title: Older patients are still under-represented in clinical trials of Alzheimer's disease.
abstract: The age gap between participants in trials and patients who could benefit from the drugs studied has been widely documented across different clinical areas. Patients with dementia included in clinical research are systematically younger than those in the general population. We examined the age gap between participants in recent clinical trials testing interventions for Alzheimer's disease and epidemiological data.
  
  
  
  We systematically searched literature databases (MedLine, EMBASE, the Cochrane Library) and ClinicalTrials.gov from 2000 to July 2015 to retrieve clinical trials testing pharmacologic treatments for Alzheimer's disease, other than cholinesterase inhibitors and memantine. We included ongoing and completed phase II/III randomized clinical trials, irrespective of their publication status. From each study reporting the participants' ages, we extracted size of sample, mean age, and standard deviation, and estimated the proportions of participants in different age classes. The number of patients with Alzheimer's disease by age class in the USA population was used for comparison.
  
  
  
  We included 165 clinical trials testing almost 100 different compounds, which enrolled or planned to enroll about 74,300 participants. Seventy-nine of these trials, accounting for about 26,800 participants, reported the age of the participants. The weighted mean age was 73.6 years (standard deviation, 8.2). People younger than 80 years were highly represented in clinical trials (78 %), despite the fact that those aged 80 and older form the majority (72 %) of patients with Alzheimer's disease. Only 8 % of clinical trial participants were 85 years or older.
  
  
  
  Patients enrolled in clinical trials on Alzheimer's disease are far from being representative of actual distribution of the patients in the general population. Clinical research should not be designed and conducted overlooking the fact that the majority of individuals with Alzheimer's disease are likely to be 80 or older.
authors: Laboratorio Politiche Regolatorie del Farmaco, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, Milan, 20156, Italy. rita.banzi@marionegri.it.
authors: Rita
authors: R
authors: Banzi
authors: Laboratorio di Neuropsichiatria Geriatrica, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, Milan, 20156, Italy.
authors: Paolo
authors: P
authors: Camaioni
authors: Laboratorio di Neuropsichiatria Geriatrica, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, Milan, 20156, Italy.
authors: Mauro
authors: M
authors: Tettamanti
authors: Laboratorio Politiche Regolatorie del Farmaco, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, Milan, 20156, Italy.
authors: Vittorio
authors: V
authors: Bertele'
authors: Laboratorio di Neuropsichiatria Geriatrica, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, Milan, 20156, Italy.
authors: Ugo
authors: U
authors: Lucca
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000628:therapy*; D017321:Clinical Trials, Phase I as Topic / Q000706:statistics & numerical data; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data
keywords: Age; Alzheimer’s disease; Clinical trials; Disease-modifying drugs; External validity; Inclusion criteria; Trial participants