Quantification of Age and Sex Ratio Differences between Trial and Target Population for New Drugs

Clinical trials are essential to understand the benefit-harm profile of new drugs. Lack of adequate representation in age and sex ratio in clinical trials can result, for example, in higher side effects for underrepresented patients. We quantified differences in age and sex ratios between trial and target populations of new drugs approved by the FDA 2011-2022. We used the FDA's database to identify all new drugs and pivotal randomized trials. Information for average age and sex ratio was obtained from clinicaltrials.gov. Each trial's indication was matched with prevalence estimates of the targeted diseases from the global burden of disease study. A total of 458 drugs (773 trials) were included. The trial populations were significantly younger, on average 4.8 years (95% CI [5.4 years, 4.2 years]), and the female ratio significantly smaller, on average 4.3 percentage points (95% CI [5.4 pp, 3.3 pp]), than the target populations. For diseases with average patient age below 40, the trial population was significantly older than the target population but significantly younger 40 years and older. For diseases with average age between 30 and 39, the female ratio in the trial population was significantly higher than in the target population but significantly lower 50 and older. Better age and sex ratio representation in the trial population is indicated to improve safety and efficacy for patients. Trials targeting diseases below 40 should enroll younger participants and increase their male ratio, while the opposite is true for trials targeting diseases with an older age.