Peer review before trial conduct could increase research value and reduce waste

Abstract

Traditional peer-review of clinical trials happens too late, after the trials are already done. However, lack of methodological rigor and presence of many biases can be detected and remedied in advance. Here, we examine several options for review and improvement of trials before their conduct: protocol review by peers, sponsors, regulatory authorities, and institutional ethical committees; registration in registry sites; deposition of protocol and/or the statistical analysis plan in a public repository; peer-review and publication of the protocol and/or the statistical analysis plan in a journal; and Registered Reports. Some practices are considered standard (e.g. registration in trial registry), while others are still uncommon but are becoming more frequent (e.g. publication of full trial protocols and statistical analysis plans). Ongoing challenges hinder a large-scale implementation of some promising practices such as Registered Reports. Innovative ideas are necessary to advance peer-review efficiency and rigor in clinical trials but also to lower the cumulative burden for peer-reviewers. We make several suggestions to enhance pre-conduct peer-review. Making all steps of research process public and open may reverse siloed environments. Pre-conduct peer-review may be improved by making routinely publicly available all protocols that have gone through review by institutional review boards and regulatory agencies.