Effect of age, sex, and morbidity count on trial attrition: meta-analysis of individual participant level data from phase 3/4 industry funded clinical trials

Lees, J. S. et al. (2022) Effect of age, sex, and morbidity count on trial attrition: meta-analysis of individual participant level data from phase 3/4 industry funded clinical trials. BMJ Medicine, 1(1), e000217. (doi: 10.1136/bmjmed-2022-000217)

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Abstract

Objectives: To estimate the association between individual participant characteristics and attrition from randomised controlled trials. Design: Meta-analysis of individual participant level data (IPD). Data sources: Clinical trial repositories (Clinical Study Data Request and Yale University Open Data Access). Eligibility criteria for selecting studies: Eligible phase 3 or 4 trials identified according to prespecified criteria (PROSPERO CRD42018048202). Main outcome measures: Association between comorbidity count (identified using medical history or concomitant drug treatment data) and trial attrition (failure for any reason to complete the final trial visit), estimated in logistic regression models and adjusted for age and sex. Estimates were meta-analysed in bayesian linear models, with partial pooling across index conditions and drug classes. Results: In 92 trials across 20 index conditions and 17 drug classes, the mean comorbidity count ranged from 0.3 to 2.7. Neither age nor sex was clearly associated with attrition (odds ratio 1.04, 95% credible interval 0.98 to 1.11; and 0.99, 0.93 to 1.05, respectively). However, comorbidity count was associated with trial attrition (odds ratio per additional comorbidity 1.11, 95% credible interval 1.07 to 1.14). No evidence of non-linearity (assessed via a second order polynomial) was seen in the association between comorbidity count and trial attrition, with minimal variation across drug classes and index conditions. At a trial level, an increase in participant comorbidity count has a minor impact on attrition: for a notional trial with high level of attrition in individuals without comorbidity, doubling the mean comorbidity count from 1 to 2 translates to an increase in trial attrition from 29% to 31%. Conclusions: Increased comorbidity count, irrespective of age and sex, is associated with a modest increased odds of participant attrition. The benefit of increased generalisability of including participants with multimorbidity seems likely to outweigh the disadvantages of increased attrition.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McAllister, Professor David and Butterly, Dr Elaine and Hanlon, Dr Peter and Mair, Professor Frances and Lees, Jennifer and Taylor, Professor Rod
Authors: Lees, J. S., Hanlon, P., Butterly, E. W., Wild, S. H., Mair, F. S., Taylor, R. S., Guthrie, B., Gillies, K., Dias, S., Welton, N. 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 > General Practice and Primary Care
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > MRC/CSO SPHSU
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
Journal Name:BMJ Medicine
Publisher:BMJ Publishing Group
ISSN:2754-0413
ISSN (Online):2754-0413
Published Online:01 September 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in BMJ Medicine 1(1): e000217
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173492Combining efficacy estimates from clinical trials with the natural history obtained from large routine healthcare databases to determine net overall treatment benefitsDavid McAllisterWellcome Trust (WELLCOTR)201492/Z/16/ZInstitute of Health & Wellbeing
305232Understanding prevalence and impact of frailty in chronic illness and implications for clinical managementFrances MairMedical Research Council (MRC)MR/S021949/1HW - General Practice and Primary Care