Dose escalation and stopping decisions

Define permitted decisions and safeguards

Rule-based, model-assisted and model-based designs use different decision mechanisms. Document allowed actions and safety constraints, including hold, stop and no acceptable dose. The diagram records decisions; it does not authorize dosing.

Flow diagram

Steps

Select reviewed design family

Select a reviewed rule-based, model-assisted or model-based design consistent with the dose-selection objective. Define the authorized review process and document validated operating characteristics.

Specify allowable decisions

Define escalation, repeat, de-escalation, expansion and stopping options.

Set safety constraints

Record overdose limits, prohibited jumps, accrual holds and protocol boundaries.

Review current evaluability

Ensure the selected algorithm handles incomplete follow-up appropriately.

Authorize and document the decision

Record reviewer authority, evidence, rationale and any override.

Escalate, repeat or de-escalate

Use the selected reviewed algorithm and safety constraints.

Expand cohort

Apply the protocol expansion rule and assessment requirements.

Hold or stop

Retain pending outcomes and safety-review evidence.