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

Jennifer S. Lees*, Peter Hanlon, Elaine Butterly, Sarah H Wild, Frances Mair, Rod S. Taylor, Bruce Guthrie, Katie Gillies, Sofia Dias, Nicky J. Welton, David A McAllister

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Objectives
To estimate the association between individual participant characteristics and attrition from randomised controlled trials (“trials”).
Design
Meta-analysis of individual participant-level data (IPD) from Phase 3 or 4 trials contained within two clinical trial repositories (Clinical Study Data Request and Yale University Open Data Access).
Participants
Eligible trials for inclusion were identified according to pre-specified criteria (PROSPERO CRD42018048202).
Main outcome measures
The association between comorbidity count (identified using medical history and/or concomitant medication data) and trial attrition (failure for any reason to complete the final trial visit) was estimated in logistic regression models, adjusting 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 0.3-2.7. Neither age nor sex was clearly associated with attrition (odds ratio (OR) 1.04, 95% CI 0.98-1.11 and OR 1.00, 95% PI 0.95-1.07 respectively). However, comorbidity count was associated with attrition (OR per additional comorbidity: 1.11, 95% CI: 1.07 to 1.14). There was no evidence of non-linearity (assessed via a second-order polynomial) in the association between comorbidity count and trial attrition, and there was minimal variation across drug classes and index conditions. At a trial level this translates to a fairly 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 appears likely to outweigh the disadvantages of increased attrition.
Original languageEnglish
Article numbere000217
Number of pages11
JournalBMJ Medicine
Volume1
Issue number1
DOIs
Publication statusPublished - 1 Sept 2022

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