PHP293 - Understanding Health Technology Assessment (HTA) Bodies in Major Latin-American (LATAM) Markets: Systematic Evaluation in 5 Latam Countries

INTRODUCTION:Historically, many Health Technology Assessment (HTA) bodies were developed with a focus on addressing rapidly rising drug costs and the unique need to evaluate each drug as a de novo entity. The degree to which the unique needs for evaluating technologies vis a vis drugs are reflected in distinct HTA methods and activity is to date understudied.METHODS:We examined HTA's reviews of two technologies: WATCHMAN™, a device to reduce the risk of stroke in certain patients and Alair™, a procedure-based treatment for severe asthma. Both technologies have been extensively reviewed by HTA bodies and payers in many countries. These HTA reviews are compared to a convenience sample of these HTA's bodies reviews of drugs and qualitative differentiators between these two categories explored.RESULTS:The differences and similarities (for example, in rigor and necessity of evidence) between US Section 510(k) clearances, US premarket approval (PMA), and US new drug application (NDA) regulatory pathways have not been clearly understood by HTA or reflected in their methodologies employed. Additionally, emergent methodologies such as Bayesian statistical analyses may encounter challenges within technologies reviews. HTA bodies may not be cognizant of development timelines or the timelines of comparators. Finally, HTA bodies may overestimate device adoption rates.CONCLUSIONS:The differences in evidence requirements for regulatory approval between US 510(k), US PMA, and US NDA pathways have not been reflected in different methodological approaches within HTA bodies reviews. Opportunities and novel methods are needed for HTA bodies to derive imputed comparisons between technologies that may have inherently incongruent timelines. Finally, HTA bodies could benefit from methods to more accurately estimate projected adoption curves. Challenges exist using frameworks, paradigms, and methodologies initially established for, and commonly used for, pharmaceuticals on device evaluations; leaders of HTA methods can improve the situation by providing guidance and recommendations for more appropriate HTA methods to evaluate devices.

PHP276 - Understanding Health Technology Assessment (HTA) Bodies in Major European Markets: Systematic Evaluation in 10 EU Countries

IntroductionThe National Institute For Health And Care Excellence (NICE) is widely acknowledged as a seminal health technology assessment (HTA) body, known for its transparent and accountable approach to decision-making. This research aimed to investigate the impact of NICE methodology and decisions on international HTA bodies. We sought to identify direct and indirect factors that may influence an international HTA body’s methods or outcomes. To the best of our knowledge, this is the first research to use a qualitative approach to understand the influence of NICE on other HTA bodies.MethodsWe conducted 13 semi-structured qualitative interviews with HTA and market access experts from industry and academia from nine countries (Brazil, Israel, Italy, Japan, Poland, Saudi Arabia, South Korea, Sweden, and the United Arab Emirates). The interview script was organized into three main sections: comparing NICE methods and processes with other HTA bodies; the impact of specific NICE decisions; and Likert scale questions (to allow for comparability of opinions).ResultsMost interviewees believed their local HTA body would consider NICE’s decision when evaluating a medicine. However, the way and extent to which NICE influences HTA varied across countries. The most common means of considering a NICE decision was as background information or context for an HTA evaluation. Generally, interviewees suggested that negative NICE decisions had more impact on local decision-making than positive decisions. Nine of the 13 interviewees agreed or strongly agreed that their country’s HTA body considers the decisions of other HTA bodies in their decision-making process. Eleven of the 13 interviewees agreed or strongly agreed that the development of their country’s HTA body methods and processes was influenced by NICE.ConclusionsNICE is perceived to be a seminal HTA body, with continued influence on HTA agencies in other countries. However, the mechanisms and extent of this influence varies considerably between countries. We suggest that implicit factors are likely to contribute more to NICE’s influence than individual decisions. Nevertheless, further research is needed to reveal these factors and increase efficiency in international HTA decision-making processes.

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.

IntroductionDue to different timing of drug launches across countries, published health technology assessment (HTA) findings from one country may impact HTA outcomes in other countries. The aim of our work was to identify the most influential HTA bodies by analyzing to what extent HTA bodies cross-reference each other in their HTA reports.MethodsWe analyzed the HTA reports on single drug assessments (SDA) published by 46 HTA bodies from 28 countries (and cross-country collaborations) with decision dates between January 2011 and November 2023. We searched the identified HTA reports by using natural language processing and a predefined set of keywords to identify whether, and to what extent, HTA bodies reference each other in their HTA reports. Additionally, we assessed if there is a trend over time in the cross-referencing, and whether any clusters could be identified.ResultsBased on the analysis of 24,793 SDAs, the National Institute for Health and Care Excellence (NICE) was referenced the most (in 4,198 HTA reports across 39 HTA bodies), followed by the Canadian Agency for Drugs and Technologies in Health (in 2,034 reports across 35 HTA bodies), and the Scottish Medicines Consortium (SMC) (in 1,960 reports across 31 HTA bodies). The HTA bodies that most often referenced other HTAs were the Agency for Health Technology Assessment and Tariff System, the Haute Autorité de santé, and NICE. Seven HTA bodies were not referenced in any HTA report, while four did not reference any other HTA body.ConclusionsOur research shows that most of the analyzed HTA agencies not only referenced other HTA bodies in their HTA reports but were also referenced by other HTA bodies. The most often referenced HTA agencies were mostly from English-speaking countries, were well recognized, and had well defined methodologies.

RS3 Evidence, Process or Context? Examining The Factors That Drive Coverage Decisions Of Pharmaceuticals By Health Technology Assessment Bodies In Europe

HS2 - Medication Adherence as a Value Message: A Rarity In Evaluation Assessments Submitted to Major Hta Bodies

Global Access to Chimeric Antigen Receptor (CAR) T-Cell Therapies: Health Technology Assessment (HTA) of CAR T in G7 Countries and Australia

PDG33 Awareness and Consideration of Confidential Listing Agreements in Cost-Effectiveness Evaluation By Health Technology Assessment (HTA) Bodies

PMU108 ASSESSING THE IMPACT OF PATIENT-REPORTED OUTCOMES IN HEALTH-TECHNOLOGY ASSESSMENT

Real-world data (RWD)-derived external controls can be used to contextualize efficacy findings for investigational therapies evaluated in uncontrolled trials. As the number of submissions to regulatory and health technology assessment (HTA) bodies using external controls rises, and in light of recent regulatory and HTA guidance on the appropriate use of RWD, there is a need to address the operational and methodological challenges impeding the quality of real-world evidence (RWE) generation and the consistency in evaluation of RWE across agencies. This systematic review summarizes publicly available information on the use of external controls to contextualize outcomes from uncontrolled trials for all indications from January 1, 2015, through August 20, 2021, that were submitted to the European Medicines Agency, the US Food and Drug Administration, and/or select major HTA bodies (National Institute for Health and Care Excellence (NICE), Haute Autorité de Santé (HAS), Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG), and Gemeinsamer Bundesausschuss (G-BA)). By systematically reviewing submissions to regulatory and HTA bodies in the context of recent guidance, this study provides quantitative and qualitative insights into how external control design and analytic choices may be viewed by different agencies in practice. The primary operational and methodological aspects identified for discussion include, but are not limited to, engagement of regulators and HTA bodies, approaches to handling missing data (a component of data quality), and selection of real-world endpoints. Continued collaboration and guidance to address these and other aspects will inform and assist stakeholders attempting to generate evidence using external controls.

The need to optimize drug development and facilitate faster access for patients has ignited discussions around the importance of improving interactions between health technology assessment (HTA) bodies and regulatory agencies. In this study, we conducted a systematic review to examine processes, progress, outcomes, and challenges of harmonization/interaction initiatives between HTA bodies and regulatory agencies. MEDLINE, EMBASE, and the International Pharmaceutical s database were searched up to 21 October 2019. Searches for gray literature (working papers, commissioned reports, policy documents, etc.) were performed via Google scholar and several institutional websites. An online cross-sectional survey was also conducted among HTA (n = 22) and regulatory agencies (n = 6) across Europe to supplement the systematic review. Overall, we found that while there are areas of divergence, there has been progress over time in narrowing the gap in evidentiary requirements for HTA bodies and regulatory agencies. Most regulatory agencies (4/6; 67%) and half (11/22, 50%) of the HTA bodies reported having a formal link for “collaborating” with the other. Several mechanisms such as early tripartite dialogues, parallel submissions (reviews), adaptive licensing pathways, and postauthorization data generation have been explored as avenues for improving collaboration. A number of pilot initiatives have shown positive effects of these models to reduce the time between regulatory and HTA decisions, which may translate into faster access for patients to life-saving therapies. Thus, future approaches aimed at improving harmonization/interaction between HTA bodies and regulatory agencies should build on these existing models/mechanisms while examining their long-term impacts. Several barriers including legal, organizational, and resource-related factors were also identified, and these need to be addressed to achieve greater alignment in the current regulatory and reimbursement landscape.

P17 Can You Design and Conduct a Real-World Evidence Study That Is Transferable Between HTA Bodies?

As more health technology assessment (HTA) bodies seek to implement patient involvement, there is a desire to learn from other HTA bodies about their experiences and understand what approaches can be used and which ones make a real difference to HTA. This is difficult, as the impact of patient involvement in HTA is not well documented. This study aims to promote further discussion about the ways in which patient involvement can impact HTAs by studying stories of impact. In a multi-stakeholder workshop, experts leading patient involvement in four HTA bodies shared examples of HTAs where they believed patient involvement made a difference, then they reflected on these impact stories within the wider context of impact evaluation. The HTA bodies drew on patient input and patient-based evidence to inform their HTAs. The patient involvement was observed to elucidate patients' experiences, needs and preferences which, in turn, was observed to influence the HTA recommendations about optimal use of technologies, including taking account of issues for sub-groups, outcomes that matter to patients and educational needs. Personal stories of patient involvement may enable a wider understanding of different approaches to and impact of patient involvement. The examples relate to both patient input and patient-based evidence and highlight the role that patient involvement can play in reducing uncertainties and complementing the clinical and economic evidence in HTA. They suggest that impact can be seen in recommendations about how and when a technology is used.

The parallel regulatory-health technology assessment scientific advice (PSA) procedure allows manufacturers to receive simultaneous feedback from both EU regulators and health technology assessment (HTA) bodies on development plans for new medicines. The primary objective of the present study is to investigate whether PSA is integrated in the clinical development programmes for which advice was sought. Contents of PSA provided by regulators and HTA bodies for each procedure between 2010 and 2015 were analysed. The development of all clinical studies for which PSA had been sought was tracked using three different databases. The rate of uptake of the advice provided by regulators and HTA bodies was assessed on two key variables: comparator/s and primary endpoint. In terms of uptake of comparator recommendations at the time of PSA in the actual development, our analysis showed that manufacturers implemented comparators to address both the needs of regulators and of at least one HTA body in 12 of 21 studies. For primary endpoints, in all included studies manufacturers addressed both the needs of the regulators and at least one HTA body. One of the key findings of this analysis is that manufacturers tend to implement changes to the development programme based on both regulatory and HTA advice with regards to the choice of primary endpoint and comparator. It also confirms the challenging choice of the study comparator, for which manufacturers seem to be more inclined to satisfy the regulatory advice. Continuous research efforts in this area are of paramount importance from a public health perspective.