Use of placebo controls in an oral contraceptive trial: methodological issues and adverse event incidence

Two multicenter, double-blind, placebo-controlled studies were conducted to evaluate the effectiveness of triphasic norgestimate/ethinyl estradiol (Ortho Tri-Cyclen) for the treatment of acne vulgaris. To our knowledge, these studies were the first double-blind, placebo-controlled trials to evaluate the efficacy of an oral contraceptive (OC) in the treatment of acne; in fact, they are probably the first placebo-controlled trials ever completed using modern OC. This article examines the conduct and feasibility of these studies including discussions on study planning enrollment, maintenance of the blind, continuation rates, and pregnancy prevention. Subjects were between the ages of 15 and 49 years, with moderate acne vulgaris, no contraindications to oral contraceptive use, and were willing to use a nonsteroidal method of birth control during the 6 months of the trial. More than 500 participants were enrolled in 1 year. Discontinuation rates between groups were similar. To explore the reasons for the similar and low discontinuation rates, OC-related side effects were evaluated in comparison to placebo. This analysis revealed that the OC exhibited a side effect profile that was similar, in many cases, to that of placebo. Although pregnancies occurred in the placebo arm, the incidence was consistent with expected failure rates for users of nonsteroidal methods in the general population.