Table 3 Identified key domains to address the challenge of comparator choice
Challenges of Comparator Choice | |||||
|---|---|---|---|---|---|
Key Domains | Criteria for the choice of comparator in an increasingly fragmented landscape | Reasonable number of comparators in PICOs | Shape Early Advice so that comparator fulfils both, regulatory and HTA needs | Acceptability of ITCs | Ensure broad stakeholder involvement in comparator selection |
Description | Agreement across all involved stakeholders on the set of requirements for the appropriate comparative therapy within a clinical development program | The comparator should be the current standard of care. If multiple standards of care exist attempt should be made to limit the number of required comparisons | Agreement for early and inclusive advice covering both, regulatory and HTA needs | Agreement on applicability of ITC and methodological requirements for ITC | Ensure involvement and alignment across a wide stakeholder group incl. HTA, regulatory, clinical, patient, and industry stakeholders |
Guiding Questions | How to manage an ever more diverging and fast-moving comparator landscape in targeted oncology? Is the current treatment standard on-label or off-label? | Is there a clear standard of care? How to manage different national Standards of Care and heterogeneous guideline recommendations? Is comparator selection based on best available alternative or other criteria? How should clinically interchangeable comparators be incorporated? | How to ensure that comparator choice fulfils both, regulatory and HTA requirements? What are alternative evidence sources and methods that can be used if required comparators differ, or a comparator cannot be ethically used with a trial? | Under what circumstances would an ITC be relevant? What are the contextual factors that can guide which ITC methods are most appropriate? | Who should be involved in the selection of appropriate comparative therapy? What are the rationales behind their choice? |