Background

In 2009, Lidegaard et al.1 published findings in the British Medical Journal, derived from a Danish retrospective cohort study of the risk of venous thromboembolism (VTE) associated with the use of combined oral contraceptives (COCs). Their analysis was based on data derived from national health registries, and they concluded that “oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of VTE than oral contraceptives with levonorgestrel”. That report has previously been reviewed in this Journal2 and at an international workshop.3

Subsequently, because of methodological limitations in the Danish study, the European Medicines Agency (EMA) requested a re-analysis. The conduct of the re-analysis was overseen by an independent three-member steering committee [KJ Rothman (Chairman), FE Skjeldestad (nominated by Lidegaard, and a co-author of the published re-analysis)4 and S Shapiro (nominated by Bayer Schering, and a co-author of this commentary)].

The completed re-analysis, together with a commentary by the steering committee, an additional commentary by S Shapiro, and an audit requested by the steering committee, was submitted to the EMA, and an abbreviated version of the EMA submission has recently been published.4 Here we review the publication of the re-analysis submitted to the EMA. The publication manuscript was not submitted to the steering committee for review before publication.

In the published re-analysis4 the authors claim to have confirmed the conclusions reached in the original analysis:1 if anything, the risk estimates were even higher than the original estimates. A difficulty, however, is that several numbers reported in the publication differ from those mentioned in the re-analysis submitted to EMA (one example is given below).

Since the mid-1990s there has been heated debate regarding the risk of VTE associated with the use of different progestogens, and those who have followed the …