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PAPERS: Jeanet M Kemmeren, Ale Algra, and Diederick E Grobbee Third generation oral contraceptives and risk of venous thrombosis: meta-analysis BMJ 2001; 323: 131 [Abstract] [Full text]

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Third generation oral contraceptives and risk of venous thromboembolism

Margaret Thorogood   (26 July 2001)

Re: Third generation oral contraceptives and risk of venous thromboembolism

Jeanet M Kemmeren, Ale Algra, Diederick E. Grobbee   (2 March 2002)

Third generation oral contraceptives and risk of venous thromboembolism 26 July 2001
Margaret Thorogood, Reader in Public Health and Preventative Medicine London School of Hygiene and Tropical Medicine Send response to journal: Re: Third generation oral contraceptives and risk of venous thromboembolism	Kemmereren et al have made a brave attempt to quantify the risks of venous thromboembolism associated with use of third generation oral contraceptives in comparison with second generation products. Meta- analysis of observational studies is always a difficult undertaking, and this task is made even more difficult by the highly controversial topic. They have chosen not to give quality scores to their studies 'because of their inherent subjectivity'. I agree it is difficult, but I do not believe that the issue of quality can be ignored. Indeed, some of the explanation for the difference in findings between industry sponsored and non-industry sponsored studies may lie in the quality of the study design. In my experience, grants awarded by industry are rarely subjected to the same rigorous peer review process that is employed by almost all the large non-industry grant awarding bodies. The summary odds ratio for first time users provided in the paper (3.1, 2.0 to 4.6) is underestimated, because the same study with a low point estimate has been included twice[1 2] The true estimate is probably nearer 3.4. Margaret Thorogood Reader in Public health and Preventative Medicine London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT Email margaret.thorogood@lshtm.ac.uk References 1. Spitzer WO Lewis MA Heinemann LA Thorogood M MacRae KD third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study BMJ 1996;312:83-8 2. Suissa S Blais L Spitzer WO Cusson J Lewis M Heinemann L First time users of newer oral contraceptives and the risk of venous thromboembolism Contraception 1997;56:141-6
Re: Third generation oral contraceptives and risk of venous thromboembolism 2 March 2002
Jeanet M Kemmeren, Research fellow Julius Centre for General Practice and Patient Oriented Research, PO Box 85500, 3508 GA Utrecht, Ale Algra, Diederick E. Grobbee Send response to journal: Re: Re: Third generation oral contraceptives and risk of venous thromboembolism	Dear Sir, In a rapid response on our meta-analysis about the risk of venous thrombosis associated with the use of third generation oral contraceptives in comparison with second generation preparations1, Thorogood argued that the issue of quality between studies can not be ignored (BMJ 2001, 26 July). We agree with Thorogood that some of the explanation for difference in findings may lie in the quality of the study design. However, in observational studies it is very difficult to give studies a quality score, and therefore we investigated this aspect in stratified and sensitivity analyses. One of the stratification factors was industry vs. non-industry sponsored studies, and we found a that the pooled odds ratio of studies without explicitly mentioned industry sponsoring was higher than that of studies without such support. This remarkable finding may be a result of differences in quality between studies, but this can also be a result of publication bias. Another point which was mentioned by Thorogood is that the summary odds ratio for first time users which we provided in our paper is underestimated, because the same study has been included twice2,3. Indeed, the study of Suissa et al3 is a re-analysis of the study of Spitzer et al2. By mistake, both studies were included in this specific subgroup analysis. Excluding the study of Suissa et al, the odds ratio for third vs. second generation oral contraceptives in first-time users was 3.3 (95% CI 2.0-5.4). The error had no further implications for the analyses presented in the paper. Jeanet M Kemmeren Ale Algra Diederick E Grobbee Julius Centre for General Practice and Patient Oriented Research, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands Email A.Algra@neuro.azu.nl References 1. Kemmeren JM, Algra A, Grobbee DE. Third generation oral contraceptives and risk of venous thrombosis. BMJ 2001: 323: 131-134. 2. Spitzer WO, Lewis MA, Heinemann LA, Thorogood M, MacRae KD. Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study. Transnational Research Group on Oral Contraceptives and the Health of Young Women. BMJ 1996; 312:83-88. 3. Suissa S, Blais L, Spitzer WO, Cusson J, Lewis M, Heinemann L. First- time use of newer oral contraceptives and the risk of venous thromboembolism. Contraception 1997;56:141-146.