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Introduction: The goal of the Health Technology Assessment (HTA) Regulation 2021/2282 is to establish a more harmonized HTA framework, fostering member states cooperation and enabling equal patient access to innovative health technologies in Europe. This research aimed to assess the impact of the regulation on national HTAs, the strategic implications for health technology developers, and its influence on price and reimbursement negotiations. Methods: A scoping literature review encompassing peer-reviewed literature as well as grey literature was conducted. Between February and March 2023, semi-structured interviews (n = 20) were performed with stakeholders from Belgian governmental institutions, European institutions, advanced therapy medicinal product developers, academics, and sickness funds. The interviews were analyzed using the framework analysis method. Results: Numerous steps, such as the development of implementing acts and procedural guidelines remain to be taken. At member state level, national/regional HTA bodies and payers must act to adopt the new concepts of Joint Scientific Consultations (JSC) and Joint Clinical Assessments (JCA) within their national legislation, as well as revise their timelines and prepare for interactions at a European level. Compiling a harmonized PICO (Population, Intervention, Comparator, and Outcome), adapting local procedures, and increasing capacity to actively take part in the JSC and JCA are seen as primary barriers by several stakeholders. Training and education will help HTA bodies, payers, and health technology developers to participate in the European processes. Conclusion: While practical and legal challenges were identified, recommendations (such as actively preparing for the upcoming changes and increasing capacity while providing training) were provided to adapt national and European procedures to the needs of the HTA Regulation 2021/2282. The importance of fostering collaborations and aligning local HTA procedures with the new way of working set out by the Regulation was demonstrated with this study.

Duchenne muscular dystrophy (DMD) is an X-linked degenerative muscle disease with no curative treatment available to date. The current long-term use of corticosteroids is associated with severe adverse effects. With the progress of promising gene therapy for DMD, this research aims to identify the key characteristics that matter most to patients, develop attributes for a subsequent quantitative preference study, ultimately aimed to inform future market access and clinical decision-making on gene therapy. A literature review was conducted, followed by semi-structured interviews with DMD patients and caregivers to explore their preferences regarding DMD treatment benefits and side effects and gene therapy as a promising treatment option. A ranking exercise helped reveal the most important treatment characteristics, forming the basis for the first step of a structured, four-step attribute and level development process: (1) attribute identification, (2) attribute selection, (3) attribute description, and (4) level development. The forthcoming six attributes and levels were determined by applying six inclusion and exclusion criteria aligned with PREFER guidelines and reaching consensus within an international multidisciplinary advisory board comprising patient representatives, clinicians, and preference method experts. A total of thirteen interviews were conducted with seven DMD patients and eleven caregivers. The literature review and interviews resulted in the identification of 48 unique disease and treatment characteristics. Furthermore, they revealed a high willingness of caregivers of especially younger children to consider gene therapy in a clinical trial setting, and that the primary treatment characteristics valued by patients and caregivers are related to muscle and heart function, and the impact on self-care activities, independence. The final attributes are patient-friendly, clinically relevant and meaningful to patients, with descriptions that are as brief as possible: the type of therapy, effect on life expectancy, risk of life-threatening side effects related to the therapy, years that ventilatory support can be postponed, number of years maintaining current physical functioning, and years and number of patients in which that therapy has been studied. This study identified the treatment characteristics most important to DMD patients and their caregivers and translated them into six key attributes with corresponding levels. It underscores the practical value of qualitative research and patient engagement in ensuring that attributes and level development for future quantitative preference elicitation studies remain clinically relevant and aligned with patient priorities.

New ways of reimbursement for high-cost, one-shot curative therapies such as advanced therapy medicinal products (ATMPs) are a growing area of interest to stakeholders in market access such as industry representatives, legislative and accounting experts, physicians, hospital managers, hospital pharmacists, patient representatives, policymakers, and sickness funds. Due to the complex nature of ATMPs, new payment models and reimbursement modalities are proposed yet not widely applied across Europe. This study aimed to elicit opinions on and insights into the governance aspect of implementing outcome-based spread payments (OBSP) in Belgium for the reimbursement of innovative therapies. Stakeholders' responsibilities and roles were analysed and proposed solutions or general beliefs were assessed to identify necessary or sufficient conditions to establish outcome-based spread payments. Semi-structured interviews (n = 33) were conducted with physicians (n = 2), hospital pharmacists (n = 4), hospital managers (n = 2), Belgian policymakers (n = 6), legislative experts (n = 2), accounting experts (n = 5), representatives of patients (n = 3), of industry (n = 5), and sickness funds (n = 4). The interviews took place between July 2020 and October 2020. The framework method analysis was performed using Nvivo software (version 20.4.1.851). Statements were allocated into six main topics: payment structure, spread payments, outcome-based agreements, governance, transparency, and regulation. Interviews revealed the necessary conditions that, fulfilled together, are seen to be sufficient for the successful implementation of OBSP, including consensus on pricing, payment logistics, robust data infrastructure and financing, clear agreement terms (duration, outcome parameters, payment triggers), long-term patient follow-up solutions, an external multi-stakeholder governance body, and transparency regarding agreement types. Despite the interest, the effective implementation of OBSP falls behind due to a lack of consensus on how this new reimbursement method can be a sustainable solution. By stating the necessary conditions that, when fulfilled together, are deemed sufficient for successful OBSP implementation, this study provides a framework towards overcoming implementation barriers and realizing the potential of OBSP in transforming healthcare reimbursement practices.

Background As new therapies for Duchenne muscular dystrophy (DMD) are entering the market, shared decision making (SDM) will become increasingly important. Therefore, this study aimed to understand (1) Belgian stakeholders’ knowledge and perceptions of SDM in DMD treatment decision making, (2) the current state of SDM implementation in DMD in Belgium, examining the role of all involved parties, and (3) the barriers and facilitators for SDM in DMD in the Belgian context. Methods In this qualitative study, semi-structured interviews with the multidisciplinary team (MDT) of individuals with DMD ( n  = 18) and caregivers thereof ( n  = 11) were conducted in Belgium. Qualitative data was analyzed thematically using the framework method. Results Most caregivers were unfamiliar with the term SDM, while MDT members were aware of it but struggled to define it consistent with existing literature. Despite acknowledging some drawbacks, participants valued SDM as an important process in DMD care, noting its presence in current practice. However, both MDT members and caregivers sometimes questioned the necessity of SDM due to limited treatment options available. Consequently, decision making predominantly relied on (child) neurologists sharing information and seeking consent from caregivers and individuals with DMD for a proposed treatment. Participants highlighted the important role of the MDT, with each professional contributing its unique expertise to SDM. To reduce existing barriers and enhance the SDM process, participants called for clear and transparent information regarding different treatment options, including clinical trials, and detailed information on how treatments might affect patients’ daily life. Conclusion This study identified an increased need for easily understandable information, particularly regarding DMD care in general, but also about clinical trials covering new and emerging therapies. Developing specific evidence-based tools could support stakeholders’ understanding of this information, thereby enhancing implementation of the SDM process in DMD care. Further, as the treatment landscape of DMD evolves, it will become increasingly important for patients to be supported by an MDT, as they can provide information on clinical trials (e.g., study coordinators), emotional support (e.g., psychologists, nurses), and decisional guidance (e.g., neurologist).

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.

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.

Involvement of all relevant stakeholders will be of utmost importance for the success of the developing EU HTA harmonization process. A multi-step procedure was applied to develop a survey across stakeholders/collaborators within the EU HTA framework to assess their current level of involvement, determine their suggested future role, identify challenges to contribution, and highlight efficient ways to fulfilling their role. The 'key' stakeholder groups identified and covered by this research included: patients', clinicians', regulatory, and Health Technology Developer representatives. The survey was circulated to a wide expert audience including all relevant stakeholder groups in order to determine self-perception by the 'key' stakeholders regarding involvement in the HTA process (self-rating), and in a second, slightly modified version of the questionnaire, to determine the perception of 'key' stakeholder involvement by HTA bodies, payers, and policymakers (external rating). Predefined analyses were conducted on the submitted responses. Fifty-four responses were received (patients 9; clinicians: 8; regulators: 4; HTDs 14; HTA bodies: 7; Payers: 5; policymakers 3; others 4). The mean self-perceived involvement score was consistently lower for each of the 'key' stakeholder groups than the respective external ratings. Based on the qualitative insights generated in the survey, a RACI Chart (Responsible/Accountable/Consulted/Informed) was developed for each of the stakeholder groups to determine their roles and involvement in the current EU HTA process. Our findings suggest extensive effort and a distinct research agenda are required to ensure adequate involvement of the key stakeholder groups in the evolving EU HTA process.

IntroductionIn response to the intricate challenges posed by high-cost, one-shot curative therapies, this study explores what hinders the wide implementation of innovative payment schemes across Europe. Drawing insights from the Belgian social healthcare system, this study focused on defining the necessary and sufficient conditions for implementing outcome-based spread payments in the context of market access to advanced medicinal productsMethodsSemi-structured interviews (n=33) were conducted with physicians (n=2), hospital pharmacists (n=4), hospital managers (n=2), patient representatives (n=3), industry representatives (n=5), Belgian policymakers (n=6), sickness fund representatives (n=4), legislative experts (n=2), and accounting experts (n=5) to elicit opinions and insights on stakeholders’ responsibilities and roles, and identify the necessary and sufficient conditions to establish outcome-based spread payments for the reimbursement of innovative therapies. The interviews took place between July 2020 and October 2020. The framework method analysis was performed using NVivo software (version 20.4.1.851). Statements were allocated into six main topics: payment structure, spread payments, outcome-based agreements, governance, transparency, and regulation.ResultsInterviewees across stakeholder groups endorsed the idea of implementing outcome-based spread payments. However, opinions varied on practical and legal feasibility, especially regarding long-term follow-up for patients, data collection burden on physicians, and implications on the financing flow of health technology developers, hospitals, and the government. Concerns were also raised regarding the potential need for new governance structures, enhanced transparency on agreements and pricing mechanisms, as well as defining data requirements to address uncertainties often seen with this type of therapy. All interviewees emphasized the importance of increasing stakeholders’ understanding of these agreements to foster broader acceptance and successful implementation.ConclusionsThe effective implementation of outcome-based spread payments falls behind because consensus on how this reimbursement method can be a sustainable solution is missing. Leveraging the concepts of necessary and sufficient conditions from organizational research, this study provides guidance on resolving challenges and defines stakeholders’ roles for successfully implementing this reimbursement approach.

IntroductionMost shared decision making (SDM) models have been limited to the patient-clinician dyad and do not include nurses. The goal of this study is to investigate nurse’s role in the SDM process in inflammatory bowel disease (IBD), multiple myeloma (MM), and Duchenne muscular dystrophy (DMD).MethodsA comparative analysis was performed, based on three disease-specific qualitative studies using semi-structured interviews with patients (n=25), caregivers (n=11), clinicians (n=18), nurses (n=14), and other members of the multidisciplinary team (n=14) involved in the care pathway of IBD, MM, or DMD patients in Belgium.ResultsAcross disease areas, participants underscored the crucial role of nurses in the SDM process as an accessible point of contact for patients that can provide emotional, informational, and decisional support. Specifically for IBD and MM, nurses’ complementary role to gastroenterologists and haematologists was emphasized, performing the steps of the OPTION instrument that clinicians either did not execute or executed to a lesser extent. However, the allocation of tasks and responsibilities to nurses varied based on the hospital and clinician, thereby influencing the extent of nurses’ role in SDM. In DMD also other members of the multidisciplinary team next to nurses and clinicians had a role in the SDM process (table 1).Discussion and ConclusionResults indicate the need for an increased recognition and a more strengthened role of the nurse in the SDM process. Future research should develop an interprofessional SDM model specific to IBD, MM, and DMD, as it could enhance the multidisciplinary nature of care delivery and its overall quality thereof.Abstract 239 Table 1Different roles in the shared decision making process of the multidisciplinary team involved in the care of individuals with Duchenne muscular dystrophy Leading role Supportive role Informative role Limited role Specialty Neurologist- Child psychologist- Nurse- Study coordinator- Physiotherapist- Social worker- Occupational therapist- Dietitian Task Primary responsibility to inform caregivers/patients, while also ensuring that the rest of the healthcare team is well-informed and able to address any additional questions or concerns caregivers/patients may raise.An intermediary between the neurologist and the patient, facilitating the transmission of questions. Exploring underlying motivations and ensuring that patients and caregivers fully comprehend all information presented.Provision of additional information on clinical trials or on physical aspects of treatments.Have a rather limited influence or involvement in the decision-making process. Supporting quote ‘I am responsible for informing patients. I believe that is my task. And the rest of the team should be well-informed so that they can handle other additional questions, because sometimes questions also come their way. They should be able to handle those and bounce them back to me if there's something they can't answer.’ (M14) ‘I do think it's my role, on one hand, to uncover the motivation behind their choice, but on the other hand, to also verify whether they have truly understood everything the physician explained.’ (M3) ‘Often before starting a treatment, they reach out to me to thoroughly discuss all the specifics, particularly focusing on practical aspects. However, the physician is the one who explains the mechanism of action of that treatment.’ (M12) ‘I see that happening here in our clinic, our physician always engages in conversations with the patients. I often see the physician consulting with study nurses and the physiotherapists.’ … ‘I see it happening regularly. But I myself am not really involved in that.’ (M8)

How alum acts as a vaccine adjuvant continues to perplex. Here Marichal et al . now report that alum induces host cell death and release of genomic DNA, which acts as an endogenous damage-associated molecular pattern that stimulates antibody and T cell responses Aluminum-based adjuvants (aluminum salts or alum) are widely used in human vaccination, although their mechanisms of action are poorly understood. Here we report that, in mice, alum causes cell death and the subsequent release of host cell DNA, which acts as a potent endogenous immunostimulatory signal mediating alum adjuvant activity. Furthermore, we propose that host DNA signaling differentially regulates IgE and IgG1 production after alum-adjuvanted immunization. We suggest that, on the one hand, host DNA induces primary B cell responses, including IgG1 production, through interferon response factor 3 (Irf3)-independent mechanisms. On the other hand, we suggest that host DNA also stimulates 'canonical' T helper type 2 (T H 2) responses, associated with IgE isotype switching and peripheral effector responses, through Irf3-dependent mechanisms. The finding that host DNA released from dying cells acts as a damage-associated molecular pattern that mediates alum adjuvant activity may increase our understanding of the mechanisms of action of current vaccines and help in the design of new adjuvants.