Abstract
Objective: Japan has resumed its health technology assessment to decide how to reduce high-cost drug prices. While drug price rules in Japan are comprehensive, they do not necessarily capture differences in product characteristics. This study examined the drug price revision strategy in Japan using migraine treatment with triptans as an example. Cost data from fiscal years (FY) 2018, 2020, and 2022 were utilized. Methods: A cost-utility analysis was conducted from the perspective of healthcare payers, focusing on Japanese patients aged over 18 years experiencing migraines. The study employed a base-case model with probabilities derived from a network meta-analysis. Direct costs included medical and drug costs. Effectiveness was assessed using the European Quality of Life 5-dimensions—3-level questionnaire. Deterministic and probabilistic sensitivity analyses were conducted to examine the level of uncertainty. Results: In FY2018, sumatriptan and eletriptan were cost-effective; however, the other triptans were dominated by sumatriptan. In FY2020, sumatriptan and eletriptan were cost-effective, and rizatriptan was extended-dominated; nevertheless, the other triptans were dominated by sumatriptan. In FY2022, naratriptan and eletriptan were cost-effective; however, the other triptans were dominated by naratriptan. The hierarchy of triptan strategies varied in each fiscal year. Conclusions: This study provides valuable insights into the drug price revision strategy in Japan. The variations could be problematic because in Japan, formulary management of triptans, for example, those for migraine, may face revaluation every other year. Discussions regarding this issue will be further explored in the future.
Keywords: drug price revision strategy, migraine, Japan, triptans, cost-utility analysis
Introduction
Japan’s healthcare system involves universal insurance coverage and its national health care expenditure (NHE) has been increasing over the years. 1 Drugs approved by the Japanese healthcare government are listed in the National Health Insurance system, 2 which has unique features not found in European countries such as its pricing methods: (1) the similar efficacy comparison method and (2) the cost-accounting method. 3 Briefly, (1) the similar efficacy comparison method is a process in which the daily drug price of a new drug is matched with the daily price of a similar existing drug. If the new drug is recognized to have higher novelty and usefulness than similar existing drugs, additional amounts are added to the daily drug price, including additional charges for staging, usefulness, marketability, pediatric patients, and so on. 3 (2) The cost-accounting method accumulates raw material costs, manufacturing costs, and other related costs. In principle, unit labor cost, operating profit margin, and distribution cost ratio are determined based on the related average from the pharmaceutical manufacturing industry (the average of the most recent 3 years obtained at the end of the previous year). 3 Recent approvals of high-cost agents, such as cancer agents, have contributed to the increase in NHE. Therefore, the Japanese government has tried to maintain the drug cost ratio at about 20% of the NHE using the drug price revision system to reduce increases in the NHE. 4
Health technology assessment (HTA) has been valuable for evaluating health technologies such as pharmaceutical drugs and devices in European countries. 5 Although its adoption in Asian countries has been slower, it was attempted in Japan between 2016 and 2019. 6 Initially, the new cost-effectiveness evaluation method was only applied to the price adjustments of pharmaceutical drugs and devices, which did not mean that the evaluation was used for reimbursement decision making. 7 The principle of the price adjustment system based on cost-effectiveness is as follows: If the incremental cost-effectiveness ratio (ICER) is over the Japanese reference value of 5 million JPY per quality-adjustment life year (QALY), the price adjustment rate is 30% lower; if ICER is over 7.5 million JPY per QALY, the price adjustment rate is 60% lower; and if ICER is over 10 million JPY per QALY, the price adjustment rate is 90% lower. 7 The HTA officially resumed in 2022 to decide how to reduce high-cost drug prices in Japan. 8 While drug price rules in Japan are comprehensive, they do not necessarily capture differences in product characteristics. 9 Furthermore, drug price revision has been regularly implemented in Japan, which may influence a cost-effective strategy.
Worldwide, formulary systems are active in healthcare; however, they were not introduced in Japan until 2005. 10 The Japanese Society of Formulary was established in 2021, coinciding with the growing adoption of formulary systems in hospitals. 11 In Japan, the term “economics” in the formulary’s definition is often used in the limited context of “reducing drug costs,” but comprehensive cost-effectiveness evaluations that consider efficacy and safety are critical. 11
Hence, it is necessary to pay attention to Japan’s healthcare cost-effective strategy and address any pharmacoeconomic problems. Some reports have already pointed out that the cost-effectiveness of anticoagulant, 12 osteoporosis, 13 and cancer 14 therapies, which are for chronic diseases, are sensitive to drug prices. Our previous studies discussed the cost-effectiveness of influenza virus infections15,16 and that of treatments for allergic rhinitis as acute diseases. 17 In both studies, drug prices were not sensitive to the results of the dominant cost-effectiveness analysis for a reference drug. During an examination of triptans used to treat migraines, we found that drug prices are sensitive to the results of the dominant cost-effectiveness analysis for a reference drug. In this study, we focused on influences of drug price-revision strategies in Japan using migraine treatment with triptans as an example of acute disease treatment. A cost-utility analysis (CUA) was conducted from the healthcare payers’ perspective to determine the cost-effectiveness of the 5 oral triptans available in the Japanese market. Cost resources for the fiscal years (FYs) 2018, 2020, and 2022 were used.
Methods
CUA Study Design
This work was conducted at a Japanese university as a simulation study. In Japan, the indications of triptans written in the package inserts state that when triptans are ineffective after the first intake, additional doses should be taken 2 hours apart. Additionally, a network meta-analysis evaluated triptan’s efficacy using 2-hour headache relief. Based on these backgrounds, a decision tree with 2-hour relief was created and is shown in Figure 1.
Figure 1.
Decision tree as a case-based scenario. <Health state 1>: “non-effective for the first 2 hours with persistent migraine,” <Health state 2>: “effective for the first 2 hours followed by migraine recurrence,” <Health state 3>: “effective for the first 2 hours with no migraine recurrence,” <Health state 4>: “healthy, with no migraine symptoms.”
The primary objective of this study was to discuss a drug price revision strategy for Japan from the perspective of healthcare payers. This study employed a 30-day model to assess the cost-utility of oral triptans in treating migraines within adult outpatient settings in Japan. Time horizons in previous pharmacoeconomic studies of triptans have ranged from 1 day to 10 years.18,19 A nationwide Japanese database study revealed that, on average, patients reported experiencing migraines for 7.70 out of the past 30 days. 20 Therefore, given the 30-day time horizon in this study, it was assumed, based on the decision tree, that patients in each health state spent 7.70 days with a migraine and 22.3 days without one.
The target population comprised adults (18 years and older) who experienced migraines and accessed outpatient settings. The decision-tree model used in this study refers to a previously reported model. 21 The effectiveness of triptan consumption was determined through a network meta-analysis. 22 The effectiveness percentages of achieving 2-hour relief after taking 20 mg eletriptan, 2.5 mg naratriptan, 10 mg rizatriptan, 50 mg sumatriptan, and 2.5 mg zolmitriptan were 60.4%, 44.5%, 57.1%, 49.7%, and 50.0%, respectively. The prevalences of non-recurrence at 2 hours after taking those triptans were 72.1%, 78.6%, 63.1%, 72.2%, and 65.8%, respectively. Health State 1 was defined as “non-effective for the first 2 hours with persistent migraine.” Health State 2 was defined as “effective for the first 2 hours followed by migraine recurrence.” Health State 3 was defined as “effective for the first 2 hours with no migraine recurrence.” Health State 4 was defined as “healthy, with no migraine symptoms.”
The direct medical costs comprised 2 categories: physicians and community pharmacies (Table 1). Physicians’ costs included the first medical examination, prescription issuance, and prescription fees. Community pharmacy costs included dispensing, pharmaceutical management fees, and pharmaceutical charges. These costs were retrieved from the 2018, 2020, and 2022 versions of the Medical Fee Index. 23 The prices of the triptan brands used in this study are presented in Table 2. Calculations of costs according to health states are summarized in Table 3. The value of the Japanese yen was calculated based on the value of USD at purchasing power parity using the Organisation for Economic Co-operation and Development 2018, 2020, and 2022 conversion factors (1 USD = 104.158636 yen for 2018; 100.742085 yen for 2020; 94.934984 yen for 2022). The willingness to pay (WTP) for Japan was set at 5,000,000 yen/QALY. 24
Table 1.
Direct Medical Costs.
| Items | Cost (yen) | Cost (USD) |
|---|---|---|
| Physician costs | ||
| First visit | ||
| First medical examination fee | ||
| FY2018 | 2820 | 27.07 |
| FY2020 | 2880 | 28.59 |
| FY2022 | 2880 | 30.34 |
| Prescription fee | ||
| FY2018 | 420 | 4.03 |
| FY2020 | 420 | 4.17 |
| FY2022 | 420 | 4.42 |
| Prescription issuance fee | ||
| FY2018 | 680 | 6.53 |
| FY2020 | 680 | 6.75 |
| FY2022 | 680 | 7.16 |
| Total | ||
| FY2018 | 3920 | 37.63 |
| FY2020 | 3980 | 39.51 |
| FY2022 | 3980 | 41.92 |
| Community pharmacy costs | ||
| Dispensing fee | ||
| Dispensing basic fee | ||
| FY2018 | 410 | 3.94 |
| FY2020 | 420 | 4.17 |
| FY2022 | 420 | 4.42 |
| As-needed medicines | ||
| FY2018 | 210 | 2.02 |
| FY2020 | 210 | 2.08 |
| FY2022 | 210 | 2.21 |
| Pharmaceutical management fee | ||
| Drug administration history management instruction fee | ||
| FY2018 | 380 | 3.65 |
| FY2020 | 570 | 5.66 |
| FY2022 | 590 | 6.21 |
| Pharmaceutical charge | (Drug price) × 5 tablets | NA |
Source. Ministry of Health, Labour and Welfare (2018, 2020, and 2022).
Table 2.
Pharmaceutical Charges for Triptans.
| Triptans | Authorized drug prices, yen/tablet (USD) | Dosage | Pharmaceutical charges per treatment, yen (USD) |
|---|---|---|---|
| 20 mg Eletriptan | |||
| FY2018 | 926 (8.89) | 5 tablets | 4630 (44.45) |
| FY2020 | 665.8 (6.61) | 3330 (33.05) | |
| FY2022 | 543.7 (5.73) | 2720 (28.65) | |
| 2.5 mg Naratriptan | |||
| FY2018 | 918.3 (8.82) | 5 tablets | 4590 (44.07) |
| FY2020 | 825.9 (8.20) | 4130 (41.00) | |
| FY2022 | 470 (4.95) | 2350 (24.75) | |
| 10 mg Rizatriptan | |||
| FY2018 | 945.1 (9.07) | 5 tablets | 4720 (45.32) |
| FY2020 | 655.3 (6.50) | 3280 (32.56) | |
| FY2022 | 523 (5.51) | 2610 (27.49) | |
| 50 mg Sumatriptan | |||
| FY2018 | 763.9 (7.33) | 5 tablets | 3820 (36.67) |
| FY2020 | 646.4 (6.42) | 3230 (32.06) | |
| FY2022 | 490.1 (5.16) | 2450 (25.81) | |
| 2.5 mg Zolmitriptan | |||
| FY2018 | 784.9 (7.54) | 5 tablets | 3920 (37.63) |
| FY2020 | 684.6 (6.80) | 3420 (33.95) | |
| FY2022 | 574.2 (6.05) | 2870 (30.23) | |
Source. Ministry of Health, Labour and Welfare (2018, 2022, and 2022).
Table 3.
Calculations of Direct Cost Based on Health States.
| Triptan, Fiscal year | Physician visit yen (USD) | Pharmacy visit yen (USD) | Drug price yen (USD) |
|---|---|---|---|
| 20 mg Eletriptan | |||
| FY2018 | 3920 (37.63) | 1000 (9.60) | 4630 (44.45) |
| FY2020 | 3980 (39.51) | 1200 (11.91) | 3330 (33.05) |
| FY2022 | 3980 (41.92) | 1200 (12.64) | 2720 (28.65) |
| 2.5 mg Naratriptan | |||
| FY2018 | 3920 (37.63) | 1000 (9.60) | 4590 (44.07) |
| FY2020 | 3980 (39.51) | 1200 (11.91) | 4130 (41.00) |
| FY2022 | 3980 (41.92) | 1200 (12.64) | 2350 (24.75) |
| 10 mg Rizatriptan | |||
| FY2018 | 3920 (37.63) | 1000 (9.60) | 4720 (45.32) |
| FY2020 | 3980 (39.51) | 1200 (11.91) | 3280 (32.56) |
| FY2022 | 3980 (41.92) | 1200 (12.64) | 2610 (27.49) |
| 50 mg Sumatriptan | |||
| FY2018 | 3920 (37.63) | 1000 (9.60) | 3820 (36.67) |
| FY2020 | 3980 (39.51) | 1200 (11.91) | 3230 (32.06) |
| FY2022 | 3980 (41.92) | 1200 (12.64) | 2450 (25.81) |
| 2.5 mg Zolmitriptan | |||
| FY2018 | 3920 (37.63) | 1000 (9.60) | 3920 (37.63) |
| FY2020 | 3980 (39.51) | 1200 (11.91) | 3420 (33.95) |
| FY2022 | 3980 (41.92) | 1200 (12.64) | 2870 (30.23) |
Calculations of Quality-Adjusted Life Years
Anonymous responses to the European Quality of Life 5 Dimension 3 Level (EQ-5D-3L) questionnaire were collected from patients undergoing migraine treatment at a community pharmacy. All patients in this study had attended a neurology clinic as outpatients. Since the community pharmacy was located near the clinic, pharmacists received prescriptions and asked patients to complete the EQ-5D-3L questionnaire while waiting for their prescriptions to be filled. Questions for health states are as follows; health state 1: you take a triptan, but it does not relieve your symptoms; health state 2: you took a triptan, which relieved your symptoms for about 2 hours, but your symptoms returned; and health state 3: your symptoms are relieved for 2 hours after taking a triptan preparation and do not recur thereafter. Patients were excluded if their prescriptions did not include triptan medications. Subsequently, the patients’ health-related utility scores were converted using a Japanese EQ-5D-3L tariff. QALYs in 3 health states were computed using the following formula:
For Health States 1, 2, and 3: QALY = ([utility score × 7.70 days] + [1 × 22.3 days])/365 days. The numerator was divided by 365 days to convert “quality-adjusted life days” to “QALY.”
Sensitivity Analyses
Deterministic sensitivity analyses (DSA) were conducted, incorporating both 1- and 2-way sensitivity analyses. One-way sensitivity analyses aimed to identify the factors exerting the most influence on cost-effectiveness. These factors included “2-hour headache relief” (95% confidence interval; CI), 21 “drug prices” (ranging from the negative percentage of the least expensive generic drug price compared with the price of brand triptan to +10%), “costs of physician visits” (±10%), and “costs of community pharmacy visits” (±10%), and QALY (95% CI). Two-way sensitivity analyses were conducted to explore the relationships between the 2 items identified in the 1-way sensitivity analyses. Tornado diagrams were generated to illustrate the results of the DSA. However, infinity signs were observed in the diagrams assessing the incremental cost-effectiveness ratio (ICER), indicating that, within the uncertainty range of a parameter, incremental effectiveness passed through zero, making the ICER calculation undefined. Consequently, this study employed incremental net monetary benefit (INMB) graphs.
Probabilistic sensitivity analyses (PSA) were conducted using a Monte Carlo simulation with 10,000 iterations to anticipate uncertainty in utility and probability inputs, utilizing TreeAge Pro Healthcare. The utilities and probabilities were input using beta distributions, while the costs were input using gamma distributions. A distribution of probabilities was adapted to convert values from the 95% CI of averages in the literature to standard deviations. 22 Clinical, utility, and cost inputs and ranges used for sensitivity analyses are summarized in Table 4.
Table 4.
Clinical, Utility, and Cost Inputs and Ranges Used for Sensitivity Analyses.
| Parameter | Base case value | Lower limits | Higher limits | Distribution | Distribution parameters (µ/σ) | References |
|---|---|---|---|---|---|---|
| Cost of pharmacy (yen) | 1000 | 900 | 1100 | Gamma | 1000:100 | 2018 Medical Fee Index |
| Cost of physician (yen) | 3920 | 3528 | 4312 | Gamma | 3920:392 | |
| Drug price of eletriptan (yen) | 3410 | 770 | 5090 | Gamma | 3410:341 | |
| Drug price of naratriptan (yen) | 4190 | 1010 | 5050 | Gamma | 4190:419 | |
| Drug price of rizatriptan (yen) | 3370 | 480 | 5190 | Gamma | 3370:337 | |
| Drug price of sumatriptan (yen) | 3350 | 580 | 4200 | Gamma | 3350:335 | |
| Drug price of zolmitriptan (yen) | 3540 | 630 | 4310 | Gamma | 3540:354 | |
| Cost of pharmacy (yen) | 1200 | 1080 | 1320 | Gamma | 1200:120 | 2020 Medical Fee Index |
| Cost of physician (yen) | 3980 | 3528 | 4312 | Gamma | 3980:398 | |
| Drug price of eletriptan (yen) | 3330 | 770 | 3663 | Gamma | 3330:333 | |
| Drug price of naratriptan (yen) | 4130 | 1010 | 4543 | Gamma | 4130:413 | |
| Drug price of rizatriptan (yen) | 3280 | 480 | 3608 | Gamma | 3280:328 | |
| Drug price of sumatriptan (yen) | 3230 | 580 | 3553 | Gamma | 3230:323 | |
| Drug price of zolmitriptan (yen) | 3420 | 630 | 3762 | Gamma | 3420:342 | |
| Cost of pharmacy (yen) | 1200 | 1161 | 1279 | Gamma | 1200:120 | 2022 Medical Fee Index |
| Cost of physician (yen) | 3980 | 3528 | 4312 | Gamma | 3980:398 | |
| Drug price of eletriptan (yen) | 2720 | 770 | 2992 | Gamma | 2720:272 | |
| Drug price of naratriptan (yen) | 2350 | 1010 | 2585 | Gamma | 2350:235 | |
| Drug price of rizatriptan (yen) | 2610 | 480 | 2871 | Gamma | 2610:261 | |
| Drug price of sumatriptan (yen) | 2450 | 580 | 2695 | Gamma | 2450:245 | |
| Drug price of zolmitriptan (yen) | 2870 | 630 | 3157 | Gamma | 2870:287 | |
| Probability of 2-hour effectiveness for eletriptan | 0.604 | 0.561 | 0.646 | Beta | 0.604:0.038 | Network meta-analysis (Cameron et al. 22 ) |
| Probability of 2-hour effectiveness for naratriptan | 0.445 | 0.356 | 0.538 | Beta | 0.445:0.114 | |
| Probability of 2-hour effectiveness for rizatriptan | 0.571 | 0.524 | 0.619 | Beta | 0.571:0.044 | |
| Probability of 2-hour effectiveness for sumatriptan | 0.497 | 0.463 | 0.531 | Beta | 0.497:0.036 | |
| Probability of 2-hour effectiveness for zolmitriptan | 0.500 | 0.455 | 0.547 | Beta | 0.500:0.048 | |
| Probability of migraine | 0.257 | 0.236 | 0.277 | Beta | 0.257:0.258 | |
| Probability of recurrence for eletriptan | 0.279 | 0.175 | 0.390 | Beta | 0.273:0.276 | |
| Probability of recurrence for naratriptan | 0.214 | 0.135 | 0.298 | Beta | 0.214:0.235 | |
| Probability of recurrence for rizatriptan | 0.369 | 0.36 | 0.425 | Beta | 0.369:0.034 | |
| Probability of recurrence for sumatriptan | 0.278 | 0.245 | 0.305 | Beta | 0.278:0.064 | |
| Probability of recurrence for zolmitriptan | 0.342 | 0.265 | 0.345 | Beta | 0.342:0.130 | |
| QALY of Health State 1 | 0.0703 | 0.0680 | 0.0726 | Beta | 0.0703:0.0071 | — |
| QALY of Health State 2 | 0.0737 | 0.0720 | 0.0754 | Beta | 0.0737:0.0053 | — |
| QALY of Health State 3 | 0.0804 | 0.0792 | 0.0815 | Beta | 0.0804:0.0036 | — |
Note. QALY = quality-adjusted life year.
Ethical Considerations
The ethics review board of a university in Japan approved this study (No. 229). The EQ-5D-3L was administered at a community pharmacy. Community pharmacists identified patients who visited the pharmacy with a prescription for any triptan. Subsequently, the pharmacists provided a letter to patients with migraines informing them of the purpose of this study. Patients willing to participate in the study provided written informed consent.
Results
The utility scores (N = 39) for Health States 1, 2, and 3 obtained using the questionnaire were 0.4374 (95% CI: 0.3284-0.5465), 0.5989 (95% CI: 0.5181-0.6797), and 0.9129 (95% CI: 0.8577-0.9681), respectively. Therefore, the QALYs for Health States 1, 2, and 3 were 0.0703 (95% CI: 0.0680-0.0726), 0.0737 (95% CI: 0.0720-0.0750), and 0.0804 (95% CI: 0.0792-0.815), respectively.
The results of the cost-effectiveness analysis are presented in Figure 2. In FY2018, sumatriptan and eletriptan were cost-effective; however, the other triptans were dominated by sumatriptan. In FY2020, sumatriptan and eletriptan were cost-effective, and rizatriptan was extended-dominated, which means that rizatrptane was not as cost-effective as sumatriptan and eletriptan; nevertheless, the other triptans were dominated by sumatriptan. In FY2022, naratriptan and eletriptan were cost-effective; however, the other triptans were dominated by naratriptan. The hierarchy of triptan strategies varied in each fiscal year. Eletriptan was the only triptan included as a cost-effective agent in all 3 fiscal years.
Figure 2.
Results of the cost-effectiveness analyses. (a) FY2018, (b) FY2020, and (c) FY2022.
Note. QALY = quality-adjusted life year.
The results of the DSA in FY2018, FY2020, and FY2022 are illustrated in Figure 3. Figure 3a shows the tornado diagram comparing eletriptan with sumatriptan for FY2018. The expected value (EV) was 919 yen (USD 9). In Figure 3b-1, the tornado diagram compares rizatriptan with sumatriptan for FY2020. The EV was 323 yen (USD 3). Figure 3b-2 shows the tornado diagram comparing eletriptan with sumatriptan for FY2020. The EV was 1102 yen (USD 11). Figure 3c shows the tornado diagram comparing eletriptan with naratriptan for FY2022. The EV was 1350 yen (USD 14).
Figure 3.
Results of the DSA. (a) FY2018, (b)-1: sumatriptan 50 mg versus rizatriptan 10 mg in FY2020, (b)-2: sumatriptan 50 mg versus eletriptan 20 mg in FY2020, (c) FY2022.
Note. QALY = quality-adjusted life year.
The results of the PSA are illustrated as acceptability curves in Figure 4. The acceptability of eletriptan in FY2018, as shown in Figure 4a, increased with the WTP, while that of sumatriptan decreased. The acceptability of eletriptan in FY2020, as shown in Figure 4b, increased with the WTP, while those of rizatriptan and sumatriptan decreased. Similarly, the acceptability of eletriptan in FY2022, as shown in Figure 4c, increased with the WTP, while that of naratriptan decreased.
Figure 4.
Results of the acceptability curves in the PSA. (a) FY2018, (b) FY2020, and (c) FY2022.
Note. CE = cost-effectiveness.
Discussion
The heavily regulated Japanese drug pricing system encompasses elements of comparative effectiveness and budget impact; however, evidence is not necessarily processed in a rigorous scientific manner. 9 Therefore, some researchers in Japan have been concerned about reimbursement restriction and drug price revisions.25,26 This study utilized the drug prices of triptans in FY2018, FY2020, and FY2022 to elucidate this issue, focusing on triptans for migraine treatment. It suggests that cost-effective triptans varied every other year in Japan. These variations could be problematic because formulary management of triptans in Japan for migraine, for example, may face revaluation every other year. However, as the drug price revision system has been in place every year since 2021, neurologists treating migraines may be confused about which triptans are cost-effective in the corresponding year. Although eletriptan is the first drug of choice for migraines in the formulary, the second drug of choice may vary annually. Mahlich et al. 9 argued that the recent introduction of cost-effectiveness as an additional requirement raises questions about how to seamlessly integrate it into the current system. The principle of drug price revision is based on current market prices, where the revised drug price is the weighted average of sales prices to wholesalers, medical institutions, and pharmacies plus consumption tax and a stabilization adjustment range (2% of the drug price before revision). 4 The calculation method may be complex for individuals from countries that use a different system. Some studies from other countries have examined the impact of drug price reduction.27,28 However, pharmacoeconomic issues in these countries differ from those that the current study aims to elucidate. Therefore, the drug price revision strategy in Japan should be discussed further to foster cost-effective viewpoints.
Although the present study reveals important findings, it has several limitations. First, we utilized the EQ-5D-3L, which has a narrower scope compared to the EQ-5D-5L. As we examined the uncertainty of the utilities obtained by EQ-5D-3L in a 1-way sensitivity analysis, such limitations could be considered minimal. Second, the decision tree in the current study was relatively simple. Incorporating recent definitions of effective treatment for a migraine attack and triptan failure could make the analysis more detailed and realistic. 29 Third, the number of patients with migraines who responded to the EQ-5D-3L was relatively small, at 39. However, the best, intermediate, and worst scenarios of the decision tree corresponded to Health States 3, 2, and 1, respectively, with corresponding utility scores of 0.9129, 0.5989, and 0.4374, which were reasonable. This gives us confidence in the reliability of the study’s results. Nonetheless, this was a pilot study and as such, has many limitations. Thus, our next steps will involve obtaining more detailed utility scores using the EQ-5D-5L, developing a more practical decision tree for CUA, and increasing the sample size.
Conclusions
This study employed a CUA to discuss the drug price revision strategy for Japan, considering healthcare payers’ perspectives and using a decision-tree model. Discussions on the drug price revision strategy for Japan will be necessary.
Acknowledgments
We thank Editage (www.editage.com) for English language editing.
Footnotes
Author Contributions: Conceptualization: Naoto Nakagawa, Mizuha Konno, Masami Kashiwabara, Jun Mochimaru, Shinya Shimoji, and Tadao Inoue; Methodology: Naoto Nakagawa, Mizuha Konno, and Tadao Inoue; Data curation: Masami Kashiwabara and Jun Mochimaru; Formal analysis and investigation: Naoto Nakagawa, Mizuha Konno, and Tadao Inoue; Writing - original draft preparation: Naoto Nakagawa; Writing - review and editing: Leanne Lai; Funding acquisition: None; Resources: None; Supervision: Leanne Lai.
Data Availability: The datasets used in this study are available at Dryad, Dataset, https://doi.org/10.5061/dryad.q573n5tnf.
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethical Considerations: The ethics review board of a university in Japan approved this study (No. 229). The EQ-5D-3L was administered at a community pharmacy. Community pharmacists identified patients who visited the pharmacy with a prescription for any triptan. Subsequently, the pharmacists provided a letter to patients with migraines informing them of the purpose of this study. Patients willing to participate in the study provided written informed consent.
Consent to Participate: Community pharmacists provided a letter to patients with migraines informing them of the purpose of the study. Patients willing to participate provided written informed consent.
Consent for Publication: Not applicable.
ORCID iD: Naoto Nakagawa 
https://orcid.org/0000-0002-8614-4894
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