Working within the principles of collaboration and transparency, each stakeholder can undertake actions to support the use of real-world evidence in Payer/HTA decisions about highly innovative technologies. This section presents the recommended actions for each stakeholder group that have been widely consulted upon.

1. Payers/HTA bodies – European/Multi-country
  • 1.1 Collaborate with academia to better understand the potential of new statistical, econometric and modelling approaches to develop robust RWE for use in Payer/HTA decisions.
  • 1.2 Encourage industry to engage in multi-stakeholder dialogues to discuss evidence generation plans including RWD collection.
  • 1.3 Use joint processes (multi-HTA and with regulators) to document evidence gaps and key uncertainties in the clinical (and economic) evidence and identify which areas might be addressed by patient-relevant RWE.
  • 1.4 Document the regulatory post-licensing evidence generation (PLEG) obligations and the additional Payer/HTA PLEG needs. Establish what PLEG is needed on national, regional, and European level.
  • 1.5 For individual HTAs, agree the core dataset that is required for HTA reappraisal, within a reasonable timeframe, so that common data collection protocols can be agreed across countries and joint analyses performed.
  • 1.6 Engage with the clinical community (particularly ERNs) to avoid conflicting or duplicative data collection.
  • 1.7 Develop methods guides to show how RWE will be critically assessed and how the validity and applicability of RWD/RWE from another country/health setting will be determined.
  • 1.8 Encourage the development of a public portal registering RWE studies that may be used in decision-making and when fully established only accept studies previously registered and reported on the portal.
2. Payers/HTA bodies – National Payers/HTA bodies
Coverage/HTA Processes
  • 2.1 Encourage establishment of national processes for data collection, analysis, critical assessment and appraisal that enable collection of relevant and reliable RWD to inform access and reimbursement decisions and optimize use of highly innovative technologies to achieve the best outcomes for patients.
  • 2.2 Inform national stakeholders about RWE needs for HTA and engage in developments to enable secondary use of health and social care data in the national context.
  • 2.3 Seek to harmonize requests to Marketing Authorization Holders (MAHs) for additional RWD collection with other HTA bodies and the regulator.
  • 2.4 Engage with stakeholders to agree responsibility for the conduct and financing of RWD collection and analysis.
  • 2.5 Engage with patient organizations to ensure data is collected on those outcomes that matter most to patients.
  • 2.6 Build capacity in data analytics and critical assessment of RWE studies.
Coverage/HTA Decisions for an Individual Technology
  • 2.7 Actively explore the opportunity to use RWD from other countries/across country (e.g. European registries), preferably in collaboration with other HTA bodies, in consultation with industry, taking account of national/context specific limitations of the data.
  • 2.8 Request RWE generation plans from companies, including protocols or plans for data collection and analysis of RWE studies related to HTA.
  • 2.9 During assessment, consider the feasibility of RWD collection, possibly combined with an outcomes-based managed entry agreement (nationally or in collaboration with other countries) to manage important uncertainties and enable reassessment.
  • 2.10 When an outcomes-based managed entry agreement is used, engage with patients and clinicians to plan for potential routine adoption or modification of reimbursement conditions or disinvestment at the end of the agreement.
3. Regulators
  • 3.1 Promote use of parallel multi-HTA Scientific Advice/Early Dialogue processes including all relevant stakeholders at various points in the development of a highly innovative technology
  • 3.2 Develop, in co-creation with all stakeholders, guidance on generic RWE issues discussed in Scientific Advice/Early Dialogues for highly innovative technologies
  • 3.3 Continue to support methodological discussions with industry about non-RCT methodologies through methods qualification and multi-stakeholder scientific advice.
  • 3.4 Involve HTA bodies in initiatives related to improving the quality of RWD such as registry qualification, quality standards for big data/RWD etc.
  • 3.5 For highly innovative technologies with conditional MA or MA under exceptional circumstances, involve HTA bodies in discussions about requirements for post-marketing data collection.
4. Pharmaceutical Industry
  • 4.1 Create a RWE generation plan early in development, which addresses essential data elements for HTA not covered in the clinical trial program and that might be studied in a real-world setting.
  • 4.2 Discuss the RWE generation plan at various stages throughout the technology life cycle including regulators, payers, HTA bodies, clinicians and patients whenever possible.
  • 4.3 Ensure the study (protocol) and statistical analysis plans for RWE studies that are answering major HTA questions are available to HTA bodies to provide transparency about the methods used to obtain and analyse data.
  • 4.4 Support the development of a public portal that provides details about the design and results of major RWE studies (ala RCT registries), particularly hypothesis evaluating treatment effect (HETE) studies.
  • 4.5 Drive non-competitive, multi-company and multi-stakeholder collaborations about the development of robust RWE for diseases treated by highly innovative technologies.
  • 4.6 Enact recommendations from the ISPOR and RWE Transparency Partnership.
  • 4.7 Use reliable data collection methods for RWD, including ehealth and digital tools and develop best practices as digital approaches evolve.
5. Registry-holders
  • 5.1 European Reference Networks (ERNs) should continue to be developed and encouraged to engage with decision-makers to discuss registries and other sources of RWD.
  • 5.2 Collaborate with regulatory authorities, HTA bodies and industry at an early stage in the development of a highly innovative technology to identify if existing registries could be used to resolve uncertainties during the development phase or for post-launch data collection, or discuss potential for new registries.
  • 5.3 Review quality standards for registries issued by EMA and EUnetHTA and apply them.
  • 5.4 Collaborate on an ongoing basis with HTA bodies/regulatory authorities/manufacturers to determine if a standard set of data can be collected and shared to enable pooling with other data sources for analysis.
  • 5.5 Collaborate with European and national policy makers to develop governance structures that facilitate data quality and accessibility.
  • 5.6 Create incentives to build and maintain disease-based, rather than product-specific, registries.
  • 5.7 All Registries should follow the FAIR data principles (Findable, Accessible, Interoperable, Re-usable) and provide “privacy by design” – ensuring data protection through technology design.
  • 5.8 If available in the health system, registries should use the unique patient-id to enable linkage with other health data sources.
6. Clinicians
  • 6.1 European Reference Networks (ERNs) and other clinical networks should systematically collaborate with regulators and Payer/HTAs when establishing their registry or other form of RWD collection to ensure it is fit for all purposes including HTA.
  • 6.2 Enhance the H2020 EU Joint-Programme for rare diseases to include regulators and HTA bodies in order to better understand their needs.
  • 6.3 ERNs and other clinical networks should advise on the most suitable and efficient way for health systems to collect RWD.
  • 6.4 Encourage clinical communities to collect high quality health data (administrative, registry, audit etc) that is required for Payer/HTA decisions.
  • 6.5 Promote the use of data driven shared decision-making processes for optimization of treatment of the individual and care pathways.
  • 6.6 Understand the importance and relevance of the role of RWD in outcomes-based managed entry agreements in order to align on right usage and adherence to collect the data needed.
7. Patient Groups
  • 7.1 Develop patient group expertise and capacity to be co-creators of RWE to ensure a holistic, patient-centred approach.
  • 7.2 Develop EU or international patient group collaborations to engage in RWD initiatives and ensure that outcomes that matter to patients are collected.
  • 7.3 Support the development of patient information and informed consent for RWE studies, clearly explaining study expectations (e.g. regularity of clinic visits and assessments) and treatment discontinuation rules.
  • 7.4 Disseminate clear unbiased, patient-relevant information about RWD and RWE to patient communities, including the value of secondary use of data
  • 7.5 Provide recommendations on novel and efficient collection methods for RWD (e.g. devices, wearables, mHealth).
  • 7.6 Help promote the scientific and policy value of data collection and provide access within strict governance frameworks ensuring appropriate confidentiality, e.g. via the #DataSavesLives initiative.
  • 7.7 Work with stakeholders to encourage alignment of views on identification, collection, analysis and evaluation of RWD for decision-making.
8. RWD/analytics groups
  • 8.1 Engage with HTA bodies and other stakeholders in demonstration projects related to highly innovative technologies.
  • 8.2 Collaborate with industry and HTA bodies to generate RWE for outcomes-based MEA.
  • 8.3 Contribute to research collaborations that lead to published guidance on the use of RWD for specific research questions relevant to HTA of highly innovative technologies
  • 8.4 Work with stakeholders to develop reporting standards, including full transparency, software audit trails and study pre-registration
  • 8.5 Collaborate with industry, regulators and HTA bodies to enhance the efficiency of preparation and submission of RWE that facilitates transparency, addresses proprietary data and privacy challenges and includes robust data governance.
  • 8.6 Work with stakeholders to develop criteria to evaluate RWD’s fitness for purpose, provenance, transparency and adherence to governance standards in order to inform the evaluation of RWE
  • 8.7 Publish analytical methods to generate reliable RWE for HTA.

Download the Paper