Periodic Reporting for period 2 - SISAQOL-IMI (Establishing international standards in the analysis of patient reported outcomes and health-related quality of life data in cancer clinical trials) Reporting period: 2022-01-01 to 2022-12-31 Summary of the context and overall objectives of the project Measuring and quantifying how a patient feels or functions during treatment is an important endpoint in cancer clinical trials. It is generally accepted that the collection of PRO data in cancer clinical trials allows the inclusion of the patient’s voice in the risk-benefit assessment of therapies. However, no standards exist on how to analyse, interpret or report health-related quality of life (HRQOL) and other patient-reported outcomes (PROs). SISAQOL-IMI’s goal is to pursue efforts in addressing the urgent need for standardization, by setting clear and robust standards that are tailored to and endorsed by all relevant stakeholders. To achieve this aim, SISAQOL-IMI has taken the first step by prioritising a set of PRO research objectives for which to evaluate and develop design and analysis recommendations. In the SISAQOL-IMI kick-off meeting in March 2021, the stakeholder groups (clinicians, patients, academic, industry, regulatory and HTA bodies) presented their views on the current practice regarding the use of PROs and their expectations from the SISAQOL-IMI project. As a result, a final set of prioritized PRO objectives was agreed by the 41 SISAQOL-IMI member organizations including the Workgroup of European Cancer Patient Advocacy Networks (WECAN), an umbrella organization representing 23 Pan-European cancer patient organisations.The scientific work packages carried out literature reviews of the current practices and guidelines for including PROs in cancer clinical trials, organized stakeholder discussions, and conducted surveys to draft their first recommendation statements on the prioritised PRO objectives. This resulted in over 40 recommendation statements that were voted in the second Consensus meeting in March 2022 with the full participation of the 41 organizations. Following this, the scientific work packages have proposed a second set of recommendations statements in December 2022, these recommendations will be voted in the third Consensus meeting in May. In the remainder of the project, the SISAQOL-IMI team will focus on refining and finalizing the recommendations produced in the first two years. A critical part of SISAQOL-IMI will be to ensure recommendations are based on consensus and address the needs of relevant, key stakeholder groups. Since the goal of SISAQOL-IMI is to improve standards, it is critical that the consensus recommendations balance high methodological quality and feasibility. To ensure this, the recommendations will go through three processes: i) the Independent Scientific Advisory Board Review, ii) independent validation by blinded members (case studies), and iii) EMA qualification advice. The feedback from these three processes will be discussed in the fourth Consensus meeting in 2024. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far The SISAQOL-IMI Consortium generated its first set of recommendation statements. The SISAQOL-IMI Consensus survey #2 in 2022 included recommendation statements from three of the five scientific WPs (WP 2, WP 3, and WP 6); 22 statements from WP 2, 17 statements from WP 3 and 7 statements from WP 6. All SISAQOL-IMI organisations (n=41) responded to the survey and 44 of the 46 proposed statements achieved 2/3 majority. Two statements (from WP 2 and WP 3) had 56% and 62% agreement. Differences in the responses between stakeholder groups were noted and, whenever needed, dialogue was initiated between the relevant parties before the Consensus meeting #2. At the SISAQOL-IMI Consensus meeting #2, the WP leaders presented the results from the survey with their comments and proposed modifications. Following a general discussion, a second round of online voting was conducted. Based on extensive discussions in the SISAQOL-IMI Consensus meeting #2, important issues such as how to handle death and intercurrent events were discussed in more detail in the interim GA in Sitges, Spain 24-25 May 2022. After a harmonisation process, the statements were finalised. Further refinements may be needed (e.g. prioritization and/or distinguishing between ideal and practical recommendations) in the following Consensus meetings. After the second Consensus meeting, it became clear that achieving 100% consensus on all statement was not possible in such a diverse multi-stakeholder Consortium. Even though, the consensus process allowed iterations of discussions on diverging views, a solution that satisfied all stakeholders was not always possible. To consistently address these various views whilst maintaining the notion of consensus and avoiding formal individual organization disclaimers for specific recommendation statements which could affect the future utility and implementation of the SISAQOL-IMI recommendations, WP1 and the Steering Committee drafted “Principles for handling divergent views in SISAQOL-IMI”. This working policy document proposed a few strategies such as presenting voting results by stakeholder group to inform users about which stakeholder might have held a different position on a given recommendation, including a preamble to note that individual organizations might hold different views, showing percentage agreement and other views under “considerations” along with the accepted recommendation statements.Overall, more time need for in-dept discussions focusing on the key challenges the scientific work packages had faced. To address this, two additional interim General Assembly (GA) meetings have been organized in the second year of the project (24-25 May and 5 December 2022). The stimulating discussions in the interim GA meetings helped refine the recommendations or provided feedback when formulating the second set of recommendations in 2022. As WP2 and WP3 have a number of overlapping recommendations, a separate harmonization process is initiated between these work packages. The recommendations from the two WPs had been compared side to side and potential solutions provided so that the two WPs are consistent. This process will be concluded before the Consensus meeting #4 so that revisions based on harmonization can be voted together with potential revisions based on independent validation (WP5) and the EMA qualification process. Two manuscripts had been drafted and reviewed by the publication review committee of SISAQOL-IMI. The first manuscript is titled “Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials - Innovative Medicines Initiative (SISAQOL-IMI): Stakeholder Views, Objectives, and Procedures”. It introduces the Consortium, explains its goals, and presents results from the priority setting survey from the kick-off meeting. The second manuscript is a literature review by WP3 titled “Single-arm studies involving patient-reported outcome data in oncology: a literature review on current practice”. Both papers are planned to be submitted to the Lancet Oncology beginning of 2023. Patient engagement activities have continued in in the second year with the planning of several seminars and workshops for patients and patient advocates that will be held in 2023. The dissemination activities have also gathered speed with the renewal of the website, release of animation videos, short interview videos of members from the in-person meeting in Spain, the preparation of an executive summary of the consensus meeting #2 with voice over. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) Too early to report.