Health Technology Assessment Organizations Research Articles

Agreement about Availability of Alternative Treatments for Innovative Drugs Assessed by the EMA and HTA Organizations.

The European Medicines Agency (EMA) and European national/regional health technology assessment (HTA) organizations consider the availability of existing treatments when evaluating a new drug. Since disagreement about the availability of alternative treatments may impact patient access to new drugs, this study aimed to investigate whether the EMA and HTA organizations agreed on the availability of alternative treatments and whether a lack of alternative treatments was associated with HTA organizations' added benefit assessment outcomes. For 97 innovative drugs authorized in 2019-2021 (excluding vaccines and diagnostic tools), assessments by the EMA and AEMPS (Spain), AIFA (Italy), HAS (France), IQWiG/G-BA (Germany), NICE (England and Wales), and ZIN (the Netherlands) were identified. Until 1 June 2022, 429 HTA drug-indication combinations were identified for these 97 drugs, of which 205 exactly matched the EMA's indication. For those, the overall agreement between the EMA and HTA organizations on whether alternative treatments were available was 87%. The agreement of HTA organizations with the EMA on whether available treatments were either pharmacological on-label, pharmacological off-label, or non-pharmacological was 87%, 21%, and 57%, respectively. For all 429 HTA drug-indication combinations, absence of alternative treatments as considered by HTA organizations was associated with a higher chance to provide added benefit: risk ratio 1.8 (95%-CI 1.4-2.3). In conclusion, although there was high overall agreement between the EMA and HTA organizations about whether alternative treatments exist, there were differences in the types of treatment considered. Parallel joint scientific consultations could inform drug developers about relevant alternative treatments to facilitate patient access to innovative drugs.

Advancing the use of real world evidence in health technology assessment: insights from a multi-stakeholder workshop.

Introduction: Real-world evidence (RWE) in health technology assessment (HTA) holds significant potential for informing healthcare decision-making. A multistakeholder workshop was organised by the European Health Data and Evidence Network (EHDEN) and the GetReal Institute to explore the status, challenges, and opportunities in incorporating RWE into HTA, with a focus on learning from regulatory initiatives such as the European Medicines Agency (EMA) Data Analysis and Real World Interrogation Network (DARWIN EU®). Methods: The workshop gathered key stakeholders from regulatory agencies, HTA organizations, academia, and industry for three panel discussions on RWE and HTA integration. Insights and recommendations were collected through panel discussions and audience polls. The workshop outcomes were reviewed by authors to identify key themes, challenges, and recommendations. Results: The workshop discussions revealed several important findings relating to the use of RWE in HTA. Compared with regulatory processes, its adoption in HTA to date has been slow. Barriers include limited trust in RWE, data quality concerns, and uncertainty about best practices. Facilitators include multidisciplinary training, educational initiatives, and stakeholder collaboration, which could be facilitated by initiatives like EHDEN and the GetReal Institute. Demonstrating the impact of "driver projects" could promote RWE adoption in HTA. Conclusion: To enhance the integration of RWE in HTA, it is crucial to address known barriers through comprehensive training, stakeholder collaboration, and impactful exemplar research projects. By upskilling users and beneficiaries of RWE and those that generate it, promoting collaboration, and conducting "driver projects," can strengthen the HTA evidence base for more informed healthcare decisions.

Synthesis of relevant information around non-core domains to support Multi-Criteria Decision Analysis (MCDA) for decision making.

Countries fundamentally base macro and micro decision making in the field of health on economic considerations, the budgetary impact of technologies being a major criterion. Nevertheless, the value of the technology of interest and its dimensions are more complex if we seek to take decisions based on the value itself. The use of structured and explicit approaches that require the assessment of multiple criteria that reflect the dimensions of this value may significantly improve the quality of the decision making. Multi-criteria decision analysis (MCDA) is a complementary decision-making tool that is able to systematically incorporate dimensions or domains such as ethical, organisational, legal, environmental and social considerations, as well as costs and benefits of medical interventions, together with the distinct perspectives of the interested parties. The objective of this article is to propose the implementation of analysis of non-core domains, in reports of Health Technology Assessment (HTA) agencies/units. To assess the scientific evidence on MCDA techniques a systematic review was conducted using structured searches in biomedical databases and websites of various HTA organisations. A consensus group was held using the nominal group technique and involving users of healthcare services, providers, managers and academics. Complementary, a survey was sent to HTA agencies to ascertain the degree of implementation of MCDA in their methods. 42 articles reporting the use of non-core criteria for the assessment of health technologies were included in the analysis. From these articles, a total of 216 non-core criteria were retrieved and categorised into domains by the researchers, and of these, 56 were classified as socioeconomic, 59 as organisational, 10 as legal, 8 as environmental and 47 as ethical, while 36 were considered to relate to other domains. The consensus group, based on the 216 non-core criteria obtained from the systematic review, proposed, and defined 26 criteria that participants considered necessary for decision making in healthcare. The consensus group did not consider that any of the domains should be given more weight than others or that any individual criteria should dominate. These approaches can serve as a framework of reference for a well-structured systematic discussion concerning the basis of individual criteria and the evidence supporting them.

OP109 The Conceptualization And Value Of A Disease Management Approach To HTA In Canada: Findings From A Qualitative Study

IntroductionOur objective was to conceptualize and assess the potential value of a disease management approach to health technology assessment (HTA) in Canada.MethodsWe conducted 18 semi-structured interviews between April 2022 and October 2022 to elicit informant views on potential opportunities for re-conceptualizing the decision-problem in HTA as a disease management problem versus a technology management problem. Participants were purposefully sampled from national and provincial HTA agencies and related organizations in Canada to achieve representation across the disease pathway including prevention, screening, and treatment, and the decision-making pathway including HTA organizations, expert committee members, and decision-makers. Data were analyzed using thematic organizations (based on the interview guide) and manual line by line coding of the data. Ethics approval was received from the Health Sciences Research Ethics Board at the University of Toronto.ResultsThree key features of a disease management approach to HTA (i.e., disease-based, multi-interventional, and dynamic) emerged from informants that differed from traditional HTA processes in Canada. The concept was generally not perceived to be a new idea – some informants indicating that it was implicit in the HTA analysis framework. There was general support for an explicit disease management approach to HTA if the impact of the approach could be demonstrated, if the assessment could be completed within an appropriate time frame, and if the assessment could include the equity, ethical and implementation domains of HTA. Informants indicated that the reconceptualization of HTA could lead to effective and efficient decision-making throughout a technology’s lifecycle, help breakdown system silos, and offer a platform for greater consideration of non-drug alternatives and upstream interventions. The impact of this approach was anticipated to contribute to a proactive health system that could improve population health, enhance the patient experience, and ensure appropriate stewardship of health care resources.ConclusionsA disease management approach to HTA has international relevance as an approach that could promote integrated, proactive, sustainable, and resilient health systems.

PP01 Health Technology Assessment Of Cervical Artificial Disc Replacement: Highlighting The Need For A Consistent International Approach

IntroductionCervical artificial disc replacement (C-ADR) is not a new technology but one that has seen many technological advances in the past 10 years. Indeed, a recent review described total disc arthroplasty as the most innovative development in the history of spinal surgery. The primary goals of C-ADR are to reduce or eliminate pain, and restore normal segmental motion. The aim of this analysis was to identify, extract and examine key health outcomes and economic data from published health technology assessment (HTA) reports on C-ADR, with the aim of understanding how the evolution of this technology has influenced assessments internationally.MethodsA comprehensive search of over 90 HTA organization websites and the INAHTA HTA database using key terms for C-ADR surgical procedures was coupled with a literature search of recent systematic reviews. No language restrictions were applied.ResultsTwenty HTA reports of C-ADR surgery published from 2005 to 2022 were included for review. Several HTAs (4/20) were updates or reassessments by the same agency and one was an update across agencies (Italy update of Belgian HTA). While many of the HTAs concluded C-ADR is as effective as standard care and superior in certain outcomes, there was no pattern or consistency in the conclusions or recommendations from these assessments, even as the evidence base expanded over time. Our analysis found this was largely due to variations in HTA approaches among agencies including: differences in research questions asked, PICO (Population, Intervention, Comparator, Outcomes) criteria and methods performed, such as: rapid versus full systematic reviews; inclusion of economic evaluations and/or budget impact analyses.Indeed, one of the only predictive factors for a positive HTA was a favorable cost-effectiveness analysis.ConclusionsC-ADR is an established technology with extensive HTA investigation internationally. The lack of a consistent approach taken by HTA bodies made prediction of successful HTA outcomes difficult. Future alignment of key evaluation processes and methods may help address current international variations and support consistent decision making on patient access.

MT44 Submission Process and Requirements of Nordic Health Technology Assessment Organisations for Medical Technologies: Results of an Online Survey

MT44 Submission Process and Requirements of Nordic Health Technology Assessment Organisations for Medical Technologies: Results of an Online Survey

Equity in Information Retrieval

Medical librarians and information specialists have unique evidence retrieval skills that can help health technology assessment organizations reduce bias in the evidence they use: They identify gaps in mainstream evidence sources and seek out alternatives that provide the perspectives of underrepresented populations. They create complex and efficient database searches that encompass the wide variety of synonyms and phrases used to describe health disparities and inequities. They use sound, logical, and efficient ways to access evidence from paywalled systems while respecting rights of ownership. They critically appraise information systems to determine if they emphasize biases and inequities or create new ones.

Real-World Persistency for Inflammatory Bowel Disease Biologics Using Patient Registry Data

Abstract Background Although it is a truism that drugs benefit patients only when taken, surprisingly little is known about real-world drug-use persistence and discontinuation, even for expensive biologic drugs. Methods We used longitudinal self-reported drug-use data from the inflammatory bowel disease (IBD) Partners registry of people with IBD to construct Kaplan–Meier drug-use persistency graphs for biologic drug-use spans that started between 2017 and 2022. Results We examined 2034 drug-use spans for 1594 survey participants. Most of the biologic drugs had a 75%+ persistency rate around the one-year mark and 60%+ persistency at the 3-year mark. The overall persistency and the differences in persistency between drugs were aligned with published literature. Conclusions This analysis demonstrates the feasibility of collecting IBD-specific patient-reported drug persistency data via a voluntary patient registry. Patient-reported persistency provides real-world drug persistency data and the patient’s perspectives as to why they discontinued use of the drug—a combination of data and perspective that is not available from any other real-world medical record, claim, and pharmacy data source that are valuable to physician, patients, payers, healthcare policymakers, and health technology assessment organizations.

Increasing transparency in indirect treatment comparisons: is selecting effect modifiers the missing part of the puzzle? A review of methodological approaches and critical considerations.

Failure to adjust for effect modifiers (EMs) in indirect treatment comparisons (ITCs) can produce biased and uncertain effect estimates. This is particularly important for health technology assessments (HTAs), where the availability of new treatments is based on comparative effectiveness results. Much emphasis has been placed on advancing ITC methods to adjust for EMs, yet whether EMs are appropriately identified for the conduct of ITCs in the first place is unclear. To understand the extent of guidance and requirements for the selection of EMs for ITCs currently available and if and how this guidance is applied in practice, a series of pragmatic reviews of guidance documents from HTA and non-payer organizations, primary published ITC analyses, and prior HTA submissions in two indications (non-small cell lung cancer and psoriasis) was conducted. The reviews showed that current ITC guidance mainly focused on developing analytical methods to adjust for EMs. Some organizations, such as HTA bodies in the UK, France and Germany, recommended the use of literature reviews, expert opinion and statistical methods to identify EMs. No detailed guidance on the selection process or the appropriate literature review approach was found. Similar trends were identified through the database search and review of prior HTA submissions; only few published ITCs and submissions included information on the EM selection process which was either based on findings from the literature, trial subgroup analyses, or clinical input. No reference to a systematic selection approach was found. There is an urgent need to fill the guidance gap identified across the reviews by including a step in ITC guidelines on how EMs should be identified through systematic reviews, formal expert elicitation, and a quantitative assessment of the EM distribution. Researchers and manufacturers are also encouraged to improve transparent reporting and justification of their selection of EMs to allow for an independent review of the set of factors being considered for adjustment. Both will contribute toward reducing bias in the ITC results and ultimately increase confidence in decision-making.

Turning CMS into a Health Technology Assessment Organization.

Turning CMS into a Health Technology Assessment Organization.

SA41 Evolving Payer Perception on Patient Centricity and Real-World Evidence: Insights from a Quantitative Survey

Regulatory bodies, including the FDA and EMA, endorse real-world evidence (RWE) as a part of patient-focused drug development, encouraging manufacturers to conduct RWE research. Despite the potential for RWE to strengthen randomized clinical trial (RCT) data, there is notable divergence in how HTA and payer organizations incorporate RWE into their decision-making. This research aimed to understand payer perception and evolution of patient-centric approaches in clinical trials and RWE in health technology assessment (HTA) submissions and payer decision-making.

Added Therapeutic Benefit of Top-Selling Brand-name Drugs in Medicare

The Inflation Reduction Act of 2022 authorizes Medicare to negotiate prices of top-selling drugs based on several factors, including therapeutic benefit compared with existing treatment options. To determine the added therapeutic benefit of the 50 top-selling brand-name drugs in Medicare in 2020, as assessed by health technology assessment (HTA) organizations in Canada, France, and Germany. In this cross-sectional study, publicly available therapeutic benefit ratings, US Food and Drug Administration documents, and the Medicare Part B and Part D prescription drug spending dashboards were used to determine the 50 top-selling single-source drugs used in Medicare in 2020 and to assess their added therapeutic benefit ratings through 2021. Ratings from HTA bodies in Canada, France, and Germany were categorized as high (moderate or greater) or low (minor or no) added benefit. Each drug was rated based on its most favorable rating across countries, indications, subpopulations, and dosage forms. We compared the use and prerebate and postrebate (ie, net) Medicare spending between drugs with high vs low added benefit. Forty-nine drugs (98%) received an HTA rating by at least 1 country; 22 of 36 drugs (61%) received a low added benefit rating in Canada, 34 of 47 in France (72%), and 17 of 29 in Germany (59%). Across countries, 27 drugs (55%) had a low added therapeutic rating, accounting for $19.3 billion in annual estimated net spending, or 35% of Medicare net spending on the 50 top-selling single-source drugs and 11% of total Medicare net prescription drug spending in 2020. Compared with those with high added benefit, drugs with a low added therapeutic rating were used by more Medicare beneficiaries (median 387 149 vs 44 869) and had lower net spending per beneficiary (median $992 vs $32 287). Many top-selling Medicare drugs received low added benefit ratings by the national HTA organizations of Canada, France, and Germany. When negotiating prices for these drugs, Medicare should ensure they are not priced higher than reasonable therapeutic alternatives.

Synergy between health technology assessments and clinical guidelines for multiple sclerosis.

Decision-making for reimbursement and clinical guidelines (CGs) serves different purposes although the decision-criteria and required evidence largely overlap. This study aimed to assess similarities and discrepancies between health technology assessment (HTA) reports as compared to CGs for multiple sclerosis (MS) medicines. All HTA reports and corresponding CGs for MS from the UK, France, Germany, the Netherlands, Poland, Sweden, and the European Union were assessed to identify synergies in recommendations for MS medicines (approved 1995-2020). A content analysis of HTA reports and CGs was performed to identify similarities and discrepancies in wording of treatment recommendations across documents. We assessed 132 HTA reports and 9 CGs for 16 MS treatments. Final recommendations for reimbursement and inclusion in CGs were mostly similar (90%), albeit with considerable differences in treatment lines and subindications. Since 2010, HTA reports refer to the use of CGs in 42% (55/132) and to consultations with clinicians in 43% (57/132) of cases. Six of nine CGs referred to HTA reports and two referred to HTA consultations, in one case having a formal relation to the HTA organization. CGs referenced pharmacoeconomic studies (4/9) for costs and cost-effectiveness. To date, not all new HTA recommendations for MS treatments are included in CGs. Some synergy exists between treatment recommendations in HTA reports and CGs, although discrepancies were seen in timelines and in recommended treatment lines and subindications. More stakeholder dialogue and/or consultation of each other's publications may further improve synergy, facilitate transparency, and enhance patient access.

Health technology assessment of diagnostic tests: a state of the art review of methods guidance from international organizations.

To identify which international health technology assessment (HTA) agencies are undertaking evaluations of medical tests, summarize commonalities and differences in methodological approach, and highlight examples of good practice. A methodological review incorporating: systematic identification of HTA guidance documents mentioning evaluation of tests; identification of key contributing organizations and abstraction of approaches to all essential HTA steps; summary of similarities and differences between organizations; and identification of important emergent themes which define the current state of the art and frontiers where further development is needed. Seven key organizations were identified from 216 screened. The main themes were: elucidation of claims of test benefits; attitude to direct and indirect evidence of clinical effectiveness (including evidence linkage); searching; quality assessment; and health economic evaluation. With the exception of dealing with test accuracy data, approaches were largely based on general approaches to HTA with few test-specific modifications. Elucidation of test claims and attitude to direct and indirect evidence are where we identified the biggest dissimilarities in approach. There is consensus on some aspects of HTA of tests, such as dealing with test accuracy, and examples of good practice which HTA organizations new to test evaluation can emulate. The focus on test accuracy contrasts with universal acknowledgment that it is not a sufficient evidence base for test evaluation. There are frontiers where methodological development is urgently required, notably integrating direct and indirect evidence and standardizing approaches to evidence linkage.

Do France, Germany, and Italy agree on the added therapeutic value of medicines?

The Health Technology Assessment (HTA) of medicines is performed separately at the country level with some differences, but Italy, France, and Germany have implemented price and reimbursement systems strongly focused on the Added Therapeutic Value (ATV). This study investigates the level of agreement on ATV assessments by Agenzia Italiana del Farmaco (AIFA), Haute Autorité de Santé (HAS), and Gemeinsamer Bundesausschuss (G-BA). A database was created collecting all information about drugs with innovativeness status requests in Italy from July 2017 to December 2022 and populated with the corresponding HAS and G-BA ATV assessments. The primary comparative analysis was conducted by grouping the ATV ratings into "higher added value" and "lower or no added value", while a secondary analysis considered the Italian innovativeness status as a criterion to include the quality of evidence assessment. The concordance between ATV assessments was investigated through percentage agreement and unweighted Cohen k-value. 189 medicines/indications were included. The greatest agreement was found when comparing G-BA versus HAS (82 percent; k=0.61, substantial agreement). Lower levels of agreements were observed for AIFA versus HAS and AIFA versus G-BA (respectively 52 percent; k=0.17 and 57 percent; k=0.25). The secondary analysis led to a reconciliation to moderate agreement for AIFA versus HAS (72 percent; k=0.45) and AIFA versus G-BA (74 percent; k=0.47). A high degree of concordance between HTA organizations is reached when considering jointly ATV and quality of evidence, suggesting that the system is extensively mature to make a Joint Clinical Assessment, avoiding duplications and reducing access inequalities.

Are Health Technology Assessments Keeping Pace with Health Equity Priorities: A Review of Existing Approaches and Discussion of Emerging Practices

Health technology assessments are evaluation tools used by decision makers and governing bodies to evaluate the relative effectiveness, safety, and cost of new health technologies. Despite the significant access and reimbursement implications of the decisions informed by health technology assessments, health equity is not consistently included in these assessments. This review explores current health technology assessment approaches using global examples, examines how health technology assessments include health equity considerations, reviews how health equity is not optimally included in health technology assessments using a case study example, and discusses emerging practices to include more health equity related metrics using examples from sponsors and health technology assessment agencies. Results show that health technology assessments do not have a consistent, clearly defined measures of health equity impact or methods to include health equity-oriented measures in assessments. Additionally, most do not provide differentiated value assessments for health equity-oriented data or impact. However, innovators and health technology assessment organizations are presenting new approaches to evaluation. Some outside groups are advocating for change and investing in developing health equity checklists and frameworks for incorporation in health technology assessments. Moving forward, more research is needed to understand how to best incorporate heath equity-oriented measures into health technology assessments and how innovators can get more involved to inform both product development and evaluation efforts. If done well, health technology assessments can be developed to reward technologies and research programs that have a significant and measurable impact on delivering more equitable health outcomes.

Alternatives to the quality-adjusted life year: How well do they address common criticisms?

To analyze whether other outcome measures used in health technology assessment (HTA) address the criticisms of quality-adjusted life years (QALYs). HTA methods guidance from 11 US comparator countries (the G10 and Australia) and six value frameworks from US organizations were reviewed to identify health outcome measures currently used to evaluate the benefits of a drug. The study involved a documentary analysis of guidelines to identify outcome measures used by the sampled HTA organizations. Similar outcomes were grouped together into outcome types. Each type was analyzed to determine the extent to which it replicates key advantages and responds to criticisms of QALYs extracted from the literature. Outcomes were included if guidance from at least one HTA organization identified the outcome as acceptable for HTA. Outcomes measuring or evaluating the benefit, clinical effect, or impact of a drug or health technology was included; methods of calculating costs were excluded. Seven types of outcome measures were identified falling into three groups: preference-based, single-dimension outcomes, and outcomes using non-health perspectives. Among the seven QALY alternative outcome measures currently used for HTA by the sampled countries, no one outcome measure addresses all the QALY criticisms while retaining the advantageous features of the QALY. Proposals to adopt health technology assessment (HTA) to support value-based pricing of prescription drugs in the US have faced pushback over the use of the QALY. There is no single "right" outcome measure, and the criticisms of QALYs apply to other outcome measures used to evaluate health. The measures identified have different features and strengths, which may be appropriate for specific decision making goals, but the QALY remains the best option for decision making that requires comparisons of the overall societal value of health gains.

OP80 ‘Green Metrics’ - Incorporating Environmental Dimensions In Health Technology Assessment

IntroductionClimate change as the result of human action and the risks it poses to human health are well established. In healthcare there is increasing attention to climate and environmental impacts of the use of medical and health technologies. As part of a lifecycle approach, health technology assessment (HTA) needs to take climate and environmental impacts into account. In 2020, the new definition of HTA added the dimension ‘environmental aspects’, with which the value of health technologies can be determined and assessed in terms of their impact on the environment. This led several HTA organizations to explore opportunities for including environmental impacts in HTA procedures. It is, however, yet unclear how many researchers and HTA organizations are already working on this sustainability dimension, in what way, with which (international) partners, and what they have achieved as of now. Furthermore, the complex relations between the climate crisis, environmental pollution, health and care are difficult to trace, and methods are scarce. In HTA, there is an increasing need for outcome measures that, in addition to clinical utility, effectiveness, efficiency or satisfaction, also quantify the environmental impact of medical interventions (i.e., green metrics).MethodsWe report on (i) a scoping of international (research) groups and (HTA) organizations that are working on green metrics; (ii) a literature review into the state of affairs with regard to metrics and methods; and (iii) an impact analysis of possible future inclusion of green metrics in HTA procedures. We supplemented a review of (grey) literature with interviews with HTA organizations pioneering with green metrics, and we have conducted a review of available scientific literature, yielding examples of incorporation of environmental aspects into HTA and reports on practical implications.ResultsCarbon dioxide emissions and pollution by the health sector are currently being explored as green metrics. Differences between direct and indirect environmental impacts complicate the evaluation.ConclusionsGreen metrics should eventually make it possible to assess sustainability in healthcare as part of a lifecycle approach.

OP49 A Systematic Review Of The Activities Of Early Advice, Early Dialogue, Scientific Advice By HTA Doers

IntroductionThere is a range of activities that health technology assessment (HTA) doers have started to improve the process of generation of required evidence for new technologies, and the alignment of regulatory and reimbursement processes that retard the access to patients to them. Different organizations call those processes early advice, early dialogue, or scientific advice to those activities.MethodsWe performed a systematic review of the activities named scientific advice (SA), early advice (EA) and early dialogue (ED). Major databases and HTA organizations were explored. The protocol and search strategy were published in PROSPERO. The selection of final articles and documents was done in pairs, and when discrepancies were found a third person resolved with the consensus of the others. A matrix was used to define the commonalities and differences of the described processes.ResultsWe initially retrieved 949 documents, after the analysis of duplications and the full text reading of the selected ones, we finally selected 39 documents and described: the type of technologies, the process, the stakeholders, the duration, the costs, and the impact. Big HTA agencies such as the Canadian Agency for Drugs and Technologies in Health (CADTH) or the National Institute for Health and Care Excellence (NICE) included EA or SA among their portfolio of activities as well as networks (European Network for HTA (EUnetHTA) or smaller agencies such as HTA Wales or Basque Office for HTA (Osteba) among others. The type of activity, the process, duration, purpose and costs differ among HTA doers.ConclusionsThere is a need to define what we meant when we are talking about SA, ED, and EA. In fact, regulators used the same processes with different purposes. Our systematic review and the lessons learnt from the European-funded SAFENMEDTECH project will propose a detailed framework that can be useful to better understanding the needs of each of the involved parties and how to make the processes involved more efficient.

PP62 Recommendations On Methodologies To Obtain Comparator Efficacy In Health Economic Assessments Of Tumor-Agnostic Drugs

IntroductionGuidance on appropriate methods to obtain a comparator arm for the cost-effectiveness analysis of tumor-agnostic drugs is needed. In recent years, multiple tumor-agnostic drugs have been submitted to health technology assessment (HTA) bodies based on data from single-arm basket trials. These target a specific genetic mutation, as opposed to targeting a specific tumor type. Since HTA bodies are interested in the comparative effectiveness of a treatment, manufacturers have used several methods to obtain a synthetic control arm in their submissions. This study provides an overview of the recommendations by HTA bodies on the methodology to obtain comparator efficacy.MethodsA targeted literature review will be conducted focusing on the methodology used to obtain a comparator arm in the context of tumor-agnostic drugs. The search will cover key HTA organizations; including the National Institute for Health and Care Excellence (NICE), Haute Autorité de Santé (HAS) and the Canadian Agency for Drugs & Technologies in Health (CADTH). Methodologies used in entrectinib and larotrectinib submissions will be extracted. Particular focus will be given on the impact of the applied methodology to the reimbursement decision, as well as key critiques by the HTA bodies. Key search terms will include the following: ‘tumor-agnostic’, ‘histology independent’, ‘HIT’, ‘entrectinib’, ‘larotrectinib’.ResultsAn overview of the results will be presented. These will include the applied methodology for obtaining a comparator arm, critiques and recommendations from HTA bodies, and the impact these methodologies had on the overall reimbursement decision. This will enable comparison of HTA decision-making across regions, and key evidence gaps that need to be further explored.ConclusionsThe results of this study could be useful in the future assessment of tumor-agnostic drug submissions, focusing on the methodology used to obtain comparator efficacy.