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Abstract Aims Decision‐makers still predominantly focus on the perspective of non‐patient stakeholders, which may deviate from the unique perspective of heart failure (HF) patients. To enhance patient‐centred decision‐making, there is a need for more patient‐based evidence derived directly from the patients themselves. Hence, this study aimed to understand (i) HF patients' unmet medical needs and preferred treatment outcomes; (ii) patients' risk tolerance; and (iii) their information needs, uncertainties and satisfaction towards HF treatment. Methods This qualitative patient preference study consisted of a literature review with a systematic search strategy and semi‐structured interviews with HF patients, analysed using the framework method. During the interviews, patients were asked to rank a predefined list of disease and treatment‐related characteristics informed by the literature review and were able to spontaneously raise additional characteristics. Results The study included 14 Belgian HF patients (age range: 58–79, mean age: 72). (i) Regarding their unmet medical needs, HF patients reported that the most important unmet medical needs were shortness of breath and fatigue, as they negatively impact their quality of life (QoL) and independence. In the ranking exercise, patients prioritized improvements in QoL over improvements in life expectancy, whereby the following characteristics received the highest cumulative score: (1) independence, (2) shortness of breath, (3) impaired renal function, (4) survival, (5) fatigue, (6) risk of hospitalization and (7) communication with and between physicians. Patients most often spontaneously raise characteristics related to the general care process. Mechanism of action, route of administration, dose frequency and weight fluctuations scored among the least important characteristics. (ii) Regarding patients' risk tolerance towards HF treatment, some of the patients expressed zero tolerance for side effects, as they had not yet experienced any discomfort caused by the treatment or disease. (iii) Regarding their information needs, patients voiced their desire to receive practical and comprehensible advice orally from their physician because they highly value individualized treatment decision‐making. Patients also expressed uncertainties regarding whether the experienced effects were due to their treatment, disease, ageing or other comorbidities. Conclusions This study shows that, besides increasing life expectancy, HF patients prioritize improvements in symptoms and side effects reducing their QoL and independence, such as shortness of breath and fatigue. The patient‐relevant characteristics identified in this study, from the perspective of HF patients themselves, may be useful to inform clinical trial endpoint selection and guide downstream drug development, evaluation and clinical decision‐making towards addressing the unmet medical needs and treatment outcomes of importance to HF patients.

IntroductionThe 2020 pharmaceutical strategy for Europe stressed that rethinking regulatory policies to foster innovation in disease areas with unmet medical needs (UMN) is one of the European Commission’s (EC) priority areas. To understand stakeholders’ views regarding appropriate UMN criteria and incentives, the EC developed a survey and launched it for public consultation between September and December 2021. This study aims to assess stakeholders’ views on the policy revisions proposed by the EC, particularly those regarding the definition of UMN, its criteria and incentives and evaluate how stakeholders’ views are reflected in the proposed reform of the EU pharmaceutical legislation of 2023.MethodsThe public consultation survey comprised 14 questions including multiple-choice and open answer questions about the reform of the pharmaceutical legislation. A mixed-method analysis was conducted on publicly available data of stakeholders’ responses, including descriptive and quantitative statistics for multiple-choice questions and a qualitative thematic framework analysis for open answer questions. A subgroup analysis was performed to assess differences and similarities in stakeholders’ views, and results were compared with the proposed reform of the EU pharmaceutical legislation.ResultsA total of 478 participants completed the survey consisting of 36% industry, 19% end-users, 17% healthcare providers, 7.5% researchers and 7.5% public bodies. All stakeholder groups favored including “absence of satisfactory authorized treatment” and “disease seriousness” as defining criteria for UMN. However, stakeholders disagreed on including the criterion “lack of access for patients,” with public bodies and industry being less in favour. Industry favored maintaining or having additional incentives like transferable exclusivity vouchers on top of current intellectual property rights to foster innovation. In contrast, other stakeholders supported alternative proposals, namely enhancing the use of scientific advice and implementing expediting measures for regulatory evaluation of medicines targeting UMN.ConclusionStakeholders agreed on including availability of alternatives and disease seriousness in the UMN definition but highlighted its ambiguity. Industry participants supported additional incentives like transferable exclusivity vouchers, whereas others preferred scientific and regulatory support. These findings underscore the need for further discussion on UMN criteria and incentives to stimulate innovation while ensuring patient-centric outcomes and equitable access to medicines across Europe.

Background At the European level, several regulatory measures (ie, priority medicines (PRIME) scheme, accelerated assessment, conditional marketing authorisation and authorisation under exceptional circumstances) are in place with the aim to expedite the marketing authorisation process for medicines targeting unmet medical needs (UMNs). However, the potential impact of these measures on subsequent decisions regarding market access at the national level, and ultimately if medicines making use of these supporting measures reach the patient earlier, remains unclear.Objectives This study seeks to (1) assess the impact of such European regulatory measures on the number of successful applications and time to reimbursement of this group of medicines in the national context of Belgium and (2) evaluate the association between the application of European regulatory measures and Belgian measures (ie, early access pathways and managed entry agreements).Design A total of 322 medicines granted a European centralised marketing authorisation between 2015 and 2020, excluding generic products/biosimilars, were included in the study. For this set of medicines, data on European and Belgian regulatory and market access measures were extracted from the websites of the responsible European and Belgian authorities and completed with requested information up to December 2022. Regression analysis was used to assess the association between the application of European regulations and Belgian measures. Survival and regression analysis was used to test the impact of such regulatory measures on the time to and rate of reimbursement in Belgium.Results From the total sample (n=322), 34% (n=108) received a European regulatory measure, and also 34% (n=108) had a Belgian measure applied. Overall, 63% (n=202) of the total sample was submitted for reimbursement in Belgium, and of these, 83% (n=167) were reimbursed at the time of assessment. The median regulatory assessment time at the European level was approximately 14 months, while the median Belgian reimbursement assessment time was approximately 11 months. The study found that regulatory measures did not significantly impact the European or national assessment times or status. A significant reduction in European regulatory assessment time was observed only in the cases of the PRIME scheme (p=0.0087) and accelerated assessment (p

National pricing and reimbursement agencies face growing challenges with complex health technologies, prompting European policy advancements. Beneluxa is a cross-country collaboration involving Belgium, the Netherlands, Luxemburg, Austria, and Ireland that aims to address sustainable access to medicines. In view of the soon-to-be-implemented EU HTA Regulation, insights and experiences from stakeholders with Beneluxa cross-country collaboration could provide possible transferable learnings. Therefore, this research aims to (i) identify the opportunities and challenges faced by Beneluxa, (ii) gather insights from stakeholders, namely (possible) applicants and policymakers, within and beyond Beneluxa on the initiative and broader cross-country collaboration principles, and (iii) transfer these insights into learnings and recommendations in anticipation of the full implementation of the new HTA Regulation. Fifteen semi-structured interviews were conducted with industry and European HTA/policy stakeholders. The principal challenges discussed by stakeholders encompass hesitancy from the industry toward Beneluxa assessments, which were attributed to procedural and timeline uncertainties, legislative framework ambiguity, and challenges in terms of industry’s internal organization. Another challenge highlighted is the resource-intensive nature of the procedure due to diverse approaches among member states. In addition, industry stakeholders mentioned limited communication and procedural complexity. Despite challenges, both stakeholder groups recognized important opportunities for cross-country collaboration. Transferable insights for future cross-country collaboration include transparent communication, clear legislative embedding, internal industry restructuring to facilitate joint HTAs, and member state support for conducting collaborative assessments. The study underscores diverging views among stakeholders on cross-country collaboration’s potential to support HTA and the market access of complex health technologies. While acknowledging benefits, there still are challenges, including industry hesitancy, emphasizing the need for transparent communication and clear guidance in the evolving EU HTA landscape.

Changes in the clinical trials landscape have been driven by advancements in digital technology. The use of electronic informed consent to inform research participants and to obtain their consent electronically has the potential to improve participant–researcher interactions over time, facilitate clinical trial participation, and increase efficiency in clinical trial conduct. A personalized electronic informed consent platform that enables long-term interactions with the research team could function as a tool to empower participant engagement in clinical trials. However, significant challenges persist impeding successful and widespread implementation. This Perspective provides insights into the opportunities and challenges for the implementation of electronic informed consent in clinical trials. It sets out key recommendations to promote the implementation of this innovative approach to the informed consent process, including the creation of uniform electronic informed consent platforms at regional and national level.

BackgroundOver the years, there has been increasing interest in electronic informed consent (eIC) in clinical research. The user-friendliness of an eIC application and its acceptance by stakeholders plays a central role in achieving successful implementation. ObjectiveThis study aims to identify insights for the design and implementation of a user-friendly, personalized, and long-term eIC application based on a usability study with (potential) research participants and semistructured interviews with stakeholders on the practical integration of such an application into their daily practice. MethodsAn eIC prototype was evaluated and refined through usability testing among Belgian citizens and iterative redesign. On the basis of a digital literacy questionnaire, a heterogeneous sample of participants was established. Participants needed to complete a series of usability tasks related to personalization and long-term interaction with the research team while using the “think aloud” technique. In addition, usability tests involved completing the System Usability Scale questionnaire and taking part in a semistructured feedback interview. Furthermore, semistructured interviews were conducted with ethics committee members, health care professionals, and pharmaceutical industry representatives active in Belgium and involved in clinical research. Thematic analysis was undertaken using the NVivo software (Lumivero). ResultsIn total, 3 iterations of usability tests were conducted with 10 participants each. Each cycle involved some participants who reported having low digital skills. The System Usability Scale scores related to the tasks on personalization and long-term interaction increased after each iteration and reached 69.5 (SD 8.35) and 71.3 (SD 16.1) out of 100, respectively, which represents above-average usability. Semistructured interviews conducted with health care professionals (n=4), ethics committee members (n=8), and pharmaceutical industry representatives (n=5) identified the need for an eIC system that can be easily set up. For example, a library could be established enabling stakeholders to easily provide background information about a clinical study, presented in the second layer of the interface. In contrast, some functionalities, such as informing participants about new studies through an eIC system, were not considered useful by stakeholders. ConclusionsThis study provides insights for the implementation of a user-friendly personalized and long-term eIC application. The study findings showed that usability testing is key to assessing and increasing the user-friendliness of an eIC application. Although this eIC system has the potential to be usable by a wide audience, participants with low digital literacy may not be able to use it successfully, highlighting the need for additional support for participants or other alternatives to an eIC system. In addition, key lessons emerging from the interviews included ensuring that the application is easy to implement in practice and is interoperable with other established systems.

Abstract Background Electronic informed consent (eIC) may offer various advantages compared to paper-based informed consent. However, the regulatory and legal landscape related to eIC provides a diffuse image. By drawing from the perspectives of key stakeholders in the field, this study aims to inform the creation of a European guidance framework on eIC in clinical research. Methods Focus group discussions and semi-structured interviews were conducted with 20 participants from six stakeholder groups. The stakeholder groups included representatives of ethics committees, data infrastructure organizations, patient organizations, and the pharmaceutical industry as well as investigators and regulators. All were involved in or knowledgeable about clinical research and were active in one of the European Union Member States or at a pan-European or global level. The framework method was used for data analysis. Results Stakeholders underwrote the need for a multi-stakeholder guidance framework addressing practical elements related to eIC. According to the stakeholders, a European guidance framework should describe consistent requirements and procedures for implementing eIC on a pan-European level. Generally, stakeholders agreed with the definitions of eIC issued by the European Medicines Agency and the US Food and Drug Administration. Nevertheless, it was raised that, in a European guidance framework, it should be emphasized that eIC aims to support rather than replace the personal interaction between research participants and the research team. In addition, it was believed that a European guidance framework should include details on the legality of eIC across European Union Member States and the responsibilities of an ethics committee in the eIC assessment process. Although stakeholders supported the idea to include detailed information on the type of eIC-related materials to be submitted to an ethics committee, opinions varied on this regard. Conclusion The creation of a European guidance framework is a much needed factor to advance eIC implementation in clinical research. By collecting the views of multiple stakeholder groups, this study advances recommendations that may facilitate the development of such a framework. Particular consideration should go to harmonizing requirements and providing practical details related to eIC implementation on a European Union-wide level.

Objective: Patients have unique insights and are (in-)directly affected by each decision taken throughout the life cycle of medicinal products. Patient preference studies (PPS) assess what matters most to patients, how much, and what trade-offs patients are willing to make. IMI PREFER was a six-year European public-private partnership under the Innovative Medicines Initiative that developed recommendations on how to assess and use PPS in medical product decision-making, including in the regulatory evaluation of medicinal products. This paper aims to summarize findings and recommendations from IMI PREFER regarding i) PPS applications in regulatory evaluation, ii) when and how to consult with regulators on PPS, iii) how to reflect PPS in regulatory communication and iv) barriers and open questions for PPS in regulatory decision-making.Methods: PREFER performed six literature reviews, 143 interviews and eight focus group discussions with regulators, patient representatives, industry representatives, Health Technology Assessment bodies, payers, academics, and clincians between October 2016 and May 2022.Results: i) With respect to PPS applications, prior to the conduct of clinical trials of medicinal products, PPS could inform regulators’ understanding of patients’ unmet needs and relevant endpoints during horizon scanning activities and scientific advice. During the evaluation of a marketing authorization application, PPS could inform: a) the assessment of whether a product meets an unmet need, b) whether patient-relevant clinical trial endpoints and outcomes were studied, c) the understanding of patient-relevant effect sizes and acceptable trade-offs, and d) the identification of key (un-)favorable effects and uncertainties. ii) With respect to consulting with regulators on PPS, PPS researchers should ideally have early discussions with regulators (e.g., during scientific advice) on the PPS design and research questions. iii) Regarding external PPS communication, PPS could be reflected in the assessment report and product information (e.g., the European Public Assessment Report and the Summary of Product Characteristics). iv) Barriers relevant to the use of PPS in regulatory evaluation include a lack of PPS use cases and demonstrated impact on regulatory decision-making, and need for (financial) incentives, guidance and quality criteria for implementing PPS results in regulatory decision-making. Open questions concerning regulatory PPS use include: a) should a product independent broad approach to the design of PPS be taken and/or a product-specific one, b) who should optimally be financing, designing, conducting, and coordinating PPS, c) when (within and/or outside clinical trials) to perform PPS, and d) how can PPS use best be operationalized in regulatory decisions.Conclusion: PPS have high potential to inform regulators on key unmet needs, endpoints, benefits, and risks that matter most to patients and their acceptable trade-offs. Regulatory guidelines, templates and checklists, together with incentives are needed to foster structural and transparent PPS submission and evaluation in regulatory decision-making. More PPS case studies should be conducted and submitted for regulatory assessment to enable regulatory discussion and increase regulators’ experience with PPS implementation and communication in regulatory evaluations.

Background: Countries are struggling to provide affordable access to medicines while supporting the market entry of innovative, expensive products. This Perspective aims to discuss challenges and avenues for balancing health care system objectives of access, affordability and innovation related to medicines in Belgium (and in other countries).Methods: This Perspective focuses on the R&D, regulatory approval and market access phases, with particular attention to oncology medicines, precision medicines, orphan medicines, advanced therapies, repurposed medicines, generics and biosimilars. The authors conducted a narrative review of the peer-reviewed literature, of the grey literature (such as policy documents and reports of consultancy agencies), and of their own research.Results: Health care stakeholders need to consider various initiatives for balancing innovation with access to medicines, which relate to clinical and non-clinical outcomes (e.g. supporting the conduct of pragmatic clinical trials, treatment optimisation and patient preference studies, optimising the use of real-world evidence in market access decision making), value assessment (e.g. increasing the transparency of the reimbursement system and criteria, tailoring the design of managed entry agreements to specific types of uncertainty), affordability (e.g. harnessing the role of generics and biosimilars in encouraging price competition, maximising opportunities for personalising and repurposing medicines) and access mechanisms (e.g. promoting collaboration and early dialogue between stakeholders including patients).Conclusion: Although there is no silver bullet that can balance valuable innovation with affordable access to medicines, (Belgian) policy and decision makers should continue to explore initiatives that exploit the potential of both the on-patent and off-patent pharmaceutical markets.

Background: By improving the affordability and accessibility of biologicals, biosimilar competition provides important benefits to healthcare systems and patients. In Belgium, biosimilar uptake and competition is limited compared to other European markets. Whereas other countries have initiated structured biosimilar introduction or switching plans, no such framework or guiding principles are yet available in Belgium.Objective: This study aims to develop recommendations that can inform policy action in Belgium on biosimilar use, especially in the context of switch decision-making, and this by drawing from the perspectives of healthcare professionals involved in procuring, prescribing, switching and dispensing biologicals including biosimilars.Methods: This study made use of the consensus-building Nominal Group Technique, consisting of a three-step process 1) individual grading, 2) three structured Focus Group Discussions, 3) final individual grading involving an expert group of Belgian healthcare professionals (physician specialists and hospital pharmacists).Results: Participants (n = 13) voiced challenges with the use of biosimilars and switching in practice, and a lack of incentives to use them. Six concrete areas for policy development to support stakeholders with biosimilar use and switch decision-making were identified: 1) address stakeholder hesitations regarding (multiple) switching, 2) provide meaningful incentives, 3) guide healthcare professionals with product decision-making, 4), align practical product modalities when possible, 5) involve healthcare professionals in policy making, and 6) provide practical switch support and patient information material, particularly in the ambulatory care setting. For each area, specific consensus-based recommendations were developed. Furthermore, a set of switch management and patient communication principles was derived, including amongst others, generating buy-in from involved stakeholders prior to switching and communicating with a one-voice message.Conclusion: Without cohesive actions to reduce hurdles and without tangible benefits or steering mechanisms, changes in biosimilar use are unlikely in Belgium. To overcome this and stimulate market competitiveness, this study advances a set of concrete policy recommendations. At large, policy makers should develop an integrated policy framework, with a pro-active, best-value biological implementation roadmap that provides guidance and compelling measures to incentivize healthcare professionals to use biosimilars. Particular consideration should go to the ambulatory care setting, since drivers for biosimilar use are quasi absent in this context.

BackgroundBeyond evaluation and approval, European and national regulators have a key role in providing reliable information on biosimilars and the science underpinning their development, approval, and use.ObjectivesThis study aims to (i) review biosimilar information and guidance provided by EMA and national medicines agencies and (ii) explore stakeholder perspectives on the role of regulators in enabling acceptance and use of biosimilars.MethodsThis study consists of (i) a comparative review of regulatory information and position statements across medicine agencies (n = 32) and (ii) qualitative interviews with stakeholders in Europe (n = 14).ResultsThe comparative analysis showed that regulatory information and guidance about biosimilars offered by national medicines agencies in Europe varies, and is limited or absent in multiple instances. Approximately 40% (13/31) of the national medicines agencies' websites did not offer any information regarding biosimilars, and for about half (15/31) no educational materials were provided. Only less than half of national medicines agencies provided guidance on biosimilar interchangeability and switching (8/31 and 12/31, respectively). Among the national medicines agencies that did offer guidance, the extent (e.g., elaborate position vs. brief statement) and content (e.g., full endorsement vs. more cautious) of the guidance differed substantially. Countries that have a strong involvement in EU level biosimilar regulatory activities generally had more elaborate information nationally. Interviewees underwrote the need for (national) regulators to intensify biosimilar stakeholder guidance, especially in terms of providing clear positions regarding biosimilar interchangeability and switching, which in turn can be disseminated by the relevant professional societies more locally.ConclusionThis study revealed that, despite strong EU-level regulatory biosimilar guidance, guidance about biosimilars, and their use differs considerably across Member States. This heterogeneity, together with the absence of a clear EU-wide position on interchangeability, may instill uncertainty among stakeholders about the appropriate use of biosimilars in practice. Regulators should strive for a clear and common EU scientific position on biosimilar interchangeability to bridge this gap and unambiguously inform policy makers, healthcare professionals, and patients. Furthermore, there is a clear opportunity to expand information at the national level, and leverage EU-developed information materials more actively in this regard.

Background and objectives: Biosimilar medicines have been on the European market for 15 years. Despite the extensive and positive experience with biosimilars across Europe, their uptake remains limited in Belgium. One of the possible factors limiting uptake in clinical practice is the inadequate understanding and lack of trust in biosimilars among patients. This study aimed to assess the level of knowledge and perceptions about biosimilar medicines among Belgian patients in the ambulatory care.Methods: This study consisted of online questionnaires among Belgian patients in the ambulatory care (i.e., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn’s disease, ulcerative colitis, diabetes mellitus type I and II). The results were collected between December 2020 and February 2021. The data were analyzed with descriptive and inferential statistics.Results: In total, 657 patients across all disease areas of interest participated in this study. Only 38% of patients had heard of biosimilars before. Of those patients, most (58%) were aware that biosimilars are as safe and effective as their reference product. The vast majority of respondents (68%) would agree with transitioning to a biosimilar if their physician prescribed it, only 3% would never agree with a transition to a biosimilar. If a physician would propose to change their current originator biological therapy with its biosimilar, nearly all patients (95%) want their physician to explain the decision and inform them. For additional information about biosimilars, Belgian patients prefer brochures or folders (41%), or available resources on the internet (35%). Physicians were indicated as the preferred source of information (95%), followed by pharmacists (51%), academia (39%), and patient associations (35%). Most patients require information regarding the safety and efficacy (78%), price and reimbursement (64%), and the clinical development process (56%) of the biosimilar.Conclusion: Belgian patients require information about biosimilar medicines. However, most patients are open and positive towards transitioning their current biological therapy with its biosimilar if sufficiently supported by their healthcare providers.