Crossover or parallel design in infertility trials? The discussion continues

Abstract

Objective: To determine whether a crossover design results in a different estimate of treatment effect compared with a parallel design.

Design: With the aid of a computer program, data sets of subfertile patients were simulated under different assumptions. These patients were subjected to 2 treatments that were compared in either a parallel-design or a crossover-design trial. Results were analyzed using logistic regression.

Setting: University hospital.

Patient(s): Simulated patients of a heterogeneous subfertile population.

Intervention(s): Two treatment modalities with a pregnancy rate of 10% and of 20% in the first cycle were offered for 6 cycles to simulated heterogeneous populations.

Main outcome measure(s): After 1,000 simulations for each assumption, median pregnancy rates and odds ratios were compared between the crossover- and parallel-design trials.

Result(s): No relevant difference in estimated treatment effect was found between the designs. The crossover design resulted in more pregnancies overall than the parallel design.

Conclusion(s): In infertility research, parallel and crossover designs will lead to about the same results. Although the crossover design showed a slight tendency to overestimate the treatment effect of the most effective treatment, this overestimation is clinically not relevant and is small in relation to the random error. Because of its practical advantages and because more pregnancies are achieved, a crossover design should be the first choice in infertility research.