Bioethics, healthcare policy, and related issues.
The FDA has instituted a much-publicized “voluntary” program, involving manufacturers, doctors, and - whether they like it or not - patients, aimed at preventing birth defects resulting from use of Accutae (isotretinoin ) for severe acne.
[A]s of the beginning of this year, the companies that make isotretinoin, together with the Food and Drug Administration, have imposed mandatory prescribing rules. Any woman of childbearing age who is given the drug must meet several requirements. Before starting the medication she must have negative pregnancy tests two months in a row. While taking it, she must either promise in writing to abstain from sex with a man or else use two forms of contraception, one of which must be a highly effective kind like birth control pills or the injectable Depo-Provera. Each month during her treatment (usually five months) she must take a pregnancy test. And she must document every step she takes by logging onto iPledge, a national online database.
The new rules are meant to prevent isotretinoin-related birth defects once and for all. But the rules are so strict, some doctors say, they might discourage or even prevent many patients from using the drug, the only treatment that can erase severe acne. Many dermatologists say the iPledge program is overkill.
“It’s one of the worst things that’s happened to our specialty,” said Dr. Ranella Hirsch, a Boston dermatologist who is the vice president of the American Society of Cosmetic Dermatology & Aesthetic Surgery. “We’re taking a very good drug that is for many people the only real choice out of reasonable access.”
The risk is real: first-trimester fetal isotretinoin exposure often causes a suite of severe birth defects including hydrocephaly, microcephaly, cleft palate, mental retardation, and developmental abnormalities; it often causes spontaneous abortion or infant death. Prior to the “iPledge” registration program, Accutane access was controlled through an aggressive patient-education program that involved repeated pregnancy testing and a sticky label placed on prescriptions to indicate to pharmacists that testing had been done and the patient was not pregnant. The program significantly reduced pregnancy rates among the user cohort, but not to zero. Mama’s Health has a good summary of the best available study on the matter:
Shortly after the Pregnancy Prevention Program began, Roche sponsored a survey of women taking Accutane to assess compliance with the program, and the company encouraged doctors to enroll patients. Run by the Slone Epidemiology Unit at Boston University’s School of Public Health, the survey set out to track pregnancy rates and outcomes, patients’ awareness of risks, and patient and physician behavior.
Of the 500,000 women enrolled in the Slone survey from 1989 to 1998, there have been 958 pregnancies, 834 of which were terminations (either elective, spontaneous or due to ectopic pregnancies), 110 that resulted in live births, and 14 patients that had unknown outcomes. Of the 60 infants with available medical records, eight had congenital abnormalities. Since Accutane’s approval, Roche has received close to 2,000 reports of Accutane-exposed pregnancies, 70 percent of which occurred after the PPP began.
According to FDA, exactly how well the PPP has worked is unclear. Experts say the PPP is a significant program that has prevented many pregnancies and is the first of its kind initiated by a pharmaceutical company. Roche has made extraordinary efforts to educate patients that they must not become pregnant while taking Accutane, says a Roche spokesperson.
At a September 2000 meeting of FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee, a Roche representative reported that from the company’s perspective, pregnancy rates have declined. Amarilys Vega, MD, an FDA medical officer, agreed. However, because use of the product has increased over the years, the actual number of pregnancies occurring while taking Accutane has not declined. One limitation is that the survey is voluntary and only captures about 30 to 40 percent of all patients on Accutane. So there’s no way to know exactly how many pregnancy exposures there have been, according to FDA experts.
The FDA makes the point that compliance rates among women who did not respond to the survey may not be the same as among those who did (meaning you cannot simply extrapolate from the 30 - 40% response rate to get a total figure). This is a good point, but, still, as a ballpark we are looking at something like 3,000 pregnancies, and maybe 50 congenital birth defects, over a 10-year period under the voluntary-compliance regimen. Double those numbers and they’re still small.
For comparison purposes, we can look at Trisomy 13, a (usually) spontaneous chromosomal abnormality with clinical results very similar to those of Accutane teratogenicity. The CDC estimates its prevalence is 1.3 per 10,000 live births, and the annual number of cases is about 530. This prevalence is vastly lower than that of Accutane-linked birth defects (about half of live births), but only because the latter are so commonly aborted. In absolute numbers, the prevalence is something like 100 times as high - yet we almost never hear anything about Trisomy 13. (It’s #17 on the CDC’s list of the 18 most-common sources of birth defects - not all of which are life-threatening.)
Obviously, the two situations are not comparable, because there is no easy way to prevent trisomies, and there is no situation in which it is known that they are particularly likely to occur. Thus, imposing heavy-handed preventive regimens on women “at risk” for that condition is not an option. But it is interesting that a nation-wide, mandatory, sexual-behavior-registration program is being imposed for a potential condition that results in so vanishingly few cases, compared with the natural rates of birth defects that are not even visible as national health problems.
Whenever women’s sexuality enters the health-policy picture, under the current administration and under this FDA, we are forced to consider ulterior motives as likely policy drivers. The utterly bizarre history of OTC emergency-contraceptive approval is all the proof needed. In that light it is suspcicious - in a way it might not be under a more rational and professional regulatory regime - how perfectly a number of hot-button ideological factors line up on this issue:
Speaking somewhat cynically, it’s as if they mixed up the worst aspects of abortion restrictions, “conscience clauses”, Taliban-style denial of women’s healthcare, Margaret Atwood-style sexual slavery, and “for the children” emotionalism into a slurry of rejectionist thinking about women’s sexuality and women’s healthcare. The Web site and multiple stages of sexual monitoring look uncomfortably like a slut registry, while their persistent touching faith in abstinence vows as a guaranteed prevention for pregnancy continues unabated. The total absence of any sense of proportionality - the idea that any level of birth defects, no matter how small, is worth a persistent, painful infection resulting in disfiguring scarring for tens of thousands of women per year - further betrays the ideology that makes such policies seem reasonable: the ideology that holds that no benefit to any number of women is worth any harm to even one fetus.
It is hard not to think that the issue of abortion creeps into this decision as well. Given the almost immeasurably-small level of birth defects recorded during the monitoring program, it is possible to suspect that what this program really aims to prevent is not the 5 birth defects per year but the 250 abortions. It is not clear how many of those were elective, but no doubt a large fraction were. And it is a certainty as well that those incidents were regarded not as adjunct therapies serving to further reduce the incidence of birth defect from Accutane, but as added “tragedies” swelling the death toll from the drug. So the apparent purpose of this policy - as we cannot avoid suspecting - is not simply to prevent women from conceiving fetuses with some probability of birth defects, but rather to prevent women from conceiving fetuses they would then be likely to abort.
Perhaps this is too cynical. Perhaps the crafters of this policy sincerely felt that reducing birth defects from 5 per year to something closer to zero was justification enough to impose an extensive and intrusive monitoring regimen on up to 100,000 women per year - even if likely driving significant numbers of them away from the only drug that can cure their ongoing infections and prevent life-long scarring. Perhaps this was “for the children” thinking in its more benign aspect, and not by way of using children as a weapon against the women who bear them. And perhaps the program will even work - most women will choose to comply, pregnancy rates will drop near zero among Accutane users, and the slut registry will not be breached or misused. But I find it curious that it is so easy, and so readily seized upon as policy, to make the most onerous inroads on women’s health whenever they are found engaged in “non-approved” sex, or whenever a (potential or even imaginary) fetus raises its tiny head.
