Impending Scandal Involving FDA’s Decision on Plan B by Frank A Sonnenberg MD

What follows is a guest blog by Dr. Frank A. Sonnenberg....

On November 15, 2005 The New York Times reported on a Government Accountability Office (GAO) investigation of the controversial and highly irregular decision by the FDA to reject over-the-counter (OTC) status for Plan B (the “morning after pill”). According to the GAO report, there is evidence that the decision was made before the agency’s own scientific review had been completed. The decision has always been considered by Plan B’s proponents to have been made on political grounds. Plan B, which consists of two oral doses of levonorgestrel (a previously available contraceptive), was originally developed by Women's Capital Corporation, which won approval from the FDA. in 1999 to sell the drug by prescription. In April 2003, Women’s Capital applied for OTC status for Plan B. In December 2003, the FDA’s advisory committee voted 23-4 in favor of granting OTC status. However, despite the fact that the scientific review was not completed until April, 2004, shortly after the December committee vote, Dr. Janet Woodcock, the FDA's acting deputy commissioner of operations, and Dr. Steven Galson, acting director of its drug center, told four top staff members that the application would be rejected. Dr. Galson justified the decision by noting that the studies included an insufficient number of adolescents. A decision was promised by last summer, but on August 26, 2005, the FDA postponed the decision indefinitely. (Science October 7, 2005).

There were a number of other irregularities in the decision. First, the NY Times reported that the FDA considered 23 applications for OTC status in the 10 years from 1994 to 2004. Plan B was the only application to be rejected. Second, according to the GAO, the rationale offered by Dr. Galson was at odds with the FDA’s previous assertion that contraception is the same in all women of childbearing age. In fact, this assertion was previously used to deny a request by oral contraceptive makers for “pediatric exclusivity” patent extensions(Couzin 2005). Finally, and perhaps of most concern, as reported in today’s New Jersey Star Ledger, attempts to determine the role of former FDA administrator Mark McClelland, now head of the Centers for Medicare & Medicaid Services (CMS) revealed that key documentation and e-mail messages had been destroyed, possibly in violation of federal records laws.

Dr. Galson said younger teenagers might act differently than older ones and might engage in riskier sex if they knew an emergency contraceptive was easily available. However, there is a plethora of data showing that the availability of Plan B does not increase risky behavior among adolescents. A major study performed in the US, published in January of this year, showed that while women 15-24 years of age were twice as likely to use emergency contraception if it was provided in-advance, they showed no differences in sexual behavior or in the use of contraception. Moreover, as detailed in Science (Couzin 2005) Plan B meets all the criteria for approval of an OTC approval; minimal side effects, lack of abuse potential, easily diagnosable condition (unprotected intercourse) and no requirement for special monitoring of treatment. OTC status for Plan B has been endorsed by a number of professional societies including the American College of Obstetrics and Gynecology.

It is obvious that the decision on Plan B has been influenced by political considerations. It is known that conservatives in Congress and conservative organizations had lobbied against the approval before the FDA’s decision (Steinbrook 2004). Because some in the “family values” movement consider Plan B to be a form of abortion [the FDA considers it to be contraception], the obvious inference is that the FDA is bowing to political pressure not to permit it to go OTC for that reason. The irony is that approximately half of unwanted teenage pregnancies result in abortion and Plan B, with its estimated 85% effectiveness, could prevent a large number of those. Since the US has one of the highest teenage pregnancy rates in the world, this seems to be a case of ideology trumping practical outcomes.

The entire episode is reminiscent of the Bush administration’s promotion of abstinence-only sex education based on the premise that sex education and contraception encourage irresponsible behavior. In fact, a wealth of data demonstrates just the opposite; that adolescents who are exposed to abstinence-only education and those who take abstinence pledges are just as likely to engage in sexual intercourse and are less likely to use contraception when they do (Planned Parenthood), (Sather and Zinn 2002), (DiCenso, Guyatt et al. 2002).

The dangers resulting from subverting sciences for political purposes are very great. In an editorial in April, 2004 (Drazen, Greene et al. 2004), New England Journal of Medicine editor Jeffrey Drazen pointed out that politicization and subversion of science will harm the credibility of the FDA, once considered to be impeccable. In the future, patients and physicians will wonder whether approval decisions will be based on scientific efficacy and safety grounds or on political considerations. The NJ Star-Ledger editorial urged Congress to press the White House on the reasons for the Plan B irregularities.

[Editor's note. The Star-Ledger also noted that "the politics of plan B, however, are only part of the FDA's problem. In crises like vaccine shortages, in addressing safety concerns for medicine like Vioxx and antidepressants and more, the FDA has been clumsy, impotent, too cozy with the drug industry and far from a trustworthy apolitical voice of science it must be if it to protect the public."]

References
Couzin, J. (2005). "Drug regulation. Plan B: A collision of science and politics." Science 310(5745): 38-9.
DiCenso, A., G. Guyatt, et al. (2002). "Interventions to reduce unintended pregnancies among adolescents: systematic review of randomised controlled trials." Bmj 324(7351): 1426.
Drazen, J. M., M. F. Greene, et al. (2004). "The FDA, politics, and plan B." N Engl J Med 350(15): 1561-2.
Sather, L. and K. Zinn (2002). "Effects of abstinence-only education on adolescent attitudes and values concerning premarital sexual intercourse." Fam Community Health 25(2): 1-15.
Steinbrook, R. (2004). "Waiting for plan B--the FDA and nonprescription use of emergency contraception." N Engl J Med 350(23): 2327-9.