideals through analysis, education, coalition-building, advocacy, and litigation. A non-profit, tax exempt organization under Section 501 (c) (3) of the Internal Revenue Code, CEI relies entirely on donations from foundations, corporations, and private individuals. Contributions are tax deductible to the extent allowed by law. For more information, contact: COMPETITIVE ENTERPRISE INSTITUTE 1001 Connecticut Avenue, N.W. Suite 1250 Washington, D.C. 20036 Phone: (202) 331-1010 Fax: (202) 331-0640 E-mail: [email protected] Web site: http://www.cei.org Jim Ardala is 202-2019 202 -2 60 1847 184 7 Lindses moose - - / i Paul Shuda 4 \ - my - 479. 47 9. 66421 - Michael Langle copies WASHINGTON THE WHITE HOUSE I FDA Reform 7/12/96 JD /Rich - funalyed ground rules for Donna-Bliley discussion He called her! She said she couldn't support if they were gous to so forward w/ Marking each with next two weeks He agreed -pendus blowing. Alan Nover Key Holoms Karen Nelson -waman Thil. it's R good Importation - through 11/2 issues - [Kassebaem Mkulshi, Dodd - -met w/piil Lee. - Croml rules - Divezil - Warnan at lable - FOA - at Table - agreement on larguage / not concepts - 2 wells w/Butey/Donna - - No Food- Bulees - wants something on derices - Rich - but we he for about - Barm is commutted to his bill - recognize they how "Banan problem Drugs and Denies. - Meetings STAVING Mon p.m 4:30 - - First negoriation sessession Wed. - (Tues is pessicide mark-emp) - 11 keep Dan Take involved" - bridge 10 Conservature duocrass- Poshicedes - 120 - Rich apprised Then of agreement 0/Builey Dorma - Tues or Wednesday - Wed, Thurs, Fri - Tracey called about FDA reforme - Sunate - Hanner Kassebaun said explicity -never want have to he truggered. - spreading out trugger lowering perception each year HHS- made argument wasen't realistic in terms 01 nevernes - Rich - menber level understander ISMI thin - Flexibility about lowerng percentage and Stretching out time frame. Has 10 be diff - Dard and Bill - No harmers on dues side an House bill - House now has a more acceptable dus hanner - Senate has heiter approach on 3rd party review - on devices agreed to our parameters - excluding life Threaterus implactal and Sone Therapeutic /dogustic derces. - Guidance - unitom Standards for diff reviewers an sane denie. - II and chass III - w/notice of intent to reclassifes - "supporting 05 Stating hunan life" "diagnotic 0) which Dealth Claims - fleus.lites Med bindes - flexibility Drod Approval Mon changes OH lahol - Dodd work out w/Frist, Macc, Bill and Jane Lowerson Whaten works hard on off label- Pess Dwiell - Phil also secing Frist Tuesday - of Lahel - that's where Senators are most dug in 1 Suly - -that's where the dun't have as much 10 - Podd would oppose an immeadiare done vote - So at least c/ days on Floor. - Senate was Selinda Withdrawal/Redaction Marker Clinton Library DOCUMENT NO. SUBJECT/TITLE DATE RESTRICTION AND TYPE 001. note re: FDA Reform [partial] (1 page) 07/12/1996 b(6) COLLECTION: Clinton Presidential Records Domestic Policy Council Elizabeth Drye OA/Box Number: 10452 FOLDER TITLE: FDA Reform 1996 [2] 2014-0046-S rc1402 RESTRICTION CODES Presidential Records Act - 144 U.S.C. 2204(a)] Freedom of Information Act [5 U.S.C. 552(b)] P1 National Security Classified Information |(a)(1) of the PRA] b(1) National security classified information [(b)(1) of the FOIA| P2 Relating to the appointment to Federal office [(a)(2) of the PRAJ b(2) Release would disclose internal personnel rules and practices of P3 Release would violate a Federal statute [(a)(3) of the PRA] an agency [(b)(2) of the FOIAJ P4 Release would disclose trade secrets or confidential commercial or b(3) Release would violate a Federal statute [(b)(3) of the FOIA] financial information [(a)(4) of the PRA| b(4) Release would disclose trade secrets or confidential or financial P5 Release would disclose confidential advice between the President information [(b)(4) of the FOIA] and his advisors, or between such advisors [a)(5) of the PRA] b(6) Release would constitute a clearly unwarranted invasion of P6 Release would constitute a clearly unwarranted invasion of personal privacy |(b)(6) of the FOIA] personal privacy [(a)(6) of the PRA] b(7) Release would disclose information compiled for law enforcement purposes [(b)(7) of the FOIA] C. Closed in accordance with restrictions contained in donor's deed b(8) Release would disclose information concerning the regulation of of gift. financial institutions |(b)(8) of the FOIA] PRM. Personal record misfile defined in accordance with 44 U.S.C. b(9) Release would disclose geological or geophysical information 2201(3). concerning wells [(b)(9) of the FOIA] RR. Document will be reviewed upon request. FDA referr - Have UP or Leen call Dodd said - he's done everything he am to get our supmort - Phil has Frust at 4:00 or easy afternoon- - -tracy 2:00 or 5:30 John Phyllis (001] - George 3954852 (b)(6) Line in sand M -Phil Lee. - Sally E- Taipun 690-7627 - Gros S- Phil-lee's 690-764 - Nance-Ann 2- sheets -. 827-3370 Jonathen - -Bill corr. 610-7694 1 Trally (Dan Take (b)(6): - who Angell - 3:00 - off lasel Use- - 26th - Day on Cott's internal Calendar for PDA reform 1 - Mach/Frist/Dodd Focus - undersent incentive to do regard — Basic minciple - done research, - represented it to The FDA before you dissemenate journal article that would be basis for supplared -3 months before sudmit data to FDA - Patient Croups - Dris in boonies - want get This info. - Need database have it for Cancer, (NCI) AIDS, 2 - in-House bill 3 - fixing supplement process - Rego type this i suplefying largely Dodd- see same circumstances where supplements wouldren be necessary. - has smiluesearch warms is U. - Mach's intense interest. - Z weeks -Dugell name indication for approval /monde of Tues. 5:30 FDA Conf-call 7626 Devices pitor resolved (3rd) touse - Open - efficacs std; off-lasel Howard Kohni idealogical nun- - Monder expects cument draft. - R's will mahe a judgment eanly in the week - LOH is telling basebarn - 1/2 day. agreement and no more than Senate New issues Jane Williams is raising - - tissue issue pharmacy compounding 15sues - -off-label Agreed to: health claims excepts 1 third party review - Coats 1 efficacy srds. - manifacturing changes - - health claims - A med gudes off the table - (resolved in approps.) 12 issues 4 Done 5 close initial classification of deres 3 humantarian devices; efficacy (we offened language), (we gave guage FDA Refan - Letters July 3, 1996 Ms. Susan Panico Executive Director National Depressive and Manic-Depressive Association Suite 501 730 North Franklin Street Chicago, Illinois 60610 Dear Susan: Thank you for writing to me. I'm glad to have the perspective of the National DMDA. Since taking office, I have worked hard to reform the Food and Drug Administration so that it can function more efficiently and rapidly to benefit the American people. As you know, we have successfully reduced the length of the approval process for many new drugs and therapies, and recently, my Administration put forward a series of regulatory reforms designed to make the FDA even more responsive to those in need of new treatments. I appreciate your suggestions, and as we work to build on our progress, I will certainly keep your views in mind. Sincerely, BILL CLINTON BC/SEM/JFB/JFB/emu-jfo (Corres. #3005417) (6.panico.s) CC: Barbara Woolley, OPL Elizabeth Drye, ODP 222 07/18/96 14:32 FDA/OFFICE OF THE COMMISSIONER -> 92024567028 NO.273 P003/006 CONCERNS RE: DEVICE BILL (H.R. 3201) A. Major Concerns 1. Privatization of Review/GMP Inspections (Sections 9, 11, 12, and 17) 2. Off Label Promotion (Section 18) B. Serious Concerns 1. Effectiveness Standards (Section 8 -- no well controlled clinical trials and no clinical outcome results for devices) 2. Devices: Modifications Without FDA Review and Specific/General Use (Section 9) C. Other Significant Concerns 1. Dispute Resolution (Section 3) 2. Investigational Device Exemptions (Section 4) 3. Humanitarian Use of Devices (Section 6) 4. Performance Standards (Section 7) 5. Initial Classification of Devices (Section 9) 6. Scientific Advisory/Classification Panels (Section 10) 7. Device Tracking (Section 14) 8. Postmarket Surveillance (Section 15) 9. GMP and Device Reports (Section 20) 10. Information Systems (Section 22) 11. Environmental Impact Review (Section 23) 07/18/96 14:32 FDA/OFFICE OF THE COMMISSIONER -> 92024567028 NO.273 P004/006 D. Other Concerns 1. Annual Report (Section 2) 2. Harmonization (Section 16) 3. Informal Agency Statements (Section 24) 4. Research and Education (Section 25) 5. Public Notice of Deviation (Section 26) 6. Civil Penalties (Section 21) 2 07/18/96 14:32 FDA/OFFICE OF THE COMMISSIONER -> 92024567028 NO.273 P005/006 CONCERNS RE: DRUG DEVICE BILL (H.R. 3199) A. Major Concerns 1. Privatization of Review/GMP Inspections (Sections 7 and 8) 2. Off Label Promotion (Section 19) B. Serious Concerns 1. Effectiveness Standards (Section 5 - one versus two clinical trials and new uses of drugs) 2. Medication Guides (Section 29) 3. Human Tissue (Section 25) C. Other Significant Concerns 1. Annual Report (Section 2) 2. Streamlining Clinical Research in Drugs and Biological Products (Section 3) 3. Content and Review of New Drug Application (Section 4) 4. Scientific Advisory Panels (Section 6) 5. Dispute Resolution (Section 9) 6. GMPs (Section 10) 7. Nonprescription Drugs (Section 14) 8. Pharmacy Compounding (Section 17) 9. Access to Unapproved Therapies (Section 26) 10. Protection of Confidential Information (Section 28) 07/18/96 14:32 FDA/OFFICE OF THE COMMISSIONER + 92024567028 NO.273 P006/006 D. Other Concerns 1. Information Systems (Section 15) 2. Environmental Impact Review (Section 16) 3. Harmonization (Section 18) 4. Informal Agency Statements (Section 20) 5. Research and Education (Section 21) 6. Public Notice of Deviation (Section 23) 7. Radiopharmaceuticals (Section 27) -2-