Table 2.

Assessment of uncertainty when extrapolating evidence for transparent decision-making.

Judgment a	Evidence assessed for each criterion a	Decision assessed from evidence for all criteria b
Important uncertainty	No research evidence identified or searched for	Use criteria to identify or plan studies for later reassessment
Possibly important uncertainty	Judgment Responses from other extrapolation criteria increase uncertainty	Identify additional evidence required pre-approval
Probably no important uncertainty	Judgment Responses from other extrapolation criteria decrease uncertainty	Provisional or regular approval, define post-approval commitments

Source: Adapted from Piggott et al. ²⁸

^aJudgment for the level of uncertainty for extrapolation should be made individually for each criterion. Judgments from other extrapolation criterion either increase or decrease certainty of each criterion.

^bThe final decision should be made based on the totality of the evidence. If there is probably no important uncertainty for most of the criteria, then there is likely sufficient evidence to support regulatory approval. Any substantial knowledge gaps identified resulting in possibly important uncertainty for one or more criteria should define additional studies required pre-approval. If there is important uncertainty for many or most of the criteria, further studies are required to address knowledge gaps for later reassessment. Judgment for decision-making should be individualized and consider estimated benefits versus risks of targeted therapy compared to alternative therapies if available.