Prioritisation and design of clinical trials

Abstract

Clinical trials require participation of numerous patients, enormous research resources and substantial public funding. Time-consuming trials lead to delayed implementation of beneficial interventions and to reduced benefit to patients. This manuscript discusses two methods for the allocation of research resources and reviews a framework for prioritisation and design of clinical trials. The traditional error-driven approach of clinical trial design controls for type I and II errors. However, controlling for those statistical errors has limited relevance to policy makers. Therefore, this error-driven approach can be inefficient, waste research resources and lead to research with limited impact on daily practice. The novel value-driven approach assesses the currently available evidence and focuses on designing clinical trials that directly inform policy and treatment decisions. Estimating the net value of collecting further information, prior to undertaking a trial, informs a decision maker whether a clinical or health policy decision can be made with current information or if collection of extra evidence is justified. Additionally, estimating the net value of new information guides study design, data collection choices, and sample size estimation. The value-driven approach ensures the efficient use of research resources, reduces unnecessary burden to trial participants, and accelerates implementation of beneficial healthcare interventions.

Keywords: Clinical trial design; Research resources; Type I and type II errors; Uncertainty; Value of information analysis; Value-driven research.

Fig. 1

Iterative research cycles. a The current research cycle based on controlling type I and II errors. This classical method for developing and designing clinical trials is called the ‘error-driven’ approach. We consider that this approach has both a long and short iterative design process. The short route is in the top left-hand portion of the Figure and only iterates between the Evidence Synthesis and the Clinical trials boxes. The longer process includes all three key boxes while the dashed line represents the disconnect between how the information from the trials is used in policy making and the subsequent design of the next clinical trial. b A novel iterative research cycle that is driven by determining the value of different research strategies and pursuing research with the maximum value. This approach is called the ‘value-driven’ approach. Here the connection between policy making and the next clinical trial is determined using ‘value of information’ methods that prioritise and guide the design of future trials

Fig. 2

Details of the ‘value-driven’ approach. Table 2 gives explanations of each of the steps