Differences between health technology assessment topics in high- and middle-income countries: a scoping review

Background The Health Technology Assessment (HTA) has encountered different issues and challenges over the last two decades. The main purpose of this research is to review the issues and challenges in high- and middle-income countries through reviewing studies related to the HTA. Methods The HTA area literature of different countries was collected from 2009 to 2020 and analyzed using scoping review, based on Scopus and WoS databases. Results Given the fact that the HTA is practically done in high- and middle-income countries, the results of reviewing the studies and articles of countries reveal that high-income countries seek to increase the participation of stakeholders and enhance the transparency of processes, policy-making, and regulation of the HTA, as well as the systematization of various participant institutions in this area. Middle-income countries, on the other hand, are mostly involved in raising awareness, training and skill development of HTA-related staff, institutionalizing the concept of HTA, and allocating appropriate resources for effective and safe decision-making in their health system. Conclusion The problem of incoordination between stakeholders (participant institutions) in the HTA, and thereby, problems in decision-making were found in many of the studied reports and articles. Thus, one of the useful efforts to be made by different countries to maintain the integrity of this system would be the process of involving all members of this system and the formation of a healthy ecosystem in the HTA.


Background
The significance of the health sector has been highlighted more than ever in recent years due to the increased threats of infectious and non-communicable diseases. In particular, with the onset of the COVID-19 pandemic in 2020, the area of health has turned into a priority for the world. The importance of this issue can be realized by considering the cost overrun of the healthcare and treatment area, as well as the per capita cost in this area. Data released on the costs of healthcare and treatment in various countries around the world indicate the rise of these costs more than the economic growth of countries. On the other hand, the increasing advancement of technologies in the world has led to the emergence of several technological solutions to solve healthcare-related problems. The industry and its major communication and information technologies have nowadays totally changed both the service sector and the world of production. This especially applies to the health sector where the Internet of things, cloud computing, and big data technologies have revolutionized the healthcare system and its entire ecosystem, leading it toward health care measures [1]. Technological solutions appear as an important stimulus in reducing the challenges of epidemics. However, the use of these solutions requires building trust and transparency for the effective management of health care requirements [2], which will be associated with a growing trend in the significance of technologies in the healthcare sector.
The importance of health technology assessment (HTA) will apparently increase in the future due to the multiplicity of technological choices and the breadth of usable technologies in the field of health and treatment. This implies that relying on HTA results allows achieving more efficient and effective solutions by generating knowledge and optimizing the decisions of policymakers and experts. However, making decisions, especially regarding the choice of expensive technologies, needs to be evidence-based given the scarcity of resources in the health sector [3]. This has led many countries to consider a mechanism for the rational introduction and the use of these technologies to, on one hand, control the costs, prevent their excessive rise, and optimally allocate these budgets, and on the other hand, to prevent the involvement of technologies with low safety and low effectiveness. HTA seems to be the most common tool to achieve this goal in many developed countries.
HTA is in fact a set of techniques designed to help decision-makers to incorporate technology in influencing the health of countries [4]. According to the definition by the World Health Organization (WHO) [5], HTA a systematic approach to evaluating the characteristics, effects, and impacts of technologies or policy interventions.
Reviewing the literature in this field, it can be concluded that the field of HTA has a very broad literature, indicating that it has considerably affected the generation of knowledge, dissemination, politics, behavior, or especially health promotion of countries [6,7]. Murphy et al., 1998 suggested that the goal of all HTA research should focus on the generation of knowledge and the creation of findings that would help policymakers and stakeholders. HTA research findings directly affect the decision-making institutions and indirectly help to improve the quality of clinical practice in the national health system [7].
HTA is used as a tool to improve evidence-based policy-making and decision-making in many studies [8]. According to a report by the WHO, a shortage of qualified human resources was the main obstacle in many countries to the implementation of the process and the use of HTA since most countries lacked an academic or training program to build the HTA implementation capacity [5].
Mathew [9] mentions that most HTA reports are limited to examining the efficiency, safety, and costeffectiveness of technology and some of them also address moral, legal, and social issues. However, HTA reports should also ideally cover other decisionmaking components. The integration of the desired technology into the current health system, the stability required to provide the health technology needed for all eligible individuals, the waiting time range for the technology to work or fail, the degree of novelty of the technology and new knowledge capacity influencing the decisions, and measuring the potential impact of rejecting this technology are generally some examples in this regard.
The HTA-based decisions can indeed pave the road only if there is already some kind of universal health coverage and the decision-makers are willing and able to use the HTA process by their health care systems. This is used as a model by many European countries, and some related institutions have been developed to guide the government in making decisions regarding the provision or non-provision of national health services accordingly.
Through a review of the literature in the field of HTA, this paper seeks to find out the issues and challenges faced by HTA studies in different countries. According to the methodology described in the second section of the article, a scoping review approach was used to explore and expand the evidence and map, and summarize the results of various articles published about different countries, which were extracted and analyzed from two databases and the reports of the WHO. The analysis results are provided in the third part (Results) of this article. Finally, the discussion and conclusion of the article will be presented in the fourth section.

Methodology
In this research, the scoping review approach is used based on the framework developed by Arksey and O'Malley, which outlines a rigorous way of transparency enabling replication of the search strategy and increasing the reliability of the study findings [10]..
A "scoping review" refers to a quick review of key concepts in a particular research topic, aiming at finding the main sources and different types of evidence concerning that topic. This review focuses on evidence and relies on summarizing and describing an existing or emerging field of research [11].
This research has conducted in 2021 and summarizes and maps HTA studies conducted in different countries from 2009 to 2020. This period of years was chosen since HTA studies conducted before 2009 were in preliminary stages in most countries without relying on data. Our aim was to find out about the issues and challenges faced by different countries in the study of HTA in this period of time. The scoping review method can help to find such evidence to answer the research question. However, these studies will enter a new paradigm with the emergence of new challenges, especially with the emergence of the COVID-19 pandemic at the beginning of 2020, and countries will encounter new and different issues in HTA. Thus, new evidence will definitely emerge in the HTA of countries in the coming years and far more new questions will arise in this area of study. Accordingly, one of the topics for future research could be that "How HTA studies will vary since 2020 with the advent of COVID-19 pandemic in comparison with previous courses?

Search strategy
The online Scopus and WoS databases were searched using the Boolean operators of keywords, i.e. "health" or "health assessment" or "assessment" and "technology" and "health" or "technology assessment". In the next stage, keywords of "European", "Asia", "Latin America", and "Africa" were added to the HTA and searched in each of the two databases. The main search strategy was "Health Technology Assessment", in addition to the names of countries that published HTA studies, which were used in the search field. The search was first set to the "Title" and "Keyword" fields. The results identified a large number of articles with often little relation to the research question. Thus, the search was set to the "Abstract" field in the next step and the output provided a more limited and relevant database. Finally, the texts of the articles were excluded and only 23 articles remained to answer the research question. The research flowchart was drawn based on the PRISMA flowchart (Fig. 1). Also the number of articles published in the field of health technology assessment during the last two decades is shown in Fig. 2.

Inclusion criteria for articles
The first step of the search retrieved 3349 articles, 1229 of which were excluded due to duplication. The titles and abstracts were the exclusion criteria of articles in the second stage. Accordingly, articles with irrelevant titles and abstracts were omitted from the review (two reviewers, review the articles and those in which both reviewers agreed to remove them were excluded). In the next stage, full texts of the articles were read to remove those that did not examine HTA in the countries. There were also articles among the reviewed studies that evaluated HTA in a very small part of a country, such as a disease in a clinic, or examined HTA in a ward of a hospital; thus, such irrelevant articles were also excluded due to incorrect generalization to the results. Since the HTA studies were generally reviewed in all parts of each country, only the texts of articles were selected that examined the general HTA in that country. Moreover, the texts of some articles were not available.

Data extraction
The criterion for data extraction from countries was determined by designing a checklist consisting of the name of the country, level of per capita income, year of study, subject and challenge of HTA, data collection method, and obtained findings. Classification of the countries based on per capita income levels helped to identify the issues and challenges in middle-and high-income countries in terms of HTA studies. The data collection method describes the methods for obtaining HTA information in different countries. Finally, the results were extracted from those drawn by countries for HTA. In the data  extraction table, a column is presented with the title of suggestions from each source for future trends in HTA. The latest report of the WHO concerning the HTA of high-and middle-income countries was also used in extracting the national data [5].

Findings
Over the past decades, health sectors in many countries have come to the need for introducing new methods of HTA and meeting the relevant demands. This important issue is also seen in the process of articles published in this area during the last two decades.
HTA is primarily performed and used in high-and middle-income countries since it requires a lot of resources. Hence, HTA cannot be used and made in many countries (including the African countries) due to low income levels and lack of the required resources. As a result, these countries do not own a health technology system and no data are found from them in the reports of the WHO. Accordingly, high-income countries have the most published documents in this area (Figs. 3 and 4).
According to the WHO report in 2015 [5], countries use HTA for various goals based on their income levels. In this regard, apart from the reports by the WHO, the issue of HTA has been addressed extensively in a variety of the reviewed studies from various perspectives and aspects around the world.
According to the articles reviewed in this study and the conclusion made from the reports by the WHO regarding countries, it can be argued that the major recommendations of most researches are that the HTA should follow clearer and more explicit methods and report the results containing certain standards. For example, our review study revealed that the results reported by the reviewed articles covered a range of topics, as shown in Table 1.
On the other hand, according to the reviews made in this study and as previously reflected in the reports of WHO, the focus on improving HTA processes is through higher participation of the stakeholders, increasing the transparency of processes, and optimizing the resource allocation in most high-income countries. In middle-income countries (Latin America), however, the focus is mostly on increasing the capacity building and standardization of methods/development of guidelines.
For example, Italy has set some processes aiming at managing legislations in the pharmaceutical industry, medical services and equipment, and service location, as well as controlling the providers of personal services and coverage-related policies. In Mexico, on the other hand, studies have focused on implementing strategies to update the table and catalog of essential supplies of the healthcare sector as a supervisory tool and to ensure the establishment of adequate and necessary criteria for safety, and effectiveness. At the same time, they seek the efficiency and development of a resource coding system, standardization of technology purchasing policies, and optimization of government resources. This, in turn, reveals the difference in priorities between developed and developing countries.
On the other hand, these studies present some recommendations to overcome the challenges faced by countries in implementing the HTA system, as summarized in Table 2.
The WHO categorizes the challenges of Asian countries in establishing an HTA system as follows [5]: The first challenge is that economic data are generally not available locally. The second and perhaps the most important challenge is that most health systems in Asian countries lack enough trained personnel to perform robust economic analyses. Although this shortcoming is fixed rapidly, there are still concerns about the impact of stakeholders on understanding, interpretation, and use of economic analyses, which can result in undesirable consequences. Thus, the third challenge would be the unfamiliarity of decision-makers with accurate differences in economic analyses, which will cause a delay in the use of appropriate health technologies.
To further explain these results, an example of our analysis is provided in Table 3. The classification of countries based on middle-and high-income ones is derived from the World Bank country classifications by income level [38]. 1 According to the table, most high-income countries are engaged in issues such as policy-making and optimal decision-making in HTA, integrating the involved institutions, and increasing the knowledge and skills in this area. In contrast, middle-income countries are generally involved in topics of raising awareness and learning from the experiences of developed countries, optimal resource allocation due to lack of resources, and establishing centralized and integrated institutions in this regard. These results are summarized in Table 4.
Despite varying health systems around the world, this study tried to provide a list of the most important challenges ahead of countries in the establishment of an HTA system, which can serve as a guiding checklist for policymakers and stakeholders in this field. Table 4 summaries the main findings of this research about the analysis of articles and reports on the HTA in different countries.

Conclusion
In this study, the HTA-related literature was comprehensively reviewed in the countries that published and analyzed the relevant reports. The documents published since 2009 in this area were collected and analyzed by referring to Scopus and WoS databases, as well as the Table 1 Various issues addressed in the HTA system review reports of the health area

Results and recommendations References
Paying attention to legislation aimed at the development of healthcare sector technologies [13] Recommendation for an active approach of countries instead of passive approaches [13] Trying to clarify the positive effects of assessing the healthcare area technologies aimed at attracting the support of policymakers and allocating resources [17,18] Investing and allocating more resources [20] Transparency of the budget allocation process [21,22] Management of local and national information and data and utilizing data analysis in decision-making and resource allocation [21,22,31] The clarity of governments' commitments [24] Continuous improvement of evaluation processes [30,34,35] Integration of assessment processes with other systems such as insurance [27,28,31,36] Paying attention to training courses to raise the awareness of the healthcare system experts concerning the concepts, tools, and processes of the assessment system [29] Trying to raise the awareness of the healthcare area stakeholders and encouraging them for participation [31] Defining the participation process of people and the public in the health technology assessment system [26] The technology assessment system supporting technological innovations in the healthcare sector      In the Asia-Pacific region, Australia was one of the first countries to implement official HTA programs followed by Singapore, Malaysia, and New Zealand. Other countries have also followed this program and HTA programs are currently available in China, Iran, Japan, Korea, the Philippines, Thailand, and Taiwan. HTA activities are also available in Pakistan and Indonesia, while evaluation research activities are done in India. Naturally, further efforts are required to launch HTA in countries with no such a program and to strengthen existing programs in other countries.

International reports Eight databases of articles and reports
Challenges that the health system should address in responsible health innovation.
For policy-makers: The justice and sustainability challenges of health systems need to be addressed preventively.
Health policymakers have to turn the system-level demand "signals" into opportunities to develop innovation. Innovation policymakers need to reward the technology-based entrepreneurial activities that closely overlap with the challenges of health systems.
International policy-oriented forums should share the lessons learned about innovation that better respond to the system-level challenges.
For the general public: People need to know about the challenges of justice and sustainability while helping the system by articulating needs and challenges.  (Table 1)indicate the common and specific challenges of the country for the integration of HTA in existing coverage, repayment, and pricing schemes. First, developing a clear, coherent, and standardized HTA framework that explicitly defines the goals, criteria, quality standards, and the best evaluation methods and guidelines seems to be highly important.

Challenges in China:
The use of HTA is fragmented and no HTA agency is currently operating nationally to supervise and coordinate all HTA activities. HTA research is scattered throughout government, academia, and industry-based centers.
The decision-making process still relies mostly on the experts' opinions and experiences rather than on evidence-based data. HTA should be fully and formally integrated into existing pricing and refund processes. Challenges of Japan: Some of the unique features of the Japanese pricing and refund system, such as the fixed cost program, will undoubtedly make the integration of HTA into existing methods challenging for the government and manufacturers. It seems that some sort of cooperation should occur between the government and drug manufacturers.
There is a need to increase internal capabilities and expertise. The key to HTA success in Japan will be the ability to produce evidence based on the national real-world data. Challenges in South Korea: The lack of specific guidelines, which initially lead to disputes between manufacturers and healthcare providers. The development of specialized staff with pharmaceutical economics expertise appears to be one of the major remaining challenges.  reports of the WHO. The literature reviewed in this research reflected that the search strategy was designated and implemented to identify various characteristics of the HTA in different countries. Although the included articles met the inclusion criteria to evaluate the HTA in countries in the scope of our study, our research does not reflect the experiences and evidence of HTA in different health sectors. The scoping review is used to map or configure a set of evidence; thus, our research was focused on studies indicating the "diversity" of evidence in the HTA of different countries with no in-depth concentration on the optimal choice and applicability of the HTA evidence in countries.
The role of the public and the government in the HTA of many countries seemed to be highlighted in reviewing the studies in countries, while the major role belonged to financing and budgeting. The countries in both groups encountered different challenges in HTA. In both groups, however, HTA was identified as an  Table 4 The summary and conclusion on the analysis of articles and reports on the HTA in different countries

Country income Main topics discussed in the HTA area
High-income countries -Governance regarding regulation -Further participation of stakeholders and increasing the transparency of processes -Moving toward political learning across the borders -The emergence and continuity of national agencies performance for HTA -Following an evolutionary model and the important role of texture factors -Making decisions on the allocation of more resources -Deciding on the prioritization of technologies -Efforts for further integration and coordination of the institutions involved in the HTA -The transparency of information and data used and creation of valid and evidence-based databases -Paying attention to judgment in decision-making -Policymakers' attention to the use of foreign knowledge and experts from other countries -Standardizing the processes of creating and using HTA -Optimal budgeting strategies -Improving the quality and reliability of the availability and efficiency of assessment methods -Increasing the stakeholders' participation in the HTA program -The demand-orientation of the HTA system -Seeking to use efficient methods for pricing -Developing programs to improve the level of knowledge and ability of individuals and institutions involved in the HTA -Paying attention to social and ethical issues in the HTA Middle-income countries -Creating official HTA programs -Increasing the awareness and training of the HTA area staff -Decision-making based on the experiences of experts rather than on evidence-based data -Determining the assessment standards and guidelines -Prioritizing the HTA to reduce financial risk -Decision-making and policy-making mostly by imitating developed countries -The lack of a centralized body for regulation and oversight -The islanding of the institutions involved in the HTA -Little knowledge of the low-level policymakers -Limited resources and low capacity to use evidence-based tools in the HTA -Political challenges and incoherent policies -New establishment of the HTA and presentation of health catalogs and tables -Institutionalizing HTA in institutions and individuals involved -Serious lack of budget and significant waste of resources -The transfer of HTA-related knowledge from developed countries -The challenge of decision-making on resource allocation essential tool to improve the management of scarce resources in the health sector. The dilemma of incoordination and segregation of participant institutions was found in the HTA process associated with resulting problems in decision-making in many of the reviewed reports and articles. It can probably be concluded that one of the useful efforts to be made by different countries to maintain the integrity of this system would be to involve all members of this system and form a health ecosystem in the HTA. As such, a large number of active actors (patients, doctors, nurses, companies and government agencies, suppliers, etc.) will develop their connections and communications with foreign actors to solve different challenges of this ecosystem.
Furthermore, the rapid growth of digital technologies (such as Big Data technologies) causes the health system of middle-income countries to face huge changes and transformations while makes the high-income countries move toward creating strategic innovation frameworks in the health ecosystem [39].
Abbreviations HTA: Health Technology Assessment; WHO: World Health Organization