AlzPED: Raising the Standards for Preclinical Efficacy Testing of Candidate Therapeutics in Alzheimer’s Disease

Abstract

AbstractBackgroundPositive findings of therapeutics and interventions from studies conducted in Alzheimer’s disease (AD) animal models are often not translated to effective treatments. Assessments of these studies highlight the lack of methodological rigor and inadequate reporting practices as contributive to the preclinical to clinical translation gap in AD therapy development. AlzPED/Alzheimer’s Disease Preclinical Efficacy Database, developed by the NIA, is a searchable and publicly available knowledgebase that prioritizes and promotes the use of rigorous methodology in the planning of animal studies through its Rigor Report Card. The Rigor Report Card, through its checklist of experimental design elements, creates awareness of reporting recommendations and standards early in the research process and provides a practical and easy approach to planning a therapeutic study in animals.MethodUsing key word‐driven literature searches published studies are acquired and curated by two experts for bibliographic details, funding source, study goals and principal findings, data on relevant translational criteria like therapy type, therapeutic agent, therapeutic target, animal models, and AD‐related outcome measures, prior to publication in the database. Rigor in study design and methodology is evaluated with the Rigor Report Card.ResultAlzPED hosts curated summaries from nearly 1300 published preclinical therapeutic studies in AD animal models, and data related to 251 therapeutic targets, 1123 therapeutic agents, 210 animal models, more than 2000 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, randomization, balancing for sex, animal genetic background, and inclusion/exclusion criteria, these being reported by fewer than 35% of the nearly 1300 curated studies. These serious deficiencies in reporting critical elements of methodology diminish the scientific rigor, reproducibility, and translational value of the preclinical studies.ConclusionRigorous experimental design and transparent reporting are clearly essential if animal studies are to inform future research, science policies, and successful clinical trials. 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.