Representation of older patients in clinical trials for drug approval in Japan.

To examine how target patients seen in clinical practice are represented in clinical trials for approved drugs in Japan, we compared the age distribution of older patients enrolled in confirmatory clinical trials for regulatory approval with that of the estimated actual patient population. Drugs for 6 chronic conditions common among older patients (diabetes mellitus, hypertension, rheumatoid arthritis, non-small cell lung cancer, depression and Alzheimer's disease) launched by 2012 in Japan were selected. The disparity in age distribution between patients in trials and patients seen in clinical practice varied depending on the disease, but older patients, especially those aged 75 or older, were generally underrepresented in clinical trials for regulatory approval in Japan. Under-representation of older patients in hypertension trials was particularly marked compared to other conditions, despite the similarity in age distribution of patients seen in clinical practice. One factor causing this disparity may be an upper age limit in clinical trial protocols. More effort is needed to properly characterize the benefits and risks of drugs for older patients. This should include the active enrollment of older patients in clinical trials, the establishment of better assessment tools such as pharmacometric approaches, and the appropriate planning and conducting of post-marketing surveys and studies.