In 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 products

Semi-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.

Interviewees 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.

The 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.

Stakeholders in the drug life cycle recognize the importance of integrating patient experience data (PED) into healthcare decision-making. PED includes patient input, patient reported outcomes (PROs), patient reported experiences, and patient preference information. However, it remains unclear if, how, and to what extent PED are used in reimbursement decisions in Belgium.

A document analysis was performed to evaluate and compare the reporting of PED in Belgian reimbursement documents for COVID-19, oncology, and cardiology. Documents of medicinal products that received a European marketing authorization between 1 January 2015 and 30 September 2023 and were reimbursed in Belgium were included. Data were analyzed descriptively and qualitatively.

Preliminary results showed that PED was generally either not reported or not explicitly reported in Belgian reimbursement documents. In some documents, patient reported outcome measures (PROMs) were mentioned. Additionally, few documents stated PROs such as quality of life. PROMs, PROs, and quality of life outcomes appeared in the reimbursement dossier section describing the therapeutic value of the product. From the preliminary findings it seems that PED were more often present in oncology documents. The reimbursement dossiers did not report whether or how PED were used to inform a particular reimbursement decision.

Preliminary findings suggest that PED are not systematically included in Belgian reimbursement documents. To improve transparent submission and reporting of PED in reimbursement dossiers, guidance from reimbursement agencies as well as checklists and evaluation templates are needed.

Patient experience data (PED), encompassing patient preferences (PP), patient-reported outcomes (PROs), and patient input, play a pivotal role in understanding patient needs and informing healthcare decision-making, including reimbursement decisions. This study aimed to assess the current barriers hindering the integration of PED into practice and its particular challenges, opportunities, and concrete policy actions for the systematic implementation of PED.

Semistructured interviews (n=38) were conducted with industry (n=12), non-profit organizations and academia (n=4), regulatory authorities (n=6), health technology assessment (HTA) bodies and reimbursement agencies (n=6), and patient organizations (n=10) in Europe. A thematic analysis was conducted to explore stakeholders’ perspectives and to gain a comprehensive understanding of challenges and opportunities related to the systematic implementation of PED. Interview transcripts were analyzed using the thematic framework analysis to extract and elucidate the insights provided by the diverse stakeholders.

HTA and reimbursement interviewees agreed on the value of including quality-of-life data, particularly when assessed using validated PRO measures. Despite acknowledging the potential of PP, there remained reluctance to integrate PP into reimbursement decision-making. Participants expressed divergent opinions regarding who should collect PED, with some regulators favoring industry, while HTA and reimbursement agencies emphasized transparency and independent PED collection. Limited experience in assessing PED also contributed to hesitancy, underscoring the need for more guidelines, especially at the national reimbursement level. Stakeholders endorsed collaboration through joint scientific consultations, expressing optimism about the impact of the Regulation (EU) 2021/2282 on health technology assessment (HTAR).

This study emphasizes the high potential of PED in informing reimbursement decision-making, fostering a more patient-centered approach. Stakeholder disparities highlight the complexity, necessitating more guidance, scientific robustness, transparency, and collaboration. In light of these stakeholder considerations, the upcoming HTAR holds promise to enhance the systematic implementation of PED, aligning healthcare decision-making with patients’ needs and preferences.

Uncertainty is a fundamental component of decision making regarding access to and pricing and reimbursement of drugs. The context-specific interpretation and mitigation of uncertainty remain major challenges for decision makers. Following the 2021 HTAi Global Policy Forum, a cross-sectoral, interdisciplinary HTAi-DIA Working Group (WG) was initiated to develop guidance to support stakeholder deliberation on the systematic identification and mitigation of uncertainties in the regulatory-HTA interface.

Six online discussions among WG members (Dec 2021–Sep 2022) who examined the output of a scoping review, two literature-based case studies and a survey; application of the initial guidance to a real-world case study; and two international conference panel discussions.

The WG identified key concepts, clustered into twelve building blocks that were collectively perceived to define uncertainty: “unavailable,” “inaccurate,” “conflicting,” “not understandable,” “random variation,” “information,” “prediction,” “impact,” “risk,” “relevance,” “context,” and “judgment.” These were converted into a checklist to explain and define whether any issue constitutes a decision-relevant uncertainty. A taxonomy of domains in which uncertainty may exist within the regulatory-HTA interface was developed to facilitate categorization. The real-world case study was used to demonstrate how the guidance may facilitate deliberation between stakeholders and where additional guidance development may be needed.

The systematic approach taken for the identification of uncertainties in this guidance has the potential to facilitate understanding of uncertainty and its management across different stakeholders involved in drug development and evaluation. This can improve consistency and transparency throughout decision processes. To further support uncertainty management, linkage to suitable mitigation strategies is necessary.

The very high costs of orphan drugs, together with the uncertainties regarding their (cost-)effectiveness raise questions regarding the efficiency and legitimacy of their health technology assessment (HTA) and appraisal process. The aim of the present, qualitative study was to investigate how experts on the reimbursement of these treatments perceive the HTA and appraisal process in their country. Moreover, it aimed to provide specific conditions and practical recommendations for their improvement.

Twenty-two European experts from 19 different countries were included in a qualitative survey and semi-structured interviews. Transcripts were analyzed using the qualitative data analysis software Nvivo. A grounded theory approach was adopted to develop a set of well-defined concepts from the cyclic analysis of the empirical data.

First, analysis of the expert interviews yielded five good practices for an efficient HTA and appraisal of orphan drugs: a high level of transparency, patient involvement, a clear decision-making structure with room for flexibility, mechanisms to minimize bias and an explicit consideration of the opportunity cost. Meanwhile, participants highlighted several barriers to the overall process, such as a lack of trust between the different stakeholders and imbalances in negotiation power. In addition, the results allowed to identify a number of ‘contextual’ determinants that may undermine the legitimacy of the final decision, such as bias and the perverse effects of the orphan drug legislation. Drawing from the experts’ experiences, a toolkit was developed that includes an extensive number of specific recommendations (and conditions) for decision-makers to improve the legitimacy and efficiency of their HTA and appraisal of orphan drugs.

Overall, the results showed that decision-makers should focus on limiting the impact of the contextual determinants rather than improving the methods included in the HTA. This will contribute to further legitimize reimbursement choices for orphan drugs towards the wider public.

Omics technologies enable the measurements of genes (genomics), mRNA (transcriptomics), proteins (proteomics) and metabolites (metabolomics) and thus proved to be valuable tools for personalized decision-making in clinical practice. For their evaluation, a health technology assessment (HTA) framework is not standardized and accepted, yet. Therefore, we aim at designing an omics-technologies HTA evaluation framework to facilitate their assessment, through a mixed-method approach. This work is part of the ExACT project, which aims to produce a range of tools to facilitate the implementation of precision health in clinical practice.

A systematic review was conducted to identify the existing HTA frameworks used for the evaluation of omics-technologies. Desk research on the HTA agencies’ websites was performed to identify the reports on omics-technologies HTA evaluation frameworks used by these agencies. A questionnaire evaluating HTA agencies’ experience on evaluation of omics-technologies was designed. The new framework will be elaborated based on the findings from the three methodological steps, and will be validated through a Delphi process.

Twenty-three articles were included in the systematic review. The main identified HTA frameworks were ACCE and “Evaluation of Genomic Applications in Practice and Prevention” (EGAPP). The desk research showed that these frameworks were seldom used by HTA agencies, which for the evaluation of omics-technologies mostly refer to the HTA Core Model®, mainly assessing the following domains: clinical effectiveness and economic evaluation. Data collection process of the questionnaire HTA agencies’ experience is in progress.

Although two main HTA frameworks for the evaluation of omics-technologies have been identified, these frameworks are sporadically used by HTA agencies in their practice. The particular interest of HTA agencies on clinical effectiveness and economic evaluation, might potentially reflect the uncertainty and difficulties when evaluating omics-technologies. This could indicate that these HTA frameworks are not feasible and practical to be used in routine HTA agency processes for omics technologies, emphasizing the need for a new framework. Our methodological approach might contribute to the development of a new HTA framework, feasible and practical to use not only for HTA agencies.

Precision medicines rely on companion diagnostics to identify patient subgroups eligible for receiving the pharmaceutical product. Until recently, the Belgian public health payer, RIZIV-INAMI, assessed precision medicines and companion diagnostics separately for reimbursement decisions. As both components are considered co-dependent technologies, their assessment should be conducted jointly from a health technology assessment (HTA) perspective. As of July 2019, a novel procedure was implemented accommodating for this joint assessment practice. The aim of this research was to formulate recommendations to improve the assessment in the novel procedure.

This study evaluated the precision medicine assessment reports of RIZIV-INAMI of the last 5 years under the former assessment procedure. The HTA framework for co-dependent technologies developed by Merlin et al. for the Australian healthcare system was used as a reference standard in this evaluation. Criteria were scored as either present or not present.

Thirteen assessment reports were evaluated. Varying scores between reports were obtained for the domain establishing the co-dependent relationship between diagnostic and pharmaceutical. Domains evaluating the clinical utility of the biomarker and the cost-effectiveness performed poorly, whereas the budget impact and the transfer of trial data to the local setting performed well.

Based on these results we recommend three amendments for the novel procedure. (i) The implementation of the linked evidence approach when direct evidence of clinical utility is not present, (ii) incorporation of a bias assessment tool, and (iii) further specify guidelines for submission and assessment to decrease the variability of reported evidence between assessment reports.