EMPIRICAL-EVIDENCE OF BIAS IN INFERTILITY RESEARCH - OVERESTIMATION OF TREATMENT EFFECT IN CROSSOVER TRIALS USING PREGNANCY AS THE OUTCOME MEASURE

Objective: To determine whether crossover trials with simple pooling o f data over different study periods leads to a different estimate of t reatment effect compared with parallel group trials in infertility res earch using pregnancy as the outcome measure. Design: An observational study using nine overviews that included trials with both crossover a nd parallel group designs. These overviews comprised 17 crossover and 17 parallel group trials. In total, there were 5,291 outcomes includin g 775 pregnancies. The association between study design and treatment effect estimate was analyzed using multiple logistic regression, contr olling for differences in the therapeutic interventions and variations in the methodological quality of the trials. Setting: Infertile patie nts in an academic research environment. Patients: Infertile patients undergoing treatment efficacy evaluation in controlled trials. Interve ntions: Random allocation to a variety of treatments including clomiph ene citrate, hCG, IUI, tamoxifen, and bromocriptine. Main Outcome Meas ure: Estimate of bias between study designs, based on the interaction of study design and treatment in the logistic regression model. Result s: Crossover trials produced a larger average estimate of treatment ef fect compared with trials with a parallel group design, overestimating the odds ratio by 74% (95% confidence interval, 2% to 197%). Conclusi on: The use of a crossover design for evaluating infertility treatment s with outcomes that prevent patients from completing later phases of the trial should be avoided because it leads to exaggerated estimates of treatment effect and may result in erroneous inferences and clinica l decisions. Furthermore, the type of study design should be taken int o account when assessing the methodological quality of therapy trials in infertility.