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

Contraception. 2015 Mar;91(3):204-10. doi: 10.1016/j.contraception.2014.11.011. Epub 2014 Nov 25.


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 (17-40years) to 13cycles of LNG/EE CP or 6cycles of COC, then 7cycles of LNG/EE CP. We defined self-reported compliance as cycles that, according to diaries, show 21days of patch wear without missed days or any patch worn >7days or 21days 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 26.4years, 46% minorities, 33% obese), 10.0% of the CP (n=998) versus 21.2% of the COC group (n=330) self-reported noncompliance after 6cycles (p<.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) ≥30kg/m(2)] versus nonobese (BMI <30kg/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.

Trial registration: NCT01181479.

Keywords: Combination oral contraceptive; Ethinyl estradiol; Levonorgestrel; Obesity; Patient diaries; Transdermal contraceptive patch.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Body Mass Index
  • Contraceptives, Oral, Combined / administration & dosage*
  • Contraceptives, Oral, Combined / blood
  • Drug Combinations
  • Ethinyl Estradiol / administration & dosage*
  • Ethinyl Estradiol / blood
  • Female
  • Humans
  • Levonorgestrel / administration & dosage*
  • Levonorgestrel / blood
  • Patient Compliance / statistics & numerical data*
  • Reproducibility of Results
  • Self Report*
  • Transdermal Patch*
  • Young Adult


  • Contraceptives, Oral, Combined
  • Drug Combinations
  • ethinyl estradiol, levonorgestrel drug combination
  • Ethinyl Estradiol
  • Levonorgestrel

Associated data