Learning from the Accutane experience - anti-acne drug which causes birth deformities

LEARNING FROM THE ACCUTANE EXPERIENCE

As headlines about the birth deformities caused by the anti-acne drug Accutane fade from view, what remains are some serious questions about the FDA's ability to protect the public. The tragedy appears to be due to a combination of inappropriate prescribing practices, an inadequate reporting system for adverse reactions, and a lack of mandated consumer information with all prescription drugs. While all these areas have been traditionally beyond the FDA's regulatory reach, Accutane may provide the impetus for some valuable changes.

Some experts have likened Accutane to thalidomide in terms of its potential human toll. (Thalidomide was a sedative drug widely used in Europe and England in the 1950's and 60's. It caused thousands of serious birth deformities in the offspring of women who took it while pregnant.) The fact that thalidomide was not approved by the FDA for sale in the U.S. is often used as proof of the agency's effectiveness. But the strength of the FDA's premarketing vigilance is seriously compromised by its traditional unwillingness to regulate drugs after they are approved. In a reversal of thalidomide roles, England and Europe, where use of Accutance is more tightly regulated, have reported a very small number of reported birth deformities compared to the U.S.

Accutane is approved as a treatment of cystic acne (a severe, painful and disfiguring kind that afflicts adults as well as teenagers) when antibiotics and topical treatments have failed. Only 2.5 to 3 percent of the millions of people with acne are estimated to have the cystic form. FDA epidemiologists have compared the frequency of cystic acne in the U.S. with the prescription rate of Accutane concluded that more than 75 percent of the prescriptions are inappropriate.

Accutane was approved in 1982, even though its potential to cause birth defects was well known from the animal experiments conducted as part of the approval process. This knowledge led to the inclusion of warnings about use in pregnancy in the original drug labeling given only to physicians. By 1983 there had been reports of at least three deformed babies born to women who used the drug while pregnant. Other adverse reactions became apparent including pseudomotor cerebri, a condition that mimics brain tumors and can cause serious vision problems.

In 1983 Accutane's manufacturer, Hoffman-LaRoche, sent a "Dear Doctor" letter to physicians alerting them to the reports of birth defects "possibly related to Accutane use." Doctors and pharmacists were also urged to distribute the manufacturer's brochure which warned about risks of use in pregnancy but cited only animal data, not the reports of birth defects in human offspring.

At two FDA advisory committee meetings in 1984, Hoffman-LARoche reported on experience with Accutane in over 200 pregnant women, over half of whom had elective abortions after their pregnancies were confirmed. At least 28 infants were born deformed. The manufacturer stated it had sent out more "Dear Doctor" and "Dear Pharmacist" letters, provided warning labels for druggists to stick on prescriptions, and improved the patient brochure which doctors or pharmacists could obtain for voluntary distribution. By 1988 FDA scientists estimated that related to their mothers' Accutane use. 500 to 600 infants were born with deformities.

Once the tragedy was announced to thr public, the FDA had to consider several options that included: revocation of the drug's approval, reliance on Hoffman-LaRoche to place limits on access to the drug voluntarily, strengthen warning labeling and require signed consent forms. The FDA has not indicated interest in revoking approval, but it recently announced a stronger warning label (which may include pictures of a deformed child), a "blister" package with an affixed warning label, and signed consents.

Many of the news stories about Accutane-caused birth defects indulged in some degree of "victim blaming" by suggesting that despite the best efforts of the FDA, doctors, pharmacists and drug manufacturers, many women ignored the warning and brought the problem on themselves (and their off-spring). There has been no study of how well doctors informed women of the risks of Accutane, whether information brochures were handed out or if prescriptions were consistently labeled with warnings by pharmacists. Similarly, there has been no research to determine whether the pregnancies were the result of birth control failures or planned despite full information on Accutane's risks. All that is known is this: doctors ignored the warning in three out of every four prescriptions for Accutane. The decision to make drug information physically inseparable from the drug itself implies the FDA had doubts about relying on doctors as the source of information.

While victim blaming may make the regulators and the regulated feel better it does nothing to redress any of the deficiencies in regulation that were highlighted by the Accutane experience. Some suggested solutions follows: