Health Technology Assessment Bodies Research Articles

HTA229 Use of Single-Arm Studies for Health Technology Assessment in Portugal

Randomized controlled trials (RCTs) are considered gold standard to determine the efficacy of a new therapy, however, Health Technology Assessment (HTA) bodies recognize situations when this is not possible. For drugs targeting a small patient population and/or in therapeutic areas of high unmet need, the use of single-arm trials, accompanied by indirect treatment comparisons, as the main evidence for HTA submissions is being used as an alternative. This study aims to explore these trends in Portugal and compare them to other European countries.

PD45 Paying For Digital Health: What Evidence Is Needed?

IntroductionDigital transformation has been promoted by the World Health Organization (WHO), Food and Drug Administration (FDA) and the European Commission (EC) to help improve health outcomes. To ensure sustainability, digital health interventions (DHI) require funding by payers. Evidence-informed decision and policy making requires an assessment of the impact on relevant outcomes vs current healthcare practice. Various national and international organizations are involved in creating or guiding the development of standards for the evidence required for digital technologies.MethodsWe undertook an intensive individual investigation of the websites of leading payer and health technology assessment (HTA) bodies in France, UK, Germany, Belgium, Austria, Finland, Canada, Australia, and the USA to identify new frameworks and any updated information. As the objective focused on evaluation frameworks which were used across DHIs by a particular payer to support pricing and reimbursement decisions, we excluded individual case studies where DHIs had been assessed, regulatory frameworks for approval of DHIs and frameworks which assessed feasibility or applicability of a DHI since these were not directly influencing the decision for funding.ResultsWe found six frameworks which directly address digital health interventions for the purposes of pricing and reimbursement: NICE Evidence Standards, FinCCHTA, MSAC, Germany BfArM, Belgium RIZIV and France HAS. The context for the framework and the requirements were compared on parameters including those normally found in HTA and for criteria related to digital technologies. The parameters included varied considerably across the frameworks as did the level of evidence expected to be available for the assessment. In some cases, these related to the level of risk or impact of the intended DHI.ConclusionsWhile DHIs are increasingly used in health, HTA is struggling to adapt to assess these technologies. Due to the multidisciplinary nature of digital health (combination of health care and technology), and the speed and rate of change of innovations in this area, an approach based upon the risk assessment posed by the technology seems reasonable. In this way the level of effort can be tailored to those interventions which seek to influence care or predict outcomes rather than those which are tailored to increased awareness of the patient about their condition.

HTA38 When and How Does RWE Impact HTA Outcomes in Oncology? A Qualitative Evaluation of Case Studies to Identify Drivers of RWE Acceptance Today and in the Future

Understand how different health technology assessment (HTA) bodies perceive and evaluate real world evidence (RWE) in oncology HTA submissions, and identify drivers of RWE acceptance today and in the future.

HTA43 Multi-Country HTA Initiatives Versus National HTA Processes: The Optimal Reimbursement Strategy

Health technology assessment (HTA) plays a crucial role in the reimbursement decision-making process in many countries, but recommendations vary widely throughout jurisdictions, even for the same drug. To harmonise methodological standards and foster collaboration among European HTA bodies, several joint HTA initiatives have been established. Our review aimed to provide a concise overview and comparison of joint HTA and drug price collaborations and to gain an understanding of how these impact pricing and market access.

OP59 The Tunisian Guidelines For Pharmacoeconomic Analysis: What We Need To Know

IntroductionAs a new milestone in health technology assessment (HTA) implementation in Tunisia, L’Instance Nationale de l’Evaluation et de l’Accréditation en Santé (INEAS)—the Tunisian HTA body—published a set of methodological guidelines to support HTA dossier submission by the pharmaceutical industry. Including, ‘guide for submitting clinical data for an HTA at INEAS’, ‘methodological choices guide for pharmacoeconomic analysis at INEAS’, and ‘methodological choices guide for budget impact analysis at INEAS’. We aim to report the major methodological recommendations of the pharmacoeconomic analysis guideline.MethodsThe ‘methodological choices for pharmacoeconomic analysis at INEAS’ guideline was reviewed and the major recommendations were retrieved and reported.ResultsThe reference analysis required by INEAS is the cost-utility analysis systematically combined with a cost-effectiveness analysis (cost per life-year gained) from the public payers’ perspective. The choice of any other type of analysis must be duly justified. Comparators should include alternative treatments which are considered to be ‘the standard of care’ (i.e., interventions routinely used in Tunisia for the same indication) and in which public resources are invested. The time horizon should be sufficiently long to reflect all differences in costs and outcomes. Additionally, a discount rate of 5 percent per year is recommended. The best available evidence for efficacy, safety and quality of life is required. An indirect measure of patient preference, through a validated measurement instrument is preferred for utility calculation. Cost inputs should be identified from Tunisian sources. Health resource utilization should reflect the care pathway in Tunisia. INEAS favors the use of a recognized model. Uncertainty and impact of the input parameters on the results should be assessed and reported through probabilistic and deterministic sensitivity analyses. Model validation tests to assess face validity and internal validity should be performed, and a discussion of the methods used provided. Demonstration of external validity is required. Results should be presented in incremental cost-utility and cost-effectiveness ratios.ConclusionsThe recommendations of ‘methodological choices for pharmacoeconomic evaluation at INEAS’ is an important step to facilitate and harmonize pharmaceutical companies’ submissions and to enhance the use of these analyses in decision-making.

PP148 The Impact Of Health Technology Wales Guidance For Autologous Hematopoietic Stem Cell Transplantation: Two Years Post-Publication

IntroductionEvaluating the impact of health technology assessment (HTA) is vital to measure its contribution to health and social care decision-making and improving citizen outcomes. Health Technology Wales (HTW) is a HTA body committed to evaluating the impact of our work. Here we present HTW’s impact evaluation approach with a case study for autologous hematopoietic stem cell transplantation (AHSCT) for highly active relapsing remitting multiple sclerosis (RRMS).MethodsUsing an outcomes-focused approach based on contribution analysis, HTW has worked with an external evaluation organization to develop a framework to measure the impact of our work. Data on impact was collected from both qualitative and quantitative sources, including social media metrics, surveys, and informal feedback from stakeholders. We engaged with various stakeholders, including clinicians, academics, patient organizations and other HTA bodies.ResultsThe technology appraisal and guidance were published in July 2020, recommending AHSCT for routine adoption to treat highly active RRMS. Patient groups welcomed the appraisal findings as an important step forward in recognising the needs of people with RRMS and felt that “people living with MS were listened to throughout the process”. Following publication online, the guidance has had approximately 500 views, and featured on the MS Trust website and in several news articles. The Welsh Health Specialist Services Committee, a commissioning body in Wales, recommended AHSCT for RRMS as a ‘high priority’ for funding in the WHSSC Integrated Commissioning Plan 2021-22.ConclusionsSince its publication, we have been able to prospectively capture the impact of this guidance through various stakeholders groups and sources. Overall, responses have been positive and the guidance has supported decision makers in Wales. Ongoing evidence capture, including through HTW’s adoption audit processes, will add further understanding to the potential impact of our work.

PD58 Implementation And Assessment Of A Lung Cancer Screening Pilot Project In Québec Through Multi-Stakeholder Collaboration

IntroductionIn 2019, the Québec provincial health technology assessment body (INESSS) recommended that lung cancer screening with low-dose computed tomography (LDCT) be accessible in Québec only within the context of an evaluation in the ‘real-world’ care setting. Based on this recommendation, the ministry of health (MSSS) decided, in 2020, to implement a screening pilot project and to conduct a formal evaluation, partnering with a clinical leader (principal investigator), participating hospitals, the provincial public health agency (INSPQ) and INESSS. The goal of this evaluation is to facilitate decision-making regarding the implementation of a province-wide screening program.MethodsTo support the implementation of the pilot project, algorithms and recommendations were developed to guide management of screening program participants. This material, based on Lung-RADS (Lung Computed Tomography Screening Reporting and Data System of the American College of Radiology), was developed by reviewing the literature and by consulting clinical experts. The evaluation plan proposes various indicators, focusing on six main topics: (i) costs, (ii) screening and investigation processes, (iii) clinical effectiveness and other effects on health, (iv) effects on smoking cessation, (v) organizational impact and (vi) implementation issues.ResultsINESSS has developed 12 algorithms and close to 50 recommendations for lung cancer screening and investigation, a tool for assessing lung cancer risk and a benefits/risks table. For the evaluation of the pilot project, MSSS, INSPQ and INESSS developed more than 100 indicators; short-term indicators are currently being measured and others will follow in the longer term. Since starting in June 2021, the pilot project is progressing well (as of November 28, 2021): 2,365 people have been referred, 1,272 were eligible for screening, 678 have had their first LDCT and 19 were Lung-RADS 4B or 4X. Results on indicators will help the ministry decide on the feasibility of scaling up screening to the provincial level and will highlight aspects to be improved.ConclusionsThis project shows how health technology assessment products can elicit changes in the health system, and how multi-stakeholder collaboration can actively support practice implementation and inform decision-making.

HTA77 The Use and Acceptability of External Comparator Studies to Support Hemato-Oncology Single-Arm Trial Submissions to Health Technology Assessment Bodies

HTA77 The Use and Acceptability of External Comparator Studies to Support Hemato-Oncology Single-Arm Trial Submissions to Health Technology Assessment Bodies

Moral and Social Values in Evidence-Informed Deliberative Processes for Health Benefit Package Design Comment on "Evidence-Informed Deliberative Processes for Health Benefit Package Design - Part II: A Practical Guide".

An evidence-informed deliberative process (EDP) is defined as "a practical and stepwise approach for health technology assessment (HTA) bodies to enhance legitimate health benefit package design based on deliberation between stakeholders to identify, reflect and learn about the meaning and importance of values, informed by evidence on these values." In this commentary, I discuss some considerations for EDPs that arise from acknowledging the difference between social and moral values. First, the best practices for implementing EDPs may differ depending on whether the approach is grounded in moral versus social values. Second, the goals of deliberation may differ when focused on moral versus social values. I conclude by offering some considerations for future research to support the use of EDPs in practice, including the need to assess how different approaches to appraisal (eg, more quantitative versus qualitative) impact perceptions of the value of deliberation itself.

Accounting for vaccines specificities in the Joint Clinical Assessment (JCA): a proposal for guiding principles

Abstract Issue/problem Vaccines are an important public health intervention protecting the population against infectious diseases. The value of vaccines is broad ranging from individual to societal as achieving community immunity protects the unvaccinated, minimizes the risk of outbreaks, reduces the emergence of antimicrobial resistance, and leads to broader societal benefits. Description of the problem Vaccines’ market access processes are characterized by the development of recommendations by NITAGs followed by the assessment of health technology assessment (HTA) bodies in less than half of 27 EU member states. Despite that HTA for therapeutic drugs is well established, there is very limited experience in applying HTA methodologies to vaccines, especially for clinical assessments, as HTA methods and frameworks are traditionally geared toward therapeutics. However, following the adoption of the EU regulation on HTA, Joint Clinical Assessments (JCAs) of vaccines are expected. Results To support a discussion on how to account for vaccine specificities in the JCA, Vaccines Europe has performed a project which aimed at developing a proposal for high-level guiding principles on processes and methodologies for clinical HTA for vaccines. The proposal is informed by findings of literature reviews on currently applied processes, methods, and clinical assessment frameworks of vaccines as well as the outcomes of an advisory board with scientific experts. Lessons A proposal for high-level guiding principles for clinical HTA for vaccines is being developed based on both evidence and the advice from scientific experts which focuses on processes (e.g., horizon scanning, early advice, consideration of vaccine-specific expertise) and methods (e.g., unmet need, safety, efficacy/effectiveness, real-world evidence and technical characteristics of the technology). Lastly, the implementation of vaccines specificities in JCA represents a call for action.

HTA and National Immunisation Program: an overview of competent bodies and of the impact of HTA on the decision-making process

Abstract Issue/problem The WHO has recommended for many years to adopt transparent and standardized methods to decide upon the introduction of vaccines at national level. For this purpose, the Global Vaccine Action Plan has envisaged the establishment of National Immunization Technical Advisory Groups (NITAGs) to issue independent advice relied on the assessment of vaccines efficacy and safety and health technology assessment (HTA). Description of the problem So far, 172 countries worldwide have a NITAG. Despite the growth in the number of NITAGs worldwide and their strengthening following process indicators identified by the WHO, the way how NITAGs issue recommendations and how they are considered in the development of vaccine policy still represent a matter to the attention of the scientific and policy community. Results The evidence shows that assessment frameworks vary across countries. Furthermore, the legal basis and the authority, namely binding or advisory, recognised to them could influence the way how NITAGs work and impact on vaccine policy. Eventually, the final decision is also led by other aspects, including financial and contextual factors that are less standardizable but should be always taken into consideration in health policy. In fact, the final decision on the inclusion of a vaccination into the national immunization program is made by the Ministry of Health also based on the evaluation of HTA bodies working in the country. Lessons Considering the central role of NITAGs in vaccine policy, some efforts should be done in order to make NITAGs more authoritative and collaborative. This could help, from one side, to make the relationship between final decision and NITAGs recommendations clearer and, on other one, to make it possible to have shared and timely evaluations. In this respect, Joint Clinical Assessment envisaged by the new EU regulation on HTA could prepare the way for a more transparent and timely vaccine policy at European level.

Connecting real-world digital mobility assessment to clinical outcomes for regulatory and clinical endorsement-the Mobilise-D study protocol.

BackgroundThe development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility. The overarching objective of the study is to establish the clinical validity of digital outcomes in patient populations impacted by mobility challenges, and to support engagement with regulatory and health technology agencies towards acceptance of digital mobility assessment in regulatory and health technology assessment decisions.Methods/designThe Mobilise-D clinical validation study is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts. The populations of the Innovative Medicine Initiative-Joint Undertaking represent neurodegenerative conditions (Parkinson’s Disease), respiratory disease (Chronic Obstructive Pulmonary Disease), neuro-inflammatory disorder (Multiple Sclerosis), fall-related injuries, osteoporosis, sarcopenia, and frailty (Proximal Femoral Fracture). In total, 17 clinical sites in ten countries will recruit participants who will be evaluated every six months over a period of two years. A wide range of core and cohort specific outcome measures will be collected, spanning patient-reported, observer-reported, and clinician-reported outcomes as well as performance-based outcomes (physical measures and cognitive/mental measures). Daily-living mobility and physical capacity will be assessed directly using a wearable device. These four clinical cohorts were chosen to obtain generalizable clinical findings, including diverse clinical, cultural, geographical, and age representation. The disease cohorts include a broad and heterogeneous range of subject characteristics with varying chronic care needs, and represent different trajectories of mobility disability.DiscussionThe results of Mobilise-D will provide longitudinal data on the use of digital mobility outcomes to identify, stratify, and monitor disability. This will support the development of widespread, cost-effective access to optimal clinical mobility management through personalised healthcare. Further, Mobilise-D will provide evidence-based, direct measures which can be endorsed by regulatory agencies and health technology assessment bodies to quantify the impact of disease-modifying interventions on mobility.Trial registrationISRCTN12051706.

Precision Oncology in Canada: Converting Vision to Reality with Lessons from International Programs.

Canada’s healthcare system, like others worldwide, is immersed in a process of evolution, attempting to adapt conventional frameworks of health technology assessment (HTA) and funding models to a new landscape of precision medicine in oncology. In particular, the need for real-world evidence in Canada is not matched by the necessary infrastructure and technologies required to integrate genomic and clinical data. Since healthcare systems in many developed nations face similar challenges, we adopted a solutions-based approach and conducted a search of worldwide programs in personalized medicine, with an emphasis on precision oncology. This search strategy included review articles published between 1 January 2016 and 1 March 2021 and hand-searches of their reference lists for relevant publications back to 1 December 2005. Thirty-nine initiatives across 37 countries in Europe, Australasia, Africa, and the Americas had the potential to lead to real-world data (RWD) on the clinical utility of oncology biomarkers. We highlight four initiatives with helpful lessons for Canada: Genomic Medicine France 2025, UNICANCER, the German Medical Informatics Initiative, and CANCER-ID. Among the 35 other programs evaluated, the main themes included the need for collaboration and systems to support data harmonization across multiple jurisdictions. In order to generate RWD in precision oncology that will prove acceptable to HTA bodies, Canada must take a national approach to biomarker strategy and unite all stakeholders at the highest level to overcome jurisdictional and technological barriers.

A call to action to harmonize patient-reported outcomes evidence requirements across key European HTA bodies in oncology.

Patient-reported outcome (PRO) data are increasingly being included in Health Technology Assessment (HTA) submissions for oncology drugs. This study aims to provide differences in PRO evidence requirements in oncology across key HTA bodies and calls for its harmonization. Method guidance provided by HTA bodies in Germany, France and the UK, and analysis of HTA reports of 20 oncology case studies were evaluated in this review. Differences exist between HTA bodies regarding guidance on how PRO data should be collected, reportedand analyzed as well as how the data are reviewed and considered in oncology HTAs. HTA bodies can play a key role to harmonize PRO method guidance in collaboration with regulators and sponsors.

Three Approaches to Improve a Practical Guide on Evidence-Informed Deliberative Processes for Health Benefit Package Design Comment on "Evidence-Informed Deliberative Processes for Health Benefit Package Design - Part II: A Practical Guide".

As countries around the world seek to deliver universal health coverage, they must prioritize which services to pay for with public funds, to whom, and at what cost. Countries are increasingly using health technology assessment (HTA) to identify which interventions provide the best value for money and merit inclusion in their health benefit packages (HBPs)-the explicit lists of health services provided using public funds. Oortwijn et al understand the importance of providing practical guidance on the foundation of HBP design, and their article, "Evidence-Informed Deliberative Processes for Health Benefit Package Design - Part II: A Practical Guide," provides recommendations for HTA bodies to improve the legitimacy of their decision-making by incorporating four elements in their HBP procedures: stakeholder involvement, evidence-informed evaluation, transparency, and appeal. This article proposes three approaches to enhance the value of the guide: moving from structure to compliance and performance, prioritizing key issues of legitimacy within HBP processes, and acknowledging potential the costs and risks associated with the use of this framework.

Pricing and Market Access Challenges in the Era of One-Time Administration Cell and Gene Therapies

With a large number of one-time administration cell and gene therapies expected to come to the market in the coming years, there is a renewed need to understand the existing and future challenges that such modalities bring about, especially as it relates to their assessment of value, pricing and access. Payer, health technology assessment (HTA) bodies and manufacturers alike are faced with a number of unprecedented challenges stemming from the fact that such therapies are 'one-time' and/or have curative intent, but often lack sufficient evidence to support such claims at the time of launch (i.e., during pricing and access negotiations). There are a number of different approaches to assessing economic value for cell and gene therapies across regions (e.g., US vs Europe), which ultimately lead to further disconnect in pricing and reimbursement outcomes across countries; yet, in many cases, affordability concerns relating to high upfront costs are raised by providers. To that end, cell and gene therapies have been frequently criticized by payers for their 'high sticker price' based on relatively limited evidence to support durability claims. New contracting solutions are increasingly being employed to overcome concerns specifically relating to the durability of clinical benefit, the comparative effectiveness of a therapy and affordability (i.e., the one-time high cost of therapy). Indeed, recent launches of cell and gene therapies have often leveraged outcome-based agreements, instalments, coverage with evidence generation, subscription models, stop-loss and payer reinsurance, etc. to mitigate concerns from payers and providers and drive access. In this paper, we aim to review challenges for cell and gene therapies from a pricing and access perspective and explore the growing role of innovative contracting solutions to overcome aforementioned challenges.

Challenges and Opportunities for Deliberative Processes for Healthcare Decision-Making Comment on "Evidence-Informed Deliberative Processes for Health Benefit Package Design - Part II: A Practical Guide".

The second edition of the practical guide for evidence-informed deliberative processes (EDPs) is an important addition to the growing guidance on deliberative processes supporting priority setting in healthcare. While the practical guide draws on an extensive amount of information collected on established and developing processes within a range of countries, EDPs present health technology assessment (HTA) bodies with several challenges. (1) Basing recommendations on current processes that have not been well-evaluated and that have changed over time may lead to weaker legitimacy than desired. (2) The requirement for social learning among stakeholders may require increased resourcing and blur the boundary between moral deliberation and political negotiation. (3) Robust evaluation should be based on an explicit theory of change, and some process outcomes may be poor guides to overall improvement of EDPs. This comment clarifies and reinforces the recommendations provided in the practical guide.

3rd Annual International Pharmacoeconomic Forum Highlights.

3rd Annual International Pharmacoeconomic Forum Highlights.

Use of the incremental cost-effectiveness ratio for decision-making policies—what is the problem? A perspective paper

ABSTRACT Introduction Drug reimbursement decisions that spark public controversy are potential signals that processes used to reach such decisions do not adequately reflect society’s goals. Such controversial decisions appear to be a characteristic of Quality-Adjusted Life Year (QALY)-based Incremental Cost Effectiveness Ratio (ICER)-dominated decision-making systems. QALY-based ICER-heavy systems have several known weaknesses that lead to individual and societal preferences being either ignored or considered in an unsystematic and inconsistent manner. Areas covered We reprise some of the key inadequacies of QALY-based ICER analyses and suggest that there are other means including multicriteria decision analysis (MCDA) and cost-benefit analysis based on willingness to pay (WTP) measures by which to partially mitigate these weaknesses. Expert opinion For long, the inadequacies of QALY-based ICER-heavy decision-making systems have been rationalized with the answer: ‘while the method is a second best, it is the best we currently have.’ In light of the equally well-developed and widely utilized alternatives available, this resistance to improve assessment processes should not be accepted by policy makers. Health technology assessment bodies should consider and, with appropriate modifications, adopt these alternatives as they have the potential to result in more comprehensive, systematic, and accountable decision-making.

How are Companion Diagnostics Considered in Economic Evaluations of Oncology Treatments? A Review of Health Technology Assessments.

BackgroundCompanion diagnostic (CDx) testing is increasingly used to identify eligible patients for targeted treatments. Guidance on how CDx testing should be incorporated into cost-effectiveness models (CEM) is limited. This review evaluated how health technology assessment bodies and research organizations considered CDx in CEMs of targeted therapies in oncology and whether this ultimately impacted their decisions or time from regulatory approval to recommendations.MethodsAn exhaustive list of approved CDx tests in oncology was compiled. For corresponding indications and treatments, NICE appraisals published between 2016 and 2019 were identified. Then, assessments for the same treatments issued from 11 other agencies were reviewed. Data extracted included background and CDx information, CDx's role in the CEM, and recommendations.ResultsTwenty-seven NICE appraisals were identified; 15 considered CDx testing in the CEM, while 12 did not, mainly because testing had already been established for the comparators within the same class or in clinical practice from a prior treatment line. Both testing costs and mutation prevalence drove CDx testing costs per patient. The cross-comparison of assessments showed that CDx test characteristics were inconsistently reported. Time from regulatory approval to recommendations was not impacted by CDx cost inclusion in CEMs.ConclusionCDx testing was included in cost-effectiveness models whenever mutation testing was required solely for patients receiving targeted treatment; cost per patient was based on test costs and mutation prevalence. It is unclear if expanded reliance on CDx testing will impact future assessments of targeted therapies. A future update is warranted to track trends over time.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-022-00350-6.