title: Examining the evidence: a systematic review of the inclusion and analysis of older adults in randomized controlled trials.
abstract: BACKGROUND
  Due to a shortage of studies focusing on older adults, clinicians and policy makers frequently rely on clinical trials of the general population to provide supportive evidence for treating complex, older patients.
  
  
  OBJECTIVE
  To examine the inclusion and analysis of complex, older adults in randomized controlled trials.
  
  
  METHODS
  A PubMed search identified phase III or IV randomized controlled trials published in 2007 in JAMA, NEJM, Lancet, Circulation, and BMJ. Therapeutic interventions that assessed major morbidity or mortality in adults were included. For each study, age eligibility, average age of study population, primary and secondary outcomes, exclusion criteria, and the frequency, characteristics, and methodology of age-specific subgroup analyses were reviewed.
  
  
  RESULTS
  Of the 109 clinical trials reviewed in full, 22 (20.2%) excluded patients above a specified age. Almost half (45.6%) of the remaining trials excluded individuals using criteria that could disproportionately impact older adults. Only one in four trials (26.6%) examined outcomes that are considered highly relevant to older adults, such as health status or quality of life. Of the 42 (38.5%) trials that performed an age-specific subgroup analysis, fewer than half examined potential confounders of differential treatment effects by age, such as comorbidities or risk of primary outcome. Trials with age-specific subgroup analyses were more likely than those without to be multicenter trials (97.6% vs. 79.1%, p < 0.01) and funded by industry (83.3% vs. 62.7%, p < 0.05). Differential benefit by age was found in seven trials (16.7%).
  
  
  CONCLUSIONS
  Clinical trial evidence guiding treatment of complex, older adults could be improved by eliminating upper age limits for study inclusion, by reducing the use of eligibility criteria that disproportionately affect multimorbid older patients, by evaluating outcomes that are highly relevant to older individuals, and by encouraging adherence to recommended analytic methods for evaluating differential treatment effects by age.
authors.affiliation: The Robert Wood Johnson Foundation Clinical Scholars Program, University of Michigan, 6312 Medical Science Building I, 1150 W Medical Center Drive, Ann Arbor, MI 48109-5604, USA. dzulman@umich.edu
authors.forename: Donna M
authors.initials: DM
authors.lastname: Zulman
authors.forename: Jeremy B
authors.initials: JB
authors.lastname: Sussman
authors.forename: Xisui
authors.initials: X
authors.lastname: Chen
authors.forename: Christine T
authors.initials: CT
authors.lastname: Cigolle
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Blaum
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Hayward
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015897:Comorbidity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D016896:Treatment Outcome