|Ahead of print
The economic burden of esophageal cancer in Iran
Rajabali Daroudi1, Azin Nahvijou2, Mohammad Arab1, Ahmad Faramarzi3, Bita Kalaghchi4, Ali Akbari Sari1
1 Department of Health Management and Economics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
2 Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
3 Department of Health Management and Economics, School of Public Health, Urmia University of Medical Sciences, Urmia, Iran
4 Department of Radiation Oncology, Radiation Oncology Research Center, Tehran, Iran
|Date of Submission||27-Nov-2019|
|Date of Decision||03-Dec-2019|
|Date of Acceptance||25-May-2020|
|Date of Web Publication||11-May-2021|
Department of Health Management and Economics, School of Public Health, Urmia University of Medical Sciences, Urmia
Source of Support: None, Conflict of Interest: None
Background: Studies on economic burden demonstrate the impacts of some diseases and provide invaluable information for specifying priorities and resource needs when designing cancer control strategies. The current study aimed to estimate the cost of esophageal carcinoma (EC) in Iran in 2018.
Methods: This study was conducted on the prevalence approach to estimate the economic burden of EC in Iran from a social perspective. The direct cost was estimated by summing the diagnosis, treatment, follow-up, terminal care, and transport costs. Additionally, a human capital approach was adopted to estimate productivity losses. Various resources were used for data collection, including the GLOBOCAN 2018 report, and the medical record in the Cancer Institute of Iran. Also, data such as exchange rates, employment, and housekeeping rates were extracted from the Central Bank of Iran Statistics.
Results: The economic burden of EC in Iran was $69.2 million in 2018, of which $38.7 million is caused by indirect costs and $30.5 million by direct costs. The mortality cost accounted for 49% of the economic burden, followed by 34% direct medical cost, 10% direct non-medical cost, and 7% morbidity cost.
Conclusions: Mortality and medical cost appeared to be the main contributor to the economic burden. Therefore, policy-makers are recommended to adopt early detection and effective treatment as a highly cost-effective strategy for controlling costs.
Keywords: Economic burden, esophageal carcinoma, Iran
More than half of esophageal cancer costs could be controlled by early detection and treatment. Gender is a significant predictor for the economic burden of esophageal cancer.
| » Introduction|| |
Esophageal carcinoma (EC) is the seventh most common cancer type in the world. This cancer shares 3.2% of all cancer cases. In 2018, approximately 572,000 new EC cases were diagnosed, and nearly 509,000 people died due to this cancer. The incidence of esophageal cancer is different across the world. The highest incidence rate has been reported in sub-Saharan Africa, China, India, and Iran. In 2008, there were 571,000 new cancer cases in Africa, including 6.2% of esophageal cancer. According to studies in Iran, the number of people suffering from esophageal cancer was 1,263 cases in 2001, while it had risen to 3,071 cases in 2010 and 4,372 cases in 2018. The EC incidence rate was 2.53, 4.3, and 5.3 per 100,000 population in 2001, 2010, and 2018, respectively., The survival rate is very low in EC, regardless of the high incidence rate. In developing countries, the survival rate for a person who has this cancer has stayed very low; for instance, studies have shown that the 5-year survival rate is 10% in Iran.
Policymakers in all countries need to know the impacts created by each health problem in society. Studies on economic burden illustrate the impacts of some diseases, provide invaluable information for specifying priorities and resource needs when designing cancer control strategies and programs, and inform decision-makers about medical research priorities. In other words, a comprehensive economic burden study provides estimates of direct (e.g., medical cost) and indirect costs (e.g., lost productivity) for the special disease.,
EC imposes a considerable economic burden on societies because of its high mortality. A limited number of studies have been conducted on the economic burden of EC worldwide. For example, Guo et al. estimated the medical expenditure of EC in China. They reported the treating costs of EC to be increased by 6.27% every year from 2002 to 2011. There is no published study that has estimated the full economic burden of EC in Iran. Nevertheless, there have been limited studies that have estimated some of the costs for EC. For instance, Khorasani et al. calculated that the productivity costs due to premature mortality of EC in Iran which was US$ 92.5 million for men and US$ 51.2 million for women. Another study in Iran reported that the mortality cost for EC patients was US$ 8.8 million for men and US$ 1.9 million for women.
Although the economic burden studies play an important role in decision-making and in identifying ways of controlling cost, no study in Iran has estimated the economic burden of esophageal cancer. Therefore, the present study aimed to estimate all costs associated with EC in Iran in 2018.
| » Subject and Methods|| |
The ethics committee of Tehran University of Medical Sciences approved this study. The current study estimated all costs (direct and indirect cost) associated with EC in Iran in 2018. For this purpose, estimations were extracted at the patient and national-level. The estimation at the patient-level was used to calculate the unit cost. Sixty-eight patients with EC were included in this study. Patients were enrolled in the study if they met the following criteria: (1) diagnosed with squamous cell carcinoma (SCC) in 2018; (2) were at least 18 years old at the time of diagnosis; (3) were admitted at the Cancer Institute of Iran for the first time; and (4) did not have other cancers. We applied a prevalence approach to estimate the economic burden at the national-level. This study was done from a social perspective by collecting data from various resources. The epidemiological data (i.e., mortality, incidence, and prevalence rate) were collected from the GLOBOCAN 2018 report. The data needed for estimating the medical costs were obtained from the medical record in the Cancer Institute of Iran. The data such as exchange rates, employment, and housekeeping rates were extracted from the Central Bank of Iran Statistics.
This study was designed in three steps. First, the epidemiological aspects of EC in Iran were considered. Using the GLOBOCAN 2018 data and the survival rate of esophageal cancer, the incidence rate was estimated from 2014 to 2018, and then the prevalence rate was calculated for 2018. The estimated prevalence number of EC in 2018 was determined by the year of infection, from 2014 to 2018. The number of estimated prevalence in 2018 was specified based on morbidity years. For this reason, the incidence number of every year was multiplied by the survival rate that year. This division was done to estimate the follow-up cost in patients who have become ill before 2018. The patients were sampled based on their disease stage and their age. Second, the pathological aspects and treatment patterns on EC in Iran were considered. Patients' distribution was determined based on the treatment methods, using different sources such as guidelines, medical records, and expert opinion. Third, the costs were estimated. The economic burden of EC is considered in two main categories [Table 1] includes direct and indirect costs. All costs were converted to 2018 USD using a 3% discount rate.
|Table 1: The component of the economic burden, sources of estimation and patient number for esophageal cancer in Iran, 2018|
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In this study, the direct cost of EC was determined at two main categories: direct medical cost and direct non-medical cost. To calculate the direct medical cost, we divided the costs into diagnosis, treatment, follow-up and terminal care. Then,the unit cost was determined. For this purpose, the unit costs of diagnostic tests and follow-up care were extracted based on the 2018 approved tariffs. The unit cost for treatment modalities was computed based on the mean. To this end, the medical records of 68 EC patients admitted in 2018 at the Cancer Institute of Iran were assessed. These patients were 5% in stage I, 79% in stage II and III, and 16% in the IV stage. Depending on the type of treatment and the disease stages, the mean cost was estimated for each treatment.
To calculate the diagnosis cost, the diagnostic tests were performed based on expert opinion. These tests include endoscopy, biopsies, endoscopic ultrasound, complete blood count (CBC), blood urea nitrogen (BUN), creatinine, serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphates, fasting blood sugar (FBS), and computed tomography (CT) scan. Then, the number of tests was multiplied by their price.
The treatment cost was estimated based on the patient distribution stage and treatment method, using medical records. The surgery and endoscopic mucosal resection (EMR) were performed in the early stage. The surgery, chemoradiotherapy (CRT) followed by surgery, or chemoradiotherapy alone were used in the middle and applied palliative care in the final stage. Finally, the average cost for each treatment in every stage estimated was multiplied by the number of patients.
The follow-up cost includes a visit, counseling, and CT scan. These costs were calculated based on the EC survival rate in Iran for four years. The terminal care cost includes the treatment cost for patients who have died due to EC in 2018 but have been affected in previous years. It was assumed that the terminal care costs were half as much as the treatment cost in the last stage.
To estimate direct non-medical cost, due to the lack of data and studies about EC, only the transportation costs were considered. For this purpose, the following formula was applied:
TC = T × D × 2
TC is the total transportation costs, T is transportation cost per visit day, and D is the number of travels. The travel cost was multiplied by two because it was assumed that each patient would have a companion. The number of travels was extracted from medical records, assuming it equal to the number of outpatient visit days. To calculate the transportation cost per visit day, the cost of a trip was estimated at US$ 15 based on the expert's opinions.
The most common approach to estimate indirect cost is the human capital method. This approach supposes that the monetary value of productivity losses due to morbidity or premature death caused by an illness equivalent to the wage value of work time. Therefore, the working population was considered and the average daily wage was derived from gross domestic product (GDP) per employee.
We considered two indirect cost categories, including morbidity and mortality costs. The number of working days missed due to EC was used to estimate the lost productivity cost due to morbidity. Medical records were reviewed to calculate the number of missed working days due to EC. This number for every patient was equal to the number of days referred for treatment. Then, we adjusted the number of lost days according to the age and employment rate. Finally, the average lost working day was multiplied by the average daily wage.
To estimate the cost of productivity lost due to premature death in EC, we first extracted and ordered the number of EC deaths based on age and sex. The GLOBOCAN 2018 data and previous literature were applied to extract EC mortality. Second, the years of potential life lost were calculated. In each age group, the age at death was subtracted from life expectancy, using the standard Iranian life table. Ultimately, the productivity loss due to premature mortality was estimated by multiplying the number of potential lost years in the daily wage rate. The following formulas were used to calculate the mortality costs:
1) Mortality cost = Tdeath × PVLEyg
Where Tdeath is the total number of deaths from EC and PVLEyg is the present discounted value of lifetime earnings for deceased of age y and gender g. SURVyg is the probability that a person will survive to age n. MAX is maximum age group. n and g denote the age and gender of the person, respectively. Yg(n) is the mean annual earnings of an employed person of gender g and age n. Eg(n) is the proportion of the population of gender g and age n that are employed in the labor market. YHg(n) is the mean annual imputed value of household production for a person of gender g and age n. EHg(n) is the proportion of the population of gender g and age n that are doing housekeeping. r is the discount rate (3% was considered).
| » Results|| |
[Table 2] describes the characteristics of the 68 EC patients. More than 90% of patients were 45 years and older, and the majority were men. About 54 (79%) were in II and III stages. The main treatments were esophagectomy alone 29 (43.5%) and CRT 14 (20.5%).
|Table 2: The characteristics of the 68 selected esophageal cancer patients, Iran 2018|
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There were 4,372 new cases of EC in Iran for both sexes in 2018. According to the survival rate, by the end of 2018, 2317 cases would die, and 2055 will survive. [Table 3] presents the EC prevalence based on the year of disease for both sexes in Iran in 2018. The EC prevalence in 2018 was 5655, of which 484 cases were affected in 2014, 864 cases in 2015, 924 cases in 2016, 1328 cases in 2017, and 2055 cases in 2018.
The treatment costs of EC are presented based on stage and treatment methods in [Table 4]. The mean cost for esophagectomy and CRT followed by surgery was $4,197 and $5,769, respectively. The total cost of esophagectomy in stages II and III was $7,248,219 and $4,580,586 for CRT followed by surgery. In stage IV, the total cost of chemotherapy and palliative radiotherapy was estimated at $3,097,500 and $56,840, respectively.
|Table 4: The treatment costs (US$) of esophageal cancer based on treatment modalities and stages, Iran 2018|
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The direct medical costs of EC in Iran are presented in [Table 5]. The majority of direct medical costs are related to esophagectomy costs with 33.5%, followed by postoperative CRT by 19.22% of costs. The least amount of costs are for palliative radiotherapy, EMR, and follow-up of less than 1%. The total direct medical costs of EC were $23,829,844, of which $7,982,694 was due to esophagectomy and $4,580,586 was due to CRT followed by surgery. The terminal care with $3,332,360 account for 13.98% of direct medical cost and diagnosis services with $1,884,332 shares 7.91% of the costs.
The total cost for direct non-medical services was $6,627,480. Of total transportation costs for EC, $5,902,200 were for affected patients in 2018 and the remaining costs were for patients who were affected from 2014 to 2017. The number of travels in patients with EC was 441,832 and the mean cost of a trip was estimated to be $15 [Table 6].
|Table 6: The transportation costs (US$) of EC based on year of diagnosis, Iran 2018|
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[Table 7] shows that the number of missed workdays due to EC was 96,678. The total morbidity cost is estimated at $4,485,859. To calculate the missed workday, medical records were used. The daily wage was extracted from GDP per employee.
[Table 8] presents the number of deaths and productivity costs due to premature mortality of EC in 2018. The number of deaths was 2,317 for EC, of which 1,315 deaths were among men and 1,002 among women. The highest number of deaths occurred in the group 65 to 69 years, with 180 cases in Women and 236 cases in men. The mortality cost was for men $20,606,309 and $13,607,218 for women. The highest mortality cost occurred in the group 60 to 64 years in both sexes ($2,509,753 in women and $2,790,742 in men).
[Figure 1] depicts the economic burden of EC in Iran in 2018. The economic burden of EC was $69,156,710. The most component of costs was attributed to mortality cost with 49%, followed by medical direct cost at 34%.
| » Discussion|| |
In this study, we estimated the economic burden of EC in Iran in 2018, using a prevalence approach and human capital methods. The prevalence was calculated at 5,655 cases and there were 2,317 deaths due to EC in 2018. The economic burden of EC was estimated at $69.2 million (or $12,229 per patient), of which $38.7 million caused to indirect costs and $30.5 million by direct costs. This estimate indicates that the EC economic burden included about 0.02% of Iran's GDP in 2018.
Our study shows that most components of the economic burden incurred by productivity losses. It accounted for 56% of EC economic burden (49% for mortality cost and 7% for morbidity cost). The direct cost was responsible for 44% of the total economic burden, 34% for direct medical cost and 10% for direct non-medical cost. There are very few economic burden studies associated with EC, and most of them have estimated the medical expenditure of EC., Besides, it is not straightforward to compare the results in economic burden studies because of the differences in characteristics of patients, economic variables (wage, unemployment, and inflation), tariff rate, and treatment patterns. Therefore, these limitations should be incorporated simultaneously when comparing the results of economic burden studies. Although our analysis showed that the economic burden of EC is valuable in Iran, when considering the percentage of GDP, it seems to be smaller than the reports in other studies. For instance, Hong et al. calculated the economic burden of gastric cancer in Taiwan. They estimated the cost of gastric cancer to be US$ 423 million, which is equivalent to about 0.08% of Taiwan's GDP. Also, the results displayed that the mortality cost per death was $US145,990. A study was estimated the economic burden of cancers in Korea in 2010. The results showed that the economic burden for all cancers and EC was US$ 20,844 million and US$ 198 million, respectively. Because of Korea's GDP, these costs accounted for about 1.9% and 0.018% of GDP. However, most studies have reported that the main component of the economic burden in cancers is due to indirect costs.,
According to our results, the esophagectomy accounted for 33.5% of the medical direct cost in EC, followed by CRT accompanied by surgery (19.22%), terminal care (13.98%), chemotherapy (13%), and CRT (11.43%). Although the total cost for esophagectomy was higher than the cost of CRT followed by surgery ($7.9 million versus $4.5 million), the mean cost per patient was lower than CRT followed by surgery ($4,197 versus $5,769). Also, the total cost for esophagectomy in the advanced stages (II and III) was 9-times higher than in the early stage (I), such that it was $734.4 thousand in stage I and $7.2 million in stages II and III. The higher total cost in esophagectomy compared to other treatments is due to its higher use frequency. This finding is consistent with other. Yang et al. analyzed the annual cost of 1483 EC patients in China. They found that the annual direct medical cost for surgical treatment was higher than other therapies. This cost was US$ 11,418 by surgery, $8,770 at CRT and $3,913 on palliative care. A study indicated that the medical cost of esophagectomy was 4-fold the cost of endoscopic therapy. This finding would be a roadmap to control the medical expenditure of EC, especially in countries with a high incidence rate of EC and low and middle-income countries that face scarce health resources. In these countries, esophagectomy is usually the most common method, although many studies show it is not cost-effective compared to other treatments.,
The analysis of the treatment costs based on the stage in our study indicated that the total treatment costs in stages II and III were higher than other stages, such that it was 17-times in stage I and 4-times in stage IV. This difference can be attributed to the following reasons: First, the mean cost per patient in stages II and III is higher in other stages. In stage I, patients with EC were usually cured by esophagectomy alone and EMR, which are relatively inexpensive. In stage IV, the medical expenditures are reduced due to shorter survival. Patients in stages II and III receive more expensive therapy such as CRT and CRT followed by surgery, and usually have more survival, which incurred the follow-up cost. Second, the number of patients in stages II and III is higher than in other stages, such that 3,454 patients suffered in stages II and III, 218 in stage I, and 700 in stage IV. Other studies have shown that the main proportion of treatment costs among cancers occur in the middle stages., For instance, Guo et al. in China estimated that the average treatment costs in the middle stage for patients of EC are higher than that of other stages. Another study in China found that the annual cost of EC patients in stages II and III was 1.5 and 2-times of stage IV, respectively. A study in Iran showed that oral cancer treatment costs were $10,532 and $2,225 respectively for advanced and early stages in 2014. These results reveal the importance of early detection and screening in controlling the cost of cancers. Based on the obtained results, early detection in EC can reduce expenses by 90%.
The present study showed that the productivity costs due to premature death in EC were approximately $34.2 million, of which 60% occurred in men and 40% in women. The higher mortality costs in men can be due to several reasons. EC is a fatal disease that occurs more frequently in men. The number of deaths was 1,315 and 1,002 for men and women, respectively. Studies have shown that the disability adjusted life years (DALYs) number of EC is higher in men than women. Also, there are more risk factors for EC in men., A part of high mortality costs in men is related to economic variables. Generally, wages and employment rates are more for men. In the human capital approach, the costs are considered for a working population.
There are some limitations to our study. First, because access to data plays an essential role in economic burden studies, we did not include some costs due to a lack of data. In the direct non-medical cost, we only accounted for the traveling cost. Other costs such as caregiver, complementary and informal treatment have been ignored. In morbidity costs, we did not estimate the expenditure for the patient's companions. Given the high mortality and low survival rate in patients with EC, these costs are meager. Also, intangible costs were not considered due to the inherent difficulty in estimating them. Most studies on the economic burden of cancers disregard these costs.,
Second, we abstracted the medical expenditure data from a single hospital; however, some patients also may be hospitalized elsewhere. In this regard, given the geographical distribution in Iran, patients' expenses are different. Thus, the generalization of the results should be made with caution. Third, we adopted the human capital approach for estimating indirect costs. The value of life was not considered in this method for some groups such as children, retired people, and unemployed people. These costs are an essential component in economic burden, especially in EC that has a high mortality. Finally, our results are probably underestimated. We utilized the treatment tariff approved by the Ministry of Health in Iran. This tariff may not reflect the real cost.
Despite the stated limitations in our study, this is the first economic burden research of EC in Iran. Our study results can guide health-policy makers, especially in countries located on the esophageal cancer belt. This study shows that EC imposes a considerable economic burden on communities and patients. Mortality and medical cost appeared to be the main contributor to the economic burden. Therefore, policy-makers are recommended to adopt early detection and effective treatment as a highly cost-effective strategy for controlling costs.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]