title: Statistical analysis, trial design and duration in Alzheimer's disease clinical trials: a review.
abstract: BACKGROUND
  The social and economic burden of Alzheimer's disease (AD) and its increasing prevalence has led to much work on new treatment strategies and clinical trials. The search for surrogate markers of disease progression continues but traditional parallel group trial designs that use well-established, but often insensitive, clinical outcome measures predominate.
  
  
  METHODS
  We performed a systematic search across the Cochrane Library and PubMed abstracts published between January 2004 and August 2009. Information regarding the clinical trial methodology, outcome measures, intervention type and primary statistical analysis techniques was extracted and categorized, according to a standard protocol.
  
  
  RESULTS
  We identified 149 papers describing results from clinical trials in AD containing sufficient detail for our purposes. The largest proportion (38%) presented results of trials based on tests of cognition as the primary outcome measure. The primary analysis in most papers (85%) was a univariate significance test of a single primary outcome measure.
  
  
  CONCLUSIONS
  The majority of trials reported a comparison of baseline and end-point assessment over relatively short patient follow-up periods, using univariate statistical methods to compare differences between intervention and control groups in the primary analysis. There is considerable scope to introduce newer statistical methods and trial designs in treatment evaluations in AD.
authors.affiliation: Centre for Health and Environmental Statistics, University of Plymouth, Plymouth, UK. paul.thompson1@plymouth.ac.uk.
authors.forename: P A
authors.initials: PA
authors.lastname: Thompson
authors.forename: D E
authors.initials: DE
authors.lastname: Wright
authors.forename: C E
authors.initials: CE
authors.lastname: Counsell
authors.forename: J
authors.initials: J
authors.lastname: Zajicek
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000628:therapy*; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D003071:Cognition; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D006801:Humans; D013223:Statistics as Topic / Q000379:methods; D013997:Time Factors; D016896:Treatment Outcome