A Comparative Analysis of Anticancer Drug Appraisals Including Managed Entry Agreements in South Korea and England.

OBJECTIVES: This study aimed to compare appraisal decisions about anticancer drugs between the health technology assessment (HTA) agencies in Korea and England, and investigate whether the decisions and supporting evidence are comparable. METHODS: This study identified 49 anticancer drugs listed by the Korean Ministry of Health and Welfare between January 2014 and December 2019. Of those, 46 anticancer drugs for 58 indications were included for analysis. Official appraisal documents from both countries for 58 drug-indication pairs were compared and assessed in terms of clinical and economic evidence. Evidence items and their groups for analysis were predefined. RESULTS: Three-quarters of cases were recommended with managed entry agreements (MEAs) in England and three-fifths in Korea. Finance-based MEA types were most common in both countries. Korean and English authorities made consistent decisions in 48 cases (83%) when classifying decisions as 'recommended' and 'not recommended', while the degree of agreement lowered to 16 cases (28%) when subdividing decisions according to MEA types. When the evidence base was identical, their decisions were more likely to be consistent. Regarding clinical evidence, while the majority of cases referred to the same pivotal studies, differences between the committees' recognized comparators and the appraisal date caused discrepancies in decisions. Economic evidence, including incremental cost-effectiveness ratio (ICER) estimates, was identical in only 12 cases (21%), which contributed to discrepancies. CONCLUSION: England relies on economic evaluation, with increasing use of data collection agreements, in contrast with Korea's new procedure exempting companies from providing economic evaluation. While there is possibility for international cooperation in the assessment of clinical evidence, transferability issues exist, particularly with regard to economic evidence.

Systematic Review and Quality Assessment of Health Economic Evaluation Studies (2007-2019) Conducted in South Korea.

BACKGROUND: South Korea formally adopted economic evaluation in December 2006 to aid drug reimbursement decision-making. While this policy change is applied only to pharmaceuticals, it has also sparked interest in economic evaluations for non-pharmaceutical interventions and programmes. OBJECTIVE: This study aimed to provide a snapshot of the current practice for published health economic evaluation studies and critically assess the quality of these studies. METHODS: An electronic search was performed on multiple databases (EMBASE, PubMed, NHS Economic Evaluation Database, Scopus, Korean Medical database, Korean studies Information Service System, and Research Information Sharing Service) to identify health economic evaluation studies published between January 2007 and December 2019. The inclusion criteria were peer-reviewed, original health economic evaluations (cost-utility, cost-effectiveness, cost-minimisation, and cost-benefit analyses) published in English or Korean. Two reviewers selected studies for inclusion and extracted data from the included studies. Key characteristics of these studies were descriptively summarised, and study quality was assessed using the Quality of Health Economic Studies (QHES) instrument on a 100-point scale. RESULTS: A total of 162 studies were included in this review (63 for drugs, 51 for non-pharmaceutical treatments/health technologies, and 48 for health programmes). These numbers confirm a significant increase in the number of publications since the policy introduction. However, the quality of these studies remained relatively low, with a mean QHES score of 57.9 (± 16.0). Study quality also varied substantially, with the QHES scores ranging from 15 to 87. The scores were notably lower in studies with non-pharmaceutical interventions and programmes, cost-effectiveness analyses or cost-benefit analyses, retrospective study-based or simple modelling-based analyses, and those locally published. In addition, a considerable proportion of these studies did not state or specify essential components of economic evaluation, such as perspectives (30.2%), time horizons (29.6%), discount rates (34.6%), and sensitivity analyses (24.7%). While the use of local data either fully or partially was relatively higher for unit costs (94.4%) and resource utilisation (90.1%), it was lower for utility weights (47.1%), treatment effects (63.0%), and baseline risks (70.4%). Transferability or generalisability issues were infrequently discussed when relying on foreign sources. In addition, the included studies were often not well structured, making it difficult to assess their quality. CONCLUSION: These findings suggest that there is still much room for improving the quality of health economic evaluation studies conducted in South Korea. Policymakers should critically evaluate available cost-effectiveness evidence, especially for non-pharmaceutical interventions and programmes, when using it for decision-making in South Korea.

How Sensitive is Sensitivity Analysis?: Evaluation of Pharmacoeconomic Submissions in Korea.

Purpose: We aimed to describe the types of uncertainties examined in the economic evaluations submitted for reimbursement in Korea and their impact on the incremental cost-effectiveness ratio (ICER). Method: Fifty dossiers were submitted by pharmaceutical companies to the economic subcommittee of the Pharmaceutical Benefit Coverage Advisory Committee (PBCAC) from January 2014 to December 2018. The types of uncertainties were categorized as structural and parametric, and the frequencies of the sensitivity analysis per variables were analyzed. The impact of uncertainties was measured by the percent variance of the ICER relative to that of the base case analysis. Results: Of the 50 submissions, varying discount rate (44 submissions), followed by time horizon (38 submissions) and model assumptions (29 submissions), were most frequently used to examine structural uncertainty, while utility (42 submissions), resource use (41 submissions), and relative effectiveness (26 submissions) were used to examine parametric uncertainty. A total of 1,236 scenarios (a scenario corresponds to a case where a single variable is varied by a single range) were presented in the one-way sensitivity analyses, where parametric and structural sensitivity analyses comprised 679 and 557 scenarios, respectively. Varying drug prices had the highest impact on ICER (median variance 19.9%), followed by discount rate (12.2%), model assumptions (11.9%), extrapolation (11.8%), and time horizon (10.0%). Conclusions: Variables related to long-term assumptions, such as model assumptions, time horizon, extrapolation, and discounting rate, were related to a high level of uncertainty. Caution should be exercised when using immature data.

Korean Guidelines for Pharmacoeconomic Evaluations: Updates in the Third Version.

The first version of the pharmacoeconomic (PE) guidelines was published in South Korea in 2006. Despite its first revision in 2011, there were still ambiguities in its interpretation. Moreover, methodologies for estimating effectiveness and costs have also evolved since then. Under these circumstances, the Health Insurance Review and Assessment Service published the third version in January 2021. This article reviews the revision process and major changes made in the new edition of the PE guidelines. The revision was processed through reviews of the previous 50 PE submissions, international guidelines, academic literature, and surveys and advisory meetings to obtain stakeholders' opinions. The analysis perspective has changed from a limited societal perspective to a healthcare system perspective. In addition to the drug with the highest market share, drugs used in clinical trials can be selected as comparators under certain conditions. The discount rate decreased from 5% to 4.5%. Furthermore, the revised guidelines provide more detailed and specific instructions for items including non-inferiority margin, extrapolation, utility elicitation, and uncertainty. Treatment switch and co-dependent technology guidelines are newly included; the budget impact analysis guideline is deleted. Through this revision, transparency and consistency of decision-making is expected to improve.

A Review of Utility Measurement Methods Used in Pharmacoeconomic Submissions to HIRA in South Korea: Methodological Consistency and Areas for Improvement.

Pharmacoeconomic (PE) guidelines, first published in 2006 and later updated in 2011, were developed to guide the preparation and submission of PE data to the Health Insurance Review and Assessment Service (HIRA) for drug reimbursement decision making in South Korea. This study, which was conducted as part of a project for revision of the PE guideline, reviewed utility values used in the PE submissions processed at HIRA during 2014-2018 to identify aspects of the current guidelines that may need to be revisited. A total of 50 PE submissions were processed at HIRA over the 5 years. Of these, 47 submissions that used quality-adjusted life-years as an outcome measure were included in this review. Data were extracted from full copies of the manufacturer's initial submissions and committee documents provided by HIRA. Of the 47 submissions, nearly half (n = 23, 48.9%) used published sources to obtain health state utility values, followed by direct methods using time trade-off (n = 7) or standard gamble (n = 2) and indirect methods with patient-level data using the EQ-5D-3L (n = 4) or the EQ-5D-5L (n = 2). Mapping, using the EQ-5D-3L as a target measure, was also adopted in six submissions, although it was somewhat unfavourably described in the guideline. Notably, 52.2% of the submissions with published sources took utility values from different sources for different health states defined in a single model. In addition, details of utility measurement methods or mapping functions taken from published sources were relatively poorly reported. Moreover, the preferences of the Korean general public, preferred by the guideline, were rarely reflected in the utility values used in submissions relying on published sources (95.7% for foreign values only/mixed) and mapping (66.7%). While most submissions with direct and indirect methods used domestic preference values, the former was occasionally criticised by assessment committees because of health state descriptions. This review highlights a considerable amount of inconsistency in the measurement of utility values used in the PE submissions during 2014-2018, indicating a strong need for methodological standardisation.

Public Preferences in Resource Allocation for Insurance Coverage of Dental Implant Service in South Korea: Citizens' Jury.

The Korean government sought to include dental implant services for the elderly in the benefits package of the national health insurance. In 2014, the Citizens' Jury was held to discuss the topic, during which thirty jurors, randomly selected from the 2665 applicants, participated in a day-long deliberation process after having an information session on the topic by a team of experts. There was a substantial shift in opinion during the deliberation session toward a more cost-conscious view. Most jurors supported limiting the coverage of dental implant to only one tooth per individual given the extent of the financial burden that will be imposed on the population. They opposed covering implant services for the front teeth, given that the implant of front teeth generally serves aesthetic purposes rather than restoring mastication function. The government's final decision in 2014 was to offer coverage up to two teeth, regardless of tooth location. This scheme based on the jury's recommendations in 2014 has been implemented without policy failure to date, which shows that the lay public can meaningfully contribute to a decision-making process regarding controversial agendas such as benefits packages for expensive health services.

Who should be given priority for public funding?

BACKGROUND: This study explored if Koreans consider the type of disease, rarity, and availability of alternative treatments as priority criteria in limited healthcare resource allocation. MATERIALS AND METHODS: A web-based survey was conducted with a representative sample of 3,482 Korean adults. Participants were divided into six cohorts, differing in terms of the disease being compared and the cost and benefits of the treatments. Each cohort was asked two questions: 1) How to allocate a fixed budget into each of the two groups (cancer vs non-cancer, rare vs common, no other treatments available vs several treatments available), all else being equal; 2) allocation choices when conditions of two groups differed. The McNemar test was used to assess changes in responses between the two questions. RESULTS: Under the control condition, the majority chose to treat an even number of patients with cancer and non-cancer diseases, and preferred to treat common diseases and those with no alternative treatments. However, when the treatment effects or costs of two comparison groups changed, choice shifted toward more effective or less costly treatment. CONCLUSIONS: While Koreans generally support the principle of health maximization, they also believe that priority should be given to diseases that previously did not have any treatments. However, no priority was given to cancer or rare diseases.

Role of Health Technology Assessment in Drug Policies: Korea.

South Korea is the first Asian country to mandate the submission of pharmacoeconomic data for reimbursement decision making. For a new drug to be listed, it must demonstrate its value in terms of comparative effectiveness and cost effectiveness. The Health Insurance Review and Assessment Service (HIRA) judges the submitted drug's value and decides whether its coverage is appropriate on the basis of the recommendation of the Pharmaceutical Benefit Coverage Assessment Committee. Once the drug has been accepted by HIRA, the National Health Insurance Service and the sponsoring company negotiate the price and expected sales volume. Even if HIRA acknowledges the value of the drug, it cannot be listed if the negotiation fails. In the off-patent market, generic and original branded drugs are treated equally in terms of pricing. Once generics enter the market, both drug prices should be lowered to 53.55% or less of the on-patent price. Since the current system was implemented, concerns have been raised about a decline in the accessibility of new drugs, especially for high-priced drugs used to treat serious diseases. In 2013, several measures had been introduced aimed at improving the accessibility of these drugs. A risk-sharing scheme and an increase in the maximum acceptable cost-effectiveness ratio were subsequently initiated. Although these schemes have been successful in improving access to high-priced drugs, they are often criticized for reducing transparency in pricing. Finding a balance between accessibility and efficiency is still a challenge in Korea.

Role of economic evidence in coverage decision-making in South Korea.

OBJECTIVES: The South Korean government required the submission of economic evidence when it implemented the Positive-List System in December 2006. This study investigates the key factors that influenced actual public insurance reimbursement decisions, including the role of economic evidence, after 10 years of decision practice under compulsory health technology assessment (HTA) for new drugs. METHOD: Logistic regression analysis was used to estimate the impact of the variables involved, including cost-effectiveness ratio as a key variable, on reimbursement decisions. The latter were defined as "yes" or "no" at a submitted price and indication. Only cases (n = 91) that present a cost-effectiveness ratio, and that have been reviewed based on this ratio from January 2007 to December 2016, were included in the analysis. RESULTS: Cases with higher cost-effectiveness ratios were less likely to be accepted. In addition, drugs that were used to treat severe diseases and drugs with no substitute were more likely to be recommended. The probability of acceptance declined along with the level of uncertainty in the submitted evidence. The acceptance rate for severe-disease drugs has increased since 2013, when the government introduced several policies that lowered the existing barriers to positive reimbursement. However, such an increase was not statistically significant. CONCLUSIONS: Cost-effectiveness is one of the most influential factors in drug-reimbursement decisions. However, inclusion of other explanatory variables, in addition to the cost-effectiveness ratio, predicted the results of decisions more accurately.

Eliciting preferences for medical devices in South Korea: A discrete choice experiment.

This study aims to identify the attributes that contribute to the value of medical devices and quantify the relative importance of them using a discrete choice experiment. Based on a literature review and expert consultation, seven attributes and their levels were identified-severity of disease (2), availability of substitutes (2), improvement in procedure (3), improvement in clinical outcomes (2), increase in survival (2), improvement in quality of life (3), and cost (4). Among 576 hypothetical profiles, optimal choice sets with 20 choices were developed and experts experienced in health technology assessment and reimbursement decision making in South Korea were surveyed. A total of 102 respondents participated in the survey. The results of the random-effect probit model showed that among the seven attributes, six, except for improvement in procedure, had a significant impact on respondents' choices on medical devices. Respondents were willing to pay the highest amount for devices that provided substantial improvements in quality of life, followed by increased survival, improved clinical outcome, treatment without substitutes, and technology for treating severe diseases. The findings of this experiment will inform decision-makers of the relative importance of the criteria and help them in reimbursement decision making of medical devices.

Eight-year experience of using HTA in drug reimbursement: South Korea.

This study describes the process and results of drug reimbursement decision-making in South Korea and evaluates its performance from the perspectives of the various stakeholders involved. Data were retrieved from the evaluation report posted on the Health Insurance Review and Assessment Service (HIRA) website. As of 2014, 253 new drugs had been submitted to the HIRA for appraisal. Of these, 175 (69.2%) were recommended in favor of listing and 78 (30.8%) were rejected. Furthermore, 68 of these drugs were deemed clinically improved relative to existing drugs. For those drugs that did not demonstrate clinical superiority (which was most of them), a simple price comparison to the existing drug was utilized as a gate toward listing. On top of the base-line analysis, 104 stakeholders from the industry, academia, public office, and civic society responded to a questionnaire designed to obtain their opinions on the South Korean positive list system (PLS). Stakeholders agreed that the consistency of reimbursement decision-making has improved since 2007, while accessibility to new drugs has apparently decreased. Respondents also indicated a preference toward improved public access to decision-making information. This examination of reimbursement decisions in South Korea will illuminate critical issues for countries that are considering the introduction of similar policies.

Same drugs, valued differently? Comparing comparators and methods used in reimbursement recommendations in Australia, Canada, and Korea.

To investigate whether the value of the same drug is evaluated differently across jurisdictions, publicly available reimbursement recommendation data from the Health Insurance Review and Assessment Service (HIRA, Korea) from January 2007 until July 2012 were compared with reimbursement recommendation data from the Pharmaceutical Benefit Advisory Committee (PBAC) of Australia, and the Common Drug Review (CDR) and the pan-Canadian Oncology Drug review (pCODR) of Canada. The most recent guidelines from the three agencies regarding the recommended methods of economic evaluation and comparator selection were also compared. During the observation period, 25 products were evaluated by all three countries. No significant differences in the comparator(s)' selection or methods of economic evaluation were found, but the CDR was significantly less likely to positively recommend products compared with the other agencies (p=0.023). The agreement between agencies on selected comparator(s) was moderate to significant (kappa statistics=0.590-0.669), whereas the reimbursement decisions (kappa statistics=0.042-0.296) and the methods of economic evaluation (kappa statistics=0.138-0.525) showed slight to fair agreement. We illustrated that the divergence in reimbursement decisions across jurisdictions is less related to comparator selection or the level of clinical evidence considered and more related to country-specific issues.

CHALLENGES FACED IN TRANSFERRING ECONOMIC EVALUATIONS TO MIDDLE INCOME COUNTRIES.

BACKGROUND: Decision makers in middle-income countries are using economic evaluations (EEs) in pricing and reimbursement decisions for pharmaceuticals. However, whilst many of these jurisdictions have local submission guidelines and local expertise, the studies themselves often use economic models developed elsewhere and elements of data from countries other than the jurisdiction concerned. The objectives of this study were to describe the current situation and to assess the challenges faced by decision makers in transferring data and analyses from other jurisdictions. METHODS: Experienced health service researchers in each region conducted an interview survey of representatives of decision making bodies from jurisdictions in Asia, Central and Eastern Europe, and Latin America that had at least 1 year's experience of using EEs. RESULTS: Representatives of the relevant organizations in twelve countries were interviewed. All twelve jurisdictions had developed official guidelines for the conduct of EEs. All but one of the organizations evaluated studies submitted to them, but 9 also conducted studies and 7 commissioned them. Nine of the organizations stated that, in evaluating EEs submitted to them, they had consulted a study performed in a different jurisdiction. Data on relevant treatment effect was generally considered more transferable than those on prices/unit costs. Views on the transferability of epidemiological data, data on resource use and health state preference values were more mixed. Eight of the respondents stated that analyses submitted to them had used models developed in other jurisdictions. Four of the organizations had a policy requiring models to be adapted to reflect local circumstances. The main obstacles to transferring EEs were the different patterns of care or wealth of the developed countries from which most economic evaluations originate. CONCLUSIONS: In middle-income countries it is commonplace to deal with the issue of transferring analyses or data from other jurisdictions. Decision makers in these countries face several challenges, mainly due to differences in current standard of care, practice patterns, or gross domestic product between the developed countries where the majority of the studies are conducted and their own jurisdiction.

Sourcing quality-of-life weights obtained from previous studies: theory and reality in Korea.

BACKGROUND: The quality-of-life weights obtained in previous studies are frequently used in cost-utility analyses. The purpose of this study is to describe how the values obtained in previous studies are incorporated into the industry submissions requesting listing at the Korean National Health Insurance (NHI), focusing on the issues discussed in theoretical studies and national guidelines. METHODS: The industry submissions requesting listing at the Korean NHI from January 2007 until December 2009 were evaluated by two independent researchers at the Health Insurance Review and Assessment Service (HIRA). Specifically, we observed the methods that were used to pool, predict joint health state utilities, and retain consistency within submissions in terms of the issues discussed in methodological research papers and recommendations from national guidelines. RESULTS: More than half of the submissions used QALY as an outcome measure, and most of these submissions were sourced from prior studies. Heterogeneous methodologies were frequently used within a submission, with the inconsistent use of upper and lower anchors being prevalent. Assumptions behind measuring joint health state utilities or pooling multiple values for single health states were omitted in all submissions. Most national guidelines were rather vague regarding how to predict joint health states, how to select the best available value, how to maintain consistency within a submission, and how to generalize values obtained from prior studies. CONCLUSIONS: Previously-generated values were commonly sourced, but this practice was frequently related to inconsistencies within and among submissions. Attention should be paid to the consistency and transparency of the value, especially if the value is sourced from prior studies.

Korean guidelines for pharmacoeconomic evaluation (second and updated version) : consensus and compromise.

The first version of the Korean guidelines for pharmacoeconomic evaluation was published by Health Insurance Review and Assessment Service (HIRA) in 2006. Since the introduction of the first version, domestic experience with the application of the recommendations has accumulated, and methodologies in certain areas have progressed considerably. Based on these experiences, HIRA initiated a guidelines revision project to address the need for revisions. The purpose of this study is to share the process used to complete these guideline revisions and to provide the contents of the revised guidelines. In developing the current revision, meetings with the advisory committee and working-level meetings with pharmaceutical companies were held several times to reach as much of a consensus as possible, and the results of a survey of pharmaceutical companies and decision makers regarding the existing guidelines were considered. The second version of the guidelines clarified the level of data requirement ('must', 'recommended', 'preferred') based on the data availability, the information needs of the decision makers and the strength of the evidence. The recommended perspective economic studies should take has been modified and additional guidance has been provided on QALY measurement. Manuals for systematic reviews and indirect comparisons have been published, and a standardized reporting format for expert opinions has been added. Sections on preferred methods for evaluations, sensitivity analysis, modelling and time horizon have been elucidated. The revised guidelines clarify the expression of the recommendations, making them more user-friendly, and provide more specific guidance to improve the quality and comparability across submissions.

Eliciting public preference for health-care resource allocation in South Korea.

OBJECTIVES: To identify the principles the public considers important and the trade-offs between different values in health-care resource allocation practices. METHODS: This study approached the issue in both qualitative and quantitative ways. In a qualitative study, two focus groups discussed the issues of resource allocation in health care. To facilitate the discussion, a simple ranking task and a series of pairwise choice practices were implemented. A discrete choice experiment survey questionnaire was also administered to a sample of the general population. Attributes and levels were determined through literature reviews and the results from the focus group interview. We used a random-effect probit model to assess the effects of each attribute. RESULTS: Through the focus group interviews, we found strong public support for the principle of equal opportunity. The participants thought that the severity of disease was the most important criterion when setting priorities. The majority supported the idea that the most disadvantaged should have the highest priority even when their health gains are less than those of others. The discrete choice experiment results showed that the severity of disease, health gains, and patients' socioeconomic status significantly influence their choices, with each parameter having an expected sign. CONCLUSION: The results showed that Koreans support not only health maximization but also equal opportunity, fair resource allocation, and equality.

Pharmacoeconomic guidelines and their implementation in the positive list system in South Korea.

This article reviews the change in the reimbursement and pricing system in South Korea, which was the precursor to the eventual implementation of evidence-based decision-making. There has been pressure on Korea's National Health Insurance system to control its skyrocketing expenditures on drugs. As a result, a series of cost-containment policies have been implemented. The idea of economic evidence-based decision-making was first introduced in Korea in 2001 when the government announced cost-effectiveness as one of the criteria for reimbursement decisions. After this announcement, the Health Insurance Review and Assessment Service (HIRA) developed guidelines, which became the standard for economic evaluations. In 2006, the drug listing system for reimbursement was changed from a negative to a positive system under the drug expenditure rationalization plan. Under this new system, only drugs that are proven economically and clinically valuable can be listed, and applicants have to submit economic evaluation studies to support the cost-effectiveness of their drugs. Once new applications are submitted, HIRA reviews them, and the Drug Reimbursement Evaluation Committee (DREC) decides whether or not to recommend the submitted drugs. In its reimbursement decisions, the DREC considers not only cost-effectiveness but also the availability of therapeutic alternatives, the severity of the condition treated, and the impact on the budget, among other measures. After the introduction of the positive list system, 56% of drugs were determined to be appropriate for reimbursement by the DREC. Despite limited human resources, experience, and quality local data, Korea is continuing to make efforts to establish a system of evidence-based decision-making.

[Guidelines for economic evaluation of pharmaceuticals in Korea].

An economic evaluation is required in order to apply to the Health Insurance Review and Assessment Service (HIRA) for a listing in the national drug formulary. To assist companies in preparing the necessary documents, HIRA published guidelines for the economic evaluation of pharmaceuticals in 2006. The guidelines are composed of two parts: guidance an explanatory notes. Each guideline reflects the best practice which meets both the theoretical consensus within the academic community and local situations, like data availability. To enhance the transparency of evaluation, guidelines emphasize the reproducibility of data and analysis result. That is, all evaluation processes are required to be described in enough detail to be replicated by reviewers. With growing experience and theoretical development in this area, HIRA guidelines will be revised periodically.

Economic evaluation and pharmaceutical reimbursement reform in South Korea's National Health Insurance.

South Korea's National Health Insurance recently announced a reform in pharmaceutical reimbursement, with the purpose of increasing rational resource use in drug spending. The new policy aims to take the cost-effectiveness and budget impact of newly introduced drugs into account in payment decisions. If the policy is implemented, South Korea will be the first Asian country to officially adopt economic evaluation as a tool for resource allocation in health care. This paper looks at the background, objectives, expected outcomes, potential issues, and resulting trade conflict regarding use of economic data in drug reimbursement decisions in South Korea.