Third generation oral contraceptives and risk of venous thrombosis: meta-analysis
BMJ 2001; 323 doi: https://doi.org/10.1136/bmj.323.7305.131 (Published 21 July 2001) Cite this as: BMJ 2001;323:131All rapid responses
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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
Competing interests: No competing interests
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.
Competing interests: No competing interests