Editor's note: This is the second of two articles.
Part 1 of this article series described the FDA's recent attempts to convince its critics that it takes drug safety seriously. In fact, no one who is familiar with the FDA culture and mind-set could possibly doubt that drug safety is paramount - if for no other reason, approving a product that proves to be dangerous can ruin a government career.
Although all drugs have side effects - which can be serious and/or frequent - modern pharmaceuticals have never been safer, more effective, more innovative - or more stringently regulated. But that seems to have escaped the notice of many members of Congress. This month senators introduced two separate bills that will further obstruct innovation and threaten public health.
Senators Edward Kennedy (D-Mass.) and Michael Enzi (R-Wyoming), the chairman and ranking Republican, respectively, of the Health, Education, Labor and Pensions Committee, proposed legislation that would grant the FDA new authority to impose safety requirements on medicines after they have been approved for marketing and would also would require registration of clinical trials and the reporting of their results in public databases. In addition, Senators Chris Dodd (D-Conn.) and Charles Grassley (R-Iowa) introduced legislation that would create within the FDA a center to oversee the safety of drugs after they go on the market.
These bills are the culmination of years of drug company-bashing by a small number of activists and members of congress who have seized on high-profile events such as deficiencies in the labeling of antidepressants and the discovery of previously unknown side effects of various widely used drugs. They will discourage drug development by making it more difficult and expensive and less profitable, at a time when an aging American population desperately needs new and improved (and cheaper) medicines, and when pharmaceutical R&D is already ailing. During the past twenty years the costs have skyrocketed, with direct and indirect expenses now exceeding $900 million dollars to bring an average drug to market. Other trends related to costs are ominous as well: The length of clinical testing for the average drug is increasing, fewer drugs are being approved, and the number of applications to FDA by industry for marketing approval has been declining for more than a decade.
The FDA is already the nation's most powerful and omnipresent regulator, but the Kennedy-Enzi bill would grant new authority, supposedly to ensure the safety of drugs. Among other unwise innovations, it would require the imposition of "risk management action plans (RiskMAPs)" when drugs are approved. Not only does the FDA already have the authority to require these when regulators feel that they are necessary, but they have been overused and abusive: At times the exhaustive (and exhausting) list of requirements for physicians, pharmacists and patients seems more appropriate for weapons-grade plutonium than a pharmaceutical. Some RiskMAPS have contained requirements such as mandatory enrollment in patient registries, limited distribution, and prescribed patient behavior (such as the use of two kinds of contraception, in the case of one drug).
The requirement that drug companies disclose advanced clinical trials in a public database is based on concerns that "negative" results are often obscured or simply not reported. It is intended to prevent companies from "cherry picking" studies, divulging only those that yield favorable results and suppressing the rest.
These concerns are exaggerated. Nothing in our society is currently more stringently regulated and monitored than drug development. During each phase of clinical testing, the FDA reviews and must grant permission for every clinical trial and has access to all of the proprietary information about the drug. When the manufacturer has accumulated evidence that the drug is safe and effective, as part of the application for marketing approval the results of every trial and everything else that is known about the drug, both in the United States and abroad, must be reported to the FDA. Statistical analysis must be performed in an appropriate and pre-specified manner. Moreover, the FDA serves as a repository for data on similar drugs made by other manufacturers. All of this prevents statistical "cherry-picking" or "data mining" that could mislead regulators.
Clinical trials databases are useful to individual patients who wish to ascertain whether they are eligible for a clinical trial that is under way - a function already served by www.ClinicalTrials.gov. But, except for offering a bonanza to plaintiffs' attorneys trolling for business, the benefit of a publicly available database of clinical trial results would be minimal.
There is also the question of the meaning of "negative results" in clinical trials. In the context of scientific and clinical experiments, the term has a meaning very different from the common usage. Such trials are seldom "negative" in the sense of revealing that the drug being tested inflicts harm but for a variety of reasons, they may not be useful or applicable to the indications (uses) for which approval is being sought. The reasons can include: insufficient statistical power (that is, number of patients) in the study; inappropriate choice of route, dose or frequency of administration, or in the stratification of subjects; or simply a failure of the drug to be effective for the indication for which it was tried.
The Dodd-Grassley proposal is even worse. It would create within the FDA an anti-drug entity with strong incentives to argue for the non-approval or withdrawal from the market drugs that have significant side effects even if they offer huge net benefits. (We have seen this already from certain factions within the agency.)
These proposed legislative remedies for the FDA's problems, with more planned for later in the year in both the House and Senate, are analogous to the discredited medical practice of bleeding the patient with leeches. By intensifying the FDA's notorious risk aversion, the new measures will inflate even further the costs, difficulty and uncertainty of drug development and reduce the number of drug candidates that begin and complete clinical testing. They will drain the life's blood from innovation and inflict harm on patients. If these pieces of legislation are enacted, they will validate yet again Will Rogers's observation about Congress: "Every time they make a joke, it's a law. And every time they make a law, it's a joke." And as usual, the joke will be on us.
Dr. Miller, a physician and fellow at the Hoover Institution and Competitive Enterprise Institute, was an FDA official from 1979 to 1994. His most recent book is "The Frankenfood Myth."