Statistical issues in the design and analysis of expertise‐based randomized clinical trials

Abstract

In order to avoid certain difficulties with the conventional randomized clinical trial design, the expertise-based design has been proposed as an alternative. In the expertise-based design, patients are randomized to clinicians (e.g. surgeons), who then treat all their patients with their preferred intervention. This design recognizes individual clinical preferences and so may reduce the rates of procedural crossovers compared with the conventional design. It may also facilitate recruitment of clinicians, because they are always allowed to deliver their therapy of choice, a feature that may also be attractive to patients.The expertise-based design avoids the possibility of so-called differential expertise bias. If a standard treatment is generally more familiar to clinicians than a new experimental treatment, then in the conventional design, more patients randomized to the standard treatment will have an expert clinician, compared with patients randomized to the experimental treatment. If expertise affects the study outcome, then a biased comparison of the treatment groups will occur.We examined the relative efficiency of estimating the treatment effect in the expertise-based and conventional designs. We recognize that expected patient outcomes may be better in the expertise-based design, which in turn may modify the estimated treatment effect. In particular, a larger treatment effect in the expertise-based design can sometimes offset a higher standard error arising from the confounding of clinician effects with treatments.These concepts are illustrated with data taken from a randomized trial of two alternative surgical techniques for tibial fractures.