title: Methodological challenges in assessing the impact of comorbidities on costs in Alzheimer's disease clinical trials.
abstract: BACKGROUND
  Alzheimer's disease (AD) is associated with considerable costs and has a significant impact on health and social care systems.
  
  
  OBJECTIVE
  This study assessed whether baseline comorbidities present in 2,594 patients with AD participating in two semagacestat randomized placebo-controlled trials (RCTs) would significantly impact overall costs.
  
  
  METHODS
  Resource utilization was captured using the Resource Utilization in Dementia Scale-Lite. Comorbidities and concomitant medications were tabulated via patient and caregiver reports. Only baseline data were analyzed. Direct and indirect costs per month were calculated per patient. The relationship between cost and explanatory variables was explored in a regression model.
  
  
  RESULTS
  The baseline monthly cost of care in this RCT population was £1,147 ± 2,483, with informal care costs accounting for 75% of costs. Gender, age, and functional status were significant predictors of costs (p ≤ 0.0001). The cost ratio was not impacted when the number of comorbidities was added to the model (cost ratio = 0.95; 95% CI 0.91-0.99) or when combined with the number of concomitant medications (cost ratio = 0.97; 95% CI 0.95-1.00). Inconsistent findings related to the impact of individual comorbidities on costs were noted in sensitivity analyses.
  
  
  CONCLUSIONS
  The number of comorbidities, alone or when combined with concomitant medications, did not impact baseline costs of care, perhaps because RCTs often enroll less severely ill and more medically stable patients. However, higher costs were consistently associated with greater functional impairment similar to non-RCT databases. Supplemental sources (e.g., claims databases) are likely needed to better estimate the effects of disease and treatment on costs of illness captured in RCTs for AD.
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. wrobleski_kristin_kahle@lilly.com.
authors.forename: Kristin
authors.initials: K
authors.lastname: Kahle-Wrobleski
authors.affiliation: Alzheimer's Drug Discovery Foundation and Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Fillit
authors.affiliation: Optum, Eden Prairie, MN, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kurlander
authors.affiliation: Eli Lilly and Company Limited, Windlesham, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Reed
authors.affiliation: Eli Lilly and Company Limited, Windlesham, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Belger
mesh_terms: D000203:Activities of Daily Living; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000188:drug therapy / Q000191:economics* / Q000453:epidemiology*; D001381:Azepines / Q000627:therapeutic use; D017028:Caregivers / Q000191:economics; D015897:Comorbidity; D017281:Cost of Illness; D005260:Female; D005102:Health Expenditures / Q000706:statistics & numerical data; D006296:Health Services / Q000191:economics / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D017059:Models, Econometric; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design / Q000592:standards*; D012720:Severity of Illness Index; D012737:Sex Factors
chemical_list: D001381:Azepines; C484278:N2-((2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl)-N1-((7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-L-alaninamide; D000409:Alanine
keywords: Alzheimer’s disease; Comorbidities; Concomitant medications; Economics; Randomized controlled trials; Semagacestat