Analytical Methods for Comparing Uncontrolled Trials with External Controls from Real-World Data: a Systematic Literature Review and Comparison to European Regulatory and Health Technology Assessment Practice.

OBJECTIVES: To provide an overview of analytical methods in scientific literature for comparing uncontrolled medicine trials to external controls from individual patient-level real-world data (IPD-RWD). In addition, to compare these methods with recommendations made in guidelines from European regulatory and health technology assessment (HTA) organizations and with their evaluations described in assessment reports. METHODS: A systematic literature review (until March 1st 2023) in PubMed and Connected Papers was performed to identify analytical methods for comparing uncontrolled trials with external controls from IPD-RWD. These methods were compared descriptively to methods recommended in method guidelines and encountered in assessment reports of the European Medicines Agency (2015-2020) and four European HTA organizations (2015-2023). RESULTS: Thirty-four identified scientific articles described analytical methods for comparing uncontrolled trial data to IPD-RWD-based external controls. The various methods covered controlling for confounding and/or dependent censoring, correction for missing data; and analytical comparative modelling methods. Seven guidelines also focused on research design, RWD quality and transparency aspects, and four of those recommended analytical methods for comparisons with IPD-RWD. The methods discussed in regulatory (n=15) and HTA (n=35) assessment reports were often based on aggregate data and lacked transparency due to the few details provided. CONCLUSION: Literature and guidelines suggest a methodological approach to comparing uncontrolled trials with external controls from IPD-RWD similar to target trial emulation, using state-of-the-art methods. External controls supporting regulatory and HTA decision-making were rarely in line with this approach. Twelve recommendations are proposed to improve the quality and acceptability of these methods.

A roadmap towards implementing health technology assessment in Oman.

PURPOSE: Health technologies are advancing rapidly and becoming more expensive, posing a challenge for financing healthcare systems. Health technology assessment (HTA) improves the efficiency of resource allocation by facilitating evidence-informed decisions on the value of health technologies. Our study aims to create a customized HTA roadmap for Oman based on a gap analysis between the current and future status of HTA implementation. DESIGN/METHODOLOGY/APPROACH: We surveyed participants of an advanced HTA training program to assess the current state of HTA implementation in Oman and explore long-term goals. A list of draft recommendations was developed in areas with room for improvement. The list was then validated for its feasibility in a round table discussion with senior health policy experts to conclude on specific actions for HTA implementation. FINDINGS: Survey results aligned well with expert discussions. The round table discussion concluded with a phasic action plan for HTA implementation. In the short term (1-2 years), efforts will focus on building capacity through training programs. For medium-term actions (3-5 years), plans include expanding the HTA unit and introducing multiple cost-effectiveness thresholds while from 6-10 years, publishing of HTA recommendations, critical appraisal reports, and timelines is recommended. ORIGINALITY/VALUE: Although the HTA system in Oman is still in its early stages, strong initiatives are being taken for its advancement. This structured approach ensures a comprehensive integration of HTA into the healthcare system, enhancing decision-making and promoting a sustainable, evidence-based system addressing the population's needs.

Stool-Based Testing for Post-Polypectomy Colorectal Cancer Surveillance Safely Reduces Colonoscopies: The Molecular Stool Testing for Colorectal Cancer Surveillance Study.

BACKGROUND & AIMS: Colonoscopy-based surveillance to prevent colorectal cancer (CRC) causes substantial burden for patients and health care. Stool tests may help to reduce surveillance colonoscopies by limiting colonoscopies to individuals at increased risk of advanced neoplasia. METHODS: This cross-sectional observational study included individuals aged 50-75 years with surveillance indication. Before bowel preparation, participants collected samples for a multitarget stool DNA test and 2 fecal immunochemical tests (FITs). Test accuracy was calculated for all surveillance indications. For the post-polypectomy indication only, which is the most common and is associated with a relatively low CRC risk, long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer model. Stool-based strategies were simulated to tune each test's positivity threshold to obtain strategies at least as effective as colonoscopy surveillance. RESULTS: There were 3453 individuals with results for all stool tests and colonoscopy; 2226 had previous polypectomy, 1003 had previous CRC, and 224 had a familial risk. Areas under the receiver operating characteristic curve for advanced neoplasia were 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test, 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR (Eiken Chemical Co, Tokyo, Japan) and 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold (Sentinel, Milan, Italy). Stool-based post-polypectomy surveillance strategies at least as effective as colonoscopy surveillance reduced the number of colonoscopies by 15%-41% and required 5.6-9.5 stool tests over a person's lifetime. Multitarget stool DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs. CONCLUSIONS: This study found that stool-based post-polypectomy surveillance strategies can be safe and cost-effective, with potential to reduce the number of colonoscopies by up to 41%. CLINICALTRIALS: gov, Number: NCT02715141.

Toward Quantitative Neurology: Sensors to Assess Motor Deficits in Dementia.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder which primarily involves memory and cognitive functions. It is increasingly recognized that motor involvement is also a common and significant aspect of AD, contributing to functional decline and profoundly impacting quality of life. Motor impairment, either at early or later stages of cognitive disorders, can be considered as a proxy measure of cognitive impairment, and technological devices can provide objective measures for both diagnosis and prognosis purposes. However, compared to other neurodegenerative disorders, the use of technological tools in neurocognitive disorders, including AD, is still in its infancy. Objective: This report aims to evaluate the role of technological devices in assessing motor involvement across the AD spectrum and in other dementing conditions, providing an overview of the existing devices that show promise in this area and exploring their clinical applications. Methods: The evaluation involves a review of the existing literature in the PubMed, Web of Science, Scopus, and Cochrane databases on the effectiveness of these technologies. 21 studies were identified and categorized as: wearable inertial sensors/IMU, console/kinect, gait analysis, tapping device, tablet/mobile, and computer. Results: We found several parameters, such as speed and stride length, that appear promising for detecting abnormal motor function in MCI or dementia. In addition, some studies have found correlations between these motor aspects and cognitive state. Conclusions: Clinical application of technological tools to assess motor function in people with cognitive impairments of a neurodegenerative nature, such as AD, may improve early detection and stratification of patients.

Yoga as Potential Therapy for Burnout: Health Technology Assessment Report on Efficacy, Safety, Economic, Social, Ethical, Legal and Organizational Aspects.

PURPOSE OF REVIEW: This health technology assessment aimed to systematically assess the efficacy and safety of yoga as therapy for burnout. Economic, ethical, legal, social and organizational aspects were considered as well. RECENT FINDINGS: Yoga as a therapy has been shown to have positive effects on a range of symptoms, including stress, anxiety and depression. Regarding work-related stress and burnout, the effects of yoga have mainly been examined in a preventative context. Meta-analyses revealed no effects on burnout severity comparing yoga with passive controls in general. Compared with passive controls, yoga had a positive effect on subjective stress. Compared to active control, yoga had an effect on the burnout subscale depersonalization on individual study level. Yoga may have positive effects on burnout, but the results are mixed. Common definitions and standardized diagnostic tools are necessary to improve research and further assess yoga as therapy for burnout. TRIAL REGISTRATION: The HTA is registered with PROSPERO, CRD42022299405, on 6th February 2022.

Is health-related quality of life sufficiently addressed in trials for breast cancer treatments? An assessment based on reimbursement opinions from the French health technology assessment body, 2009-2023.

BACKGROUND: Breast cancer treatments can impact the patients' health-related quality of life (HR-QoL). This criterion is relevant for drug reimbursement decisions. We wanted to assess the usage of HR-QoL in health technology assessments (HTA). METHODS: All HAS (Haute Autorité de Santé, the French HTA body) opinions published between January 1, 2009 and March 31, 2023 for the reimbursement of breast cancer drugs were analysed. RESULTS: 51 distinct appraisals were found during the period, corresponding to 45 product-specific indications, of which 36 (80 %) including clinical studies in which HR-QoL was an endpoint. HAS explicitly rejected HR-QoL data in 25 out of 36 (69 %) indications with such data. Rejections are justified by methodological weaknesses, including lack of adjustment for type I error inflation (n=21 indications), open-label treatment (n=7), lack of a pre-specified clinically relevant HR-QoL threshold (n=6) or missing data (n=6). Regardless of rejection status, HR-QoL results were not mentioned as a determinant of value assessment in 3/36 (8 %) instances (2/25 for rejected data). CONCLUSIONS: HR-QoL data are inconsistently present in HTA assessments of new breast cancer drugs. Their methodological quality often hinders their use in determining the drug's value. POLICY SUMMARY: A rigorous and acceptable comparative experimental framework is expected for HR-QoL assessments. More detail on the precise impact of the absence or presence of HR-QoL data in the determination of the drug's added value could help understanding how this dimension is influential in the assessments.

Development of a Canadian Guidance for Reporting Real-world Evidence for Regulatory and Health-Technology Assessment (HTA) Decision Making.

Real-world evidence (RWE) can complement and fill knowledge gaps from randomized controlled trials to assist in health-technology assessment (HTA) for regulatory decision-making. However, the generation of RWE is an intricate process with many sequential decision points, and different methods and approaches may impact the quality and reliability of evidence. Standardization and transparency in reporting these decisions is imperative to appraise RWE and incorporate it into HTA decision-making. A partnership between Canadian health system stakeholders, namely Health Canada and Canada's Drug Agency (formerly the Canadian Agency for Drugs and Technologies in Health (CADTH)), was established to develop a guidance for standardization of reporting of RWE for regulatory and HTA decision-making in Canada. In this article, we describe the methods to develop the Guidance for Reporting Real-World Evidence document and checklist for reporting RWE for regulatory and HTA decision-making in Canada. This guidance can be adapted for other jurisdictions and will have future extensions to incorporate emerging issues with RWE and HTA decision-making.

Early health technology assessment of gene silencing therapies for lowering lipoprotein(a) in the secondary prevention of coronary heart disease.

BACKGROUND: Olpasiran and pelacarsen are gene-silencing therapies that lower lipoprotein(a). Cardiovascular outcome trials are ongoing. Mendelian randomisation studies estimated clinical benefits from lipoprotein(a) lowering. OBJECTIVE: Our study estimated prices at which olpasiran and pelacarsen, in addition to standard-of-care, would be deemed cost-effective in reducing risk of recurrent coronary heart disease (CHD) events in the Australian healthcare system. METHODS: We developed a decision tree and lifetime Markov model. For olpasiran, participants had CHD and lipoprotein(a) 260 nmol/L at baseline and three-monthly injections, profiled on OCEAN(a) Outcomes trial (NCT05581303). Baseline risks of CHD, costs and utilities were obtained from published sources. Clinical trial data were used to derive reductions in lipoprotein(a) from treatment. Mendelian randomisation study data were used to estimate downstream clinical benefits. Annual discounting was 5 %. For pelacarsen, participants had CHD and lipoprotein(a) 226 nmol/L at baseline and one- monthly injections, profiled on Lp(a) HORIZON (NCT04023552) trial. RESULTS: Olpasiran in addition to standard-of-care saved 0.87 discounted quality-adjusted life years (QALYs) per person. Olpasiran in addition to standard-of-care would be cost- effective at annual prices of AU$1867 (AU$467 per dose) at threshold AU$28,000 per QALY. Pelacarsen would be cost-effective at annual prices of AU$984 (AU$82 per dose). For ICER threshold AU$50,000 per QALY, olpasiran and pelacarsen would be cost-effective at annual prices AU$4207 and AU$2464 respectively. CONCLUSION: This early health technology assessment model used inclusion criteria from clinical trials. Olpasiran and pelacarsen would be cost-effective if annual treatment prices were AU$1867 and AU$984 respectively, from the Australian healthcare perspective.

Silicone adhesive multilayer foam dressings to prevent hospital-acquired sacrum pressure ulcers: An economic evaluation based on a publicly funded pragmatic randomized controlled trial linked with real-world data.

OBJECTIVES: To estimate the cost-effectiveness of sacrum multilayer silicone foam dressings as an adjuvant prophylactic therapy compared to standard pressure ulcer prevention in a hospital population at high risk for pressure ulcer development. METHODS: An economic evaluation is performed from a healthcare payer's perspective. This evaluation is based on a Belgian publicly funded pragmatic randomized controlled trial (RCT), linked with real-world data from administrative claims database and a Belgian cost analysis. A cost-consequences analysis with a one-year time horizon is performed. RESULTS: The RCT has shown that the risk of developing a new pressure ulcer on the sacrum was statistically significantly reduced by 41 % in the treatment group (RR = 0.59, 95 % CI 0.35-0.98, p = 0.04). The absolute risk reduction of 2.0 % (95 % CI -0.1-4.1 %) coincides with a number needed to treat of 50.0 to prevent one new pressure ulcer of category II or worse. The evolution of quality of life is on average negative for patients who developed a pressure ulcer before day 3, while it is positive for patients without pressure ulcers. In a scenario with conservative assumptions, i.e. without inclusion of price discounts for the multilayer silicone foam dressings and only including costs during the hospitalization, pressure ulcer prevention with dressings on the sacrum was already cost-neutral. CONCLUSIONS: The preventive use of silicone adhesive multilayer foam dressings on the sacrum for a population similar to the pragmatic trial population can be supported both from a clinical and economic point of view.

Systematic Review of the Cost of Illness of Parkinson's Disease from a Societal Perspective.

Previous reviews on the cost of illness (COI) of Parkinson's disease (PD) have often focused on health-care costs due to PD, underestimating its effects on other sectors. This systematic review determines the COI of PD from a societal perspective. The protocol was registered in PROSPERO (ID: CRD42023428937). Embase, Medline, and EconLit were searched up to October 12, 2023, for studies determining the COI of PD from a societal perspective. From 2812 abstracts, 17 studies were included. The COI of PD averaged €20,911.37 per patient per year, increasing to almost €100,000 in the most severely affected patients. Health-care costs accounted for 46.1% of total costs, followed by productivity loss (37.4%) and costs to patient and family (16.4%). The COI of PD strongly varied between different geographical regions, with costs in North America 3.6 times higher compared to Asia. This study is the first to identify the relative importance of different cost items. Most important were reduced employment, government benefits, informal care, medication, nursing homes, and hospital admission. There was strong variety in the cost items that were included, with 55.2% of cost items measured in fewer than half of articles. Our review shows that PD-COI is high and appears in various cost sectors, with strong variety in the cost items included in different studies. Therefore, a guideline for the measurement of COI in PD should be developed to harmonize this. This article provides a first step toward the development of such a tool by identifying which cost items are most relevant. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Value based healthcare and Health Technology Assessment for emerging market countries: joint efforts to overcome barriers.

INTRODUCTION: This paper summarizes the results from a forum of healthcare experts, academia representatives, and public agency officials from emerging and established market countries on Value-Based Healthcare (VBHC) and Health Technology Assessment (HTA). Presentations from experts provided insights into current developments and challenges, followed by interactive roundtable discussions. Emerging markets have unique healthcare systems, patient populations, resource constraints and needs. AREAS COVERED: Each roundtable explored specific topics including the role of HTA and Real-world evidence (RWE) in healthcare decision-making, challenges in biosimilar value assessment and incorporating non-price criteria reflecting context-related specifications of emerging markets such as the multifaceted nature of value in healthcare decision-making, emphasizing stakeholder perspectives and system complexities. EXPERT OPINION: RWE emerged as important in understanding biosimilar value recognition and decision-making processes, with insights into its applications and challenges. Recommendations were provided for utilizing Multi-Criteria Decision Analysis (MCDA) in pharmaceutical procurement, particularly for off-patent medicines, underscoring the importance of comprehensive evaluation frameworks and adherence to value-based principles. Overall findings suggest avenues for collaboration between industry, academia, and public agencies to address implementation barriers and promote equitable, efficient, and high-quality healthcare systems in emerging markets through public-private partnerships, joint capacity building and training initiatives, and knowledge transfers.

How to mobilise users' experiential knowledge in the evaluation of advanced technologies and practices in Quebec? The example of the permanent users' and relatives' panel.

INTRODUCTION: With the purpose of supporting scientific professionals and helping them to better integrate the expertise of users in their work, a users' and relatives' panel (URP) was set up at the National Institute for Excellence in Health and Social Services in Quebec (INESSS), Canada for the social services and mental health directorate. URPs are advisory structures that mobilise the experiential knowledge of people affected by various issues. OBJECTIVES: The objective of this study is to assess from a diverse stakeholders' perceptions: (1) the experience of developing and implementing the URP within the context of an Agencies for Health Technology Assessment and Assessment of Social Services (AHTAASS), (2) the contribution of such a URP, (3) the challenges encountered and (4) the perspectives of improvement for the following years. METHODOLOGY: We conducted a qualitative descriptive evaluation study. Nineteen interviews were conducted: six with URP members and 13 with staff representatives. The documents related to the creation of the panel, the URP minutes summarising the discussions and the reports published during that period were collected and analysed. Following a preliminary round of data analysis, a debriefing meeting was conducted with a few participants to validate the results. RESULTS: The panel was set up as part of the INESSS' desire to better integrate experiential knowledge into its recommendations. Twelve projects were presented to the panel on various themes. The URP enabled health professionals to consider dimensions they had not identified, to better integrate the experiential data collected from users into their work and to develop recommendations that made more sense to users. Panel members and INESSS professionals learned to work together, moving the working methods from consultation to collaboration and even coconstruction. Based on the panel's significant contribution, the INESSS decided to maintain it and to strengthen its place in its system to better integrate the experiential knowledge of users into its work. CONCLUSION: This research illustrates how AHTAASS can set up a URP composed exclusively of users, and how it can contribute and be evaluated. It shows that URPs are structures that value the sharing of experiential knowledge of its members, humanise decision-making and give meaning to the work done by scientific professionals. PATIENT OR PUBLIC CONTRIBUTION: One patient-researcher has contributed to the preparation and writing of this manuscript.

The Impact of Additive Population(s), Intervention, Comparator(s), and Outcomes in a European Joint Clinical Health Technology Assessment.

OBJECTIVES: To assess the potential number of European Union (EU) population(s), intervention, comparator(s), and outcomes (PICOs) based on European Network for Health Technology Assessment 21 (EUnetHTA 21) guidance and to explore further evidence-based opportunities to produce more predictable and workable EU PICOs. METHODS: The consolidated EU PICOs of 2 future hypothetical medicines in first-line non-small cell lung cancer (1L NSCLC) and third line multiple myeloma (3L MM) were derived using published health technology assessment reports of 2 recent medicines in similar indications based on EUnetHTA 21 proposed guidance. Sensitivity analysis assessed the impact of additional PICO requests. The number of analyses requested was estimated. RESULTS: In 1L NSCLC and 3L MM, 6 and 9 EU Member States (MS), respectively, had published health technology assessment reports. PICO consolidation resulted in 10 PICOs for 1L NSCLC and 16 PICOs for 3L MM, increasing to 14 and 18 PICOs, respectively, when England's National Institute for Health and Care Excellence scope was included to proxy remaining MS. A minimum of 280 and 720 analyses would be requested, exponentially increasing as additional outcome measures and subgroups are requested. CONCLUSIONS: The PICO approach outlined by EUnetHTA 21 results in a significant number of analysis requests and substantial resources. Use of complementary analyses alongside evidence-based methods to derive PICOs and engaging with the health technology developer throughout the process would create a workable EU PICO that is predictable and most impactful for the EU, resulting in a timely and high-quality assessment report that is more usable at a MS level.

Application of health technology assessment: a new need for an ethical neonatology.

New health technologies are constantly developing. However, their impacts on health and implications for health systems are not always clear. Faced with this situation, in the last 45 years, Health Technology Assessment (HTA) has taken an important role in the decision-making process related to the implementation of technologies in healthcare systems. According to the Core Model® EUnetHTA, a "full HTA" should cover nine domains: health problems and current use of technology, description and technical characteristics, safety, clinical effectiveness, costs and economic evaluation, ethical analysis, organizational aspects, patients and social aspects, legal aspects. In all domains of a HTA, the approach is evidence-based and uses epidemiological data, systematic reviews to gather the best level of proofs regarding clinical efficacy and safety of interventions and comparators and organizational and economic models. One exception is the ethical analysis, that uses value-based approach. Although in Neonatal Intensive Care Units (NICUs) there are highly advanced technological environments, HTA has not yet been widely used in this field for determining the "value" of the diagnostic and therapeutic procedures. An example of diagnostic tool used in NICUs is the near-infrared spectroscopy (NIRS), a noninvasive device that enables real-time monitoring of the condition of peripheral tissues in critically ill newborns. The availability of this diagnostic tool could improve the choice of the most appropriate treatment to the clinical situation of the newborn. The expected benefit of NIRS motivates the need of a full HTA. Conclusion: HTA is still little used in Neonatal Critical Care, but it may be the appropriate tool to determine the "value" of technologies used in this field. The implementation of clinical trials and HTA may help in an evidence-based evaluation of new technologies for the neonatal critical care. This could facilitate the rapid introduction of the best health technologies into clinical practice. What is Known: • Health Technology Assessment (HTA) has taken an important role in the decision-making process related to the implementation of technologies in healthcare systems • The centrality of ethics in HTA has been known. In fact, ethics is everywhere in HTA, and value judgments permeate all levels of HTA What is New: • HTA is still little used in Neonatal Critical Care, but it may be the appropriate tool to determine the "value" of technologies used in this field • The implementation of clinical trials and HTA may help in an evidence-based evaluation of new technologies for the neonatal critical care and in introduction of the best and ethically acceptable health technologies into clinical practice.

Assessing Global Evidence on Cost-Effectiveness to Inform Development of Pakistan's Essential Package of Health Services.

BACKGROUND: Countries designing a health benefit package (HBP) to support progress towards universal health coverage (UHC) require robust cost-effectiveness evidence. This paper reports on Pakistan's approach to assessing the applicability of global cost-effectiveness evidence to country context as part of a HBP design process. METHODS: A seven-step process was developed and implemented with Disease Control Priority 3 (DCP3) project partners to assess the applicability of global incremental cost-effectiveness ratios (ICERs) to Pakistan. First, the scope of the interventions to be assessed was defined and an independent, interdisciplinary team was formed. Second, the team familiarized itself with intervention descriptions. Third, the team identified studies from the Tufts Medical School Global Health Cost-Effectiveness Analysis (GH-CEA) registry. Fourth, the team applied specific knock-out criteria to match identified studies to local intervention descriptions. Matches were then cross-checked across reviewers and further selection was made where there were multiple ICER matches. Sixth, a quality scoring system was applied to ICER values. Finally, a database was created containing all the ICER results with a justification for each decision, which was made available to decision-makers during HBP deliberation. RESULTS: We found that less than 50% of the interventions in DCP3 could be supported with evidence of cost-effectiveness applicable to the country context. Out of 78 ICERs identified as applicable to Pakistan from the Tufts GH-CEA registry, only 20 ICERs were exact matches of the DCP3 Pakistan intervention descriptions and 58 were partial matches. CONCLUSION: This paper presents the first attempt globally to use the main public GH-CEA database to estimate cost-effectiveness in the context of HBPs at a country level. This approach is a useful learning for all countries trying to develop essential packages informed by the global database on ICERs, and it will support the design of future evidence and further development of methods.

Designing a Roadmap for Health Technology Assessment Implementation in Algeria.

Background The scarcity of resources restricts healthcare financing decisions, affecting the population's health. Health technology assessment (HTA) balances restricted budgets with the best possible health outcomes. We aim to characterize the current status of HTA in Algeria and describe the future directions for HTA implementation according to the priorities set by local stakeholders. Methods Stakeholders from the public and private sectors responded to a policy survey about the current and preferred future status of HTA implementation in Algeria. The survey was administered during an online workshop and used a widely accepted international scorecard covering eight domains: capacity building, HTA financing, process and organizational structure, scope of HTA implementation, decision criteria, standardization of methodology, use of local data, and international collaboration. After that, one-on-one interviews with another local expert were conducted to validate and modify the draft recommendations. The interviewees were representatives from government agencies, hospitals, and pharmaceutical companies. Results Thirty-one experts filled out the HTA scorecard survey; most of them were from the public sector (74%). They highlighted that project-based HTA workshops or short courses were the most common form of HTA education in Algeria and recommended the establishment of postgraduate HTA training programs in the future to build sustainable capacities. They reported a lack of funding for HTA research and critical appraisal and recommended an increased public budget for HTA and the introduction of submission fees by manufacturers. There was consensus about the need for local HTA evidence generation in the future. Most of the experts advocated an explicit soft decision threshold. The interviewees further recommended using multi-criteria decision analysis in the short term. The application of quality indicators was believed to improve the reliability of the HTA process. Conclusion The results of our policy research delineate the gap between the current and preferred future status of HTA in Algeria based on insights from multiple stakeholders. The need to improve the educational HTA programs in Algeria, use local data in policy decisions, and increase funding for HTA were the most advocated recommendations.

Market Access Challenges and Solutions in Cell and Gene Therapy in The Netherlands.

With the increasing pipeline of cell and gene therapies (CGTs) and the expected surge in the number of approvals, understanding the market access landscape becomes crucial for timely patient access. This study evaluates the challenges Dutch stakeholders encounter in CGT market access, offering insights for improving time-to-patient access. A traditional literature review was conducted to identify market access challenges and solutions for CGTs. Based on the findings, participants for semi-structured interviews, designed using an interview guide adapted to the Dutch context, were selected to capture diverse perspectives on market access. This review included 124 relevant articles out of 2449, covering several aspects of market access of CGTs. Subsequently, interviews with 16 stakeholders from academia, patient advocacy groups, manufacturers, health insurers, payers, hospital pharmacists, healthcare practitioners, and the Association of Innovative Medicines were conducted. Stakeholders identified challenges and proposed solutions for reimbursement package management, clinical trials, health economics, payment models, and procedural and organisational aspects. Thematic analysis revealed unique country-specific challenges and solutions in the Netherlands. This research provides insights into these challenges and potential solutions, emphasising the need for collaborative efforts among stakeholders to develop practical and multidisciplinary measures to improve the market access landscape for CGTs in the country.

A scoping review of the use of minimally important difference of EQ-5D utility index and EQ-VAS scores in health technology assessment.

OBJECTIVES: Estimates of minimally important differences (MID) can assist interpretation of data collected using patient-reported outcomes (PRO), but variability exists in the emphasis placed on MIDs in health technology assessment (HTA) guidelines. This study aimed to identify to what extent information on the MID of a commonly used PRO, the EQ-5D, is required and utilised by selected HTA agencies. METHODS: Technology appraisal (TA) documents from HTA agencies in England, France, Germany, and the US between 2019 and 2021 were reviewed to identify documents which discussed MID of EQ-5D data as a clinical outcome assessment (COA) endpoint. RESULTS: Of 151 TAs utilising EQ-5D as a COA endpoint, 58 (38%) discussed MID of EQ-5D data. Discussion of MID was most frequent in Germany, in 75% (n = 12/16) of Gemeinsamer Bundesausschuss (G-BA) and 44% (n = 34/78) of Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, (IQWiG) TAs. MID was predominantly applied to the EQ-VAS (n = 50), most frequently using a threshold of > 7 or > 10 points (n = 13). G-BA and IQWiG frequently criticised MID analyses, particularly the sources of MID thresholds for the EQ-VAS, as they were perceived as being unsuitable for assessing the validity of MID. CONCLUSION: MID of the EQ-5D was not frequently discussed outside of Germany, and this did not appear to negatively impact decision-making of these HTA agencies. While MID thresholds were often applied to EQ-VAS data in German TAs, analyses were frequently rejected in benefit assessments due to concerns with their validity. Companies should pre-specify analyses of continuous data in statistical analysis plans to be considered for treatment benefit assessment in Germany.

Development of a Prioritization Framework to Aid Healthcare Funding Decision Making in Health Technology Assessment in Australia: Application of Multicriteria Decision Analysis.

OBJECTIVES: This study develops a prioritization framework to aid healthcare funding decision making in health technology assessment (HTA) in Australia using a multiple criteria decision analysis (MCDA) approach. METHODS: MCDA frameworks for HTAs were reviewed through literature survey to identify the initial criteria and levels within each criterion. Key stakeholders and experts were consulted to confirm these criteria and levels. A conjoint analysis using 1000Minds was undertaken with policy makers from the Department of Health to establish ranking criteria and weighting scores. Monte Carlo simulations were used to examine the sensitivity of findings to factors affecting the ranking and weighting scores. The MCDA was then applied to 6 examples of chronic care models or technologies projects to demonstrate the performance of this approach. RESULTS: Five criteria (clinical efficacy/effectiveness, safety and tolerability, severity of the condition, quality/uncertainty, and direct impact on healthcare costs) were consistently ranked highest by healthcare decision makers. Among the criteria, patient-level health outcomes were considered the most important, followed by social and ethical values. The analyses were robust to inform the uncertainty in the parameter. CONCLUSIONS: This study has developed an MCDA tool that effectively integrates key priorities for HTA reviews, reflecting the values and preferences of healthcare stakeholders in Australia. Although this tool aims to align the assessment process more closely with health benefits, it also highlights the importance of considering other criteria.