The document presents an overview of ongoing initiatives by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institutes of Health (NIH) to enhance the rigor and transparency of preclinical and clinical research, with a focus on neurological disorders such as amyotrophic lateral sclerosis (ALS). It highlights historical shortcomings in preclinical drug research, referencing the case of minocycline, which after promising preclinical results in ALS mouse models, ultimately proved harmful in clinical trials. Such disparities have prompted large-scale reviews revealing pervasive limitations in study design, including publication bias, methodological flaws, and lack of reproducibility. In response, NINDS and NIH have implemented a series of policies and guidelines to promote robust experimental design—emphasizing randomization, blinding, sample size estimation, data handling, transparency in reporting, and authentication of key resources—as critical criteria in funding and publication mechanisms.
To institutionalize these standards, NIH has introduced directives necessitating explicit documentation of methodological rigor in grant applications and publications, including new requirements for biographical sketches and explicit attention to experimental design, scientific premise, and biological variables such as sex. Additional efforts focus on increasing community awareness, enhancing formal training, improving peer review, and ensuring stable funding. Ongoing evaluation suggests progress, with researchers and reviewers showing increased attention to rigor, though challenges remain, particularly in clearly defining scientific premise and minimizing unconscious bias. The overarching message is that meaningful improvements in research quality require a coordinated effort by all stakeholders—investigators, reviewers, editors, and funders—to foster a culture of transparency, rigor, and trust in biomedical science.
