SC02: PROviding Harmonized Standards in the Design and Analysis of Patient-Reported Outcomes in Cancer Clinical Trials: The SISAQOL-IMI Recommendations

The role of patient-reported outcomes (PROs) in oncology has become increasingly important for clinical and regulatory review. While overall survival (OS) and progression-free survival (PFS) remain as traditional efficacy endpoints in oncology trials, PRO data and analysis provide essential insight by characterizing the patient's experience with anti-cancer product(s), including disease- and treatment-related symptoms (e.g., pain, fatigue) and functional impairments. PRO data are critical for a comprehensive understanding of the benefit-risk profile of a cancer drug and serve as an important component of regulatory submissions and health technology assessments. However, the lack of consistency and questionable quality of reported PRO findings have negatively affected its efficient use to inform the benefit/risk assessment of anti-cancer treatments. In 2021, the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials - IMI (SISAQOL-IMI) was formed through a collaboration among 41 international organizations, including regulatory agencies, health technology assessment bodies, industry, academia, and patient organizations, to formulate a set of recommendations to improve the analysis and interpretation of PRO data in cancer clinical trials. The key recommendations were recently published in "Lancet Oncology." Moreover, the consortium has developed a detailed guidebook and interactive webtool to assist practitioners with establishing PRO research questions, selecting appropriate estimands, and identifying approaches for handling missing values and intercurrent events under SISAQOL-IMI recommendations. These modern and interactive tools will help clinical and statistical teams seamlessly implement the recommendations in real trials and improve the utility of PRO analyses in cancer drug development. This will enable better use of these data to support regulatory and HTA decision-making and enhance patient-physician communication. The first part of the short course will provide an overview of the SISAQOL-IMI recommendations. These sessions will highlight a number of practice-changing design and analysis consensus-based recommendations in oncology trials that are anchored on the estimand framework. The materials will cover the use of PROs in a) randomized controlled trials; b) single-arm trials; c) defining a clinically meaningful estimated treatment effect; and d) presentation and visualization of PRO findings. This will be followed by a presentation on how the SISAQOL-IMI and estimand framework has been useful for FDA statistical review of anti-cancer drugs. The second part of this short course will introduce the interactive webtool and implementation of these recommendations on a case study using actual cancer clinical trial protocols, statistical analysis plans, and/or published reports with PRO-based endpoints. Attendees will be provided with standard templates to guide them in the update of their own protocols and SAPs and improve efficiency in the development and analysis of PRO-based endpoints in their trials.