How robust are clinical trials in heart failure?

Docherty, K. F. , Campbell, R. T., Jhund, P. , Petrie, M. C. and McMurray, J. J.V. (2017) How robust are clinical trials in heart failure? European Heart Journal, 38(5), pp. 338-345. (doi: 10.1093/eurheartj/ehw427) (PMID:27742808)

Abstract

Aims: Guidelines for the management of chronic heart failure (CHF) cite the results of randomized controlled trials (RCTs) to support treatment recommendations. The significance of an observed treatment-effect relies on the use of a boundary p-value, most commonly p<0.05. There is concern about relying on arbitrary threshold p-values to report results as “statistically significant”. The “fragility index” (FI) has been proposed as an additional measure of the robustness of trial findings. FI is the minimum number of events needing to change from a non-event to an event in order to render a significant result non-significant. We calculated the FI to examine the robustness of statistically significant RCTs in CHF. Methods and results: Two reviewers extracted data from RCTs supporting treatment recommendations in CHF guidelines. 25 eligible trials were identified with a median sample size of 2331 patients (range 129-8399) and a median number of primary endpoints of 688.5 (range 88-2031). For the primary endpoint (analysed for 20 trials), the median FI was 26 (range 0-118). The FI was ≤10 in 7 (35%) of these 20 trials, and in 4 (20%) trials the number of patients lost to follow-up in the treatment group exceeded the FI. Conclusion: The results of some large RCTs in CHF hinge on a small number of events. The FI offers an additional, easy to understand metric, which augments the standard reporting of boundary p-values for statistical significance. The FI helps in the interpretation of the robustness of the results of RCTs.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Docherty, Dr Kieran and Jhund, Professor Pardeep and Campbell, Dr Ross and McMurray, Professor John and Petrie, Professor Mark
• Authors: Docherty, K. F., Campbell, R. T., Jhund, P., Petrie, M. C., and McMurray, J. J.V.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: European Heart Journal
• Publisher: Oxford University Press
• ISSN: 0195-668X
• ISSN (Online): 1522-9645
• Published Online: 14 October 2016
• Copyright Holders: Copyright © 2016 Oxford University Press
• First Published: First published in European Heart Journal 38(5): 338-345
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher