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Introduction to economic evaluation and health technology assessment
Chapter 110
Introduction to economic evaluation and health technology assessment Oriana Ciania,b, Carlo Federicia,c a
Center for Research on Health and Social Care Management, SDA Bocconi, Milan, Italy, bEvidence Synthesis & Modelling for Health Improvement, University of Exeter Medical School, Exeter, United Kingdom, cSchool of Engineering, University of Warwick, Coventry, United Kingdom
Background Last decades have been characterized by a significant increase in the availability of medical technologies, thanks to the scientific development and discoveries occurred across many research disciplines. The ability of technological innovation to improve the diagnosis, care and, ultimately, outcomes for patients relies on the ability of the healthcare systems to manage the introduction, adoption, and diffusion of health technologies in the clinical practice. The implementation of medical technology also needs to ensure financial stability, as well as equity of patient access and choice within the system. As a result, a paradigm known under the name of health technology assessment (HTA) has spread rapidly to support funding, coverage, reimbursement and, recently, procurement decisions globally. Generally speaking, the HTA paradigm supports systematic generation and collection of the evidence to understand the value of new and existing technologies in order to inform decision-making, at different levels, in health care (Ciani and Taylor, 2017). In the following sections, we provide a brief overview of the concept, methods, and processes that underpin a framework for HTA that has become internationally accepted and implemented, with a focus on the economic dimensions of the assessment of technologies in health care.
Health technology assessment Health technologies include all pharmaceutical compounds, medical instruments, tools, devices, programs, or organizational procedures used to promote health; to prevent, diagnose, or treat acute or chronic disease; or for rehabilitation (Office of Technology Assessment, 1978). According Clinical Engineering Handbook. https://doi.org/10.1016/B978-0-12-813467-2.00111-5 Copyright © 2020 Elsevier Inc. All rights reserved.
to this definition, an antiarrhythmic drug, an implantable heart valve, a lung tumor screening program are health technologies. HTA is defined as the systematic evaluation of the properties and effects, both direct as well as indirect, of a technology within the healthcare system and is aimed mainly at informing decision-making in health care (International Network of Agencies for Health Technology Assessment, n.d.). The concept of HTA dates back to the 1970s when the Office of Technology Assessment (OTA) was founded in the United States (Office of Technology Assessment, 1976). The main objective of the OTA was to assess the impact of large medical equipment (such as nuclear magnetic resonance machines), on patients’ outcomes. However, given the rapid growth of healthcare expenditure in almost all developed countries, allocation of scarce financial resources in health care according to formal optimization criteria became an objective of primary importance. Since the establishment of the OTA in the US, the HTA approach has experienced an extraordinary international growth and it is now recognized as a crucial step to support funding, coverage, reimbursement decisions or procurement and price negotiation about health technologies in many jurisdictions (Oortwijn et al., 2010; Franken et al., 2012; Banta, 2009). The previous definition of HTA highlights its multidisciplinary nature and the close link with the policy- and decision-making phase. The paradigm of HTA draws from the principles of the evidence-based medicine (EBM) (Sackett et al., 1996) and clinical practice guidelines definition, with a shared aim of collecting and analyzing the best evidence to inform the assessment of health technologies. While EBM is focused on the improvement of clinical practice based on the latest high-quality scientific research 789
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and individual patient’s preferences, HTA aims at informing policy-making and population or group-level decisions. In this respect, HTA is often considered “a bridge between the research and policy communities” (Borlum Kristensen et al., 2008) as it provides evidence-based input to guide decisions within the health system. A commonly seen configuration is that of “institutionalized” HTA, that is, third-party payers, pricing and reimbursement agencies, or HTA bodies undertaking assessment activities to determine the reimbursement status of a new compound to recommend about the appropriate use of a medical device procedure within the healthcare system, or to support the price negotiation process with the manufacturer. Based on the scope of the organization or the structure of the h ealthcare system, this role is played at the central/ national level, regional/provincial level or local level (Ciani et al., 2012). Depending on the decisional level where it is conducted, HTA actually serves different scopes: while at a central/national level HTA informs nation-wide coverage/reimbursement decisions or recommendations, at the hospital-level HTA provides useful guidance on technologies’ adoption and management (Sampietro-Colom et al., 2015). This may take place by assessing their impact on the hospital budget (see below) or the organizational consequences in terms of health technology management (HTM) in each phase of the technologies’ life cycle. Given the different levels where HTA is performed, transparency, and efficient exchanges of information among the different levels are essential to avoid duplication of assessment efforts, and ultimately inconsistencies in their impact on clinical practice. HTA involves a structured process and multidimensional analytical framework. Properties and attributes assessed vary across countries and agencies; however, it is common to include, as part of the HTA, a comparative effectiveness evaluation. In contrast to regulatory bodies such as the Food and Drug Administration (FDA) or the European Medicines Agency (EMA) that are focused on the risk–benefit profile of a product, safety, efficacy, and quality of manufacturing, HTA agencies are interested in comparative effectiveness, that is, evidence that the intervention has beneficial health outcomes under “real-world” conditions and in comparison with the local standard of care. In terms of health outcomes, comparative harms and benefits can be measured on one or more patient-relevant outcomes, such as death or major cardiovascular events. Such outcomes are preferred over the so-called surrogate endpoints, that is, biomarkers that are predictive of how patients feel, function, or how long they survive. Surrogate endpoints are often used in clinical trials to reduce the follow-up, sample size, or costs. However, their adoption should be ideally subject to a proper validation (Ciani et al., 2016). In addition, the evaluation of functional status or health-related quality of life, through validated patient reported outcomes measures (PROMs), has consistently developed over the past 30 years (Nelson et al., 2015).
Economic evaluation Many HTA agencies also consider the economic impact of health technologies, including associated costs and resource use, in relation to their effectiveness. Particularly, the main aim of measuring the economic impact of technologies is to ensure that limited healthcare resources are allocated efficiently according to the maximization objectives of those who are responsible for deciding on budget allocations. In fact, since in most healthcare systems budgets are fixed in the short time, expanding the range of health intervention, by providing coverage for a new technology inevitably requires displacing resources from other programs covered by the same budget, which in turn will have consequences in terms of reduced health in the population. Therefore, due to the existence of a fixed budget constraint, when taking coverage/reimbursement decisions, decision makers need to balance the expected health gains generated by the new intervention (should it be introduced and reimbursed within the budget), against the consequences of displacing resources from other parts of the healthcare system. In short, if the expected health gains generated by the new intervention are higher than the health losses incurred by such displacement, the technology is deemed cost effective, as its introduction is expected to yield a positive increment in the overall population health. Assessing whether technologies are cost-effective is indeed the ultimate scope of economic evaluations. In order to ascertain cost effectiveness of technologies, economic evaluations need to fulfill two essential requirements. First, they require a comparison of two or more alternatives. Second, economic evaluations must consider both the costs and consequences associated with each of the alternatives considered. The joint presence of these two requirements is what distinguishes full economic evaluations from other types of partial analyses that can be found in the literature as depicted in Fig. 1 (Drummond et al., 2015). There exist three main types of full economic evaluations, mainly differing in how health consequences are measured and valued. Cost-effectiveness analyses (CEA) compare the effectiveness of the different alternatives in terms of some specific unit of health effect, such as for example, life-years gained, deaths averted, or the number of cancers detected. Cost utility analyses (CUA) are essentially a variant of CEAs, which use more generic measures of health. Typical measures used in CUAs are quality-adjusted life years (QALYs), where life years are weighted for the preferences that individuals or society may have for any particular set of health conditions. Several methods to measure preferences-based measures of health-related quality of life have been developed. These include direct approaches such as standard gamble, time trade off or visual analog scales, and indirect approaches that use prescored multiattribute
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FIG. 1 Characteristics of healthcare evaluations. (Adapted from Drummond, M.F., Sculpher, M.J., Claxton, K., Stoddart, G.L., Torrance, G.W., 2015. Methods for the Economic Evaluation of Health Care Programmes, fourth edition. Oxford University Press, Oxford.)
health status classification systems such as the EQ5D from the EuroQOL group, or the Short Form 6D tool. Lastly, cost–benefit analyses express the consequences of an intervention in monetary terms, that is, by estimating how much individuals would be willing to pay for a certain amount of health gains. While CEAs and CUAs can only inform how to maximize health gains by choosing the most cost-effective alternative given a fixed budget, CBAs can serve a wider objective. In fact, by measuring both costs and consequences in monetary term, they provide insights on the absolute value of the interventions, and therefore they can also support judgments on whether the existing budget should be expanded to make room for them. However, attaching monetary values to health gains, such as life years gained or avoided cardiovascular events is not trivial and present both ethical and methodological challenges. Therefore, the use of CBA in economic evaluations is still highly controversial, and its use has not seen many practical applications in the literature (Rice, 2014). Once both costs and consequences for two or more alternatives have been estimated, judgments on cost- effectiveness for any of the available alternatives can be made by examining the incremental costs of one technology with respect to another compared with the additional effects it delivers. This comparison is often expressed as the incremental cost-effectiveness ratio (ICER), that is, the ratio between the incremental costs of the new technology compared to a relevant alternative, and its incremental effects. For example, the ICER of a new technology (technology B) compared to its best (and cheaper) alternative (technology A) will be ICER BA =
CostsB − CostsA EffectsB − EffectsA
In order to be cost effective, the ICER (i.e., the incremental cost of producing an additional unit of benefit) must be inferior to a cost-effectiveness threshold which is expression of the payer maximum willingness to pay (WTP) for the new technology. There exist different views about the meaning and implications of cost-effectiveness thresholds, however, in budget constrained healthcare systems, a common interpretation is that thresholds are expression of the consequences of displacing resources to fund a new technology (Thokala
et al., 2018). For example, a cost-effectiveness threshold of 20,000£ per QALY would mean that for each £20,000 displaced 1 QALY would be loss in the system. Therefore, if the incremental costs required to produce one extra QALY with the new technology (i.e., the ICER) is less than the cost-effectiveness threshold, the benefit of introducing it will overweight the losses due to the displacement of resources. Economic evaluations in health care have developed methodologically and currently rely on a range of techniques that allow the estimation of the cost-effectiveness profile of a new technology, as well as a characterization of its uncertainty and heterogeneity between any subgroups. Since assessment of new technologies require to estimate both costs and consequences along the whole patients’ lifetime, economic evaluations often employ mathematical models to extrapolate available data to longer time horizons and estimate the overall ICER (Briggs and Claxton, 2006). Most HTA agencies in different jurisdictions have published methodological guidance on how to conduct and report economic evaluations to be used in their decisionmaking processes. Some examples are the reference case from the UK national institute for health care excellence (NICE) (NICE, UK, 2013) or the guidelines on methods for economic evaluations from the French Haute Autorité de la Santé (HAS, France, 2012). Also other methodological contributions have been provided in the literature. For example, checklists are widely used to judge the quality of economic evaluations. Some, such as the consolidated health economic evaluation reporting standards (CHEERS) checklist (Husereau et al., 2013), concentrate on the quality of reporting. Others, such as those developed by the BMJ Working Party (Drummond and Jefferson, 1996), Drummond et al. (2015), and Evers et al. (2005), judge both aspects of methods and reporting. While economic evaluations, such as CEAs and CUAs provide insights on whether a new technology is “good value for money”, that is, whether it is more cost effective than any other alternative available to treat a certain condition, decision makers may also be interested in understanding what will be the overall financial impact of introducing the technology in the actual clinical practice. Budget impact analyses (BIAs) require estimating the number of target patients that could benefit of the
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intervention, the rate of penetration of the technology in the actual clinical practice, and the variation in healthcare resources utilization following its introduction (e.g., by increasing the number of patients treated, or the time they are on treatment, or by reducing the rate of complications and adverse events) (Goettsch and Enzing, 2014). For example, Yu et al. estimated that the introduction of a next-generation sequencing test for molecular assessment of advanced nonsmall cell lung cancer vs single-gene testing in the US would increase first-line and maintenance treatment costs, offset by a decrease in second-line treatment and palliative care costs; and that the overall increase in spending for the healthcare payer would be equal to $432k over 5 years (Yu et al., 2018).
Other dimensions of assessment Other dimensions of HTA include organizational, social, legal, or ethical issues associated with the use of the technology within the health system. In this respect, the HTA should address questions around any potential influence of the use of the technology on human dignity, privacy, autonomy, justice, or equality. For example, an HTA report of screening for lung cancer in the high-risk population (smokers) may take into account the social justice issues raised by its implementation; or the introduction of a home-based service for dialysis, instead of the traditional hospital-based, should investigate what impact is expected on patients, their families or carers. Organizational impact relates to the management of challenges and opportunities arising by the implementation
of the technology in the healthcare system, including changes to current work processes, training of staff, and mechanisms to ensure and facilitate access across the target population. For example, innovation in the cardiosurgical continuous innovation on ICDs has progressively reduced the invasiveness of the implantation, from an open heart surgery with extracorporeal circulation to an endovascular approach where an electrophysiology laboratory and new professional expertise (i.e., electrophysiology) were needed instead of standard operating rooms and cardiac surgeons. In relation to the dimensions of the assessment, the European Network for Health Technology Assessment (EUnetHTA) has developed a HTA Core Model that defines the typical components of a HTA report, facilitates identification of relevant information and exchange of work within the EU region. In line with the multidisciplinary nature of HTA, the structure of the model covers nine domains that can be relevant in the assessment of the value of new or existing health technologies (Fig. 1). EUnetHTA is an example of an EU funded initiative set out as a voluntary network of HTA bodies with the aim of promoting good practices, exchange of resources and methods, cooperation and reuse, or joint work between countries (European Network for Health Technology Assessment (EUnetHTA), n.d.).
HTA process HTA is an interactive process that follows some common steps described in Fig. 2 (Borlum Kristensen et al., 2008). Given the large number of new health technologies coming into the market, a first necessary step is
Legal aspects
Social aspects
Organisational aspects
Ethical analysis
Costs and economic evaluation
Clinical effectiveness
Safety
Description and technical characteristics of technology
Health problem and current use of the technology
HTA
FIG. 2 EUnetHTA Core Model EUnetHTA, European Network for Health technology assessment. (Adapted from EUnetHTA Joint Action 2, Work Package 8. HTA Core Model version 3.0 (Pdf); 2016. © EUnetHTA, 2016.)
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p riority-setting. Prioritization in HTA is based on consultation with stakeholders in the healthcare system, research recommendations from systematic reviews, or horizon scanning (HS). HS seeks to identify new or emerging health technologies before launch that might require evaluation, given their expected impact on to the healthcare system (Ciani and Jommi, 2014). Criteria adopted to set priorities across agencies in North America or Europe include economic, budgetary, or clinical impact; disease burden; availability of evidence; timeliness of assessment; and variation and controversies about the use of the technology (Noorani et al., 2007). Once a technology has been prioritized, the assessment phase starts. A preparatory step, called scoping, usually takes place to frame the decision problem into a clearly defined policy question of direct significance to decision makers. On the basis of the scope, a protocol is developed that details the methods of the assessment and its reporting. For example, to address the clinical effectiveness, a systematic review and metaanalysis of the evidence is often performed following a comprehensive search, unbiased selection of studies, and data extraction and clinical appraisal of the evidence (Centre for Reviews and Dissemination, 2009; Higgins and Green, 2011). Evidence is collated, analyzed, and interpreted according to a multidimensional framework of evaluation in order to provide an evidencebased answer to the policy question of interest and to inform policy makers in their recommendations for use, coverage, or reimbursement of the health technology under evaluation (appraisal). The assessment and appraisal phases should be followed by dissemination of results and related recommendations as widely as possible, usually through a website, including clear communication to the lay public. Ideally, a mechanism to monitor the adherence to the recommendations and plan for any follow-up action should be in place, as well as a systematic reassessment to account for the new postmarketing generated evidence. Through all the different steps, the input and contribution of all relevant stakeholders has the potential to enrich the discussion and make the results of the HTA fit to its intended use maximizing usable and accessible evidence-based support for decision-making. Key stakeholder groups in health care include patients, industry, healthcare providers and professionals, third-party payers, and regulators. Public and patient involvement (PPI) in all the stages of the HTA process is increasingly encouraged in order to maximize the relevance, acceptability, and uptake of related recommendations. The practice and literature report multiple approaches adopted and describe an involvement mainly focused on the early stages: the identification of HTA topics, prioritization, and development of the assessment plan of the topic prioritized Fig. 3 (Abelson et al., 2016).
FIG. 3 The HTA process.
Conclusions Rational allocation of public resources based on the principle of value for money has become a key issue for governments faced with increasing healthcare expenditure and declining budgets. HTA was established as a framework to inform decision-making in health care based on the best available evidence on the comparative effectiveness and cost effectiveness of health technologies. There is considerable variability in the funding, remit, and practice of HTA across different international settings and organizations. There is a need for HTA to develop and evolve with increasing standards of transparency, harmonization, data integration, and cooperation worldwide.
References Abelson, J., Wagner, F., De Jean, D., et al., 2016. Public and patient involvement in health technology assessment: a framework for action. Int. J. Technol. Assess. Health Care 32 (4), 256–264. Banta, D., 2009. Health technology assessment in Latin America and the Caribbean. Int. J. Technol. Assess. Health Care 25 (Suppl. 1), 253–254. Borlum Kristensen, F., Palmhj Nielsen, C., Chase, B., et al., 2008. What is health technology assessment? In: Velasco Garrido, M., Borlum Kristensen, F., Palmhj Nielsen, C., Busse, R. (Eds.), Health Technology Assessment and Health Policy-Making in Europe: Current Status, Challenges and Potential. World Health Organization, on behalf of the European Observatory on Health Systems and Policies, Copenhagen, pp. 31–51. Briggs, A., Claxton, K., Sculpher, M. (Eds.), 2006. Decision Modelling for Health Economic Evaluation. Oxford University Press, Oxford. Centre for Reviews and Dissemination, 2009. Systematic Reviews. University of York, York. Ciani, O., Jommi, C., 2014. The role of health technology assessment bodies in shaping drug development. Drug Des. Devel. Ther. 8, 2273–2281. Ciani, O., Taylor, R., 2017. Health Technology Assessment. Wiley StatsRef: Statistics Reference Online.
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Ciani, O., Tarricone, R., Torbica, A., 2012. Diffusion and use of health technology assessment in policymaking: what lessons for decentralised healthcare systems? Health Policy 108, 194–202. Ciani, O., Buyse, M., Drummond, M., et al., 2016. Use of surrogate end points in healthcare policy: a proposal for adoption of a validation framework. Nat. Rev. Drug Discov. 15 (7), 516. Drummond, M.F., Jefferson, T.O., 1996. Guidelines for authors and peer reviewers of economic submissions to the BMJ. The BMJ Economic Evaluation Working Party. Br. Med. J. 313 (7052), 275–283. Drummond, M.F., Sculpher, M.J., Claxton, K., Stoddart, G.L., Torrance, G.W., 2015. Methods for the Economic Evaluation of Health Care Programmes, fourth ed. Oxford University Press, Oxford. European Network for Health Technology Assessment (EUnetHTA), Available from: https://www.eunethta.eu. Evers, S., Goossens, M., De Vet, H., Van Tulder, M., Ament, A., 2005. Criteria list for assessment of methodological quality of economic evaluations: Consensus on health economic criteria. Int. J. Technol. Assess. Health Care 21 (2), 240–245. Franken, M., Le Polain, M., Cleemput, I., Koopmanschap, M., 2012. Similarities and differences between five European drug reimbursement systems. Int. J. Technol. Assess. Health Care 28, 349–357. Goettsch, W.G., Enzing, J., 2014. Report of the ISPOR 2012 budget impact analysis good practice II task force. Value Health 17 (1), 1–2. HAS, France, 2012. Choices in Methods for Economic Evaluation. Available from: https://www.has-sante.fr/portail/upload/docs/application/pdf/2012-10/choices_in_methods_for_economic_evaluation.pdf. Higgins, J.P.T., Green, S. (Eds.), 2011. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0., [Updated March 2011]. Available from, The Cochrane Collaboration. www.handbook.cochrane.org. Husereau, D., Drummond, M., Petrou, S., Carswell, C., Moher, D., Greenberg, D., et al., 2013. Consolidated health economic evaluation reporting standards (CHEERS) statement. Cost Effectiveness and Resource Allocation 11 (1), 6. International Network of Agencies for Health Technology Assessment, HTA Glossary. http://htaglossary.net/HomePage. Nelson, E.C., Eftimovska, E., Lind, C., et al., 2015. Patient reported outcome measures in practice. Br. Med. J. 10 (350), g7818.
NICE, UK, 2013. Guide to the Methods of Technology Appraisal. PMG9. Available from: https://www.nice.org.uk/process/pmg9/chapter/ the-reference-case. Noorani, H.Z., Husereau, D.R., Boudreau, R., Skidmore, B., 2007. Priority setting for health technology assessments: a systematic review of current practical approaches. Int. J. Technol. Assess. Health Care 23 (3), 310–315. Office of Technology Assessment, 1976. Development of Medical Technology: Opportunities for Assessment. Government Printing Office, Washington, DC. Office of Technology Assessment, 1978. Assessing the Efficacy and Safety of Medical Technologies. Government Printing Office, Washington, DC. Oortwijn, W., Mathijssen, J., Banta, D., 2010. The role of health technology assessment on pharmaceutical reimbursement in selected middleincome countries. Health Policy 95, 174–184. Rice, T., 2014. “The Humble Economist: Tony Culyer on Health, Health Care and Social Decision Making” By Cookson Richard and Claxton Karl, University of York and Office of Health Economics, New York, UK, 2012. Health Econ. Policy Law 9 (1), 113–118. https://doi. org/10.1017/S1744133113000261. Sackett, D., Rosenberg, W., Gray, M., et al., 1996. Evidence-based medicine: what it is and what it isn’t. Br. Med. J. 312, 71–72. Sampietro-Colom, L., Lach, K., Pasternack, I., Wasserfallen, J.B., Cicchetti, A., Marchetti, M., Kidholm, K., Arentz-Hansen, H., Rosenmöller, M., Wild, C., Kahveci, R., Ulst, M., 2015. Guiding principles for good practices in hospital-based health technology assessment units. Int. J. Technol. Assess. Health Care 31 (6), 457–465. https://doi.org/10.1017/S0266462315000732. Epub 2016 Feb 22. Thokala, P., Ochalek, J., Leech, A.A., Tong, T., 2018. Cost-effectiveness thresholds: The past, the present and the future. Pharmacoeconomics 36, 509–522. https://doi.org/10.1007/s40273-017-0606-1. Yu, T.M., Morrison, C., Gold, E.J., Tradonsky, A., Arnold, R.J., 2018. Budget impact of next generation sequencing for molecular assessment of advanced non-small cell lung cancer. Value Health 21 (11), 1278–1285.
Introduction to economic evaluation and health technology assessment Oriana Ciania,b, Carlo Federicia,c a
Center for Research on Health and Social Care Management, SDA Bocconi, Milan, Italy, bEvidence Synthesis & Modelling for Health Improvement, University of Exeter Medical School, Exeter, United Kingdom, cSchool of Engineering, University of Warwick, Coventry, United Kingdom
Background Last decades have been characterized by a significant increase in the availability of medical technologies, thanks to the scientific development and discoveries occurred across many research disciplines. The ability of technological innovation to improve the diagnosis, care and, ultimately, outcomes for patients relies on the ability of the healthcare systems to manage the introduction, adoption, and diffusion of health technologies in the clinical practice. The implementation of medical technology also needs to ensure financial stability, as well as equity of patient access and choice within the system. As a result, a paradigm known under the name of health technology assessment (HTA) has spread rapidly to support funding, coverage, reimbursement and, recently, procurement decisions globally. Generally speaking, the HTA paradigm supports systematic generation and collection of the evidence to understand the value of new and existing technologies in order to inform decision-making, at different levels, in health care (Ciani and Taylor, 2017). In the following sections, we provide a brief overview of the concept, methods, and processes that underpin a framework for HTA that has become internationally accepted and implemented, with a focus on the economic dimensions of the assessment of technologies in health care.
Health technology assessment Health technologies include all pharmaceutical compounds, medical instruments, tools, devices, programs, or organizational procedures used to promote health; to prevent, diagnose, or treat acute or chronic disease; or for rehabilitation (Office of Technology Assessment, 1978). According Clinical Engineering Handbook. https://doi.org/10.1016/B978-0-12-813467-2.00111-5 Copyright © 2020 Elsevier Inc. All rights reserved.
to this definition, an antiarrhythmic drug, an implantable heart valve, a lung tumor screening program are health technologies. HTA is defined as the systematic evaluation of the properties and effects, both direct as well as indirect, of a technology within the healthcare system and is aimed mainly at informing decision-making in health care (International Network of Agencies for Health Technology Assessment, n.d.). The concept of HTA dates back to the 1970s when the Office of Technology Assessment (OTA) was founded in the United States (Office of Technology Assessment, 1976). The main objective of the OTA was to assess the impact of large medical equipment (such as nuclear magnetic resonance machines), on patients’ outcomes. However, given the rapid growth of healthcare expenditure in almost all developed countries, allocation of scarce financial resources in health care according to formal optimization criteria became an objective of primary importance. Since the establishment of the OTA in the US, the HTA approach has experienced an extraordinary international growth and it is now recognized as a crucial step to support funding, coverage, reimbursement decisions or procurement and price negotiation about health technologies in many jurisdictions (Oortwijn et al., 2010; Franken et al., 2012; Banta, 2009). The previous definition of HTA highlights its multidisciplinary nature and the close link with the policy- and decision-making phase. The paradigm of HTA draws from the principles of the evidence-based medicine (EBM) (Sackett et al., 1996) and clinical practice guidelines definition, with a shared aim of collecting and analyzing the best evidence to inform the assessment of health technologies. While EBM is focused on the improvement of clinical practice based on the latest high-quality scientific research 789
790 SECTION | 12 Health technology assessment
and individual patient’s preferences, HTA aims at informing policy-making and population or group-level decisions. In this respect, HTA is often considered “a bridge between the research and policy communities” (Borlum Kristensen et al., 2008) as it provides evidence-based input to guide decisions within the health system. A commonly seen configuration is that of “institutionalized” HTA, that is, third-party payers, pricing and reimbursement agencies, or HTA bodies undertaking assessment activities to determine the reimbursement status of a new compound to recommend about the appropriate use of a medical device procedure within the healthcare system, or to support the price negotiation process with the manufacturer. Based on the scope of the organization or the structure of the h ealthcare system, this role is played at the central/ national level, regional/provincial level or local level (Ciani et al., 2012). Depending on the decisional level where it is conducted, HTA actually serves different scopes: while at a central/national level HTA informs nation-wide coverage/reimbursement decisions or recommendations, at the hospital-level HTA provides useful guidance on technologies’ adoption and management (Sampietro-Colom et al., 2015). This may take place by assessing their impact on the hospital budget (see below) or the organizational consequences in terms of health technology management (HTM) in each phase of the technologies’ life cycle. Given the different levels where HTA is performed, transparency, and efficient exchanges of information among the different levels are essential to avoid duplication of assessment efforts, and ultimately inconsistencies in their impact on clinical practice. HTA involves a structured process and multidimensional analytical framework. Properties and attributes assessed vary across countries and agencies; however, it is common to include, as part of the HTA, a comparative effectiveness evaluation. In contrast to regulatory bodies such as the Food and Drug Administration (FDA) or the European Medicines Agency (EMA) that are focused on the risk–benefit profile of a product, safety, efficacy, and quality of manufacturing, HTA agencies are interested in comparative effectiveness, that is, evidence that the intervention has beneficial health outcomes under “real-world” conditions and in comparison with the local standard of care. In terms of health outcomes, comparative harms and benefits can be measured on one or more patient-relevant outcomes, such as death or major cardiovascular events. Such outcomes are preferred over the so-called surrogate endpoints, that is, biomarkers that are predictive of how patients feel, function, or how long they survive. Surrogate endpoints are often used in clinical trials to reduce the follow-up, sample size, or costs. However, their adoption should be ideally subject to a proper validation (Ciani et al., 2016). In addition, the evaluation of functional status or health-related quality of life, through validated patient reported outcomes measures (PROMs), has consistently developed over the past 30 years (Nelson et al., 2015).
Economic evaluation Many HTA agencies also consider the economic impact of health technologies, including associated costs and resource use, in relation to their effectiveness. Particularly, the main aim of measuring the economic impact of technologies is to ensure that limited healthcare resources are allocated efficiently according to the maximization objectives of those who are responsible for deciding on budget allocations. In fact, since in most healthcare systems budgets are fixed in the short time, expanding the range of health intervention, by providing coverage for a new technology inevitably requires displacing resources from other programs covered by the same budget, which in turn will have consequences in terms of reduced health in the population. Therefore, due to the existence of a fixed budget constraint, when taking coverage/reimbursement decisions, decision makers need to balance the expected health gains generated by the new intervention (should it be introduced and reimbursed within the budget), against the consequences of displacing resources from other parts of the healthcare system. In short, if the expected health gains generated by the new intervention are higher than the health losses incurred by such displacement, the technology is deemed cost effective, as its introduction is expected to yield a positive increment in the overall population health. Assessing whether technologies are cost-effective is indeed the ultimate scope of economic evaluations. In order to ascertain cost effectiveness of technologies, economic evaluations need to fulfill two essential requirements. First, they require a comparison of two or more alternatives. Second, economic evaluations must consider both the costs and consequences associated with each of the alternatives considered. The joint presence of these two requirements is what distinguishes full economic evaluations from other types of partial analyses that can be found in the literature as depicted in Fig. 1 (Drummond et al., 2015). There exist three main types of full economic evaluations, mainly differing in how health consequences are measured and valued. Cost-effectiveness analyses (CEA) compare the effectiveness of the different alternatives in terms of some specific unit of health effect, such as for example, life-years gained, deaths averted, or the number of cancers detected. Cost utility analyses (CUA) are essentially a variant of CEAs, which use more generic measures of health. Typical measures used in CUAs are quality-adjusted life years (QALYs), where life years are weighted for the preferences that individuals or society may have for any particular set of health conditions. Several methods to measure preferences-based measures of health-related quality of life have been developed. These include direct approaches such as standard gamble, time trade off or visual analog scales, and indirect approaches that use prescored multiattribute
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FIG. 1 Characteristics of healthcare evaluations. (Adapted from Drummond, M.F., Sculpher, M.J., Claxton, K., Stoddart, G.L., Torrance, G.W., 2015. Methods for the Economic Evaluation of Health Care Programmes, fourth edition. Oxford University Press, Oxford.)
health status classification systems such as the EQ5D from the EuroQOL group, or the Short Form 6D tool. Lastly, cost–benefit analyses express the consequences of an intervention in monetary terms, that is, by estimating how much individuals would be willing to pay for a certain amount of health gains. While CEAs and CUAs can only inform how to maximize health gains by choosing the most cost-effective alternative given a fixed budget, CBAs can serve a wider objective. In fact, by measuring both costs and consequences in monetary term, they provide insights on the absolute value of the interventions, and therefore they can also support judgments on whether the existing budget should be expanded to make room for them. However, attaching monetary values to health gains, such as life years gained or avoided cardiovascular events is not trivial and present both ethical and methodological challenges. Therefore, the use of CBA in economic evaluations is still highly controversial, and its use has not seen many practical applications in the literature (Rice, 2014). Once both costs and consequences for two or more alternatives have been estimated, judgments on cost- effectiveness for any of the available alternatives can be made by examining the incremental costs of one technology with respect to another compared with the additional effects it delivers. This comparison is often expressed as the incremental cost-effectiveness ratio (ICER), that is, the ratio between the incremental costs of the new technology compared to a relevant alternative, and its incremental effects. For example, the ICER of a new technology (technology B) compared to its best (and cheaper) alternative (technology A) will be ICER BA =
CostsB − CostsA EffectsB − EffectsA
In order to be cost effective, the ICER (i.e., the incremental cost of producing an additional unit of benefit) must be inferior to a cost-effectiveness threshold which is expression of the payer maximum willingness to pay (WTP) for the new technology. There exist different views about the meaning and implications of cost-effectiveness thresholds, however, in budget constrained healthcare systems, a common interpretation is that thresholds are expression of the consequences of displacing resources to fund a new technology (Thokala
et al., 2018). For example, a cost-effectiveness threshold of 20,000£ per QALY would mean that for each £20,000 displaced 1 QALY would be loss in the system. Therefore, if the incremental costs required to produce one extra QALY with the new technology (i.e., the ICER) is less than the cost-effectiveness threshold, the benefit of introducing it will overweight the losses due to the displacement of resources. Economic evaluations in health care have developed methodologically and currently rely on a range of techniques that allow the estimation of the cost-effectiveness profile of a new technology, as well as a characterization of its uncertainty and heterogeneity between any subgroups. Since assessment of new technologies require to estimate both costs and consequences along the whole patients’ lifetime, economic evaluations often employ mathematical models to extrapolate available data to longer time horizons and estimate the overall ICER (Briggs and Claxton, 2006). Most HTA agencies in different jurisdictions have published methodological guidance on how to conduct and report economic evaluations to be used in their decisionmaking processes. Some examples are the reference case from the UK national institute for health care excellence (NICE) (NICE, UK, 2013) or the guidelines on methods for economic evaluations from the French Haute Autorité de la Santé (HAS, France, 2012). Also other methodological contributions have been provided in the literature. For example, checklists are widely used to judge the quality of economic evaluations. Some, such as the consolidated health economic evaluation reporting standards (CHEERS) checklist (Husereau et al., 2013), concentrate on the quality of reporting. Others, such as those developed by the BMJ Working Party (Drummond and Jefferson, 1996), Drummond et al. (2015), and Evers et al. (2005), judge both aspects of methods and reporting. While economic evaluations, such as CEAs and CUAs provide insights on whether a new technology is “good value for money”, that is, whether it is more cost effective than any other alternative available to treat a certain condition, decision makers may also be interested in understanding what will be the overall financial impact of introducing the technology in the actual clinical practice. Budget impact analyses (BIAs) require estimating the number of target patients that could benefit of the
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intervention, the rate of penetration of the technology in the actual clinical practice, and the variation in healthcare resources utilization following its introduction (e.g., by increasing the number of patients treated, or the time they are on treatment, or by reducing the rate of complications and adverse events) (Goettsch and Enzing, 2014). For example, Yu et al. estimated that the introduction of a next-generation sequencing test for molecular assessment of advanced nonsmall cell lung cancer vs single-gene testing in the US would increase first-line and maintenance treatment costs, offset by a decrease in second-line treatment and palliative care costs; and that the overall increase in spending for the healthcare payer would be equal to $432k over 5 years (Yu et al., 2018).
Other dimensions of assessment Other dimensions of HTA include organizational, social, legal, or ethical issues associated with the use of the technology within the health system. In this respect, the HTA should address questions around any potential influence of the use of the technology on human dignity, privacy, autonomy, justice, or equality. For example, an HTA report of screening for lung cancer in the high-risk population (smokers) may take into account the social justice issues raised by its implementation; or the introduction of a home-based service for dialysis, instead of the traditional hospital-based, should investigate what impact is expected on patients, their families or carers. Organizational impact relates to the management of challenges and opportunities arising by the implementation
of the technology in the healthcare system, including changes to current work processes, training of staff, and mechanisms to ensure and facilitate access across the target population. For example, innovation in the cardiosurgical continuous innovation on ICDs has progressively reduced the invasiveness of the implantation, from an open heart surgery with extracorporeal circulation to an endovascular approach where an electrophysiology laboratory and new professional expertise (i.e., electrophysiology) were needed instead of standard operating rooms and cardiac surgeons. In relation to the dimensions of the assessment, the European Network for Health Technology Assessment (EUnetHTA) has developed a HTA Core Model that defines the typical components of a HTA report, facilitates identification of relevant information and exchange of work within the EU region. In line with the multidisciplinary nature of HTA, the structure of the model covers nine domains that can be relevant in the assessment of the value of new or existing health technologies (Fig. 1). EUnetHTA is an example of an EU funded initiative set out as a voluntary network of HTA bodies with the aim of promoting good practices, exchange of resources and methods, cooperation and reuse, or joint work between countries (European Network for Health Technology Assessment (EUnetHTA), n.d.).
HTA process HTA is an interactive process that follows some common steps described in Fig. 2 (Borlum Kristensen et al., 2008). Given the large number of new health technologies coming into the market, a first necessary step is
Legal aspects
Social aspects
Organisational aspects
Ethical analysis
Costs and economic evaluation
Clinical effectiveness
Safety
Description and technical characteristics of technology
Health problem and current use of the technology
HTA
FIG. 2 EUnetHTA Core Model EUnetHTA, European Network for Health technology assessment. (Adapted from EUnetHTA Joint Action 2, Work Package 8. HTA Core Model version 3.0 (Pdf); 2016. © EUnetHTA, 2016.)
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p riority-setting. Prioritization in HTA is based on consultation with stakeholders in the healthcare system, research recommendations from systematic reviews, or horizon scanning (HS). HS seeks to identify new or emerging health technologies before launch that might require evaluation, given their expected impact on to the healthcare system (Ciani and Jommi, 2014). Criteria adopted to set priorities across agencies in North America or Europe include economic, budgetary, or clinical impact; disease burden; availability of evidence; timeliness of assessment; and variation and controversies about the use of the technology (Noorani et al., 2007). Once a technology has been prioritized, the assessment phase starts. A preparatory step, called scoping, usually takes place to frame the decision problem into a clearly defined policy question of direct significance to decision makers. On the basis of the scope, a protocol is developed that details the methods of the assessment and its reporting. For example, to address the clinical effectiveness, a systematic review and metaanalysis of the evidence is often performed following a comprehensive search, unbiased selection of studies, and data extraction and clinical appraisal of the evidence (Centre for Reviews and Dissemination, 2009; Higgins and Green, 2011). Evidence is collated, analyzed, and interpreted according to a multidimensional framework of evaluation in order to provide an evidencebased answer to the policy question of interest and to inform policy makers in their recommendations for use, coverage, or reimbursement of the health technology under evaluation (appraisal). The assessment and appraisal phases should be followed by dissemination of results and related recommendations as widely as possible, usually through a website, including clear communication to the lay public. Ideally, a mechanism to monitor the adherence to the recommendations and plan for any follow-up action should be in place, as well as a systematic reassessment to account for the new postmarketing generated evidence. Through all the different steps, the input and contribution of all relevant stakeholders has the potential to enrich the discussion and make the results of the HTA fit to its intended use maximizing usable and accessible evidence-based support for decision-making. Key stakeholder groups in health care include patients, industry, healthcare providers and professionals, third-party payers, and regulators. Public and patient involvement (PPI) in all the stages of the HTA process is increasingly encouraged in order to maximize the relevance, acceptability, and uptake of related recommendations. The practice and literature report multiple approaches adopted and describe an involvement mainly focused on the early stages: the identification of HTA topics, prioritization, and development of the assessment plan of the topic prioritized Fig. 3 (Abelson et al., 2016).
FIG. 3 The HTA process.
Conclusions Rational allocation of public resources based on the principle of value for money has become a key issue for governments faced with increasing healthcare expenditure and declining budgets. HTA was established as a framework to inform decision-making in health care based on the best available evidence on the comparative effectiveness and cost effectiveness of health technologies. There is considerable variability in the funding, remit, and practice of HTA across different international settings and organizations. There is a need for HTA to develop and evolve with increasing standards of transparency, harmonization, data integration, and cooperation worldwide.
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