An approach to explore for a sweet spot in randomized trials.

Pubmed ID: 31874202

Journal: Journal of clinical epidemiology

Publication Date: April 1, 2020

Link: https://www.sciencedirect.com/science/article/abs/pii/S089543561930438X

MeSH Terms: Humans, Male, Female, Middle Aged, Randomized Controlled Trials as Topic, Heart Failure, Treatment Outcome, Severity of Illness Index, Death, Sudden, Cardiac, Defibrillators, Implantable

Authors: Redelmeier DA, Tibshirani RJ

Cite As: Redelmeier DA, Tibshirani RJ. An approach to explore for a sweet spot in randomized trials. J Clin Epidemiol 2020 Apr;120:59-66. Epub 2019 Dec 23.

Studies:

Abstract

OBJECTIVE: The objective of the study was to demonstrate how a conventional randomized trial can be analyzed through a stratified or a matched approach to identify a potential sweet spot where observed differences might be accentuated in the mid range of disease severity. DESIGN AND SETTING: We review a landmark randomized trial of heart failure patients that tested whether implantable defibrillators reduce mortality (n = 2,521). RESULTS: Overall, 22% (182/829) of the patients in the defibrillator group died compared with 29% (484/1,692) of patients in the control group. Proportional hazards analysis yielded a modest 25% survival benefit (hazard ratio = 0.75, 95% confidence interval: 0.63 to 0.89). Stratified analysis of the trial yielded a larger 52% survival benefit for those in the middle quintile of disease severity (hazard ratio = 0.48, 95% confidence interval: 0.29 to 0.79). In contrast, little of the survival benefit was explained by patients with the greatest disease severity (hazard ratio = 0.89, 95% confidence interval: 0.69 to 1.15). The discrepancy between crude and stratified analyses could be visualized by graphical displays and replicated with matched comparisons. CONCLUSION: Our approach for analyzing a randomized trial could help identify a potential sweet spot of an accentuated treatment effect.