title: Participation of older people in preauthorization trials of recently approved medicines.
abstract: OBJECTIVE
  To investigate the inclusion of older people in clinical trials of recently authorized medicines, evaluating adherence to the 20-year-old International Conference of Harmonisation (ICH) guideline on geriatrics (E7).
  
  
  METHODS
  Observational.
  
  
  METHODS
  European public assessment reports, published clinical trials, World Health Organization International Clinical Trials Registry Platform.
  
  
  METHODS
  Individuals aged 65 and older and 75 and older.
  
  
  METHODS
  Number and proportion of randomized participants and all exclusion criteria of studies involving diseases characteristically associated with aging (venous thromboembolism, osteoporosis, atrial fibrillation) and diseases not unique to older adults (type 2 diabetes mellitus, depression, bipolar disorder, epilepsy).
  
  
  RESULTS
  In 114 Phase II and III trials of 12 medicines, 43.1% of participants were aged 65 and older, and 16.1% were aged 75 and older. In trials involving diseases characteristically associated with ageing, 57% were aged 65 and older; 22% were aged 75 and older. In trials involving diseases not unique to old age, 9% were aged 65 and older, and 1% were aged 75 and older. Upper age limits were applied in 30.7% of the trials; the frequency did not differ between larger (sample size ≥ 500) and smaller trials (P = .36), although it was significantly lower in trials involving diseases characteristically associated with aging (18.0%) than in trials of diseases not unique to old age (45.3%; P = .002). Age-sensitive exclusion criteria, based on comorbidity (75.4%), concomitant medication (71.9%), and other criteria correlated with age (60.5%) were applied more frequently in larger trials (P < .02).
  
  
  CONCLUSIONS
  Studies of diseases not uniquely associated with old age included an unacceptably low proportion of older people, contrary to the recommendations of the ICH E7 guideline. Although the proportion of older participants in trials of diseases characteristically associated with aging was appropriate for certain medicines, the use of age-sensitive exclusion criteria limits the representativeness of the trial population for daily practice.
authors.affiliation: Department of Geriatric Medicine, University Medical Center, Utrecht, The Netherlands; Expertise Centre Pharmacotherapy in Old Persons, University Medical Center, Utrecht, The Netherlands.
authors.forename: Erna
authors.initials: E
authors.lastname: Beers
authors.forename: Dineke C
authors.initials: DC
authors.lastname: Moerkerken
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Leufkens
authors.forename: Toine C G
authors.initials: TC
authors.lastname: Egberts
authors.forename: Paul A F
authors.initials: PA
authors.lastname: Jansen
mesh_terms: D000368:Aged / Q000706:statistics & numerical data*; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000188:drug therapy; D001714:Bipolar Disorder / Q000188:drug therapy; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003863:Depression / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004827:Epilepsy / Q000188:drug therapy; D005060:Europe; D017408:Guidelines as Topic; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy; D035842:Research Subjects / Q000706:statistics & numerical data*; D054556:Venous Thromboembolism / Q000517:prevention & control
keywords: clinical trial; exclusion; geriatric medicine; older participant; regulatory agency