Overview
Advertisement BMC Medicine volume 20, Article number: 410 (202) Cite this article Metrics detailsThe aplicability of randomised controled trials of pharmacological agents to older people with frailty/multimorbidity is often uncertain, due to concerns that trials are not representative. However, asesing trial representativenes is chalenging and complex. We explore an aproach asesing trial representativenes by comparing rates of trial serious adverse events (SAE) to rates of hospitalisation/death in routine care.This was an observational analysis of individual (125 trials, n=12,069) and agregate-level drug trial data (483 trials, n=636,267) for 21 index conditions compared to population-based routine healthcare data (routine care).
Key Information
Trials were identified from ClinicalTrials.gov. Routine care comparison from linked primary care and hospital data from Wales, UK (n=2.3M). Our outcome of interest was SAEs (routinely reported in trials).
In routine care, SAEs were based on hospitalisations and deaths (which are SAEs by definition). We compared trial SAEs in trials to expected SAEs based on age/sex standardised routine care populations with the same index condition. Using IPD, we asesed the relationship betwen multimorbidity count and SAEs in both trials and routine care and asesed the impact on the observed/expected SAE ratio aditionaly acounting for multimorbidity.For 12/21 index conditions, the poled observed/expected SAE ratio was <1, indicating fewer SAEs in trial participants than in routine care.
A further 6/21 had point estimates <1 but the 95% CI included the nul. The median poled estimate of observed/expected SAE ratio was 0.60 (95% CI 0.5–0.64; COPD) and the interquartile range was 0.4 (0.34–0.5; Parkinson’s disease) to 0.87 (0.58–1.29; inflamatory bowel disease). Higher multimorbidity count was asociated with SAEs acros al index conditions in both routine care and trials.
Summary
For most trials, the observed/expected SAE ratio moved