Recently I had the honor to serve as Acting Chair of a Food and Drug Administration (FDA) advisory committee meeting called to provide advice to the Agency on the creation of new guidelines to improve manufacturer-sponsored clinical trials for hormonal contraceptive (HC) agents. . .
About one half of all pregnancies in the United States are unintended and about one half of reproductive-aged women in the US will have unintended pregnancies.1 While not all unintended pregnancies are unwanted, half end in elective abortion. Those women who choose not to terminate are more likely to receive inadequate prenatal care and less likely to achieve their full socioeconomic potential. For their offspring, there are higher rates low birthweight and childhood behavioral abnormalities.1 Clearly, the availability of a wide menu of safe, effective, and readily accessible contraceptive methods would reduce the occurrence of unintended pregnancies and help meet the 30% goal set by the Federal government in its Healthy People 2010 national objective.
Hormonal contraceptives represent a crucial arrow in this contraceptive quiver and are used by nearly 20 million women a year.2 They are also remarkably safe. The HC preparations used in the 1960s contained very high (≥ 50 μg) levels of ethinyl estradiol that increased the threat of venous thrombotic events up to eightfold. In contrast, today's low (30–35 μg) and very low (20 μg) estrogen dose agents carry half that thrombotic risk (i.e., 1–3 per 10,000 women years).3 Furthermore, for thin, nonthrombophilic patients the risk may be exceedingly low. In addition, HCs have numerous potential non-contraceptive benefits including preservation of bone mass, and reduced rates of epithelial ovarian, endometrial and colorectal cancers, pelvic inflammatory disease, ectopic pregnancy, acne, and benign ovarian cysts.4 While it is unclear whether recently introduced very low-dose agents retain all these advantages, they likely further reduce the risk of venous thromboembolism.
Why we don't have enough reliable data
Unfortunately, because of the way new contraceptive agents are approved by the FDA, providers have very little reliable information with which to counsel individual patients about their actual risk of contraceptive failure. Phase 3 trials seeking FDA approval for new HC agents generally use strict inclusion criteria including narrow weight and age ranges. Moreover, better educated and more compliant patients are more likely to enroll in such studies, and they may receive various compliance cues through maintenance of a diary or daily contact with study personnel. Thus, failure rates tend to be far lower in manufacturer-sponsored trials than with typical use in the general population. For example, for oral HC agents, the difference between the perfect and typical use annual failure rate is 0.3% versus 8%.5