title: Prevalence of diabetes treatment effect modifiers: the external validity of trials to older adults.
abstract: OBJECTIVE
  Potential treatment effect modifiers (TEMs) are specific diseases or conditions with a well-described mechanism for treatment effect modification. The prevalence of TEMs in older adults with type 2 diabetes mellitus (DM) is unknown. Objectives were to 1) determine the prevalence of pre-specified potential TEMs; 2) demonstrate the potential impact of TEMs in the older adult population using a simulated trial; 3) identify TEM combinations associated with number of hospitalizations to test construct validity.
  
  
  METHODS
  Data are from the nationally-representative United States National Health and Examination Survey, 1999-2004: 8646 Civilian, non-institutionalized adults aged 45-64 or 65+ years, including 1443 with DM. TEMs were anemia, congestive heart failure, liver inflammation, polypharmacy, renal insufficiency, cognitive impairment, dizziness, frequent mental distress, mobility difficulty, and visual impairment. A trial was simulated to examine prevalence of potential TEM impact. The cross-sectional association between TEM patterns and number of hospitalizations was estimated to assess construct validity.
  
  
  RESULTS
  The prevalence of TEMs was substantial such that 19.0% (95% CI 14.8-23.2) of middle-aged adults and 38.0% (95% CI 33.4-42.5) of older adults had any two. A simulated trial with modest levels of interaction suggested the prevalence of TEMs could nullify treatment benefit in 3.9-27.2% of older adults with DM. Compared to having DM alone, hospitalization rate was increased by several combinations of TEMs with substantial prevalence.
  
  
  CONCLUSIONS
  We provide national benchmarks that can be used to evaluate TEM prevalence reported by clinical trials of DM, and correspondingly their external validity to older adults.
authors.affiliation: Division of Geriatric Medicine & Gerontology, Baltimore, MD 21224-2734, USA. cweiss9@jhmi.edu
authors.forename: Carlos O
authors.initials: CO
authors.lastname: Weiss
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Boyd
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Wolff
authors.forename: Bruce
authors.initials: B
authors.lastname: Leff
mesh_terms: D000367:Age Factors; D000368:Aged; D003430:Cross-Sectional Studies; D003625:Data Collection; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000628:therapy*; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D014481:United States / Q000453:epidemiology