Journal article
Methods for randomized, blinded, controlled evaluation of putative disease interventions in multilaboratory, preclinical assessment networks
Lab animal, Vol.55(3), pp.74-82
03/2026
DOI: 10.1038/s41684-026-01683-z
PMCID: PMC12956586
PMID: 41709026
Abstract
Science faces a reproducibility crisis, and public trust in science declines when large clinical trials, which had been qualified by promising preclinical studies, fail. While some clinical trial designs may have been inadequate, preclinical assessments of disease interventions might have lacked key elements of rigor such as treatment concealment, randomization, blinded outcomes, prespecified and adequate sample sizes, and models including comorbidities. Here, to demonstrate feasibility and practicality of enhanced rigor in preclinical assessment, we designed a six-laboratory network that implemented rigorous study elements, using acute ischemic stroke for demonstration. This network enrolled 2,615 rodents in 5 different models and implemented a multistage, multiarm statistical design that sequentially eliminated candidate interventions during interim analyses. The methods included centralized intervention packaging, randomization, data quality assessment and data archiving. Blinded analysis of 9,274 video-recorded behavioral tasks and 3,652 magnetic resonance images were evaluated. All tools and protocols are presented and could be adapted to preclinical assessment in other disease areas.
Details
- Title: Subtitle
- Methods for randomized, blinded, controlled evaluation of putative disease interventions in multilaboratory, preclinical assessment networks
- Creators
- Jessica Lamb - Keck Hospital of USCKarisma Nagarkatti - Keck Hospital of USCMarcio A Diniz - Cedars-Sinai Medical CenterRyan Cabeen - University of Southern CaliforniaMonica Estrada - University of Southern CaliforniaKaren L Crawford - University of Southern CaliforniaAndre Rogatko - Cedars-Sinai Medical CenterSungjin Kim - Cedars-Sinai Medical CenterCenk Ayata - Harvard UniversityDavid C Hess - Augusta UniversityMohammad Badruzzaman Khan - Augusta UniversityRakesh B Patel - University of IowaMariia Kumskova - University of Iowa, Internal MedicineEnrique C Leira - University of IowaAnil K Chauhan - University of IowaPatrick Lyden - Keck Hospital of USCSPAN Consortium
- Resource Type
- Journal article
- Publication Details
- Lab animal, Vol.55(3), pp.74-82
- DOI
- 10.1038/s41684-026-01683-z
- PMID
- 41709026
- PMCID
- PMC12956586
- NLM abbreviation
- Lab Anim (NY)
- ISSN
- 1548-4475
- eISSN
- 1548-4475
- Publisher
- NATURE PORTFOLIO
- Grant note
- 1U24NS113452-01 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) U01NS113388 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) 5U24NS130600-03 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) UL1 TR001881-01 / U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS) R35HL139926, R01NS109910, and U01NS113388 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) NS099455, 1UO1NS113356, and R01NS112511 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01 NS099455, 1UO1NS113356, and R01NS112511 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) 1U24NS113452-01 and U24NS113452 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) U01 NS113443 / NINDS NIH HHS
- Language
- English
- Date published
- 03/2026
- Academic Unit
- Neurology; Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
- Record Identifier
- 9985139492202771
Metrics
1 Record Views