Differences in reporting Pearl Indices in the United States and Europe: Focus on a 91-day extended-regimen combined oral contraceptive with low-dose ethinyl estradiol supplementation

Abstract

Background Regulatory agencies in the United States (US) and Europe differ in requirements for defining pregnancies after the last dose of oral contraceptive, sometimes resulting in discrepant Pearl Indices (PIs) for the same product despite identical clinical data. This brief report highlights one such example, a 91-day extended-regimen combined oral contraceptive (COC).

Methods The US- and European-based PI methodologies were compared for a 91-day extended-regimen COC consisting of 84 days of active levonorgestrel/EE 150 μg/30 μg tablets, followed by seven days of EE 10 μg tablets in place of placebo.

Conclusions At the times of approval of the 91-day extended-regimen COC in the US and Europe, the requirements for defining ‘on-treatment’ pregnancies differed (14-day vs. 2-day rule, respectively). This difference resulted in a higher PI in the US- vs. European-based calculation (1.34 and 0.76, respectively). The differences in the PI should not be interpreted as the extended-regimen COC being less effective in preventing pregnancy in the US compared with Europe.

Abstract

摘要

背景 由于美国和欧洲的调控部门对于口服避孕药最后一片药后多长时间发生的妊娠定义为避孕药失败存在差异，在一定程度上是造成同一个避孕产品在不同的地方皮尔指数不同的原因，尽管从临床数据上来看是相同的。这篇简短的报道将以91天复方口服避孕药扩展方案来进行分析。

方法 该91天的扩展方案，应用84天的复方口服避孕药左炔诺孕酮/炔雌醇150ug/30ug，之后是用7天的10ug炔雌醇代替了安慰剂，在美国和欧洲的研究和皮尔指数的的方法学均为一致。

结论 在这个相同的方案中，美国和欧洲在对于避孕药停药后多长时间发生妊娠的定义为避孕药失败存在差异，在美国，将停药14天内发生的妊娠定义为避孕药失败，而在欧洲，仅将停药后2天内发生的妊娠定义为避孕药失败，因此美国有着较高的皮尔指数为1.34，而欧洲仅为0.76。这个皮尔指数的差异并不能解释为复方口服避孕药的扩展方案在美国使用避孕的有效性不如欧洲。

Keywords:

• Pearl Index
• Combined oral contraceptive
• Extended-regimen

ACKNOWLEDGEMENTS

Medical writing assistance was provided by MedVal Scientific Information Services, LLC, and was funded by Teva Branded Pharmaceutical Products R&D, Inc. (Frazer, PA, USA). Teva provided a full review of the article. The authors thank Rebecca Miles, PhD, of MedVal Scientific Information Services, LLC (Skillman, NJ, USA), for providing professional writing and editorial assistance. This manuscript was prepared according to the International Society for Medical Publication Professionals’ ‘Good Publication Practice for Communicating Company-Sponsored Medical Research: the GPP2 Guidelines’ and the International Committee of Medical Journal Editors’ ‘Uniform Requirements for Manuscripts Submitted to Biomedical Journals.’

Declaration of interest: Dr Giljanovic is an employee of Teva Pharmaceutical Europe. Dr Howard and Dr Weiss are employees of Teva Global Medical Affairs. Prof. Trussell is on advisory committees for Teva and Merck and is a consultant to Bayer. Dr Lobo Abascal has received lecture fees and is a member of advisory boards and/or a consultant for Bayer, Effik, HRA Pharma, Merck Sharp & Dohme, and TEVA. Prof. Luzar-Stiffler is Director of Statistical Methods at CAIR Center – The House of Statistics.

This work was supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grant for Infrastructure for Population Research at Princeton University, Grant P2CHD047879 (JT).