Still, there are concrete figures to establish that the PPP program is insufficient, Vega says. Based upon the responses of about 500,000 women that voluntarily enrolled in a study conducted by Boston University's Slone Epidemiology Unit, an estimated 25% of women prescribed Accutane receive no pregnancy test and another 33% begin treatment without first obtaining the results of their pregnancy test, she says.
"There are unacceptable high percentages of physicians and patients not complying with the components of the PPP," Vega says.
Birth defects also are only one of several pregnancy-related problems women confront while on the drug, adds FDA consultant Ed Lammer, MD, a practicing medical geneticist from Oakland, Calif. Even children who appear normal at birth may suffer long-term effects such as learning disabilities, he says. About 40% of these pregnancies result in miscarriage, an often-overlooked side effect, Lammer observes.
"The point is that surveillance of major malformations only hits the tip of the iceberg," he says.
But further regulation over the distribution of Accutane does not enjoy universal support.
"It is education, not mandatory registration, that is the most effective tool," says Barbara Reed, MD, a dermatologist and a member of the American Academy of Dermatology. Mandatory registration disrupts the physician/patient relationship while also restricting the number of physicians able to prescribe the drug, she explains. If patients are forced to give mandatory documentation, they may also seek the drug from underground sources, she says.
Since its approval, the drug has been used by about 2.5 million women, of whom approximately 75% were of childbearing age. This demonstrates that although pregnancies continue to occur, the dimension and challenges of this undesirable outcome has at least been minimized, adds Russell Ellison, MD, vice president of medical affairs at Hoffmann-La Roche.
During the hearing, Hoffmann-La Roche also argued that no additional prescribing or dispensing conditions are needed because of recent changes made to the PPP designed to enhance its effectiveness. These changes include the development of a targeted program specifically aimed at the 3 out of every 1,000 women that truly are at risk of getting pregnant, Roche said.