By Steve Weinstein
By Devon Maloney
By Tessa Stuart
By Alison Flowers
By Albert Samaha
By Jesse Jarnow
By Eric Tsetsi
By Raillan Brooks
A decision about whether to put the emergency contraceptive marketed as Plan B on drug store shelves has been stalled inside the Food and Drug Administration for nearly two years. Plan B, in essence, is a booster dose of the ordinary birth-control pill.
Scientific review panels for the FDA and FDA staff studied the morning-after pill and said it was safe enough to sell over the counter. But in May 2004, the upper management of the FDA, perhaps with an ear toward the religious right's objections, said no. At issue, said FDA management, is that teenagers could buy the drug.
Monday's GAO report on the morning-after pill came at the request of a group of several dozen lawmakers, including senators Ted Kennedy and Hillary Clinton. Barr Pharmaceuticals, which makes Plan B, has had a revised application pending for more than yearthis one to allow over the counter sale to women older than 16. Clinton in particular has continued to press for a decision.
In its report, the GAO describes a paternalistic government agency that made its mind with little regard for science. The GAO notes: The Acting Director of CDERthe Center for Drug Evaluation and Researchtold us he signed the not-approvable letter because of his concerns about the lack of cognitive development and the potential for risky behaviors among younger adolescents resulting from increased access to Plan B.
What follow are more excerpts from the report, titled Food and Drug Administration: Decision Process to Deny Initial Application for Over-the-Counter Marketing of the Emergency Contraceptive Drug Plan B Was Unusual.
Though filled with government-speak, the report is a must-read for anyone who cares about women's access to contraception.
"Four aspects of FDA's review process were unusual: officials who would normally have been responsible for signing an action letter disagreed with the decision and did not sign the not-approvable letter for Plan B; high-level management was more involved than for other OTC switch applications; conflicting accounts exist of whether the decision to not approve the application was made before the reviews were completed; and the rationale for the not-approvable decision was novel and did not follow FDA's traditional practices.
[. . .]
(Editor's note: The FDA's director of the Center for Drug Evaluation and Research met with review staff on January 15, 2004, about the position of the FDA commissioner on the morning-after pill.)
"FDA's minutes from this meeting stated that the Acting Director of CDER informed review staff that a not-approvable letter was recommended based on the need for more data to clearly establish appropriate use in younger adolescents.
[. . .]
"According to review staff . . . at this January 2004 meeting the Acting Director of CDER also told them that the decision on the Plan B OTC switch application would be made at a 'level higher than them. . . .'
[. . .]
"On February 18, 2004, review staff . . . presented their findings to high-level management, including the Commissioner and the Acting Director of CDER. According to interviews with officials from the Office of New Drugs and review staff . . . they said these data provided sufficient evidence that there was neither an increase in risky behaviors nor any difference in appropriate use between younger adolescents and older populations. According to FDA's minutes of this meeting, the Commissioner expressed multiple points, including the potential for changes in future contraceptive behaviors after adolescents took Plan B and that counseling by a learned intermediary might be beneficial, particularly for adolescents.
[. . .]
"By early April 2004, the reviews from the Offices of Drug Evaluation III and V were completed. The directors of these offices agreed with the recommendations of the joint advisory committee and review staff that Plan B should be made available without a prescription. Nonetheless, the office directors told us that they were asked by high-level management to draft a not-approvable letter. Both office directors also told us they did not agree with a not-approvable action and did not sign the not-approvable letter.
"The issue was then raised to the Office of New Drugs. The Director of the Office of New Drugs reviewed the staff's analysis of the application and concurred with the recommendations of both office directors. He also did not sign the not-approvable letter. The Director of the Office of New Drugs told us that it was 'very, very rare' that his office would become involved in the signing of an action letter.
[. . .]
"According to review staff . . . 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. According to minutes from a subsequent meeting between review officials and the sponsor on January 23, 2004, the Director of the Office of New Drugs informed the sponsor that such a high-level decision was not typical of CDER's procedures for drug approvals.
"The Acting Director of CDER told us that management needed to be comfortable with review staff's final decision because of the high visibility and sensitivity of the Plan B OTC switch application. He and other senior FDA officials told us that involvement by high-level management stemmed from the agency's practice of delegated authority. In addition to highly visible and sensitive cases, they said that the Commissioner and the Director of CDER would also generally become involved in cases that would potentially have a far-reaching impact or in cases in which management had a different view or disagreed with review staff.
[. . .]
"FDA officials gave conflicting accounts of when the not-approvable decision for the Plan B OTC switch application was made. FDA officials . . . 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 43 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.
[. . .]
"However, the Acting Director of CDER told us that he made the decision to not approve the Plan B OTC switch application shortly before signing the action letter. He also informed us that his decision was made in consultation with other high-level management officials, including the Commissioner and the Acting Deputy Commissioner for Operations, but that he was not directed to reach a particular decision.
[. . .]
"The Acting Director of CDER told us he signed the not-approvable letter because of his concerns about the lack of cognitive development and the potential for risky behaviors among younger adolescents resulting from increased access to Plan B. For example, he noted increased access to Plan B could potentially result in an increase in unsafe sexual activity, particularly among younger adolescents-an age group, he noted, that has a tendency to engage in risky behaviors because of their level of cognitive development.
[. . .]
"Although review staff . . . presented him with additional data on sexual behaviors of younger adolescents in association with increased access to ECPs [emergency contraceptive pills], the Acting Director of CDER determined that these data were not adequate to support the approval of Plan B for OTC use.
[. . .]
"FDA review staff, the Directors of the Offices of Drug Evaluation III and V, and the Director of the Office of New Drugs disagreed with the Acting Director of CDER's rationale for not approving the Plan B OTC switch application. FDA review officials . . . noted that traditionally FDA has not considered whether younger adolescents would use an OTC product differently than older adolescents, and the Director of the Office of New Drugs told us that it was 'atypical' to raise the question of maturity during a drug review.. . .
"Review staff told us they examined benefit-risk issues for Plan B, and they concluded that concerns regarding the potential for unsafe sexual behaviors among adolescents could not be supported.
[. . .]
"From 1994 through 2004, Plan B was the only prescription-to-OTC switch decision that was not approved after the joint advisory committee voted to recommend approval of the application. FDA advisory committees considered 23 OTC switch applications during this period; the Plan B OTC switch application was the only 1 of those 23 that was not approved after the joint advisory committee voted to recommend approval of the application. In addition, there has been only 1 other decision for an OTC switch application that did not follow the recommendations of the joint advisory committee.
[. . .]
"According to the Deputy Director of the Office of New Drugs, there are no age-related marketing restrictions for any FDA-approved contraceptives, and FDA has not required any pediatric studies. Condoms and spermicides are available to anyone OTC, while intrauterine devices; diaphragms; cervical caps; and hormonal methods of contraception, including ECPs, are available to anyone with a prescription. For hormonal contraceptives, FDA has assumed that suppression of ovulation is the same in all postmenarcheal females, regardless of age.
[. . .]
"While we agree with FDA that the Director of CDER and other high-level officials generally are more likely to become directly involved in high-profile regulatory decisions and noted that in the draft of the report, we found that this level of involvement is unusual for OTC switch applications.
[. . .]
"FDA commented . . . that it is inaccurate to conclude that a decision to deny the application was made several months before the not-approvable letter was issued. However . . . the Director and Deputy Director of the Office of New Drugs and other officials told us that they were informed during December 2003 and January 2004 that the application would not be approved.
[. . .]
"FDA disagreed with our finding that the Acting Director's rationale for denying the application was novel and did not follow FDA's traditional practices. FDA commented that the Acting Director's focus on the potential implications to the sexual behavior of adolescent women of approving the Plan B OTC switch application was appropriate and consistent with FDA's treatment of other OTC switch applications.
[. . .]
"We found that the Acting Director's rationale was novel because it explicitly considered the differing levels of cognitive maturity of adolescents of different ages, and that because of the Acting Director's views about these cognitive maturity differences, he concluded that it was inappropriate to extrapolate data related to risky sexual behavior from older to younger adolescents.