{"entity":{"id":"idea-tr2-prospective-retrospective-path","kind":"idea","name":"A formal regulatory route for validating a biomarker on archived trial samples","aka":[],"tldr":"Completed trials have stored samples. Testing a new biomarker on them with the plan written in advance is nearly as good as a new trial and far cheaper, but regulators have no clear route to accept it.","summary":"The prospective-retrospective design (Simon, Paik and Hayes) uses archived samples from a completed randomised trial with a pre-specified analysis plan to validate a predictive biomarker. It rescued KRAS testing for anti-EGFR antibodies and Oncotype DX. Regulators accept it case by case. A published guidance with requirements (sample availability above a threshold, pre-registered analysis plan, independent statistical execution) would make the route predictable and encourage sponsors to bank and share samples.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["idea-tr2-failed-trial-biobank","tailorx","rxponder"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["oncotype-dx"],"companies":[],"institutions":[],"pathways":[],"terms":["companion-diagnostic-term"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-negative-results"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Guidance will double the number of biomarker label changes supported by prospective-retrospective analyses within five years and cut the average time from biomarker hypothesis to label from six years to three.","rationale":"The design is accepted in the methodological literature and has produced several practice changes; the barrier is regulatory uncertainty and sample access.","test":"Draft and publish guidance; track submissions and outcomes; compare with the preceding five years.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},"route":"/ideas/idea-tr2-prospective-retrospective-path/","neighbours":{"idea":[{"id":"idea-tr2-failed-trial-biobank","kind":"idea","name":"Rescue the biological samples from failed trials for biomarker research","route":"/ideas/idea-tr2-failed-trial-biobank/"}],"trial":[{"id":"rxponder","kind":"trial","name":"RxPONDER (SWOG S1007)","route":"/trials/rxponder/"},{"id":"tailorx","kind":"trial","name":"TAILORx","route":"/trials/tailorx/"}],"drug":[{"id":"oncotype-dx","kind":"drug","name":"Oncotype DX","route":"/drugs/oncotype-dx/"}],"term":[{"id":"companion-diagnostic-term","kind":"term","name":"Companion diagnostic","route":"/terms/companion-diagnostic-term/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-negative-results","kind":"bottleneck","name":"Failures are hidden","route":"/bottlenecks/b-negative-results/"}],"paper":[{"id":"paper-fernandez-jama-oncol","kind":"paper","name":"Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue","route":"/key-papers/paper-fernandez-jama-oncol/"}]}}