A Government Accountability Office report released Monday indicates that the Food and Drug Administration did not follow its normal procedures when deciding whether to allow the “morning after” contraceptive Plan B to be sold over the counter. The report shows that the FDA deviated from its normal science-based approach and allowed politics to dictate the decision on Plan B.

The contraceptive, manufactured by Barr Laboratories and marketed as Plan B, contains a higher dose of a hormone than is used in regular birth-control pills. It should be taken within 72 hours of unprotected sex but is most effective in preventing pregnancy when taken in the first 24 hours. Plan B has been available by prescription since 1999, but a decision on over-the-counter sales remains in regulatory limbo after another round of delays this year by the FDA.

“GAO’s final report describes an appalling level of manipulation and suppression of the science,” said Rep. Henry Waxman, D-Los Angeles, who requested the inquiry. “It appears that the decision … was preordained from the outset.”

His criticism was joined by that of Sens. Patty Murray, D-Wash., and Hillary Rodham Clinton, D-N.Y., who also had sought a GAO probe.

“How can American consumers regain confidence in the FDA if science is so clearly overlooked by its leading officials?” they said in a joint statement. “Despite overwhelming evidence that Plan B is safe and effective, politics trumped science in this case.” — Los Angeles Times

In an editorial appearing separately in the Los Angeles Times, the paper blasted religious conservatives, pointing out that Plan B does not cause abortions, but prevents fertilization — that is, it’s a contraceptive — and that restricting access to Plan B will likely cause more abortions, as it should be taken within 24 hours of having sex to be most effective.

Research has shown that levonorgestrel-only hormonal emergency contraception, such as Plan B, interferes with prefertilization events. It reduces the number of sperm cells in the uterine cavity, immobilizes sperm, and impedes further passage of sperm cells into the uterine cavity. In addition, levonorgestrel has the capacity to delay or prevent ovulation from occurring.

ECPs have not been shown to cause a postfertilization event — a change in the uterus that could interfere with implantation of a fertilized egg. — GAO

That means if you wait too long to take it, you’re going to get pregnant, and it won’t abort the pregnancy. Interesting question. Do religious conservatives want more abortions? Is that why they’re opposed to Plan B? Or do they want more teen pregnancy? Religion and birth control is another topic entirely, unfortunately, and it’ll have to wait… On with the story.

In April 2003, Women’s Capital Corporation submitted an application to the Food and Drug Administration (FDA) requesting the marketing status of its emergency contraceptive pill(ECP), Plan B, be switched from prescription to over-the-counter (OTC). ECPs can be used to prevent an unintended pregnancy when contraception fails or after unprotected intercourse, including cases of sexual assault. In May 2004, the Acting Director for the Center for Drug Evaluation and Research (CDER) issued a “not-approvable” letter for the switch application, citing safety concerns about the use of Plan B in women under 16 years of age without the supervision of a health care practitioner. Because the not-approvable decision for the Plan B OTC switch application was contrary to the recommendations of FDA’s joint advisory committee and FDA review staff, questions were raised about FDA’s process for arriving at this decision. GAO was asked to examine (1) how the decision was made to not approve the switch of Plan B from prescription to OTC, (2) how the Plan B decision compares to the decisions for other proposed prescription-to-OTC switches from 1994 through 2004, and (3) whether there are age-related marketing restrictions for prescription Plan B and other prescription and OTC contraceptives. To conduct this review, GAO examined FDA’s actions prior to the May 6, 2004, not-approvable letter for the initial application.

On May 6, 2004, the Acting Director of CDER rejected the recommendations of FDA’s joint advisory committee and FDA review officials by signing the not-approvable letter for the Plan B switch application. While FDA followed its general procedures for considering the application, four aspects of FDA’s review process were unusual. First, the directors of the offices that reviewed the application, who would normally have been responsible for signing the Plan B action letter, disagreed with the decision and did not sign the not-approvable letter for Plan B. The Director of the Office of New Drugs also disagreed and did not sign the letter. Second, FDA’s high-level management was more involved in the review of Plan B than in those of other OTC switch applications. Third, there are conflicting accounts of whether the decision to not approve the application was made before the reviews were completed. Fourth, the rationale for the Acting Director’s decision was novel and did not follow FDA’s traditional practices. The Acting Director stated that he was concerned about the potential behavioral implications for younger adolescents of marketing Plan B OTC because of their level of cognitive development and that it was invalid to extrapolate data from older to younger adolescents. FDA review officials noted that the agency has not considered behavioral implications due to differences in cognitive development in prior OTC switch decisions and that the agency previously has considered it scientifically appropriate to extrapolate data from older to younger adolescents.

The Plan B decision was not typical of the other 67 proposed prescription-to-OTC switch decisions made by FDA from 1994 through 2004. The Plan B OTC switch application was the only one during this period that was not approved after the advisory committees recommended approval. The Plan B action letter was the only one signed by someone other than the officials who would normally sign the letter. Further, there are no age-related marketing restrictions for any prescription or OTC contraceptives that FDA has approved, and FDA has not required pediatric studies for them. FDA identified no issues that would require age-related restrictions in the review of the original prescription Plan B new drug application.

In its comments on a draft of this report, FDA disagreed with GAO’s finding that high-level management was more involved with the Plan B OTC switch application than usual, with GAO’s discussion about when the not-approvable decision was made, and with GAO’s finding that the Acting Director of CDER’s rationale for denying the application was novel. However, GAO found that high-level management’s involvement for the Plan B decision was unusual for an OTC switch application and FDA officials gave GAO conflicting accounts about when they believed the decision was made. The Acting Director acknowledged to GAO that considering adolescents’ cognitive development as a rationale for a not-approvable decision was unprecedented for an OTC application, and other FDA officials told GAO that the rationale differed from FDA’s traditional practices. — Government Accountability Office (PDF)

Let’s look at these four deviations in some more detail.

First, the heads of the FDA’s offices that would normally sign the FDA’s decision to block Plan B did not sign it, because they disagreed with it. After all, it had no basis in science. “Dr. Florence Houn, whose office deals with reproductive drugs, and Dr. Jonca Bull, responsible for over-the-counter medicines, refused to sign the agency’s decision because they disagreed with it. Dr. John Jenkins, director of the Office of New Drugs, also disagreed and did not sign the decision,” said the Times.

Second, high-level management was more involved in the review of Plan B than in other applications to switch a drug from prescription to over-the-counter. At “a meeting held on January 15, 2004, the Acting Director of CDER informed them that the decision for the Plan B OTC switch application would be made by high-level management. This action removed decision-making authority from the directors of the reviewing offices who would normally make the decision,” the GAO report said.

Third, there are conflicting accounts as to whether the decision to reject the OTC switch was made before scientific reviews were completed.

FDA officials, including the Director and Deputy Director of the Office of New Drugs and the Directors of the Offices of Drug Evaluation III and V, told us that they were told by high-level management that the Plan B OTC switch application would be denied months before staff had completed their reviews of the application. The Director and Deputy Director of the Office of New Drugs told us that they were told by the Acting Deputy Commissioner for Operations and the Acting Director of CDER, after the Plan B public meeting in December 2003, that the decision on the Plan B application would be not-approvable. They informed us that they were also told that the direction for this decision came from the Office of the Commissioner. The Acting Deputy Commissioner for Operations and the Acting Director of CDER denied that they had said that the application would not be approved. In addition, although minutes of the January 15, 2004, meeting stated that the Acting Director told review staff that a not-approvable decision was “recommended,” review staff documented that they were told at this meeting that the decision would be not-approvable. Both office reviews were not completed until April 2004. — GAO

It turns out that the acting director of CDER, Dr. Steven Galson, needed more time to come up with an excuse to justify his decision to reject the OTC switch. “The Acting Director of CDER told us that the rationale for his decision was not fully developed until a few days before the action letter was issued on May 6, 2004,” the GAO report says, and wait until you hear what it was.

Fourth, the rationale for Galson’s decision did not follow normal FDA practices.

The Acting Director was concerned about the potential impact that the OTC marketing of Plan B would have on the propensity for younger adolescents to engage in unsafe sexual behaviors because of their lack of cognitive maturity. The Acting Director further concluded that because these differences in cognitive development made it inappropriate to extrapolate data from older to younger adolescents in this case, there was insufficient data on the use of Plan B among younger adolescents. FDA review officials disagreed with the Acting Director’s rationale and noted that the agency had not considered behavioral implications resulting from differences in cognitive development in prior OTC switch decisions. — GAO

Now that’s a good one. In short, Galson is saying that young teenagers will have more sex if they have better access to birth control. As if they’re not having sex already. Perhaps Galson wants these 13, 14 and 15 year olds to have children.

Let’s get down to reality here. You aren’t going to prevent a teenager from doing something you don’t want them to do. If you doubt this, you either have never been a parent, or you’re incredibly naïve, should go find out what your children have been doing behind your back, and give up trying to strip away everyone else’s freedom.