{"entity":{"id":"idea-bio1-multicentre-mouse-trials","kind":"idea","name":"Multi-centre randomised animal trials before committing to a human trial","aka":[],"tldr":"A drug that works in one laboratory's mice often fails elsewhere. Running the confirmatory animal study as a randomised, blinded, multi-laboratory trial, as stroke and amyotrophic lateral sclerosis research has done, would catch this before a human trial; oncology has no such standing infrastructure.","summary":"The confirmatory preclinical trial concept borrows randomisation, blinding, power calculation and multi-site replication from clinical research. Multi-laboratory preclinical trials have been run in stroke (the MULTI-PART approach) and in amyotrophic lateral sclerosis, and reversed several accepted findings. Oncology, where phase 2 attrition is highest, has no equivalent standing infrastructure.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":["nci","cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-reproducibility","b-translational-valley"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Candidates that pass a randomised, blinded, three-laboratory confirmatory preclinical trial have a materially higher phase 2 success rate than candidates advanced on single-laboratory data.","rationale":"The main source of translational failure is unreliable effect estimates rather than species differences alone; replication is the cheapest available fix and costs a fraction of a failed phase 2.","test":"Fund a preclinical trials network to run confirmatory studies for ten agents heading into phase 2 and track subsequent clinical outcomes against matched controls.","maturity":"preclinical-evidence","actor":"philanthropy","cost":"medium","horizonYears":6},"route":"/ideas/idea-bio1-multicentre-mouse-trials/","neighbours":{"technology":[{"id":"pdx-models","kind":"technology","name":"Patient-derived xenografts","route":"/technologies/pdx-models/"}],"institution":[{"id":"cruk","kind":"institution","name":"Cancer Research UK","route":"/institutions/cruk/"},{"id":"nci","kind":"institution","name":"National Cancer Institute (NIH)","route":"/institutions/nci/"}],"bottleneck":[{"id":"b-preclinical-models","kind":"bottleneck","name":"Lab models that fail to predict what happens in patients","route":"/bottlenecks/b-preclinical-models/"},{"id":"b-reproducibility","kind":"bottleneck","name":"Preclinical results do not reproduce","route":"/bottlenecks/b-reproducibility/"},{"id":"b-translational-valley","kind":"bottleneck","name":"The valley of death between lab and product","route":"/bottlenecks/b-translational-valley/"}],"paper":[{"id":"paper-wong-biostatistics","kind":"paper","name":"Estimation of clinical trial success rates and related parameters","route":"/key-papers/paper-wong-biostatistics/"}]}}