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Am J Neurodegener Dis 2012;1(3):205-216

Original Article
Advances in designs for Alzheimer’s disease clinical trials

Jeffrey Cummings, Heath Gould, Kate Zhong

Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nevada; Cleveland, Ohio; Weston, Florida, USA

Received October 3, 2012; Accepted October 29, 2012; Epub November 18, 2012; Published November 30, 2012

Abstract: There is an urgent need to identify new treatments for the rapidly growing population of people with
Alzheimer’s disease (AD). Innovations in clinical trial designs many help to reduce development time, provide more
definitive answers regarding drug efficacy, and facilitate prioritizing compounds to be advanced to Phase III clinical
trials. Standard designs compare drug and placebo changes from baseline on a rating scale. Baysian adaptive clinical
trials allow the use of data collected in the trial to modify doses, sample size, trial duration, and entry criteria in an on
-going way as the data are collected. Disease-modification is supported by findings on staggered start and delayed
withdrawal designs. Futility designs can use historical controls and may shorten trial duration. Combination therapy
designs may allow investigation of additive or synergistic treatment effects. Novel trial selection criteria allow
investigation of treatment effects in asymptomatic or minimally symptomatic, prodromal AD populations. The Clinical
Dementia Rating-Sum of Boxes (CDR-SOB) can be considered as a single trial outcome in early disease populations.
Alternate forms of the Alzheimer’s Disease Assessment Scale-Cognitive Portion (ADAS-cog), computerized measures,
and pharmacoeconomic scales provide new and relevant information on drug effects. Comparative dose strategies
are used in trials of symptomatic agents, and novel methods including withdrawal designs, symptom emergence
analyses, and sequential designs are being utilized to assess the efficacy of putative psychotropic agents. The choice
of trial design is driven by the question to be answered by the clinical trial; an increasing number of design approaches
are available and may be useful in accelerating and refining AD drug development. (AJND1210001).

Keywords: Clinical trials, Alzheimer’s disease, designs, drug development

Address all correspondence to:
Dr. Jeffrey L Cummings
Cleveland Clinic Lou Ruvo Center for Brain Health
Camille and Larry Ruvo Chair for Brain Health
Cleveland Clinic Lou Ruvo Center for Brain Health
888 W Bonneville Avenue, Las Vegas, NV 89106.
Tel: 702.483.6029; Fax: 702.483.6028
E-mail: cumminj@ccf.org