GMHC Treatment Issues, Volume 10, Number 1 - January 1996
Derek Link

AIDS drugs are now approved faster, and access to them granted earlier, than anyone thought possible just a few years ago. Because of pressure and creative ideas from AIDS activists, the FDA pioneered accelerated approval and expanded access programs. One need only look at the recent past for a vivid example of the success of AIDS activists' efforts. Saquinavir, the first of the new generation of protease inhibitor drugs, was approved in a record three months, the fastest AIDS drug approval ever. All is surely not perfect at the FDA, but the agency has made substantial progress. AIDS activists still have a full regulatory agenda covering such issues as how best to use the accelerated approval process while insuring that sufficient information on drugs' actual potential is generated through post- marketing studies.

After the Republican landslide in the 1994 Congressional elections, the new Congress immediately took up the cause of FDA reform as one of its highest priorities. Accusing the FDA of murderous delays and inept bureaucracy, the new Congress adopted much of the confrontational language of AIDS activists in its debates on the FDA. The similarities between AIDS activists and Congressional Republicans end with the rhetoric, however. AIDS activists have helped to organize a national campaign in support of responsive and efficient drug regulation, but in opposition to ideological, political attacks on our nation's public health safety net. Congressional "FDA reform" could halt medical research and innovation, harm people with serious and life-threatening disease, and undermine the nation's health.

A Debate About the Role of Government

Reform of the FDA, AIDS activists recognized early, was a problem of policy, management, resources and administration. The FDA implemented faster drug approvals and expanded access programs without Congress ever passing a law. This is because the organization, policies and procedures of the FDA are not established by Federal law. With wide discretion over drug regulation, the FDA could approve drugs faster by implementing internal policy changes. This flexibility is perhaps its greatest asset; it gives the agency the ability to respond rapidly and in a non-political manner when public health emergencies, like AIDS, arise.

Instead of focusing on the management problems at the FDA, the Republican Congress has set its sites on the Food, Drug and Cosmetic (FDC) Act itself. The FDC Act gives the federal government the duty to insure that drugs, biological products and medical devices are safe and effective for the treatment of specific health conditions and evidence of that safety and efficacy is accurately represented to the American people. By seeking to amend fundamental government authority over drug regulation, the Congress has opened a debate not on the problems at the FDA but instead on the role of the federal government in medicine, pharmaceuticals and clinical research. The FDA can sometimes be frighteningly bureaucratic, but the FDC Act itself is not an obstacle for drug development. The Act fosters an environment in which medical innovation grows out of solid clinical research. People with AIDS, as well as other life-threatening diseases, need this research more than anyone else to point the way to effective treatments.

The FDA regulates the core elements of life, totaling a quarter of all consumer spending. Any change in the government's authority over such a large segment of the economy brings out armies of industry lobbyists, each promoting its own self-interest. Encouraged by the Republican landslide, FDA-regulated industries and their advocates initiated a major lobbying and public relations campaign within a month of the 1994 election.

Industry and Politics in Congress

HIMA (the medical device manufacturers group), BIO (the biotech industry group) and PhRMA (the drug industry group) are the main industry groups pressing for substantial changes to the Food, Drug and Cosmetic Act. BIO's president, Carl Feldbaum, told the National Journal, "We're pushing [FDA reform] very hard. We have a lot of irons in the fire with the FDA."

Each of these groups has released FDA reform proposals, and has dispatched their lobbyists to the Capitol. "I think they'd like to eviscerate the FDA, but if they can't do that, they'd like to intimidate the FDA," Henry Waxman, a senior Democrat on the House Commerce committee and a leading consumer protectionist, told the National Journal. Right-wing political organizations, with heavy funding from regulated industries, have gone on the offensive too. The Washington Legal Foundation (WLF), the Progress and Freedom Foundation and Citizens for a Sound Economy, are the three most prominent right-wing advocacy groups working on FDA reform legislation.

The WLF has run several full page ads in The New York Times and Washington Post harshly criticizing the FDA with the tag line, "The Problem with Health Care in America is the FDA." The WLF furthermore has filed several lawsuits over FDA regulations, mostly over the type of marketing strategies pharmaceutical companies can pursue. The Foundation argues that limiting the claims companies can make to the applications approved by the FDA is a violation of the First Amendment's protection of free speech.

The President of the WLF, Alan Slobodin, temporarily stepped down from his post to become a senior staff member of the House Commerce Committee, which has authority over the FDA and will draft reform legislation in the House. The Lilly Endowment, a foundation whose funds come from Indianapolis- based drug maker Eli Lilly, gave the WLF $150,000, making it one of the organization's largest financial backers.

The Progress and Freedom Foundation is perhaps the biggest player among the advocacy groups. The Foundation is closely associated with House Speaker Newt Gingrich. The Foundation is run by close Gingrich supporter Jeffrey Eisenach, and handles many of the Speaker's political activities, including organizing Progress Report, Gingrich's talk show on National Empowerment Television. Major industry contributors to the Foundation have included Burroughs Wellcome, Glaxo, Genzyme, Searle, Johnson & Johnson, Direct Access Diagnostics (now a Johnson & Johnson subsidiary), Health South Corporation, Amgen and Solvay. "This was an organization that looked like it was going to have some influence, and we wanted to have some influence with them," Lisa Raines, chief Washington lobbyist for Genzyme, has stated.

Speaker Gingrich has already interceded on behalf of some of these Foundation contributors. Last summer, Gingrich urged the FDA to move faster to approve Luvox, a Solvay drug for obsessive-compulsive disorders. Gingrich also has urged the FDA to move faster in approving an HIV home test kit manufactured by Direct Access Diagnostics. The House Ethics Committee is investigating Gingrich's relationship to Direct Access Diagnostics, as part of its overall ethics investigation of the Speaker.

The Tobacco Industry's Shadowy Role

Last year, the FDA proposed sweeping new regulations which would substantially change the way cigarettes are sold in the United States -- limiting advertising and restricting sales to minors. The new FDA regulations could have a devastating impact on tobacco industry profits -- almost all smokers start when they are teenagers.

The tobacco industry has responded with a full-scale assault on the FDA and the FDC Act. On January 2, it submitted to the FDA a 2,000 page document with 45,000 pages of supporting documents challenging its authority to regulate cigarettes. The industry also launched an aggressive campaign contribution drive to the Republican party. In the first half of 1995, the tobacco industry pumped $1.5 million into Republican party coffers, over five times the amount from the same period in 1994, and a record level contribution of so- called "soft money" to a political party. In addition the tobacco industry has sharply increased donations to individual Republican Congressmen. Most tellingly, Thomas Bliley (R-VA), Chair of the House Commerce Committee -- the committee responsible for FDA reform legislation in the House -- received $126,476 from the tobacco industry, more than any other member of Congress.

Richard Burr (R-NC), who has received $11,350 from tobacco interests and also is a Commerce Committee member, wrote in Roll Call "I cannot understand why the FDA, which cannot efficiently perform its core mission, should be rewarded with historic jurisdiction increases [over the tobacco industry]." Although the tobacco industry has been a driving force that keeps FDA reform high on the Republican agenda, it has not been publicly identified with the reform effort. "A veteran tobacco industry hand said that Bliley has asked companies to lay low for their own benefit and his and that he doesn't want to be perceived as beating the FDA over the head because of tobacco. That message has come through loud and clear," reported the National Journal.

Preserving Patients' Rights

In response to the industry-driven assault on the FDA, patient advocacy groups have joined together in an historic coalition. The Patients' Coalition, which formed last summer, includes over 80 leading national organizations from prominent AIDS groups, such as the American Foundation for AIDS Research and GMHC, to the American Cancer Society, the National Organization for Rare Disorders and the National Health Council, which represent the largest voluntary health organizations in the country.

The coalition wrote a set of FDA reform principles informed by the common experiences of all patients with serious and life-threatening diseases. It also released a policy white paper on the real problems at the FDA. One much discussed proposal is a "sunshine law" that would permit the FDA to publicly discuss its private interactions with drug developers. Currently, companies frequently complain of FDA delays in processing their drug approval applications while the FDA refuses any comment on the grounds that such applications constitute proprietary information.

The coalition is working together on Capitol Hill and in the media, trying to ensure that FDA reform legislation serves patients' true interests. Such diverse patient groups have never worked together in such an intensive way. They have come together because all patients need federal regulations that encourage medical research and innovation while continuing to ensure that drugs are safe and effective.

Legislative Maneuvers

FDA reform legislation has taken much longer to move through the Congress than many had predicted. Numerous hearings have been held on FDA reform issues in both the House and Senate during the first year of the 104th Congress. But legislation has been very slow to emerge. The Republicans now realize that FDA reform is more complicated than they first imagined, placing core values into question, and opening a Pandora's box of competing interests.

In both the House and Senate, there is no consensus on FDA reform. Nancy Kassebaum (R-KS), chairwoman of the Senate Labor Committee -- which has jurisdiction over the FDA in the Senate -- introduced a comprehensive ("Omnibus") FDA reform bill. Sen. Kassebaum's bill has no co-sponsors, indicating that both industry advocates and consumer protectionists in the Senate are dissatisfied with its provisions. The House Commerce Committee has had an even more difficult time with FDA reform legislation. The House committee has altogether given up drafting a single, "omnibus" FDA bill. Instead the Commerce Committee now plans many individual bills on discrete areas of the FDA's authority. The lack of consensus means the course and outcome of the FDA reform legislation is unpredictable and volatile. Individual bills or amendments to bills could be introduced that radically change the federal government's authority over drug development and marketing.

The Congress now anticipates taking up FDA reform early this year. Sen. Kassebaum plans hearings on her bill over the next few weeks, and the House could start introducing bills as well. It is still unclear, though, if the Republicans can move such major legislation through while budget debates and election campaigns heat up. In any event, if a bill is eventually passed by Congress, it may bear little resemblance to the proposals being considered now.

The Kassebaum Bill

As the first introduced, Sen. Kassebaum's FDA reform bill (S.1477) is worth a close look. Written primarily by senior staffer Jane Williams, the bill is considered a moderate proposal. Sen. Kassebaum's staff have been open to the concerns and views of the Patients' Coalition. When a draft of the proposal was circulated this fall, the coalition sent a detailed analysis, some of which was incorporated into the final version.

The bill does reject many of the most radical FDA reform proposals, and, as Ms. Williams said to a meeting of the coalition, "it's the best you're going to get." Be that as it may, the bill as it now stands would harm patients with serious and life-threatening diseases by undermining incentives for medical research and innovation.

The Kassebaum bill establishes that only one efficacy study of a new drug is necessary to meet the requirement of safety and efficacy. The FDC Act presently does not define how many studies are required, but the FDA has interpreted the law to mean that two are required. On a scientific level, two studies greatly increase the likelihood of making the correct interpretation of data, especially when results are ambiguous or marginal. The FDA in any case already uses a one efficacy study requirement for new drugs if the study is a large multi-center one, or the drug in question is a high priority or the results are unambiguous. Without the FDA's discretion over the number of required studies in drug development, less clinical research will be performed, reducing the scientific foundation for new therapies.

The bill sets strict approval schedules, requiring FDA action within 120 days on New Drug Applications. Strict time-lines sound wonderful, but they in fact can slow access to drugs for patients with serious and life-threatening diseases. If the FDA must approve everything rapidly, then resources will be pulled away from high priority approvals, like break- through drugs for serious diseases, to lower priority approvals, like fourth generation sleeping pills. The FDA has inadequate resources for every drug to be a high priority. The FDA must devote more resources and staff time to reviewing drugs for the sickest patients. This proposal also fails to acknowledge the FDA's progress. Saquinavir, the first of the new generation protease inhibitor drugs, was approved in 90 days, for example.

The bill also proposes increasing the authority of the FDA's advisory committees. The FDA maintains a host of independent advisory committees that review research data and make recommendations to the agency. The decisions of FDA advisory committees are not binding on the agency. Sen. Kassebaum's bill enhances the authority of the advisory committees, making their decisions binding on the FDA. The bill would also mandate that representatives of regulated industries be included as members of the committees, a move which is presently prohibited under conflict-of-interest regulations.

The Kassebaum bill ignores ample evidence of the mediocrity and ineffectiveness of advisory committees. A 1992 study of the FDA advisory committees by the Institute of Medicine found multiple problems with them. Well-qualified people often do not serve on FDA advisory committees because of long time commitments (members serve two year terms) and low pay for professionals ($150 a day). Sen. Kassebaum's bill does nothing to fix the recruitment problems for advisory committees, and instead aggravates it by extending service to three years. Breakthrough drugs should be evaluated by skilled FDA scientists and professionals, not mediocre, part- time committee members.

The bill's most radical proposal is to create a "presumption of approvability" for some new drugs. If a drug were approved in the United Kingdom, it would have an automatic "presumption of approvability" in the United States. The FDA would have thirty days to block the automatic approval of the drug in this country. This proposal ignores some key facts. The United Kingdom has a slower drug approval process than the United States. Many AIDS drugs -- d4T, 3TC and saquinavir among them -- are not yet approved in the U.K. Every AIDS drug has been approved first in the U.S.

The presumption that the U.K. is faster is simply wrong, and it abrogates the federal government's fundamental responsibility over the safety and efficacy of drugs marketed in this country. It also ignores that the U.S. has far fewer drugs withdrawn from the market for safety reasons than other countries -- just the classic case of thalidomide.

The bill also would allow drug companies to promote and advertise so-called "off-label" uses of their products. Promotion of off-label uses refers to advertising health claims for a product that are not approved by the FDA but that are considered part of standard medical practice. The bill seeks to solve a real problem. Many drugs -- especially for cancer -- are used in ways that are not FDA-approved.

Many drugs have multiple uses, but some are approved for just a single specific purpose. While many off-label uses of drugs are standard medical practice, many others are ineffective or harmful. Sen. Kassebaum's bill would allow marketing of any "medically accepted" use of a product, without saying what constitutes "medically accepted." The bill cannot distinguish between legitimate and harmful off-label uses.

Advocates for rare diseases are especially concerned about off-label promotion. They fear Sen. Kassebaum's bill will undermine the incentives for research into rare diseases created by the Orphan Drug Act. The Orphan Drug Act establishes financial, tax and patent incentives for industry to research drugs for rare diseases.

Many of the drugs used to treat rare diseases are already approved for other, more common maladies. Say two companies make the same product, but only one company conducts research into the product's use in a rare disease. The Orphan Drug Act authorizes the government to grant the company that did the research an exclusive right to market the drug for this disease. If adopted, Sen. Kassebaum's bill may well undermine this exclusivity because any manufacturer could promote all the "medically accepted" uses of its drugs, even if the company did not conduct the research on the orphan indication.

Patient advocates agree that their goal for off-label drugs should be to encourage industry and the FDA to work together to submit data on off-label uses. Applications for secondary indications should be easier and cheaper to file.

Preserving the FDC Act

More broadly, the Patients' Coalition sees the FDC Act as critical for sustaining the unprecedented era of medical research and progress, an era in which American science has been preeminent. The FDC is vital to the nation's, and indeed the world's, health because its high standards help protect the public against new therapeutic products backed only by dubious or fraudulent data.

Congressional meddling with the Act may well end up harming patients with serious diseases by reducing the amount of medical information available. Questionable, ill-advised treatment would become more likely in such circumstances. Many AIDS activists have pressed for reform of the FDA, but not for changes to the Food, Drug and Cosmetic Act. These AIDS activists, along with their allies among patient advocacy groups, are continuing to call for an efficient and responsible FDA. At the same time, this coalition considers paramount the preservation of the federal government's crucial role in drug development and marketing.

960101
GM100101

Copyright © 1996 - Treatment Issues. Reproduced with permission. Treatment Issues is published twelve times yearly by GMHC, Inc. All rights reserved. Noncommercial reproduction is encouraged. Subscription lists are kept confidential. GMHC Treatment Issues, The Tisch Building, 119 West 24th Street, New York, NY 10011  fredg@gmhc.org  http://www.gmhc.org

AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, Elton John AIDS Foundation, iMetrikus, Inc., John M. Lloyd Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2003. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2003. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .