International consensus-driven recommendations for patient-reported outcome research objectives in early phase dose-finding oncology trials:OPTIMISE-ROR

Purpose: There is growing scientific interest in incorporating Patient-reported Outcomes (PROs) in early phase dose-finding oncology trials (DFOTs) to assess tolerability, inform dose selection, and guide later stage trial design.<br/><br/>However, research indicates that PRO objectives in DFOTs are often unclear. The OPTIMISE-ROR (incOrporating PaTIent-reported outcoMes In doSE-finding trials–Research Objectives Recommendations) project was established to support trialists to effectively incorporate PROs into DFOTs.<br/><br/>Materials and Methods: Using the Enhancing Quality and Transparency of Health Research (EQUATOR) Network’s methodological framework, guideline development included: (1) a methodological review of published DFOTs incorporating PROs; (2) candidate item generation, refined through expert consultation; (3) a two-round international multi-stakeholder Delphi survey [n=109 in Round 1 (October 2024); n=96 in Round 2 (December 2024)]; and (4) an independently-chaired virtual consensus meeting [n=31; January 2025] where multidisciplinary, international experts reviewed and voted to finalise items for inclusion.<br/><br/>Results: Consensus was reached on six recommendations emphasising three core PRO tolerability concepts: overall side effect impact, symptomatic adverse events, and overall health-related quality of life. The integration of PROs to inform final dose-recommendations in dose escalation and optimisation trials should be considered, regardless of trial design. The recommendations highlight the importance of PRO data analysis over time and across dose levels; defining PRO research objectives as descriptive or statistically powered; and assessing PRO-related endpoints to guide endpoint selection for follow−on studies.<br/><br/>Conclusion: This foundational guidance outlines key PRO research objectives in DFOTs. By facilitating the systematic integration of PROs, this guidance supports the utilisation of patient-centred evidence for the tolerability and efficacy assessment of therapies to inform dose escalation, optimisation, and regulatory evaluation – ultimately contributing to the development of safer, more effective therapies.<br/>