Older Patients on Maintenance Dialysis Underrepresented in RCTs

New data show an average younger age reflected in randomized controlled trials evaluating maintenance dialysis, despite the general dialysis population being > 65 years of age.1,2

These findings report a limited consideration of older age in trial analyses, randomization, and overall inclusion, highlighting modifiable barriers to trial design and generalizability.1

“This may be related to an overlap between advanced age and other exclusion criteria related to advanced age, as there are many known barriers to participation in RCTs among older persons related to safety or ethical, or logistical concerns,” wrote study investigator David Collister, MD, PhD, an assistant professor at the University of Alberta, and colleagues.1

Older adults have differences in pharmacology, multimorbidity, polypharmacy, and healthcare utilization patterns compared to younger patients. This population has also been historically underrepresented in clinical trials due to participation barriers. As a result, the disproportionate exclusion of older adults in randomized controlled trials might lead to limited generalizability in trial outcomes.3

To assess these limitations in the context of dialysis, investigators conducted a meta-epidemiologic study of older patients receiving maintenance dialysis in randomized controlled trials to determine how age is incorporated into design, conduct, and analysis.1

The study included 561 randomized controlled trials with 106,000 participants, and the mean age was 58.5 years (standard deviation, 6.6), notably younger than the 61.5-63.5 age range of the US hemodialysis cohort from the Dialysis Outcomes and Practice Patterns Study.1

Investigators found age-based eligibility in 16.9% of randomized controlled trials (n = 95). Of these, 3.9% had a cutoff at >75 years of age (n = 22), 7.8% at >80 years of age (n = 44), and 2.5% at >85 years of age (n = 14). In >5% of trials, relevant exclusion criteria included mild cognitive impairment/dementia, psychiatric disorders, language barriers, and inability to provide informed consent.1

Overall, investigators noted that 6.4% of trials reported age as a factor for randomization, minimization, or stratification (n = 36). In trial analyses, 3.6% used age as a subgroup for the primary outcome (n = 20) and 20.5% reported age as a covariate in the analysis of treatment effects (n = 115).1

In the trials’ multivariable linear regression model, investigators observed that mean/median population age, publication year, dialysis population type, geography, and intervention type were independently associated with age. Notably, studies with recent publication years and a follow-up time were associated with age-based exclusion criteria. Of note, follow-up duration >1 year was the only independent predictor of having an upper age eligibility cutoff, which investigators suggest may be due to concerns about long-term adherence or the competing risk of death.1

Going forward, Collister and colleagues suggest ethical or safety concerns, including informed consent, should be the main reasons for implementing upper age cutoffs in trial designs. Otherwise, they suggest including sufficient representation of participants from age groups that approximate the general dialysis population, reporting age as a demographic variable, and including it as a factor in randomization, covariate adjustment, and subgroup analyses.1

“In summary, contemporary maintenance dialysis RCTs sometimes exclude older participants through eligibility criteria and are not representative of the general dialysis population with respect to age,” concluded investigators. “Trialists should consider how they can design and conduct studies to address the unique barriers to participation faced by older patients.”1

References

1. Wang K, Bamber Z, Pyne L, et al. Representation of Older Patients Receiving Maintenance Dialysis in Randomized Controlled Trials: A Meta-Epidemiologic Study. American Journal of Kidney Diseases. Published online December 1, 2025. doi:https://doi.org/10.1053/j.ajkd.2025.09.023

2. Latos DL. Chronic dialysis in patients over age 65. Journal of the American Society of Nephrology. 1996;7(5):637-646. doi:https://doi.org/10.1681/asn.v75637

3. Florisson S, Aagesen EK, Bertelsen AS, Nielsen LP, Rosholm J. Are older adults insufficiently included in clinical trials?—An umbrella review. Basic & Clinical Pharmacology & Toxicology. 2020;128(2):213-223. doi:https://doi.org/10.1111/bcpt.13536‌