Study Design
Prospective benchmarking of an observational analysis against a randomized trial: beta blockers after myocardial infarction with preserved ejection fraction Anthony A. Matthews* Anthony A. Matthews Issa J. Dahebreh Conor J. MacDonald Bertil Lindahl Robin Hofmann David Erlinge Troels Yndigegn Anita Berglund Tomas Jernberg Miguel A. Hernán
Prospective benchmarking of an observational analysis against a randomized trial increases confidence in the benchmarking process as it relies exclusively on aligning the protocol of the trial and the observational analysis, while the trials findings are unavailable. The Randomized Evaluation of Decreased Usage of Betablockers After Myocardial Infarction (REDUCE-AMI) trial started recruitment in September 2017 and results are expected in 2024. REDUCE-AMI aimed to estimate the effect of long-term beta blockers on the risk of death and myocardial following a myocardial infarction with preserved left ventricular systolic ejection fraction. We designed a target trial with a protocol as similar as possible to that of REDUCE-AMI, and then emulated the target trial using observational data from Swedish healthcare registries.
Had everyone followed the protocol, the observational analysis estimated a reduction in the 5-year risk of death or myocardial infarction of 0.8 percentage points for beta blockers compared with no beta blockers, but effects ranging from a reduction of 4.5 percentage points to an increase of 2.8 percentage points are compatible with our data under conventional statistical criteria.
Once results of REDUCE-AMI are published, we will compare results of our observational analysis against those from the trial. If this prospective benchmarking is successful, the observational data can rapidly provide additional answers to questions that could not be answered by the initial trial, such as the treatment effect in those not eligible for the trial. If it is not, we will conduct a “postmortem” analysis to identify the reasons for the discrepancy. Prospective benchmarking shifts the investigator focus away from an endeavour to use observational data to obtain similar results as a randomized trial, to a systematic attempt to align the design and analysis of the trial and observational analysis.