Journal article
A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke
Science translational medicine, Vol.15(714), eadg8656
09/20/2023
DOI: 10.1126/scitranslmed.adg8656
PMID: 37729432
Abstract
Human diseases may be modeled in animals to allow preclinical assessment of putative new clinical interventions. Recent, highly publicized failures of large clinical trials called into question the rigor, design, and value of preclinical assessment. We established the Stroke Preclinical Assessment Network (SPAN) to design and implement a randomized, controlled, blinded, multi-laboratory trial for the rigorous assessment of candidate stroke treatments combined with intravascular thrombectomy. Efficacy and futility boundaries in a multi-arm multi-stage statistical design aimed to exclude from further study highly effective or futile interventions after each of four sequential stages. Six independent research laboratories performed a standard focal cerebral ischemic insult in five animal models that included equal numbers of males and females: young mice, young rats, aging mice, mice with diet-induced obesity, and spontaneously hypertensive rats. The laboratories adhered to a common protocol and efficiently enrolled 2615 animals with full data completion and comprehensive animal tracking. SPAN successfully implemented treatment masking, randomization, prerandomization inclusion and exclusion criteria, and blinded assessment of outcomes. The SPAN design and infrastructure provide an effective approach that could be used in similar preclinical, multi-laboratory studies in other disease areas and should help improve reproducibility in translational science.
Details
- Title: Subtitle
- A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke
- Creators
- Patrick D Lyden - Keck Hospital of USCMárcio A Diniz - Cedars-Sinai Medical CenterFrancesca Bosetti - National Institute of Neurological Disorders and StrokeJessica LambKarisma A NagarkattiAndré Rogatko - Cedars-Sinai Medical CenterSungjin Kim - Cedars-Sinai Medical CenterRyan P CabeenJames I Koenig - National Institute of Neurological Disorders and StrokeKazi Akhter - Johns Hopkins UniversityAli S Arbab - Augusta UniversityBrooklyn D Avery - Johns Hopkins UniversityHannah E Beatty - Yale UniversityAdnan Bibic - Johns Hopkins UniversitySuyi Cao - Johns Hopkins UniversityLigia Simoes Braga BoisserandAngel Chamorro - University of IowaAnjali ChauhanSebastian Diaz-Perez - Yale UniversityKrishnan Dhandapani - Augusta UniversityNirav Dhanesha - University of IowaAndrew GohAlison L Herman - Yale UniversityFahmeed Hyder - Yale UniversityTakahiko Imai - Massachusetts General HospitalConor W Johnson - Yale UniversityMohammad B Khan - Augusta UniversityPradip Kamat - Augusta UniversitySenthilkumar S Karuppagounder - Johns Hopkins UniversityMariia Kumskova - University of IowaJelena M Mihailovic - Yale UniversityJoseph B Mandeville - Massachusetts General HospitalAndreia Morais - Massachusetts General HospitalRakesh B Patel - University of IowaBasavaraju G Sanganahalli - Yale UniversityCameron Smith - Augusta UniversityYanrong Shi - Johns Hopkins UniversityBrijesh Sutariya - University of IowaDaniel Thedens - University of IowaTao Qin - Massachusetts General HospitalSofia E Velazquez - Yale UniversityJaroslaw AronowskiCenk Ayata - Massachusetts General HospitalAnil K Chauhan - University of IowaEnrique C Leira - University of IowaDavid C Hess - Augusta UniversityRaymond C Koehler - Johns Hopkins UniversityLouise D McCulloughLauren H Sansing - Yale University
- Resource Type
- Journal article
- Publication Details
- Science translational medicine, Vol.15(714), eadg8656
- DOI
- 10.1126/scitranslmed.adg8656
- PMID
- 37729432
- ISSN
- 1946-6234
- eISSN
- 1946-6242
- Language
- English
- Date published
- 09/20/2023
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Radiology; Electrical and Computer Engineering; Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
- Record Identifier
- 9984466696902771
Metrics
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