A narrative review of integrating medical ethics and cost-effectiveness evaluation in Japan’s clinical practice guidelines

Introduction

In Japan, recent socioeconomic trends surrounding the healthcare system have intensified pressures, prompting a growing need for deeper policy discussions regarding the stable provision of medical services and the equitable allocation of healthcare resources. Against this backdrop, there has been heightened interest in cost-effectiveness analysis (CEA), a key component of health technology assessment (HTA), within healthcare policy in Japan. For example, the government’s strategic policy document, Basic Policy 2025 (approved by the Cabinet), outlines a plan to ensure that CEA functions effectively within the healthcare system and that its results are actively utilized in clinical practice.

Taking these developments into account, this article aims to examine the relationship between economic evaluations in healthcare—particularly CEA—and medical ethics, with reference to clinical practice guidelines. The goal is to outline a pathway for appropriately disseminating CEA within Japanese clinical practice. In response to the above purpose, this study takes the following two approaches. As an overview article (narrative review), the structure of this article is as follows: first, it discusses socioeconomic trends and health insurance policy (with a focus on CEA), followed by an exploration of the role of CEA in clinical practice guidelines, based on the preceding discussion.

Notably, while this study partially builds upon a previous report (1), which examined the conceptual relationship between economic trends and medical ethics in Japan, it also presents a newly developed line of argument. Although the discussion in the present article is limited to issues within Japan, little research on “cost-effectiveness and medical ethics in Japan” had existed previously to the authors’ knowledge, making the previous report one of the earliest attempts in this field. While this study overlaps with the preceding report in its core structure, it expands upon the practical outcomes of the cost-effectiveness evaluation (CEE) system and the role of health economics within medical ethics. Furthermore, the present article also introduces examples of CEEs as described in the latest clinical practice guidelines. This article is presented in accordance with the Narrative Review reporting checklist (available at https://jhmhp.amegroups.com/article/view/10.21037/jhmhp-25-95/rc).

Methods

The literature cited consists of publicly available sources published between January 2000 and September 2025. The academic databases used include MEDLINE, the Cochrane Library, and EMBASE. The search terms were ‘health economics’ AND ‘medical ethics’ were applied to titles and abstracts, with results limited to English-language publications. The period during which the search was conducted was 1 August and 15 September 2025. No exclusion criteria based on literature type were applied; original articles, reviews, and policy reports were all considered. Government documents and policy statements are sourced from the official websites of relevant agencies and organizations. Regarding the organization of CEE systems at the time of their introduction in each country, the collection focused on reviews compiled on the topic. The search summary strategy can be found in Table 1.

The analytical perspective adopted in this article emphasizes in this article is primarily a societal perspective, with particular emphasis on the sustainability of the public health insurance system, in line with the objectives of the study. In this study, the retrieved literature was qualitatively synthesized, and its critique and interpretation took into account the historical context at the time of publication and the authors’ expertise. Given the objectives of this study, it is essential to present arguments grounded in Japan-specific healthcare system characteristics and clinical realities. Therefore, the sources for this narrative review were limited to articles concerning phenomena in Japan, except in cases of interdisciplinary methodologies for CEA, philosophy, and ethics.

Socioeconomic trends and health insurance policy (focusing on CEA)

Socioeconomic background necessitating CEE

Japan is experiencing an accelerating demographic shift characterized by a declining birthrate and an aging population. According to recent projections by the National Institute of Population and Social Security Research (2), by 2050, all prefectures except Tokyo will see a population decrease, with 20% of them expected to experience a decline of over 30%. Although population decline has been anticipated for more than two decades, the recent sharp drop in the fertility rate (1.26 in 2022) suggests that even the most severe projections may become reality. This demographic trend poses a profound challenge to the foundations of Japan’s social systems and compels a reevaluation of the nation’s structural framework. Naturally, population decline presents significant challenges to the social security system, including health insurance and hospital management. Outpatient visits are already decreasing nationwide, and inpatient numbers are projected to follow suit, with 261 secondary medical care zones expected to reach their peak by 2035 (3). As medical demand contracts, hospital bed occupancy rates and surgical facility utilization are likely to decline, leading to increasingly difficult financial conditions for healthcare institutions.

Looking back over the past 20 years, the aging population has driven increased medical demand and a rise in public healthcare expenditures. In contrast, the next 20 years are expected to bring a contraction in medical demand and a shrinking labor force, necessitating the evolution or transformation of traditional healthcare management models (Figure 1) (4). Some of these phenomena are already evident in Japan. For example, the field of obstetrics—recently spotlighted due to increased childbirth and childcare lump-sum allowances and discussed on insurance coverage—is at the forefront of the demographic crisis. Obstetrics, which typically serves a younger patient population, stands in contrast to geriatric care, the primary driver of medical demand. However, as the total number of patients begins to decline, the fundamental management challenges faced by both fields are likely to converge.

Figure 1 Impact of declining patient and working-age populations due to low birth rate and aging: implications for demand and healthcare financing (4).

Meanwhile, Japan’s national healthcare expenditure has continued to rise annually. From ¥19.7 trillion in 1989, it doubled to ¥40.0 trillion in FY2013 and reached ¥47.3 trillion in FY2023 (5). Commonly cited factors include increased demand due to aging, the rising cost of advanced medical technologies, and the growing complexity of disease structures (e.g., comorbidities). Recently, ultra-expensive drugs costing several hundred million yen per dose have emerged, driven by medical innovation. On the other hand, Japan’s real economy—which indirectly affects healthcare financing—has shown stagnation. Since around FY1991, the growth of gross national income (GNI) has slowed, and since FY1997, it has hovered around US$5 trillion (6). From a more relatable perspective, while per capita gross domestic product (GDP) growth has slowed markedly since the 1990s, per capita healthcare expenditure has continued to rise. This imbalance suggests that the range of policy options regarding benefits and burdens is narrowing, as economic harmony between healthcare provision and utilization becomes increasingly difficult to maintain (Figure 2) (7). In particular, there are concerns that the national burden of medical costs will structurally increase due to a decline in international competitiveness in medical development (pharmaceutical import value: 4.3 trillion yen/year) and the progress of exchange rates (an increase in pharmaceutical import value due to the weak yen against the US dollar: 670.5 billion yen/year, FY2020 base) (Figures S1,S2).

Figure 2 Annual trends in per capita gross domestic product and national healthcare expenditures. Extracted with permission from (7) source. GDP, gross domestic product; JYP, Japanese Yen.

To ensure the sustainability of Japan’s universal health insurance system, it is essential to clarify the relationship between healthcare and the surrounding economic environment. This includes deepening discussions on the financial burden borne by citizens and establishing mechanisms for the efficient use of limited medical resources. In this context, actively incorporating HTA tools such as CEA into the reimbursement system is indispensable. Historically, concerns have been raised about the financial impact of increasingly expensive medical technologies (8), and there has been limited emphasis on cost-effectiveness in decisions regarding insurance coverage and reimbursement pricing (9). Against this background, there seems to be increasing discussion in clinical settings about harmonizing with socio-economic factors (10). In other words, there appears to be a broadening consensus among stakeholders on the importance of maximizing patient well-being through the efficient use of limited healthcare resources.

Core concepts and policy positioning of CEE

CEE is generally applied to healthcare systems in two primary ways: (I) as a criterion for determining reimbursement eligibility; and (II) as a basis for adjusting reimbursement prices (11). In the first case, CEE is used to assess whether a medical technology should be covered under public health insurance. Technologies deemed to have poor cost-effectiveness are typically excluded (non-recommended), while those with favorable cost-effectiveness—including appropriate usage—are recommended for coverage. In the second case, CEE is used to determine whether the proposed reimbursement price falls within an acceptable cost-effectiveness range. If it does not, price adjustments are made accordingly (12). Various methods exist for implementing such adjustments. CEE is often introduced into healthcare and long-term care systems with the aim of ensuring sustainability. Therefore, evaluations are typically conducted from a societal perspective, reflecting the interests of the general public.

Building on these principles, the global expansion of CEE systems in the 2000s saw diverse applications across countries (11). Nations such as the UK and Australia, which fund healthcare primarily through taxation, utilize CEE both to determine reimbursement eligibility and to adjust reimbursement prices. Sweden (also tax-funded) applies CEE solely for eligibility decisions, while Germany (funded through social insurance) uses it exclusively for price adjustments. Even among countries that have adopted CEE, the criteria for selecting medical technologies for evaluation vary. However, countries that apply CEE to both eligibility and pricing tend to evaluate a broader range of technologies. The term “medical technology” encompasses pharmaceuticals, medical devices, and procedures performed by healthcare professionals.

In Japan, following a pilot implementation in fiscal year 2016, CEE was formally introduced into the national health insurance system in FY2019. The objective was to assess the balance between clinical utility and economic burden for high-priced, large-market pharmaceuticals and medical devices. Japan’s approach to CEE is characterized by its consideration for patient access: initial pricing is determined using conventional methods, followed by a focused evaluation of any additional pricing components. The evaluation process begins with the manufacturer submitting data to a specialized CEE committee composed of experts. This committee conducts a reanalysis and verification of the submitted data, culminating in a comprehensive appraisal (13). The final results are reported to the Central Social Insurance Medical Council, which approves the findings before price adjustments are implemented.

As of the first half of FY2025, 48 medical technologies had undergone CEE, of which 28 had completed price adjustments by October 2023, with an average adjustment rate of –3.2% (Figure 3) (14). Recent notable examples include discussions surrounding price adjustments for aortic stent graft systems and Alzheimer’s disease treatments. In the CEE system, the median projected market size at the time of insurance coverage for designated items was ¥15.6 billion per year (67 items, at peak projection). As previously noted, Japan’s CEE system assesses only the additional portion (not the total price). Consequently, it inadequately verifies not only the appropriateness of the price level for the comparator product but also the impacts on hospital management, patient burden, and fiscal implications. Further consideration of these issues, alongside methods for expanding the system’s adoption, is desirable.

Figure 3 Results of CEEs in the health insurance system: price adjustment rates for 28 assessed products (as of October 1, 2023). *, the price adjustment range excludes pharmaceutical products and medical devices that were used as comparators in the evaluation of the target item (e.g., newly listed drugs) (14). CEE, cost-effectiveness evaluation.

Fundamental theories and methodologies of CEE

CEA is a widely used method for evaluating the economic positioning of health programs within policy frameworks. Although not strictly defined, CEA is often used as a general term encompassing various cost-effectiveness methodologies. Depending on the type of outcome selected—such as patient health outcomes or societal benefits—CEA can be further categorized into cost-utility analysis (CUA) and cost-benefit analysis (CBA) (15). CEA typically assesses performance by calculating the ratio of cost to effect. In other words, this CEA is generally measured in units of “cost/effectiveness”, with lower values indicating better performance. When comparing technologies with different dimensions of clinical outcomes and resource consumption levels, or when verifying pricing levels through HTA, the incremental cost-effectiveness ratio (ICER)—defined as the ratio of additional cost to additional effect—is commonly employed (16). This approach requires careful consideration of analytical validity, clinical relevance, and the representativeness of outcomes.

ICER is expressed as “incremental cost/incremental effect”. If a new medical technology incurs higher costs but yields proportionally greater benefits, it is considered to have superior cost-effectiveness. Conversely, if the cost is higher and the effect is lower than the comparator, the technology is deemed “inferior”. If the cost is lower and the effect is greater, it is considered “dominant” (Figure 4) (17,18). A dominant ICER supports the economic performance (balance) of the technology and can serve as justification for enhancing patient access. Thus, ICER functions as a benchmark for determining whether a technology offers favorable cost-effectiveness at a given price level. It also facilitates stakeholder consensus on the appropriateness of additional cost required to achieve incremental effectiveness. These methodologies are codified in Japan through guidelines for analytical methods in health economic evaluation research (19).

Figure 4 Cost-effectiveness plane (four evaluation quadrants): conceptual framework for calculating ICER. Adapted from (17), licensed under CC BY 4.0. ICER, incremental cost-effectiveness ratio.

In clinical settings, patient utility—encompassing usefulness, satisfaction, and well-being—is measured as a form of health-related quality of life (HRQOL), which reflects subjective preferences and value systems. CUA applies this concept within the framework of CEA. One widely accepted outcome measure is the quality-adjusted life year (QALY), which integrates utility levels with survival duration (20). QALY captures both qualitative [quality of life (QOL)] and quantitative (life expectancy) aspects of health outcomes (21). One year of perfect health is quantified as 1 QALY, while death is quantified as 0 QALY. These concepts are also reflected in international clinical guidelines, such as those issued by the American Heart Association (AHA) for cardiovascular health economics (22). When QALY is selected as the outcome, ICER is often referred to as the incremental cost-utility ratio (ICUR). In Japan, the acceptable public threshold for cost-effectiveness is estimated at approximately ¥5 million to ¥7.5 million per QALY, based on national consensus regarding economic burden, including metrics such as GDP and willingness to pay (WTP) (23).

In practice, newly launched pharmaceuticals are often subject to evaluation, but limited clinical trial data necessitate reliance on simulation studies that extrapolate and integrate multiple existing datasets. Even in such cases, extrapolated data and assumptions should be based on reliable sources—such as high-quality study designs and statistically significant findings. Particularly in cost-minimization analysis, where outcomes are equivalent but costs are reduced, it is essential to rigorously assess the significance and magnitude of cost savings. As emphasized in frameworks such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE), empirical evidence is desirable for analyzing resource consumption (24,25). In Japan, observational studies on analgesics and cardiac devices have been conducted, in which individual-level utility data and direct cost data are linked over a long-term period (exceeding 12 months), and cumulative healthcare costs are statistically processed to perform CEA (26,27). However, many CEAs rely on expert opinion and cost estimates derived from reimbursement schedules.

These issues intersect with medical ethics and clinical guidelines, discussed later in this article. Moreover, when evaluating from the perspective of individual patients, more precise contextualization—such as out-of-pocket costs and treatment duration—is required compared to evaluations conducted from a societal perspective.

Considerations on the role of CEE in clinical practice guidelines

Perspectives for the future development of medical ethics

While it may be redundant to reiterate this to healthcare professionals, medical ethics are indispensable as normative principles that guide the attitudes of those engaged in medicine when interacting with patients or conducting research. Looking back at historical healthcare systems, it appears that meaningful discussions of medical ethics could emphasize the rights of individual patients—such as the sanctity of life and the significance of health—only when the domestic and international environments surrounding the medical field were socioeconomically stable and healthcare was comprehensively supported by public assistance mechanisms. However, in light of the pressing socioeconomic challenges that underpin recent efforts to redesign healthcare systems (28,29), a certain degree of consideration of medical economic factors is desirable in order to further deepen medical ethics in a future-oriented manner. Although such issues have begun to surface in clinical ethics practices both domestically and internationally, the unique characteristics of medical care, the prioritization required in clinical settings, the limited accumulation of relevant discourse, and the involvement of complex stakeholders have hindered the development of a coherent framework.

Therefore, despite the breadth and complexity of the topic, this section attempts to organize the relationship between medical ethics and health economics from the aforementioned perspectives.

To uphold the core ethical principles—such as the sanctity of life and the rights of individual patients—it is essential to ensure the equitable and stable provision of adequate healthcare services to all patient populations. For instance, the global goal of universal health coverage (UHC) emphasizes that “all people and communities can use the promotive, preventive, curative, rehabilitative and palliative health services they need, of sufficient quality to be effective, while also ensuring that the use of these services does not expose the user to financial hardship” (30). At the same time, the financial foundation of such health policies—e.g., public health insurance systems—is clearly influenced by macroeconomic indicators such as GDP, population size, unemployment rate, and poverty rate, all of which affect the level of UHC achieved (Table 2) (31). Consequently, pursuing the ideals of medical ethics requires consideration of economic factors and proactive development of healthcare financing and public systems.

Medical ethics encompass a wide range of topics (e.g., paternalism and informed consent, the fair innings argument, assisted reproductive and regenerative medicine). When viewed through the lens of health economics, particularly in the context of resource allocation, the central theme becomes the deepening and expansion of the balance—or harmony—between “individual and society” and “clinical and economic” dimensions.

One area where these issues become particularly salient is in clinical practice guidelines. These guidelines aim to standardize care and improve quality while supporting decision-making among healthcare providers, with the ultimate goal of delivering the most appropriate care to patients. From a systems perspective, clinical practice guidelines in Japan are increasingly referenced in the formulation of reimbursement policies within the universal health insurance system, which aligns with the concept of UHC (32). On the other hand, due to the economic burden on patients and their families and the sustainability of the healthcare system, discussions on medical ethics and social acceptance are also occurring around clinical practice guidelines (e.g., facility equalization, shared decision-making, cancer genomic medicine) (33-36). In this context, CEE—which is being adopted globally to promote the appropriate use of high-cost pharmaceuticals—has the potential to reduce financial burdens. Yet, concerns remain that such evaluations may restrict access to care (37).

Discussions regarding how CEE should be handled in clinical practice guidelines are thought to have only just begun. Therefore, the following sections will further explore the relationship between medical ethics and health economics, with clinical practice guidelines as a focal point.

The significance of harmonizing medical ethics and socioeconomic considerations

In medical ethics, four foundational principles are commonly cited: respect for autonomy, non-maleficence, beneficence, and justice. These principles, proposed by Tom L. Beauchamp and James F. Childress in Principles of Biomedical Ethics, serve as a framework for healthcare professionals when confronting ethical dilemmas (38). Furthermore, declarations such as the Patient’s Charter [1991, later incorporated into the National Health Service (NHS) Charter] and the Declaration of Geneva [2017] affirm patients’ rights to participate in medical decisions, receive optimal care, and access equitable healthcare services (39-41). Domestic legal frameworks also reflect these ethical standards. For example, Japan’s Medical Practitioners Act stipulates a duty to provide care under justifiable circumstances, establishing a public legal obligation. Based on these ethical foundations, it is inappropriate to determine the provision of medical care solely on economic grounds. However, the exercise of these rights presupposes the existence of a robust and sustainable healthcare system. In other words, when socioeconomic factors undermine the healthcare system itself and the stable provision of medical services diminishes or collapses, patients lose access to medical care and experience adverse consequences.

For example, maximizing the rights of specific patients by consuming excessive medical resources may lead to shortages of necessary resources for other patients, creating challenges in terms of the system’s objectives. To resolve such dilemmas, it is necessary to also discuss the health economics of clinical interventions (Figure 4).

Consequently, medical ethics must be interpreted in light of broader discussions about social responsibility and public interest. From this perspective, the three fundamental principles and ten key points of the Physician Charter [2002] are particularly noteworthy, especially the principle of social justice (fairness) and the obligation to allocate limited medical resources appropriately (42). Additionally, the World Medical Association Declaration (formerly the WMA Declaration of Madrid, 1987), which emphasizes professional autonomy, remains significant (43). When broadly interpreted, these principles guide medical professionals to deliver appropriate care and nursing while avoiding excessive consumption of resources for the “current patient”, thereby preserving treatment opportunities for the “next patient” (6). In essence, this approach seeks to balance individual and societal interests. Even within medical ethics frameworks that prioritize patient rights, it is essential to consider the societal contributions that sustain the clinical infrastructure. In other words, the interests of the individual and society can be discussed in the same direction through this framework. One theoretical approach to this perspective is the healthcare value assessment model, which incorporates ethical and societal values (Figure 5) (7,44).

Figure 5 Conceptual framework for medical value evaluation: applying marginal utility and cost-effectiveness theory in public sector discussions grounded in the real economy. Medical value can be quantified—made visible—through the application of utility theory and CEA, particularly when examining the mechanisms of social systems that govern benefits and burdens. The following section outlines the theoretical framework and methodology. In microeconomics, prices converge and efficiency is maximized through supply-demand equilibrium, which is grounded in utility theory. However, the evaluation of the medical domain incorporates considerations of equity (well-being), addressing the balance between patients’ expectations (preferences and willingness to pay) and government finances (income redistribution and fiscal sustainability) from the standpoint of public interest. Accordingly, within a given budget, maximizing utility leads to greater cost-effectiveness, thereby enhancing the overall utility of the population and increasing the “value” perceived by stakeholders. Compared to conceptual discussions of value, this approach enables a more concrete examination of its relationship with the real economy and broader value systems, making it particularly suitable for evaluating medical service pricing within the public healthcare sector. Notably, in the medical field, methodologies have been developed to measure and analyze patients’ utility values as indicators of health-related QOL. When this concept is integrated into CEA, it constitutes CUA. Adapted from (44), licensed under CC BY 4.0. CEA, cost-effectiveness analysis; CUA, cost-utility analysis; QOL, quality of life.

While patient-centered care is fundamental to maximizing healthcare value across generations—including future ones—a sustainable system must be designed that accounts for the differing roles of individuals (patients) and society (the public). With regard to this issue, within the scope of this study’s survey, there were relatively few Japanese publications that intersected medical ethics and health economics.

In practice, existing systems and guidelines often impose restrictions on treatment choices (e.g., transcatheter aortic valve replacement, age limits for infertility treatment). When value gains for both individuals and society (including various proxy indicators) are not anticipated, there remains room for discussion regarding patient selection (target population) and treatment options (treatment content), based on clinical economic evidence and consensus-based appraisal (Figure 6). Looking ahead, it is hoped that such discussions will continue and that the role of health economics will be critically examined in clinical practice guidelines and related documents. For example, Minds notes that recommendations may be “considered” when evidence shows differences in intervention outcomes, particularly in relation to resource consumption (24). Regarding CEEs, while limiting the application of societal-level evidence to individual patient decisions, it also acknowledges that such evidence may be “considered” when highlighting key points and determining recommendation strength. Examples of this include prioritizing low-cost medical technologies, focusing on treatments with comparable effectiveness, narrowing target populations, and sequencing the order of use and application. These evaluations must also account for the balance of benefits and harms, patient and public values and preferences, and resource consumption, including delivery systems (45).

Figure 6 Treatment choices and medical economics: socioeconomic considerations when value enhancement for individuals and society is limited.

Importantly, when incorporating societal benefit perspectives, simplistic applications of utilitarianism—such as Jeremy Bentham’s “greatest happiness for the greatest number”—should be avoided. Ethical deliberations must also respect individual rights, well-being, and the diversity of values (46,47). Ultimately, medical ethics refers to a systematic set of norms and standards that guide healthcare professionals’ conduct. These values serve as a reference point in times of ethical conflict or ambiguity and must be preserved as such.

The role of clinical practice guidelines and health economic evaluation

As previously discussed, when contemplating medical ethics within a healthcare system based on public and mutual support, it is meaningful—in clinical practice to consider—to account for the balance between individual patient benefit and societal welfare. In this context, the equilibrium between the equilibrium between individual interests and societal welfare, as well as between clinical care and economic considerations becomes a critical issue when evaluating the positioning of health economic assessments within clinical practice guidelines. This includes considerations related to ethical recommendations and societal acceptance, making it a longstanding yet continually relevant topic. One key analytical method for assessing such balance is CEA.

However, many CEAs are based on models or simulations that cannot be evaluated using conventional evidence grading systems such as those from the Centre for Evidence-Based Medicine (CEBM) or the GRADE framework. For example, 77.7% of reports on the cost-effectiveness of drug selection based on the CYP2C19 loss-of-function (LOF) allele were simulation studies (48). These studies tend to emphasize consensus-building rather than empirical validation, suggesting the need for further discussion regarding their appropriate use (48-50). Moreover, when interpreting the results of such analyses, it is necessary to consider whether the application of a uniform threshold for the ICER is appropriate, especially without accounting for disease-specific characteristics. For example, while the “dominant” and “inferior” quadrants in Figure 4 follow conventional classification and vector orientation, the interpretation of the “effective” quadrant—which encompasses the majority of cases—remains subject to debate, particularly from the perspectives of medical ethics and evidentiary standards.

That said, the process of evaluating health economics does not fundamentally differ from the general development of clinical guidelines, despite requiring attention to ethical and societal dimensions, as well as the unique methodologies and judgments found in model-based studies. In fact, meta-analyses of the cost-effectiveness of cardiac rehabilitation (measured in USD/QALY) have been cited in chronic heart failure guidelines issued by leading organizations such as the AHA and the American College of Cardiology (ACC) (17,51). The recently updated Japanese Clinical Practice Guidelines for Hepatocellular Carcinoma 2025 now include a section on health economic evaluation (52).

If it proves difficult to incorporate health economic evaluations directly into guideline recommendations due to ethical concerns, an alternative approach may be to develop these evaluations independently and later integrate them through supplementary statements or explanatory frameworks. This strategy warrants consideration.

Recommendations in clinical guidelines are generally regarded as the consensus of expert groups. Therefore, the cited studies should ideally meet a certain evidentiary threshold to facilitate consensus-building. Historically, interdisciplinary medical communities have pursued scientific validity through objectivity, representativeness, robustness, and reproducibility—principles foundational to evidence-based medicine (EBM). On the other hand, in actual clinical practice, it is often difficult to build evidence, and there are many cases where consensus is formed in the field based on the experience of those involved. More recently, decision-making has increasingly considered not only statistical significance but also trial conditions and real-world clinical contexts—for example, the Minimal Clinically Important Difference and the GRADE system (50). Regarding confidence in cost-effectiveness model outputs, there are also discussions aimed at ensuring their certainty (GRADE Working Group). Some scholars argue that guideline recommendations need not rely solely on evidence levels (53,54). Therefore, if reasonable explanatory power can be ensured, simulation studies may have a valid role in guideline development. Nonetheless, clinical practice guidelines are widely applied not only in medical settings but also in health insurance and litigation contexts. Given this broad societal impact, future consensus-building may benefit from incorporating perspectives outside academia or placing greater emphasis on evidence levels (Figure 7).

Figure 7 Key considerations for incorporating medical economic evidence in clinical guidelines. Extracted with permission from (1) source.

In discussions of resource consumption, it is important to consider not only reimbursement burdens but also actual medical costs, particularly from the standpoint of stable supply. Depending on the characteristics of the clinical domain, the scope of comparators in CEEs may be broad, and the mechanisms of care (e.g., treatment stages or combinations) may be complex. In such cases, depending on how the clinical questions (CQs) are formulated, a more comprehensive discussion of the evidence to be used is expected, taking into account factors such as actual usage (rates), patient burden, and the characteristics of evaluation indicators. Ultimately, the key lies in ensuring the reliability of net outcomes and providing a rational basis for recommendations.

Conclusions

Health economic assessments, which contribute to the sustainability of healthcare systems, are expected to become increasingly necessary as medical innovation advances, given ongoing socioeconomic trends, including changes in medical demand. Against this backdrop, discussions on the allocation of limited healthcare resources underscore the importance of achieving an appropriate balance between individual and societal needs, as well as between clinical and economic considerations. Enhancing the transparency and communication of healthcare value will be essential for the continued development of medical practice. Furthermore, clinical practice guidelines should actively address the relationship between medical ethics and health economics as part of broader societal progress.

Publicly funded healthcare resources—such as physicians, medical facilities, and financial support—must be utilized sustainably and efficiently to maximize clinical outcomes. This requires not only long-term system-level planning for healthcare financing and service provision but also the cultivation of stakeholder consensus and rational decision-making based on scientific evidence. However, compared to domains focusing primarily on clinical efficacy and safety outcomes, health economic assessments tend to receive relatively less attention regarding the level of supporting evidence. To promote the integration of CEE into clinical practice guidelines, it is imperative to strengthen the explanatory power and clarity of related evaluations.

Moving forward, to implement health economic evaluations within clinical practice guidelines, it is desirable to secure a robust level of evidence for CEA, including measures to reduce patients’ financial burden and avoid unsustainable deterioration of healthcare system financing and service capacity. To achieve this, it is essential for the government, professional societies, and academic institutions to strengthen human resource development and institutional coordination related to health economic evaluation. To foster medical innovation and ensure equitable patient access, it is essential to examine the role of health economic evaluations within the frameworks of medical ethics and clinical practice guidelines.

Acknowledgments

I would like to express my gratitude to the administrative staff in the laboratory for their support in managing the research.

Footnote

Reporting Checklist: The author has completed the Narrative Review reporting checklist. Available at https://jhmhp.amegroups.com/article/view/10.21037/jhmhp-25-95/rc

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Funding: None.

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