Knowledge gaps and national research priorities for COVID-19 in Iran

Background In the present COVID-19 crisis, one of the greatest challenges for research funding at both the international and national level is selecting the best research topic to achieve efficiency and equity in health research and to address the knowledge gap urgently raised due to the event. Despite international recommendations, countries should consider their context-specific situation and define local research priorities. We aimed to exercise a priority-setting activity to identify the knowledge gaps and suggest research priorities in response to the COVID-19 epidemic in Iran. Methods First, we tried to identify the contextual knowledge gaps based on an online survey, performing key informant interviews (i.e. health professionals, policy-makers and managers) and media analysis. We also performed a literature review and considered international research priorities for COVID-19. Subsequently, we prepared a list of research questions and challenges to respond to the COVID-19 crisis in Iran using a systems approach. Then we mapped approved COVID-19 research projects in the country to research questions. Finally, we compared the identified research questions (not challenges) with the prioritized research from international organizations and then prioritized them for Iran. Results We found risk factors and epidemiological dissemination patterns of the virus and its consequences in an epidemiology domain, implementation of clinical and hygiene in a clinical management domain, genetic studies for targeting prevention and treatment in a candidate treatment and vaccine research and development (R&D) knowledge domain, examination of the manifestations of ethics in society instead of ethics in research in an ethics domain, “care, access and health system” and “public health and participation in response to public health and clinical research” as two sub-domains of a social sciences domain, and finally, no new questions in either the virology, transmission, diagnosis or animal and environmental domain. Conclusions In the event of global health crises like COVID-19, prioritization of research questions can be done globally, but some of the research priorities are context-specific and may vary by regional needs. To better manage research resources, researchers must respond to the challenges faced in each country based on its political, economic, social and cultural characteristics, and to make evidence-informed decisions, global knowledge gaps must be customized in each country. Supplementary Information The online version contains supplementary material available at 10.1186/s12961-021-00805-y.


Background
Health research funding organizations have always faced the question of what research to fund to maximize efficiency for themselves and their community. Therefore, in evaluating a research system, efficiency (compared with the costs, are the impacts of the research acceptable) and equity (is the research based on the needs of society) are typically considered in addition to effectiveness (whether the research has led to the desired impact) [1]. The COVID-19 virus epidemic has cornered research funding organizations in a new tight spot by creating an urgent need to answer new questions, along with a persistent lack of funding for research in some countries.
In the context of the COVID-19 epidemic, there is an urgent need for knowledge to understand the epidemiology of the disease, disease transmission and prevention strategies, vaccines, clinical characteristics of the patients, appropriate treatments and new technologies, socioeconomic factors of the patients, behavioural and psychosocial issues, and governance of the health system and making effective policies for the prevention and control of the disease at the regional, national and international levels [2].
Research system efficiency is related to reducing the waste of research resources, and equity is related to research prioritization. Research priority-setting exercises will help increase the efficiency of the research system [3] and improve the resilience of the health system in responding to the COVID-19 epidemic and similar crises in the future [4]. For these reasons, COVID-19 research priority-setting was considered at the international and national levels.
World experts on COVID-19 met at the WHO headquarters in Geneva in collaboration with the Global Research Collaboration for Infectious Disease Preparedness (GloPID-R) on 11-12 February 2020 to collect and assess the current knowledge about COVID-19 and reach a consensus on critical research questions that needed to be answered. This road map aimed at a proper diagnosis and optimum care for affected people, prevention of COVID-19, and supporting research priorities that would lead to the development of a global research platform. Eight immediate research actions, a crosscutting, interdisciplinary approach, and practical implications with international solidarity were suggested in this road map [2,5].
To apply these research priorities, each country should keep the following considerations in mind: • There are some knowledge needs that are relevant to all countries, and their response to them can be generalized and applicable for all countries.
• There are some knowledge needs for which the answers are different for different countries, and the countries themselves must find the answers to those needs. • There are some knowledge needs that are specific to each country and have not been identified by the international organizations' research prioritization.
Iran has 64 medical universities/schools with 20 966 academic staff and 755 health and biomedical research centres [6], with a growing need for and interest in COVID-19-related research worldwide. Iranian researchers and the scientific community became motivated to enhance their impact in combatting the COVID-19 epidemic. The Vice-Chancellor for Research and Technology at the Ministry of Health and Medical Education and the National Institute for Medical Research Development (NIMAD) in Iran decided to support research projects that would answer the national knowledge gaps and answer the research questions that are both novel and applied in a national and international context during the first 3 months of the epidemic. We then designed this study to identify the knowledge needs for which responses were required to address the COVID-19 epidemic in Iran, prevent such crises in the future, increase health system resilience in the face of future epidemics, and find the necessary considerations when we use international organizations' research priority-setting.

Methods
This study was conducted during the first 3 month of the COVID-19 epidemic in Iran (first wave) from 20 February 2020 until 20 May 2020 to identify the mentioned knowledge needs. We followed a two-step procedure to determine the contextual knowledge needs and define research priorities.

Stage 1: Extracting knowledge needs at the national level
Three different methods were used to identify the knowledge needs for controlling COVID-19; the details of each method are described below. The main approach to finding the context-specific knowledge gap was identifying challenges in the response to COVID-19 in the country. We believed that for addressing these challenges, we must investigate each barrier to respond to four groups of questions: (1) the magnitude of the challenge, (2) the root causes of the challenge in the system, (3) the mechanism by which the challenges affect the response to COVID-19 and (4) the solutions for resolving the challenge.

Method 1: Online survey
An online questionnaire was designed, and research subjects were collected from professional groups and researchers. This questionnaire link was posted on the websites of both the Research and Technology Department at the Deputy of Ministry of Health and Medical Education and the National Institute for Medical Research Development (NIMAD), its address link was announced through professional social media groups and news reporters, among others, and people were encouraged to complete it. In this questionnaire, the respondents were first asked, "What do you think about the most important challenges of controlling the current epidemic? Also, what research questions should be answered to control and manage the COVID-19 epidemic in the country and prevent similar events?" They were then asked to state their top five priorities. A total of 162 persons completed this survey, of which about 80% were directly involved in COVID-19 because of their job.

Method 2: Interview with the stakeholders
Semi-structured interviews were selectively conducted with policy-makers and senior managers, healthcare providers, health executive managers, faculty members and health researchers. Due to time constraints and problems in accessing individuals, we used convenient sampling to select the interviewees. We tried to recruit individuals from different provinces. The interview guide included two main questions: What were the challenges of managing and controlling the country's epidemic, and which research is needed to manage and control the country's epidemic?

Method 3: Media analysis
Analysis of news and social media groups was performed to identify challenges from the public perspective. The news agencies were purposefully selected from the two groups of government news agencies and independent news agencies. One government news agency and five independent news outlets were also chosen from the pages of individual and social virtual networks of activists in this field. The review time was between 4 February and 20 March 2020.
Media news was searched with the keywords COVID, corona, Wuhan China disease, and coronavirus, and related news was extracted. The news was then selected for further review that met the following criteria: For each news item, the date, headline, summary, name of the organization/reporter, link and source of the data were extracted and recorded.
Data analysis method To analyse the data obtained from these three methods, a manifest content analysis approach was used [7]. In media analysis, after extracting the news, all news summaries were analysed and coded by two independent researchers. One of them is a specialist in social media (MH), and the other one in health policy and management (EE). To avoid missing any data, all summarized data were included in the study. In these data (gathered from the abovementioned methods), two main categories were identified from the beginning; the first one was needed research questions, and the other was existing challenges, and each went through a separate path. All challenges which were expressed were related to the health policy and systems research (HPSR) field. Therefore, according to the two variables (questions or challenges) and research area, we developed a matrix in which we put research areas A and B in rows and research questions and challenges as variables in columns (Table 1). In this matrix, the cell representing the intersection of research area A and challenges remained blank. The research areas were defined as outlined below: Research area A: Research questions that were asked directly by individuals were added to the list of GloPID-R priorities [8]. This list was then quantitatively prioritized (stage 2).
Research area B: In this area, research questions and challenges were expressed independently by the participants. Independent means that participants articulated challenges and research questions without relating them, some referring to both and some referring to one. Research questions were added to the list of GloPID-R priorities. The challenges expressed by the participants were analysed and classified according to National Public Health Performance Standards [9]. Finally, HPSR and areas of ethics and social sciences from the GloPID-R classification in this area were addressed.

Stage 2: Prioritizing the knowledge topics
We used two steps to select and prioritize knowledge needs.

Step 1: Comparing the results of the first part with the ongoing projects in the country
At the time of this study, medical universities in Iran had started researching COVID-19. The titles of the approved projects in Iran during the period from 1 March 2020 to 20 April 20 2020 were extracted from the National Research Ethics Committee website (http:// nimad. ac. ir/ conte nt/ 200/ COVID-% DB% B1% DB% B9-Prior ities) and were then adapted to the proposed priorities by GloPID.
One of the team's researchers who is familiar with medical science (BY) made this adaptation. This adaptation was then reviewed and modified by two specialists in clinical and basic clinical sciences. The purpose of this step was to prevent rework and identify needs for which appropriate research is not being conducted. Then, the research team and representatives of NIMAD (as the most important stakeholder of the prioritizing list) eliminated several research questions. The exclusion criteria at this stage were two main variables: the mission of NIMAD (the research topic about vaccine was then excluded because it was funded by another funding agency) and the adequacy of ongoing research projects, mainly which caused the elimination of the research questions related to the identification of main and alternative therapies and the infeasibility of conducting those research projects in Iran. Finally, the prepared list was used in the quantitative section (step 2).

Step 2: Prioritizing research questions quantitatively
The list of research questions in areas A and B were included in this step. Then, in order to value the research questions, we used three indicators for the decision, including importance, feasibility according to the human resources and feasibility according to the physical resources.
The checklist of research questions was provided to the health system's executive and academic experts in the form of a questionnaire. These experts comprised the National Research Committee for COVID-19 and a few Ministry of Health Deputy of Research managers; 17 experts participated in this stage. The experts were asked to assign a score between 1 and 3 to the specified titles according to the definitions provided for each of the indicators, and by performing a simple average, their opinions were summarized in a matrix.
Finally, based on the experts' evaluation and the weights obtained from Shannon entropy method, the following research priorities were extracted through a multi-criteria decision-making model (MCDM). The methodological details of this part are presented in Additional file 1: Appendix S1.

Results
The results are presented according to the research questions and their prioritization (group A) and then the identified challenges for responding to the COVID-19 epidemic (group B).
The identified research questions are presented in Table 2 (starred questions). No new questions were identified in virology, transmission or diagnosis. No new questions were identified in the domain of animal and environmental research on the origin of the virus and management measures regarding the link between humans and animals.
In the epidemiology domain, the issue of disease outcome was added to the knowledge needs, although it overlapped significantly with disease susceptibility and severity. In the sensitivity section, a range of risk factors were specifically mentioned, in which illicit drug abuse and shisha (water pipe) smoking received special attention. In this domain, another knowledge gap was added as a sub-domain, which was titled the epidemiological dissemination pattern of the COVID-19 virus and its consequences in the country.
The domain of clinical management is more affected by the context and the access to facilities and equipment, and its knowledge needs were identified as contextspecific, such as the implementation of clinical practice guidelines, the quality and standards of diagnostic tests, the changes in the course of the disease in various service centres and the needed information to compile general and comprehensive clinical guidelines for high-risk groups.
In the infectious control domain, knowledge needs related to waste management in hospitals as well as the method of infection control at the level of the city, organizations and communities were identified.
Another point that was identified in this regard as to cultural conditions was the attention that was paid to following the hygienic guidelines for issues related to the deceased while considering the cultural issues.
In the domain of candidate treatment and vaccine R&D knowledge, an important knowledge need was suggested: "genetic studies of the population of patient profiles and using the collecting biobanks, which are applicable in targeting prevention and treatment". It was also suggested that an observational evaluation of the treatment methods used in the country and its changes      and consequences be examined using data science and machine learning approach.
In the domain of ethics, in the prioritization presented by GloPID-R, the main focus was on ethical considerations in COVID-19 research, while the subject proposed in this study was the examination of the manifestations of ethics in society, which is, of course, very context-specific.
In the social sciences domain, research questions were identified in the two sub-domains of "care, access and health system" and "public health and participation in response to public health and clinical research". All these recognized questions were new.
The results of prioritizing the identified research questions are presented in Table 2. As shown in the table, the first 12 priorities are the knowledge needs identified in this study, and all belong to the two fields of epidemiology (transmission dynamics) and social sciences.
All identified challenges in the field of social sciences were about HPSR. As shown in Table 3, multiple challenges were identified in all subareas of this framework. It is worth emphasizing that this study was completed during the first 4 months of the COVID-19 epidemic in Iran, and all these challenges might be time-dependent. Since that time, some challenges have been addressed, but research is needed to find the best intervention to reduce these challenges for similar future crises.

Discussion
The present study was designed to answer two main questions. First, to identify the knowledge needs to respond to the current COVID-19 epidemics and future crises. We also aimed to investigate how to adapt international organizations' research priorities in the COVID-19 setting in each country. These results were important in this situation because countries like Iran have limited resources for research, and it is important that these limited resources are allocated to fill the knowledge gaps and clarify the country research map during the COVID-19 epidemic.
According to the results of this study, the knowledge needs, in addition to what was identified in the GloPID-R's road map, are of two categories. The first group was knowledge needs that are not context-specific but its responses are context-specific (such as evaluating the implementation of standard international protocols). In addition to the two areas of "virology, transmission, diagnosis" and "animal and environmental research", knowledge needs were identified in other areas in which research is required in every country in order to produce the knowledge it needs.
This issue is fundamental in the social sciences and the sub-field of HPSR. Therefore, it is recommended that a suitable framework be added to the list of knowledge needs in international research priority-setting, but countries must certainly conduct specific research in order to find the answers.
We also found that one of the main priorities in any country is implementing protocols and interventions at the individual, organizational and societal levels. In fact, these types of action research and participatory research projects should be considered as priority by funding organizations.
The second group is the context-specific knowledge needs, such as examining the causes of differences in symptoms, disease severity and development of COVID-19 in different parts of the country or by social variables that determine health. Therefore, countries should pay special attention to identifying their specific knowledge needs according to the regions (provinces).
There are two studies which investigated the applicability of WHO/GloPID-R after a few months at the beginning of the COVID-19 pandemic, but both were found to place greater emphasis on social science and the temporal nature of research priorities [10,11]. Our study confirmed their conclusion by adding the need to have a special theme for HPSR.

Strengths and limitations
This research priority-setting was ordered by a funding agency, and this was the most important strength.
In the systematic review of research priority-setting in Iran, it was found that a lack of implementation plans for research priority-settings was a problem, but the results of this study were used by NIMAD to fund research [12]. One of the strengths of this study was the use of existing challenges in responding to the COVID-19 epidemic to identify context-specific knowledge needs, which was done for the first time in this study. Although the involvement of patients and the community in research priority-setting is routine, identifying the challenges in responding to a crisis in order to find knowledge needs is the dominant feature of this study. Dr Glison and her colleagues have clearly described why we need HPSR to respond to the existence of the COVID-19 epidemic and transform it into a resilient health system for future crises. They have explained the essential features of including a systematic approach that is multidisciplinary and context-specific. One approach to lead HPSR and meet this need is to start from "challenges" [13], challenges of countries in having the ideal response to the COVID-19 epidemic. The advantages of this approach are as follows: 1. When we use "challenges" to define HPSR priorities, we have chosen a context-specific approach. Some challenges are specific to the context and need context-specific solutions. For some challenges which are common among countries, their solution would be unique for each context. 2. To address the challenges in response to the COVID-19 epidemic, it is inevitable to produce an actionable message to solve challenges. In other words, we should clarify for policy-makers what should be done, by whom, where and when. It is necessary to conduct interdisciplinary and multidisciplinary research to produce an actionable message. Research with a narrow question cannot address the challenges alone. 3. When we consider "challenges'' as the starting point for identifying HPSR questions, we have chosen the system thinking approach. We have to think about the governance, financial and delivery structure of the health system, implementing current policy and programmes, and contextualizing solutions according to the health system and political system considerations in each country.
Four research questions have to be answered to solve each challenge: (1) What is the magnitude of the challenge? (2) What factors have created the challenge? (3) What is the mechanism of the impact of the challenge in responding to the epidemic? (4) How should the identified challenge be solved? Therefore, countries should design an active and up-to-date system to identify their challenges in determining the required research priorities and direct research funding in that direction.
Also, the use of the methodology of accountability for reasonability (A4R), which is used to ensure the legitimacy of decisions in health based on the five pillars of "relevance", "publicity", "revision and appeals", "empowerment" and "enforcement", was a strength of this study and could be suggested for future actions in this field [14].
One limitation in this study was the unavailability of policy-makers to do in-depth interviews. This limitation was expected; alternatively, it is suggested to participate in the policy-making meetings as a broker [4], but it was not possible in this study.

Conclusions
The COVID-19 pandemic has led to an increase in the demand for healthcare services in all countries. Due to a lack of knowledge and the urgency of the situation, several research questions were raised to increase the effectiveness and efficiency of public health programmes to  14. Weakness in the implementation of protocols such as disinfection of schools, public centres, prisons, rehabilitation centres, public health services, bakeries, banks, welfare centres, etc.