FDA Reform Signed into Law
After three years of attempts, Congressional efforts to change the law under which FDA operates achieved bipartisan consensus. The result, the FDA Modernization Act of 1997, was signed into law by President Clinton on November 21. Major provisions are:
"Fast track" review for the most important drugs--those "intended for the treatment of a serious or life-threatening condition and [which demonstrate] the potential to address unmet medical needs for such a condition." Drug companies must apply for fast-track status--which they may do when they apply for an IND (permission to test the drug in humans) or any time afterwards--and then the FDA must decide within 60 days whether to grant it. The fast-track section is closely based on procedures the FDA has already developed and used for accelerated approval of some AIDS and cancer treatments. The new law encourages the development of new surrogate markers of drug efficacy; however, fast-track status can apply whether or not surrogate markers are used.
Allowing drug companies to promote "off label" drug uses by sending peer-reviewed articles to physicians; this is probably the most controversial major provision of the law. Also, companies will be allowed to make economic claims to HMOs (health maintenance organizations)--but not to patients or physicians--without running controlled clinical trials, as previously required, which would often be impractical or unethical.
Changing the mission of the FDA. In addition to protecting the public from unsafe drugs, its mission now will also be to speed research, innovation, and access to care.
Renewing PDUFA (the Prescription Drug User Fee Act), which allows the FDA to charge companies for reviewing their drugs, and use the money to hire more reviewers so that approval decisions can be made more quickly. PDUFA has been a huge success and is universally supported--especially by the companies which have to pay the fees, since the advantage of earlier approval greatly outweighs the cost. PDUFA would almost certainly have been renewed in any case, but was delayed by the politics around other aspects of the bill.
Legislation on compounding of drugs by pharmacists or physicians. According to Julie Gossman of Emord and Associates, a law firm in Washington D.C., the new law regulates the current practice of compounding, and should not cause major changes there.
Substantial legislation in other areas, including medical devices, and health claims for foods.
Also, there can always be "sleepers," inconspicuous phrases which are added by special interests and become law by surprise. Today it is common that neither the public nor members of Congress know exactly what is in a major bill when the final vote is taken.
The bill will probably not fix the very serious delays early in the development process, when an experimental drug is first entering clinical trials. This issue unfortunately dropped out of the discussion early on, and has never received sustained national attention. It is hard to build political momentum around events which occur early, before a compound has become a therapeutic option for people.
Most AIDS organizations and activists have not been involved in the discussion and debate about this bill. Of those who were involved, most were strongly opposed; they worked through a new group called the Patients' Coalition. One organization, the Log Cabin Republicans, strongly supported the bill.
Comment
We doubt that the new law will have a major near-term impact on AIDS drug development, since the fast-track provisions mostly legislate what the FDA has done already for the most clearly important AIDS drugs. The law should, however, encourage more attention to surrogate markers for drugs other than antiretrovirals--for AIDS and other serious illnesses as well.
The other big change, allowing limited promotion of off-label uses, has become framed as a debate between consumer protectionists and industry. ("Off-label" use means that a drug approved by the FDA for one use is prescribed by doctors for another purpose. It has long been recognized as legal and proper for physicians to do this; however, pharmaceutical companies could not promote such uses. They could give doctors peer-reviewed articles if asked, but could not take the initiative to provide them, even to a doctor.) Opponents say that the new law will allow companies to profit from uses not proved safe and effective, will remove incentive for companies to get their drugs approved for new uses, and will result in more prescriptions not being covered by insurance. They fear that companies could start promoting new uses just by announcing that they will file an IND, doing the minimal paperwork, and repeating the process whenever necessary; the law requires an IND (so that the offlabel uses will be researched and, if proven, come onto the label), but cannot stipulate that the IND be a credible one. On the other side, industry sees the new revenue streams from off-label uses as particularly important to small biotech companies which can only afford to go for one approval at a time.
What needs more attention is the apparently large number of people with serious health problems which could be successfully treated with available drugs, but who are never told that by their doctors, even though credible evidence has been published. The number of cases of people who learn by happenstance, through friends, newsletters, or noticing a story in the news, suggests that there are probably hundreds of thousands, possibly millions, who could benefit substantially from known off-label uses of available drugs, but who are not receiving that help today. Most doctors will not bring up treatments which are outside the mainstream and are not promoted.
In recent years the FDA has made it easier for companies to get these new indications approved, which is commendable; but many valid uses will never be submitted for approval (with or without the new legislation), especially if they are inexpensive and therefore will not generate revenue to cover development costs. The new law may have created the first institutional incentive to bring such treatments into use.
Hopefully industry will use this new power responsibly--and medical and public-service organizations will be ready to call companies on any abuses.
