Conict-Related Population Health Research in Syria, 2011-2019: An Assessment of Information Gaps, Research Needs and Challenges, for The Lancet - AUB Commission on Syria

Backgorund. While there has been a growth of research on health and the Syrian conict, most such research covers Syrian refugees. There is limited information about the scope and focus of research on health and population inside Syria. While there are several systemtic and scoping literarure reviews of health of Syrian refugees, there has not been a sccoping review of research literature on health issues inside Syria. Methods. As part of a broader scoping review covering January 2011 to December 2019, we examined English-language conict-related research papers that studied health issues inside Syria and focused on Syrians or those permanently resident in Syria. We classied research articles based on the major thematic areas studied. We abstracted bibliometric information, study characteristics, funding statements and reported key limitations and challenges of conducting research. To gain additional insights or data, we examined separately publications reporting eld and operational activities as well as personal reections and narrative accounts of rst-hand experiences inside Syria. Results. Of papers identied in the scoping review, 708 (34%) exclusively focus on health issues of Syrians inside Syria, which 350 (49%) are conict-related with. Of conict-related publications, 89 (25%) are research papers. increased from in 2013 27 publications Damascus is most frequently studied governorate (n=33), followed by Aleppo (n=25). Papers used a wide range of research methodologies, primarily quantitative (n=68). The country of institutional aliation(s) of rst and last authors are Syria (n=30, 20 respectively), the United States (n=25, or the United Kingdom health status, health system and humanitarian assistance, response or needs (n=38, operational activities


Introduction
It is commonly said that the armed con ict in Syria is among the most extensively studied and documented contemporary con icts (Sigal 2016). There is an expanding volume of literature on a diverse range of health issues relating to the con ict, from attacks on healthcare and use of chemical weapons to refugee health status assessment. Research in and on active con ict zones is inherently di cult, and these challenges are re ected in the focus, nature and volume of research outputs produced while an armed con ict is ongoing. For example, while the challenges facing the health systems of countries hosting large numbers of Syrian refugees have been examined (El-Khatib, Scales et al. 2013, Mipatrini, Stefanelli et al. 2017), research assessments of the fragmented health system(s) inside war-torn Syria are limited. Similarly, compared with populations inside Syria, Syrian refugee populations are more accessible and therefore have received comparatively more research attention, including reviews and syntheses of this large volume of published research (El Arnaout, Rutherford et al. 2019). To the best of our knowledge, to date a review of con ict-related research on health inside Syria has not been conducted. Such a review is essential to understand what thematic issues, population subgroups and geographic areas have been examined, identify knowledge gaps, and inform the health research agenda.
In this paper, we aim to characterise con ict-related research published on health issues and populations inside Syria over the course of the con ict, in order to a) understand who is researching what, where, when and how; b) identify knowledge gaps and needs, including understudied population groups and geographic areas or issues that warrant further attention; and c) better understand the speci c challenges encountered by those who have published research on war-torn Syria, in order to consider strategies to mitigate the impacts of such challenges on future research.

Search strategy
This study is part of a broader scoping review of the health peer-reviewed literature published in Arabic, English, or French over the period spanning January 2011 to December 2019. Full methodological details are available elsewhere (Elzalabany et al, in progress). Brie y, we conducted a comprehensive scoping search of literature indexed in seven health databases (PubMed, Medline (OVID), CINAHL Complete, Global Health, EMBASE, Web of Science, Scopus), which identi ed a total of 2088 peer-reviewed papers focusing on human health and Syria or Syrians published during the speci ed period. For this analysis, we examined only English-language con ict-related research papers that studied health issues inside Syria and focused on Syrians or those permanently resident in Syria (e.g. Palestinian or Iraqi refugees in Syria). We de ned research papers as publications of any type (including traditional research papers, letters, commentaries and other) whose major focus is to report studies that involve the primary collection of data, or the secondary analysis and interpretation of existing data. Therefore, review publications and other literature evidence syntheses are not included in this research review. We also excluded clinical case studies and case series, con ict-related papers focused only on Syrians outside Syria (e.g. studies of Syrian refugees), and studies conducted in multiple settings where Syria was one of many countries examined (including studies examining populations both inside Syria and refugees). Field and operational activities publications, de ned as papers describing operational activities or organizational eld experiences inside Syria but not presenting research per se (e.g. papers describing set-up of a eld facility and number of patients seen, or describing humanitarian operations), which provide important insights or data about health inside Syria during the con ict, were considered separately to the research papers. Similarly, personal re ections and narrative accounts of rst-hand experiences inside Syria were considered separately. News reports and news interviews with personnel inside Syria were not included in this review.

Literature dataset analysis
We classi ed research articles into six categories based on the major thematic areas studied: mortality; population health status; health determinants and risks (including behavioural, physiological, environmental and social determinants of health); humanitarian assistance, response or needs (including any studies conducted by humanitarian agencies or analysis of services provided by humanitarian actors); healthcare system (including papers examining any of the six health system pillars as de ned by the World Health Organization (World Health Organization 2007), namely service delivery (unless delivered by humanitarian actors), health workforce, health information systems, pharmaceuticals and essential medicines, nancing, governance); and war strategies & alleged international humanitarian law (IHL) violations (including studies reporting on warfare, besiegement, and related human rights violations, attacks on civilian infrastructures such as health facilities, and publications on chemical attacks). A single paper could be classi ed into multiple thematic categories if it had a major focus on more than one theme.
For each paper, we abstracted bibliometric information and study characteristics (including country of a liation(s) of rst and last authors, aims, study period, methodology, governorates/ geographic location of the study, study population). We also extracted qualitative data on key limitations and challenges of conducting research as described by the authors, and categorized these as contextual, methodological or administrative. Where available, funding statements were also reviewed and assigned to one of three categories (funded, not funded, not reported). Classi cation of each paper was discussed by three reviewers.
We used basic descriptive statistics to summarise key bibliometric characteristics of the research papers and changes in the volume and focus of research over time. Key challenges encountered were summarized narratively.

Results
Of 2,088 papers identi ed in the scoping review, 708 (34%) exclusively focus on health issues of Syrians inside Syria, of which 350 (49%) are con ict-related. Of these 350 con ict-related publications, 89 (25%) are research papers and form the material of this analysis. We also identi ed 31 eld and operational activities papers focused on health inside Syria and eight personal narrative re ections, which we examine separately. Table 1 presents summary characteristics of the 89 con ict-related research papers. The con ict in Syria started in 2011 but there were no research papers published during 2011-2012. Thereafter the annual volume of research increased over time, from one publication in 2013, three in 2014, to 27 publications in each of 2018 and 2019. There is considerable variation in the governorates studied by thematic focus and over time ( Table 1, Fig. 1). Damascus is the most frequently studied governorate (n = 33), followed by Aleppo (n = 25), Idlib (n = 20), Lattakia (n = 15) and Hama (n = 14). Deir Al Zour (n = 3), Quenietra (n = 3) and Al-Sweida (n = 3) are the least frequently studied. Thirteen papers have a national scope. Several papers do not identify speci c governorates, instead referring to the controlling factions, describing for example opposition-controlled territories generally. There are no papers on health in areas while controlled by the so-called Islamic State (IS).
Papers have used a wide range of research methodologies, including primary quantitative methods (n = 40) such as surveys, questionnaires and clinical trials; secondary quantitative data analysis (n = 28) mainly using surveillance system, medical record or program data, and qualitative methodologies (n = 15). Six papers used mixed methods (Table 1).
For the majority of papers, the country of institutional a liation(s) of rst and last (assumed to be the senior) authors are Syria (n = 30, 20 respectively), the United States (n = 25, 19 respectively) or the United Kingdom (n = 12, 10 respectively). For 19 papers (21%), both rst and last authors had a Syrian a liation. Of the 37 papers reporting a speci c funding source, ve listed Syrian universities as the funding source. Table 2 presents detailed summaries of each research paper. Of these health status studies, a few also report on socioeconomic associations with disease burden (Albaroudi, Khodder et al. 2018

Research themes by governorate
Themes studied vary by governorate (Table 1, Fig. 1). In Damascus, health status is the most frequently studied theme (n = 14), followed by the healthcare system (n = 13). The healthcare system was also the main theme examined in studies of Aleppo (n = 12) and Idlib (n = 9). Humanitarian assistance, response or needs are most frequently studied in the north-west of Syria, including Aleppo (n = 7), Idlib (n = 6) and Lattakia (n = 6), and of the studies examining speci c governorates, all 14 governorates were covered in at least one paper. Of the papers examining war strategies and alleged IHL violations, the majority include a focus on Aleppo (n = 6) or Damascus (n = 5). On the national level, the healthcare system is the most frequently studied theme (n = 7), followed by health status (n = 5), war strategies and alleged IHL violations (n = 4) and mortality (n = 3).

Research themes by author country of a liation
Themes examined vary by country of a liation of authors (Table 1). Authors with Syrian a liations commonly publish on health status (n = 21 for rst authors, n = 14 for last authors), the healthcare system (n = 11 for rst authors, n = 5 for last authors), and health determinants and risks (n = 4 for rst authors, n = 3 for last authors), while the most frequently researched themes among US-a liated authors are the healthcare system (n = 11 for rst authors, n = 10 for last authors), humanitarian assistance, response or needs (n = 9 for rst authors, n = 5 for last authors), health status (n = 8 for rst authors, n = 3 for last authors) and war strategies and alleged IHL violations (n = 6 for rst authors, n = 8 for last authors).
Field and operational activities publications Table 3

Challenges reported in researching Syria
Researchers discuss a range of considerations and challenges of conducting research in and on Syria (Table 4). Contextual challenges are largely related to safety and security issues, including the impact of con ict on access to both geographic areas (access often being limited to speci c governorates or relatively safer areas) and study participants (including participant willingness to engage). Security considerations have impacted the ability to conduct research as planned.
Researchers report numerous methodological challenges, including limited data availability and access, data quality and completeness concerns, lack of population denominator data, and potential for bias at all stages of the research process.
Administrative considerations are largely related to securing permissions to conduct research and ethical review board processes, most notably the absence of such formal in-country governance structures.
Con ict also impacted other aspects of research administration, including the availability of research funding.

Discussion
Although it is commonly stated that Syria is among the most documented of recent wars, our analysis shows that a relatively limited number of research studies focused on health or populations inside Syria have been published over the nine years of the con ict. There are several geographic and thematic information gaps which likely re ect a myriad of factors, including issues of access and other challenges of conducting research during active con ict. There is a relative paucity of research on several key pillars of the healthcare system such as governance, nancing and essential medicines, and on a number of critical population health issues such as NCDs. Research coverage of governorates shows a heavy emphasis on Damascus and the north-west, with comparatively little research covering the north-east and the south of Syria. Our analysis does not identify any research on some speci c vulnerable populations such as the current or formerly imprisoned/detainees, and very few studies of besieged areas.

Some thematic areas have received limited research attention.
Health status is the most frequently researched theme, with communicable diseases the most common focus. Given the disruption of health and social infrastructures during con ict, with attendant impacts on communicable disease surveillance and control, and the broad biosecurity and global health threat posed by outbreaks of communicable diseases such as polio, it is not surprising that communicable disease epidemiology and control is a major focus of research attention. Similarly, mental health is the focus of addition to modelling estimates of disease burden and associated workforce requirements for the general population (Charlson, Lee et al. 2016). This is a crucial area of research in a con ict context and in a cultural setting where mental health issues remain stigmatized.
Other direct health effects of con ict receive comparatively little research attention. For example, injury epidemiology is covered in just ve papers, three of which described a cohort of inpatients with abdominal (Arafat, Alsabek et al. 2017), paediatric chest (Darwish, Mahfouz et al. 2018) or blast injuries (Okeeffe, Vernier et al. 2019). Understanding injury epidemiology is critical to informing health and social system needs, both to address immediate acute care needs but also to inform estimates of likely disability burden in future and requirements for health and social infrastructures and adaptive measures. This limited research focus may re ect data gaps, with lifesaving provision of care clearly a priority above record-keeping in acute emergencies and mass casualty events. The referral of many wounded individuals for treatment in neighboring countries may also partly explain this gap, supported by an observation from our broader scoping review that there is more injury research from Turkey, Israel and Jordan than there is from within Syria. Additionally, for injury epidemiology as well as other thematic areas, data access and data sharing arrangements may be an issue, with much service provision information, however (in)complete, held by humanitarian agencies and government bodies. Sharing of information with researchers for secondary data analysis is often a fraught process. This information divide and limited collaboration between researchers and operational organisations must be bridged, to minimize duplication of effort and ensure best outcomes for the populations who are the ultimate bene ciaries of all this work. Further, even when data are available to researchers, institutional processes, research governance mechanisms and data access arrangements may mean that data cannot actually be used and published in a timely manner.
NCDs represent another major research gap despite being identi ed as such in 2015 and a call for action issued . Prior to the onset of the con ict, Syria was in the midst of a demographic and epidemiological transition, with NCDs dominating disease burden and health expenditure (Taleb, Bahelah et al. 2015). Left unaddressed and due to disruptions to the health system, preventive measures and altered health behaviours, this underlying disease burden is likely to have magni ed, and indeed studies among Syrian refugees indicate a high NCD burden (Rehr, Shoaib et al. 2018). It is likely that a similar high burden exists among populations inside Syria. This warrants urgent research attention.
For a protracted con ict that has caused a large number of deaths, surprisingly few research studies have examined mortality. Notably, most of the mortality research considers direct war-related deaths. Few studies report on general mortality or examine indirect con ict-related deaths, such as those due to treatment forgone and service unavailability, for instance cancer deaths due to lack of access to chemotherapy or end-stage renal failure deaths due to lack of dialysis services (one paper provides an anecdotal estimate of renal deaths for one centre (Sekkarie, Zanabli et al. 2015)). Such information is essential at the facility, governorate and national levels, both to inform immediate needs and to drive accountability -the effects of war, and the impacts of atrocities such as killing a doctor or attacking a hospital, extend far beyond the immediate acute losses.
Accurately estimating mortality in con ict presents numerous challenges (Price, Gohdes et al. 2015) and several factors may explain the relative paucity of mortality research in Syria. Some data collections such as VDC are reliant on ground reporters, and relative inaccessibility of some geographic areas in uences data collection and completeness. While multiple organizations are reportedly tracking con ict-related deaths, there is a gross disconnect between data collected by and available to humanitarian and human rights organizations and that available to researchers. National researchers based inside Syria may nd it di cult to investigate this sensitive issue. Insecurities may render conducting household assessment on representative samples di cult, or generate security threats to families, witnesses or data collectors. In sources. With standardized methodologies to monitor and report the attacks on healthcare lacking, and as reporting commonly depends on ground reporting systems which are subject to their own inherent limitations, sustaining monitoring systems is challenging (Elamein, Bower et al. 2017, Wong and. Notably, to date the population health impact of such attacks in Syria has not been well described or quanti ed.
The limited research on key health system pillars, namely governance, nancing and essential medicines, is also of concern, particularly as governance and nancing are critical to any consideration and planning for health system rebuilding.
There is geographic variation in research volume and thematic issues examined.
Focus of research covering areas such as Damascus, a Syrian government stronghold, is heavily on population health status and the healthcare system, while research on northwest Syria (Aleppo and Idlib) focused more on the healthcare system, particularly attacks on healthcare and other IHL violations, and humanitarian needs and assistance. This likely re ects con ict events and response to evolving issues and operational needs on the ground, in addition to issues of access. International agencies and humanitarian organizations based in Turkey have access to the opposition-controlled areas of north/northwest Syria, directly or through Syrian/diasporic health and humanitarian organizations, Novel methodologies have been applied to study health in an active con ict zone.
Numerous challenges are reported in the conduct of this body of research, largely consistent with those described by researchers who have worked in and studied a range of other active con ict zones. These include issues of access, data quality, quantity and availability (including lack of denominator data due to ongoing population displacement), and security considerations, including impacts on participant willingness to engage. A number of novel tools and methodologies were developed and described in this literature in order to overcome research constraints and to study con ict-related health issues. Such barriers to local research production must be addressed. Utilization of various techniques, e.g. use of pseudonyms to address security concerns, and implementation of contextually appropriate capacity building initiatives and frameworks, such as that proposed by others (El Achi, Papamichail et al. 2019), to support more Syrian researchers and Syrian institutions to lead research on the health issues affecting their country and its people, is warranted.

Strengths and limitations
To the best of our knowledge, this is the rst review to characterize the body of published peer-reviewed research examining health inside Syria over the course of the con ict. Themes assigned re ect the major focus of each paper and do not necessarily capture all issues covered. Relevant studies may have been excluded, or missed if published in journals not indexed in the seven health bibliographic databases searched. For example, Arabic language papers published in local or regional journals are not captured in this review. Furthermore, much operational research is published in non-peer reviewed platforms and organizational reports, so the ndings of this review likely to do not fully capture all operational and eld research undertaken by humanitarian organisations.

Conclusions
Whilst there is a growing body of research examining population health issues inside con ict-ravaged Syria, there are considerable geographic and thematic gaps, and issues and populations that warrant focused research attention. Recognising the myriad of complexities of researching active con ict zones, including issues of data completeness, coverage and politicisation, it is essential that research in and on Syria continues, in order to build the evidence base and inform policy and programmatic actions that are required to protect and promote health in Syria following nearly a decade of con ict.

Declarations ETHICS APPROVAL AND CONSENT TO PARTICIPATE
Not applicable as this is a literature review.

CONSENT FOR PUBLICATION
Not applicable as this is a literature review.

AVAILABILITY OF DATA AND MATERIAL
Research data and material are available for peer review.   Supplementary Files This is a list of supplementary les associated with this preprint. Click to download. AbouzeidElzalabanyCRRSyriaTablessubmitted.docx