保健医療科学

2021

Vol.70 No.1 p.22－27

Topics: Recent topics in public health in Japan 2021

＜ Review ＞
Cost effectiveness evaluation of health care technologies in Japan:
New HTA system and the role of C2H
FUKUDA Takashi, SHIROIWA Takeru
Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health
Abstract
Advancing medical technologies is one of the main reasons to increase medical expenditure. One possible
way to consider efficiency is to evaluate cost effectiveness of medical technologies and make decisions upon
the results. It is often described as health technology assessment, HTA. In Japan, introduction of HTA system was discussed since 2010. After 10 years of discussion, a new HTA system was established in 2019.
In the new HTA system, the manufacturer must submit the data first. The submitted analysis is reviewed
and reanalyzed by academic analysis groups and is finalized by Center for Outcomes Research and Economic Evaluation for Health(C2H) at the National Institute of Public Health. Based on the manufacturer’ssubmission and the C2H public analysis, the Expert Committee on Cost-Effectiveness Evaluation at theCentral Social Insurance Medical Council (CSIMC) examines the scientific quality of the analysis and determines the most likely incremental cost effectiveness ratio (ICER) figure or range for the product in theappraisal process.
The target drugs and medical devices are principally selected when they are newly listed at the general
assembly of CSIMC based on the predetermined selection criteria. The results of the evaluation will be
used for reimbursement price adjustment, not for coverage decision. When ICER exceeds 5 million JPY per
QALY, the price will be adjusted. For some diseases, such as rare or pediatric diseases and cancer, 7.5 million JPY per QALY will be used as threshold for price adjustment.
In order to implement full scale cost effectiveness evaluation, a new unit, “Center for Outcomes Research and Economic Evaluation for Health”, was established in 2018 at the National Institute of Public
Health.
keywords: cost effectiveness, health technology assessment, drug, medical device, Central Social Insurance
Medical Council, reimbursement price, Japan(accepted for publication, January 29, 2021)

I. Background
Advancing medical technologies is one of the main reasons to increase medical expenditure. Though new treatment technologies, including drugs and medical devices,
generally contribute to better outcome of patients, some ofthem are very costly. This is an issue not only in Japan. In
many countries health care delivery system is funded by either tax or public insurance scheme. In the system, healthcare budget is restricted and it is important to consider
efficient use of the budget. One possible way to consider
efficiency is to evaluate cost effectiveness of medical technologies and make decisions upon the results. It is often
described as health technology assessment, HTA. In HTA,
individual technology is evaluated by means of medical,
social, ethical and economic aspects. Cost effectivenessanalysis is the main tool to evaluate efficiency.
HTA system has been adopted in many countries, such as

Corresponding author: FUKUDA Takashi
2-3-6 Minami, Wako, Saitama 351-0197, Japan.
E-mail: fukuda.t.aa@niph.go.jp

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Cost effectiveness evaluation of health care technologies in Japan: New HTA system and the role of C2H
UK, Australia, Canada for many years. It is also introducedin Asian countries[1]. In Japan, introduction of HTA system
was discussed since 2010. After 10 years of discussion, anew HTA system was established in 2019.

II. Pilot program
Before implementing a new HTA system, a pilot programof cost effectiveness evaluation was introduced in 2016[2].
Target products were determined by the Central Social
Insurance Medical Council (CSIMC) based on the selection
criteria of the degree of innovation and market size. Target
products were chosen among the products, for which reimbursement decisions were made between FY 2012 andFY 2015. For the pilot program, 13 products (7 drugs and6 medical devices) were selected by CSIMC[3]. Drugs foranti-hepatitis C and PD-L1 antibody, which received muchattention in the press, were included as targeted products.
The manufacturers of the target products were requested to submit economic evaluation data by the end of FY
2016[4]. Once this was completed, academic groups, including experts on clinical epidemiology and health economics,
independently reviewed the data in early FY 2017. Because
Japan had no official HTA agency, such as the National
Institute for Health and Care Excellence (NICE) in theUnited Kingdom (UK) at that time, the National Instituteof Public Health (NIPH) coordinated this review process.
The reviewed data were finally sent to sub-committee under CSIMC, the “expert committee of cost-effectiveness”,
which was established in FY2016. The expert committee
had a role to perform “appraisal” of the data including a so-cial and ethical perspective. The results of this evaluation
were reflected in official prices during the next revision,from FY 2018.
In March 2018, based on the cost effectiveness results,
prices of the two of the target products were reduced,
though actual reduction rate were not disclosed.
However, 7 products out of 13 in the pilot program, analysis results submitted by manufacturers and reanalysis
group were markedly different, even though both analyses
followed the guideline. Major reasons for the discrepancy were; difference of the scope (eg. target population,comparator), difference in the selection of data used in theanalyses (eg. data sources, definition of the target patientsgroup). Because it was a pilot program, it was decided toverify the reasons of the discrepancy in order to consider amore rational analysis. For this purpose, analyses as a verification were performed in 2018.
In the same year, intensive discussion toward full implementation of a new HTA system was made in CSIMC.

III. The new HTA system
1. Target products of the new cost-effectiveness evaluation system
Due to the CSIMC discussions following the submissionof the pilot program, the new cost-effectiveness evaluation
is being used initially only for the price adjustment of drugs
and medical devices, not for reimbursement decision making[5]. The cost-effectiveness evaluation process starts after the products are launched in the market. The results arereflected in the product prices after approximately 15–18

Table 1 Selectedproducts as of December 2020
Table 1 Selected products as of December 2020

ID

Brand name

Generic nameCategory

C2H1901

TrelegyFluticasone, Umeclidinium, Vilanterol

H1

2019/05/15

C2H1902

KymriahTisagenlecleucel

H3

2019/05/15

C2H1903

Ultomiris

Ravulizumab

H1

2019/08/28

C2H1904

Breztri

Budesonide, Glycopyrronium, Formoterol

H5

2019/08/28

C2H1905

Trintellix

Vortioxetine

H1

2019/11/13

C2H1906

CoralanIvabradine

H2

2019/11/13

C2H2001

NoxafilPosaconazole

H1

2020/4/8

C2H2002

Cabometyx

Cabozantinib

H1

2020/5/13

C2H2003

Enhertu

Trastuzumab Deruxtecan（GeneticalRecombination）

H1

2020/5/13

C2H2004

Zolgensma

Onasemnogene abeparvovec

H3

2020/5/13

C2H2005

Entresto

Sacubitril Valsartan

H5

2020/8/19

C2H2006

EnerzairIndacaterol, Glycopyrronium, Mometasone

H52020/8/19

C2H2007

Rybelsus

Semaglutide (Genetical Recombination)

H1

2020/11/11

J. Natl. Inst. Public Health, 70 (1) : 2021

Designatedday23FUKUDA Takashi, SHIROIWA Takeru
months.
The target drugs and medical devices are principally selected when they are newly listed at the general assemblyof the CSIMC (Table 1). At the time of the introduction of
the cost-effectiveness evaluation in 2019, the evaluation
results are initially used for:(A) Adjusting premiums when the price is calculated using
a “similar efficacy comparison method” (i.e., “new drugprice” = “existing drug price” + “premium”), and(B) adjusting the premium and regulated constant profit
rate for manufacturers (the latter is adjusted only if thedisclosure level is 50% or less) when the price is calculated using the “cost calculation method”.
Pediatric products, or products intended for designatedintractable and rare diseases as defined by Japanese law, areexempt from the evaluation. Moreover, in the case of (B), if
the disclosure level of the product is more than 50% and nopremium is added, the product is exempt from cost-effectiveness evaluation.
However, not all products that satisfy the above conditions are selected as targets; only products with a large budget impact are seleced. The selection criteria are as follows:･ Category H1: Annual peak sales of JPY 10 billion andover. In Japan, new products (drugs and devices) arelisted 4 times in a year. Products from category H1 areselected at the time of their listing and the cost-effectiveness evaluation process starts.
･ Category H2: Annual peak sales from JPY 5 billion to JPY
10 billion. H2 category products are considered candidate
targets. They are kept in reserve as candidates and thetarget products are selected from these candidates basedon their peak sales twice a year, considering the numberof selected products and the capacity for evaluation.
･ Category H3: The CSIMC can select target products under some conditions such as significantly high cost of theproduct.
･ Category H4: Products with premiums listed before theimplementation of the policy and whose annual actual
sales exceed JPY 100 billion. The criteria for categories
H1 to H3 are meant for products newly listed after thestart of the cost-effectiveness evaluation, and the criteria
for H4 are intended for existing, older technologies.
･ Category H5: In this final category, the drugs and devices
similar to the target products selected for evaluation areincluded. Such products are not individually evaluated but
their prices will be adjusted in the same manner as thesimilar product already targeted.

of products using the results of the cost-effectiveness evaluation[6]. In the case of products evaluated using the similar efficacy comparison method, only the premium (part ofthe whole price) is adjusted. In contrast, both the profit rate
and the premium are adjusted if the cost calculation method
is applied (the profit rate is adjusted only for products witha profit rate of 50% or less).
When additional benefits to a comparator can be proven,an incremental cost-effectiveness ratio (ICER) is calculated
by using quality adjusted life year (QALY) as common outcome measure. The adjustment rate is determined using
the ICER interval and the premium or profit rate. 5 million
JPY per QALY is used as reference value. When the resultshows that ICER is beyond 5 million JPY per QALY, theprice of the product should be adjusted. 7.5 million and 10
million JPY are also reference values. The price is adjusted
stepwise with those reference values.
In the case of oncology, pediatric, and designated intractable and rare disease products, the reference value isincreased by a factor of 1.5. The factor is based on the consensus of the CSIMC.
Finally, if price is reduced based on the calculation above,the cost/QALY may fall below JPY 5 million (or JPY 7.5 million) as a result of the adjustment, and it may be over-adjusted for manufacturers. In this case, the reduction stops
at the threshold price. In addition, the maximum reduction
rate is limited to 10%–15% of the entire price before adjustment. Such safeguards may be put in place when the premium rate is high.
3. Process of cost-effectiveness evaluation
The target products are selected after the CSIMC decides the listing. If a product is selected for cost-effectiveness evaluation, the manufacturer must submit the data
within nine months from selection. During the first 3–6months, the analysis framework (including the target population, comparator, etc.) should be determined based on preliminary consultations with the Center for Outcomes Research and Economic Evaluation for Health (C2H) at NIPH.
The submitted analysis is reviewed by academic analysis
groups and is finalized by C2H within 3–6 months. Based on
the manufacturer’s submission and the C2H public analysis,the Expert Committee on Cost-Effectiveness Evaluation
examines the scientific quality of the analysis and determines the most likely ICER figure or range for the productin the appraisal process. This result is then reported to theCSIMC general assembly and the prices may be adjusted.
The entire process takes 15–18 months.

2. Price adjustment system based on cost-effectiveness
The CSIMS decides the reimbursement price adjustment

24J. Natl. Inst. Public Health, 70 (1) : 2021

Cost effectiveness evaluation of health care technologies in Japan: New HTA system and the role of C2H

IV. Role of C2H

ited, assessment of the products are jointly worked with
contracted research teams at universities. This structure
is similar to the NICE in UK and academic groups. In orderto provide reasonable analyses, C2H issues guidelines foranalysis based on discussion in a research group funded by
MHLW (Figure 2). C2H also provides information on evaluation methods, including preliminary consultation processfor manufacturers.
Even though C2H provides public analyses and reports tosubcommittee of CSIMC, C2H does not perform appraisal.
Appraisals and decisions are made in CSIMC. After the final
decision is made for a product, C2H will open its report topublic.
Because capacity for evaluation is limited, it is important
to increase the number of experts. C2H contributes to develop a training program as well.
A new HTA system has just started in Japan. C2H iswilling to provide good information for decision makers forefficient use of medical technologies.

Health technology assessment is often used to decide
coverage of medical technologies under the public schemeor reimbursement prices. For this purpose, analyses must
be made from a fair and neutral perspective. HTA agencies
are publicly funded in most countries. For example, NICE
in UK is a non-departmental public body funded by thegovernment. In Australia, Pharmaceutical Benefit Advisory
Committee (PBAC), as a committee in the government,
plays the main role of HTA. In Japan, no HTA agency has
been existed. In order to implement full scale cost effectiveness evaluation, a new unit, “Center for Outcomes
Research and Economic Evaluation for Health”, was established in 2018 at the National Institute of Public Health.
Abbreviation is “CORE2-Health” or “C2H”. The main roleof C2H is assessment of the products which are selected byCSIMC (Figure 1). As mentioned earlier, manufactures areresponsible for submitting cost effectiveness analysis of theproduct. C2H reviews the results and perform reanalysis
when necessary. Before manufactures start their analysis,
Reference
it is important to discuss framework of analysis between
Figurecapacity
1 Flow ofofcost
effectivenessevaluation
the role
C2HJ, Kamae I, Xie J, Yang H. The[1] Liu andG, Wu
EQ, ofAhn
manufactures and C2H. Because
C2H
is limFlow of Cost Effectiveness EvaluationRole C2H

Target selection at CSIMC
Preliminary Consultation
Manufacturer’s submission
Review and Re-analysis

Preliminary consultation with manufacturer
Consultation with manufacturer upon request
Conduct review and re-analysis process withacademic groups
Final report of review and re-analysis

Appraisal
Price adjustment

Figure2 1Guideline
Preparing
Cost-Effectivenessto theFigure
Flow offor
costeffectivenessevaluationEvaluationand the roleof C2H2
Central Social Insurance Medical Council, Version 2.0
1. Objectives
2. Analysis perspective
3. Target population
4. Comparator(s)5. Additional benefit
6. Methods of analysis
7. Time horizon
8. Choice of outcome measure
9. Sources of clinical data (except costs)
10. Calculation of healthcare costs
11. Public long-term care costs and productivity loss
12. Discounting
13. Modelling
14. Uncertainty(downloadable form C2H website)
3

Figure 2 Guideline for Preparing Cost-Effectiveness Evaluation tothe Central Social Insurance Medical Council, Version 2.0J. Natl. Inst. Public Health, 70 (1) : 2021

25

FUKUDA Takashi, SHIROIWA Takeru
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sion-making processes for the pricing of health technologies in Japan: The FY 2016/2017 pilot phase forthe introduction of economic evaluations. Health Policy. 2017;121(8):836-841.
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J. Natl. Inst. Public Health, 70 (1) : 2021

Cost effectiveness evaluation of health care technologies in Japan: New HTA system and the role of C2H＜総説＞
日本における医療技術の費用対効果評価―新 HTA 制度と C2H の役割―
福田敬，白岩健
国立保健医療科学院保健医療経済評価研究センター

抄録
医療技術の進歩は医療費増加の一つの要因となっている．効率的な医療提供を推進するための一つの方策は，医療技術の費用対効果の評価を行い，その結果に基づき意思決定する方法である．一般に医療技術評価（HTA）と呼ばれる．日本ではHTA導入の議論が2010年頃にスタートし，約10年の議論を経て2019年に制度化された．
新HTA制度では，まず製造販売業者がデータを提出する必要がある．提出されたデータについて国立保健医療科学院保健医療経済評価研究センターおよび学術グループがレビューを行う．この結果に基づき中央社会保険医療協議会（中医協）の費用対効果評価専門組織が分析の科学的妥当性を検討し，増分費用効果比（ICER）の段を確定する．
分析対象となるのは中医協において新規に保険収載される医薬品および医療機器で，一定の条件を満たすものが選定される．分析結果は保険償還の可否ではなく，償還価格の調整に用いられる．
ICERが500万円/QALYを超えるものについて価格調整の対象となるが，希少疾患や小児特有の疾患および抗がん剤については750万円/QALYを超えるものが対象となる．
このような費用対効果評価制度を実施するために，2018年に国立保健医療科学院に保健医療経済評価研究センター（C2H）が設置された．
キーワード：費用対効果，医療技術評価，医薬品，医療機器，中央社会保険医療協議会，償還価格，日本

J. Natl. Inst. Public Health, 70 (1) : 2021

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