Health Technology Assessment Guidelines Research Articles

Challenges and Opportunities in Interdisciplinary Research and Real-World Data for Treatment Sequences in Health Technology Assessments.

With an ever-increasing number of treatment options, the assessment of treatment sequences has become crucial in health technology assessment (HTA). This review systematically explores the multifaceted challenges inherent in evaluating sequences, delving into their interplay and nuances that go beyond economic model structures. We synthesised a 'roadmap' of literature from key methodological studies, highlighting the evolution of recent advances and emerging research themes. These insights were compared against HTA guidelines to identify potential avenues for future research. Our findings reveal a spectrum of challenges in sequence evaluation, encompassing selecting appropriate decision-analytic modelling approaches and comparators, deriving appropriate clinical effectiveness evidence in the face of data scarcity, scrutinising effectiveness assumptions and statistical adjustments, considering treatment displacement, and optimising model computations. Integrating methodologies from diverse disciplines-statistics, epidemiology, causal inference, operational research and computer science-has demonstrated promise in addressing these challenges. An updated review of application studies is warranted to provide detailed insights into the extent and manner in which these methodologies have been implemented. Data scarcity on the effectiveness of treatment sequences emerged as a dominant concern, especially because treatment sequences are rarely compared in clinical trials. Real-world data (RWD) provide an alternative means for capturing evidence on effectivenessand future research should prioritise harnessing causal inference methods, particularly Target Trial Emulation, to evaluate treatment sequence effectiveness using RWD. This approach is also adaptable for analysing trials harbouring sequencing information and adjusting indirect comparisons when collating evidence from heterogeneous sources. Such investigative efforts could lend support to reviews of HTA recommendations and contribute to synthesising external control arms involving treatment sequences.

Understanding Canadian stakeholders’ views on measuring and valuing health for children and adolescents: a qualitative study

ObjectiveValuing child health is critical to assessing the value of healthcare interventions for children. However, there remain important methodological and normative issues. This qualitative study aimed to understand the views of Canadian stakeholders on these issues.MethodsStakeholders from health technology assessment (HTA) agencies, pharmaceutical industry representatives, healthcare providers, and academic researchers/scholars were invited to attend an online interview. Semi-structured interviews were designed to focus on: (1) comparing the 3-level and 5-level versions of the EQ-5D-Y; (2) source of preferences for valuation (adults vs. children); (3) perspective of valuation tasks; and (4) methods for valuation (discrete choice experiment [DCE] and its variants versus time trade-off [TTO]). Participants were probed to consider HTA guidelines, cognitive capacity, and potential ethical concerns. All interviews were recorded and transcribed verbatim. Framework analysis with the incidence density method was used to analyze the data.ResultsFifteen interviews were conducted between May and September 2022. 66.7% (N = 10) of participants had experience with economic evaluations, and 86.7% (N = 13) were parents. Eleven participants preferred the EQ-5D-Y-5L. 12 participants suggested that adolescents should be directly involved in child health valuation from their own perspective. The participants were split on the ethical concerns. Eight participants did not think that there was ethical concern. 11 participants preferred DCE to TTO. Among the DCE variants, 6 participants preferred the DCE with duration to the DCE with death.ConclusionsMost Canadian stakeholders supported eliciting the preferences of adolescents directly from their own perspective for child health valuation. DCE was preferred if adolescents are directly involved.

Acceptability of Using Real-World Data to Estimate Relative Treatment Effects in Health Technology Assessments: Barriers and Future Steps

ObjectivesEvidence about the comparative effects of new treatments is typically collected in randomized controlled trials (RCTs). In some instances, RCTs are not possible, or their value is limited by an inability to capture treatment effects over the longer term or in all relevant population subgroups. In these cases, nonrandomized studies (NRS) using real-world data (RWD) are increasingly used to complement trial evidence on treatment effects for health technology assessment (HTA). However, there have been concerns over a lack of acceptability of this evidence by HTA agencies. This article aims to identify the barriers to the acceptance of NRS and steps that may facilitate increases in the acceptability of NRS in the future. MethodsOpinions of the authorship team based on their experience in real-world evidence research in academic, HTA, and industry settings, supported by a critical assessment of existing studies. ResultsBarriers were identified that are applicable to key stakeholder groups, including HTA agencies (eg, the lack of comprehensive methodological guidelines for using RWD), evidence generators (eg, avoidable deviations from best practices), and external stakeholders (eg, data controllers providing timely access to high-quality RWD). Future steps that may facilitate future acceptability of NRS include improvements in the quality, integration, and accessibility of RWD, wider use of demonstration projects to highlight the value and applicability of nonrandomized designs, living, and more detailed HTA guidelines, and improvements in HTA infrastructure relating to RWD. ConclusionNRS can represent a crucial source of evidence on treatment effects for use in HTA when RCT evidence is limited.

Assessing medical devices: a qualitative study from the validate perspective.

Our objective was to explore procedures and methods used at health technology assessment (HTA) agencies for assessing medical devices and the underlying views of HTA practitioners about appropriate methodology to identify challenges in adopting new methodologies for assessing devices. We focused on the role of normative commitments of HTA practitioners in the adoption of new methods. An online survey, including questions on procedures, scoping, and assessments of medical devices, was sent to members of the International Network of Agencies for Health Technology Assessment. Interviews were conducted with survey respondents and HTA practitioners involved in assessments of transcatheter aortic valve implantation to gain an in-depth understanding of choices made and views about assessing medical devices. Survey and interview questions were inspired by the "values in doing assessments of health technologies" approach towards HTA, which states that HTA addresses value-laden questions and information. The current practice of assessing medical devices at HTA agencies is predominantly based on procedures, methods, and epistemological principles developed for assessments of drugs. Both practical factors (available time, demands of decision-makers, existing legal frameworks, and HTA guidelines), as well as commitments of HTA practitioners to principles of evidence-based medicine, make the adoption of a new methodology difficult. There is a broad recognition that assessments of medical devices may need changes in HTA methodology. In order to realize this, the HTA community may require both a discussion on the role, responsibility, and goals of HTA, and resulting changes in institutional context to adopt new methodologies.

OP125 How Can Health Technology Assessment Evolve To Better Consider Benefits For Patients, Their Families, And Carers?

IntroductionIn Australia, technical guidelines for the health technology assessment (HTA) of medical technologies do not formally include broader societal benefits in the base case economic evaluation; they are considered supplementary analyses. If what matters to patients is relevant and valuable, then why shouldn’t these broader benefits play a more important role? This presentation will consider the challenges and opportunities for HTA guidelines to change to allow this, and the broader implications for decision makers.MethodsA targeted literature review was undertaken to assess whether economic evaluation methods and their application in HTA are well positioned to assess what matters to patients. Practical challenges for this will be considered, particularly from the perspective of decision makers having a full understanding of broader societal benefits.ResultsPreliminary findings from the literature review suggested that taking a broader societal perspective in economic evaluations used in HTA has the potential to enable more informed decisions for policy makers. However, there are practical considerations regarding consistent approaches to assessing broader societal and patient benefits.ConclusionsFor decision makers to be fully informed on the impact of their decisions beyond healthcare budgets alone, explicit consideration of a societal perspective is necessary. However, for decisions to be equitable across different patient groups, there must be consistency in methodological approaches. Fixing this current limitation should not prevent HTA from giving what matters to patients a central role now, and refining methods on an ongoing basis.

OP66 Adoption Of The World Health Organization Algorithm For Essential Medicines In The Philippine National Formulary Listing Process

IntroductionThe Philippine National Formulary (PNF) System preceded the health technology assessment (HTA) process in the Philippines, which was institutionalized in 2019. The transition led to previously prioritized topics of expert bodies overseeing the PNF System being endorsed to the HTA Council. However, the advent of COVID-19 forced the HTA Philippines to focus on emergency assessment needs and financing recommendations for the national government, resulting in limited capacity to assess non-public health emergency topics. To address this and improve patient access to medicines, we adopted the World Health Organization (WHO) process for evaluating and selecting medicines in the National Essential Medicines List (NEML).MethodsIn assessing the pre-pandemic topics, we matched the population, intervention, comparator, and outcomes of the WHO clinical evidence reviews with those scoped with relevant stakeholders and performed local costing analyses to ensure applicability of findings to the Philippine setting. When needed, we subjected the topics to price negotiation or conducted qualitative assessments.ResultsWe found the method efficient in expediting the decision-making process of the HTA Council. However, given the limited internal capacity of the HTA Philippines to conduct assessments for all ongoing HTA tracks, some of the topics responsive to Universal Health Care will be outsourced to the HTA Research Network, which is yet to be established. There is also a need to improve alignment among the topics being assessed, since the priorities of the proponents, national health program, and national payer have already evolved.ConclusionsIt is important to identify the priority areas for stakeholders as part of the topic nomination process, account for analytic capacity when setting the number of topics for HTA, establish mechanisms to allow proponents to conduct HTAs based on the HTA Council’s methodological standards, and proactively work with the national regulatory agency on horizon scanning and early HTA. We also recommend efficient monitoring, evaluation, and updating of the Philippine HTA guidelines so that they are more responsive to the needs of the healthcare system and the Filipino people.

Development of the Indian Reference Case for undertaking economic evaluation for health technology assessment.

Health technology assessment (HTA) is globally recognised as an important tool to guide evidence-based decision-making. However, heterogeneity in methods limits the use of any such evidence. The current research was undertaken to develop a set of standards for conduct of economic evaluations for HTA in India, referred to as the Indian Reference Case. Development of the reference case comprised of a four-step process: (i) review of existing international HTA guidelines; (ii) systematic review of economic evaluations for three countries to assess adherence with pre-existing country-specific HTA guidelines; (iii) empirical analysis to assess the impact of alternate assumptions for key principles of economic evaluation on the results of cost-effectiveness analysis; (iv) stakeholder consultations to assess appropriateness of the recommendations. Based on the inferences drawn from the first three processes, a preliminary draft of the reference case was developed, which was finalised based on stakeholder consultations. The Indian Reference Case provides twelve recommendations on eleven key principles of economic evaluation: decision problem, comparator, perspective, source of effectiveness evidence, measure of costs, health outcomes, time-horizon, discounting, heterogeneity, uncertainty analysis and equity analysis, and for presentation of results. The recommendations are user-friendly and have scope to allow for context-specific flexibility. The Indian Reference Case is expected to provide guidance in planning, conducting, and reporting of economic evaluations. It is anticipated that adherence to the Reference Case would increase the quality and policy utilisation of future evaluations. However, with advancement in the field of health economics efforts aimed at refining the Indian Reference Case would be needed. This research received no specific grant from any funding agency, commercial, or not-for-profit sectors. The research was undertaken as part of doctoral thesis of Sharma D, who received scholarship from the Indian Council of Medical Research (ICMR), New Delhi, India.

Economic Evaluation of Medically Assisted Reproduction: A Methodological Systematic Review.

Medically assisted reproduction (MAR) is a challenging application area for health economic evaluations, entailing a broad range of costs and outcomes, stretching out long-term and accruing to several parties. To systematically review which costs and outcomes are included in published economic evaluations of MAR and to compare these with health technology assessment (HTA) prescriptions about which cost and outcomes should be considered for different evaluation objectives. HTA guidelines and systematic searches of PubMed Central, Embase, WOS CC, CINAHL, Cochrane (CENTRAL), HTA, and NHS EED. All economic evaluations of MAR published from 2010 to 2022. A predetermined data collection form summarized study characteristics. Essential costs and outcomes of MAR were listed based on HTA and treatment guidelines for different evaluation objectives. For each study, included costs and outcomes were reviewed. The review identified 93 cost-effectiveness estimates, of which 57% were expressed as cost-per-(healthy)-live-birth, 19% as cost-per-pregnancy, and 47% adopted a clinic perspective. Few adopted societal perspectives and only 2% used quality-adjusted life-years (QALYs). Broader evaluations omitted various relevant costs and outcomes related to MAR. There are several cost and outcome categories for which available HTA guidelines do not provide conclusive directions regarding inclusion or exclusion. Studies published before 2010 and of interventions not clearly labeled as MAR were excluded. We focus on methods rather than which MAR treatments are cost-effective. Economic evaluations of MAR typically calculate a short-term cost-per-live-birth from a clinic perspective. Broader analyses, using cost-per-QALY or BCRs from societal perspectives, considering the full scope of reproduction-related costs and outcomes, are scarce and often incomplete. We provide a summary of costs and outcomes for future research guidance and identify areas requiring HTA methodological development. The cost-effectiveness of MAR procedures can be exceptionally complex to estimate as there is a broad range of costs and outcomes involved, in principle stretching out over multiple generations and over many stakeholders.We list 21 key areas of costs and outcomes of MAR. Which of these needs to be accounted for alters for different evaluation objectives (determined by the type of economic evaluation, time horizon considered, and perspective).Published studies mostly investigate cost-effectiveness in the very short-term, from a clinic perspective, expressed as cost-per-live-birth. There is a lack of comprehensive economic evaluations that adopt a broader perspective with a longer time horizon. The broader the evaluation objective, the more relevant costs and outcomes were excluded.For several costs and outcomes, particularly those relevant for broader, societal evaluations of MAR, the inclusion or exclusion is theoretically ambiguous, and HTA guidelines do not offer sufficient guidance.

Toward Best Practices for Economic Evaluations of Tumor-Agnostic Therapies: A Review of Current Barriers and Solutions

ObjectivesCancer therapies targeting tumor-agnostic biomarkers are challenging traditional health technology assessment (HTA) frameworks. The high prevalence of nonrandomized single-arm trials, heterogeneity, and small benefiting populations are driving outcomes uncertainty, challenging healthcare decision making. We conducted a structured literature review to identify barriers and prioritize solutions to generating economic evidence for tumor-agnostic therapies. MethodsWe searched MEDLINE and Embase for English-language studies conducting economic evaluations of tumor-agnostic treatments or exploring related challenges and solutions. We included studies published by December 2022 and supplemented our review with Canadian Agency for Drugs and Technologies in Health and National Institute for Health and Care Excellence technical reports for approved tumor-agnostic therapies. Three reviewers abstracted and summarized key methodological and empirical study characteristics. Challenges and solutions were identified through authors’ statements and categorized using directed content analysis. ResultsTwenty-six studies met our inclusion criteria. Studies spanned economic evaluations (n = 5), reimbursement reviews (n = 4), qualitative research (n = 1), methods validations (n = 3), and commentaries or literature reviews (n = 13). Challenges encountered related to (1) the treatment setting and clinical trial designs, (2) a lack of data or low-quality data on clinical and cost parameters, and (3) an inability to produce evidence that meets HTA guidelines. Although attempted solutions centered on analytic approaches for managing missing data, proposed solutions highlighted the need for real-world evidence combined with life-cycle HTA to reduce future evidentiary uncertainty. ConclusionsTherapeutic innovation outpaces HTA evidence generation and the methods that support it. Existing HTA frameworks must be adapted for tumor-agnostic treatments to support future economic evaluations enabling timely patient access.

HTA71 Transition Probabilities in State-Transition Models: A Synopsis of HTA Guidelines Worldwide

State Transition Models (STMs) are the most common type of models used in the economic evaluation of health technologies. Transition probabilities (TPs) are central to the STMs which determine the movement of patients between the health states. This study aims to identify and summarize the existing Health Technology Assessment (HTA) guidelines around estimating TPs.

National Health Technology Assessment in Turkiye after a decade: Are key principles followed?

Health technology assessment (HTA) is growing in low- and middle-income countries (LMICs) to ensure optimal use of limited resources. However, the impact of HTAs on decision making in LMICs has been limited. The study aimed to provide an overview of Turkiye's progress since establishing the first HTA agency in 2012. The web sites of three national HTA agencies in Turkiye were searched for HTA guidelines and national HTA reports. The HTA guidelines were assessed by two researchers independently against the key principles of HTA developed by Drummond et al., and the HTA reports against the national guidelines. The study included one HTA guideline and eight national HTA reports. The guideline included very limited technical guidance. Compliance with the principles was poor to moderate, and significant methodological limitations were identified. The reports were inconsistent regarding the scope and the HTA assessment criteria. The link between HTA findings, HTA decision making, and health policies were not clear. The inconsistencies between the reports and the methodological limitations demonstrate the need for national HTA guidelines. Improving the characteristics of the HTA might impact implementation. Among the key issues is transparency regarding priority setting, the HTA process, and decision making. Establishing and adopting national HTA guidelines at international standards is needed. Involving external scientific committees and health economists in the HTA processes might help ensure that the key principles of HTA are followed. The study findings might be helpful for countries that are developing their HTA systems.

How is the Societal Perspective Defined in Health Technology Assessment? Guidelines from Around the Globe.

Some researchers have argued that the aim of an economic evaluation should be to offer guidance on resource allocation based on public interest from a societal perspective. The application of a societal perspective in health technology assessment (HTA), while common in many published studies, is not mandated in most countries, and there is limited discussion on what the societal perspective should encompass. This study aimed to systematically compare and contrast the HTA guidelines in different countries. HTA methods guidelines were identified through international HTA networks, such as the Professional Society for Health Economics and Outcomes Research (ISPOR) and Guide to Economic Analysis Research (GEAR). The respective HTA agencies were grouped into two categories: well-established and newly developed, based on the establishment date. Data extracted from the guidelines summarised the methodological details in the reference cases, including specifics on the societal perspective. The database search yielded 46 guidelines, and 65% explicitly considered the societal perspective. The maturity of these agencies is reflected in their attitudes towards the societal perspective; the societal perspective is defined in 73% of the guidelines of well-established agencies and only 56% of those of newly developed agencies. The guidelines from multipayer healthcare systems are more likely to consider the societal perspective. Although most guidelines from the well-established agencies recommend the inclusion of a societal perspective, the types of costs and consequences that should be included and the recommended approaches to valuing them are variable. The direct costs to family and carers were included in 73% of the societal perspective definitions, while non-health outcomes were considered in only 40%. Most HTA guidelines lack clear guidance on what to include under specific perspectives. Considering the recent advancements in economic evaluation methods, it is timely to rethink the role of the societal perspective in HTA guidelines and adopt a more comprehensive perspective to include all costs and consequences of healthcare services.

PP82 First Educational Trainings According To New Health Technology Assessment Guideline For Medicines In Ukraine

IntroductionThe success of the health technology assessment (HTA) implementation depends on the level of communication efficiency between all stakeholders. Taking this into consideration, the leading HTA experts of HTA Department of State Expert Center of the Ministry of Health of Ukraine launched the new educational initiative which includes training programs for pharmaceutical companies.MethodsСomprehensive review of the first developed HTA training programs based on the HTA Guideline (Number 593) “The state health technology assessment for medicines” approved on 29 March 2021 was conducted.ResultsLeading HTA experts of the HTA Department developed a training program, which was conducted for industry representatives according to the provisions of the HTA Guideline. In 2021 over twelve training sessions and two webinars were conducted. These learning events reflect harmonized international recommendations and approaches to HTA training programs, The Professional Society for Health Economics and Outcomes Research, ISPOR short courses in particular, European Network for Health Technology Assessment (EUnetHTA), The National Institute for Health and Care Excellence (NICE), Institute for Clinical and Economic Review (ICER), Agency for Health Technology Assessment and Tariff System (AOTMiT) guidelines. Two-hour webinars were aimed at giving theoretical and practical bases for building a Markov model with the help of Excel and TreeAge Software. Training sessions titled “HTA as a tool for assessing the value of health technology” differ by duration (7-hour, 4-hour, 3-hour) and cover core topics adapted to the needs of the audience. The main program components include HTA Roadmap in Ukraine, clinical section, economic section and practical case studies of building a Markov model. All training options included questionnaires at the beginning and i end to assess the quality of each program. Questionnaires are the tool that gives presenters the possibility to trace progress and transform the training material accordingly.ConclusionsDevelopment of extended capacity building programs in HTA for users and doers is highly prospective for further steps in HTA institutionalization in Ukraine.

Value Set for the EQ-5D-Y-3L in Hungary.

BackgroundThe Hungarian health technology assessment guidelines recommend the use of the EuroQol instrument family in quality-adjusted life-year calculations. However, no national value set exists for the EQ-5D-Y-3L or any other youth-specific instrument.ObjectiveThis study aims to develop a national value set of the EQ-5D-Y-3L for Hungary based on preferences of the general adult population.MethodsThis study followed the international valuation protocol for the EQ-5D-Y-3L. Two independent samples, representative of the Hungarian general adult population in terms of age and sex were recruited to complete online discrete choice experiment (DCE) tasks and composite time trade-off (cTTO) tasks by computer-assisted personal interviews. Adults valued hypothetical EQ-5D-Y-3L health states considering the health of a 10-year-old child. DCE data were modelled using a mixed logit model with random-correlated coefficients. Latent DCE utility estimates were mapped onto mean observed cTTO utilities using ordinary least squares regression.ResultsOverall, 996 and 200 respondents completed the DCE and cTTO surveys, respectively. For each domain, the value set resulted in larger utility decrements with more severe response levels. The relative importance of domains by level 3 coefficients was as follows: having pain or discomfort > feeling worried, sad or unhappy > mobility > doing usual activities > looking after myself. Overall, 12.3% of all health states had negative utilities in the value set, with the worst health state having the lowest predicted utility of − 0.485.ConclusionThis study developed a national value set of the EQ-5D-Y-3L for Hungary. The value set enables to evaluate the cost utility of health technologies for children and adolescents based on societal preferences in Hungary.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40273-022-01190-2.

HTA29 Value Assessment Framework of Therapeutic Medical Devices in China - Based on Seven-Country Health Technology Assessment Guidelines

Compared to pharmaceuticals, it is more difficult to conduct HTA for medical devices (MDs) due to different efficacy dynamics and unique product life cycles. HTA methodology and guidance in China have not been established yet, while recent policies have implied the use of HTA in MDs, especially in the therapeutic medical devices (TMDs) in following years. It is important to design the HTA framework in China.

P57 Mapping Quality of Life - Alzheimer's Disease (QOL-AD) Scores to EQ-5D-5L Utilities in the Ambar Trial Population

Health state utilities are required to model the cost/benefit of novel treatments in accordance with Health Technology Assessment guidelines. The AMBAR phase 2b/3 trial (NCT01561053) evaluated the efficacy and safety of plasma exchange with albumin replacement in mild-to-moderate Alzheimer’s disease (AD) patients. Health-related quality of life was measured through the disease-specific Quality of Life - Alzheimer’s disease (QoL-AD) questionnaire. EQ-5D-5L utilities were estimated from AMBAR QoL-AD data using a validated mapping algorithm developed by Rombach et al.

Methodological Approaches to Cost-Effectiveness Analysis in Saudi Arabia: What Can We Learn? A Systematic Review.

ObjectiveThe recent establishment of the health technology assessment (HTA) entity in the Kingdom of Saudi Arabia (KSA) has resulted in increased interest in economic evaluation. The aim of this study is to evaluate the technical approaches used in published economic evaluations and the limitations reported by the authors of the respective studies that could affect the ability to perform economic evaluations in the KSA.MethodsWe conducted a systematic literature review of published economic evaluations performed for the KSA over the past 10 years. An electronic literature search of the PubMed, EMBASE, and Cochrane databases was performed. A CHEERS checklist was used to assess the quality of reporting. Reported limitations were classified into domains including the definition of perspectives, identification of comparators, estimation of costs and resources, and use of the incremental cost-effectiveness ratio threshold.ResultsTwelve evaluations were identified; most involved cost-effectiveness analysis (92%). Missing and unclear data were found within the CHEERS criteria. Regardless of the perspective used, most described the perspective as an “institutional” perspective (70%) and almost half were reclassified by the current reviewer (42%). Most did not clearly state the comparator (83%), and published model comparators were commonly used (50%). Resource estimation was mostly performed by the authors of the respective studies (67%), and costs were mostly obtained from hospital institutional data (75%). The lack of an established threshold for the country-specific willingness to pay was observed in 50% of the analyses.ConclusionsEconomic evaluations from the KSA are limited. Capacity building and country-specific HTA guidelines could improve the quality of evaluations to better inform decision making.HighlightsEconomic analysis of health technology should follow standard guidelines. Unfortunately, these guides are often underutilized, and our findings identify considerable missing, not clearly stated, or incomplete data within the analyses, which can weaken the impact of the recommendations.The limitations reported by the authors of the respective studies emphasize the suboptimal quality of the reporting. A lack of data was frequently identified and resulted in using “institutional” practice as a major source of data input for the analyses.In light of the call for the establishment of an HTA entity in the KSA, framing a standard analytic approach when conducting economic evaluations will support HTA in informing resource allocation decisions. We hope that our findings highlight the need for country-specific guidance to improve practice and enhance future research.

POSA280 Using Artificial Intelligence and Machine Learning to Inform Evidence Development for Optimising HTA Outcomes in Europe

Biopharmaceutical companies prepare for European Health Technology Assessment (HTA) submission of their products by understanding HTA guidelines and looking at past analogue examples, supplemented with primary market research. This work explores the application of advanced analytics techniques including AIML (artificial intelligence and machine learning) and their potential to improve understanding of submission factors leading to specific HTA outcomes.

Review and Assessment of Patient-Reported Outcomes (PRO) in Patients with Chemotherapy-Induced Anemia (CIA)

OBJECTIVES: Chemotherapy-induced anemia (CIA) is a common adverse event of cancer treatment and is associated with several symptoms that negatively impact health-related quality of life (HRQoL). Due to the nature of CIA signs and symptoms, the use of fit-for-purpose PRO measures reflecting patients' experience of the disease and its treatment is an important step in drug development and evaluation. In this project, we aimed to review and assess the most commonly used PRO measures to best capture the experiences of patients with non-myeloid malignancies.METHODS: A targeted literature review (TLR), including searches of the OVID database, US FDA/European Medicines Agency (EMA), clinical trial databases, regulatory labelling data and health technology assessment (HTA) reports/payer landscape recommendations, was conducted to identify PRO measures used to capture symptoms and HRQoL outcomes in non-myeloid cancer patients with CIA (2008-2021). PRO measures were identified from published studies, phase 2-4 clinical trials, and categorized according to the concept(s) measured and cancer type. Study outcomes were used to determine the optimal PRO strategy to capture the CIA symptoms of patients with non-myeloid cancer. The concepts captured from PROs identified in the TLR were used to develop a preliminary ‘conceptual model’: a graphical representation of signs and symptoms, and the perceived impact on HRQoL.Selected PRO measures, most relevant to the study objectives, were evaluated for their reliability, validity, responsiveness, and extent to which they cover HRQoL domains of interest and, in relation to the current regulatory environment, industry standards and guidance (e.g., FDA Guidance For Industry: Patient-Reported Outcome Measures, 2009). Reviews of the HTA guidelines and reports were conducted to provide insights into the applicability of PRO data from an HTA perspective.RESULTS: The conceptual model captured fatigue as the most important disease-related symptom experienced by non-myeloid cancer patients with CIA (Figure). The OVID search identified 17 PRO measures, which were then categorized by the key CIA-related concepts they assessed, including: sleep quality; HRQoL; anemia-related symptoms; depression/anxiety; and work productivity/activity impairment. The most frequently used PRO was the Functional Assessment of Cancer Therapy-Fatigue (FACT-F, N=11), followed by the FACT-Anemia (FACT-An, N=6). Ten PRO measures were identified from Phase 2-4 ongoing/completed US clinical trials and 6 PROs from EU clinical trials, with FACT-F (N=13) being the most common instrument used . FDA and EMA HRQoL-related product labelling information included the FACT-An, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Cancer Linear Analogue Scale (CLAS).From the TLR results, 9 PRO measures were selected for further review: FACT-An (An, Anemia); FACT-F; FACT-G (G, General); Functional Assessment of Chronic Illness Therapy-F; Patient-reported Outcomes Measurement Information System-F; Brief Fatigue Inventory; Visual Analogue Scale-F; Fatigue Symptom Inventory; and EORTC QLQ-C30. Of these, FACT-An was the only PRO measure specifically developed to measure fatigue and HRQoL in anemic cancer patients. FACT-An includes four HRQoL domains (assessing physical, social/family, emotional and functional wellbeing) from the FACT-G, plus an anemia subscale that comprises a fatigue subscale (13 items) and 7 anemia-specific questions.Results from the HTA/payer landscape review also indicated that the majority of recent HTA submissions reported findings from EORTC QLQ-C30 alongside the EORTC disease-specific adaptations for oncology-related indications and the EQ-5D. Many of the recent HTAs reported data from 2 or more different PRO measures.CONCLUSIONS: CIA impacts various aspects of patients' HRQoL; however, current PRO measures may only partially capture concepts of interest to patients. Multiple measures may be needed to adequately reflect all domains affected by CIA. Future studies may consider conducting concept elicitation interviews with patients and clinicians, to inform future updates to the conceptual model, and validation work to estimate meaningful change thresholds for these measures if not available. [Display omitted] DisclosuresMorga: Astellas Pharma Europe Ltd.: Current Employment. Atzinger: Astellas Pharma Inc.: Current Employment. Barsdorf: Clinical Outcomes Solutions: Current Employment. New: IQVIA: Current Employment. Alexandre: Astellas Pharma Europe B.V.: Current Employment.

A Review of Current Approaches to Defining and Valuing Innovation in Health Technology Assessment

ObjectivesThe growing focus on the value of new drugs for patients and society has led to a more differentiated notion of innovation in the context of pharmaceutical products. The goal of this article is to provide an overview of the current debate about the definition and assessment of innovation and how innovation is considered in reimbursement and pricing decisions. MethodsTo compile the relevant literature, we followed a 2-step approach. First, we searched for peer-reviewed literature that deals with the definition of pharmaceutical innovation. Second, we reviewed health technology assessment (HTA) guidelines of 11 selected countries (Australia, Belgium, Canada, England, France, Germany, Italy, Japan, Norway, Sweden, and The Netherlands) regarding aspects of innovation that are currently considered as relevant by the respective HTA bodies. ResultsAll countries in our sample use 1 of 2 types of reward mechanism for novel drugs that they consider provide some sort of benefit. Generally, the focus is on the therapeutic benefit of a drug, whereas, depending on the exact arrangement, other aspects can also be taken into account. A reduction in side effects and aspects of treatment convenience can be invoked in some of the countries. Mostly, however, they are not considered unless they are already captured in the clinical outcomes used to measure the therapeutic benefit. ConclusionOur review shows that although the health economic literature discusses a range of aspects on how innovation may generate value even without providing an immediate added therapeutic benefit (or on top of it), these are only selectively considered in the reviewed HTA guidelines. For most part, only the added therapeutic value is crucial when it comes to pricing and reimbursement decisions.