Self-reported and verified compliance in a phase 3 clinical trial of a novel low-dose contraceptive patch and pill

Abstract Objective Pregnancy rates in US contraceptive clinical trials are increasing due to decreased treatment compliance. This study compared compliance with a new low-dose levonorgestrel (LNG) and ethinyl estradiol (EE) contraceptive patch (CP, Twirla™) with that of a low-dose combination oral contraceptive (COC) in a demographically diverse population. Study design This analysis was part of an open-label, parallel-group, multicenter phase 3 study that randomized healthy sexually active women (17–40 years) to 13 cycles of LNG/EE CP or 6 cycles of COC, then 7 cycles of LNG/EE CP. We defined self-reported compliance as cycles that, according to diaries, show 21 days of patch wear without missed days or any patch worn > 7 days or 21 days of pill-taking without missed pill days. We verified compliance by detectable plasma presence of LNG and EE at cycles 2, 6, and 13. Results Of the intention-to-treat population with diary information ( N = 1328, mean age 26.4 years, 46% minorities, 33% obese), 10.0% of the CP ( n = 998) versus 21.2% of the COC group ( n = 330) self-reported noncompliance after 6 cycles (p 2 ] versus nonobese (BMI 2 ) participants in both groups or when stratified by age, education, or race/ethnicity in the CP group. Conclusions Self-reported compliance was significantly greater in the CP than COC group and did not vary by obesity status. Discrepancies between self-reported and verified compliance question reliability of patient diaries. Implications statement This paper, based on an analysis of a phase 3 trial, shows that compliance was significantly greater with a new weekly transdermal CP than with a once-daily COC in obese as well as nonobese participants. Discrepancies between self-reported compliance and laboratory-verified compliance raise questions regarding the reliability of patient diaries.