Co-authored by PAASP’s managing partner, Anton Bespalov, the correspondence article ‘Failed trials for central nervous system disorders do not necessarily invalidate preclinical models and drug targets’ was published last week in Nature Reviews Drug Discovery. Here, the authors discuss the great importance of 1. Data robustness, 2. Data generalizability and 3. Target engagement when designing preclinical studies: The decline of drug development over the last decade in the fields of neurology and psychiatry has largely been attributed to a high failure rate in the translation of preclinical efficacy findings, caused by multiple factors, including limited training and poor protocol design, inadequate animal models, insufficiently validated therapeutic targets and problems with data handling and reporting.
However, a failed clinical trial does not necessarily invalidate the potential of a drug target or animal model. It rather indicates the need for improved experimental designs and robust translational strategies to better inform compound and dose selection for clinical trials. Therefore, an increase in robustness, generalizability and evidence of target engagement could significantly increase the probability of successful translation of innovation to novel treatments for patients.