Global and regional estimates of clinical and economic burden of low back pain in high-income countries: a systematic review and meta-analysis

Introduction Low back pain (LBP) is a common health problem, and the leading cause of activity limitation and work absence among people of all ages and socioeconomic strata. This study aimed to analyse the clinical and economic burden of LBP in high income countries (HICs) via systematic review and meta-analysis. Methods A literature search was carried out on PubMed, Medline, CINAHL, PsycINFO, AMED, and Scopus databases was from inception to March 15th, 2023. Studies that assessed the clinical and economic burden of LBP in HICs and published in English language were reviewed. The methodological quality of the included studies was assessed using the Newcastle-Ottawa quality assessment scale (NOS) for cohort studies. Two reviewers, using a predefined data extraction form, independently extracted data. Meta-analyses were conducted for clinical and economic outcomes. Results The search identified 4,081 potentially relevant articles. Twenty-one studies that met the eligibility criteria were included and reviewed in this systematic review and meta-analysis. The included studies were from the regions of America (n = 5); Europe (n = 12), and the Western Pacific (n = 4). The average annual direct and indirect costs estimate per population for LBP ranged from € 2.3 billion to € 2.6 billion; and € 0.24 billion to $8.15 billion, respectively. In the random effects meta-analysis, the pooled annual rate of hospitalization for LBP was 3.2% (95% confidence interval 0.6%–5.7%). The pooled direct costs and total costs of LBP per patients were USD 9,231 (95% confidence interval −7,126.71–25,588.9) and USD 10,143.1 (95% confidence interval 6,083.59–14,202.6), respectively. Discussion Low back pain led to high clinical and economic burden in HICs that varied significantly across the geographical contexts. The results of our analysis can be used by clinicians, and policymakers to better allocate resources for prevention and management strategies for LBP to improve health outcomes and reduce the substantial burden associated with the condition. Systematic review registration https://www.crd.york.ac.uk/prospero/#recordDetails?, PROSPERO [CRD42020196335].

Introduction: Low back pain (LBP) is a common health problem, and the leading cause of activity limitation and work absence among people of all ages and socioeconomic strata. This study aimed to analyse the clinical and economic burden of LBP in high income countries (HICs) via systematic review and meta-analysis.
Methods: A literature search was carried out on PubMed, Medline, CINAHL, PsycINFO, AMED, and Scopus databases was from inception to March th, . Studies that assessed the clinical and economic burden of LBP in HICs and published in English language were reviewed. The methodological quality of the included studies was assessed using the Newcastle-Ottawa quality assessment scale (NOS) for cohort studies. Two reviewers, using a predefined data extraction form, independently extracted data. Meta-analyses were conducted for clinical and economic outcomes.
Results: The search identified , potentially relevant articles. Twenty-one studies that met the eligibility criteria were included and reviewed in this systematic review and meta-analysis. The included studies were from the regions of America (n = ); Europe (n = ), and the Western Pacific (n = ). The average annual direct and indirect costs estimate per population for LBP ranged from e . billion to e . billion; and e . billion to $ . billion, respectively. In the random e ects meta-analysis, the pooled annual rate of hospitalization for LBP was . % ( % confidence interval . %-. %). The pooled direct costs and total costs of LBP per patients were USD , ( % confidence interval − , . -, . ) and USD , . ( % confidence interval , . -, . ), respectively.
Discussion: Low back pain led to high clinical and economic burden in HICs that varied significantly across the geographical contexts. The results of our analysis can be used by clinicians, and policymakers to better allocate resources for prevention and management strategies for LBP to improve health outcomes and reduce the substantial burden associated with the condition.

Introduction
Low back pain (LBP) is a common health problem in people of all ages and socioeconomic strata (1). LBP occurs in highincome, middle, and low-income countries. It is the leading cause of activity limitation and work absence (2). Estimates of the 1-year incidence of a first-ever episode of LBP range between 6.3 and 15.4%, while estimates of the 1-year incidence of any episode of LBP range between 1.5 and 36% (3). The global point prevalence of LBP was 9.4% (95% CI 9.0-9.8), while the disability-adjusted life years (DALYs) due to the condition increased from 58.2 million in 1990 to 83.0 million in 2010 (4). LBP is one of the primary reasons that patients visit primary care physicians (5) and it represents the highest percentage of referrals and workload for physical therapy utilization (6,7). For example, in the United States, LBP accounts for 2.5-3% of all physician visits (8). Furthermore, LBP is a major cause of hospitalization, for example, during 1990-2002 period a total of 7,240 LBP hospitalizations were identified among 5,061 (1.3%) Finnish military conscripts (9).
LBP constitutes a significant economic burden on the individual, caregivers and society (10,11). The economic impact of LBP can be assessed from a number of different perspectives, including that of the patient, hospital, healthcare providers, thirdparty payer, government agency, and society (12). Regardless of who incurs the costs or who receives the benefits, societal perspective that incorporates direct and indirect costs (13). In context, direct costs are defined as costs for goods and services used in the diagnosis and treatment, and prevention of the problem in question (13). Further, rehabilitation and other medical consequences of LBP and all the private costs incurred by the patient and family are also included in direct costs. On the other hand, indirect costs include the value of the output that is lost because people are impaired from working, typical cost items in this category are costs for early retirement pensions caused by disability, short term absence from work, and premature death (14). The direct and indirect costs associated with LBP are among the highest for chronic health conditions mainly in terms of the significant number of workdays lost (10). In 2006, a review of total costs associated with LBP in the United States showed that it exceeds $100 billion per year (15). Among studies providing estimates of direct costs, the largest proportion of direct medical costs for LBP was spent on physical therapy (17%) and inpatient services (17%) (16). Overall, the clinical and economic burden of LBP are substantial when its prevention and management of LBP are suboptimal (16).
Many studies have investigated the clinical and economic burden of LBP in HICs (3,10,16,17). The biggest challenge for aggregating the clinical and economic burden data is due to the studies adoption of different methodological designs. The sources of this methodological difference could be the size of the underlying populations, the treatments applied, differences in health care systems regarding access to health care, and the prices of the treatments (18). This is the first systematic review that that assessed the clinical and economic burden of LBP in HICs via meta-analysis.

Search protocol and registration
In this study, we used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline (19). A protocol for this systematic review was prospectively registered on PROSPERO and can be found at https://www.crd.york.ac.uk/ prospero/#recordDetails? ID = CRD42020196335.

Search strategy
A literature search using PubMed, Medline, CINAHL, PsycINFO, AMED, and Scopus databases with studies published from inception to March 15th, 2023. The following keywords were used in the search: Low back pain, hospitalization, cost of illness, absenteeism, ambulatory care, drug costs, emergency medical services, healthcare costs, nursing services, economics, physicians visit, clinical impact, utilization, burden of illness, cost, nursing cost (Appendix 1). These search terms were combined using conjunctions words "AND" or "OR". Further, a manual search of reference sections of the included studies was also checked for additional studies. The search was performed one author (TG) and cross checked by another author (FF) to reduce the presence of bias in the selection and exclusion of studies.

Inclusion and exclusion criteria
This review involved original research conducted among patients with LBP in HICs that reported findings related to costs (direct and indirect). The World Bank's definition of high come country was adopted. Eligible studies included observational (cross-sectional or surveys), randomized controlled trials (RCTs) and modeling analyses of patients with LBP in hospitals, primary healthcare clinics and home care contexts that were published in peer-reviewed journals. Language filter was applied to delimit the search to studies published in English language only. Review articles, editorials, letters to the editor, news reports, conference abstracts, comments, as well as the results of dissertations were excluded in this review.

Study selection and assessment of methodological quality
After selection of the articles in each database, duplicate articles were removed electronically: https://access.clarivate.com/login? app=endnote and manually. Following the removal of duplicates, titles and abstracts were screened independently by two reviewers (FF & TG) to identify eligible studies. The full texts of the identified studies were checked against the inclusion and exclusion criteria. When there was disagreement, it was addressed through consultation with the third reviewer (CM). Having retrieved the full  text of studies that met the inclusion criteria, they were assessed for methodological quality using the Newcastle-Ottawa quality assessment scale (NOS) for cohort studies (20). The NOS contains nine items, categorized into three dimensions including selection and comparability. Studies were scored using a scale with a possible maximum of nine points where a score ≥ 6 indicated high-quality studies, a score between 3 and 6 as moderate and a score ≤ 3 as low quality (20).

Data extraction
Data were extracted by two independent review authors (TG & FF). The following information was extracted for each study: authors, country and year of publication, study objective, data source, inclusion criteria, LBP definition, population characteristics (size, % male, and mean age), hospitalization, emergency department visit, physician visits, average total annual cost per patient and annual population cost. The cost per population indicates the annual costs estimate of the disease in a specific country. A summary table was used to display the extracted data.

Data synthesis
A weighting procedure regarding the clinical and economic burden of LBP of the included studies was applied only when combining data from multiple studies was satisfied. Meta-analyses were undertaken using Comprehensive Meta-analysis software (Biostat, Inc., New Jersey, USA) version 3 for Windows, to determine the pooled clinical and economic burden of LBP in HICs. The random-effects method was used to provide more confident data considering the heterogeneity within and between reports.
All costs were converted from local currencies to United States Dollar using purchasing power parities (21). We adjusted the cost data to the reference year of March 2022 using consumer price index from the World Bank Website (22). This methodology is useful for cost of illness studies to reach better comparability between the different currencies (23).

Included studies
The literature search identified 4,801 potentially relevant articles in PubMed (n = 2,636), Scopus (n = 115) and Medline (n  The UK General Practice Research Database.
To assess 12-month health care costs associated with the treatment of CLBP.  We included workers who were registered in the database with LBP associated sick leave episode.

The National Ambulatory Medical Care Survey
To characterize the frequency of office visits for LBP/the contempt of ambulatory care, and how these vary by physician specialty.
It included nearly 3,000 office-based physician respondents not employed by the federal government in the 1990 survey.     (Figure 1). Of these, 643 were duplicates. After screening the titles and abstracts 4,015 publications were excluded, leaving 143 articles for further full text review. Twenty-one studies met the inclusion criteria and were included in the review. The majority of studies included in this systematic review were of moderate to high quality based on the NOS score (Appendix 2). A further updated search yield two new articles that met the inclusion criteria (out of 1,230 identified potentially relevant articles).

Characteristics of the included studies
Characteristics of the included studies are summarized and presented in Table 1. Of the 21 articles included, eight reported the clinical burden of LBP (8,9,28,35,(38)(39)(40). Whereas, the remaining 13 studies reported the costs of LBP (11, 17, 24-26, 29-34, 36, 37). The included studies were conducted in United States, Spain, Switzerland, France, Finland, Japan, Netherland, Germany, United Kingdom, Sweden, and Australia (Table 1). According to the World Health Organization (WHO) classifications the included studies were from the regions of America (n = 5); Europe (n = 12) and the Western Pacific (n = 4). Table 2 provides an overview of hospitalization rates, physician visits and ambulatory visits. Of the six articles meeting the inclusion criteria, six contained hospitalization data (9,28,35,(39)(40)(41) and

Clinical burden
.

Patient-level costs
Six studies reported patient-level direct and indirect costs for LBP ( Table 3). The average direct cost estimate of LBP during 6 months were USD 959.43 (26) and USD 1,236.99 (31) in France and Germany, respectively. Average annual direct cost estimates in the general population ranged from USD 4,671.13 (9) to USD 10,430.20 (17) per LBP patient. Annual indirect costs, mainly productivity loss because of lost workdays of USD 26,579.57 per patient were reported for LBP in Sweden (33).

Population-level costs
Seven studies reported population level direct and indirect costs of LBP (Table 4). The average annual direct costs estimate per population for LBP ranged from USD 3.4 billion (29)

Discussion
This is the first systematic review and meta-analysis to assess the clinical and economic burden of LBP in HICs. The findings of the included studies varied substantially across the studies and countries. Our findings suggest that LBP is associated with a prolonged hospital length of stay, physician visit and ambulatory care. The meta-analysis, which derives from many patients, found that the rate of hospitalization, direct costs and total costs were 3.2% (95% CI 0.6-5.7%), USD 9,231 (95% CI −7,126.71-25,588.9) and USD 10,143.1 (95% CI 6,083.59-14,202.6), respectively.
The finding of the current study is in line with other studies (10,16,17) that assessed the economic impact of LBP. In those studies that reported the total costs, the indirect costs associated with LBP were higher than direct costs. Indirect costs in Spain, for example, represented 74.5% of the total costs of LBP (24). According to Alonso-García and Sarría-Santamera (24) the contributing factor to the high indirect costs of LBP was absenteeism and presenteeism. On the other hand, a cost-of-illness study in Australia reported that the costs of LBP in public hospitals was higher than in private hospitals (36). The high costs of LBP in public hospitals in Australia .

FIGURE
The pooled mean of annual rate of hospitalization of LBP.
may be due to the universal health system, it provides medical, and hospitals cares for persons incapacitated with illness or injury including low back pain.
A total of six studies were included in this systematic review that reported the clinical burden of LBP in HICs. The reviewed literature suggested that the substantial clinical burden was reflected by high annual rate of hospitalisations, physician visits and ambulatory visits. In Finland, 1.3% annual rate of hospitalization was reported for LBP among military conscripts, this is much higher compared to the one reported in 1996 among 25-to 64year-olds (9, 28). The annual rate of hospitalization for LBP in the current review are lower than other types of health conditions such as asthma where the overall rate of asthma hospitalization was 42 per 1,000 (41).
The key findings of this study confirm that LBP is associated with high clinical and economic burden in HICs. The review also revealed that the findings of the included studies varied significantly in terms of geographical location. The contributing factors to the differences of clinical and economic burden of LBP across the geographic areas could be the health system, health financing system, and sociodemographic characteristics of the people. The results of our analysis can be used by clinicians, and policymakers to better allocate resources for prevention and management strategies for LBP to improve health outcomes and reduce the substantial burden associated with the condition. We also hope our results will be of use to researchers planning to evaluate the cost-effectiveness of various strategies for preventing LBP in HICs.
There are a number of strengths and limitations of this study that need to be considered. The main strength of this review is the comprehensiveness of the search terms, screening of numerous data bases, and assessment of methodological quality of the studies. Only studies published in English language were included. Therefore, it is possible that relevant studies published in other languages may have been excluded. We did not use back pain as a search term, this is because "low back pain" is the key term used primarily in the literature and major international studies such as the global burden of disease study. Further, reported clinical and economic burden of LBP in HICs are limited by a large heterogeneity of available data. In spite of these limitations, we believe that this review was systematic in nature and summarizes all available and relevant clinical and economic burden results from the literature.

Conclusion
LBP leads to high clinical and economic burden in HICs that varies significantly across the geographical contexts. We also found that LBP is a common hospital-associated problem with a clear impact on length of stay and hospital costs. Knowledge of the clinical and economic impact of LBP in HICs is useful to influence programs and behavior in healthcare facilities, to guide policy makers and funding agencies to improve the health outcomes of individuals with the condition and reduce its huge economic burden.

Data availability statement
The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.
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