@article{e3079a82473e42b5b58a283c4ab3a5a4,
title = "Variability in Contraceptive Clinical Trial Design and the Challenges in Making Comparisons Across Trials",
abstract = "Clinical trials of contraceptives have often differed in their study designs, making cross-trial comparisons difficult. This brief report outlines some of the technical design features that can vary from trial to trial. For example, the overall number of menstrual cycles in a study has substantial impact on the final efficacy determination; however, the rules related to qualifying cycles can differ based on the length of the study and the statistical analysis plan. In two commonly used methods of calculating efficacy, the Pearl Index and the time-to-event analysis, inclusion of fewer menstrual cycles results in higher calculated failure rates. Statistical analysis plans for contraceptive trials have sometimes excluded menstrual cycles because of an absence of documented vaginal intercourse and the concomitant use of another birth control method. Other design features that have varied between contraceptive trials relate to body mass index inclusion/exclusion criteria and the definition of “on-treatment” pregnancy. In addition, study designs of non-hormonal products can differ from those of hormonal products in their length and rules for qualifying cycles. The Draft Guidance for Hormonal Contraception, published in 2019 by the US Food and Drug Administration (FDA), will hopefully lead to more uniform trial design in the future, particularly for hormonal products. In the meantime, health care providers and patients should be aware of the nuances in trial design that make direct comparisons about relative efficacy challenging.",
keywords = "Contraception, Effectiveness, Efficacy determination, Life table analysis, Pearl Index, Study design, Time-to-event analysis",
author = "David Portman and Eisenberg, {David L.} and Patty Cason and Brandon Howard",
note = "Funding Information: Brandon Howard received compensation for the writing of this commentary as an employee of Evofem Biosciences, Inc. The other authors received no funding for the writing of the commentary. The Rapid Service Fee and the Open Access fee were also funded by Evofem Biosciences, Inc. Funding Information: Brandon Howard received compensation for the writing of this commentary as an employee of Evofem Biosciences, Inc. The other authors received no funding for the writing of the commentary. The Rapid Service Fee and the Open Access fee were also funded by Evofem Biosciences, Inc. Medical writing assistance was provided by Rebecca D. Miles, PhD, of PharmaWrite, LLC, and was funded by Evofem Biosciences, Inc. Evofem Biosciences, Inc. (San Diego, CA, USA), reviewed this article for medical accuracy. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. All authors were involved in the concept, design, and drafting of the manuscript. Perfect-use cumulative failure rates of VPM have been previously presented at the Virtual Annual Clinical and Scientific Meeting of the American College of Obstetricians and Gynecology (ACOG); October 30?31, 2020 (poster #301). David Portman: Consultant or Advisory Board/Panel for Agile Therapeutics, Sebela Pharmaceuticals, Evofem Biosciences; Employee, Officer/Board Member and Shareholder of Sermonix Pharmaceuticals; Grant Recipient/Research Support from Agile Therapeutics; David L. Eisenberg: Consultant or Advisory Board/Panel for Femasys, Medicines360, Sebela; local site PI and Speakers Bureau for Evofem Biosciences, Inc.; Trainer for Merck; Patty Cason: Consultant trainer for Sebela; Advisory Board/Panel for Evofem Biosciences, Inc.; Trainer for Merck; Brandon Howard: Employee and Shareholder of Evofem Biosciences, Inc. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Data sharing is not applicable to this article as no datasets were generated or analyzed. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = nov,
doi = "10.1007/s12325-021-01915-3",
language = "English",
volume = "38",
pages = "5425--5430",
journal = "Advances in Therapy",
issn = "0741-238X",
number = "11",
}