Benoît Delabays, Chiara De Paoli, Andrea Miller-Nesbitt, Vincent Mooser
{"title":"Genetically Enriched Clinical Trials for Precision Development of Noncancer Therapeutics: A Scoping Review.","authors":"Benoît Delabays, Chiara De Paoli, Andrea Miller-Nesbitt, Vincent Mooser","doi":"10.1146/annurev-pharmtox-031524-021631","DOIUrl":null,"url":null,"abstract":"<p><p>Genetically driven clinical trial enrichment has been proposed to accelerate and reduce the cost of developing new therapeutics. Usage of this approach has not been comprehensively reviewed. We searched Ovid MEDLINE, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, and WHO ICTRP for articles published between 2010 and 2023. Excluding absorption, distribution, metabolism, and elimination pharmacogenetic studies and anti-infectives, we found 95 completed, 4 terminated, and 22 ongoing prospective genetically enriched trials on 110 drugs for 48 nononcology, nonrare syndromic indications. Trial sizes ranged from 4 to 6,147 participants (median 72) and covered numerous disease areas, particularly neurology (30), metabolism (22), and psychiatry (17). Fifty-six completed studies (60%) met their primary end point. Overall, this scoping review demonstrates that genetically enriched trials are feasible and scalable across disease areas and provide critical information for further development, or attrition, of investigational drugs. Large, appropriately designed disease-, hospital-, or population-based biobanks will undoubtedly facilitate this type of precision drug development approach.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":11.2000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of pharmacology and toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-pharmtox-031524-021631","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Genetically driven clinical trial enrichment has been proposed to accelerate and reduce the cost of developing new therapeutics. Usage of this approach has not been comprehensively reviewed. We searched Ovid MEDLINE, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, and WHO ICTRP for articles published between 2010 and 2023. Excluding absorption, distribution, metabolism, and elimination pharmacogenetic studies and anti-infectives, we found 95 completed, 4 terminated, and 22 ongoing prospective genetically enriched trials on 110 drugs for 48 nononcology, nonrare syndromic indications. Trial sizes ranged from 4 to 6,147 participants (median 72) and covered numerous disease areas, particularly neurology (30), metabolism (22), and psychiatry (17). Fifty-six completed studies (60%) met their primary end point. Overall, this scoping review demonstrates that genetically enriched trials are feasible and scalable across disease areas and provide critical information for further development, or attrition, of investigational drugs. Large, appropriately designed disease-, hospital-, or population-based biobanks will undoubtedly facilitate this type of precision drug development approach.
期刊介绍:
Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.