Understanding how the research question impacts trial design: Examples from discectomy trials.

BACKGROUND: Formulating a pertinent research question is of the utmost importance in clinical research. An ill-conceived question may lead to an erroneous trial design, which may adversely affect the care of patients and provide uninformative or even misleading results. METHODS: We review the research question of a randomized trial on the timing of lumbar discectomy. We compare the resulting design with other trials, real or hypothetical, that would have been more appropriate. RESULTS: The RCT we examine randomly allocated patients to early or delayed surgery to answer a theoretical question of the effect of time on the efficacy of surgery. The trial was interpreted to have shown that early surgery was associated with better clinical and functional outcomes as compared to delayed surgery. This conclusion is clinically misleading. Valid comparisons between groups should be performed on intent-to-treat analyses and at the same time points after randomization (and not at a fixed follow-up period after surgery). The clinically pertinent comparison is not between the theoretical efficacy of surgery performed at various times, but between surgery and conservative management in patients presenting at various times. Better-designed trials on the clinical benefits of lumbar discectomy, including the treatment of chronic sciatica, have been published. CONCLUSION: Theoretical research questions inspired from observational data can lead to erroneous trial design. Prospective randomized trials impact practice immediately: they are unique occasions to address clinical problems and optimize care under uncertainty in real time. However, they require the research question to be formulated with great care.