{"entity":{"id":"idea-tr1-pk-informed-organ-thresholds","kind":"idea","name":"Replace fixed kidney and liver cut-offs with drug-specific, pharmacology-based thresholds","aka":[],"tldr":"Most trials copy the same kidney and liver cut-offs, such as creatinine clearance above 60, regardless of how the drug is cleared. Setting each threshold from the drug's own clearance route and organ-impairment pharmacokinetic studies would let patients with mild organ impairment join safely instead of being excluded.","summary":"Organ-function eligibility criteria (creatinine clearance, bilirubin, transaminases) would be set per drug from its clearance route and the results of early organ-impairment pharmacokinetic studies, rather than the default 'creatinine clearance above 60 ml/min' copied between protocols. Drugs with negligible renal clearance would have no renal cut-off; drugs with hepatic clearance would have a dose-adjusted cohort instead of an exclusion.","asOf":"2026-09-08","links":[{"label":"FDA: Eligibility Criteria: Patients with Organ Dysfunction or Prior or Concurrent Malignancies","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cancer-clinical-trial-eligibility-criteria-patients-organ-dysfunction-or-prior-or-concurrent"}],"tags":[],"related":[],"cancers":["multiple-myeloma","urothelial","rcc"],"sections":[],"technologies":["monoclonal-antibody","adc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-dose-optimisation","b-aging-comorbidity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pharmacology-based thresholds will make at least 10-20 percent more patients eligible in older-skewed cancers without increasing dose-limiting toxicity, and will produce label dosing guidance for organ impairment at the time of approval rather than years later.","rationale":"Renal impairment is common in patients over 70 and in myeloma, bladder and kidney cancer; many modern agents (monoclonal antibodies, most ADCs) are not renally cleared, so the criterion excludes without protecting. The FDA organ-dysfunction eligibility guidance supports this approach.","test":"A sponsor applies PK-informed thresholds across its oncology portfolio for two years and reports the eligible fraction, DLT rates and organ-impairment sub-cohort outcomes versus its historical protocols.","maturity":"speculative","actor":"industry","cost":"small","horizonYears":3},"route":"/ideas/idea-tr1-pk-informed-organ-thresholds/","neighbours":{"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"bottleneck":[{"id":"b-aging-comorbidity","kind":"bottleneck","name":"Older and multimorbid patients are excluded and undertreated","route":"/bottlenecks/b-aging-comorbidity/"},{"id":"b-trial-enrolment","kind":"bottleneck","name":"Trials enrol too few, too slowly","route":"/bottlenecks/b-trial-enrolment/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}]}}