How Do Type 2 Diabetes Mellitus-Related Chronic Complications Impact Direct Medical Cost in Four Major Cities of Urban China?vhe_

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1 Volume 12 Number VALUE IN HEALTH How Do Type 2 Diabetes Mellitus-Related Chronic Complications Impact Direct Medical Cost in Four Major Cities of Urban China?vhe_ Weibing Wang, PhD, 1 Chao Wei Fu, MSc, 1 Chang Yu Pan, MD, 2 Weiqing Chen, MD, PhD, 3 Siyan Zhan, MD, PhD, 4 Rongsheng Luan, MD, PhD, 5 Alison Tan, MD, PhD, 6 Zhaolan Liu, MSc 1, Biao Xu, MD, PhD 1 1 School of Public Health, Fudan University, Shanghai, China; 2 Department of Endocrinology, PLA General Hospital, Beijing, China; 3 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China; 4 Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing, China; 5 Department of Epidemiology,West China School of Public Health, Sichuan University, Chengdu, China; 6 Department of Health Economist and Epidemiology, GlaxoSmithKline (China) Investment Co. Ltd., Shanghai, China ABSTRACT Objective: The purpose of this study was to evaluate the direct medical costs of type 2 diabetes mellitus with or without complications, and to determine the economic impact of complications on type 2 diabetic patients. Methods: We performed a cross-sectional study of prevalent type 2 diabetes carried out in four major cities of China. The study populations were 1530 outpatients and 524 inpatients from clinics or wards of a total of 20 hospitals, using a two-phase subject enrolment process, by face-to-face interview with a unique questionnaire. Results: The annual direct medical cost per patient was estimated to be 4800 Chinese Yuan (CNY) in median or 10,164 CNY in mean. There is a difference between annual direct medical costs for patients with or without complications (6056 vs CNY; P < 0.001). It is also significantly different for the pay-out-of-pocket proportions (P = 0.015) between the patients with (44.6%) and without complications (40.4%). The direct medical cost varied significantly among the four cities (P < 0.001). Patients who simultaneously suffered microvascular and macrovascular diseases had higher direct medical cost (7600) than those with macrovascular (6000) (P = 0.012) and microvascular disease (5364) (P < 0.001), and those without both (3600) (P < 0.001). The correlation was statistically significant between the number of complications and direct medical costs (P < 0.001). Conclusions: The high economic burden raised by diabetes and its complications challenges the Chinese health-care system. It implicates an urgent need of intervention to prevent the development of long-term complications among the diabetic population, especially on the development of complications in high-cost body system. Keywords: cross-sectional, diabetes, diabetes-related complications, direct costs. Introduction Diabetes mellitus is a high-profile, costly disease to patient and society because of debilitating complications [1]. The World Health Organization (WHO) projects that there will be 366 million people with diabetes worldwide by the year In China, the estimated prevalence of diabetes is 23 million [2], with a predicted rise to 42 million by 2030 [3]. The prevalence of type 2 diabetes mellitus increased rapidly in urban China, from 4.58% (1996) to 6.13% (2002), and to 7.67% (Beijing, 2006) [4 7], and was much higher in urban cities (6.1%) than in small cities (3.7%) and rural areas (1.8%). Lifestyle change, aging of the population, improvements in disease detection and treatment, and lower mortality are often cited as factors in the increased prevalence of diabetes [1]. Recent studies have consistently shown that people with diabetes are more likely to develop many complications, both acute and long term [8]. The complications result in hospitalization, disability, and premature death [9]. Type 2 diabetes, therefore, has increasingly become the main cause of growing costs in hospitalization and drugs [10,11]. In many countries, the costs of Address correspondence to: Biao Xu, Department of Epidemiology, School of Public Health, Fudan University, 138 Yi Xue Yuan Road, Shanghai , China. bxu@shmu.edu.cn; Catherinexu61@yahoo.com /j x medications for diabetes patients with complications are dramatically higher than patients without complications [12,13]. In China, a recent estimate put the overall annual economic burden of diabetes at more than 17.6 billion Chinese Yuans (CNY, 1 USD ª 7 CNY) [14]. Annually, 81% of the economic cost had been used for treatment of diabetic complications [15]. The annual direct medical cost of health care associated with type 2 diabetes patients who had complication(s) was estimated to be 13,833 CNY, compared with 3726 for those without complications [16]. The tremendous economic burden of diabetes makes the disease an important clinical and public health problem. To formulate an effective health planning and resource allocation, it is important to determine economic burden with or without the absence of chronic complications. The purpose of this study, therefore, was to evaluate and estimate the direct medical costs of type 2 diabetes among patients with or without complications, and to determine the economic impact of complications on type 2 diabetic patients. Methods Study Setting This was a cross-sectional surveillance carried out in four major cities of China Shanghai, Beijing, Guangzhou, and Chengdu. In 2007, the per capita disposable incomes of Shanghai, Beijing, Guangzhou, and Chengdu were 20,668, 19,978, 19,850 and 12,789 CNY, respectively. 2009, International Society for Pharmacoeconomics and Outcomes Research (ISPOR) /09/

2 924 Wang et al. Study Subjects Eligible subjects were adult patients at any of 20 sampled secondary/tertiary hospitals that met WHO criteria for diagnosing type 2 diabetes [17] and had lived in the city for at least 2 years. Patients in outpatient group (hereafter be shorted as outpatients) were recruited consecutively from the hospitals outpatient clinics from March 2007 to May Patients were categorized in inpatient group (hereafter be shorted as inpatients) if they were recruited from hospitals wards from March 2007 to September 2007 using selection probability proportional to size sampling. The number of inpatients with different complications was determined according to the proportions of type 2 diabetesrelated complications from the study conducted by Chen et al. [15]. Patients were excluded if they had received treatment of type 2 diabetes for less than 1 year. Subjects Recruitment and Data Collection Study coordinators who majored in clinical medicine or preventive medicine were recruited from each study site and trained with the unique training plan by the investigators in the four cities. The subjects were face-to-face interviewed in the hospitals with the questionnaire designed by the School of Public Health, Fudan University. The questionnaire includes patients demographics, diabetes description, comorbidity, any complications because of type 2 diabetes, treatment history, and the evaluation of cost on type 2 diabetes and diabetic complications. The definition of costs are presented below. Written informed consent was obtained from the study subjects. The Ethics Committee of the School of Public Health of Fudan University approved the study. Definition of Costs Direct costs of illness are expenditures for medical supplies and services (e.g., medications, doctor visits, and hospitalization). Direct medical costs include all expenditure of treating type 2 diabetes or any diabetic complications, comprising the co-payment, diagnosis, treatment, diagnostic testing, prescription drugs, and medical supplies. Annual direct medical cost was estimated according to health-care visits in the past year, and payment on visiting outpatient departments and hospitalization, respectively, which was obtained from hospital billing department when patients discharge. Specifically, for outpatients, annual direct medical cost = direct medical cost per outpatient visit outpatient visits in past 6 months 2 + annual hospitalization cost; for inpatients, annual direct medical cost = annual direct medical cost associated with outpatient visits 2 + direct medical cost per hospitalization times of hospitalization in past 12 months. Statistical Analysis All data were entered into a Chinese database (EpiData version 3.1, EpiData Association, Odense, Denmark) and transferred into SPSS 16 (SPSS Inc., Chicago, IL) (Sn: ) for statistic analyses. Categorical variables were presented as counts and percentage, and compared with chi-square tests. Because the cost data were skewed, medians and quartiles were reported together with means. Mann Whitney U-tests were used to compare the pattern of cost between two groups, and the Kruskal Wallis tests were used to compare among three groups or above. Statistical significance was established at a P-value below Table 1 Variables General characteristics of subjects Number of outpatient (%) Number of inpatient (%) P value* City Beijing 375 (24.6) 121 (23.4) Guangzhou 376 (24.7) 127 (24.6) Shanghai 373 (24.5) 140 (27.1) Chengdu 400 (26.2) 128 (24.8) Sex Male 637 (41.8) 231 (44.9) Female 887 (58.2) 283 (55.1) Individual income < (68.3) 365 (70.7) (31.7) 151 (29.3) Admission hospital Secondary 196 (12.9) 163 (31.6) <0.001 Tertiary 1328 (87.1) 353 (68.4) Complications Yes 792 (52.0) 468 (90.7) <0.001 No 732 (48.0) 48 (9.3) *Chi-square test. Note: total number amounts may vary because of missing values. Results General Characteristics of the Study Population A total of 2054 subjects were recruited, including 1530 outpatients from March 2007 to July 2007 and 524 inpatients from March 2007 to September All but 14 were eligible for analysis (1524 outpatients and 506 inpatients; the 14 were excluded for having less than 1 year of type 2 diabetes mellitus treatment history or not providing cost information) (see Table 1). Of the 2040 subjects, 42.5% (868) were male, and the age averaged years (range 18 97). The majority (91.6%) of them reported to have some kinds of medical insurances, and 68.3% of outpatients and 70.7% of inpatients reported a personal income below 2000 CNY/month at the interview. Among 516 inpatient subjects, only 9.3% did not have any complication, compared with 48.0% (P < 0.001) among 1524 outpatients; the median number of complications was two (range: 0 10) and one (range: 0 8) among inpatients and outpatients, respectively, and four-fifth of the inpatients had two or more complications. Direct Medical Cost among Patients with or without Complications Direct medical cost for outpatient visit at the time of interview was 244 CNY in median (313 in mean), and it was 9897 CNY in median (17,652 in mean) for each hospitalization in the previous year. Table 2 shows the itemized direct medical cost for diabetesrelated outpatient visits and hospitalizations among those with and without complications. Patients with complications had higher treatment costs than those without complications when they visited outpatient clinics (239 CNY vs. 194 CNY, P < 0.001), but there were no differences for the costs of diagnosis and medical supplies. As for hospitalizations, cost for medical supplies was the only significantly different item between the two groups. Taking into account the direct medical cost in the current visit, the number of outpatient visit, and hospitalization cost in the recent year, the annual direct medical cost per patient was estimated to be 4800 CNY in median (10,164 CNY in mean). There is a difference between annual direct medical costs for patients with (6056 CNY) and without complications (3583

3 Complications and Cost of Type 2 Diabetes 925 Table 2 Itemized direct medical cost and annual medical costs among the type 2 diabetic patients with and without complications (CNY) Without complication With complication Item Median (P25 P75) Mean (SD) Median (P25 P75) Mean (SD) Z, P Current outpatient visit Diagnosis (n = 1,418) 9 (5 16) 28.2 (67.1) 9 (5 16) 33.9 (82.8) , Medical supplies (n = 1,414) 0 (0 0) 0.5 (5.2) 0 (0 0) 1.1 (14.2) , Treatment (n = 1,422) 194 ( ) (196.0) 239 ( ) (317.6) , <0.001* Current hospitalization Nursing (n = 417) 18 (0 130) 85.7 (102.3) 78 (0 156) (181.3) , Diagnosis (n = 431) 3,002 (1,907 3,651) 3,218.0 (2,531.0) 2,396 (1,108 3,576) 3,048.2 (1,960.0) , Medical supplies (n = 418) 0 (0 36) (2,441.1) 0 (0 269) 2,282.2 (8,655.6) , 0.010** Treatment (n = 417) 3,012 (827 7,711) 10,102.6 (15,686.2) 3,983 (1,286 7,528) 11,182.5 (23,491.6) , Other (n = 431) 78 (0 288) (226.7) 81 (0 259) (439.1) , Annual direct medical cost Total (1,913) 3,583 (1,512 6,802) 5,313.2 (7,260.4) 6,056 (1,895 13,344) 13,320.1 (31,512.5) , <0.001* Outpatients (1,478) 3,600 (1,560 6,790) 10,319.7 (17,482.0) 6,131 (2,400 12,000) 5,372.4 (7,367.5) , <0.001* Inpatients (435) 2,400 (0 7,200) 4,227.5 (4,834.2) 6,000 (0 18,000) 19,101.0 (47,652.5) , 0.008* Pay-out-of-pocket payment (%) , 0.015** *<0.01. **<0.05. Total number amounts may vary because of missing values of itemized costs. Mann Whitney U-test. CNY, Chinese Yuan; SD, standard deviation. CNY) (Mann Whitney U-test, Z =-8.317, P < 0.001). For all the subjects, 42.1% of annual direct medical cost had been paid out of pocket. Specifically, there is a significant difference (Mann Whitney U-test, Z =-2.432, P = 0.015) in pay-out-ofpocket payments between the patients with complications (44.6%) and those without (40.4%) (Table 2). Whether or not there is complication(s), the annual direct medical cost varied significantly among the four cities (Kruskal Wallis test, chi-square = , P < 0.001). Shanghai had the highest direct medical cost among both patients with complications and those without complication; Chengdu had the lowest direct medical cost in the two groups of patients (Fig. 1). Direct Medical Costs among Patients with Intercurrent Microvascular and/or Macrovascular Diseases Table 3 shows that diabetic patients who suffered macrovascular diseases harbored higher direct medical cost (6000 in median) than those with microvascular disease (5364) (Mann Whitney U-test, Z =-6.269, P < 0.001), and those without microvascular and macrovascular diseases (3600) (Mann Whitney U-test, Z =-3.698, P < 0.001). When the patients simultaneously harbored microvascular and macrovascular diseases, the annual direct medical cost increased to 7600 CNY, which was significantly higher than those with microvascular (Mann Whitney Figure 1 Direct medical costs among patients with or without complications.

4 926 Wang et al. Table 3 Median and quartile cost of type 2 diabetes medical care with different kinds of complications Variables Annual direct medical cost (CNY) Microvascular diseases (n = 380) 5,364 (1,488, 10,606) Macrovascular diseases (n = 357) 6,000 (2,130, 11,916) Microvascular and macrovascular diseases (n = 420) 7,600 (2,166, 18,862) Nonmicrovascular and macrovascular 3,600 (1,518, 6,827) diseases (n = 756) CNY, Chinese Yuan. U-test, Z =-4.497, P < 0.001) or macrovascular diseases (Mann Whitney U-test, Z =-2.503, P = 0.012). Direct Medical Costs among Patients with Complications Targeting Different Systems Figure 2 shows that diabetic inpatients that had cardiovascular disease ranked the highest median direct medical cost that is 3.8 times as that of those without any complication, followed by cardiovascular disease, and nephrosis. Among prevalent diabetic outpatients, cardiovascular disease, eye disorder, and peripheral neuropathy had the highest direct medical cost. Direct Medical Costs and the Number of Complications As Figure 3 shows, the annual direct medical cost increased with the number of complications. Patients having more complications harbored higher direct medical cost than those with fewer complications. Inpatients with two and four complications paid 2.0 and 6.7 folds direct medical costs as those without complications, respectively; outpatients with two and three complications paid 2.0 and 2.6 folds as those without complications. The correlation was statistically significant between the number of complications and direct medical costs both among prevalent outpatients (Kruskal Wallis test, chi-square = , P < 0.001) and inpatients (Kruskal Wallis test, chi-square = 21.27, P < 0.001). Discussion How Do the Chronic Complications Aggravate the Economic Burdens of Type 2 Diabetes in Urban China? It is important to identify patients with high medical costs of type 2 diabetes to incorporate them into cost-reducing diabetes management programs. A number of cost-of-illness studies have recorded that the costs for patients with complications were times as that of noncomplications population [13,18 20]. Our results unsurprisingly showed that the patients with complications had higher economic burden than those without compilations. In the current study, we have found that the patients with two complications doubled direct medical cost as the patients without complication(s), and the inpatients having four and more than four complications paid 6.7 folds as those without complication(s). The high prevalence of diabetic patients who currently live with complications (52.0% of the outpatients) obviously aggravated the economic burden of the type 2 diabetes. Although it is rarely reported, a fact should also be noted that the number of the complications had been ranged from 1 to 10 among the inpatients and 1 to 8 among the outpatients. Especially in the inpatients, four-fifth of patients had two or more complications. In addition, the burden had been impacted by the high proportion of pay-out-of-pocket payment by diabetic patients in the cities who paid a considerable proportion (42.1%) of medical costs from their pockets. The proportion is higher than the 2002 estimates (19.2%) indicated by a recent study [21], partly because the study failed to include complication-induced cost. And those with complications paid a significant higher proportion from their pocket than those without, indicating a lower insurance coverage of the medication for the complications. Figure 2 Direct medical costs among patients with the complications targeting different systems. Note: Only the subjects without any complication or those with complication(s) in one system have been included in this figure. The number of valid subjects in the groups outpatients: none (590), nephrosis (40), foot damage (0), cardiovascular disease (291), cerebral vascular disease (11), eye disorder (40), and peripheral neuropathy (100); inpatients: none (33), nephrosis (17), foot damage (4), cardiovascular disease (73), cerebral vascular disease (4), eye disorder (15), and peripheral neuropathy (9).

5 Complications and Cost of Type 2 Diabetes 927 Figure 3 Direct cost among the patients with different numbers of complications. Despite a relatively high coverage of medical insurance in urban China, complications-induced direct medical cost still caused a high economic burden on the side of diabetic patients. The results of this analysis suggest a great disparity in the provision of care for diabetes in urban China. This may produce poorer clinical outcomes for the great majority of that population, favoring disability by increasing the occurrence and worsening chronic complications, and increasing premature mortality among those affected by diabetes. The result also shows that the difference of direct medical costs between complications and noncomplications patients was mainly because of the cost for treatment among outpatients, i.e., medications and surgical operation, and medical supplies among inpatients, i.e., fee for blood transfusion and oxygen therapy. Previous studies that addressed diabetes had shown that overall management costs are mostly because of the treatment of complications [10,22]. Which Type of Complications Impacts the Cost of Type 2 Diabetes Most? The management of diabetes alone renders considerable expenditure, however, macrovascular and microvascular complications are the major cause of health-care costs [11]. Previous evidences have showed that it took 1.3 to 4.1 times as much for a patient with diabetes who developed macrovascular or microvascular complications compared with one without type 2 diabetes [18,19]. The current study shows that in the presence of microvascular diseases, the median direct medical costs were 1.5 times higher as compared with patients with no complications, although with macrovascular disease, it was 1.7 times higher as compared with patients with no complications, and when both microvascular and macrovascular disease were present, the cost was 2.1 times higher compared with when no complications were present. The similar difference was also observed in European countries. In European patients with both microvascular and macrovascular complications, the total cost was increased by up to 250% compared with those without complications [11]. The cost of type 2 diabetes in Europe CODE-2 study reported that the presence of microvascular complications resulted in an increase of 70% compared with people with no evidence of complications [19]. The results show that cerebral vascular disease, cardiovascular disease, and nephrosis were associated with particularly high direct medical costs among the prevalent type 2 diabetic inpatients. In urban China, cerebral vascular disease, cardiovascular disease, and nephrosis have been reported to be present in 17.3%, 66.9% and 39.7% among type 2 diabetic inpatients, respectively [23]. It is similar to previous results in Western countries that indicated that renal, cardiovascular complications were the most prevalent and were associated with particularly high costs [24,25]. It can be explained by unawareness and delayed diagnosis of the complications, and a higher cost of these complications brought about, e.g., stroke, making the highest economic burden per case. As for prevalent outpatients, those with cardiovascular disease, eye disorder, and peripheral neuropathy have the highest economic burden annually. These high proportions combined with the highest cost have incurred a considerable economic burden both on the patients and society. Unlike Western type 2 diabetic populations, where diabetic nephropathy has been reported to be of relatively low prevalence [26], Chinese urban type 2 diabetic patients have a 39.6% detection rate [23]. Moreover, the management of end-stage nephropathy consumes resources considerably, requiring dialysis and renal transplantation. As a consequence, the impact of nephropathy on the total costs for managing type 2 diabetes is likely to be high. Implications for the Chinese Health-Care System This study provides reliable and valuable information for health resource allocation and health policy decision of diabetes care. To address the economic impact of chronic diseases like diabetes, industrialized countries have launched many effective programs against diabetes, including those for preventing the disease, those

6 928 Wang et al. for detecting the disease in its asymptomatic stage, and those for managing the disease to reduce its complications [1]. From the experience of these cases, prevention first is the best, most important, and effective strategy with a relative endurable cost for China [27]. Apparently, as a resource-scare country, China is facing problems associated with financing and delivering health care; therefore, it is particularly important to optimize the limited health-care resources to address the health problems efficiently and equitably. It is the strategy that may potentially save the direct costs of diabetes and would contribute to the Chinese health-care system. China s health-care institutions are managed at three levels in urban areas primary institutions (community hospitals or health centers that provide basic health-care services for communities), secondary institutions (regional hospitals that provide comprehensive medical care), and tertiary institutions (crossregional, providing comprehensive and specialized medical care). It was reported that there was a total of 997 (6%, 997/17,148) tertiary hospitals in China that consumed 54.73% of the total health-care expenditure in 2007 [28]. Diabetes is a common chronic disease that is increasingly managed in primary care, and most of the patients can be treated by primary care of high quality other than service with high price. To control the medical expenditure of diabetes, redistribution of the diabetic patients among primary, secondary, and tertiary care services should also be a priority, to channel treatment of chronic diseases to the most cost-efficient levels of the health-care system. Limitations The findings in this study may be subject to three limitations. First, this was a hospital-based cross-sectional study. The subjects were enrolled in the settings of secondary or tertiary hospitals, which might limit the validity to general population of the current result, and therefore overestimated the economic burden in China. At the same time, the crude cost estimates determined in this study were not justified by the prevalence rate of diabetes in different cities. To know the population information about the care and treatment of type 2 diabetes in the health-care setting of China, community-based study was preferable in the future. Second, the cost data, especially direct nonmedical cost and indirect cost were, to some extent, from recalling by the patients, which may be subject to recall bias. The direct medical cost data, however, mainly depended on the medical history combined with billing information, which raised the accuracy of the estimates. Third, there are also challenges in differentiating type 2 diabetesrelated complications from coincident diseases, particularly among the elderly, and it is possible that some patients may have been misdiagnosed, and therefore, stratified incorrectly. Notwithstanding its limitations, this study does suggest a considerable impact of implications on the type 2 diabetic populations. Conclusions The results of this study are consistent with the previously published literature. It therefore implicates an urgent need of intervention to prevent the development of long-term complications among the diabetic population, especially on the development of complications in high-cost body system, that is, cardiovascular, cerebral vascular, and eye disorder. Early and aggressive treatment may delay or even prevent many of the complications associated with diabetes, therefore leading to improved quality of life and reduced expenditures in patients with type 2 diabetes. 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