Pitfalls in the design and analysis of efficacy trials in subfertility.

The introduction, more than half a century ago, of the randomized trial in which allocation to the experimental and control interventions occurs by chance has been a pivotal point in the evaluation of therapeutic ef®cacy. It is now well accepted that the gold standard in such evaluation is the welldesigned controlled, clinical experiment that has high methodological rigour so that bias can be minimized and the magnitude of treatment effect can be estimated reliably and con®dently. The acceptance of the randomized controlled trial (RCT) in the ®eld of reproductive medicine is evident by the increasing numbers of such trials being published. In the mid-1990's the importance of improving the quality of reports of RCTs led to the publication of the Consolidated Standards of Reporting Trials (CONSORT) statement (1996) which was developed by an international group of experts, comprising clinical trialists, statisticians, epidemiologists and biomedical editors. The CONSORT statement, which consists of a checklist and ̄ow diagram for reporting RCTs, has gained widespread support by many journals and organizations representing science editors. This format prompts investigators to ensure that important elements in clinical trials design and reporting have been addressed so that the information conveyed has more value. Unfortunately, this approach seems to be lacking in journals in reproductive medicine and science as evidenced by the ®ndings of the research conducted by Vail and Gardener (2003). In their review of published controlled trials in subfertility, (published in the journals Human Reproduction and Fertility and Sterility in the year 2001), they found methodological errors including fatal ̄aws in design, a misunderstanding of the intention-to-treat principle and statistical errors arising from the unit of analysis being inappropriate.