REBECCA – D7.4: Best practices for integration of multi-source RWD into existing clinical workflows

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 965231. Horizon 2020 EUROPEAN COMMISSION Directorate-General for Research and Innovation People, Combating Diseases D7.4 – Best practices for integration of multi-source RWD into existing clinical workflows Project Acronym: REBECCA Grant Agreement No: 965231 Project Full Title: Research on breast cancer induced chronic conditions supported by causal analysis of multi-source data Starting Date: 1/4/ 2021 Duration in Months: 54 H2020SC1-DTH-12-2020 D7.4 2 | 62 Deliverable version 1.0 Date 17 October 2025 Nature of deliverable Report Dissemination level Public Work Package WP7 – Improving research and clinical workflows using multi-source RWD Lead Beneficiary KI Author(s) / Contributor(s) Alkyoni Glympi (KI), Ioannis Ioakimidis (KI) Status Submitted H2020SC1-DTH-12-2020 D7.4 3 | 62 Document History Version1 Issue Date Status2 Content and Changes 0.1 14 October 2025 Draft First complete draft 1.0 17 October 2025 Submitted Internally reviewed and finalised 1 Please use a new number for each new version of the deliverable. Use “0.#” for Draft and PeerReviewed. “x.#” for Submitted and Approved”, where x>=1.Add the date when this version was issued and list the items that have been added or changed. 2 A deliverable can be in one of these stages: Draft, Peer-Reviewed, Submitted and Approved. H2020SC1-DTH-12-2020 D7.4 4 | 62 Table of Contents Document History ..................................................................................................................... 3 Abbreviations and Acronyms ................................................................................................ 5 Executive Summary ................................................................................................................... 6 1 Introduction ......................................................................................................................... 7 1.1 Aim ................................................................................................................................................................... 8 1.2 Intended audience ..................................................................................................................................... 8 1.3 Project partners and acronyms ............................................................................................................. 8 1.4 Methodology ............................................................................................................................................... 9 1.5 Organization of the document ............................................................................................................. 9 2 Integration of patient-driven feature into the pApp ......................................... 10 2.1 Background ................................................................................................................................................. 10 2.2 Co-Creation as a design principle ...................................................................................................... 11 2.3 Identification of the need ...................................................................................................................... 12 2.4 Development process ............................................................................................................................. 13 3 Development of a unified advisory guide for personalized consultations with BCP 15 3.1 Background and rationale ..................................................................................................................... 15 3.2 Development process ............................................................................................................................. 17 3.3 Structure and content of the guide .................................................................................................. 18 Conclusions ................................................................................................................................ 23 References .................................................................................................................................. 24 Annex ........................................................................................................................................... 25 A. ANNEX A: Advisory lifestyle guidelines ................................................................ 26 B. ANNEX B: Positive annotation categories ............................................................. 51 H2020SC1-DTH-12-2020 D7.4 5 | 62 Abbreviations and Acronyms BCP Breast Cancer Patient BCS Breast Cancer Survivor CDC Centers for Disease Control and Prevention HCP Health Care Professional KI Karolinska Institutet pApp REBECCA’s Patient App PROM Patient-Reported Outcome Measures QoL Quality of Life RWD Real-World Data WCRF World Cancer Research Fund WHO World Health Organization H2020SC1-DTH-12-2020 D7.4 6 | 62 Executive Summary This deliverable presents the methodology and outcomes of co-creation and evidence synthesis activities conducted within the REBECCA project to support the integration of multi-source real-world data (RWD) into clinical workflows for breast cancer patient management. The REBECCA project, which was implemented between April 2021 and September 2025, aimed to leverage RWD collected from the patient application (pApp), smartphones, smartwatches, and patient-reported outcomes to complement traditional clinical research and enhance understanding of lifestyle, emotional wellbeing, and quality of life in breast cancer patients and survivors. The pApp is a mobile application for RWD collection that combines wearable connectivity, photo logging, short questionnaires, and GPS-based mobility tracking. A structured co-creation approach ensured that the digital tools developed were both clinically relevant and meaningful to patients. Breast cancer patients (BPCs), healthcare professionals (HCPs), and researchers from Sweden, Spain, and Norway actively participated in workshops, focus groups and validation sessions to enhance the integration of real-world data into existing clinical workflows. These collaborative efforts contributed to several improvements to the system and its usage. In this deliverable, we focus on two examples from the REBECCA project and analyse them as good practices for integrating RWD: the addition of the “Life Events” feature in the pApp and the creation of a unified advisory guide for HCPs. Specifically, in response to patient feedback, the “Life Events” feature was introduced in the pApp, replacing the original “environment stressor” annotation category. This change enabled patients to record both positive and negative daily experiences, offering a more balanced and comprehensive view of their life. Furthermore, to ensure consistent implementation of the REBECCA-assisted lifestyle consultations across the clinical sites, Karolinska Institutet developed a comprehensive advisory guide to support personalized lifestyle consultations. Drawing on international guidelines and adapting them to the REBECCA context, the guide was organized across six lifestyle domains plus an additional category of REBECCA-specific indicators, including mobility, work status, eating behaviours, and social support. The guide provided coded recommendations and practical examples to facilitate consistent, structured consultations by the HCPs across all clinical sites. The guide is publicly available as a standalone document on Zenodo at https://doi.org/10.5281/zenodo.17425256. Together, the enhanced reporting through the pApp and the development of the advisory guide for HCPs exemplify best practices for integrating patient-generated data into clinical workflows. H2020SC1-DTH-12-2020 D7.4 7 | 62 1 Introduction Breast cancer stands as the most prevalent cancer among women globally, representing the second-highest number of yearly incidences (approximately 11.6% of global new cancer cases in 2018 3 ), contributing to one-fifth of overall global cancer mortality. In Europe alone, breast cancer emerges as the most frequently diagnosed cancer annually, with approximately 523,000 new cases reported in 2018. 4 Breast cancer patients (BCPs) constitute the largest subgroup within the expanding community of cancer patients worldwide. 5 Beyond primary cancer treatment, which increasingly yields success, breast cancer survivors (BCSs) grapple with substantial life challenges. These challenges encompass the management of medical conditions, adjustments in lifestyle resulting from cancer and its treatment, intense fear of cancer recurrence, 6 and difficulties in resuming personal and professional responsibilities. These challenges often lead to additional long-term financial burdens. 7 Surviving breast cancer becomes a transformative event, becoming the focal point in a multifaceted framework of health dependencies that significantly impact the patients’ Quality of Life (QoL), mental/emotional state, and overall lifestyle. 8 REBECCA aims to harness the potential of “real-world data” (RWD) – including clinical data, patient-reported outcome measures (PROMs), and data collected from smartphones and smartwatches, along with episodic patient reports – to support clinical research on complex chronic conditions as a complementary approach to randomized controlled trials, and to improve clinical workflows through personalised follow-ups. Going beyond traditional research and clinical data analysis, REBECCA collaborated with AMAZONA, the largest Swedish breast cancer association and a member of the REBECCA consortium. AMAZONA’s input through the co-creation activities played a key role in shaping the REBECCA system, which facilitates detailed monitoring of data from clinical resources, multiple wearables, online behaviour, and registry data (the “REBECCA 360°” monitoring). This comprehensive approach allows for the monitoring of patients’ physical, physiological, emotional, and QoL trajectories. 3 Global Cancer Observatory. https://gco.iarc.fr/ 4 Ferlay et al. Cancer incidence and mortality in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer (2018) 5 American Cancer Society (2016). Cancer Treatment and Survivorship Facts and Figures. Online: https://tinyurl.com/yaugv727 6 Ellegaard et al. Fear of cancer recurrence and unmet needs among breast cancer survivors in the first five years. Acta Oncologica 56.2 (2017):314 7 Fenn et al. Impact of financial burden of cancer on survivors' quality of life. J Oncol Pract 10.5 (2014):332 8 Koch et al. Quality of life in long-term breast cancer survivors, 10-year longitudinal population-based study. Acta Oncol 52.6 (2013): 1119 H2020SC1-DTH-12-2020 D7.4 8 | 62 The project commenced in April 2021 and finished in September 2025, holding the potential to generate new insights into the clinical management of cancer patients and potentially shaping future breast cancer rehabilitation guidelines. Best practices derived from the REBECCA studies will be disseminated to researchers, public health entities, and regulatory bodies across Europe, fostering the broader adoption of RWD in clinical research. Furthermore, the REBECCA platform, equipped for detailed monitoring and privacy-preserving federated cross-country data analysis, will serve as an infrastructure for ongoing advancements in RWD usage beyond the project’s conclusion. Through these endeavours, REBECCA aims to encourage the widespread adoption of RWD for comprehending chronic health conditions, ultimately establishing it as a valuable tool in clinical research and patient management. 1.1 Aim The aim of this deliverable is to describe the co-creation activities and evidence synthesis processes conducted within the REBECCA project to support the integration of multi-source RWD into existing clinical workflows. These activities focused on the introduction of the “Life event” feature in the pApp and the development of the advisory guide to facilitate the use of RWD by healthcare professionals (HCPs) in improving patient management and QoL. 1.2 Intended audience This public deliverable is intended for HCPs and managers, clinical researchers, policy makers, regulators, patient organisations, and other relevant stakeholders interested in novel digital monitoring tools such as the REBECCA 360°. It is particularly relevant for those involved in breast cancer care and the management of complex chronic conditions, as it provides a methodology for integrating multimodal real-world data into clinical workflows. The document also aims to inform stakeholders about cocreation practices involving patients as the end-users. 1.3 Project partners and acronyms Throughout this deliverable, the following acronyms are used to refer to REBECCA consortium partners. H2020SC1-DTH-12-2020 D7.4 9 | 62 Acronym Partner name Country AMAZONA BROSTCANCERFORENINGEN AMAZONA I STOCKHOLMS LAN Sweden INCLIVA FUNDACION PARA LA INVESTIGACION DEL HOSPITAL CLINICO DE LA COMUNITAT VALENCIANA, FUNDACION INCLIVA Spain KI KAROLINSKA INSTITUTET Sweden SUH HELSE STAVANGER HF Norway 1.4 Methodology For the integration of patient-driven features into the pApp, a co-creation approach was applied. Patients, clinicians, and researchers participated in workshops and validation sessions to refine app features and ensure their relevance for both patients and clinical use. This process led to the development of the “Life Events” feature, which allows patients to report both positive and negative daily experiences, improving engagement with the pApp as well as the quality and balance of the RWD collected. For the development of the unified advisory guide, KI conducted a literature review of international guidelines from authoritative sources (e.g., WHO, WCRF, CDC) to identify evidence-based recommendations relevant to breast cancer survivorship. These were adapted to the REBECCA context and organized across six lifestyle domains – diet, physical activity, sleep, alcohol use, tobacco use, and anxiety/distress – along with REBECCA-specific indicators. The resulting guide was reviewed and validated by consortium partners to ensure consistency across clinical sites. 1.5 Organization of the document The rest of the document is organized as follows. Section 2 describes the patient-driven development of the pApp feature “Life Events” and Section 3 presents the process of creating the advisory guide for personalized consultations. Annex A includes the advisory lifestyle guidelines. Annex B provides the list of categories proposed as life events (initial, grouped for discussion, and finalised after co-creation), as well as the minutes from the co-creation activities. H2020SC1-DTH-12-2020 D7.4 16|62 Figure 6. The data collection devices used in REBECCA studies. To ensure consistent implementation of the REBECCA-assisted lifestyle consultations across the participating clinical sites, a common reference framework was required. This framework would provide harmonized guidance in line with both international standards and local clinical practice, while at the same time supporting HCPs in their day-to-day work. Importantly, it would also establish a standardized approach for documenting what had been delivered during the consultations, ensuring comparability across sites. In response to this need, KI developed a comprehensive advisory guide, designed to serve as a practical tool and a training resource for the HCP. H2020SC1-DTH-12-2020 D7.4 17|62 3.2 Development process In May 2023, KI carried out an extensive literature review to identify and synthesize best practices in post-cancer lifestyle guidance. The review drew on authoritative international sources, including the World Health Organization (WHO), 11 the World Cancer Research Fund (WCRF), 12 and the Centres for Disease Control and Prevention (CDC). 13 Where breast cancer–specific recommendations were available, these were prioritized. In cases where no breast cancer–focused material was identified; general population guidelines were reviewed and adapted to the REBECCA context. Figure 7. Resources for the advisory guide. The evidence collected was then systematically organized across six lifestyle domains known to influence the health outcomes and QoL of BCP and BCS: diet, physical activity, sleep, alcohol use, tobacco use, and anxiety and distress. In addition to these six lifestyle domains, an additional category for REBECCA-specific indicators was introduced. This category included dimensions such as daily mobility, work after 11 https://www.who.int/news-room/fact-sheets/detail/physical-activity 12 https://www.wcrf.org/research-policy/evidence-for-our-recommendations/after-a-cancer-diagnosis-follow-recommendations/ 13 https://www.cdc.gov/cancer-survivors/healthy-livingguides/sleep.html?CDC_AAref_Val=https://www.cdc.gov/cancer/survivors/healthy-living-guides/physical-health/sleep.htm H2020SC1-DTH-12-2020 D7.4 18|62 treatment, social relationships and support networks, and eating behaviours (e.g., eating rate and portion size). The outcome of the process described above was a comprehensive, coded document that brought together international and national guidelines and adapted them to the REBECCA context. The guide provides HCPs with clear, domain-specific recommendations and practical examples on how to engage BCPs in constructive discussions about lifestyle topics, such as physical activity or diet, in a supportive way. To facilitate consistency across sites, the guide adopted a standardized reporting format and incorporated coded guidelines, allowing HCPs to document consultations in a uniform manner. Figure 8. Development process of the advisory guide. 3.3 Structure and content of the guide The final guide was a 27-page PDF divided into seven sections (six lifestyle domains identified via the literature review plus one section for the REBECCA specific indicators): 1. Guidelines and Advice on Diet for BCS 2. Guidelines and Advice on Physical Activity for BCS 3. Guidelines and Advice on Sleep for BCS 4. Guidelines and Advice on Alcohol Use for BCS H2020SC1-DTH-12-2020 D7.4 19|62 5. Guidelines and Advice on Tobacco Use for BCS 6. Guidelines and Advice on Anxiety and Distress for BCS 7. REBECCA-specific indicators for BCS Figure 9. Advisory Guidelines. Each section of the guide consisted of two parts. The first part listed the guidelines with their codes and references (e.g. D1, D2, and so forth for dietary recommendations) (Figure 10). H2020SC1-DTH-12-2020 D7.4 20|62 Figure 10. Example of the coded lifestyle recommendations included in the advisory guide. The second part provided practical examples showing how HCPs could deliver advice based on the RWD collected (Figure 11). These examples included simple explanations and codes, allowing the HCP to easily record which aspects were discussed with the BCP at the end of each session. H2020SC1-DTH-12-2020 D7.4 21|62 Figure 11. Example of the advice included in the advisory guide. Figure 12 Example of indicators visualised in the REBECCA dashboard. ! ! H2020SC1-DTH-12-2020 D7.4 22|62 All the relevant lifestyle indicators connected to the seven domains were monitored through the various data collection methods and visualised for the HCPs via the REBECCA dashboard (Figure 12). Lifestyle and behavioural data were collected through multiple sources connected to the REBECCA system. Dietary patterns and alcohol consumption were assessed through meal and drink photos uploaded to the pApp. Physical activity and sleep were continuously monitored via the smartwatch, while tobacco use was reported through questionnaires. Emotional well-being, including anxiety and distress, was evaluated using questionnaires and complemented by smartwatch, companion’s questionnaires and online activity data. Daily mobility was captured through the smartwatch, which was Bluetooth-paired with the BCP’s smartphone and the pApp. These devices locally recorded IMU data, including accelerometer and gyroscope signals, while the pApp logged geolocation (GPS) data from the phone. The pApp also maintained an internal usage log, which served as an indicator of compliance with the data collection protocol. Work status after treatment could be inferred through a combination of questionnaire responses and mobility patterns, such as repeated daily visits to the same location for extended periods, suggesting a workplace. Eating rate was estimated through smartwatch data, while information about relationships and support systems was derived from the companion, internet history and mobility patterns (e.g., identifying individuals who rarely left their homes). Together, these diverse data sources provided a comprehensive picture of each BCP’s lifestyle and behaviour, forming the foundation for the REBECCA-assisted consultations. During these consultations, HCPs used the advisory guide alongside the RWD collected for each BCP. HCPs created a list with the coded lifestyle aspects warranted attention (e.g., D1, P3, AN1, S2) and engaged with patients to explore tailored strategies for improving these specific aspects of their life based on the examples in the guide. At the end of each consultation, the guide enabled HCP to clearly and efficiently document which recommendations had been discussed, supporting consistent reporting and comparability across clinical sites. H2020SC1-DTH-12-2020 D7.4 23|62 Conclusions Deliverable D7.4 illustrates how multi-source RWD can be integrated into clinical workflows to enhance the management of BCPs. The REBECCA project applied a structured co-creation approach, engaging patients, HCPs, and researchers to ensure that digital tools and advisory resources were both clinically relevant and meaningful to patients. The “Life Events” feature in the pApp enabled patients to report both positive and negative daily experiences, providing a more comprehensive view of their lives. Simultaneously, the unified advisory guide offered HCPs a standardized, evidencebased framework to deliver personalized lifestyle consultations, supporting consistent reporting and comparability across clinical sites. Together, these tools demonstrate best practices for the use of patient-generated RWD in clinical care. They allowed HCPs to systematically interpret complex behavioural and lifestyle data, identify areas requiring intervention, and provide tailored recommendations, thereby improving patient-centred care. The REBECCA methodology and outputs provide a scalable model for integrating RWD into healthcare practice, fostering evidence-based decision-making, enhancing postcancer rehabilitation, and promoting the broader adoption of RWD in clinical research. H2020SC1-DTH-12-2020 D7.4 24|62 References 1. Global Cancer Observatory. https://gco.iarc.fr/ 2. Ferlay et al. Cancer incidence and mortality in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer (2018) 3. American Cancer Society (2016). Cancer Treatment and Survivorship Facts and Figures. Online: https://tinyurl.com/yaugv727 4. Ellegaard et al. Fear of cancer recurrence and unmet needs among breast cancer survivors in the first five years. Acta Oncologica 56.2 (2017):314 5. Fenn et al. Impact of financial burden of cancer on survivors' quality of life. J Oncol Pract 10.5 (2014):332 6. Koch et al. Quality of life in long-term breast cancer survivors, 10-year longitudinal population-based study. Acta Oncol 52.6 (2013): 1119 7. Cancer Research UK [Internet]. 2019 [cited 2025 September 29]. What is a healthy diet? Available from: https://www.cancerresearchuk.org/aboutcancer/causes-of-cancer/diet-and-cancer/what-is-a-healthy-diet 8. World Health Organization. (2024, June 26). Physical activity [Fact sheet]. https://www.who.int/news-room/fact-sheets/detail/physical-activity World Health Organization 9. World Cancer Research Fund. (n.d.). After a cancer diagnosis, follow our recommendations, if you can [Evidence & recommendations]. https://www.wcrf.org/research-policy/evidence-for-ourrecommendations/after-a-cancer-diagnosis-follow-recommendations/ World Cancer Research Fund 10. Centers for Disease Control and Prevention. (2024, August 26). Sleeping Well [Guide for cancer survivors]. https://www.cdc.gov/cancer-survivors/healthyliving-guides/sleep.html H2020SC1-DTH-12-2020 D7.4 25|62 ANNEX H2020SC1-DTH-12-2020 D7.4 32|62 H2020SC1-DTH-12-2020 D7.4 33|62 H2020SC1-DTH-12-2020 D7.4 34|62 H2020SC1-DTH-12-2020 D7.4 35|62 H2020SC1-DTH-12-2020 D7.4 36|62 H2020SC1-DTH-12-2020 D7.4 37|62 H2020SC1-DTH-12-2020 D7.4 38|62 H2020SC1-DTH-12-2020 D7.4 39|62 H2020SC1-DTH-12-2020 D7.4 40|62 H2020SC1-DTH-12-2020 D7.4 41|62 H2020SC1-DTH-12-2020 D7.4 48|62 H2020SC1-DTH-12-2020 D7.4 49|62 H2020SC1-DTH-12-2020 D7.4 50|62 H2020SC1-DTH-12-2020 D7.4 51|62 B. ANNEX B: Positive annotation categories B.1 Initial list from brainstorming at KI H2020SC1-DTH-12-2020 D7.4 52|62 H2020SC1-DTH-12-2020 D7.4 53|62 H2020SC1-DTH-12-2020 D7.4 54|62 H2020SC1-DTH-12-2020 D7.4 55|62 H2020SC1-DTH-12-2020 D7.4 56|62 B.2 List after grouping the events into categories H2020SC1-DTH-12-2020 D7.4 57|62