The aftermath of a pill scare: regression to reassurance

In October 1995, following confidential exchanges of findings among investi gators in several epidemiological studies, the UK Medicines Control Agency sent a 'Dear Doctor' letter to all clinical practitioners in the country. T he letter alerted them to the possibility of an excess risk of venous throm boembolism among women taking combined oral contraceptives (OC) with the 'n ewer' progestins, notably desogestrel and gestodene. The communication prov oked a major pill scare, not just in the United Kingdom but in other countr ies. The preliminary and unpublished findings from the four initial 1995-96 studies reported odds ratios (OR) ranging from 1.5 to 2.3 in the point est imates. These are very low relative risks but were communicated in a way th at the public perceived as a 'doubling of the risks'. In the 3 years since the pill scare, additional research has been done. First, deliberate and ca reful analysis of some of the studies and replication of others have shown that the epidemiological investigations were affected by unavoidable system atic error. Three types of bias were demonstrated empirically namely, presc ription bias, referral bias and healthy user effect or attrition of suscept ibles. All those biases would tend to drive OR spuriously upwards. Addition al epidemiological studies have progressively shown lower ORs, some of them under the threshold of 1.0, i.e. 'no association'. Two major consensus ass essments, one carried out by a World Health Organization Scientific Group a nd another undertaken by the International Federation of Fertility Societie s, both attach little importance to differences between older (second gener ation) combined OC and newer ones (third generation). This paper is a synth esis of all published evidence since October 1995, at the time of the pill scare and in the 3 years since. In conclusion, all combined oral contracept ive pills are equally safe.