Due to a shortage of studies focusing on older adults, clinicians and policy makers frequently rely on clinical trials of the general population to provide supportive evidence for treating complex, older patients.
To examine the inclusion and analysis of complex, older adults in randomized controlled trials.
A PubMed search identified phase III or IV randomized controlled trials published in 2007 in JAMA, NEJM, Lancet, Circulation, and BMJ. Therapeutic interventions that assessed major morbidity or mortality in adults were included. For each study, age eligibility, average age of study population, primary and secondary outcomes, exclusion criteria, and the frequency, characteristics, and methodology of age-specific subgroup analyses were reviewed.
Of the 109 clinical trials reviewed in full, 22 (20.2%) excluded patients above a specified age. Almost half (45.6%) of the remaining trials excluded individuals using criteria that could disproportionately impact older adults. Only one in four trials (26.6%) examined outcomes that are considered highly relevant to older adults, such as health status or quality of life. Of the 42 (38.5%) trials that performed an age-specific subgroup analysis, fewer than half examined potential confounders of differential treatment effects by age, such as comorbidities or risk of primary outcome. Trials with age-specific subgroup analyses were more likely than those without to be multicenter trials (97.6% vs. 79.1%, p < 0.01) and funded by industry (83.3% vs. 62.7%, p < 0.05). Differential benefit by age was found in seven trials (16.7%).
Clinical trial evidence guiding treatment of complex, older adults could be improved by eliminating upper age limits for study inclusion, by reducing the use of eligibility criteria that disproportionately affect multimorbid older patients, by evaluating outcomes that are highly relevant to older individuals, and by encouraging adherence to recommended analytic methods for evaluating differential treatment effects by age.
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The authors would like to thank Gupreet K. Rana, Clinical Education Librarian at the University of Michigan Taubman Medical Library, for her assistance with the literature search for this manuscript.
Donna Zulman and Jeremy Sussman are supported by the Robert Wood Johnson Foundation Clinical Scholars Program and an associated VA Advanced Fellowship. This work was also supported by the Department of Veterans Affairs Health Services Research & Development Service (QUERI DIB), and utilized the Measurement Core of the Michigan Diabetes Research and Training Center funded by DK020572 from the NIDDK. Dr. Cigolle is supported by the NIH-NCRR K12 Mentored Clinical Scholars Program at the University of Michigan and the VA Ann Arbor Healthcare System’s Geriatric Research Education and Clinical Center (GRECC).
Conflict of Interest
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Zulman, D.M., Sussman, J.B., Chen, X. et al. Examining the Evidence: A Systematic Review of the Inclusion and Analysis of Older Adults in Randomized Controlled Trials. J GEN INTERN MED 26, 783–790 (2011). https://doi.org/10.1007/s11606-010-1629-x
- clinical trial methodology
- exclusion criteria
- subgroup analysis