Using Mendelian Randomization to Improve the Design of Randomized Trials
- 1Centre for Naturally Randomized Trials, University of Cambridge; the National Institute for Health Research Cambridge Biomedical Research Centre at the University of Cambridge and Cambridge University Hospitals; and the British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge CB1 8RN, United Kingdom
- 2MRC Population Health Research Unit at the University of Oxford and the Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford OX3 7LF, United Kingdom
- 3MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, United Kingdom
- Correspondence: baf29{at}medschl.cam.ac.uk
Abstract
Randomized controlled trials and Mendelian randomization studies are two study designs that provide randomized evidence in human biological and medical research. Both exploit the power of randomization to provide unconfounded estimates of causal effect. However, randomized trials and Mendelian randomization studies have very different study designs and scientific objectives. As a result, despite sometimes being referred to as “nature's randomized trial,” a Mendelian randomization study cannot be used to replace a randomized trial but instead provides complementary information. In this review, we explain the similarities and differences between randomized trials and Mendelian randomization studies, and suggest several ways that Mendelian randomization can be used to directly inform and improve the design of randomized trials illustrated with practical examples. We conclude by describing how Mendelian randomization studies can employ the principles of trial design to be framed as “naturally randomized trials” that can provide a template for the design of future randomized trials evaluating therapies directed against genetically validated targets.
