# Default-inclusive eligibility: sponsors must justify every exclusion criterion

Source: https://onco.cc/ideas/idea-tr1-justify-every-exclusion/  
OnCo record `idea-tr1-justify-every-exclusion` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Trials should let people in unless there is a scientific or safety reason to keep them out. Every exclusion rule would need a written reason, reviewed like the rest of the protocol.

## Summary

Regulators and ethics committees would require a one-line scientific or safety justification for each exclusion criterion, with a default set of permitted criteria (the ASCO-Friends of Cancer Research broadened criteria on brain metastases, organ function, prior malignancies, HIV and hepatitis) needing no justification and anything stricter needing one. The FDA's 2020 eligibility guidances describe what is reasonable; this idea makes the reasonable set the default and puts the burden of proof on restriction.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Tags: protocol-upgrade; upgrade:proven-unevenly-used; evidence:moderate
- Hypothesis: Protocols written under a justify-every-exclusion rule will have at least a third fewer exclusion criteria and a measurably higher fraction of real-world patients eligible (as simulated against a real-world oncology dataset), without an increase in grade 5 adverse events attributable to the broadened population.
- Rationale: Analyses of protocol eligibility against real-world data show that many criteria are copied from earlier protocols and that relaxing them changes the eligible pool substantially with little effect on the estimated hazard ratio. Ethics review already asks for justification of risk; asking for justification of exclusion is symmetric and cheap.
- Proposed test: A cooperative group or single regulator pilots the rule for 12 months on all new phase 2/3 oncology protocols, comparing criterion counts, simulated eligible fraction and later serious-adverse-event rates against the prior year's protocols.
- Maturity: early-clinical
- Actor: regulator

## Notes

- Protocol upgrade, graded proven but unevenly used. Applying common strict laboratory and performance-status cut-offs to 235,234 United States patients receiving systemic therapy left 48 per cent eligible; broadened criteria increased the eligible number by 78 per cent, most for older, female, Black and lower-income patients, and those eligible only under the broader criteria had shorter real-world survival (hazard ratio 1.31), which trials would need to account for (Kaur, 2024).
- Adoption gap, as measured for one criterion: among 3,077 United States trials in advanced breast, colorectal, lung cancer and melanoma from 2012 to 2022, the share that did not exclude patients with brain metastases rose from 11.5 to 17.3 per cent after the 2017 ASCO, Friends of Cancer Research and FDA recommendations, while wholesale exclusion did not change (7.5 against 6.2 per cent) (Xiao, 2024).

## Sources

- Kim et al., Broadening Eligibility Criteria to Make Clinical Trials More Representative: ASCO and Friends of Cancer Research Joint Research Statement (J Clin Oncol 2017): https://doi.org/10.1200/JCO.2017.73.7916
- Xiao et al., Impact of Broadening Trial Eligibility Criteria on the Inclusion of Patients With Brain Metastases: time series analyses 2012 to 2022 (J Clin Oncol 2024): https://doi.org/10.1200/JCO.23.01777
- Kaur et al., Broadening Eligibility Criteria and Diversity among Patients for Cancer Clinical Trials (NEJM Evid 2024): https://doi.org/10.1056/EVIDoa2300236
- FDA: Enhancing the Diversity of Clinical Trial Populations (guidance): https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enhancing-diversity-clinical-trial-populations-eligibility-criteria-enrollment-practices-and-trial
- Friends of Cancer Research: https://friendsofcancerresearch.org/
- Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021): https://doi.org/10.1016/S0140-6736(21)01789-X

## Connected records

- collections: [ClinicalTrials.gov](https://onco.cc/collections/clinicaltrials-gov/)
- institutions: [American Society of Clinical Oncology (ASCO)](https://onco.cc/institutions/asco/), [National Cancer Institute (NIH)](https://onco.cc/institutions/nci/)
- terms: [Accelerated approval](https://onco.cc/terms/accelerated-approval/), [Standard of care](https://onco.cc/terms/standard-of-care/)
- bottlenecks: [Older and multimorbid patients are excluded and undertreated](https://onco.cc/bottlenecks/b-aging-comorbidity/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/), [Trials do not represent the people who get cancer](https://onco.cc/bottlenecks/b-trial-diversity/), [Trials enrol too few, too slowly](https://onco.cc/bottlenecks/b-trial-enrolment/)
- key papers: [Broadening Eligibility Criteria to Make Clinical Trials More Representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement](https://onco.cc/key-papers/paper-kim-j-clin-oncol/)
- ideas: [Geriatric assessment by default for every older patient, and trials that admit them](https://onco.cc/ideas/idea-moon-geriatric-assessment-default/)
- roadmaps: [Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on](https://onco.cc/roadmaps/trial-modernisation-roadmap/)

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