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Politics trumps science at the FDA

In May, 2004, the US Food and Drug Administration (FDA) rejected an application to make the emergency contraceptive Plan B, a two-dose regimen of levonorgestrel (0·75 mg), available without prescription.

In rejecting the emergency contraceptive, FDA officials ignored not only the advice of the outside experts serving on the agency's advisory committee but also the recommendations of their own internal reviewers. In the letter explaining the decision, the acting director of the FDA's Center for Drug Evaluation and Research said the application was being rejected because of concerns that Plan B might not be safe for use by women younger than 16 years. Advocates for over-the-counter access, however, scoffed at the claim: the concerns were not about the health of women, they charged, but politics.

In response to the rejection, Plan B's manufacturer, Barr Pharmaceuticals (Woodcliff Lake, NJ, USA), resubmitted an application for over-the-counter access for women older than 16 years, but the agency has repeatedly delayed a decision. The handling of the application has been so irregular that the director of the agency's Office of Women's Health, Susan Wood, resigned in August in protest.

A new report, released on Nov 14, adds further support to allegations that politics trumps science at the FDA. The report, prepared by the Government Accountability Office (GAO), an investigative agency of the US Congress, finds that four aspects of the FDA's review process were, as the report tactfully puts it, "unusual".

First, the directors of the offices that reviewed the application did not agree with the decision and did not sign the action letter rejecting the application. Ordinarily these officers would be responsible for signing such documents.

Second, the GAO investigators found that high-level FDA managers were more involved in the review process than they have been in other so-called "OTC switch" applications.

Third, and particularly worrying, GAO investigators wrote that they had heard conflicting accounts of whether the decision to reject had been made before the review process had been completed.

And, fourth, the justification of the decision "was novel and did not follow FDA's traditional practices". In particular, the investigators questioned the acting director's explanation that he made the decision because of concerns that marketing Plan B to younger adolescents might affect their behaviour, because of their level of cognitive development and because it was invalid to extrapolate safety data derived from older adolescents to younger individuals. Such considerations have never been raised for other applications requesting over-the-counter status for prescription drugs.

If taken within 72 h of unprotected intercourse, the Plan B regimen has been shown to prevent 85 pct. of the pregnancies that would be expected without treatment; this percentage increases to 95 pct. if taken in the first 24 h. The later treatment is started, however, the less effective it is. Over-the-counter access would make it possible for women to obtain the drug quickly when it will be most effective.

Although treatment is thought to prevent pregnancy by suppressing ovulation and interfering with fertilisation—ie, as a contraceptive—critics argue that because the drug may interfere with post-fertilisation events it is tantamount to abortion.

In addition, opponents contend that making the contraceptive easily available will promote unsafe sexual activity in young people. The GAO report suggests that FDA officials, despite their protestations to the contrary, decided to sacrifice the agency's reputation for independence and scientific rigour to satisfy these critics, most of whom are strong political supporters of the Bush Administration.

Ironically, because of the FDA officials' decision, more women are likely to have unwanted pregnancies and as a result there will be more, rather than fewer, abortions.

The report is another blow to the FDA, which is coming under increasing scrutiny. Serious questions have been raised over its handling of drug-safety issues, in particular its handling of rofecoxib, the cyclo-oxygenase 2 inhibitor that was withdrawn from the market after being linked to an increased risk of myocardial infarction and stroke. And there are growing concerns that the agency, which now depends on fees from manufacturers for a substantial proportion of its budget for drug assessment and research, has become too dependent on the industry it is supposed to regulate.

Trust in this agency is fast eroding. To restore the FDA's reputation, its leadership needs to move quickly. A first step would be to allow the Plan B review to proceed according to standard procedure without any further interference.

The Lancet

2005; 366:1827