Under-representation of elderly in clinical trials: An analysis of the initial approval documents in the Food and Drug Administration database

Br J Clin Pharmacol. 2019 Apr;85(4):838-844. doi: 10.1111/bcp.13876. Epub 2019 Feb 23.

Abstract

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.

Keywords: clinical trials; efficacy; elderly; pharmacokinetics; safety.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Clinical Trials as Topic / standards
  • Clinical Trials as Topic / statistics & numerical data*
  • Cross-Sectional Studies
  • Databases, Factual / statistics & numerical data
  • Drug Approval*
  • Humans
  • Patient Selection*
  • Risk Assessment / standards
  • Risk Assessment / statistics & numerical data
  • United States
  • United States Food and Drug Administration / standards
  • United States Food and Drug Administration / statistics & numerical data*