Background

Two case-control studies, both with the involvement of the Boston Collaborative Drug Surveillance Program, have recently been published in the British Medical Journal (Jick et al.1 and Parkin et al.2) in which increased risks of venous thromboembolism (VTE) among users of drospirenone (DRSP)-containing oral contraceptives (OCs) compared with levonorgestrel (LNG)-containing OCs were reported. Both studies used electronic medical databases [USA: managed care plans (Pharmetrics)1; UK: general practices (GPRD)2].

Risk assessments of VTE in a predominantly young and healthy population identified in electronic databases always face similar methodological problems concerning the validity and completeness of the recorded diagnoses, the selection of comparison groups, and the completeness and validity of the information on potential confounders.3,–,5

These problems are reminiscent of the issues experienced during the ‘third vs second generation’ pill crisis. Recently in Austria, where the impact of the crisis in the mid-1990s on OC use was negligible, a study was conducted in which the risk of VTE for ‘third vs second generation pills’ was investigated. The methods were the same as those used 10 years earlier. However, over the intervening 10 years the characteristics of the third- and second-generation pill user populations had grown similar, and – importantly – the elevated risks reported in the mid-1990s were not found.6

In the two database studies now reported it is unlikely that the characteristics of the populations of DRSP- and LNG-containing OC users were sufficiently similar to permit valid comparisons, for the reasons given below.

Under-ascertainment of VTE incidence

There was major under-ascertainment of the incidence of VTE, as has also been the case in previous database studies. Among OC users it is now well established that the incidence is of the order of 9–10 per 10 000 woman-years (WY), and in some studies it …