A systematic review of trends in the selective exclusion of older participant from randomised clinical trials

Introduction: The unjustified exclusion of older participants from clinical trials creates research populations that are non-representative, in turn creating difficulties applying research to the target populations. The aim of this study was to assess the proportion of randomised control trials (RCTs) that have unexplained upper age limits and review whether this proportion is reducing over time. Methods: All RCTs in BMJ, Lancet, JAMA and NEJM from 1998 to 2015 were reviewed to identify any specified upper-age cut off and, if so, whether this exclusion criterion had an explanation in the text. The proportion of RCTs with an unexplained cut off was then correlated over time to look for any changes. Results: 5680 papers were identified and 1339 excluded as they did not meet the search criteria. Of the remaining 4341 RCTs, 1258 (29%) had upper age limits specified, 1168 (92.8%) of which did not have any explanation for this cut off, a total of 26.9% of the RCTs reviewed. Over the 18-year period there was limited but statistically significant decrease in the proportion of RCTs with unexplained upper age limits (Pearson Correlation -0.609, P valve 0.007). Conclusion: Despite being the highest consumers of medical interventions and medications, this review highlights that older patients remain under-represented in clinical trial with only modest improvements despite increasing awareness of the problem. Future research must continue to adapt to provide insight into the differential effects of medical treatments in older patients by ensuring that trial participants are representative of the patient population receiving the intended therapy.