Methodological and reporting standards for quality of life data eligible for European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) credit

Abstract

Background: The ESMO-MCBS has been developed to grade clinical benefit of cancer therapies. Improvement in quality of life (QoL) is considered relevant, especially in the non-curative setting. This is reflected by an upgrade of the preliminary ESMO-MCBS score if QoL is improved compared to the control arm or a downgrade if an improvement in progression free survival is not paralleled by an improvement in QoL or overall survival. Given the importance of QoL for the final score, a need to ensure the robustness of QoL data was recognised. Design: A checklist was created based on existing guidelines for QoL research. Field-testing was performed using clinical trials that either received an adjustment of the preliminary ESMO-MCBS score based on QoL, or had QoL as the primary endpoint. Several rounds of revision and re-testing of the checklist were undertaken until a final consensus was reached. Results: The final checklist consists of four items and can be applied if three prerequisites are met: (1) QoL is at least a secondary endpoint, (2) evidence of reliability and validity of the instrument is provided and (3) a statistically and clinically significant improvement in QoL is observed. The four items on the checklist pertain to the (1) hypothesis, (2) compliance and missing data, (3) presentation of the results, and (4) statistical and clinical relevance. Field-testing revealed that a clear QoL hypothesis and correction for multiple testing were mostly lacking, while the main statistical method was always described. Conclusions: Implementation of the ESMO-MCBS QoL checklist will facilitate objective and transparent decision-making on QoL data within the ESMO-MCBS scoring process. Trials published until 1 January 2025 will have to meet the prerequisites and at least two items for crediting QoL benefit in the final ESMO-MCBS score. Trials published thereafter will have to meet all four items