AlzPED: Optimizing the predictive power of drug efficacy studies in Alzheimer’s disease animal models

Abstract

AbstractBackgroundPoor translation of preclinical efficacy from animal models to the clinic is a major challenge to successful therapy development for Alzheimer’s disease (AD). Assessments of preclinical animal studies highlight the need for an emphasis on rigor in study design and methodology and a consensus towards a uniform set of study design elements and best practices. The Alzheimer’s Disease Preclinical Efficacy Database (AlzPED), a searchable and publicly available knowledgebase developed by the National Institute on Aging, has identified and compiled a standardized set of best practices and experimental design guidelines to effectively promote the translation of preclinical therapeutic studies in AD animal models to the clinic.MethodUsing key word‐driven literature searches published studies are acquired and curated by two experts for data on authors, funding source, AD animal models, therapeutic targets and therapeutic agents, study design, and outcome measures, prior to publication in the database. Rigor in study design and methodology is evaluated with a Rigor Report Card consisting of a standardized set of expert‐recommended study design elements.ResultAlzPED hosts curated summaries from more than 1100 published preclinical therapeutic studies in AD animal models, and data related to 223 therapeutic targets, 1020 therapeutic agents, 200 animal models, more than 1500 AD‐related outcome measures, and thousands of principal findings. Evaluation of Rigor Report Cards from each study demonstrates significant under‐reporting of critical elements of methodology such as power/sample size calculation, blinding for treatment, blinding for outcomes, randomization, balancing for sex, animal genetic background, and inclusion/exclusion criteria, these being reported by fewer than 30% of the more than 1100 curated studies.ConclusionAnalysis of curated studies demonstrates serious deficiencies in reporting critical elements of methodology. These deficiencies diminish the scientific rigor, reproducibility, and translational value of the preclinical studies. Adopting a standardized set of best practices like those proposed by AlzPED can improve the predictive power of preclinical studies in AD animal models and promote the effective translation of preclinical drug testing data to the clinic.