Guidance for biostatisticians on their essential contributions to clinical and translational research protocol review

Abstract

Rigorous scientific review of research protocols is critical to making funding decisions, and to the protection of both human and non-human research participants. Given the increasing complexity of research designs and data analysis methods, quantitative experts, such as biostatisticians, play an essential role in evaluating the rigor and reproducibility of proposed methods. However, there is a common misconception that a statistician's input is relevant only to sample size/power and statistical analysis sections of a protocol. The comprehensive nature of a biostatistical review coupled with limited guidance on key components of protocol review motived this work. Members of the Biostatistics, Epidemiology, and Research Design Special Interest Group of the Association for Clinical and Translational Science used a consensus approach to identify the elements of research protocols that a biostatistician should consider in a review, and provide specific guidance on how each element should be reviewed. We present the resulting review framework as an educational tool and guideline for biostatisticians navigating review boards and panels. We briefly describe the approach to developing the framework, and we provide a comprehensive checklist and guidance on review of each protocol element. We posit that the biostatistical reviewer, through their breadth of engagement across multiple disciplines and experience with a range of research designs, can and should contribute significantly beyond review of the statistical analysis plan and sample size justification. Through careful scientific review, we hope to prevent excess resource expenditure and risk to humans and animals on poorly planned studies.

Keywords: Biostatistician; Protocol; Review; Scientific rigor; Translational research.

Fig. 1.

Illustration of varying degrees of relevance for protocol items across common study types. This figure supplements the accompanying checklist of protocol items a biostatistical reviewer should consider in reviewing study protocols. The heat map illustrates the high-level summary view, among coauthors and other quantitative methodologists (N = 20 respondents), of relevance for each checklist item. Individual respondents rated each item from 1 (most relevance) to 4 (no relevance/not applicable). Darker cells correspond to higher importance or relevance for a given item/study type, while lighter cells indicate less relevance or importance. If we use the randomized controlled trial (RCT) as a benchmark, we note that the majority of the checklist items are important to consider and review in a research protocol for this study type. The ordering of study types from left to right reflects the order in which respondents were presented these items when completing the survey. The dark column to the left illustrates this. As the study type strays from the RCT, we illustrate the varying degrees of relevance for each of these items. For example, a statistical reviewer should not put weight on things like interim analyses for several of these other study types (cohort studies, case-control, etc.), and the group determined that the use of validated instruments and minimizing bias in enrollment in animal studies are less relevant. On the other hand, the need for clear objectives and hypotheses is consistent throughout, no matter what the study type.