Just days before the Food and Drug Administration rejected an application to make the emergency contraceptive Plan B available without a prescription, top agency scientists dismissed the reasoning that was used to justify the rejection as unfounded, internal agency documents reveal.
The documents, which contain the scientific conclusions of three separate levels of FDA reviewers, show that the scientists disagreed in particular with the contention that there was not enough information to assess how easier availability of the drug would affect the sexual behavior of young teenagers. That was the primary reason given for the FDA's dismissal of the application as "non-approvable."
One top official wrote that by raising the issue of teenage use, former commissioner Mark B. McClellan and Center for Drug Evaluation and Research acting Director Steven K. Galson appeared to be introducing a different standard for evaluating Plan B than the FDA had applied to other contraceptives.
"The agency has not [previously] distinguished the safety and efficacy of Plan B and other forms of hormonal contraception among different ages of women of childbearing potential, and I am not aware of any compelling scientific reason for such a distinction in this case," wrote John Jenkins, director of the FDA's Office of New Drugs, which oversees all drug reviews for the agency.
When Galson announced the surprise rejection on May 6, he acknowledged that the FDA staff disagreed. But there was no further explanation, and the internal documents offer the first look at the depth and breadth of the disagreement.
FDA spokesman Lawrence Bachorik said the agency "will not comment on internal deliberative documents that were part of our decision-making process."
The May 6 decision set off intense criticism from legislators and advocates, many of whom accused the FDA of succumbing to political pressure from social conservatives who opposed making the emergency contraceptive more accessible. Forty-nine conservative members of Congress wrote a letter to President Bush in January asking that the application be rejected, in large part because of concerns over use by teenagers.
The ensuing criticism of the FDA, which has been leveled by Democrats and some Republicans, led this week to a formal request by Sen. Hillary Rodham Clinton (D-N.Y.) for a Senate hearing and a General Accounting Office inquiry into the decision. In her letter to Sen. Judd Gregg (R-N.H.) requesting a hearing, Clinton wrote that reports of "irregularities" in FDA decision making required an oversight hearing.
The letter was signed by 23 other senators, including presumed Democratic presidential nominee Sen. John F. Kerry (D-Mass.).
When the FDA rejected the application from Barr Laboratories Inc. to make Plan B an over-the-counter drug, Galson, a physician and civil servant, said he made the decision based on scientific concerns and not political pressure.
In an internal memo, Galson acknowledged that "some staff have expressed the concern that this decision is based on non-medical implications of teenage sexual behavior, or judgments about the propriety of this activity." He called the staff's concerns unfounded.
While the FDA documents are written in bureaucratic and sometimes technical language, they also reflect a level of frustration among some of the reviewers and their managers. For instance, Jonca Bull, head of the office that oversees decisions to make drugs available without prescription, referred to some of the issues raised against immediate Plan B approval as "speculative and unbalanced."
Addressing the contention that easy availability of Plan B might result in decreased condom use and an increase in sexually transmitted diseases, Bull wrote that, "again, the logic is flawed and speculative."
The differences between Galson's conclusions in rejecting the applications and the assessments of his staff are often stark. According to Office of New Drugs chief Jenkins, the data submitted are "fully consistent with the agency's usual standards for meeting the criteria" for a switch to over-the-counter, or non-prescription, status. He said all the reviewers agreed, as did an advisory panel, which voted 23 to 4 for approval in December.
The staff reviewers concluded that studies indicated that teenagers would not change their sexual behavior if Plan B became available on open drugstore shelves, that there would be no additional risk of sexually transmitted diseases, and that there was no basis for deeming Plan B any less safe or effective for teenagers than for older women.
In addition, Bull said the FDA had approved numerous contraceptives for non-prescription use, setting a precedent for the proposed Plan B switch.
Galson, however, ruled that there was insufficient information on how adolescents, especially sexually active 11-to-14-year-old girls, might behave. He added that information about mid-adolescents cannot be used to extrapolate how younger girls would act. In addition, he said there was insufficient information that young teenagers would use the product correctly without the help of health care providers or parents.
Galson did not respond to the precedents cited by Bull that made some other contraceptive products available over-the-counter. On June 2, Rep. James C. Greenwood (R-Pa.,) chairman of a subcommittee with jurisdiction over the FDA, had a private meeting with Galson after House members also called for a hearing on the Plan B decision.
Greenwood said Wednesday that he considered the FDA decision to be a "horrible one" and met with Galson to determine whether to hold hearings. Greenwood said he was surprised to hear from Galson that the FDA was leaning toward approving Plan B for women older than 16 within six months.
"There was no guarantee from Galson, but he said their only concerns were for girls under 16, and I took that to mean they would approve it OTC for everyone else quite soon," Greenwood said in an interview.
Asked if he thought the rejection of the initial Plan B application was influenced by political considerations, Greenwood said he had no direct information, but "maybe some folks thought it would be more comfortable politically to give an approval after the election."