Pharmacoeconomics is a discipline that combines clinical pharmacology with health economics to decide whether specific pharmaceutical treatments are cost-effective or not. Indeed, such an appraisal takes on added significance in the light of the available limited amount of health resources and rising demand for new costly therapies. The fact of the matter is that the healthcare authorities need strong economic assessments like this to make decisions regarding the most effective use of available budget in securing the most significant enhancement in people's health(1).  By using pharmacoeconomic appraisal when making policies, healthcare systems can identify interventions that generate the most value in terms of money thus maximizing public health within a constrained budget. Other than promoting fairness in the allocation of scarce medical resources, this approach ensures the sustainability of healthcare systems. The common practice of conducting detailed cost-effectiveness analyses means that policymakers have a much better feel for how much funds are required to be allocated in certain areas to achieve maximum health gains(2).

1.1. Background on Pharmacoeconomics and Health Policy

The term 'Pharmacoeconomics' describes an interdisciplinary field of study involving both clinical pharmacology and health economics together to study drug costs and their impact on the patient's life. This area is also called an interdisciplinary one since there was no structured approach for a quantitative measurement of the financial consequences of healthcare interventions in the low-resource settings(3). This is when people wanted to know how much a new treatment would cost them, especially during times when costs for medicine were at their peak. Thus, it was toward such a purpose that pharmacoeconomics was conceived to look not only at clinical benefits but also cost effectiveness the two things that should always be followed in any decision made regarding medical care provision(4). This discipline employs a variety of methods, which include cost-minimization analysis (CMA), cost-benefit analysis (CBA), cost-utility analysis (CUA) amongst others that shall be used to compare pharmaceuticals based on health outcomes and economic values.

Among these is the CEA or cost-effectiveness analysis, which systematically compares drug benefits against alternative interventions by considering health benefits and costs associated with the different treatment methods. Here, the incremental cost-effectiveness ratio is computed to show the additional cost spent in achieving each extra benefit(5). Health policy is closely linked to pharmacoeconomic. It is concerned with strategic decisions, plans, and their implementations that target setting pre-set healthcare goals within a given community. This is where resources in health are shared fairly among different healthcare interventions. Health policies guided by information from pharmacoeconomic studies influence whether or not medicines should be included into national formularies thus making pricing systems and reimbursement procedures equitable with therapeutic gains extended towards patients(6).

1.2. Importance of Cost-Effectiveness Analysis in Healthcare

CEA is incredibly useful in deciding on what medical procedure should be done when so many of them need attention because it provides a systematic way of assessing economic and health outcomes associated with different interventions so one can know which ones work best for him or herself as well as others using limited resources. Its value is in directing funds to those areas of need that yield maximum health benefits per unit expenditure. CEA guides decisions on payment for treatment as well as inclusion into clinical guidelines based on evidence about how much improvement may occur in patient outcome measures per unit of cost. CEA furthermore helps in the comparative effectiveness research for identifying the best practices and refining treatment pathways. Lastly, it also contributes to mitigating the differences in health outcomes across the diverse population groups to address health disparities through the guidance of resource allocation(7).

Obviously, CEA is to be a prime force for innovation within any healthcare system a strong incentive toward the development of economically viable interventions and technologies. It is also to bring transparency and accountability into healthcare decision-making by thoroughly considering costs and outcomes. It enables better-informed treatment decisions taking into consideration clinical efficacy and economic factors, empowering both patients and healthcare providers. When a healthcare system is able to integrate CEA into the frameworks of decision-making, it achieves efficiency, equity, and long-term sustainability on the road to improving overall population health and well-being(8).

Figure 1: Overview of the components of the pharmacoeconomic model

1. Cost AnalysisDirect Costs.

Direct costs are very critical when it comes to pharmacoeconomics and they are included among the most important components which make up cost analysis(9). Such expenditures which have effects on money can be divided into two groups: direct medical expenses and direct non-medical expenses. Both provide varied perspectives for assessing healthcare treatments under an economic perspective. Direct medical costs include expenses directly related to patient treatment, such as medical procedures, consultations, drugs, and hospitalizations. In contrast, direct non-medical costs include supplementary expenses related to healthcare services, such as transportation, caring, and lodging (10). In addition to this, direct costs are grouped into variable and fixed costs because they respond differently depending on the number of services offered.

Variable costs alter according to changes in output, while fixed costs do not. For instance, expenses incurred to run health facilities are fixed cost items, while those of purchasing drugs or lab tests are variable cost items(11). These classifications provide the means for a more detailed identification of knowledge concerning the financial impact of healthcare interventions. The direct costs determine how best to allocate resources and evaluate how cost-effective different treatment options are. Identifying and quantifying direct

costs will go a long way in developing good reasons for the adoption of cost-effective interventions and allocating scarce resources adequately, policymakers and other actors in the health industry. The direct costs are part of the key elements in the assessment of pharmacoeconomic modeling that researchers use to evaluate the financial impact of healthcare treatments and compare the relative cost-effectiveness of various treatment approaches(12).

2. Indirect Costs

Indirect costs play a significant role in pharmacoeconomic evaluations, yet they are often challenging to estimate accurately due to a lack of robust primary data (13). Indirect costs are often estimated or measured using data from sources outside the immediate reporting area that provide benchmark or normative data. Indirect costs are essential for understanding the entire economic impact of a disease beyond direct medical costs, despite these challenges. Stakeholders who seek to reduce the overall financial impact of increased healthcare costs include governments, payers, and employers as interest in this expands. This includes accurate estimates or measures of indirect costs in addition to direct costs of disease morbidity and death. The concept of presenteeism, which includes the work quality, job satisfaction, and productivity of an individual while at work, is the newest addition to the study of indirect costs(14).

Indirect costs are most easily measured when individuals miss work due to a medical condition (15). The amount of time lost from illness varies depending on factors such as the nature and severity of the condition. Individuals with poorer health are likely to miss more work and experience reduced productivity while at work compared to healthier individuals. Treatments for illness may also lead to temporary alterations in health, resulting in short-term work absences. However, these absences may only affect short-term earnings and may not significantly decrease annual or longer-term worker income. Furthermore, such absences may not require significant employer commitments for replacement costs compared to longer-term absences (16).

1. Effectiveness Measures

1. Clinical Outcomes

Clinical outcomes are the observable effects of medication interventions on patients' health and quality of life. The list of metrics used in clinical outcomes is very comprehensive and includes blood pressure and serum glucose levels, among others, and certain clinical goals like mortality, morbidity, and disability. Clinical outcomes form the very important variables for a pharmacoeconomic study, along with pharmaceutical outcomes research, in assessing the value and efficacy of pharmaceutical treatments. They provide actual evidence of changes in health status effected by alterations in the physiological process of a disease. Measuring clinical outcomes using pharmacoeconomics is very important. Clinical results provide clear indication of the effectiveness of interventions with pharmaceuticals in attaining the desired health outcomes(17). Outcomes such as mortality, morbidity, symptom improvement, and quality of life will help the decision-maker understand the impact drugs can have on the health and well-being of patients. Clinical outcomes enable the decision-maker to compare different treatment options and thereby determine which interventions are most efficient and cost-effective. This information will ensure proper patient outcomes and optimize resource deployment. This could mean that pharmacoeconomics can be measured through clinical outcomes as it delivers patient-centered care that enhances health delivery.

An example of economic evaluations is the cost-effectiveness of preventing cardiovascular events through the use of statin therapy by comparing the costs and clinical outcomes of statin treatment against alternative interventions. Studies examining biologic therapies versus conventional DMARDs for the treatment of rheumatoid arthritis have considered clinical outcomes such as

improvements in disease activity, physical function, and quality of life (18). In largely real-life contexts, the availability of the data is limited or non-existent. In addition, it is quite unachievable to evaluate the long-term impacts of pharmacological treatment in the clinical outcome in economic assessments by ignoring patient preferences, evolution of the disease, and treatment compliance. Patient opinions and preferences should be included in pharmacoeconomic assessments considering patients' clinical outcomes despite being challenging due to differences in patient demography, cultural beliefs, and healthcare settings.

2. Patient-Reported Outcomes

By capturing the patient's perspectives on symptom relief, functional improvements, and overall well-being, PROs present a direct assessment of treatment efficacy from the patient's perspective (19). Economic decision-makers can make a more informed choice while considering the value of health interventions when PROs are included in the economic analysis by also considering patient-reported outcomes together with clinical outcomes. For instance, cost-utility analyses of antidepressant drugs to treat depression include the PROs of mood and functional status along with costs, to compare which course of action is more economical. PROs such as symptom burden and health-related quality of life are also considered to determine access to treatment and reimbursement in cancer treatment evaluations(20). PROs such as treatment satisfaction and the perceived gain in health are also considered to evaluate the value of telemedicine services used to manage chronic disease. However, there are some challenges while evaluating the pharmacoeconomics of PROs and the selection of proper metrics, ensuring the validity and reliability, and the proper interpretation of the data. This means that more patient-centered treatment and better health outcomes will come as a result of validity and utility issues in economic evaluations in healthcare decision-making.

3. Quality-Adjusted Life Years (QALYs)

One of the most important metrics in healthcare decision-making is the Quality-Adjusted Life Year, which is the most common way to assess the trade-offs between life quality and life length. QALYs provide a holistic assessment of health status by integrating morbidity and mortality outcomes. However, it needs to be remembered, too, that because QALYs are derived indirectly from utility functions, they could not truly reflect individual preferences. For this reason, there is a likelihood that treatments will not be chosen in a way that truly reflects patients' preferences, leading to less-than-ideal choices (21-22). To resolve such a limitation, another measure such as the Healthy-Years Equivalent, or HYE is proposed. Unlike QALYs, which are indirect measures of utility functions, HYE are directly reflected in individual utility functions, providing a more accurate portrayal of preferences. HYE is a unifying unit of measure across healthcare programs because it incorporates results related to morbidity and mortality, enabling comparisons and decision-making processes. There are descriptions of several techniques in measuring HYE that can be flexible and adaptable to a variety of populations and situations. In essence, HYE can be a usable way to enhance the pertinence and accuracy of health outcome assessments, ensuring that decisions are in alignment with actual patient preferences and maximize the use of healthcare resources, even as QALYs remain one of the most common metrics used in health economics.

3.1. Overview of Pharmaceutical Interventions

Pharmacoeconomics is one of the key elements when presenting the financial implications of a pharmaceutical intervention and service. According to the dictionary of pharmacoeconomics, it is defined as balancing the price of medicinal treatments against their consequences. This chapter looks at the effects that a particular drug would have on all the use of the health resources and the charges, in addition to the direct cost of purchase. Pharmacoeconomics aims to provide the evaluation of the effectiveness of pharmaceutical interventions in the view of affecting patient outcomes in the real-life setting. An ECHO model is given that considers that a drug has both clinical, economic, and humanistic characteristics. The model acknowledges the fact that the impact of a drug in terms of   health resource consumption across the board, cost, and quality of life should not be neglected besides its safety and effectiveness (9-10).

3.2. Types of Economic Evaluation

1. Cost-Minimization Analysis (CMA)

Cost-minimization analysis (CMA) is a vital method in pharmacoeconomics used to compare the costs of different treatment options when their outcomes are assumed to be equivalent. The analysis aims to identify the least expensive alternative among therapeutically similar treatments. In CMA, the outcomes of the alternatives are presumed to be identical, focusing solely on estimating the cost of each alternative (9). It is important that the study properly document the assumption of identical outcomes, given the difficulty of proving clinical equivalence between different therapeutic interventions. Comparable cases for conducting a CMA include multitude of similarly effective generic medications or different forms of the same drug. Comparable treatments for a particular disease exist in order to conduct a CMA. The costs for the direct charges for each treatment are then established, such as the cost of the medicines, cost of the administering agents, cost of monitoring, and cost of management of adverse events (23).

The less expensive treatment option is then determined through the comparison of these costs. It may even be necessary to apply statistical means to ensure that the cost comparison is exact and reliable. The value of CMA rests in its ability to aid healthcare decision makers in utilizing scarce resources effectively through its determination of the most cost-effective strategy. This, since it provides information about the cost effects of one treatment compared to another, assist with budgeting. CMA also helps to weigh the costs of healthcare procedures with their results, and it helps to determine the value of them. A substantial problem is that of therapeutic equivalency between the compared treatments, though, since it is not always the case because of variations in patient preferences, safety, or efficacy. Another is that it can be difficult to obtain specific cost information for various therapies, particularly for long-term effects and indirect costs. Research results on CMA also can not be applicable for other patient populations, other medical settings, or for other regions (24).

2. Cost-Benefit Analysis (CBA)

A major tool in decision-making processes is cost-benefit analysis, CBA, which compares the benefits and costs of alternative projects or interventions to select the best action. The costs and benefits of each alternative have to be estimated. For example, other alternatives might include the different treatment choices or policy action. Benefits may include increased productivity, health benefits, or fewer unfavorable events. Charges will include the initial investment, ongoing charges, and maintenance costs. Benefits are monetized so that comparisons are easier and to give a straight assessment against costs. The outcome will be whichever option yields the greatest net benefit. Resource allocation is one of the most important applications of CBA because it enables the decision-maker to rank interventions or projects according to their benefit(25). It allows policy alternatives to be tested by policy actors and adds transparency about the making of such decisions. Considerations about unobservable social goods such as better health are not easy and subjective to value in money terms. There is, in addition, the necessity for forecasting future costs and benefits and the fact that making the assumptions can introduce bias.

3. Cost-Utility Analysis (CUA)

Cost-utility analysis (CUA) is a method used in healthcare decision-making to compare the costs and outcomes of different interventions while considering patient preferences or utility. Unlike cost-effectiveness analysis, which measures outcomes in terms of life years saved, CUA adjusts outcomes based on QALYs, accounting for variations in patient health states and preferences (26). The cost per QALY gained is a standard way of expressing the results of CUA, therefore allowing for comparability in health care

interventions. After this, expected costs are given for each intervention, including direct medical costs, indirect medical costs, and patient-related costs. Surveys and other tools are used to quantify utility values that is, preferences or values a person place on various health outcomes. These utility values are necessary to calculate QALYs which combine the quantity and quality of life that an intervention gains.

Thus, cost-effectiveness of an intervention is estimated by the comparison of the total costs and the QALYs gained; interventions with relatively lower costs per QALY gained are more cost-effective. It aids in allocating the scarce healthcare resources by identifying interventions that give the greatest improvement in quality of life at the cost incurred. Besides, CUA allows for comparisons between various interventions in different healthcare spheres to make evidence-based decisions(27). CUA is patient-centered because it takes into account the values and preferences of the patient. It is, however, difficult to determine exact and trustworthy utility values since different people have different preferences for different health outcomes.

4. Cost-Effectiveness Analysis (CEA)

Cost-effectiveness analysis (CEA) is a method used in healthcare decision-making to compare the costs and consequences of alternative approaches to achieving a common objective or outcome. Unlike cost-benefit analysis, which measures outcomes in monetary terms, CEA utilizes natural or physical units as outcome measures (28). The objective of therapy is specified, and the alternative that achieves this objective at the least cost is pursued. For instance, if the goal is to reduce mortality due to stroke, CEA could compare various approaches to reducing serum triglyceride concentrations, assuming that such a reduction will save years of life. The approach with the lowest cost per year of life saved would be preferred. CEA assumes adequate resources are available for pursuing the alternative with the most favorable cost-effectiveness ratio (29). Selecting appropriate and meaningful health outcomes for comparison can be challenging, especially for interventions targeting complex conditions with multiple dimensions of health. CEA also relies on high-quality data on costs, outcomes, and effectiveness, which may not always be readily available or reliable. Determining the appropriate time horizon for CEA is also challenging, as the long-term impacts of interventions may not be fully captured within the study period. Table 1 interprets pros and cons of different analysis.

Table 1: Advantages and disadvantages of different types of economic evaluation methods.

3.3. Case Studies of Economic Evaluations

1. Drug Therapies

May and Jellison performed a pharmacoeconomic analysis of Metronidazole and Vancomycin for pseudomembranous colitis using the 10 step approach (30). After cost-effectiveness analysis, incremental cost analysis and sensitivity analysis, the study shows that using metronidazole for pseudomembranous colitis treatment is $420.53 cheaper per patient than vancomycin. While vancomycin is 9.5% more expensive, metronidazole's cost-effectiveness ratio is $187.29 less per patient. Metronidazole remains cost-effective despite being 5% less effective. Overall, using metronidazole as first-line treatment lowers patient costs without compromising care quality at Baylor University Medical Center. Another research aimed to analyze the duration patients remained on various antihypertensive drugs in clinical practice settings (31). Using an administrative database, new users of antihypertensive drugs aged ≥20 were tracked from January 1, 2000, to December 31, 2000, for 365 days.

Persistence was defined as therapy lasting >273 days. Among 14,062 patients, 39.7% remained on treatment (persistent patients), who were typically older, taking other medications for concurrent disorders, and initially prescribed angiotensin II receptor antagonists. Persistent patients accounted for 80.6% of the overall antihypertensive drug cost. Factors influencing drug cost included age, persistence pattern, number of prescribed classes, and specific medication. The study underscores the importance of measuring treatment persistence to assess appropriateness and cost-effectiveness of drug use in clinical practice.

2. Medical Devices

Trippoli and colleagues aimed to explore the integration of complex pharmacoeconomic models assessing effectiveness and cost into the in-hospital procurement of thrombectomy devices for acute ischemic stroke (32). Clinical modeling involved extracting three-month outcomes from randomized trials for four thrombectomy devices and projecting long-term results using Markov modeling. QALYs were estimated for each device using the same model. Economic modeling determined the net monetary benefit (NMB) per patient and simulated a competitive tender across the four products to establish tender-based scores. Prices of devices were obtained from manufacturers, and extensive sensitivity testing was conducted. Results revealed varying QALYs and NMBs across the four devices: Solitaire (1.86 QALYs, $101,824 NMB), Trevo (1.52 QALYs, $83,546 NMB), Penumbra (1.79 QALYs, $101,923 NMB), and Solumbra (1.35 QALYs, $69,440 NMB). Tender-based scores ranged from 0 to 100, with Solitaire and Penumbra scoring the highest and Solumbra scoring the lowest. Sensitivity analysis corroborated the base-case findings.

To assess the feasibility of value-based pricing and product design for a hypothetical vascular closure device in the pre-clinical stage, targeting the reduction of bleeding events, Brandes et al conducted a study (33). A deterministic decision-analytic model was  developed to estimate the cost-effectiveness of established vascular closure devices, considering perspectives from the Statutory Health Insurance system. Three strategies for determining the product's value were explored: savings from complications avoided, valuation based on willingness-to-pay thresholds, and value associated with modifying care pathways. Results indicated that established vascular closure devices were dominated by manual compression, while the hypothetical device reduced complication rates at higher costs. Maximum cost savings of approximately €4 per catheterization were projected with the hypothetical device. Extrapolation of an efficiency frontier was feasible for one subgroup. Modifying care pathways, such as same-day discharge for patients treated with vascular closure devices, could yield significant cost savings of €400-600 per catheterization. Conclusions suggested partial feasibility in calculating value-based prices for the novel closure device to inform product design. However, modifying care pathways appeared to offer greater value from payers' perspectives than modifying the device itself. Manufacturers were advised to explore reimbursement arrangements combined with incentives for same-day discharge to hospitals. Due to the product's early stage, results were subject to substantial uncertainty.

3. Health Services and Programs

Lomas et al. conducted a case study that investigates the application of pharmacoeconomic methods to assess the health impacts of exposure to poor air quality, enabling direct comparison of interventions aimed at reducing such exposure in terms of cost-effectiveness against other public health initiatives (34). Using data from a health impact assessment on a Low Emission Zone strategy in West Yorkshire, the study quantifies the cost-saving and health-improving implications of transport policy on air quality. Based on estimates from Leeds and Bradford, the study reveals that averting all-cause mortality generates 8.4 QALYs, while each avoided coronary event saves £28,000 in National Health Service (NHS)/Personal Social Services (PSS) costs and generates 1.1 QALYs. Furthermore, preventing childhood asthma cases leads to a £3,000 NHS/PSS cost saving and 0.9 QALYs gained per case avoided. Similarly, avoiding preterm births and low birthweight births results in significant cost savings and QALY gains. The study also models a scenario from the Low Emission Zone Feasibility Study, indicating substantial annual and one-off benefits compared to implementation costs, supporting the cost-effectiveness of air quality improvement interventions. Overall, the paper advocates for the evaluation of such interventions using cost-effectiveness analysis, employing a framework that considers NHS/PSS costs and QALYs, particularly when improving population health is the primary objective.

Over the period from 2007 to 2011, diabetes treatment costs surged by 41%, prompting exploration into the economic benefits of pharmacist involvement in managing type 2 diabetes. A 12-month prospective study analyzed the cost-effectiveness of a collaborative pharmacist-physician care model for type 2 diabetes. This study, including 206 English-speaking adults with type 2 diabetes, found that pharmacists spent approximately 983 hours on patient care, resulting in an average of 7.8 encounters per patient. Despite labor and program costs per patient being -$66.77 and $106.81, respectively, improvements in hemoglobin A1c (A1C) and systolic blood pressure (SBP) generated significant cost savings of $421.01 per patient. The average costs per patient for achieving specific outcomes, such as A1C reduction by at least 1% and SBP reduction by at least 5.6 mm Hg, were found to be favorable. While the study demonstrated cost savings associated with pharmacist labor costs, total program costs, inclusive of overhead, showed a slight increase in the cost of care (35) and presented in  Table 2.

Table 2: Case studies of economic evaluations in healthcare.

Policy Implications of Economic Evaluation refers to examining how economic evaluations of interventions, such as healthcare programs or policies, impact decision-making processes within the realm of public policy. This involves assessing the financial costs and benefits associated with various policy options and determining their effectiveness in achieving desired outcomes.

4.1. Evidence-based public health and Decision-Making

The aspect of evidence-based public health and decision-making is of utmost importance when it comes to the policy implications that arise from economic assessments. This means making good use of solid evidence gathered from economic evaluations to educate and direct public health policies and decisions. In essence, evidence-based public health refers to the process of developing policies and plans of action that improve population health outcomes by fusing the best available research data with contextual variables and professional insights (36). Economic evaluations are crucial in this regard because they offer insightful information about the cost-effectiveness and cost-benefit characteristics of various health interventions and programs. Through thorough evaluations of expenses and results, policymakers can determine which treatments are most beneficial to health about their costs. This in turn makes it easier to distribute limited resources in a way that optimizes health benefits while staying within financial limits (37). Moreover, the joint endeavors of scholars, legislators, practitioners, and other interested parties are critical to the success of evidence-based decision-making in public health. Transparency, accountability, and open communication are encouraged, which makes it possible to translate research findings into policies and programs that effectively address the health issues that communities face most urgently (38).

4.2. Pricing and Reimbursement Policies

Economic evaluations significantly impact reimbursement and pricing decisions for healthcare products and services. Health technology assessment agencies rely on economic evidence to negotiate prices with manufacturers and ascertain the value-for-money proposition of new technologies. By conducting thorough economic assessments, these agencies determine whether a healthcare intervention justifies its cost by considering its clinical benefits relative to its expenses. This process aids in establishing fair

reimbursement rates and pricing structures that align with the healthcare system's budgetary constraints while ensuring access to cost-effective treatments for patients. Through this rigorous evaluation, healthcare stakeholders can prioritize the adoption of interventions that offer the greatest health outcomes per unit of expenditure, thereby optimizing resource allocation and enhancing overall healthcare efficiency and effectiveness (39-40). 

4.3. Priority Setting and Resource Allocation

Priority setting in healthcare involves deciding which interventions or programs should receive funding or implementation focus. This decision is based on criteria such as cost-effectiveness, severity of the health condition, potential impact on population health, and equity considerations. The goal is to direct resources towards interventions that offer the greatest health gains per unit of investment (41-42).  Resource allocation, on the other hand, refers to the process of distributing available resources, such as healthcare budgets, personnel, and facilities, among competing interventions or programs. This process requires making trade-offs between different healthcare options to optimize health outcomes given the constraints of available resources. Resource allocation decisions also consider factors like efficiency, equity, and sustainability to ensure that resources are used effectively to improve overall health outcomes (43).

A study conducted by researchers aims to explore how economic evaluation influences the decision-making process of family physicians (FPs) in primary care settings. This intervention research project adopts a qualitative approach, employing a multiple-case study design involving ten FPs. Drawing on Pierre Bourdieu's sociological theory, the study seeks to understand the interplay between economic evaluation and clinical practice at both the individual (micro) and systemic (macro) levels. Data will be collected through life history interviews with FPs and interviews with key informants from medical associations and academic institutions. Through rigorous data analysis, the study aims to shed light on the impact of economic evaluation on FPs' decision-making, contributing to both empirical and theoretical knowledge in healthcare (44).

4.4. Patient Access and Affordability

The policy implications of economic evaluation concerning patient access and affordability are multifaceted. Firstly, such evaluations provide policymakers with crucial insights into the cost-effectiveness of healthcare interventions, aiding in the decision-making process regarding which treatments or services should be prioritized for funding. By understanding the economic impact of different healthcare options, policymakers can allocate resources more efficiently, ensuring that limited funds are directed towards interventions that offer the greatest value in terms of health outcomes (45). Moreover, economic evaluations shed light on the affordability of healthcare for patients. By assessing the costs associated with accessing healthcare services and treatments, policymakers can identify barriers to access and develop policies to address them. This might include measures to reduce out-of-pocket expenses for patients, such as subsidies or insurance coverage expansions (46). Additionally, economic evaluations can inform policies aimed at promoting competition and cost containment within healthcare markets, ultimately contributing to improved affordability for patients (47). Overall, economic evaluation plays a crucial role in shaping policies related to patient access and affordability by providing policymakers with evidence-based insights into the cost-effectiveness of interventions and identifying strategies to address barriers to access and affordability.

There are numerous challenges associated with the pharmacoeconomic evaluation. The most important of all the challenges is the data availability and quality of the data. Especially, in real life, it gets very difficult to get hold of the data for estimation of direct costs and indirect costs such as productivity costs and costs related to the burden on the caregivers(48-49). Also defining the outcomes

for the evaluation is difficult, it depends on the context of the evaluation whether it is from the caregiver’s perspective, and the healthcare professional or healthcare authority’s perspective(50). Many of the parameters are subjective and they change from person to person, leading to problems in evaluation. Estimating the cost associated with the health care intervention done to the patient is also a complicated task as it is likely to differ from place to place. As a result, the pharmacoeconomic findings from one study may not be generalizable to all populations. The patient’s preferences are very important when it comes to assess intervention’s benefit in respect to patient’s perspective. As it can bring in lot of uncertainties (51-52).

Addressing these problems in pharmacoeconomic evaluation is very important in order to understand the more realistic picture of the scenario(2). Improving data collection and ensuring the quality of the collected data becomes highly important for it. Also, the standardised system for measuring the outcomes and ensuring the transparency along with consistency and accuracy becomes essential for cost analyses. Incorporating the perspective of patients, health care professional and health care authorities along with the testing of the pharmacoeconomic evaluation to ensure its robustness is also very important (53-54). Pharmacoeconomic evaluation confronts challenges that transcend mere data accessibility and reliability, extending into the realm of methodological divergence, patient population heterogeneity, and ethical deliberations.

The absence of methodological uniformity in cost and effectiveness assessments presents a substantial obstacle. Divergent approaches utilized in valuing costs and benefits among studies impede cross-study result comparison. Selection between societal and healthcare payer perspectives significantly influences pharmacoeconomic analysis outcomes. Establishing standardized methodologies or formulating alignment guidelines can mitigate disparities and bolster the comparability of pharmacoeconomic investigations(55). Variability within patient populations poses a significant hurdle, primarily stemming from factors like age, comorbidities, and genetic diversity, which can intricately impact treatment outcomes and economic implications. Such diversity impedes the extrapolation of results across different demographic cohorts. Mitigating this challenge necessitates stratified analyses based on pivotal patient attributes or the execution of subgroup assessments. However, these approaches mandate larger data sets and sophisticated statistical methodologies, thereby adding layers of complexity to the evaluation endeavor(56).

Incorporating ethical considerations is pivotal within pharmacoeconomic assessments. The utilization of cost-effectiveness analyses to inform decisions may introduce contentious issues, particularly in instances where it could lead to the allocation of healthcare resources, potentially resulting in the withholding of beneficial treatments from specific populations. To address this, the integration of ethical frameworks into pharmacoeconomic evaluations is imperative, ensuring decision-making processes remain transparent and equitable, balancing economic efficacy with moral obligations(57).

Another challenge is temporal considerations which plays crucial role in pharmacoeconomic assessments, as they determine the scope and depth of the evaluation process. The timing of data collection and the duration of the analysis period wield substantial influence on the perceived value of interventions. Short-term studies risk overlooking long-term costs and outcomes, thereby presenting an incomplete portrayal of intervention efficacy. Extending the time horizon in pharmacoeconomic inquiries facilitates a more holistic understanding of intervention impact but necessitates the employment of sophisticated modeling methodologies and assumptions, thereby introducing heightened levels of uncertainty(2). Moreover, regulatory and policy disparities across regions pose challenges to the generalizability of pharmacoeconomic findings. Variations in healthcare systems, drug pricing, delivery models, and reimbursement practices among countries can influence the perceived cost-effectiveness of interventions. Consequently, researchers must tailor their evaluations to accommodate the intricacies of local healthcare contexts, a process that demands substantial resources and a nuanced comprehension of diverse healthcare systems(58). The challenges and its possible respective solutions in the pharmacoeconomic model of evaluation are presented in Fig. 2.

Figure 2: A summary of the challenges and its possible respective solutions in the pharmacoeconomic model of evaluation.

Addressing these complexities is imperative for advancing pharmacoeconomic research and ensuring that healthcare decisions are informed by robust and ethically sound data. Fostered collaboration among researchers, policymakers, and healthcare providers, alongside the development of international standards for pharmacoeconomic analyses, emerge as potential strategies to mitigate these challenges.

The important activities performed by different stakeholders in the health policy decision making is shown in figure 3.

Figure 3: The role of different stakeholders and their importance

6.1. Government Agencies and Regulatory Bodies

Health policy-making relies heavily on regulatory agencies and is especially important for Western countries where such agencies have specialized public authority that is not directly elected or managed by elected officials. IRAs are formal and have a specific organizational model: an appointed chairperson or director, a board or similar body, and their secretariat. They have several regulatory functions, which include rule-making, supervision, adjudication, and sanctioning (59-60). The development of IRAs can be traced to the challenges to post-war settlements of 'welfare capitalism' since the 1980s (61). Instead of just liberalization, privatization, or deregulation, scholars have seen the emergence and proliferation of the regulatory state, also known as regulatory capitalism. The idea is that greater regulatory arrangements will delegate execution competencies to non-majoritarian regulators. They are advanced for several reasons(62). The role of IRAs in health policy-making is multifaceted (63). First, they possess technical expertise and exclusive information crucial for developing optimal solutions to healthcare issues (64).

Second, their agreement is often deemed necessary by political decision-makers to ensure the effective implementation of new laws or policies. Moreover, agencies can legitimize preformatted solutions crafted by political actors in favor of specific reforms (65). The development of the regulatory state and the transformation of policy styles in Western Europe have led to extensive research on the impact of agencification on policy-making. This expansion may lead to unintended consequences and alter modes of political interaction. For instance, competition agencies, initially created for symbolic purposes, gradually exert material impacts on market economies (66). Contextual factors also shape agency functioning, influencing decision-making processes and opening them up to greater scrutiny.

Independent regulatory agencies have emerged as a 'third force' in regulation, distinct from elected politicians and regulators, constituting a separate group of actors (67). However, various questions remain regarding the varied roles of IRAs in policy-making across different contexts. Addressing these gaps requires a systematic comparative perspective, examining the entire policy process. To operationalize the role of agencies, measures of their centrality in policy-making are utilized, assuming that central actors hold key roles in the process (68). Research questions focus on the comparative centrality of IRAs in different stages of the policy-making

process and factors explaining variations in their roles. This entails an analysis of decision-making processes using qualitative comparative methods. Regulatory agencies in healthcare policy-making serve as essential pillars globally, ensuring the safety, efficacy, and accessibility of healthcare products and services. Among these, the Food and Drug Administration (FDA) in the United States stands out for its comprehensive oversight of drugs, biologics, medical devices, food, cosmetics, and more. Similarly, the European Medicines Agency (EMA) plays a pivotal role in the European Union by evaluating and supervising medicines for human and veterinary use (69).

In the United Kingdom, the Medicines and Healthcare Products Regulatory Agency (MHRA) oversees the quality, safety, and effectiveness of medicines and medical devices. Health Canada, as the national regulatory authority in Canada, ensures the safety and efficacy of health products, including drugs and medical devices (70). Australia's Therapeutic Goods Administration (TGA) and Ireland's Health Products Regulatory Authority (HPRA) also contribute significantly to healthcare policy-making by regulating therapeutic goods and healthcare products to uphold public health and safety standards (71-72). These agencies, through their regulatory functions, help shape healthcare policies, enforce regulations, and ensure the delivery of safe and effective healthcare interventions to the public.

6.2. Healthcare Payers and Insurers

For several reasons, health payers and insurance providers play an important role in health policy. They are financiers of medical operations, treatments, and prescription drugs. Thus, they affect the way resources are allocated, services provided, and how healthcare spending changes. Because they stand between patients and healthcare providers, health payers and insurance companies are in a crucial position to control costs and risks and promote access to care. Healthcare use patterns, provider conduct, and patient choice will be influenced by their policies and practices. These are the major stakeholders and sources of key information on patient outcomes, cost factors, and healthcare utilization that support evidence-based policy decisions and healthcare reforms. Last but not least, through different payment plans, incentives, and performance measures, they have a significant role to play in advancing healthcare quality, efficiency, and innovation(73). In the formulation of health policy, insurance companies and healthpayers assume several roles. They support laws that advance their strategic goals of improving health care cost and quality, in line with their financial interests. To further their goals, this advocacy entails engagement in public consultations, lobbying legislators, and financing projects and research.

They also create payment models and reimbursement rules that specify how healthcare professionals are paid for the services they perform. These rules affect how doctors behave, how they practice, and how they administer treatment, which affects patient access, prices, and quality(74). Thirdly, they make decisions on which healthcare services, treatments, and medications are covered under insurance plans, shaping patient access, treatment options, and out-of-pocket costs (75). They utilize provider network contracts, utilization monitoring, and preauthorization requirements as cost containment tools to manage healthcare spending and financial risks. They also develop and initiate programs pertaining to value-based purchasing, performance metrics, and quality improvement in an effort to enhance effectiveness, safety, and quality of healthcare. These programs inspire healthcare professionals to provide high-quality treatment and optimize patient outcomes. Commercial health insurance corporations such as UnitedHealthcare, Anthem, and Aetna, in their advocacy roles, reimbursement practices, and coverage decisions, hold big roles in developing the healthcare policies of the United State(76).

They participate in government-funded programs, including Medicare and Medicaid, that stipulate program design, payment reforms, and models for service delivery. In the case of countries with universal healthcare schemes, like the United Kingdom, public and private insurance plans, such as NHS, partner with public and private insurers to negotiate prices, manage healthcare budgets, and implement quality improvement initiatives. Similarly, in countries with mixed healthcare systems like Germany and France, a combination of public and private health insurers collaborates with government agencies to regulate the healthcare market, ensure universal coverage, and promote healthcare quality and affordability(77-78).

It is a very serious challenge, since costs in health care are rising, straining budgets, increasing premiums, and limiting coverage for health payers and insurance providers. Therefore, it is very challenging to provide an answer that addresses this challenge of cost pressures while retaining quality and access to care Inequalities in insurance coverage and access to healthcare services remain acute, particularly among minorities, low-income groups, and rural areas. Health payers and insurance providers have to start network expansion projects, affordability programs, and targeted outreach to bridge these gaps. Health payers and insurance providers face the challenge of complying with ever-evolving regulatory standards, which demand substantial resources and experience to handle. Healthcare reform legislation and insurance market reform legislation are just two of the many regulatory changes that might impact financial performance, corporate operations, and strategic planning (79-80). The rapidness of innovations and technological breakthroughs in healthcare brings on both opportunities and challenges for health payers and providers.

Value-based care models, predictive analytics, and digital health solutions require cooperation, investment, and adaptation from all parties involved in the healthcare system. Health payers and insurance providers have to embrace value-based care models, putting the patient's needs, quality, and outcomes at the forefront in order to deliver more accessible and affordable healthcare. In the long run, spending on preventative treatments, care coordination, and population health management will lead to better outcomes and cheaper costs(81). Health payers and insurance providers will identify high-risk populations through the use of data analytics and population health management tools and focus interventions and optimize care coordination and management. Predictive analytics, artificial intelligence, and machine learning can track trends, patterns, and opportunities for interventio(82). Health payers and insurance providers will need to engage with healthcare providers, government agencies, employers, and community organizations to accomplish the challenging tasks of dealing with rising costs, chronic disease management, and health disparities. Public–private partnerships, accountable care organizations, and integrated delivery networks can be very helpful in the creation of conditions for collaboration and innovation in the care process along the healthcare continuum(83).

6.3. Pharmaceutical Industry

Global health policy is largely under the influence of the pharmaceutical industry. Through its activities, the industry impacts public health outcomes and healthcare systems in ways that are directly related to drug R&D, pricing, regulation, and access. As such, the pharmaceutical industry should ideally contribute to the development of health policy for at least three reasons. First, the industry is responsible for the development of new medicines and therapies that improve patient outcomes, add life years, and reduce suffering

from several diseases and conditions. Second, through R&D investment, setting up factories, and marketing campaigns, pharmaceutical companies contribute to economic growth and job creation. The industry develops vaccines, antiviral medicines, and other important medicines and, in the process, helps respond to public health disasters like pandemics and epidemics. Last but not least, the involvement of the pharmaceutical industry in the development of health policy ensures that policies, plans, and programs are based on patient needs and industry expertise and scientific evidence and lead to equitable and efficient changes in healthcare.

Lobbies of pharmacies such as Pfizer, Johnson & Johnson, and Merck influence legislation by lobbying politicians to consider drug price, healthcare reform programs, and regulatory policie. They also participate in public-private partnerships, such as the Biomedical

Advanced Research and Development Authority (BARDA), to develop vaccines and therapeutics for public health emergencies (84-85). In Europe, pharmaceutical companies collaborate with the European Medicines Agency (EMA) and national regulatory agencies to obtain marketing authorizations for new drugs and ensure compliance with European Union regulations (86). They also contribute to healthcare policy debates through industry associations like the European Federation of Pharmaceutical Industries and Associations (EFPIA), advocating for policies that support innovation, patient access, and regulatory harmonization across member states (87).

The pharmaceutical industry faces several challenges in health policy-making. Firstly, escalating drug prices and affordability concerns pose significant hurdles, attracting scrutiny from policymakers, payers, and the public alike. The pressures on drug prices also undermine the incentives for innovation and patient's access to needed medicines, combined with reimbursement limitations and restrictions to market access. With a multitude of moving parts in regulatory compliance, this requires a lot of resource and experience in navigating through complex approval procedures and post-marketing surveillance requirements and intellectual property laws. Third, although protection of intellectual property rights is a positive driver of innovation and investment in the development of new medicines, there is much moral, legal, and societal debate over issues such as patent exclusivity, generic competition, and availability of needed medicine  (88). Last but not least, difficulties in market access and reimbursement do not allow launching innovative medicines and do not allow them to achieve widespread acceptance.

Market uptake, sales revenues, and return on investment for innovative treatments are driven to a great extent by payer restrictions, formulary decisions, and price negotiation. These problems talk to the complexity and multi-dimensionality of the influence of the pharmaceutical industry on health policy and underline the need for cooperative measures to solve them. In the future, there will be a range of factors that will shape how the pharmaceutical business goes about health policy formation. First, value-based pricing models are to ensure that patients can access drugs, pay for drugs, and innovate by tying the prices of drugs to clinical outcomes, patient benefits, and health costs. Future pricing strategies will be based on value-based agreements, outcome-based reimbursement, and health technology assessment frameworks. Second, streamlined regulatory processes, industry-regulatory agency cooperation, and the harmonization of global standards will expedite drug development, improve market access, and enhance patient safety for improved regulatory reform agenda in integrity, value, and public health (89).

The pharmaceutical industry will play a crucial role in addressing new health challenges, enhancing patient outcomes, and formulating sustainable healthcare systems by promoting efforts to transform healthcare using digital health, personalized medicine, and population health management strategies. Finally, collaboration among pharmaceutical companies, healthcare providers, payers, policymakers, and patient advocacy groups are critical matters of common goals, innovating solutions, and addressing healthcare concerns together. Through multi-stakeholder platforms and public-private partnerships, cross-sectoral collaborations can help share knowledge, mobilize resources, and foster collective action to improve health outcomes (90).

6.4. Healthcare Providers and Clinicians

Because of their firsthand knowledge, proficiency, and understanding of patient care, healthcare professionals and providers are essential in developing health policy. They come out with various views on healthcare policy, best practice, and system improvement because they are some stakeholders in the delivery of healthcare. For a number of reasons, involvement in health policymaking is important to doctors and other health professionals. Firstly, since they are directly familiar with diagnosing, treating, and managing a wide variety of health concerns, they provide a prime position to identify gaps in care, clinical inefficiencies, and areas for improvement (91). Secondly, in order for policies to be patient-centered, fair, and sensitive to various needs of healthcare, healthcare professionals and clinicians act as patient advocates by speaking on behalf of patients' interests and concerns in policy discussions.

Thirdly, by providing clinical knowledge, evidence-based practice, and practical experiences of the policymaking process, provision increases the legitimacy and credibility of those decisions. Fourthly, healthcare practitioners and clinicians play a vital role in translating policy directives into actual clinical practice by applying guidelines, procedures, and quality standards to enhance patient outcomes and healthcare delivery (92). Due to their firsthand knowledge and experience in providing critical insights into patient care, physicians and other healthcare providers wield great influence in shaping health policy. Their engagement is therefore critical to ensuring that policies are evidence-based, patient-centered, and sensitive to the varied healthcare needs of communities. Healthcare professionals are critical in shaping policies that prioritize population health and illness prevention because of their support for public health efforts, encouragement of healthy habits, and attention to social determinants of health. In addition, engagement by their input in quality improvement programs, policy formulation, and evidence-based practice promotes the legitimacy and efficacy of health policies (93). Through collaborative efforts with policymakers, regulators, and other stakeholders, healthcare providers and clinicians strive to translate policy directives into meaningful improvements in healthcare delivery and patient outcomes (94).

Healthcare professionals are committed to promoting equity in healthcare, improved access to care, and improved patient outcomes even as they face such challenges as time constraints, complex policies, and stakeholder pressures. Healthcare professionals and clinical champions continue to be engaged in making health policies as the healthcare systems become dynamic and face new challenges to support optimal and patient-centered care. Professional medical societies that support patient care, provider autonomy, and healthcare equity include the AMA, ACP, and ANA (95). They lobby policymakers, participate in legislative hearings, and publish policy statements on key healthcare issues, such as access to care, healthcare disparities, and healthcare workforce shortages (96). The healthcare professions, in liaison with government agencies, professional bodies, and patient advocacy groups, develop clinical recommendations, quality standards, and national health policies. To help clinical practice and resource allocation and clinical policy decisions, for example, the National Institute for Health and Care Excellence (NICE) in the United Kingdom provides evidence-based guidelines and recommendations (97).

6.5. Patient Advocacy Groups

Patient advocacy groups represent patients and caregivers, raise awareness of health issues, and influence legislative decisions to enhance healthcare access, quality, and results (98). These organizations, often led by individuals who have themselves been afflicted with a particular disease or health condition, push legislation that takes into account the patients' interests and concerns, raise public consciousness, and garner support for reforms in healthcare. Patient advocacy organizations offer powerful avenues through which patients and their family members are able to voice their concerns to policy makers, who in turn influence legislators on laws that put patient-centered care, treatment accessibility, and quality of life at the forefront. These organizations are of great importance in pushing policies that take into account the needs and preference of patients and their families through stories, focus, and contact with legislators. The HIV/AIDS advocacy movement is but one example of how patient advocacy groups make a difference (99).

Organizations such as TAC and the AIDS Healthcare Foundation (AHF) have helped to promote extended HIV testing and prevention programs, less stigma and discrimination for people living with HIV/AIDS, and greater access to antiretroviral therapy (ART). These organizations have provided access to life-extending therapies for millions of people in the world, influenced global health policies, and acquired money for HIV/AIDS programs through grassroots mobilization, lobbying campaigns, and legal challenges. The United States has various patient advocacy groups that include the American Cancer Society and the Alzheimer's Association, which in turn provide the lead in the raising of the awareness levels of the great illnesses of cancer and AD and the call for increased funding and

supportive legislation to foster policies for early detection, diagnosis, and effective treatment options (100-101).

These groups advocate for comprehensive policies that include equity in affordable healthcare, insurance coverage, and supportive care services and, at the same time, they provide resources, support services, and education for patients, caregivers, and health care professionals. European patient advocacy organizations like Rare Diseases Europe, EURORDIS, and the European Patients' Forum, EPF, span a broad spectrum of diseases and illnesses while advocating for the rights and interests of patients throughout the continent (102). It involves representing patient voices in the decision-making table for health policies, research funding, and regulatory procedures. They also provide support, information, and resources for patients and families while lobbying for access-improving policies related to the availability of orphan drugs, specialised care services, or patient-centered research endeavours. In developing countries, patient advocacy faces a different set of challenges because of the lack of resources, infrastructure, and government support. Organizations like the GAVI and the Global Fund to Fight AIDS, Tuberculosis, and Malaria come into play in terms of mobilizing resources, building capacity, and supporting advocacy to improve access to vaccines, treatments, and healthcare services in low-income and middle-income countries (103).

The groups collaborate with international partners, governments, and civil society organizations in a common purpose to respond to global health challenges and to improve health equity for all. In various ways but with similar goals, patient advocacy groups focus on enabling patients to improve health outcomes and to effect change for the good in health care systems. These groups are notably involved in shaping health policy-making, strengthening patient rights, and ensuring that health policies reflect the sensitivity of policies to patients' needs and aims through grassroots mobilization, public awareness campaigns, and lobbying efforts.

Progress in pharmacoeconomic methodologies shows potential for improving the accuracy, credibility, and relevance of healthcare economic assessments. An evolving facet concerns the enhancement and broadening of modeling methodologies, encompassing decision-analytic modeling, Markov modelling, and simulation modelling (104). These methodologies facilitate the enhanced emulation of prolonged repercussions and financial implications linked with healthcare interventions. Consequently, they furnish decision-makers with a heightened depth of understanding regarding the comparative value of diverse treatment approaches. Furthermore, progress in statistical methodologies, including Bayesian inference and machine learning algorithms, present avenues for enhancing the resilience and efficacy of pharmacoeconomic evaluations through the integration of intricate data frameworks and the encapsulation of non-linear interdependencies among variables(105).

In addition, the incorporation of patient-centered outcomes research (PCOR) methodologies, such as the elicitation of patient preferences and the implementation of shared decision-making frameworks, holds promise for enhancing pharmacoeconomic assessments by integrating patient viewpoints and preferences into decision-making paradigms(106). A. Incorporating Real-World

Evidence and Big Data Analysis- The convergence of real-world evidence (RWE) and big data analytics heralds a paradigm shift in pharmacoeconomic inquiry. RWE, sourced from observational investigations, electronic health records, claims repositories, and akin founts, furnishes invaluable perspectives on the efficacy, safety, and economic viability of healthcare modalities within authentic clinical settings(107).

Through the application of big data analytics methodologies, such as data excavation, natural language processing, and predictive modeling, investigators can distill salient patterns and correlations from expansive healthcare datasets, thereby facilitating more nuanced and precise pharmacoeconomic assessments. Moreover, the deployment of sophisticated data visualization and decision support instruments aids in the comprehension and dissemination of intricate findings across diverse stakeholders, encompassing

healthcare practitioners, policymakers, and patients. Nevertheless, challenges concerning data integrity, privacy safeguards, and methodological stringency necessitate concerted attention to optimize the utility and credibility of RWE within pharmacoeconomic appraisals(108). Future research endeavors should prioritize the development of standardized protocols for RWE acquisition and analysis, delineation of optimal strategies for integrating RWE into pharmacoeconomic frameworks, and assessment of the ramifications of RWE-guided decision-making on healthcare outcomes and resource allocation.

Global Harmonization of Pharmacoeconomic Standards- Achieving global alignment of pharmacoeconomic standards is imperative to uphold uniformity, comparability, and transparency in healthcare economic assessments across diverse regions and healthcare infrastructures. This necessitates the establishment of standardized guidelines, protocols, and reporting frameworks for conducting and documenting pharmacoeconomic investigations. Endeavors such as the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Good Practices for Outcomes Research Task Force strive to instate shared principles and methodologies for conducting pharmacoeconomic analyses, fostering inter-country cooperation and knowledge exchange(109). also, endeavours to enhance capacity development and

knowledge dissemination in pharmacoeconomic research, particularly in low- and middle-income nations, are crucial to ensuring universal proficiency and resources for conducting rigorous economic evaluations. Through advancing global harmonization of pharmacoeconomic standards, policymakers, healthcare providers, and patients can make more informed decisions regarding healthcare resource allocation and the implementation of cost-effective interventions, thereby enhancing health outcomes and promoting equitable access to healthcare services worldwide.

The review reflects on appropriate economic assessments that facilitate proper policy decision-making on pharmaceutical interventions. Using various techniques, such as cost-utility analysis, cost-effectiveness analysis, and cost-benefit analysis, decision-makers will be able to weigh which health care interventions are worth its costs and outcomes. This evidence-based approach allows policymakers to make efficient resource allocation by choosing which programs to prioritize and design pricing strategies, either through reimbursement policies or formulary systems. In summary, the integration of pharmacoeconomics into health policy is pivotal in ensuring that the economical redistribution of resources becomes a reality, increasing access for patients to a good quality of medical care and, ultimately, great population health outcomes.

ACKNOWLEDGMENTS             

Authors are thankful to healthcare practitioner; those are involved in interventions that generate the most value in terms of money for maximizing public health gains within a constrained budget. Authors are also grateful to open access publisher like DOAJ and the open access library to providing the required data to make this successful article.

Conflict of interest statement

Authors declare they don’t have any conflicts of interest in form of finance and other things.

1. Ahmad A, Patel I, Parimilakrishnan S, Mohanta GP, Chung H, Chang J. The role of pharmacoeconomics in current Indian healthcare system. Journal of research in pharmacy practice. 2013;2(1):3-9.
2. Tonin FS, Aznar-Lou I, Pontinha VM, Pontarolo R, Fernandez-Llimos F. Principles of pharmacoeconomic analysis: the case of pharmacist-led interventions. Pharmacy practice. 2021;19(1):2302.
3. Ahuja J, Gupta M, Gupta AK, Kohli K. Pharmacoeconomics. The National medical journal of India. 2004;17(2):80-3.
4. Adamiak G. Methods for the economic evaluation of health care programmes, 3rd ed: J Epidemiol Community Health. 2006 Sep;60(9):822-3.
5. Edlin R, Round J, Hulme C, McCabe C. Cost-effectiveness analysis and efficient use of the pharmaceutical budget: the key role of clinical pharmacologists. British journal of clinical pharmacology. 2010;70(3):350-5.
6. Bodrogi J, Kaló Z. Principles of pharmacoeconomics and their impact on strategic imperatives of pharmaceutical research and development. British journal of pharmacology. 2010;159(7):1367-73.
7. Mandelblatt JS, Fryback DG, Weinstein MC, Russell LB, Gold MR. Assessing the effectiveness of health interventions for cost-effectiveness analysis. Panel on Cost-Effectiveness in Health and Medicine. Journal of general internal medicine. 1997;12(9):551-8
8. Avanceña ALV, Prosser LA. Innovations in cost-effectiveness analysis that advance equity can expand its use in health policy. BMJ global health. 2022;7(2).
9. Freund DA, Dittus RS. Principles of pharmacoeconomic analysis of drug therapy. PharmacoEconomics. 1992;1(1):20-9.
10. Ibrahim N, Pozo-Martin F, Gilbert C. Direct non-medical costs double the total direct costs to patients undergoing cataract surgery in Zamfara state, Northern Nigeria: a case series. BMC health services research. 2015;15:1-7.
11. Roberts RR, Frutos PW, Ciavarella GG, Gussow LM, Mensah EK, Kampe LM, et al. Distribution of variable vs fixed costs of hospital care. Jama. 1999;281(7):644-9.
12. Chhatwal J, He T, Lopez-Olivo MA. Systematic review of modelling approaches for the cost effectiveness of hepatitis C treatment with direct-acting antivirals. Pharmacoeconomics. 2016;34:551-67.
13. Hughes D, Charles J, Dawoud D, Edwards RT, Holmes E, Jones C, et al. Conducting economic evaluations alongside randomised trials: current methodological issues and novel approaches. Pharmacoeconomics. 2016;34:447-61.
14. Kigozi J, Jowett S, Lewis M, Barton P, Coast J. The estimation and inclusion of presenteeism costs in applied economic evaluation: a systematic review. Value in Health. 2017;20(3):496-506.
15. Boccuzzi SJ. Indirect health care costs: An overview. Cardiovascular health care economics. 2003:63-79.
16. Mennini FS, Gitto L. Approaches to estimating indirect costs in healthcare: motivations for choice. Journal of European Economy. 2022;21(1):17-45.
17. Kane SL, Weber RJ, Dasta JF. The impact of critical care pharmacists on enhancing patient outcomes. Intensive care medicine. 2003;29:691-8.
18. Boyadzhieva V, Tachkov K, Stoilov N, Mitov K, Stoilov R, Petrova G. Quality of life and disease activity of patients with rheumatoid arthritis on tofacitinib and biologic disease-modifying antirheumatic drug therapies. Rheumatology International. 2022;42(10):1775-83.
19. Sanderson T, Morris M, Calnan M, Richards P, Hewlett S. Patient perspective of measuring treatment efficacy: the rheumatoid arthritis patient priorities for pharmacologic interventions outcomes. Arthritis care & research. 2010;62(5):647-56.
20. Gilbert A, Sebag-Montefiore D, Davidson S, Velikova G. Use of patient-reported outcomes to measure symptoms and health related quality of life in the clinic. Gynecologic oncology. 2015;136(3):429-39.
21. Prieto L, Sacristán JA. Problems and solutions in calculating quality-adjusted life years (QALYs). Health and quality of life outcomes. 2003;1:1-8.
22. Gafni A, Birch S. Preferences for outcomes in economic evaluation: an economic approach to addressing economic problems. Social science & medicine. 1995;40(6):767-76.
23. Haycox A. What is cost-minimisation analysis? Pharmacoeconomics: CRC Press; 2020. p. 109-20.
24. Hutubessy R, Chisholm D, Edejer TT-T, Who C. Generalized cost-effectiveness analysis for national-level priority-setting in the health sector. Cost effectiveness and resource allocation. 2003;1:1-13.
25. Ochalek J, Revill P, Drummond M. Allocating Scarce Resources—Tools for Priority Setting. Global Health Economics: Shaping Health Policy in Low-and Middle-Income Countries: World Scientific; 2020. p. 53-73.
26. Lau VI, Xie F, Basmaji J, Cook DJ, Fowler R, Kiflen M, et al. Health-related quality-of-life and cost utility analyses in critical care: a systematic review. Critical care medicine. 2021;49(4):575-88.
27. Custer B, Janssen MP, Alliance of Blood Operators Risk‐Based Decision‐Making I. Health economics and outcomes methods in risk‐based decision‐making for blood safety. Transfusion. 2015;55(8):2039-47.
28. Luce BR, Simpson K. Methods of cost-effectiveness analysis: areas of consensus and debate. Clinical Therapeutics. 1995;17(1):109-25.
29. Gold MR. Cost-effectiveness in health and medicine: Oxford university press; 1996.
30. May DM, Jellison KL, editors. A Case for Using Pharmacoeconomic Analysis to Assess the Cost-Effectiveness of Metronidazole for Pseudomembranous Colitis1994: Taylor & Francis.
31. Esposti LD, Martino MD, Saragoni S, Sgreccia A, Capone A, Buda S, et al. Pharmacoeconomics of Antihypertensive Drug Treatment: An Analysis of How Long Patients Remain on Various Antihypertensive Therapies. The Journal of Clinical Hypertension. 2004;6(2):76-82.
32. Trippoli S, Caccese E, Marinai C, Messori A. Value-based procurement of medical devices: Application to devices for mechanical thrombectomy in ischemic stroke. Clinical neurology and neurosurgery. 2018;166:61-5.
33. Brandes A, Sinner MF, Kääb S, Rogowski WH. Early decision-analytic modeling – a case study on vascular closure devices. BMC Health Services Research. 2015;15(1):486.
34. James L, Laetitia S, Sally J, Maureen M, Elizabeth B, Mike H, et al. A pharmacoeconomic approach to assessing the costs and benefits of air quality interventions that improve health: a case study. BMJ Open. 2016;6(6):e010686.
35. Franklin BE, Farland MZ, Thomas J, McFarland MS, Ray SM, Byrd DC. Pharmacoeconomic Analysis of the Diabetes Initiative Program: A Pharmacist-Physician Collaborative Care Model. Annals of Pharmacotherapy. 2013;47(12):1627-34.
36. Rabarison KM, Bish CL, Massoudi MS, Giles WH. Economic Evaluation Enhances Public Health Decision Making. Frontiers in public health. 2015;3:164.
37. Mays GP, Smith SA. Evidence links increases in public health spending to declines in preventable deaths. Health affairs (Project Hope). 2011;30(8):1585-93.
38. Krist AH, Tong ST, Aycock RA, Longo DR. Engaging Patients in Decision-Making and Behavior Change to Promote Prevention. Studies in health technology and informatics. 2017;240:284-302.
39. Russo P, Zanuzzi M, Carletto A, Sammarco A, Romano F, Manca A. Role of Economic Evaluations on Pricing of Medicines Reimbursed by the Italian National Health Service. PharmacoEconomics. 2023;41(1):107-17.
40. Chen Y. Health technology assessment and economic evaluation: Is it applicable for the traditional medicine? Integrative medicine research. 2022;11(1):100756.
41. Baltussen R, Niessen L. Priority setting of health interventions: the need for multi-criteria decision analysis. Cost effectiveness and resource allocation : C/E. 2006;4:14.
42. Sabik LM, Lie RK. Priority setting in health care: Lessons from the experiences of eight countries. International Journal for Equity in Health. 2008;7(1):4.
43. Kluge EH. Resource allocation in healthcare: implications of models of medicine as a profession. MedGenMed : Medscape general medicine. 2007;9(1):57.
44. Lessard C, Contandriopoulos A-P, Beaulieu M-D. The role of economic evaluation in the decision-making process of family physicians: design and methods of a qualitative embedded multiple-case study. BMC Family Practice. 2009;10(1):15.
45. Mosadeghrad AM, Jaafaripooyan E, Zamandi M. Economic Evaluation of Health Interventions: A Critical Review. Iranian journal of public health. 2022;51(10):2159-70.
46. Kim Y, Kim Y, Lee HJ, Lee S, Park SY, Oh SH, et al. The Primary Process and Key Concepts of Economic Evaluation in Healthcare. Journal of preventive medicine and public health = Yebang Uihakhoe chi. 2022;55(5):415-23.
47. Hoomans T, Severens JL. Economic evaluation of implementation strategies in health care. Implementation Science. 2014;9(1):168.
48. van Dongen JM, El Alili M, Varga AN, Guevara Morel AE, Jornada Ben A, Khorrami M, et al. What do national pharmacoeconomic guidelines recommend regarding the statistical analysis of trial-based economic evaluations? Expert review of pharmacoeconomics & outcomes research. 2020;20(1):27-37.
49. Kließ MK, Martins R, Connolly MP. Major cost drivers in assessing the economic burden of Alzheimer’s disease: a structured, rapid review. The journal of prevention of Alzheimer's disease. 2021;8(3):362-70.
50. Rehman Au, Muhammad SA, Tasleem Z, Alsaedi A, Dar M, Iqbal MO, et al. Humanistic and socioeconomic burden of COPD patients and their caregivers in Malaysia. Scientific reports. 2021;11(1):22598.
51. Wagner TH, Yoon J, Jacobs JC, So A, Kilbourne AM, Yu W, et al. Estimating costs of an implementation intervention. Medical Decision Making. 2020;40(8):959-67.
52. Mason JM, Mason AR. The Generalisability of Pharmacoeconomic Studies. PharmacoEconomics. 2006;24(10):937-45.
53. McGhan WF, Arnold RJG. Introduction to pharmacoeconomics. Pharmacoeconomics: CRC Press; 2020. p. 1-20.
54. Min C, Xue M, Haotian F, Jialian L, Lingli Z. An overview of the characteristics and quality assessment criteria in systematic review of pharmacoeconomics. PloS one. 2021;16(2):e0246080.
55. Kadu M, Ehrenberg N, Stein V, Tsiachristas A. Methodological Quality of Economic Evaluations in Integrated Care: Evidence from a Systematic Review. International journal of integrated care. 2019;19(3):17.
56. Ramaekers BL, Joore MA, Grutters JP. How should we deal with patient heterogeneity in economic evaluation: a systematic review of national pharmacoeconomic guidelines. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research. 2013;16(5):855-62.
57. Schwarzer R, Rochau U, Saverno K, Jahn B, Bornschein B, Muehlberger N, et al. Systematic overview of cost-effectiveness thresholds in ten countries across four continents. Journal of comparative effectiveness research. 2015;4(5):485-504.
58. Alzarea AI, Khan YH, Alanazi AS, Butt MH, Almalki ZS, AlAhmari AK, et al. Barriers and Facilitators of Pharmacoeconomic Studies: A Review of Evidence from the Middle Eastern Countries. International journal of environmental research and public health. 2022;19(13).
59. Haeder SF, Yackee SW. A Look Under the Hood: Regulatory Policy Making and the Affordable Care Act. Journal of Health Politics, Policy and Law. 2020;45(5):771-86.
60. Thatcher M. Regulation after delegation: independent regulatory agencies in Europe. Journal of European Public Policy. 2002;9(6):954-72.
61. Van Kersbergen K. Social Capitalism: A study of Christian democracy and the post-war settlement of the welfare state. 1991.
62. Gilardi F. The Institutional Foundations of Regulatory Capitalism: The Diffusion of Independent Regulatory Agencies in Western Europe. The ANNALS of the American Academy of Political and Social Science. 2005;598(1):84-101.
63. Nelson N, Geltzer A, Hilgartner S. Introduction: the anticipatory state: making policy-relevant knowledge about the future. Science and Public Policy. 2008;35(8):546-50.
64. Chen P-T, Lin C-L, Wu W-N. Big data management in healthcare: Adoption challenges and implications. International Journal of Information Management. 2020;53:102078.
65. Maggetti M. Regulation in practice: The de facto independence of regulatory agencies: ECPR press; 2012.
66. Tilcsik A. From Ritual to Reality: Demography, Ideology, and Decoupling in a Post-Communist Government Agency. Academy of Management Journal. 2010;53(6):1474-98.
67. Thatcher M. The Third Force? Independent Regulatory Agencies and Elected Politicians in Europe. Governance. 2005;18(3):347-73.
68. Ingold K, Fischer M, Christopoulos D. The roles actors play in policy networks: Central positions in strongly institutionalized fields. Network Science. 2021;9(2):213-35.
69. Potts J, Genov G, Segec A, Raine J, Straus S, Arlett P. Improving the Safety of Medicines in the European Union: From Signals to Action. Clinical Pharmacology & Therapeutics. 2020;107(3):521-9.
70. Leslie K, Nelson S, Deber R, Gilmour J. Policy Tensions in Regulatory Reform: Changes to Regulation of Health Professions in Australia, the United Kingdom, and Ontario, Canada. Journal of Nursing Regulation. 2018;8(4):32-42.
71. Kumari BS, Hanuja GS, Nagabhushanam MV, Reddy DN, Bonthagarala B. Current Regulatory Requirements for Registration of Medicines, Compilation and Submission of Dossier in Australian Therapeutic goods Administration. International Journal of Advanced Scientific and Technical Research, ISSN. 2016:2249-9954.
72. O'Dwyer L, Nolan L, Fisher C. Supporting Innovation through Regulation and Science: Ireland as an Innovation Hub for Health Products. Biomedicine Hub. 2017;2(Suppl. 1):1-8.
73. Wharam JF, Daniels N. Toward Evidence-Based Policy Making and Standardized Assessment of Health Policy Reform. JAMA. 2007;298(6):676-9.
74. Friedberg MW, Chen PG, Van Busum KR, Aunon F, Pham C, Caloyeras J, et al. Factors Affecting Physician Professional Satisfaction and Their Implications for Patient Care, Health Systems, and Health Policy. Rand health quarterly. 2014;3(4):1.
75. Mekuria GA, Achalu DL, Tewuhibo D, Ayenew W, Ali EE. Perspectives of key decision makers on out-of-pocket payments for medicines in the Ethiopian healthcare system: a qualitative interview study. BMJ open. 2023;13(7):e072748.
76. Cooper Z, Craig SV, Gaynor M, Van Reenen J. THE PRICE AIN'T RIGHT? HOSPITAL PRICES AND HEALTH SPENDING ON THE PRIVATELY INSURED. The quarterly journal of economics. 2019;134(1):51-107.
77. Mytton OT, Jackson C, Steinacher A, Goodman A, Langenberg C, Griffin S, et al. The current and potential health benefits of the National Health Service Health Check cardiovascular disease prevention programme in England: A microsimulation study. PLoS medicine. 2018;15(3):e1002517.
78. Abstracts from the 2017 Society of General Internal Medicine Annual Meeting. Journal of general internal medicine. 2017;32(Suppl 2):83-808.
79. Glied S. Health Care Costs: On the Rise Again %J Journal of Economic Perspectives. 2003;17(2):125-48.
80. Gilson L, Mills A. Health sector reforms in sub-Saharan Africa: lessons of the last 10 years. Health policy. 1995;32(1-3):215-43.
81. Handmaker K, Hart J. 9 steps to effective population health management: the success of an accountable care organization ultimately depends on the extent to which it intelligently deploys technology solutions for data analytics, care team workflows, and patient engagement to improve population health while reducing costs. Healthcare Financial Management. 2015;69(4):70-7.
82. Schwalbe N, Wahl B. Artificial intelligence and the future of global health. The Lancet. 2020;395(10236):1579-86.
83. Bazzoli GJ, Stein R, Alexander JA, Conrad DA, Sofaer S, Shortell SM. Public–Private Collaboration in Health and Human Service Delivery: Evidence from Community Partnerships. The Milbank Quarterly. 1997;75(4):533-61.
84. Wouters OJ. Lobbying expenditures and campaign contributions by the pharmaceutical and health product industry in the United States, 1999-2018. JAMA internal medicine. 2020;180(5):688-97.
85. Gronvall GK, Smith BT, Matheny J, Mair M, Chamberlain A, Deitch S, et al. Biomedical advanced research and development authority (BARDA) Roundtable. Biosecurity and bioterrorism: biodefense strategy, practice, and science. 2007;5(2):174-9.
86. Saesen R, Machado M, Crifo B, Liu L, de Vries C, Herold R, et al. Involvement of the European Medicines Agency in multi-stakeholder regulatory science research projects: experiences of staff members and project coordinators. 2023;10.
87. Powrie-Smith A. European federation of pharmaceutical industries and associations. Impact. 2017;2017(2):38-9.
88. Neumann PJ, Cohen JT, Ollendorf DA. The right price: a value-based prescription for drug costs: Oxford University Press; 2021.
89. Schoonveld E. The role of Value in Market Access and pricing negotiations. The Future of Health Economics. 2017:7-19.
90. Bhavnani SP, Parakh K, Atreja A, Druz R, Graham GN, Hayek SS, et al. 2017 Roadmap for innovation—ACC health policy statement on healthcare transformation in the era of digital health, big data, and precision health: a report of the American College of Cardiology Task Force on Health Policy Statements and Systems of Care. Journal of the American College of Cardiology. 2017;70(21):2696-718.
91. Warwick RJ. The experience of policymaking in healthcare: the interaction of policy formulation and frontline staff practice. 2010.
92. Niessen LW, Grijseels EWM, Rutten FFH. The evidence-based approach in health policy and health care delivery. Social science & medicine. 2000;51(6):859-69.
93. Atkins D, Fink K, Slutsky J. Better information for better health care: the Evidence-based Practice Center program and the Agency for Healthcare Research and Quality. Annals of internal medicine. 2005;142(12_Part_2):1035-41.
94. Scott I. What are the most effective strategies for improving quality and safety of health care? Internal medicine journal. 2009;39(6):389-400.
95. Ober S, Wilkie S. Effective Policy and Advocacy for Nurses Engaged in Advanced Practice. DNP Education, Practice, and Policy: Redesigning Advanced Practice for the 21st Century. 2018:283.
96. Mund A, Zaccagnini ME, White K. Healthcare policy for advocacy in health care. The doctor of nursing practice essentials: A new model for advance practice nursing. 2011:193-234.
97. Kelly M, Morgan A, Ellis S, Younger T, Huntley J, Swann C. Evidence based public health: A review of the experience of the National Institute of Health and Clinical Excellence (NICE) of developing public health guidance in England. Social science & medicine. 2010;71(6):1056-62.
98. Negarandeh R, Oskouie F, Ahmadi F, Nikravesh M, Hallberg IR. Patient advocacy: barriers and facilitators. BMC nursing. 2006;5:1-8.
99. Howell A, Mills C, Rushton S. The (Mis)appropriation of HIV/AIDS advocacy strategies in Global Mental Health: towards a more nuanced approach. Globalization and health. 2017;13(1):44.
100. Leach CR, Hudson SV, Diefenbach MA, Wiseman KP, Sanders A, Coa K, et al. Cancer health self-efficacy improvement in a randomized controlled trial. Cancer. 2022;128(3):597-605.
101. Luo J, Agboola F, Grant E, Morris JC, Masters CL, Albert MS, et al. Accelerated longitudinal changes and ordering of Alzheimer disease biomarkers across the adult lifespan. Brain : a journal of neurology. 2022;145(12):4459-73.
102. Vandenplas Y, Simoens S, Van Wilder P, Vulto AG, Huys I. Informing patients about biosimilar medicines: the role of European patient associations. Pharmaceuticals. 2021;14(2):117.
103. World Health O. Global Alliance for Vaccines and Immunization (GAVI). Global Alliance for Vaccines and Immunization (GAVI)2001. 2-7.
104. Ademi Z, Kim H, Zomer E, Reid CM, Hollingsworth B, Liew D. Overview of pharmacoeconomic modelling methods. British journal of clinical pharmacology. 2013;75(4):944-50.
105. Dhillon SK, Ganggayah MD, Sinnadurai S, Lio P, Taib NA. Theory and Practice of Integrating Machine Learning and Conventional Statistics in Medical Data Analysis. Diagnostics (Basel, Switzerland). 2022;12(10).
106. Snyder CF, Jensen RE, Segal JB, Wu AW. Patient-reported outcomes (PROs): putting the patient perspective in patient-centered outcomes research. Medical care. 2013;51(8 Suppl 3):S73-9.
107. Magalhães T, Dinis-Oliveira RJ, Taveira-Gomes T. Digital Health and Big Data Analytics: Implications of Real-World Evidence for Clinicians and Policymakers. International journal of environmental research and public health. 2022;19(14).
108. Raghupathi W, Raghupathi V. Big data analytics in healthcare: promise and potential. Health information science and systems. 2014;2:3.
109. Thokala P, Devlin N, Marsh K, Baltussen R, Boysen M, Kalo Z, et al. Multiple Criteria Decision Analysis for Health Care Decision Making--An Introduction: Report 1 of the ISPOR MCDA Emerging Good Practices Task Force. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research. 2016;19(1):1-13.