Alzheimer’s Disease Preclinical Efficacy Database (AlzPED): Optimizing the Scientific Rigor and Reproducibility of Preclinical Research in Alzheimer’s Disease

Abstract Background Assessments of preclinical animal studies in Alzheimer’s disease (AD) highlight the lack of methodological rigor and inadequate reporting practices as contributive to the preclinical to clinical translation gap in AD therapy development. The Alzheimer’s Disease Preclinical Efficacy Database (AlzPED), a searchable and publicly available knowledgebase developed by the National Institute on Aging aims to illuminate key elements of experimental design and reporting practices of preclinical efficacy testing studies for researchers, funding agencies, and the public. The database is missioned to improve transparency in reporting, increase awareness of the need for greater rigor in study design, and identify critical experimental design elements and methodology missing from studies that make them susceptible to over‐interpretation and reduce their reproducibility and translational value. Method Using 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 a Rigor Report Card consisting of a standardized set of expert‐recommended study design elements. Result AlzPED hosts curated summaries from nearly 1200 published preclinical therapeutic studies in AD animal models, and data related to 225 therapeutic targets, 1019 therapeutic agents, 195 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 30% of the nearly 1200 curated studies. Conclusion Our analysis 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.