Importance: In poor-prognosis children's cancers, new therapies may carry fresh hope for patients and parents. However, there is an absolute requirement for any new therapy to be properly evaluated to fulfill scientific, regulatory, and reimbursement requirements. Randomized clinical trials (RCTs) are considered the gold standard, but no consensus exists on how and when they should be deployed to best meet the needs of all stakeholders.
Objective: To conduct a multistakeholder meeting to foster a greater shared understanding of perspectives regarding RCTs of new therapies for children with poor-prognosis cancers and develop consensus recommendations on when and how they should be used.
Evidence review: During October 2022 and April 2023, 2 structured workshops were convened, bringing together individuals representing the perspectives of patient advocates and academic clinician-researchers, regulators, and health technology assessment bodies. A premeeting briefing document was prepared and circulated to all attendees. During the workshops, selected attendees presented on behalf of each stakeholder group, focused topic discussions were conducted, and each meeting concluded by agreeing on a consensus set of recommendations. Meeting organizers drafted meeting summary reports that were circulated to all attendees, who commented on and revised them as a group to produce final recommendations from the workshops.
Findings: Though the workshops did not reconcile all stakeholder differences, sufficient areas of agreement enabled a set of conclusions to be drawn, resulting in 8 consensus recommendations: (1) drug development strategies for new therapies, including the role of RCTs, should be established at the time of first-in-child studies; (2) engagement with regulators and health technology assessment bodies about RCT design is crucial; (3) involvement of patient advocates is necessary to ensure that an RCT is patient focused; (4) timing of an RCT is critical to preserve clinical equipoise; (5) use of crossover in an RCT can be of benefit, but with important caveats; (6) end point maturity and overall survival in an RCT may be important for regulatory and health technology assessment approvals; (7) in the absence of an RCT, contemporaneous control cohorts are preferred over historical control cohorts; and (8) quality of life should be captured in all prospective RCTs.
Conclusions and relevance: The agreed-upon workshop conclusions provide a basis for key considerations while undertaking future drug development activities for children with poor-prognosis cancers, ensuring that the needs and perspectives of all stakeholders are factored in from the outset.