Original research article Self-reported and verified compliance in a phase 3 clinical trial of a novel low-dose contraceptive patch and pill ☆,☆☆,★

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 N7 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: Oftheintention-to-treatpopulationwithdiaryinformation(N=1328,meanage26.4 years,46%minorities,33%obese),10.0%oftheCP (n=998) versus 21.2% of the COC group (n=330) self-reported noncompliance after 6 cycles (pb.001). Laboratory assessments verified 10–14% of participants in both groups as noncompliant. Self-reported perfect use did not vary between obese [body mass index (BMI) ≥30 kg/m 2 ] versus nonobese (BMI b30 kg/m 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.