Under-representation of elderly in clinical trials - an analysis of the initial approval documents in the FDA database.

Aims To evaluate the availability of pharmacokinetic, safety and efficacy analyses specifically targeted at elderly, prior to the authorization of drugs. Methods A cross-sectional, structured review of publicly available initial approval documents of Food and Drug Administration-approved drugs was performed. The 10 most frequently on-label prescribed drug classes, drugs with known pharmacokinetic differences in the elderly or drugs that are relatively contraindicated in elderly (e.g. anticholinergics or benzodiazepines) were included in the analyses. Results In total, 1129 unique active pharmaceutical ingredients were found eligible for the analyses, of these, 506 were found in the Food and Drug Administration database (45%). The initial approval documents were available for 182 drugs. For the majority of the drugs, the initial approval documents in the database showed information on pharmacokinetics in elderly (n = 113; 62%). Furthermore, over time, the availability of information with regard to elderly increased statistically significantly from 0% in the period 1970-1979 to 76% for the period 2010-2018. Information on safety and efficacy was less frequently present, i.e. 42% and 45%, respectively and, moreover, the availability of information did not improve over time. Conclusion The under-representation of elderly in clinical trials thereby challenging the external validity of benefit/risk assessments of launched drugs was confirmed. Priority should be given to a study population that is representative for the target population.