The Journal of the American Medical Association has published an important set of articles on the drug approval and post-approval surveillance process. In their overview article Fontanarosa et al. characterize the general problem as follows:

“Physicians and patients expect that when medications are prescribed correctly for labeled indications and are used as directed, these medications generally will have beneficial effects and will not cause significant harm. This confidence in pharmaceutical products reflects trust in the effectiveness and integrity of the drug approval and monitoring process… However, the current approval process for drugs and biological agents in the United States has come under intense scrutiny, most notably because of concerns about influence from industry… In addition, an investigation of 18 FDA expert advisory panels revealed that more than half of the members of these panels had direct financial interests in the drug or topic they were evaluating and for which they were making recommendations.

The drug review process has been described as structurally similar to many decisions made by other regulatory agencies, such that it is characterized by high uncertainty, avoidance of observable error, and low (reputational) reversibility, with drug recalls harming the reputation of the FDA for a faulty approval decision, and often severely affecting the manufacturer. Given that new products are the financial lifeblood of pharmaceutical companies, the stakes are raised higher due to intense lobbying by interested parties such as health professionals and patient advocacy groups, as well as pharmaceutical and technology companies, so it is no wonder that, in 2003, the pharmaceutical industry earmarked $4.9 million to lobby the FDA… While these concerns are noteworthy, they pale in comparison to the shortcomings and failures of the current imperfect system for postmarketing surveillance… Yet the major problem with the current system for ensuring the safety of medications is that drug manufacturers are largely responsible for collecting, evaluating, and reporting data from postmarketing studies of their own products. This approach has many inherent problems. For instance, it appears that fewer than half of the postmarketing studies that manufacturers have made commitments to undertake as a condition of approval have been completed and many have not even been initiated. Moreover, despite the mandatory adverse event reporting system for companies subject to the FDA’s postmarketing safety reporting regulations, drug manufacturers may be tempted to conceal available data that may signal the possibility of major risks. In some cases, the FDA and drug manufacturers may fail to act on that information and fail to conduct appropriate studies to examine a potential risk rigorously and promptly.”

The article concludes:

“The postmarketing surveillance system requires a long overdue major restructuring. Until that occurs—as indicated by the articles in this issue of JAMA, as epitomized by recent evidence of serious harms from widely used and heavily promoted medications, as demonstrated by the influence of industry over postmarketing data, and as illustrated by the lengths to which some manufacturers will go to protect their interests—the United States will still be far short of having an effective, vigilant, and trustworthy system of postmarketing surveillance to protect the public.”

Fontanarosa et al. are exactly right to recognize that the issues faced in postmarketing surveillance of drugs are part of a larger class of issues at the interface of politics, parochial interests, uncertainty, and science. They note that the FDA has asked the Institutes of Medicine to organize a study to “study the effectiveness of the United States drug safety system with emphasis on the post-market phase, and assess what additional steps could be taken to learn more about the side effects of drugs as they are actually used. The committee will examine FDA’s role within the health care delivery system and recommend measures to enhance the confidence of Americans in the safety and effectiveness of their drugs.”

Given the attention being paid to advisory panel composition, it will be very interesting to see how the IOM comprises this panel.

This case highlights the need for honest brokers in important political issues with a scientific element. As Dr. Alastair Wood of Vanderbilt University, commented on the issue in today’s New York Times,

“When we have a drug problem it’s analogous to a plane crashing off the coast of New York City, and being investigated by the air traffic controllers who controlled the flight and the airline flying the plane. They’re not bad people, but it’s not the way we do things in this country.”