Synthesizing existing evidence to design future trials: survey of methodologists from European institutions

Adriani Nikolakopoulou,Matthias Egger,Georgia Salanti,Sven Trelle,Alex J Sutton

doi:10.1186/s13063-019-3449-6

Abstract

Background‘Conditional trial design’ is a framework for efficiently planning new clinical trials based on a network of relevant existing trials. The framework considers whether new trials are required and how the existing evidence can be used to answer the research question and plan future research. The potential of this approach has not been fully realized.MethodsWe conducted an online survey among trial statisticians, methodologists, and users of evidence synthesis research using referral sampling to capture opinions about the conditional trial design framework and current practices among clinical researchers. The questions included in the survey were related to the decision of whether a meta-analysis answers the research question, the optimal way to synthesize available evidence, which relates to the acceptability of network meta-analysis, and the use of evidence synthesis in the planning of new studies.ResultsIn total, 76 researchers completed the survey. Two out of three survey participants (65%) were willing to possibly or definitely consider using evidence synthesis to design a future clinical trial and around half of the participants would give priority to such a trial design. The median rating of the frequency of using such a trial design was 0.41 on a scale from 0 (never) to 1 (always). Major barriers to adopting conditional trial design include the current regulatory paradigm and the policies of funding agencies and sponsors.ConclusionsParticipants reported moderate interest in using evidence synthesis methods in the design of future trials. They indicated that a major paradigm shift is required before the use of network meta-analysis is regularly employed in the design of trials.

Highlights

Systematic reviews can identify knowledge gaps that may direct the research agenda toward questions that need further investigation
This part pertains to interpreting meta-analysis results, which is related to deciding whether existing evidence is conclusive, whether multiple testing is needed when a meta-analysis is regularly updated, and how to interpret evidence from multiple outcomes
Some questions allowed or requested free text answers by participants; we present some illustrative written quotes regarding participants’ willingness to consider a clinical trial design informed by meta-analysis and the biggest barriers to adopting such a design

Summary

Introduction

Systematic reviews can identify knowledge gaps that may direct the research agenda toward questions that need further investigation. Primary research (e.g., trials) may be designed and conducted to fill such gaps. Such considerations, along with implementation strategies, have appeared in the literature. Methodological developments that use network metaanalysis as a basis for further research [3, 8] have been recently collated to form a holistic framework for planning future trials based on a network of interventions [9]. The first part asks whether the existing evidence answers the research question. The second part of the framework is related to how best to use the existing evidence to answer the research question. The third and last part of the framework addresses how to use the existing evidence to plan future research. In the case of violation of the transitivity assumption (that for each comparison there is an underlying true relative treatment effect which applies to all studies regardless of the treatments compared), or in the presence of studies with a high risk of bias, the existing network of interventions would not provide reliable evidence and should not be used to inform the planning of new studies

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Conclusion