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 (Or tho Tri-Cyclen(R)) for the treatment of acne vulgaris. To our knowledge, th ese studies were the first double-blind, placebo-controlled trials to evalu ate 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 thes e 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 contra indications to oral contraceptive use, and were willing to use a nonsteroid al 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 discontinuatio n rates, OC-related side effects were evaluated in comparison to placebo. T his analysis revealed that the OC exhibited a side effect profile that was similar, in many cases, to that of placebo. Although pregnancies occurred i n the placebo arm, the incidence was consistent with expected failure rates for users of nonsteroidal methods in the general population. CONTRACEPTION 1999;60: 81-85 (C) 1998 Elsevier Science Inc. All rights reserved.