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The Development of Health Technology Assessment in Asia: Current Status and Future Trends

Open ArchivePublished:October 19, 2019DOI:https://doi.org/10.1016/j.vhri.2019.08.472

      Highlights

      • What is known about the topic?
        • Health technology assessment (HTA) has been employed for decades by many countries around the word, including many European countries, Canada, and Australia.
        • Asian countries have been historically slow to adopt HTA, but recently, several have made significant strides in adopting HTA to inform pricing and reimbursement decisions.
      • What does the article add to the existing knowledge?
        • An overview of the development of HTA in Asia is provided, and the key challenges that Asian countries have faced and still face in implementing HTA are described.
        • The experiences of 3 countries—South Korea, Japan, and China—at different stages of HTA development are described to highlight both unique and common challenges that individual Asian countries face in implementing HTA.
      • What insights does the article provide for informing healthcare-related decision making?
        • There is no one-size-fits-all approach to building HTA; therefore, healthcare decision makers in Asian countries that are considering or are in the process of implementing HTA can learn important lessons from the experiences of countries that have gone through the same process in the past.
        • This review provides important insights on the status of HTA in Asia as well as an overview of the challenges that lie ahead for Asian countries with and without established HTA capabilities.

      Abstract

      Health technology assessment (HTA) has long been employed by many countries around the world, but its adoption in Asia has been slower. Only recently have a growing number of Asian countries started to implement HTA for pricing and reimbursement decisions. The objective of this article is to provide an overview of how HTA has been or is being implemented in Asia within the context of a country’s existing—and often complex—coverage, reimbursement, and pricing schemes. Three countries at different stages of HTA implementation were selected as case studies: South Korea, where there is a young yet established HTA program; Japan, where a 3-year HTA pilot program has just concluded; and China, where HTA efforts are underway but have not been formally implemented. Not only do the experiences of these 3 countries well exemplify how the organization and scope of HTA can be customized to meet a country’s unique healthcare needs, but they also provide the opportunity to outline some common key challenges that must be overcome to implement and develop HTA competencies and capabilities.

      Keywords

      Introduction

      Over the past 3 decades, health technology assessment (HTA) has been employed by many countries—including France, Spain, Sweden, England, Germany, Italy, The Netherlands, Canada, and Australia—to inform pricing and reimbursement decisions in an effort to control rapidly increasing healthcare costs.
      • Banta D.
      • Kristensen F.B.
      • Jonsson E.
      A history of health technology assessment at the European level.
      • Hailey D.
      The history of health technology assessment in Australia.
      • Battista R.N.
      • Cote B.
      • Hodge M.J.
      • Husereau D.
      Health technology assessment in Canada.
      • Xie J.
      • Chalkidou K.
      • Kamae I.
      • et al.
      Policy considerations: ex-US payers and regulators.
      Nevertheless, in Asia, the adoption of HTA has been historically slow.
      • Sivalal S.
      Health technology assessment in the Asia Pacific region.
      • World Health Organization
      Regional Office for the Western Pacific. Factors conducive to the development of health technology assessment in Asia: impacts and policy options.
      • Ikegami N.
      • Drummond M.
      • Fukuhara S.
      • Nishimura S.
      • Torrance G.W.
      • Schubert F.
      Why has the use of health economic evaluation in Japan lagged behind that in other developed countries?.
      Only recently, the growing necessity to provide the best value for money, while safeguarding accessibility of care, has led a growing number of Asian countries to implement HTA for the evaluation of the clinical and economic value of healthcare technologies, defined as any type of drugs, devices, and procedures.
      • World Health Organization
      Regional Office for the Western Pacific. Factors conducive to the development of health technology assessment in Asia: impacts and policy options.
      • Oortwijn W.
      • Mathijssen J.
      • Banta D.
      The role of health technology assessment on pharmaceutical reimbursement in selected middle-income countries.
      The first Asian HTA agency was established in Malaysia in 1995, followed by Thailand in 2007, South Korea in 2006, Vietnam in 2013, and Indonesia in 2014.
      • Lee S.-S.
      • Salole E.
      Market access for new medical technology in South Korea: a case study in health technology assessment policy development and implementation.
      Some factors that have contributed to the slow adoption of HTA in Asia are lack of awareness and of country-specific epidemiological, clinical, and health economics data, as well as disjointed research efforts.
      • Sivalal S.
      Health technology assessment in the Asia Pacific region.
      • Ikegami N.
      • Drummond M.
      • Fukuhara S.
      • Nishimura S.
      • Torrance G.W.
      • Schubert F.
      Why has the use of health economic evaluation in Japan lagged behind that in other developed countries?.
      Indeed, outcomes research and pharmacoeconomics, which are the bedrock of HTA, were introduced in Asia in the late 1990s,
      • Sivalal S.
      Health technology assessment in the Asia Pacific region.
      at which point many European countries, Canada, and Australia had already institutionalized HTA.
      • Banta D.
      • Kristensen F.B.
      • Jonsson E.
      A history of health technology assessment at the European level.
      • Hailey D.
      The history of health technology assessment in Australia.
      • Battista R.N.
      • Cote B.
      • Hodge M.J.
      • Husereau D.
      Health technology assessment in Canada.
      • Xie J.
      • Chalkidou K.
      • Kamae I.
      • et al.
      Policy considerations: ex-US payers and regulators.
      Several initiatives have contributed to fostering interest in HTA and provide guidance on how to build HTA capabilities in Asia.
      • Sivalal S.
      Health technology assessment in the Asia Pacific region.
      The Asian HTA network was established in the 1990s with the goal to advance HTA in the Asia-Pacific region, and its first meeting was held in 1996.
      • Sivalal S.
      Health technology assessment in the Asia Pacific region.
      In 2011, a network of Asian HTA agencies, HTAsiaLink, was formed to strengthen collaborations and encourage joint research projects in Asia.
      HTAsiaLink
      HTAsiaLink: history.
      A pivotal force in promoting HTA worldwide has been the International Society for Pharmacoeconomics and Outcomes Research (ISPOR).
      ISPOR
      The Professional Society for Health Economics and Outcomes Research.
      The ISPOR Asia-Pacific meetings and the formation of the ISPOR Asia Consortium have been instrumental in spreading awareness of the benefits of HTA to inform and guide healthcare policies and practices in Asia.
      ISPOR
      About the ISPOR Asia Consortium.
      In addition, several journals—particularly the official journal of ISPOR, Value in Health—have contributed to publishing peer-reviewed pharmacoeconomic research on HTA methodologies and principles such as cost-effectiveness thresholds and cost-utility analyses and have provided a valuable platform to share HTA expertise and capabilities around the world.
      • Ngorsuraches S.
      • Chaiyakunapruk N.
      • Jianfei Guo J.
      • Yang B.-M.
      Is it time for joint health technology assessment in Asia? Opportunities and challenges.
      • Doshi J.A.
      • Willke R.J.
      Advancing high-quality value assessments of health care interventions.
      • Kulsomboon V.
      • Yang B.-m.
      • Hu S.
      Bridging the gap in pharmacoeconomics and outcomes research between researchers, policymakers, and practitioners in the Asia-Pacific region.
      • Lee Y.K.
      • Nam H.S.
      • Chuang L.H.
      • et al.
      South Korean time trade-off values for EQ-5D health states: modeling with observed values for 101 health states.
      • Shiroiwa T.
      • Fukuda T.
      • Ikeda S.
      • Takura T.
      • Moriwaki K.
      Development of an official guideline for the economic evaluation of drugs/medical devices in Japan.
      There is no one-size-fits-all approach to building HTA, and efforts should be customized to fit existing and often complex coverage, reimbursement, and pricing schemes.
      • Xie J.
      • Chalkidou K.
      • Kamae I.
      • et al.
      Policy considerations: ex-US payers and regulators.
      • Dankó D.
      Health technology assessment in middle-income countries: recommendations for a balanced assessment system.
      This review aims to provide an overview of how HTA has been and is being implemented in Asia within the context of a country’s healthcare system and priorities. To this end, 3 countries at different stages of HTA implementation have been selected as case studies: South Korea, where there is a young yet established HTA program; Japan, where a 3-year HTA pilot program has just concluded; and China, where efforts are underway but HTA has not been formally implemented (Table 1). The experiences of these 3 countries exemplify how HTA can be adopted to meet a country’s unique healthcare needs and provide the opportunity to outline some key challenges that must be overcome to implement and develop HTA competencies and capabilities.
      Table 1Summary of the current HTA status in each country.
      Healthcare systemYear HTA establishedHTA agencyEvidence evaluated by HTA
      South KoreaUniversal coverage2006









      2008
      Health Insurance Review and Assessment Agency (HIRA)







      National Evidence-based healthcare Collaborating Agency (NECA)
      Clinical benefits

      Cost-effectiveness

      Budget impact analysis

      Reimbursement status in other countries

      Public health considerations

      Clinical benefits

      Safety

      Cost-effectiveness

      Roundtable consensus building
      JapanUniversal coverage2016 three-year pilot program

      2019 Institutionalization
      Central Social Insurance Medical Council (“Chuikyo”)

      2018 C2H, National Institute of Public Health
      Clinical benefits

      Budget impact analysis

      Cost-effectiveness

      Considerations on rare diseases, cancers, etc

      Reimbursement and price status of the same drug in other countries
      ChinaNear universal (95%)

      Universal coverage expected by 2020
      Not yet formally establishedN/AN/A
      HTA indicates health technology assessment; N/A, none available.

      South Korea

       Healthcare System

      South Korea has had a universal healthcare system since 1989, when the National Health Insurance (NHI) service was established.
      • Song Y.J.
      The South Korean health care system.
      After a major reform in 2000, all medical insurance societies were merged into the NHI, which then became the country’s single payer.
      • Kwon S.
      • Lee T.-j.
      • Kim C.-y.
      Republic of Korea: health system review.
      Since the NHI was formed, total healthcare expenditures have steadily increased. From 2000 to 2009, the average yearly rate of increase was 9.8%, more than twice than that of the Oceania-Pacific region.
      • Seo H.-J.
      • Park J.J.
      • Lee S.H.
      A systematic review on current status of health technology reassessment: insights for South Korea.
      In 2016, nearly 8% of the total gross domestic product (GDP) was spent on healthcare, up 4% from 2000.
      Statista
      South Korea’s national health expenditure as a percent of GDP from 2000 to 2016.
      Such a steep increase in healthcare spending has been attributed to rising pharmaceutical prices, population aging, increased prevalence of chronic diseases, as well as the growing number of reimbursable drugs.
      • Park S.E.
      • Lim S.H.
      • Choi H.W.
      • et al.
      Evaluation on the first 2 years of the positive list system in South Korea.
      • Kim C.Y.
      Health technology assessment in South Korea.
      • Ahn J.
      • Kim G.
      • Suh H.S.
      • Lee S.M.
      Social values and healthcare priority setting in Korea.

       HTA Structure and Appraisal Process

      To curb healthcare spending, South Korea became the first Asian country to officially implement HTA to inform reimbursement decisions and introduced the positive list system (PLS) in 2006, which includes a formal HTA process for new drugs.
      • Park S.E.
      • Lim S.H.
      • Choi H.W.
      • et al.
      Evaluation on the first 2 years of the positive list system in South Korea.
      • Bae E.Y.
      • Hong J.M.
      • Kwon H.Y.
      • et al.
      Eight-year experience of using HTA in drug reimbursement: South Korea.
      The agency responsible for reimbursement decisions is the Health Insurance Review and Assessment Agency (HIRA), which acts independently but is under the supervision of the Ministry of Health and Welfare.
      • Kwon S.
      • Lee T.-j.
      • Kim C.-y.
      Republic of Korea: health system review.
      Before the PLS, most drugs approved by the Ministry of Food and Drug Safety were almost automatically listed on the NHI benefit schedule (the official list of reimbursable drugs) and priced based on predetermined formulae.
      • Ahn J.
      • Kim G.
      • Suh H.S.
      • Lee S.M.
      Social values and healthcare priority setting in Korea.
      • Bae E.Y.
      • Hong J.M.
      • Kwon H.Y.
      • et al.
      Eight-year experience of using HTA in drug reimbursement: South Korea.
      After the PLS, the decision to list a new drug on the benefit schedule was based on both clinical and pharmacoeconomic considerations.
      • Park S.E.
      • Lim S.H.
      • Choi H.W.
      • et al.
      Evaluation on the first 2 years of the positive list system in South Korea.
      • Bae E.Y.
      • Hong J.M.
      • Kwon H.Y.
      • et al.
      Eight-year experience of using HTA in drug reimbursement: South Korea.
      If a drug is deemed appropriate for reimbursement by HIRA, its price is negotiated by the National Health Insurance Service directly with the manufacturer and may be listed on the schedule afterward.
      • Bae E.Y.
      • Hong J.M.
      • Kwon H.Y.
      • et al.
      Eight-year experience of using HTA in drug reimbursement: South Korea.
      Should price negotiations fall apart, the drug is not listed or considered reimbursable; however, if the drug is regarded as medically necessary, the price is reviewed by an independent arbitration committee and a decision made within 60 days. Exceptions exist for some orphan drugs, which can be listed without providing evidence on their cost-effectiveness at a price equal or lower than that in 7 other countries (the United States, the United Kingdom, Germany, France, Italy, Switzerland, and Japan).
      • Bae E.Y.
      • Hong J.M.
      • Kwon H.Y.
      • et al.
      Eight-year experience of using HTA in drug reimbursement: South Korea.
      According to HIRA guidelines, reimbursement decisions hinge on 5 main criteria
      • Park S.E.
      • Lim S.H.
      • Choi H.W.
      • et al.
      Evaluation on the first 2 years of the positive list system in South Korea.
      :
      • 1.
        Clinical benefits assessed considering clinical trial data, clinical guidelines, systematic reviews, and expert opinions
      • 2.
        Cost-effectiveness based on the “therapeutic superiority to a comparator” criterion: if a new drug is therapeutically comparable to an existing drug (comparator), the costs of the 2 drugs are compared and cost minimization is applied, precluding any drug that is more expensive than its comparator(s) to be listed. If a new drug has improved effectiveness but is more expensive than its comparator(s), 2 measures of value are considered: the incremental cost-effectiveness ratio (ICER) and the quality-adjusted life-year (QALY). HIRA decided against setting an ICER threshold value, instead relying on the per-capita GDP. This was done to make more flexible decisions based not just on ICER values but also on quality of life, disease severity, and societal burden. For example, recently, a drug aimed at reducing progression to blindness was recommended for listing even though the ICER was higher than the per-capita GDP.
        • Park S.E.
        • Lim S.H.
        • Choi H.W.
        • et al.
        Evaluation on the first 2 years of the positive list system in South Korea.
      • 3.
        Budget impact analysis estimating changes in net costs associated with the entry of a new treatment over a period of 3 years using epidemiologic data, market-share data, costs associated with treatment and side effects, and other relevant healthcare costs
      • 4.
        Reimbursement status of the same drug in 7 other countries, the United States, United Kingdom, Germany, France, Italy, Switzerland, and Japan
      • 5.
        Public health considerations
      Although not officially part of the assessment process, decisions issued by 3 other HTA agencies (Australia’s Pharmaceutical Benefits Advisory Committee, the Canadian Expert Drug Advisory Committee, and the United Kingdom’s Technical Appraisal Committee
      • Park S.E.
      • Lim S.H.
      • Choi H.W.
      • et al.
      Evaluation on the first 2 years of the positive list system in South Korea.
      ) are taken into consideration, if deemed applicable to South Korea’s population and clinical setting.
      Generally, a positive recommendation from HIRA is necessary for a new drug to be placed in the benefit schedule.
      • Bae E.Y.
      • Hong J.M.
      • Kwon H.Y.
      • et al.
      Eight-year experience of using HTA in drug reimbursement: South Korea.
      Nevertheless, a positive recommendation does not guarantee that the drug will be listed at the manufacturer-proposed price, and the final negotiated price may be lower than the one initially submitted by the manufacturer.
      • Bae E.Y.
      • Hong J.M.
      • Kwon H.Y.
      • et al.
      Eight-year experience of using HTA in drug reimbursement: South Korea.
      During price negotiations, an expected annual drug usage volume is also established; a price cut of up to 10% is applied to drugs that exceed the agreed annual usage volume.
      Over the first 2 years after the incorporation of HTA into reimbursement decision making, manufacturers submitted 91 new drug applications, and 70% of them resulted in a positive recommendation.
      • Park S.E.
      • Lim S.H.
      • Choi H.W.
      • et al.
      Evaluation on the first 2 years of the positive list system in South Korea.
      The 2 criteria that have had the most impact in determining a final recommendation are clinical benefits and cost-effectiveness.
      • Park S.E.
      • Lim S.H.
      • Choi H.W.
      • et al.
      Evaluation on the first 2 years of the positive list system in South Korea.
      • Ahn J.
      • Kim G.
      • Suh H.S.
      • Lee S.M.
      Social values and healthcare priority setting in Korea.
      In 2008, the National Evidence-based healthcare Collaborating Agency (NECA) was established to conduct HTA research, and in 2010, the HTA processes pertaining to procedures and diagnostics were transferred from HIRA to NECA.
      • Lee S.-S.
      • Salole E.
      Market access for new medical technology in South Korea: a case study in health technology assessment policy development and implementation.
      • Seo H.-J.
      • Park J.J.
      • Lee S.H.
      A systematic review on current status of health technology reassessment: insights for South Korea.
      NECA also introduced a topic solicitation program in which topics suggested by the general public or experts were selected for HTA review.
      • Seo H.-J.
      • Park J.J.
      • Lee S.H.
      A systematic review on current status of health technology reassessment: insights for South Korea.
      This program has had an important impact on policy and reimbursement decisions. For example, cost-effectiveness analyses conducted by NECA led the prostate-specific antigen test to not be included in the National Cancer Screening Program and the human papilloma virus vaccination to be included in the National Immunization Program.

       Future Challenges

      South Korea represents an ideal case study to illustrate how HTA capabilities can be quickly and successfully implemented within a universal healthcare system. Some of the challenges faced by South Korea during the HTA implementation process—for example, a lack of clear guidelines that initially led to dissatisfaction among manufacturers and healthcare providers, requiring corrective measures
      • Lee S.-S.
      • Salole E.
      Market access for new medical technology in South Korea: a case study in health technology assessment policy development and implementation.
      —can serve as an example to other countries adopting HTA.
      One of the biggest remaining challenges is the development of professional staff with the necessary pharmacoeconomic expertise.
      • Oortwijn W.
      • Mathijssen J.
      • Banta D.
      The role of health technology assessment on pharmaceutical reimbursement in selected middle-income countries.
      • Kim C.Y.
      Health technology assessment in South Korea.
      A shortage of experts with a profound understanding of the HTA framework and methodologies can significantly hamper its implementation and institutionalization.
      • Sivalal S.
      Health technology assessment in the Asia Pacific region.
      Thus, one key future challenge to further develop HTA capabilities in South Korea will be training and recruiting human resources.
      • Oortwijn W.
      • Mathijssen J.
      • Banta D.
      The role of health technology assessment on pharmaceutical reimbursement in selected middle-income countries.
      In addition, developing and maintaining clear and standardized guidelines, along with fostering open communication among all healthcare stakeholders, will be crucial to facilitate and streamline the submission and review processes, allowing cost-effective treatments to promptly reach patients.
      • Lee S.-S.
      • Salole E.
      Market access for new medical technology in South Korea: a case study in health technology assessment policy development and implementation.
      The generation of clinical and economic data at the local level should also be encouraged.
      Lastly, given that HTA may be a difficult concept in South Korea, awareness should be raised regarding the benefits of the HTA appraisal process among the general public, clinical settings, and pharmaceutical and medical device industries.
      • Oortwijn W.
      • Mathijssen J.
      • Banta D.
      The role of health technology assessment on pharmaceutical reimbursement in selected middle-income countries.
      Emphasis should be placed on principles such as accountability for reasonableness, which calls for fair process, decision-making transparency, and clear procedures for revising decisions.
      • Daniels N.
      Accountability for reasonableness: establishing a fair process for priority setting is easier than agreeing on principles.

      Japan

       Healthcare System

      Japan achieved universal health insurance coverage in 1961.
      • Sakamoto H.
      • Rahman M.
      • Nomura S.
      • et al.
      Japan: health system review.
      The Employees’ Health Insurance System provides coverage for fully employed people and their dependents, funded by contributions from employees and employers.
      • Sakamoto H.
      • Rahman M.
      • Nomura S.
      • et al.
      Japan: health system review.
      Coverage for nearly everybody else is provided by the Japanese National Health Insurance, and all seniors are entitled to government-sponsored insurance.
      • Sakamoto H.
      • Rahman M.
      • Nomura S.
      • et al.
      Japan: health system review.
      International Commonwealth Fund
      The Japanese health care system.
      Monthly insurance premiums are based on annual income, and patients are responsible for copayments and 10% to 30% of medical costs, depending on age and income, with the government covering the remainder.
      • Sakamoto H.
      • Rahman M.
      • Nomura S.
      • et al.
      Japan: health system review.
      International Commonwealth Fund
      The Japanese health care system.
      Patients are free to choose any healthcare provider and medical facility and cannot be denied coverage.
      • Sakamoto H.
      • Rahman M.
      • Nomura S.
      • et al.
      Japan: health system review.

       Current Pricing and Reimbursement System

      The coverage and prices of all pharmaceuticals, medical devices, and healthcare services are set by the Ministry of Health, Labor, and Welfare (MHLW) uniformly throughout the country and are scheduled for reassessment every 2 years.
      • Sakamoto H.
      • Rahman M.
      • Nomura S.
      • et al.
      Japan: health system review.
      • Kamae I.
      Value-based approaches to healthcare systems and pharmacoeconomics requirements in Asia: South Korea, Taiwan, Thailand and Japan.
      • Shiroiwa T.
      • Fukuda T.
      • Ikeda S.
      • Takura T.
      New decision-making processes for the pricing of health technologies in Japan: the FY 2016/2017 pilot phase for the introduction of economic evaluations.
      In 2017, a one-time price revision was conducted to counterbalance an increase in consumption tax.
      • Sakamoto H.
      • Rahman M.
      • Nomura S.
      • et al.
      Japan: health system review.
      Drug prices are set by comparison with similar drugs available in Japan or other markets or, if no comparator exists, based on cost-plus pricing to cover the drug development costs sustained by manufacturers.
      • Shiroiwa T.
      • Fukuda T.
      • Ikeda S.
      • Takura T.
      New decision-making processes for the pricing of health technologies in Japan: the FY 2016/2017 pilot phase for the introduction of economic evaluations.
      The reimbursement rate of all new health technologies is initially set by the MHLW at 70% of the listed price and reduced every 2 years, with few exceptions.
      • Hisashige A.
      History of healthcare technology assessment in Japan.
      • Kennedy-Martin T.
      • Mitchell B.D.
      • Boye K.S.
      • et al.
      The health technology assessment environment in mainland China, Japan, South Korea, and Taiwan—implications for the evaluation of diabetes mellitus therapies.
      The use of pharmacoeconomic data to demonstrate value for money was recommended in the early 1990s but was not compulsory, and such data have had minimal to no weight in pricing and reimbursement
      • Shiroiwa T.
      • Fukuda T.
      • Ikeda S.
      • Takura T.
      New decision-making processes for the pricing of health technologies in Japan: the FY 2016/2017 pilot phase for the introduction of economic evaluations.
      • Hisashige A.
      History of healthcare technology assessment in Japan.
      until a pilot program to assess cost-effectiveness was introduced in April 2016. Once approved, nearly all drugs are automatically added to the National Formulary.
      • Shiroiwa T.
      • Fukuda T.
      • Ikeda S.
      • Takura T.
      • Moriwaki K.
      Development of an official guideline for the economic evaluation of drugs/medical devices in Japan.
      As a result, pharmaceutical companies had mostly shied away from presenting cost-effectiveness evidence until 2016,
      • Ikegami N.
      • Drummond M.
      • Fukuhara S.
      • Nishimura S.
      • Torrance G.W.
      • Schubert F.
      Why has the use of health economic evaluation in Japan lagged behind that in other developed countries?.
      • Ikegami N.
      • Ikeda S.
      • Kawai H.
      Why medical care costs in Japan have increased despite declining prices for pharmaceuticals.
      and data were presented for only 8 new drugs between 2006 and 2011.
      • Shiroiwa T.
      • Fukuda T.
      • Ikeda S.
      • Takura T.
      • Moriwaki K.
      Development of an official guideline for the economic evaluation of drugs/medical devices in Japan.

       The HTA Pilot Program and Subsequent Institutionalization

      Over the past 2 decades, Japan’s economic slowdown, negative population growth coupled with a high life expectancy, an increase in chronic diseases, and the increasing use of expensive drugs have placed a significant strain on the healthcare system.
      • Kamae I.
      Value-based approaches to healthcare systems and pharmacoeconomics requirements in Asia: South Korea, Taiwan, Thailand and Japan.
      • Shiroiwa T.
      • Fukuda T.
      • Ikeda S.
      • Takura T.
      New decision-making processes for the pricing of health technologies in Japan: the FY 2016/2017 pilot phase for the introduction of economic evaluations.
      • Tokuyama M.
      • Gericke C.A.
      Health technology assessment in Japan: history, current situation, and the way forward.
      • Fukuda T.
      • Shiroiwa T.
      Application of economic evaluation of pharmaceuticals and medical devices in Japan.
      As a result, healthcare spending increased from 6.3% of the GDP in 1995 to 10.9% in 2015.
      • Sakamoto H.
      • Rahman M.
      • Nomura S.
      • et al.
      Japan: health system review.
      In response to escalating healthcare demands and costs, in April 2016, Japan started a 2-year HTA pilot program that was extended to 3 years, supervised by the Central Social Insurance Medical Council (“Chuikyo”), part of the MHLW.
      • Shiroiwa T.
      • Fukuda T.
      • Ikeda S.
      • Takura T.
      • Moriwaki K.
      Development of an official guideline for the economic evaluation of drugs/medical devices in Japan.
      • Shiroiwa T.
      • Fukuda T.
      • Ikeda S.
      • Takura T.
      New decision-making processes for the pricing of health technologies in Japan: the FY 2016/2017 pilot phase for the introduction of economic evaluations.
      Also, in collaboration with the Chuikyo, the Center for Outcomes Research and Economic Evaluation for Health (CORE2HEALTH or C2H) was established in April 2018 as an organization of the National Institute of Public Health. The C2H conducts official analyses of cost-effectiveness evaluations from a scientific viewpoint.
      As part of the HTA pilot program, 7 drugs, including sofosbuvir, daclatasvir, and nivolumab,
      • Sakamoto H.
      • Rahman M.
      • Nomura S.
      • et al.
      Japan: health system review.
      Decision Resources Group
      Early HTA developments in Japan offer some positives for the pharma industry.
      and 6 medical devices were selected for cost-effectiveness assessment, reported using an ICER.
      • Shiroiwa T.
      • Fukuda T.
      • Ikeda S.
      • Takura T.
      New decision-making processes for the pricing of health technologies in Japan: the FY 2016/2017 pilot phase for the introduction of economic evaluations.
      Subsequently, the Chuikyo employed the ICER to adjust the price based on a QALY threshold of 5 million yen for a 10% reduction in premium, after which the premium will be reduced by up to 90% until the threshold of 10 million yen is reached.
      • Kristensen F.B.
      • Husereau D.
      • Huic M.
      • et al.
      Identifying the need for good practices in health technology assessment: summary of the ISPOR HTA Council working group report on good practices in HTA.
      This approach for ICER-based pricing uses a “slope” method, not adjusting if the ICER is smaller than 5 million yen per QALY or keeping the flat reduction rate of 90% if the ICER is 10 million yen per QALY or greater. In the case of dominance, adjusting upward was considered. Following the end of the pilot program, in April 2019, Japan instituted new HTA processes for ICER-based pricing, targeting new and existing drugs and medical devices of significant budget impact. The standard assessment route was changed into a “step,” instead of “slope,” with 3-step reductions of premium, 30%, 60%, and 90% according to 5, 7.5, and 10 million yen per QALY, respectively. There is a special assessment route for rare disease, pediatric, or anticancer therapies, which will use QALY thresholds that are 50% higher. Nevertheless, there is concern that the new HTA policies do not completely conform to ISPOR’s HTA Task Force recommendations.
      • Kristensen F.B.
      • Husereau D.
      • Huic M.
      • et al.
      Identifying the need for good practices in health technology assessment: summary of the ISPOR HTA Council working group report on good practices in HTA.

       Future Challenges

      As Japan looks to fully embrace HTA, several challenges lie ahead. In particular, some unique features of the Japanese pricing and reimbursement system, such as the fixed-fee schedule, will undoubtedly make the incorporation of HTA into existing practices challenging for both the government and manufacturers.
      ISPOR
      Challenges and best practices for the Japan health technology assessment pilot program.
      In April 2018, cost-effectiveness results were used to reduce the price of 2 drugs selected for the HTA pilot program, nivolumab and ado-trastuzumab emtansine.
      • Fukushima A.
      • Dorey J.
      • Ueyama M.
      • François C.
      • Toumi M.
      Evolution of HTA system in Japan: progress and conservatism.
      As the new HTA processes from the pilot program are fully implemented, cooperation between the government and pharmaceutical manufacturers will be needed to reach pricing agreements. Japan’s tightly regulated healthcare system has led the pharmaceutical industry to only sparingly, if ever, generate and use pharmacoeconomics data. Therefore, there is a need to increase the building of in-house capabilities and expertise. The government will need to recruit and develop experts to conduct HTA assessment and review, as the present reliance on academia will no longer be sustainable as the HTA program expands.
      • Kamae I.
      Value-based approaches to healthcare systems and pharmacoeconomics requirements in Asia: South Korea, Taiwan, Thailand and Japan.
      • Shiroiwa T.
      • Fukuda T.
      • Ikeda S.
      • Takura T.
      New decision-making processes for the pricing of health technologies in Japan: the FY 2016/2017 pilot phase for the introduction of economic evaluations.
      Key to the success of HTA in Japan will be the ability to generate evidence based on real-world national data,
      ISPOR
      Challenges and best practices for the Japan health technology assessment pilot program.
      and the development of a nationwide electronic medical record system is expected to provide this.
      Export.gov
      Japan—healthcare IT.
      In addition, the pharmaceutical industry’s concerns regarding the use of measures such as ICER and QALY will need to be assuaged, and the rationale that cost-effectiveness will have in determining final pricing and reimbursement decisions will need to be clarified.
      • Xie J.
      • Chalkidou K.
      • Kamae I.
      • et al.
      Policy considerations: ex-US payers and regulators.
      • Shiroiwa T.
      • Fukuda T.
      • Ikeda S.
      • Takura T.
      New decision-making processes for the pricing of health technologies in Japan: the FY 2016/2017 pilot phase for the introduction of economic evaluations.
      ISPOR
      Challenges and best practices for the Japan health technology assessment pilot program.
      Patients, patient advocates, and physicians who are not familiar with HTA principles may have difficulty understanding how the value of a drug can be converted into a metric upon which decisions are made. HTA may also be seen as an attempt to limit patient access in an effort to reduce government spending. Therefore, engaging all stakeholders will be essential for a successful implementation of HTA in Japan.
      ISPOR
      Challenges and best practices for the Japan health technology assessment pilot program.

      China

       Healthcare System

      Publicly funded health insurance coverage for basic services is currently near universal, with more than 95% of Chinese citizens having basic medical insurance since 2011.
      • Sun Y.
      • Gregersen H.
      • Yuan W.
      Chinese health care system and clinical epidemiology.
      Under the Healthy China 2020 reform, the government plans to reach universal coverage by 2020.
      • Qingyue M.
      • Hongwei Y.
      • Wen C.
      • Qiang S.
      People’s Republic of China: health system review.
      There are 3 types of public health insurance: 1 for urban residents employed in a corporate setting; 1 for employed urban residents, students, children, and senior citizens; and 1 for rural residents.
      • Sun Y.
      • Gregersen H.
      • Yuan W.
      Chinese health care system and clinical epidemiology.
      • The Commonwealth Fund
      The Chinese health care system.
      The insurance for employed urban residents is mostly funded through employee and employer contributions, whereas the other 2 are primarily funded by government subsidies.
      • Sun Y.
      • Gregersen H.
      • Yuan W.
      Chinese health care system and clinical epidemiology.
      • The Commonwealth Fund
      The Chinese health care system.
      Public health insurance includes all medical visits, prescription drugs, and traditional Chinese medicine, with varying deductibles and copayments.
      • Qingyue M.
      • Hongwei Y.
      • Wen C.
      • Qiang S.
      People’s Republic of China: health system review.
      • The Commonwealth Fund
      The Chinese health care system.
      An initiative is underway to reduce the percentage of out-of-pocket spending, which mostly goes toward prescription drugs and high-cost services, to 28% of the total healthcare spending by 2020 and to 25% by 2030.
      • Fu W.
      • Zhao S.
      • Zhang Y.
      • Chai P.
      • Goss J.
      Research in health policy making in China: out-of-pocket payments in Healthy China 2030.
      Private insurance is encouraged but not mandatory and mainly covers cost-sharing charges as well as any gap in public insurance coverage.
      • Qingyue M.
      • Hongwei Y.
      • Wen C.
      • Qiang S.
      People’s Republic of China: health system review.
      • The Commonwealth Fund
      The Chinese health care system.

       Development of HTA Capabilities

      Initial efforts to introduce HTA in China were made in the 1990s and mostly consisted of research projects and activities conducted at local universities within research units established by the Minister of Health.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      • Chen Y.
      • Banta D.
      • Tang Z.
      Health technology assessment development in China.
      HTA activity substantially increased in the mid-2000s, when more advanced but costly medical technologies (such as a magnetic resonance imaging) were introduced.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      HTA was still perceived as research versus as a healthcare policy tool, although interest in HTA continued to increase steadily. In 2008, several government-led HTA initiatives were undertaken under the auspices of the China National Health Development Research Center (CNHDRC) with the goal of informing healthcare policy decisions, and in 2010, the CNHDRC organized a National HTA Forum.
      • Zhao K.
      • Li X.
      • Guo W.
      • Xiao X.
      Coming rapidly of age: health technology assessment in China.
      Since then, efforts to further develop and expand HTA capabilities have noticeably intensified, as evidenced by the increase in the number of HTA-related publications and projects funded by the National Natural Science Foundation.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      For example, HTA was applied to assess the economic impact of antiviral therapies for hepatitis B and C, and budget impact analyses of pneumococcal and human papillomavirus vaccines were performed.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      In 2016, the China Health Policy and Technology Assessment Network—comprising 29 agencies, universities, hospitals, and professional associations—was established by the CNHDRC to develop HTA capacity and expertise.
      • Zhao K.
      • Li X.
      • Guo W.
      • Xiao X.
      Coming rapidly of age: health technology assessment in China.
      • Zhen X.
      • Sun X.
      • Dong H.
      Health technology assessment and its use in drug policies in China.
      Guidelines to strengthen the implementation of HTA were also issued, starting with the publication in 2015 of the China Guidelines for Pharmacoeconomic Evaluations.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      In 2018, a nationwide task force initiated a formal update of these guidelines, with the final guidelines expected to be released in 2019.
      Recently, several concrete steps to formally incorporate HTA into pricing and reimbursement decisions have been undertaken.
      • Zhen X.
      • Sun X.
      • Dong H.
      Health technology assessment and its use in drug policies in China.
      For instance, in 2017, select medical device manufacturers were asked, but not mandated, to submit both clinical and HTA-based data during price negotiations.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      • Zhen X.
      • Sun X.
      • Dong H.
      Health technology assessment and its use in drug policies in China.
      Also in 2017, an important change was made to the criteria used to establish whether a drug should be included in the National Reimbursement Drug List—and thus become reimbursable at the national level—as both clinical and economic evaluations were specified as requirement for inclusion.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      • Li H.
      • Liu G.G.
      • Wu J.
      • Wu J.H.
      • Dong C.H.
      • Hu S.L.
      Recent pricing negotiations on innovative medicines pilot in China: experiences, implications, and suggestions.
      After this change, the Ministry of Human Resources and Social Security, the agency responsible for reimbursement decisions, conducted price negotiations with the manufacturers of 44 drugs; 36 of them (31 Western drugs and 5 traditional Chinese medicines) were approved for inclusion in the National Reimbursement Drug List, with a 10% to 20% copay and an average price reduction of 44%, with the highest price reduction amounting to 70%.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      • Li H.
      • Liu G.G.
      • Wu J.
      • Wu J.H.
      • Dong C.H.
      • Hu S.L.
      Recent pricing negotiations on innovative medicines pilot in China: experiences, implications, and suggestions.
      These value-based price negotiations marked a significant shift from the Ministry of Human Resources and Social Security’s previous approach to price and reimbursement decisions, which were mostly based on qualitative expert consensus.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.

       Future Challenges

      While HTA continues to mature in China, it is still not fully incorporated into the health policy-making process.
      • Zhen X.
      • Sun X.
      • Dong H.
      Health technology assessment and its use in drug policies in China.
      The use of HTA is fragmented, and there is currently no single HTA agency operating at the national level that supervises and coordinates all HTA activities.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      • Zhen X.
      • Sun X.
      • Dong H.
      Health technology assessment and its use in drug policies in China.
      Instead, HTA research is scattered across governmental, academic, and industry-based centers, both at the local and national level.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      Although the government appears to place increasing importance on HTA to rein in healthcare costs while expanding access to care, decision making still relies heavily on expert opinion and experience rather than evidence-based data.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      To influence policy decisions, HTA would need to be fully and formally integrated into the existing pricing and reimbursement processes. This integration would require an official and well-recognized authority to regulate and implement the use of HTA.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      • Chen Y.
      • Banta D.
      • Tang Z.
      Health technology assessment development in China.
      • Zhen X.
      • Sun X.
      • Dong H.
      Health technology assessment and its use in drug policies in China.
      China should also increase efforts to nurture in-country expertise able to conduct independent and high-quality research needed to advance the use of HTA.
      • Chen Y.
      • Banta D.
      • Tang Z.
      Health technology assessment development in China.
      The number of HTA experts is low, and the quality of the research needs improvement.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      • Zhen X.
      • Sun X.
      • Dong H.
      Health technology assessment and its use in drug policies in China.
      In addition, more in-country real-world data are necessary to conduct HTA research that can take into consideration the characteristics of the Chinese patient population.
      • Li H.
      • Liu G.G.
      • Wu J.
      • Wu J.H.
      • Dong C.H.
      • Hu S.L.
      Recent pricing negotiations on innovative medicines pilot in China: experiences, implications, and suggestions.
      Another issue is the scarce awareness of HTA among both healthcare providers and policy makers. In one study, 60% of policy makers were unable to understand HTA studies, and only 3.5% reported to fully understand the concept of HTA.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      • Shi L.
      • Mao Y.
      • Tang M.
      • et al.
      Health technology assessment in China: challenges and opportunities.
      Even among those who had some knowledge of the principles of HTA, the HTA studies were difficult to understand and interpret, partly because of the complex pharmacoeconomic jargon.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      Among the general public, very few people are aware of the existence and concept of HTA.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      Promoting a more thorough understanding of HTA and its associated benefits among all stakeholders is necessary for a successful nationwide implementation of HTA.
      • Chen Y.
      • He Y.
      • Chi X.
      • Wei Y.
      • Shi L.
      Development of health technology assessment in China: New challenges.
      • Zhen X.
      • Sun X.
      • Dong H.
      Health technology assessment and its use in drug policies in China.

      Discussion

      The adoption of HTA has been slow and uneven across Asia.
      • Sivalal S.
      Health technology assessment in the Asia Pacific region.
      • World Health Organization
      Regional Office for the Western Pacific. Factors conducive to the development of health technology assessment in Asia: impacts and policy options.
      • Ikegami N.
      • Drummond M.
      • Fukuhara S.
      • Nishimura S.
      • Torrance G.W.
      • Schubert F.
      Why has the use of health economic evaluation in Japan lagged behind that in other developed countries?.
      Although HTA research activity has been present in Asia since the 1990s, it is only over the past decade that an increasing number of Asian countries are recognizing the value of HTA in setting prices and reimbursement rates to contain growing healthcare costs and more efficiently allocate resources.
      • Sivalal S.
      Health technology assessment in the Asia Pacific region.
      The 3 case studies presented here—South Korea, Japan, and China (Table 1)—well exemplify the common and nation-specific challenges of integrating HTA into existing coverage, reimbursement, and pricing schemes. First, it is important to establish a clear, coherent, and standardized HTA framework that clearly defines objectives, measures, quality standards, best practices, and assessment guidelines. To this end, how the evaluation should proceed requires careful consideration based on country-specific situations. Decisions should be made as to whether evaluations should be conducted based on manufacturer submissions, using independent review or specialized assessment groups, by groups, or using a hybrid approach. Specific guidance should be provided on how to select comparators and outcomes, which types of economic evaluation are required, and the acceptable budget impact and cost-effectiveness thresholds. In addition, there should be clarity as to how the evaluation results will affect reimbursement and price negotiation.
      Second, the generation of country-specific real-world data to be used in HTA evaluations should be encouraged and national databases established or expanded. In addition, in-country expertise and human resources should be developed to ensure the rigorous application of HTA methodologies and principles. To this end, international collaborations and networks can provide crucial guidance and support, particularly during the initial phases of HTA implementation. Further, to ensure the transparency of the HTA appraisal process, all stakeholders should be involved at each step of implementation, from manufacturers to healthcare providers and patients. This will avoid the misperceptions that HTA adoption is a way to limit patient access to expensive but clinically beneficial health technologies or that it is an attempt to increase government leverage over pharmaceutical companies during pricing and reimbursement negotiations.
      Finally, to sustain the continued adoption and maturation of HTA nationally and internationally, it is important to demonstrate and measure the beneficial impact of HTA on healthcare delivery, clinical outcomes, and quality of life. Importantly, any reduction in healthcare expenditures resulting from the use of HTA should be quantified, whenever possible, to illustrate the economic value the HTA appraisal process and justify the investments made in supporting and fostering it.

      Acknowledgments

      Cinzia Metallo, PhD, and Shelley Batts, PhD, provided research and writing assistance. The authors have no other financial relationships to disclose.

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