January 1, 2006 (Vol. 26, No. 1)

Proposal Builds on Existing Law for Politically Achievable Reform

In the wake of the Vioxx debacle, physicians and consumers alike have lost confidence in the FDA’s ability to ensure patient safety. And no one can blame them.

Since Vioxx, nothing has really changed. The FDA continues to review drugs before they get to the market, but does virtually nothing to compare drugs and systematically assess them for safety once they get there.

Millions of Americans now take a new class of antidepressant drug called SSRIs, millions of Americans rely on drugs such as Celebrex for pain relief, and millions of Americans take statin drugs such as Crestor and Lipitor for high cholesterol.

Will Celebrex be the next Vioxx? Will Paxil? Lipitor? We don’t know. There have been no comparative long-term clinical trials to test the safety of these medications now that they are on the market. This needs to change.

In the next two years, policymakers will revisit how the FDA spends user fees it collects from pharmaceutical companies. The user-fee program charges drug companies a fee for every drug they submit to the FDA, and the funds are used to expand the FDA’s review staff.

It is clear that the user-fee program has accelerated the pace of FDA drug approval. To many physicians, patient advocates, consumer advocates, academic researchers, and members of Congress, however, the user-fee program has also compromised the FDA’s regulation of drug safety; they say it has changed the culture of the agency, diverted resource, and emphasis on pre-market review, and imposed stringent deadlines on FDA reviewers. The user-fee program, these critics believe, has worsened the FDA’s scrutiny of drug safety, especially long-term safety.

In 2007, policymakers have a chance to re-vamp the user-fee system. They should use that opportunity to increase user fees and use those funds for rigorous post-marketing study of drugsnot simply quick approvals.

The current user-fee arrangement exacts a per-application fee upon pharmaceutical sponsors who submit new product applications to the FDA. In theory, these funds are then used to purchase more reviewers. But this is not enough to ensure patient safety.

The FDA should increase these fees and use the new monies on post-marketing safety studies, preferably long-term randomized and controlled clinical trials that directly compare one drug to another.

Comparative Safety Information

It’s as simple as that. A small (25%) increase in the user-fee could generate $42 million per year. That money could be spent most fruitfully by producing better information on the long-term comparative safety of medicines widely used for chronic conditions.

Think of drugs with Vioxx-like marketsfen-phen, Prozac, Viagrawhere even small changes in aggregate risk can translate to thousands of deaths and injuries, and billions of dollars in of damages.

Such information is extremely scarce in the U.S. healthcare system. It is chronically undersupplied in the global pharmaceutical economyin part because Phase IV studies are too poorly designed to get at it, and because they are carried out slowly and rarely completed.

While we have plenty of epidemiological data, there is a dire need for randomized, clinical trials comparing the safety of drugs for chronic conditions. Let a committee of drug safety specialists pick the five to ten drugs they are most worried about and test each of them in long-term comparative clinical trials.

Compare one blockbuster to anotherCialis to Viagra, Paxil to Effexor, Crestor to Lipitoracross large populations, even testing subpopulations with specific genotypes. This would give valuable information to physicians, consumers, companies, the FDA, and health plans, in addition to saving lives.

So the targets for this money are easy enough to identify. Who gets to allocate the cash? The best solution would be an independent committee empowered to make funding choiceslike those that currently decide on grants at the National Science Foundation and the National Institutes of Health.

It would be perhaps best to exclude company representatives from this committee, in part because if companies were included, then a representative from Merck could be voting on whether a blockbuster drug from Pfizer gets postmarketing scrutiny, or vice versa, and we end up back in the same boat.


The plan, of course, comes with risks. Unlike the current user-fee system, a reformed system would not be limited to generating a product that all companies find to be in their short-term interest. The studies could reveal serious long-term safety programs with drugs that generate immense cash flow.

Yet these very risks would function as an inexpensive but visible act of commitment to a better-informed marketplace on the part of the FDA and companies. As political scientist Jon Elster wrote in Ulysses and the Sirens, many of the most important (and interesting) problems in politics are those of pre-commitment.

Because Ulysses knew the Sirens would tempt him with their beautiful song as he passed their coast, he plugged the ears of his sailors with wax and had himself lashed to the mast of his vessel. Ulysses’ self-immobilization was not only life-saving, but it was also a credible signal to his political community, to his shipmates, and others that he was serious about completing his voyage.

The FDA and the pharmaceutical industry would do well to undertake such a commitment by modestly but imaginatively changing the user fee program.

Of course user-fee-funded studies might shed negative light on drugs from which companies generate significant cash flow. But that is not a valid reason to oppose the reform. As the Vioxx example shows, if a drug is unsafe, the truth will eventually come out and the patients, as well as the company, will pay dearly.

On the other hand, if an FDA-sponsored study shows problems with a drug, companies’ product liability will be much less severe. Plaintiffs will not be able to claim that the company knew about the drug safety problem ahead of time because the crucial studies are being run independently.

This idea is not a solution to all of the ills currently afflicting the FDA, the pharmaceutical industry, and the U.S. healthcare system. The nice thing about the proposal is that it builds on existing law, it is a politically achievable, incremental reform, and it can be combined with radical or cosmetic surgery as policymakers prefer.

At the very least, it would supply us all with information that we sorely need, and it would give much-needed credibility to a regime that seems to be running out of it.

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