Gaps, Tensions, and Conflicts in the FDA Approval Process: Implications for Clinical Practice

Richard A. Deyo, MD, MPH

Disclosures

J Am Board Fam Med. 2004;17(2) 

In This Article

Abstract and Introduction

Despite many successes, drug approval at the Food and Drug Administration (FDA) is subject to gaps, internal tensions, and conflicts of interest. Recalls of drugs and devices and studies demonstrating advantages of older drugs over newer ones highlight the importance of these limitations. The FDA does not compare competing drugs and rarely requires tests of clinical efficacy for new devices. It does not review advertisements before use, assess cost-effectiveness, or regulate surgery (except for devices). Many believe postmarketing surveillance of drugs and devices is inadequate. A source of tension within the agency is pressure for speedy approvals. This may have resulted in "burn-out" among medical officers and has prompted criticism that safety is ignored. Others argue, however, that the agency is unnecessarily slow and bureaucratic. Recent reports identify conflicts of interest (stock ownership, consulting fees, research grants) among some members of the FDA's advisory committees. FDA review serves a critical function, but physicians should be aware that new drugs may not be as effective as old ones; that new drugs are likely to have undiscovered side effects at the time of marketing; that direct-to-consumer ads are sometimes misleading; that new devices generally have less rigorous evidence of efficacy than new drugs; and that value for money is not considered in approval.

The process of drug development and approval by the United States Food and Drug Administration (FDA) was recently reviewed by Lipsky and Sharp.[1] Using clinical literature and web sites addressing FDA procedures, that review concisely described the FDA's history, the official approval process, and recent developments in drug approval. However, it did not delve into common misconceptions about the FDA, tensions within the agency, or conflicts of interest in the drug approval process. The rapidly growing business of medical device development, distinct from the drug approval process, also was not addressed. Although most aspects of the FDA review process are highly successful, its limitations deserve careful consideration, because they may have important implications for choosing treatments in practice.

Recent recalls of drugs and devices call attention to limitations of the approval process.[2,3,4] Recent news about complications of hormone replacement therapy[5,6] and new data supporting the superiority of diuretic therapy over newer, more expensive alternatives for hypertension[7] emphasize gaps in the process. Clinicians should be aware of regulatory limitations as they prescribe treatments and counsel patients, so they have realistic ideas about what FDA approval does and does not mean.

Because controversies relating to internal conflicts or political issues are infrequently reported in scientific journals, this discussion draws not only on scientific articles, but also internet resources, news accounts, and interviews. The goal was not to be exhaustive, but to provide examples of tensions, conflicts, and gaps in the FDA process.

As Lipsky and Sharp noted, the FDA approves new drugs and devices (as well as assuring that foods and cosmetics are safe). It monitors over $1 trillion worth of products, which represents nearly a fourth of consumer spending.[1] In the medical arena, the basic goal of the FDA is to prevent the marketing of treatments that are ineffective or harmful. However, the agency faces limitations that result from many factors, including the agency's legal mandate, pressures from industry, pressures from advocacy groups, funding constraints, and varied political pressures.

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