Safety review and dose selection

Integrate evidence into dose recommendations

Selection should use the protocol-defined evidence and authorized review. A recommended regimen need not be the maximum tolerated dose; include uncertainty, pending outcomes and the possibility of no recommendation.

Flow diagram

Safety review and dose selectionF1.S1Assemble review evidenceF1.S2Verify decision readinessF1.S3Apply prespecified selection rulesF1.S4Decide expansion, recommendation orno doseF1.S5Document recommendation limitsF1.N1Dose-review evidence registerDomainEvidence sourcePending dataDecisionrelevanceReviewerToxicityActivityExposurePharmacologyProtocoladherenceF1.N2Assumptions and rationaleF1.N3Method and protocol evidenceF1.S0 Start flowSafety review and dose selectionF1.S999 End flowEnd flow

Steps

Assemble review evidence

Combine toxicity, activity, exposure and pharmacology evidence as planned.

Verify decision readiness

Review pending outcomes, safety signals and protocol deviations.

Apply prespecified selection rules

Use the approved design with documented human review.

Decide expansion, recommendation or no dose

Allow no acceptable dose and unresolved evidence as explicit outcomes.

Document recommendation limits

Record authority, uncertainty and any further evaluation required.

Safety review and dose selection

End flow

Tables and supporting information

Dose-review evidence register

Dose-review evidence registerDomainEvidence sourcePending dataDecisionrelevanceReviewerToxicityActivityExposurePharmacologyProtocoladherence

This is an authoring aid, not automated clinical dose advice.

Assumptions and rationale

A recommended dose need not be the maximum tolerated dose; selection follows the study objective and totality of evidence.

Method and protocol evidence

Attach the protocol, methodological sources and versioned software specification supporting these decisions. Record citations and provenance; do not enter participant identifiers.

Sources