title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Florida College of Medicine, Jacksonville, 653-1 West 8th Street, Jacksonville, FL 32209, USA. Electronic address: andrew.kaunitz@jax.ufl.edu.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Kaunitz
authors.affiliation: Columbus Center for Women's Health Research, 99 Brice Road North, Columbus, OH 43213, USA.
authors.forename: David
authors.initials: D
authors.lastname: Portman
authors.affiliation: Mailman School of Public Health, Columbia University, 722 West 168th Street, New York, NY 10032, USA.
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Westhoff
authors.affiliation: Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, 601 Colley Avenue, Norfolk, VA 23507, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Archer
authors.affiliation: Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, 2020 Zonal Avenue, Room 220, Los Angeles, CA 90033, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Mishell
authors.affiliation: Department of Pharmacology, New York Medical College, Basic Science Building, 15 Dana Road, Valhalla, NY 10595, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Foegh
mesh_terms: D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage* / Q000097:blood; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000097:blood; D010349:Patient Compliance / Q000706:statistics & numerical data*; D015203:Reproducibility of Results; D057566:Self Report; D057968:Transdermal Patch; D055815:Young Adult
chemical_list: D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; C072593:ethinyl estradiol, levonorgestrel drug combination; D004997:Ethinyl Estradiol; D016912:Levonorgestrel
keywords: Combination oral contraceptive; Ethinyl estradiol; Levonorgestrel; Obesity; Patient diaries; Transdermal contraceptive patch