Abstract
BackgroundClinicians are less likely to prescribe guideline-recommended treatments to people with multimorbidity than to people with a single condition. Doubts as to the applicability of clinical trials of drug treatments (the gold standard for evidence-based medicine) when people have co-existing diseases (comorbidity) may underlie this apparent reluctance. Therefore, for a range of index conditions, we measured the comorbidity among participants in clinical trials of novel drug therapies and compared this to the comorbidity among patients in the community.MethodsData from industry-sponsored phase 3/4 multicentre trials of novel drug therapies for chronic medical conditions were identified from two repositories: Clinical Study Data Request and the Yale University Open Data Access project. We identified 116 trials (n = 122,969 participants) for 22 index conditions. Community patients were identified from a nationally representative sample of 2.3 million patients in Wales, UK. Twenty-one comorbidities were identified from medication use based on pre-specified definitions. We assessed the prevalence of each comorbidity and the total number of comorbidities (level of multimorbidity), for each trial and in community patients.ResultsIn the trials, the commonest comorbidities in order of declining prevalence were chronic pain, cardiovascular disease, arthritis, affective disorders, acid-related disorders, asthma/COPD and diabetes. These conditions were also common in community-based patients.Mean comorbidity count for trial participants was approximately half that seen in community-based patients. Nonetheless, a substantial proportion of trial participants had a high degree of multimorbidity. For example, in asthma and psoriasis trials, 10–15% of participants had ≥ 3 conditions overall, while in osteoporosis and chronic obstructive pulmonary disease trials 40–60% of participants had ≥ 3 conditions overall.ConclusionsComorbidity and multimorbidity are less common in trials than in community populations with the same index condition. Comorbidity and multimorbidity are, nevertheless, common in trials. This suggests that standard, industry-funded clinical trials are an underused resource for investigating treatment effects in people with comorbidity and multimorbidity.
Highlights
Clinicians are less likely to prescribe guideline-recommended treatments to people with multimorbidity than to people with a single condition
Since factors other than eligibility criteria are likely to influence which people are recruited to clinical trials [18], such approaches provide only indirect evidence about the prevalence of comorbidity and multimorbidity in trial participants
We examined the prevalence of comorbidity and multimorbidity among 122,969 participants from 116 industry-funded trials of novel drug therapies for 22 index conditions and compared these results with comorbidity and multimorbidity prevalence in 2.3 million patients living in the community
Summary
Study design This cross-sectional analysis compares the distribution of comorbidity and multimorbidity in participants enrolled in 116 industry-sponsored trials and a representative community sample from the UK. The following comorbidities (detailed in Additional file 4) were identified based on medication use: cardiovascular disease, chronic pain, arthritis, affective disorders, acidrelated disorders, asthma/chronic obstructive pulmonary disease, diabetes mellitus, osteoporosis, thyroid disease, thromboembolic disease, inflammatory conditions, benign prostatic hyperplasia, gout, glaucoma, urinary incontinence, erectile dysfunction, psychotic disorders, epilepsy, migraine, parkinsonism and dementia These drug-based definitions were developed in consultation with a steering committee comprising clinicians, epidemiologists and statisticians and were finalised before the analysis of the primary care data. Taking posterior samples from this model, we applied the probability mass function for the Poisson distribution to obtain the proportion with comorbidity counts ranging from 0 to 12 In both cases, we obtained 1000 samples, from which we calculated the following pre-specified statistics: the ratio of mean counts of conditions, the ratio of the proportion with a count ≥ 2 and the proportion of community patients with a count greater than the trial median count. SAIL analyses were approved by SAIL Information Governance Review Panel (Project 0830)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
