Underrepresentation of elderly people in randomised controlled trials. The example of trials of 4 widely prescribed drugs

Abstract

Background: We aimed to determine the representation of elderly people in published reports of randomized controlled trials (RCTs). We focused on trials of 4 medications--pioglitazone, rosuvastatin, risedronate, and valsartan-frequently used by elderly patients with chronic medical conditions.

Methods and findings: We selected all reports of RCTs indexed in PubMed from 1966 to April 2008 evaluating one of the 4 medications of interest. Estimates of the community-based "on-treatment" population were from a national health insurance database (SNIIR-AM) covering approximately 86% of the population in France. From this database, we evaluated data claims from January 2006 to December 2007 for 1,958,716 patients who received one of the medications of interest for more than 6 months. Of the 155 RCT reports selected, only 3 studies were exclusively of elderly patients (2 assessing valsartan; 1 risedronate). In only 4 of 37 reports (10.8%) for pioglitazone, 4 of 22 (18.2%) for risedronate, 3 of 29 (10.3%) for rosuvastatine and 9 of 67 (13.4%) for valsartan, the proportion of patients aged 65 or older was within or above that treated in clinical practice. In 62.2% of the reports for pioglitazone, 40.9% for risedronate, 37.9% for rosuvastatine, and 70.2% for valsartan, the proportion of patients aged 65 or older was lower than half that in the treated population. The representation of elderly people did not differ by publication date or sample size.

Conclusions: Elderly patients are poorly represented in RCTs of drugs they are likely to receive.

Figure 1. Flow chart of the number of published reports of randomized controlled trials identified and reviewed.

Figure 2. Funnel plots displaying (1) mean age, (2) estimated proportion of subjects aged 65 or older and (3) estimated proportion of subjects aged 75 or older plotted for each trial against the trial's sample size.

(1) Mean age, (2) proportion of subjects aged 65 or older and (3) proportion of subjects aged 75 or older in clinical practice calculated from the SNIIR-AM database were plotted as horizontal lines (plain lines) with the corresponding 95% confidence interval (95% CI; dashed lines). For each medication, the plot shows how many RCTs had a proportion of older subjects below or above the 95% CI limits (0.05 probability of exceeding these limits) (i.e., RCTs with significantly lower or higher representation of elderly people as compared with the community-based “on-treatment” population). The plot allows for assessing how the proportion of elderly people varies with trial size and time. White dots represent older trials (i.e., trial reports published before 2006) and black dots represent recent trials (i.e. trial reports published in or after 2006).

Figure 3. Box plots for the relative difference between the randomized controlled trials (RCTs) and clinical practice in proportion of patients aged 65 years and older and 75 years and older.

Boxes represent median values (horizontal rule) with 25th and 75th percentiles (top and bottom of box). Error bars represent the 10th and 90th percentiles.