Transportability of two heart failure trials to a disease registry using individual patient data

Wei, L. , Phillippo, D. M., Shah, A., Cleland, J. G.F. , Lewsey, J. and McAllister, D. A. (2023) Transportability of two heart failure trials to a disease registry using individual patient data. Journal of Clinical Epidemiology, 162, pp. 160-168. (doi: 10.1016/j.jclinepi.2023.08.019) (PMID:37659583)

Abstract

Objective: RCTs are the gold-standard for determining therapeutic efficacy, but are often unrepresentative of real-world settings. Statistical transportation-methods (hereafter transportation) can partially account for these differences, improving trial applicability without breaking randomisation. We transported treatment effects from two heart failure (HF) trials to a HF registry. Study Design and Setting: Individual-patient-level data from two trials (COMET, comparing carvedilol and metoprolol, and DIG, comparing digoxin and placebo) and a Scottish HF registry were obtained. The primary endpoint for both trials was all-cause mortality; secondary outcomes were all-cause mortality/hospitalisation for COMET and HF-related death or hospitalisation for DIG. We performed transportation using regression-based and inverse odds of sampling weights (IOSW) approaches. Results: Registry patients were older, had poorer renal function and received higher-doses of loop-diuretics than trial participants. For each trial, point estimates were similar for the original and IOSW (e.g., DIG composite outcome: OR 0.75 (0.69, 0.82) versus 0.73 (0.64, 0.83)). Treatment effect estimates were also similar when examining high-risk (0.64 (0.46, 0.89)) and low-risk registry patients (0.73 (0.61, 0.86)). Similar results were obtained using regression-based transportation. Conclusion: Regression-based or IOSW approaches can be used to transport trial effect estimates to patients administrative/registry data, with only moderate reductions in precision.

• Item Type: Articles
• Additional Information: This work was supported by a grant from the Wellcome Trust (201492/Z/16/Z) and the Hutchison foundation.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Wei, Dr Lili and McAllister, Professor David and Lewsey, Professor Jim and Cleland, Professor John
• Authors: Wei, L., Phillippo, D. M., Shah, A., Cleland, J. G.F., Lewsey, J., and McAllister, D. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Health Economics and Health Technology Assessment
• Journal Name: Journal of Clinical Epidemiology
• Publisher: Elsevier
• ISSN: 0895-4356
• ISSN (Online): 1878-5921
• Published Online: 01 September 2023
• Copyright Holders: Copyright © 2023 The Author(s)
• First Published: First published in Journal of Clinical Epidemiology 162:160-168
• Publisher Policy: Reproduced under a Creative Commons licence

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
173492		Combining efficacy estimates from clinical trials with the natural history obtained from large routine healthcare databases to determine net overall treatment benefits	David McAllister	Wellcome Trust (WELLCOTR)	201492/Z/16/Z	School of Health & Wellbeing