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The Economic Costs of Cardiovascular Disease, Diabetes Mellitus, and Associated Complications in South Asia: A Systematic Review

Open ArchivePublished:July 03, 2017DOI:https://doi.org/10.1016/j.vhri.2017.05.003

      Abstract

      Background

      More than 80% of global deaths caused by cardiovascular disease (CVD) and diabetes mellitus (DM) occur in developing countries. The burden of noncommunicable disease in South Asia is increasing rapidly.

      Objectives

      To estimate the costs of CVD and the costs of DM to individuals and society in Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka.

      Methods

      We systematically searched six health and economic databases for studies identifying costs related to CVD or DM and their respective complications. Costs were extracted from included studies and converted to US $ for the price year 2015 to enable meaningful comparisons.

      Results

      Of the 71 articles suitable for full-text review, 29 studies met the inclusion criteria. Most were cost-of-illness studies (n = 27) and were from the patient perspective (n = 23). Most collected data since 2000 (n = 23) and included data from India (n = 24). No studies included longitudinal costs at the patient level. Medical costs for routine management of CVD and DM were broadly similar. These costs escalate significantly once complications occur, which require treatment, particularly for stroke, major coronary events, and amputations. Costs are mainly borne by the individual and family. Some included studies modeled rapidly rising future costs. Most studies included had methodological weaknesses.

      Conclusions

      Marked increases in costs have been identified when complications of these chronic diseases occur, underlining the importance of secondary prevention approaches in disease management in South Asia. Higher quality studies, especially those that include longitudinal costs, are required to establish more robust cost estimates.

      Keywords

      Introduction

      The prevalence of noncommunicable diseases such as cardiovascular disease (CVD) and diabetes mellitus type 2 (DM) is increasing worldwide, especially in low- and middle-income countries (LMICs) [
      World Health Organization
      Global Status Report on Non-Communicable Diseases.
      ]. Ischemic heart disease was the single biggest cause of disability-adjusted life-years in the Global Burden of Disease Study [
      • Murray C.J.
      • Vos T.
      • Lozano R.
      • et al.
      Disability-adjusted life-years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010.
      ], with an estimated 31% of all worldwide deaths being due to CVD [
      • Lozano R.
      • Naghavi M.
      • Foreman K.
      • et al.
      Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.
      ].
      The South Asia region has a population of 1.7 billion people, which has tripled since 1950. Life expectancy in the region has increased dramatically from 39 years in 1950 to 65 years today. India’s population is by far the largest, with three-quarter of the region’s total [

      Bloom DE, Rosenberg L. The Future of South Asia: Population Dynamics, Economic Prospects, and Regional Coherence, Program on the Global Demography of Aging, Working Paper No. 68. 2011. Boston: Harvard Initiative for Global Health. Available at: https://www.hsph.harvard.edu/pgda/working/. [Accessed Nov 22, 2016]

      ]. Along with the global trend, the prevalence of CVD and DM in the region is expected to continue to increase in the coming years [

      Bloom DE, Cafiero E, Jané-Llopis E, et al. The global economic burden of non-communicable diseases, 2011, Geneva: World Economic Forum. Available at: www.weforum.org/EconomicsOfNCD. [Accessed Nov 22, 2016]

      ]. In South Asia, some of the main drivers for this expected rise are economic transition, urbanization, and lifestyle changes [
      • Yusuf S.
      • Reddy R.
      • Ôunpuu S.
      • et al.
      Global burden of cardiovascular diseases, part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization.
      ]. The burden of disease is shifting from infectious, maternal, and childhood diseases to noncommunicable diseases. This epidemiological transition has occurred rapidly and CVD, DM, and their complications now contribute a significant burden of disease in these LMICs [
      • Goyal A.
      • Yusuf S.
      The burden of cardiovascular disease in the Indian subcontinent.
      ]. For example, in India CVDs are now the leading cause of death in men and women in both rural and urban areas [
      World Health Organization
      Global Status Report on Non-Communicable Diseases.
      ,
      World Health Organization
      Noncommunicable Diseases in the South-East Asia Region.
      ]. In addition, India is now the country with the second largest number of people living with diabetes at 65.1 million (second only to China at 98.4 million).
      According to the World Bank [

      World Bank. Gross domestic product 2015—World DataBank. Available from: http://databank.worldbank.org/data/download/GDP.pdf. [Accessed April 17, 2017].

      ], the South Asian region has been the fastest growing economic region in recent years. In 2015, the combined gross domestic product (GDP) of all countries in the region was US $2,689,862 million. By far the largest economy in the region is India (2015 GDP US $2,088,841 million). Other economies include Pakistan (US $271,050 million), Bangladesh (US $195,079 million), Sri Lanka (US $82,316 million), Nepal (US $21,195 million), Afghanistan (US $19,331 million), Maldives (US $3,435 million), and Bhutan (US $2,058 million).
      Chronic diseases have a significant health impact on individuals and their families. Analysis of noncommunicable diseases in South Asia highlights that although the burden is currently greatest among affluent groups, many adverse risk factors are concentrated among the poor, portending future increases among those with the least resources to manage their condition [
      • Siegel K.R.
      • Patel S.A.
      • Ali M.K.
      Non-communicable diseases in South Asia: contemporary perspectives.
      ]. The International Diabetes Foundation estimated diabetes-related health care expenditure in 2014 to be approximately US $6.9 billion in the South Asia region [

      International Diabetes Federation. IDF Diabetes Atlas 2014 update. 2014. Available from: http://www.idf.org/diabetesatlas. [Accessed February 23, 2016]

      ]. With limited capacity within the public health system to effectively identify and manage CVD and DM, health care costs are usually borne as out-of-pocket expenditure by the individual and their families in this region, often with catastrophic financial consequences [
      • Guariguata L.
      • Whiting D.
      • Hambleton I.
      • et al.
      Global estimates of diabetes prevalence for 2013 and projections for 2035.
      ,
      • Rahman M.S.
      • Akter S.
      • Abe S.K.
      • et al.
      Awareness, treatment, and control of diabetes in Bangladesh: a nationwide population-based study.
      ,
      • Xu Y.
      • Huang C.
      • Colón-Ramos U.
      Moving toward universal health coverage (UHC) to achieve inclusive and sustainable health development: three essential strategies drawn from Asian experience: comment on “Improving the World’s Health Through the Post-2015 Development Agenda: Perspectives from Rwanda”.
      ].
      Although some countries in the region are beginning to explore social insurance schemes to fund health care expenditure, there is limited existing evidence to inform policymakers of these costs [
      • Vilcu I.
      • Probst L.
      • Dorjsuren B.
      • et al.
      Subsidized health insurance coverage of people in the informal sector and vulnerable population groups: trends in institutional design in Asia.
      ]. A few literature reviews have been conducted, exploring some relevant aspects of this issue. Brouwer et al.’s [
      • Brouwer E.D.
      • Watkins D.
      • Olson Z.
      • et al.
      Provider costs for prevention and treatment of cardiovascular and related conditions in low- and middle-income countries: a systematic review.
      ] review of provider costs related to CVD in LMICs found a wide variation in costs but little evidence from low-income countries. Yesudian et al.’s [
      • Yesudian C.A.
      • Grepstad M.
      • Visintin E.
      • et al.
      The economic burden of diabetes in India: a review of the literature.
      ] review of the costs of DM in India found medication to be a large proportion of costs, with the burden falling heaviest on the poor and urban populations. Seuring et al.’s [
      • Seuring T.
      • Archangelidi O.
      • Suhrcke M.
      The economic costs of type 2 diabetes: a global systematic review.
      ] review of the economic costs of DM in relation to levels of national GDP found direct costs to be generally higher than indirect costs, with these direct costs being positively associated with a country’s GDP per capita. None of these studies adequately addressed the question of all relevant economic costs, focused specifically on the South Asian region.
      The aim of this systematic review was to estimate the costs of CVD and the costs of diabetes to individuals and society, in the LMICs of the South Asia region according to the World Bank definition [
      The World Bank
      ], which includes Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka. This review sought to identify and collate data from peer-reviewed studies to address the following question: What are the economic costs related to CVD and the economic costs related to DM and their complications on society, the health sector, individuals, and their families in South Asia?

      Methods

      This review was undertaken according to the Centre for Reviews and Dissemination guidelines for systematic reviews and meta-analyses [
      • Akers J.
      • Aguiar-Ibáñez R.
      • Baba-Akbari Sari A.
      CRD’s Guidance for Undertaking Reviews in Health Care.
      ]. A protocol was developed to plan the review, which is available from the authors on request. The review is reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines [
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • et al.
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      ].

       Search Strategy

      In April 2015, we searched the following databases for studies containing costs of CVD and DM in the countries of South Asia:
      • EconPapers (RePec)
      • Embase Classic Embase (Ovid) 1947 to April 1, 2015
      • Global Health (Ovid) 1973 to 2015 week 12
      • Ovid MEDLINE(R) 1946 to March week 5 2015
      • Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations April 1, 2015
      • NHS Economic Evaluation Database: Issue 1 of 4, January 2015 (Wiley)
      • WHOLIS World Health Organization Library & Information Networks for Knowledge Database
      The search strategy comprised subject headings and text words identified by the project team and known relevant articles for the search concepts CVD, DM, Costs, and South Asia. The CVD search concept was adapted from a Cochrane CVD review [

      Li C, Lv Z, Shi Z, et al. Periodontal therapy for the management of cardiovascular disease in patients with chronic periodontitis. Cochrane Database Syst Rev 2014;(8):CD009197.

      ]. Table 1 lists some of the terms we used; however, the full search strategy can be found in the appendices in Supplemental Materials found at doi:10.1016/j.vhri.2017.05.003. The results of the electronic searches were stored and managed in an EndNote library. Relevant references, cited in the identified studies, were also included, as well as any relevant studies that the authors already had from previous work. We did not have the financial and human resources to contact study authors.
      Table 1Example search terms used in the search strategy
      ConceptSubject headingsText words
      Diabetes mellitusDiabetes Mellitus/Diabet*, niddm, mody
      CVDCardiovascular Diseases/Heart Diseases/Hypertension/Vascular diseas*, cardiovascular diseas*, stroke, thrombosis, heart attack*
      South AsiaIndia/Pakistan/Bangladesh/ etc…Indian, India, Pakistan*, Nepal*, Afghanistan*
      CostCosts and Cost Analysis/Budgets/Cost* of illness, economic* burden, medical expenditure*, economic evaluation*

       Inclusion Criteria

      Studies were considered as eligible for inclusion if they related to the specified countries in the World Bank South Asia region and if they related to any aspects of “cost” in relation to CVD or DM.
      Our aim was to obtain to the fullest extent possible relevant costs related to CVD, DM, and their complications. We used a broad definition of cost including all perspectives and elements of costs or economic impacts. Therefore, we included costs related to CVD or costs related to DM as incurred by service users and their families, service providers, governmental organizations, and society. We included any types of costs regardless of any categorization made by authors including direct, indirect, and/or intangible costs. Inclusion of studies was not restricted by specific participants or settings with the aim of capturing all relevant costs of CVD, relevant costs of DM, and complications of either disease. Study designs included in the review were randomized controlled trials, observational studies, cost-of-illness studies, and systematic reviews.
      We included all participants diagnosed with either DM or CVD (including ischemic heart disease, stroke, hypertension, and congestive heart failure) and their complications. We also included studies that included patients with comorbid CVD and DM. In regard to costs of diabetes, our study aims were focused on type 2 DM. However, studies not clearly specifying which type of DM or combining results for both type 1 and 2 were included. We did not include studies exclusively looking at type 1 or gestational diabetes mellitus.

       Exclusion Criteria

      We excluded studies if there was no full-text publication available; if it was a conference abstract; if it was written in a language other than English, Hindi, Urdu, or Bengali; and if it included costs that did not relate to usual care in that setting at the time (e.g., only related to costs of a novel intervention). Cost-benefit, cost-effectiveness, cost-minimization, and cost-utility analyses were not completely excluded but reviewed separately to identify possible sources of cost data. Systematic reviews were included to ensure that any relevant studies included in other reviews were also identified in ours. The systematic review itself was not included in our analysis because this would have led to double counting of data.

       Study Selection

      Following implementation of these search strategies, the title and abstract of each identified study were reviewed by one author and the inclusion/exclusion criteria applied. The full-text articles of the short-listed studies were then reviewed independently by two authors using an extraction form and quality checklist. The two sets of quality scores were then reviewed by both authors together and discrepancies discussed to agree a consensus score for each study. If the two reviewers were unable to reach consensus on the scoring, a third reviewer was asked to assess the relevant points in the study and adjudicate.

       Data Extraction, Quality Scoring, and Risk of Bias

      We developed a data extraction tool and two of the study team members (F.G. and H.E.) tested it on five studies before it was used to extract the relevant data from the reviewed studies. The tool can be found in the appendices in Supplemental Materials. Only information available in the publication was used for assessing inclusion criteria, for data extraction, and for quality assessment.
      A number of different quality checklists are available in relation to economic evaluation but there is currently no universally accepted checklist that was suitable for this review. Therefore, we developed a quality assessment checklist for this study, on the basis of a review of a number of existing checklists [
      • Akers J.
      • Aguiar-Ibáñez R.
      • Baba-Akbari Sari A.
      CRD’s Guidance for Undertaking Reviews in Health Care.
      ,
      • Céilleachair A.J.Ó.
      • Hanly P.
      • Skally M.
      • et al.
      Cost comparisons and methodological heterogeneity in cost-of-illness studies: the example of colorectal cancer.
      ,
      • Costa N.
      • Derumeaux H.
      • Rapp T.
      • et al.
      Methodological considerations in cost of illness studies on Alzheimer disease.
      ,
      • Drummond M.
      • Jefferson T.
      Guidelines for authors and peer reviewers of economic submissions to the BMJ.
      ,
      • Evers S.
      • Goossens M.
      • De Vet H.
      • et al.
      Criteria list for assessment of methodological quality of economic evaluations: consensus on health economic criteria.
      ,
      • Hendriks M.E.
      • Kundu P.
      • Boers A.C.
      • et al.
      Step-by-step guideline for disease-specific costing studies in low-and middle-income countries: a mixed methodology.
      ,
      • Husereau D.
      • Drummond M.
      • Petrou S.
      • et al.
      Consolidated Health Economic Evaluation Reporting Standards (CHEERS)—explanation and elaboration: a report of the ISPOR Health Economic Evaluation Publication Guidelines Good Reporting Practices Task Force.
      ,
      • Larg A.
      • Moss J.R.
      Cost-of-illness studies: a guide to critical evaluation.
      ,
      • Morris S.
      • Devlin N.
      • Parkin D.
      ]. This checklist enabled an assessment of risk of bias to be undertaken using a scoring system across 38 quality criteria. These criteria covered a full description of methods, context, and economic study design; quantification of resources and costs; currency, price year, and discounting; uncertainty and sensitivity analysis; and appropriate reporting of results and conclusion. We scored the studies with 1 point for “yes,” 0.5 for “partial” or “unclear,” and 0 for “no” or “NA” for each of these criteria. The total score is presented as a percentage of the available scores for each study; thus, we did not score studies down for nonapplicable ratings. This assumes that each criterion carries equal weight in the overall score. We did not exclude studies for a poor quality score; however, the score is presented in Table 3 and should be considered in the interpretation of results.

       Summary Measures

      The vast majority of studies included in this review are cost-of-illness studies. We reported our findings in standard health economics terms [
      • Morris S.
      • Devlin N.
      • Parkin D.
      ]: medical direct costs (financial transactions for health services), nonmedical costs (financial transactions for nonmedical services, e.g., transport), indirect costs (lost productivity), and intangible costs (disvalue to an individual such as pain or suffering). Most units of measurement are reported as mean annual cost per patient or mean annual cost per hospital admission. Once we extracted these costs from each included study, we converted them to US $ for the price year 2015 (using Purchasing Power Parity data from the International Monetary Fund), to enable meaningful comparisons. This was done using an online cost converter (v1.5 accessed in May 2016) designed for this purpose and found at http://eppi.ioe.ac.uk/costconversion/ [
      • Shemilt I.
      • Thomas J.
      • Morciano M.
      A web-based tool for adjusting costs to a specific target currency and price year.
      ]. We grouped our findings by disease and by the presence of complications to assist with further comparison. Where studies collected data over several years and had not been adjusted to one price year, we took the midyear as the original price year for conversion.
      Because studies included in this review reported findings for different diseases, with a range of complications in various settings, it was not possible for us to synthesize the data into a meta-analysis. The findings of this systematic review are therefore descriptive in nature.

      Results

      We identified 1437 articles from our searches (after duplicates had been removed). Five of these came from reference lists of other systematic reviews. Of these, 1366 were excluded after screening titles and abstracts as not meeting our inclusion criteria. Of the remaining 71 articles that were eligible for full-text review, 42 were excluded (the reasons are listed in Fig. 1), which left 29 studies to be included in our review.
      Fig. 1
      Fig. 1Flow Diagram of the Study Selection Process.

       Study Characteristics

      The vast majority of the studies (n = 27) were cost-of-illness studies (see Table 2). The two remaining studies were economic modeling studies [
      • Abegunde D.O.
      • Mathers C.D.
      • Adam T.
      • et al.
      The burden and costs of chronic diseases in low-income and middle-income countries.
      ,
      • Srivastava A.
      • Mohanty S.K.
      Age and sex pattern of cardiovascular mortality, hospitalisation and associated cost in India.
      ]. Most studies assessed costs from the patient perspective (n = 24), with the rest being from the societal perspective (n = 5). An important gap in the evidence base is the lack of information from half of the countries, with only four of the eight South Asian countries contributing to included studies. The results will, to a degree, be Indo-centric because most studies (n = 23) provided data from India. The other three countries represented were Pakistan (n = 5), Bangladesh (n = 1), and Nepal (n = 1). Most studies were set in public or private hospitals (n = 22, of which 8 were across multiple sites and 4 were outpatient departments only). Other settings included a district/region (n = 3) and nationwide settings (n = 4). Most studies were quite recent; only six studies had collected data before the year 2000.
      Table 2Characteristics of included studies
      ReferenceCountrySettingSample sizeSample characteristicsYear of data collectionConditionIncludes complicationsEconomic study type & perspectiveStudy typeSources of cost dataCost types & descriptionsCurrency reported
      Abegunde et al.
      • Abegunde D.O.
      • Mathers C.D.
      • Adam T.
      • et al.
      The burden and costs of chronic diseases in low-income and middle-income countries.
      Pakistan, India, BangladeshNationalNot applicableNot applicable1950–2002CVD (heart disease & stroke) and DMYesEconomic growth models; societalMulticountry comparative analysisDeath registers, MoH surveillance, World Bank estimates, WHO disease scenariosEffect of premature deaths from chronic diseases on the countries’ national income, which is measured in gross domestic product (GDP) losses per working-age populationUS $
      Adiga et al.
      • Adiga S.
      Health care cost incurred by patients of diabetes mellitus in a tertiary care hospital setting in coastal Karnataka district.
      India (Karnataka)Specialty hospital238 patients3 groups: mean age 57.8–65.5 y, males 43%–57%2008DM type 2YesCost of illness; patientCross-sectional case note review studyHospital medical records departmentDirect medical cost: medicine, consultations, laboratory, bed charge, surgery, total annual cost during hospitalizationIndian rupees (INR)
      Akari et al.
      • Akari S.
      • Mateti U.V.
      • Kunduru B.R.
      Health-care cost of diabetes in South India: a cost of illness study.
      India (Andhra Pradesh)Speciality hospital150 patientsMales 67%, 24% illiterate2012DMYesCost of illness; patientCase note reviews and interviewsPatient’s notes; self-reporting; interviewing health care professionalsDirect medical costs: medication, laboratory, consultation, hospitalizationINR/US$
      Direct nonmedical: travel, food
      Indirect costs: productivity loss
      Ali et al.
      • Ali S.M.
      • Fareed A.
      • Humail S.M.
      • et al.
      The personal cost of diabetic foot disease in the developing world--a study from Pakistan.
      PakistanSpecialty hospital21464% males, mean age 52.7 y1997– 2004DM (foot ulcers)Yes Diabetic foot ulcerCost of illness; patientRetrospective case note reviewHospital chargesDirect medical costs:Pakistan rupees & £
      OP consultation, investigations, medicines, hospitalization, surgery, home visits, plaster casts
      Chandra et al.
      • Chandra P.
      • Gogate B.
      • Gogate P.
      • et al.
      Economic burden of diabetes in urban Indians.
      India (Pune)Specialty clinic219 patientsMales 58.1%, mean age 54.9 y2011–2012DMYes (ophthalmology clinic)Cost of illness; patientQuestionnaire survey and interviewsSelf-reportingDirect medical costs: medicines, doctor’s fees, investigations, spectacle, laser treatment, surgeryINR
      Direct nonmedical costs: travel, food, dietary advice
      Indirect costs: productivity loss
      Clarke et al.
      • Clarke P.M.
      • Glasziou P.
      • Patel A.
      • et al.
      Event rates, hospital utilization, and costs associated with major complications of diabetes: a multicountry comparative analysis.
      India215 clinical centers in 20 countries471Over 55 y old with mean age 65.1 y, males 53%2001–2006DMYes (macrovascular)Cost of illness; patientMulticountry comparative analysisWHO CHOICE economic model for bed day unit costsUnit inpatient bed day cost per countryInternational $
      Hussain et al.
      • Hussain M.
      • Naqvi S.
      • Khan M.A.
      • et al.
      Direct cost of treatment of diabetes mellitus type 2 in Pakistan.
      Pakistan (Karachi)15 different OP clinics at five sites885 patientsMales 46.2%, graduate or higher 46%Not mentionedDM type 2Not specifiedCost of illness; patientPatient questionnaire surveySelf-reportingDirect medical costs: consultations, laboratory tests, home testing, medicine & syringesPakistani rupees
      Direct nonmedical: travel, food
      Jhaj et al.
      • Jhaj R.
      • Goel N.K.
      • Gautam C.S.
      • et al.
      Prescribing patterns and cost of antihypertensive drugs in an internal medicine clinic.
      India (Chandigarh)OP department (OPD) of government hospital300 prescriptions (173 patients)Males 51%; mean age 53.4 y (men) and 51.8 y (women)June 1999–November1999HypertensionYes, not specificCost of illness; patientPrescription reviewCurrent Index of Medical Specialities (CIMS) 1999, Indian Pharmaceutical Guide 1999Only including costs of prescriptions/ drugs for patients with hypertensionINR
      Kapur
      • Kapur A.
      Economic analysis of diabetes care.
      India187 towns across India5516 patientsMean age 53.7 y (for DM type 2: 55.2 y)1999DMYes- not specificCost of illness; patientPatient questionnaire surveySelf-report & responses of cliniciansDirect medical costs: estimated total monthly expenditure on investigations, OP clinic, medicines, laboratory testsINR
      Direct nonmedical costs: travel & miscellaneous costs
      Karan et al.
      • Karan A.
      • Engelgau M.
      • Mahal A.
      The household-level economic burden of heart disease in India.
      India (national)Community (household survey) in India74, 000 households, 383, 000 individuals45% rural, males 50%2004CVDYes- CVDCost of illness; patientNational household surveySelf-reporting (from national household survey, India)Direct medical costs: hospital care, OP, drugsInternational $
      Direct nonmedical costs: travel
      Khealani et al.
      • Khealani B.A.
      • Javed Z.F.
      • Syed N.A.
      • et al.
      Cost of acute stroke care at a tertiary care hospital in Karachi, Pakistan.
      PakistanSpecialty hospital443Mean age 58 y, males 61%1998–2001CVD (acute stroke)Yes-strokeCost of illness; patientCase note reviewMedical billing recordsDirect medical costs: hospitalization, drug, diagnosisPakistani rupees/US $
      Khowaja et al.
      • Khowaja L.A.
      • Khuwaja A.K.
      • Cosgrove P.
      Cost of diabetes care in out-patient clinics of Karachi, Pakistan.
      Pakistan (Karachi)Six outpatient clinics in three different sites (public, private, and NGO)345Males 36.5%, 38% aged 51–60 y, 36% aged 41–50 y, 26% aged 20–40 y2006DMNot specifiedCost of illness; patientPatient questionnaire surveySelf-reported, The Pharmacy guide 2004, National Health Survey Pakistan (NHSP), Government of PakistanDirect medical costs: medicines, OP consultation, laboratory testsPakistani rupees
      Direct nonmedical costs: travel and food
      Indirect costs: loss of productivity
      Kumar et al.
      • Kumar A.
      • Nagpal J.
      • Bhartia A.
      Direct cost of ambulatory care of type 2 diabetes in the middle and high income group populace of Delhi: the DEDICOM survey.
      India (Delhi)High- income wards of Delhi819 subjects from 20,666 householdsMales 51%, mean age 54 ySeptember 2005–December 2005DM type 2NoCost of illness, patient perspectiveHousehold, cross-sectional surveySelf-reportedDirect medical costs: medicine use, laboratory tests, glucose testing, and consultationsINR
      Kumpatla et al.
      • Kumpatla S.
      • Kothandan H.
      • Tharkar S.
      The costs of treating long term diabetic complications in a developing country: a study from India.
      India (Chennai)Hospitalized patients in a tertiary hospital- Specialized diabetes care center368 (Stratified into six groups depending on complications)Mean age 58 y, 70% urbanJune 2008–December 2009DM type 2 with complicationsYesCost of illness, patient perspectiveCross-sectional patient questionnaire surveySelf-reported and hospital billsDirect medical costs: current admission (medical consultations, laboratory,INR
      medicines, admission, surgery, investigations) and previous 2 y expenditure
      Direct nonmedical costs: carer costs, transportation
      Kwatra et al.
      • Kwatra G.
      • Kaur P.
      • Toor G.
      • et al.
      Cost of stroke from a tertiary center in northwest India.
      India (Punjab)Stroke unit and neurology clinic of a tertiary referral center189Mean age 58 y, males 68%April 2009–October2011Stroke (CVD)NoCost of illness, societal perspectivePatient questionnaire survey, medical records reviewHospital bills, self-reportedDirect medical costs: admission, laboratory, radiology, investigations, drugs, nursing, appointments, rehabilitationINR
      Direct nonmedical costs:
      travel, relocation, food, lodgings, changes to house, etc.
      Indirect costs: productivity losses
      Malhotra et al.
      • Malhotra S.
      • Grover A.
      • Verma N.K.
      • et al.
      A study of drug utilisation and cost of treatment in patients hospitalised with unstable angina.
      India (Chandigarh)Tertiary public sector hospital336Mean age 62 y, males 68%6-mo period in 1999Unstable angina (CVD)NoCost of illness, patient perspectiveCase note review & patient interviewsPharmacy price list and self-reportingDirect medical costsUS $ and INR
      (single admission): admission, prescription, coronary care unit, ward, interventions, investigations
      Malhotra et al.
      • Malhotra S.
      • Karan R.S.
      • Pandhi P.
      • et al.
      Pattern of use and pharmacoeconomic impact of hypertensive drugs in a north Indian referral hospital.
      India (Chandigarh)Tertiary hospital OP department1076Males 56%, mean age males: 51 y, females: 53 yJanuary–December 2000Hypertension (CVD)NoCost-of- illness study, patient perspectiveMedical records review and patient interviewSelf-reported, hospital billing, pharmacy price listDirect medical costs:US $ (INR)
      laboratory investigations, drugs, physician fees, ADRs (adverse drug reactions)
      Marfatia et al.
      • Marfatia S.
      • Monz B.
      • Suvarna V.
      • et al.
      Treatment costs of stroke related to nonvalvular atrial fibrillation patients in India—a multicenter observational study.
      India (Mumbai & Bangalore)Tertiary hospitals400Mean age 61 y, males 62%January 2010–December 2011Stroke, with nonvalvular atrial fibrillationNoCost of illness, societalPatient questionnaire survey and case note reviewHospital billing recordsDirect medical costs: inpatient (hospitalization, surgery, imaging, laboratory, medicines, rehabilitation, ambulance)INR and US $
      OP (consultations, imaging, laboratory, medicines, rehabilitation, nursing)
      Direct nonmedical costs: home modifications, transport
      Indirect costs: lost productivity
      Ramachandran et al.
      • Ramachandran A.
      • Ramachandran S.
      • Snehalatha C.
      • et al.
      Increasing expenditure on health care incurred by diabetic subjects in a developing country: a study from India.
      IndiaVarious hospitals, clinics, and rural areas of seven states in India55656% urban, males 61%, mean age 56 y (urban) and 55 y (rural)2005 (1 mo)DM type 2NoCost of illness, patient perspectivePatient questionnaire surveySelf-reportedDirect medical costs: medicines, laboratory, investigations, consultations, hospitalization, surgeryINR
      Rao et al.
      • Rao K.D.
      • Bhatnagar A.
      • Murphy A.
      Socio-economic inequalities in the financing of cardiovascular & diabetes inpatient treatment in India.
      India (national)Nationwide India (all 35 states/union territories)Diabetes: 438 inpatientsCVD group: mean age 52 y, males 54%January 2004–June2004CVD and DMNoCost of illness; patient perspectiveCross- sectional household surveySelf-reportedDirect medical costs: doctors, medicines, laboratory, bed fee, nursing, physio, appliances, other (food, blood, oxygen, ambulance)INR
      For CVD: 2129 inpatientsDM group: mean age 55 y, males 51%
      Direct nonmedical costs: transport, food, and lodgings
      Rayappa et al.
      • Rayappa P.
      • Raju K.
      • Kapur A.
      • et al.
      The economic cost of diabetes care: the Bangalore urban district diabetes study.
      India (Bangalore)Various hospitals and primary and community health centers (public and private)611Males 55%, illiterate 21%1997DMNoCost of illness, patient perspectivePatient questionnaire surveySelf-reportedDirect medical costs: weekly expenditure on care, tests undertaken, hospitalizationsINR
      Indirect costs: working days lost and loss of personal/family income
      Satyavani et al.
      • Satyavani K.
      • Kothandan H.
      • Jayaraman M.
      • et al.
      Direct costs associated with chronic kidney disease among type 2 diabetic patients in India.
      IndiaA specialized diabetes care center and a private hospital209 (split into four groups depending on status of CKD)Mean age 64 y, males 58%, 60%, 76%, and 57% in four groupsAugust 2008 –January 2010DM type 2 with or without CKDYes only CKDCost of illness, patient perspectivePatient questionnaire survey and medical billing reviewSelf-reported and hospital billsDirect medical costs: first admission (laboratory & consultations), medicines (monthly), and per hospitalization (surgery, bed fee, nursing), dialysis, total expenditure in past 2 yINR
      Direct nonmedical costs: travel
      Shastry et al.
      • Shastry R.
      • Sheetal U.
      • Sowjanya D.
      • et al.
      Cost analysis of drugs used in elderly patients with cardiovascular disorder.
      India (Karnataka)OP department of tertiary hospital20450% males, mean age 70 yNot statedCVD (DM as a comorbidity)YesCost of illness (medicines only), patient perspectiveCase note reviewwww.cimsasia.com (online drug information system for Asia)Direct medical cost:INR
      cost of each drug in all the prescriptions for average cost of medications per day
      Shobhana et al.
      • Shobhana R.
      • Rama Rao P.
      • Lavanya A.
      • et al.
      Expenditure on health care incurred by diabetic subjects in a developing country–a study from southern India.
      India (Chennai)One private hospital and one free government hospital596 (422 private hospital, 174 government hospital)Private hospital: 55% males, mean age 58 yJanuary 1998– June1998DMNoCost of illness, patient perspectivePatient questionnaire surveySelf-reportedDirect medical costs: medicines, laboratory, doctors fee, hospitalization, surgeryINR
      Government hospital: 46% males, mean age 55 y
      Direct nonmedical costs: travel
      Shobhana et al.
      • Shobhana R.
      • Rao P.R.
      • Lavanya A.
      • et al.
      Cost burden to diabetic patients with foot complications–a study from southern India.
      India (Chennai)Specialist hospital270Foot complications group: 68% males, mean age 58 yJanuary–June 1998DM type 2 onlyYes foot complicationsCost-of- illness study, patient perspectivePatient interviewsSelf-reportedDirect medical costs: doctors fees, specialist fees, surgery, hospitalizations, laboratory, medicinesINR
      No foot complications group: 50% males, mean age 55 y
      Direct nonmedical costs: travel, footwear
      Shrestha et al.
      • Shrestha N.
      • Lohani S.P.
      • Angdembe M.R.
      • et al.
      Cost of diabetes mellitus care among patients attending selected outpatient clinics.
      NepalA public hospital, a private hospital, and two poly clinics227Mean age 49 y, males 59%July 2010–September2010DMNoCost of illness, patient perspectivePatient questionnaire surveySelf-reportedDirect medical costs: doctors fee, laboratory, medicineUS $
      Direct nonmedical costs: travel, food, and physical exercise
      Indirect cost: earnings lost because of clinic visit and having DM
      Srivastava and Mohanty
      • Srivastava A.
      • Mohanty S.K.
      Age and sex pattern of cardiovascular mortality, hospitalisation and associated cost in India.
      IndiaNational Indian surveysNA (modeling study)NANational data sets: 2004, 1995–1996, 2001–2003CVDNot specificallyMacroeconomic modeling study, societal perspectiveCross-sectional secondary data analysisSelf-reported (national household survey, India)Direct medical costs: admission fee, drugs, laboratory, doctors feeINR
      Direct nonmedical costs: travel, “other nonmedical costs”
      Tharkar et al.
      • Tharkar S.
      • Satyavani K.
      • Viswanathan V.
      Cost of medical care among type 2 diabetic patients with a co-morbid condition—hypertension in India.
      IndiaDiabetes speciality center (100 beds): location not stated443 (269 without hypertension, 174 with hypertension)Mean age 55 y, males 53%October 2007–December 2007DM (with or without hypertension)Only hypertensionCost of illness, patient perspectivePatient questionnaire surveySelf-reportedDirect medical costs: doctor’s fees, medicines, laboratory, admission, investigations, miscellaneousINR
      Direct nonmedical costs: miscellaneous (food, travel)
      Tharkar et al.
      • Tharkar S.
      • Devarajan A.
      • Kumpatla S.
      • et al.
      The socioeconomics of diabetes from a developing country: a population based cost of illness study.
      IndiaHousehold, Chennai, India71853% males, mean age 56 yAugust 2009–December 2009DM with or without complicationsYesCost of illness, societal perspectiveCross- sectional household surveySelf-reportedDirect medical costs: hospital service, consultation, laboratory, medicineINR
      Direct nonmedical costs: food, transport
      Indirect costs: productivity losses
      Intangible cost: willingness to pay
      CKD, chronic kidney disease; CVD, cardiovascular disease; DM, diabetes mellitus; MoH, Ministry of Health; NA, not applicable/available; NGO, nongovernment organization; OP, outpatient; WHO, World Health Organization.
      Table 3Mean annual costs per patient of cardiovascular disease (CVD), diabetes mellitus (DM), and their complications (in US $ 2015)
      ReferenceYearConditionCountryQuality scoreTotal costsDirect medical costsDirect nonmedical costsIndirect costsIntangible costs
      CVD
      Karan et al.
      • Karan A.
      • Engelgau M.
      • Mahal A.
      The household-level economic burden of heart disease in India.
      2004CVDIndia (national)78.1%Mean annual costs US $563Mean annual costs US $ 175.21Not includedNot included
      Srivastava and Mohanty
      • Srivastava A.
      • Mohanty S.K.
      Age and sex pattern of cardiovascular mortality, hospitalisation and associated cost in India.
      2004CVDIndia83.8%The total cost of hospitalization for CVDs in India in 2004: US $10.2 billionMean cost of hospitalization for CVDs per person:Not disaggregatedNot includedNot included
      Modeled estimated costs:1995–1996: US $1318
      2010: US $11.7 billion2004: US $1523
      2016: US $14.4 billion
      2020: US $16.6 billion
      Malhotra et al.
      • Malhotra S.
      • Grover A.
      • Verma N.K.
      • et al.
      A study of drug utilisation and cost of treatment in patients hospitalised with unstable angina.
      1999CVD (angina, unstable)India75.8%Mean total costs per hospitalization episode: US $677Mean admission fee: US $11Not includedNot includedNot included
      Cost of prescription per stay: US $96
      Cost of coronary care unit: US $145
      Cost of ward stay: US $43
      Cost of investigation: US $154
      Cost of interventions: US $229
      Jhaj et al.
      • Jhaj R.
      • Goel N.K.
      • Gautam C.S.
      • et al.
      Prescribing patterns and cost of antihypertensive drugs in an internal medicine clinic.
      1999CVD (hypertension)India (Chandigarh)67.7%Annual mean drug cost: US $79Not includedNot includedNot included
      Malhotra et al.
      • Malhotra S.
      • Karan R.S.
      • Pandhi P.
      • et al.
      Pattern of use and pharmacoeconomic impact of hypertensive drugs in a north Indian referral hospital.
      2000CVD (hypertension)India51.5%Mean total annual cost: US $386Mean annual laboratory costs: US $113Not includedNot includedNot included
      Mean annual drug costs: US $231
      Mean annual physician fees: US $26
      CVD with DM
      Shastry et al.
      • Shastry R.
      • Sheetal U.
      • Sowjanya D.
      • et al.
      Cost analysis of drugs used in elderly patients with cardiovascular disorder.
      2014
      No year of data collection reported, so year is assumed.
      CVD (with or without DM)India (Karnataka)50.0%Mean cost of prescription per day:Mean cost of prescription per day:Not includedNot includedNot included
      All medications: US $1.14All medications: US $1.14
      CVDs: US $0.51CVDs: US $0.51
      Diabetic medications: US $ 0.21Diabetic medications: US $ 0.21
      Rao et al.
      • Rao K.D.
      • Bhatnagar A.
      • Murphy A.
      Socio-economic inequalities in the financing of cardiovascular & diabetes inpatient treatment in India.
      2004CVD and DMIndia (national)74.1%Average costs per hospitalization:Not disaggregated from nonmedical costs so unable to calculateNot disaggregated from direct medical costs so unable to calculateNot includedNot included
      US $1343 (CVD) and US $646 (diabetes)
      Proportion of annual household income: 30% for CVD and 17% for diabetes
      Abegunde et al.
      • Abegunde D.O.
      • Mathers C.D.
      • Adam T.
      • et al.
      The burden and costs of chronic diseases in low-income and middle-income countries.
      1950–2002
      Midyear used to calculate conversion into 2015 US$.
      CVD and DMPakistan, India, Bangladesh83.3%Not includedNot includedNot includedLoss of GDP in 2015:Not included
      India: US $1.96 billion
      Pakistan: US $0.21 billion
      Bangladesh: US $0.14 billion
      DM (not specified)
      Shresta et al.
      • Shrestha N.
      • Lohani S.P.
      • Angdembe M.R.
      • et al.
      Cost of diabetes mellitus care among patients attending selected outpatient clinics.
      2010DMNepal76.6%Mean total cost per outpatient visit: US $14Mean cost per visit: US $12Mean cost per visit: US $2.70Mean cost per visit: US $2.24Not included
      Mean total cost per month: US $44Mean cost per annum:Mean annual cost: All patients: US $21Mean cost per annum:
      Mean total cost per year:All patients: US $463Public sector: US $9
      All patients: US $483Public sector: US $212Private sector: US $27
      Public sector: US $219Private sector: US $590
      Private sector: US $606
      Akari et al.
      • Akari S.
      • Mateti U.V.
      • Kunduru B.R.
      Health-care cost of diabetes in South India: a cost of illness study.
      2012DMIndia (Andhra Pradesh)71.0%Without complications: US $31 With comorbidities: US $ 328Without complication: US $29 With comorbidities: US $303Without complication: US $0.37 With comorbidities: US $3.91Without complications: US $2.31 With comorbidities: US $21Not included
      Chandra et al.
      • Chandra P.
      • Gogate B.
      • Gogate P.
      • et al.
      Economic burden of diabetes in urban Indians.
      2011–2012DMIndia (Pune)45.3%Average annual cost: US $575Average annual cost: US $258Average annual cost: US $235Not included
      Kapur
      • Kapur A.
      Economic analysis of diabetes care.
      1999
      Midyear used to calculate conversion into 2015 US$.
      DMIndia61.3%Total estimated annual cost: US $2637Mean total direct cost: US $948Not clearly presentedMean total indirect cost: US $1689Not included
      Khowaja et al.
      • Khowaja L.A.
      • Khuwaja A.K.
      • Cosgrove P.
      Cost of diabetes care in out-patient clinics of Karachi, Pakistan.
      2006DMPakistan (Karachi)80.6%Mean annual cost US $ 1048Annual mean direct cost US $951Mean cost for travel: US $10Mean lost productivity of patients: US $9Not included
      Mean cost for food: US $2.71Mean lost productivity of attendants: US $17
      Rayappa et al.
      • Rayappa P.
      • Raju K.
      • Kapur A.
      • et al.
      The economic cost of diabetes care: the Bangalore urban district diabetes study.
      1997DMIndia (Bangalore)72.7%Total annual costs of diabetes per person:Average annual direct cost for routine care (nonhospitalization): US $882Not includedTotal annual indirect cost: US $2803Not included
      Personal: US $973
      Family: US $1843Average direct cost per hospitalization: US $1471
      Society: US $2468Average annual cost of laboratory investigations and monitoring: US $122
      Shobhana et al.
      • Shobhana R.
      • Rama Rao P.
      • Lavanya A.
      • et al.
      Expenditure on health care incurred by diabetic subjects in a developing country–a study from southern India.
      1998DMIndia (Chennai)77.9%Median total annual expenditure:Private hospital patients median spend:Median transport costs for private hospital patients: US $33Not includedNot included
      Private hospital patients: US $618Medicine: US $411
      Public hospital patients: US $34Laboratory tests: US $49Median transport costs for public hospital patients: US $26
      Estimated national costs for 20 million patients with DM could be US $12.4 billionFamily doctor: US $41
      Specialist: US $41
      Hospitalization: US $685
      Surgery: US $1233
      Public hospital patients median spend:
      Medicine: US $4101
      Laboratory tests: US $33
      Family doctor: US $16
      Specialist: US $75
      Hospitalization and surgery: Free care
      DM type 2
      Ramachandran et al.
      • Ramachandran A.
      • Ramachandran S.
      • Snehalatha C.
      • et al.
      Increasing expenditure on health care incurred by diabetic subjects in a developing country: a study from India.
      2005DM type 2India65.2%Median total expenditure:Median total expenditure:Not includedNot includedNot included
      Urban patients: US $1046Urban patients: US $1046
      Rural patients: US $655Rural patients: US $655
      Adiga et al.
      • Adiga S.
      Health care cost incurred by patients of diabetes mellitus in a tertiary care hospital setting in coastal Karnataka district.
      2008DM type 2India (Karnataka)58.1%For hospitalized: US $1216Annual medicine costs: US $ 648–US $1963Not includedNot includedNot included
      Annual consultation costs: US $19–US $88
      Hussain et al.
      • Hussain M.
      • Naqvi S.
      • Khan M.A.
      • et al.
      Direct cost of treatment of diabetes mellitus type 2 in Pakistan.
      2013
      No year of data collection reported, so year is assumed.
      DM type 2Pakistan (Karachi)40.9%Average cost: US $213/mo (US $2551 annually)Not disaggregatedNot disaggregatedNot includedNot included
      Kumar et al.
      • Kumar A.
      • Nagpal J.
      • Bhartia A.
      Direct cost of ambulatory care of type 2 diabetes in the middle and high income group populace of Delhi: the DEDICOM survey.
      2005DM type 2India (Delhi)73.4%Average costs: ~US $628 per annumNot includedNot includedNot included
      Shobhana et al.
      • Shobhana R.
      • Rao P.R.
      • Lavanya A.
      • et al.
      Cost burden to diabetic patients with foot complications–a study from southern India.
      1998DM type 2India (Chennai)66.1%Group without foot complications: US $599Not disaggregated from nonmedical costs so unable to calculateGroup without foot complications: US $38Not includedNot included
      Group with foot complications: US $2116Group with foot complications: US $68
      Foot complications OP only: US $986Foot complications OP only: US $58
      Foot complications IP + OP: US $2316Foot complications IP + OP: US $68
      DM with complications
      Clarke et al.
      • Clarke P.M.
      • Glasziou P.
      • Patel A.
      • et al.
      Event rates, hospital utilization, and costs associated with major complications of diabetes: a multicountry comparative analysis.
      2001–2006
      Midyear used to calculate conversion into 2015 US$.
      DM with complicationsIndia (part of multicountry study)75.0%Major coronary event: US $2087Not includedNot includedNot included
      Major cerebrovascular event: US $2396
      Heart failure: US $2469
      Peripheral vascular: US $502
      Nephropathy: US $293
      History of:
      Major coronary event: US $131
      Major cerebrovascular event: US $122
      Heart failure: US $205
      Peripheral vascular: US $168
      Nephropathy: US $161
      Kumpatla et al.
      • Kumpatla S.
      • Kothandan H.
      • Tharkar S.
      The costs of treating long term diabetic complications in a developing country: a study from India.
      2008–2009
      Midyear used to calculate conversion into 2015 US$.
      DM with complications (type 2)India69.1%Total cost of hospital admission without complications: US $362Not disaggregated from nonmedical costs so unable to calculateTransportation charges: US $28–US $81 per admissionNot includedNot included
      Total cost of hospital admission with complications: US $1024–US $1534
      Estimated 2-y costs (no complications): US $ 2420
      Estimated 2-y costs (with complications): US $8,066–US $22,787
      Ali et al.
      • Ali S.M.
      • Fareed A.
      • Humail S.M.
      • et al.
      The personal cost of diabetic foot disease in the developing world--a study from Pakistan.
      1997–2004
      Midyear used to calculate conversion into 2015 US$.
      DM with foot ulcersPakistan58.8%Total costs:Not includedNot includedNot included
      Grade 1 foot ulcer: US $246
      Grade 2: US $3406
      Grade 3: US $4466
      Major amputation: US $ 4204
      Minor amputation: US $4597
      Satyavani et al.
      • Satyavani K.
      • Kothandan H.
      • Jayaraman M.
      • et al.
      Direct costs associated with chronic kidney disease among type 2 diabetic patients in India.
      2008–2010
      Midyear used to calculate conversion into 2015 US$.
      DM (type 2) with or without CKDIndia67.2%Total expenditure per hospitalization:Not disaggregated from nonmedical costs so unable to calculateThe transportation charges per hospitalization:Not includedNot included
      Transplantation group: US $31,694Transplantation group: US $262
      Dialysis group: US $4,934Dialysis group: US $281
      CKD group: US $1,020CKD group: US $50
      No complication group: US $259No complication group: US $24
      2-y total expenditure estimate:
      Transplantation group: US $27,828
      Dialysis group: US $40,331
      CKD group: US $8,066
      No complication group: US $2,420
      Tharkar et al.
      • Tharkar S.
      • Devarajan A.
      • Kumpatla S.
      • et al.
      The socioeconomics of diabetes from a developing country: a population based cost of illness study.
      2009DM with or without complicationsIndia89.1%Median annual direct cost per patient: US $2048Not disaggregated from nonmedical costs so unable to calculateDirect nonmedical cost:Median annual cost: US $401Patients׳ willingness to pay to stay well:
      Modeled annual national cost of diabetes to Indian population (range): US $ 99.2 billion to US $148.2 billion)Per hospitalization: US $202Per month: US $161
      Per OP attendance: US $57Per year: US $1936
      Tharkar et al.
      • Tharkar S.
      • Satyavani K.
      • Viswanathan V.
      Cost of medical care among type 2 diabetic patients with a co-morbid condition—hypertension in India.
      2007DM with or without hypertensionIndia59.4%Mean total expenditure for hospital admissions over 2- y period:Median total cost for treatment of diabetes by hospitalization or IP procedure:Food and travel costs per hospitalization episode:Not includedNot included
      Nonhypertensive group: US $2603Nonhypertensive group: US $1734Nonhypertensive group: US $399
      Hypertensive group: US $3533Hypertensive group: US $1952Hypertensive group: US $470
      Average cost per routine OP check-up: US $288
      CVD-Stroke
      Khealani et al.
      • Khealani B.A.
      • Javed Z.F.
      • Syed N.A.
      • et al.
      Cost of acute stroke care at a tertiary care hospital in Karachi, Pakistan.
      1998–2001
      Midyear used to calculate conversion into 2015 US$.
      StrokePakistan66.1%Total costs per stroke: US $8480Not includedNot includedNot included
      Kwatra et al.
      • Kwatra G.
      • Kaur P.
      • Toor G.
      • et al.
      Cost of stroke from a tertiary center in northwest India.
      2009–2011
      Midyear used to calculate conversion into 2015 US$.
      StrokeIndia71.9%The mean overall cost at 6 mo: US $5966Mean direct medical costs: US $ 3890Mean direct nonmedical costs: US $357 (at 6 mo)Mean indirect costs: US $1719 (at 6 mo)Not included
      IP care: US $2298Travel cost: US $128Patients: US $1088
      OP care: US $72Other expenditures: US $229Caregiver: US $631
      IP rehabilitation: US $73
      OP rehabilitation: US $470
      Total drugs charges: US $1411
      Marfatia et al.
      • Marfatia S.
      • Monz B.
      • Suvarna V.
      • et al.
      Treatment costs of stroke related to nonvalvular atrial fibrillation patients in India—a multicenter observational study.
      2010–2011
      Midyear used to calculate conversion into 2015 US$.
      Stroke, with nonvalvular atrial fibrillationIndia86.8%Mean total costs per patient during first 12 mo: US $32,927 (median US $29,706)Index hospitalization: US $15,366Mean home modification costs US $1,552Mean costs for informal care (days of lost productivity): US$ 872Not included
      OP care: US $13,085
      GP visits: US $3,671
      Rehabilitation services: US $2,322
      Laboratory visits: US $261
      Imaging visits: US $875
      Pharmacotherapy: US $5,956
      Nursing home/services: US $2,083
      GP, general practitioner; IP, inpatient; OP, outpatient.
      low asterisk No year of data collection reported, so year is assumed.
      Midyear used to calculate conversion into 2015 US$.
      Sample sizes within the cost-of-illness studies ranged from 150 to 383,000 individuals, with a median sample size of 400. Twenty studies included data for DM (type 2 [n = 7] or not stated [n = 13], with 11 of these DM studies including complications of the disease). Eleven studies included data for CVD, of which some included participants with DM (n = 2) and some related specifically to stroke (n = 3), hypertension (n = 2), and angina (n = 1). Of the 23 studies that reported the mean age of the sample, the range of means was 49 to 70 years old. Of the 24 studies that reported on the sex ratio of the sample, males were in the majority in 20 studies (% males pooled across 24 studies = 56%).
      Sources of cost data were obtained from self-reporting (n = 21), hospital records (n = 9), national reference costs (n = 5), and international reference costs (n = 2), with some studies combining several sources. Because most were cost-of-illness studies, it is not surprising that the vast majority of included studies reported direct medical costs (n = 28). These were mainly costs for consultation fees, medicines, laboratory investigations, admission charges, bed fees, surgery costs, nursing charges, and rehabilitation fees. A lesser proportion of studies included direct nonmedical costs (n = 17), which were mostly transport and food costs. Fewer studies still included indirect costs (n = 5), which were all estimates of loss of productivity. One study included intangible costs, which estimated a willingness-to-pay value using a bidding method. The currencies that studies reported in were Indian rupees (n = 20), US dollars (n = 7), Pakistan rupees (n = 4), international dollars (n = 2), and pounds sterling (n = 1).
      Seven studies were authored by researchers from the same World Health Organization Collaborating Centre for Research in Chennai, India [
      • Kumpatla S.
      • Kothandan H.
      • Tharkar S.
      The costs of treating long term diabetic complications in a developing country: a study from India.
      ,
      • Ramachandran A.
      • Ramachandran S.
      • Snehalatha C.
      • et al.
      Increasing expenditure on health care incurred by diabetic subjects in a developing country: a study from India.
      ,
      • Satyavani K.
      • Kothandan H.
      • Jayaraman M.
      • et al.
      Direct costs associated with chronic kidney disease among type 2 diabetic patients in India.
      ,
      • Shobhana R.
      • Rama Rao P.
      • Lavanya A.
      • et al.
      Expenditure on health care incurred by diabetic subjects in a developing country–a study from southern India.
      ,
      • Shobhana R.
      • Rao P.R.
      • Lavanya A.
      • et al.
      Cost burden to diabetic patients with foot complications–a study from southern India.
      ,
      • Tharkar S.
      • Devarajan A.
      • Kumpatla S.
      • et al.
      The socioeconomics of diabetes from a developing country: a population based cost of illness study.
      ,
      • Tharkar S.
      • Satyavani K.
      • Viswanathan V.
      Cost of medical care among type 2 diabetic patients with a co-morbid condition—hypertension in India.
      ], and three studies were from a study group in Bangalore [
      • Kapur A.
      Economic analysis of diabetes care.
      ,
      • Kumar A.
      • Nagpal J.
      • Bhartia A.
      Direct cost of ambulatory care of type 2 diabetes in the middle and high income group populace of Delhi: the DEDICOM survey.
      ,
      • Rayappa P.
      • Raju K.
      • Kapur A.
      • et al.
      The economic cost of diabetes care: the Bangalore urban district diabetes study.
      ]. The results from our quality checklist indicate that many studies failed to report substantial elements of their methods; therefore, poor internal validity is a risk for these studies (Table 2).

       Risk of Bias within Studies

      Using our quality checklist, we identified scores for included studies that ranged between 40.9% and 89.1% (see Table 2). The median score was 71.0%. The distribution of scores for the 29 studies is represented in Figure 2. Seven studies had a quality score below 60%. Five studies had a quality score exceeding 80%. There were no obviously similar study characteristics between poorly scoring studies. There was a similar range of quality scores for studies that included participants with DM compared with studies for CVD. The studies with low-quality scores were spread across all diseases and study types (see Table 3).
      Fig. 2
      Fig. 2Distribution of quality scores for included studies.

       Annual Economic Costs of CVD Per Person

      There were 11 studies that estimated economic costs for CVD in some of the countries of South Asia (see Table 3). One study from India [
      • Malhotra S.
      • Karan R.S.
      • Pandhi P.
      • et al.
      Pattern of use and pharmacoeconomic impact of hypertensive drugs in a north Indian referral hospital.
      ] estimated the annual direct medical cost of managing hypertension on an outpatient basis as US $386. Another study from India [
      • Karan A.
      • Engelgau M.
      • Mahal A.
      The household-level economic burden of heart disease in India.
      ] estimated the annual cost of all CVD care as US $563. When patients are admitted to hospital with CVD, significant costs are incurred with a range of US $677 to US $1523 [
      • Srivastava A.
      • Mohanty S.K.
      Age and sex pattern of cardiovascular mortality, hospitalisation and associated cost in India.
      ,
      • Malhotra S.
      • Grover A.
      • Verma N.K.
      • et al.
      A study of drug utilisation and cost of treatment in patients hospitalised with unstable angina.
      ,
      • Rao K.D.
      • Bhatnagar A.
      • Murphy A.
      Socio-economic inequalities in the financing of cardiovascular & diabetes inpatient treatment in India.
      ] per hospitalization. Among the studies that estimated hospitalization costs for CVD, the earlier studies tended to have lower costs than later studies (even after adjusting for price year). For the routine management of CVD, drug costs were estimated in four studies [
      • Malhotra S.
      • Karan R.S.
      • Pandhi P.
      • et al.
      Pattern of use and pharmacoeconomic impact of hypertensive drugs in a north Indian referral hospital.
      ,
      • Malhotra S.
      • Grover A.
      • Verma N.K.
      • et al.
      A study of drug utilisation and cost of treatment in patients hospitalised with unstable angina.
      ,
      • Jhaj R.
      • Goel N.K.
      • Gautam C.S.
      • et al.
      Prescribing patterns and cost of antihypertensive drugs in an internal medicine clinic.
      ,
      • Shastry R.
      • Sheetal U.
      • Sowjanya D.
      • et al.
      Cost analysis of drugs used in elderly patients with cardiovascular disorder.
      ]. For the management of hypertension, the range of annual drug costs was US $79 to US $231 [
      • Malhotra S.
      • Karan R.S.
      • Pandhi P.
      • et al.
      Pattern of use and pharmacoeconomic impact of hypertensive drugs in a north Indian referral hospital.
      ,
      • Malhotra S.
      • Grover A.
      • Verma N.K.
      • et al.
      A study of drug utilisation and cost of treatment in patients hospitalised with unstable angina.
      ,
      • Jhaj R.
      • Goel N.K.
      • Gautam C.S.
      • et al.
      Prescribing patterns and cost of antihypertensive drugs in an internal medicine clinic.
      ] and for CVD (defined broadly) the drug costs were estimated to be US $1.14/d, or US $415/y [
      • Shastry R.
      • Sheetal U.
      • Sowjanya D.
      • et al.
      Cost analysis of drugs used in elderly patients with cardiovascular disorder.
      ].
      Given that stroke care requires significant treatment and rehabilitation as an inpatient and that all three studies that captured costs for stroke care (Pakistan = 1, India = 2) sampled inpatients, it is not surprising that estimates of costs were some of the highest found in this review. The range of direct medical costs associated with each stroke [
      • Khealani B.A.
      • Javed Z.F.
      • Syed N.A.
      • et al.
      Cost of acute stroke care at a tertiary care hospital in Karachi, Pakistan.
      ,
      • Kwatra G.
      • Kaur P.
      • Toor G.
      • et al.
      Cost of stroke from a tertiary center in northwest India.
      ,
      • Marfatia S.
      • Monz B.
      • Suvarna V.
      • et al.
      Treatment costs of stroke related to nonvalvular atrial fibrillation patients in India—a multicenter observational study.
      ] was US $3,890 to US $28,451, with the range of direct nonmedical costs being US $357 to US $1552. Along with direct costs, indirect costs for transport and home adaptations for stroke were also substantial, estimated at US $872 to US $1719 per hospitalization [
      • Kwatra G.
      • Kaur P.
      • Toor G.
      • et al.
      Cost of stroke from a tertiary center in northwest India.
      ,
      • Marfatia S.
      • Monz B.
      • Suvarna V.
      • et al.
      Treatment costs of stroke related to nonvalvular atrial fibrillation patients in India—a multicenter observational study.
      ]. Overall costs of each stroke from a societal perspective were estimated [
      • Kwatra G.
      • Kaur P.
      • Toor G.
      • et al.
      Cost of stroke from a tertiary center in northwest India.
      ,
      • Marfatia S.
      • Monz B.
      • Suvarna V.
      • et al.
      Treatment costs of stroke related to nonvalvular atrial fibrillation patients in India—a multicenter observational study.
      ] to be US $5,966 to US $32,927. Given that the included studies only captured poststroke data for 6 or 12 months, the longer term cost to society is likely to be substantially more (particularly indirect costs).
      From a societal perspective, the direct and indirect costs of CVD are considerable. Direct medical costs for CVD were estimated [
      • Srivastava A.
      • Mohanty S.K.
      Age and sex pattern of cardiovascular mortality, hospitalisation and associated cost in India.
      ] to be US $10.2 billion for India in 2004. These data were then projected for the years 2016 and 2021 as US $14.4 billion and US $16.6 billion, respectively, which suggests a significant rise, in line with the growth in both population and prevalence. The authors emphasize that this impact falls predominantly on the working age population. Another study [
      • Abegunde D.O.
      • Mathers C.D.
      • Adam T.
      • et al.
      The burden and costs of chronic diseases in low-income and middle-income countries.
      ] modeled the estimated indirect costs of loss of productivity to the economies of India, Pakistan, and Bangladesh from CVD in 2015, which were estimated to be US $1.96 billion, US $0.21 billion, and US $0.14 billion, respectively.

       Annual Economic Costs of DM per Person

      There were 18 studies that estimated costs for DM in some of the countries of South Asia (see Table 3). Estimated costs for DM differed in terms of the type of costs that were included. Where costs were limited to outpatient care [
      • Kapur A.
      Economic analysis of diabetes care.
      ,
      • Kumar A.
      • Nagpal J.
      • Bhartia A.
      Direct cost of ambulatory care of type 2 diabetes in the middle and high income group populace of Delhi: the DEDICOM survey.
      ,
      • Rayappa P.
      • Raju K.
      • Kapur A.
      • et al.
      The economic cost of diabetes care: the Bangalore urban district diabetes study.
      ,
      • Chandra P.
      • Gogate B.
      • Gogate P.
      • et al.
      Economic burden of diabetes in urban Indians.
      ,
      • Khowaja L.A.
      • Khuwaja A.K.
      • Cosgrove P.
      Cost of diabetes care in out-patient clinics of Karachi, Pakistan.
      ,
      • Shrestha N.
      • Lohani S.P.
      • Angdembe M.R.
      • et al.
      Cost of diabetes mellitus care among patients attending selected outpatient clinics.
      ], a range of US $463 to US $951 was found for mean direct medical costs. In studies that disaggregated these totals further for subsamples within their data, the range of costs increased. For instance, one study [
      • Shrestha N.
      • Lohani S.P.
      • Angdembe M.R.
      • et al.
      Cost of diabetes mellitus care among patients attending selected outpatient clinics.
      ] in India reported that patients who used a government-funded outpatient service (compared with a private outpatient service) had lower costs at US $212 and a different study [
      • Ramachandran A.
      • Ramachandran S.
      • Snehalatha C.
      • et al.
      Increasing expenditure on health care incurred by diabetic subjects in a developing country: a study from India.
      ] identified mean direct costs of US $1046 for urban patients and US $655 for rural patients. When hospital admissions were included in direct medical costs, the range of mean direct medical costs rose slightly to US $575 to US $1216 [
      • Shobhana R.
      • Rama Rao P.
      • Lavanya A.
      • et al.
      Expenditure on health care incurred by diabetic subjects in a developing country–a study from southern India.
      ,
      • Rayappa P.
      • Raju K.
      • Kapur A.
      • et al.
      The economic cost of diabetes care: the Bangalore urban district diabetes study.
      ,
      • Chandra P.
      • Gogate B.
      • Gogate P.
      • et al.
      Economic burden of diabetes in urban Indians.
      ,
      • Sachidananda A.
      • Lin J.T.
      • Usha A.
      Health care cost incurred by patients of diabetes mellitus in a tertiary care hospital setting in coastal Karnataka district.
      ]. However, the largest direct medical costs reported by studies [
      • Tharkar S.
      • Satyavani K.
      • Viswanathan V.
      Cost of medical care among type 2 diabetic patients with a co-morbid condition—hypertension in India.
      ,
      • Ali S.M.
      • Fareed A.
      • Humail S.M.
      • et al.
      The personal cost of diabetic foot disease in the developing world--a study from Pakistan.
      ,
      • Clarke P.M.
      • Glasziou P.
      • Patel A.
      • et al.
      Event rates, hospital utilization, and costs associated with major complications of diabetes: a multicountry comparative analysis.
      ] were for patients with DM with complications, which had a range of US $246 to US $4597. The studies [
      • Ali S.M.
      • Fareed A.
      • Humail S.M.
      • et al.
      The personal cost of diabetic foot disease in the developing world--a study from Pakistan.
      ,
      • Clarke P.M.
      • Glasziou P.
      • Patel A.
      • et al.
      Event rates, hospital utilization, and costs associated with major complications of diabetes: a multicountry comparative analysis.
      ] reported that complications with lower costs (US $246–US $502) were nephropathy and peripheral vascular complications such as minor foot ulcers. Higher costs (US $2087–US $4597) related to severe foot ulcers, amputations, and coronary events.
      Similar patterns to direct medical costs were seen for direct nonmedical costs, with lowest costs for patients with DM seen in outpatients only [
      • Khowaja L.A.
      • Khuwaja A.K.
      • Cosgrove P.
      Cost of diabetes care in out-patient clinics of Karachi, Pakistan.
      ,
      • Shrestha N.
      • Lohani S.P.
      • Angdembe M.R.
      • et al.
      Cost of diabetes mellitus care among patients attending selected outpatient clinics.
      ] (range US $12–US $21), with higher costs for those who were also admitted to hospital [
      • Chandra P.
      • Gogate B.
      • Gogate P.
      • et al.
      Economic burden of diabetes in urban Indians.
      ] (US $258) and a greater range for those with complications [
      • Kumpatla S.
      • Kothandan H.
      • Tharkar S.
      The costs of treating long term diabetic complications in a developing country: a study from India.
      ,
      • Satyavani K.
      • Kothandan H.
      • Jayaraman M.
      • et al.
      Direct costs associated with chronic kidney disease among type 2 diabetic patients in India.
      ,
      • Tharkar S.
      • Devarajan A.
      • Kumpatla S.
      • et al.
      The socioeconomics of diabetes from a developing country: a population based cost of illness study.
      ,
      • Tharkar S.
      • Satyavani K.
      • Viswanathan V.
      Cost of medical care among type 2 diabetic patients with a co-morbid condition—hypertension in India.
      ] (cost per admission range US $50–US $470). A wide range of mean annual indirect costs was estimated by studies [
      • Tharkar S.
      • Devarajan A.
      • Kumpatla S.
      • et al.
      The socioeconomics of diabetes from a developing country: a population based cost of illness study.
      ,
      • Kapur A.
      Economic analysis of diabetes care.
      ,
      • Rayappa P.
      • Raju K.
      • Kapur A.
      • et al.
      The economic cost of diabetes care: the Bangalore urban district diabetes study.
      ,
      • Chandra P.
      • Gogate B.
      • Gogate P.
      • et al.
      Economic burden of diabetes in urban Indians.
      ,
      • Khowaja L.A.
      • Khuwaja A.K.
      • Cosgrove P.
      Cost of diabetes care in out-patient clinics of Karachi, Pakistan.
      ,
      • Shrestha N.
      • Lohani S.P.
      • Angdembe M.R.
      • et al.
      Cost of diabetes mellitus care among patients attending selected outpatient clinics.
      ] for DM and its complications, which ranged from US $9 up to US $2803.
      One study [
      • Tharkar S.
      • Devarajan A.
      • Kumpatla S.
      • et al.
      The socioeconomics of diabetes from a developing country: a population based cost of illness study.
      ] estimated intangible costs for DM, as a willingness to pay, using a bidding method. This study found that on average patients were willing to pay US $1936 a year to stay well. However, there was a significant range when broken down by number of complications (US $1452 for no complications to US $7260 for more than four complications) and by hemoglobin A1c (HbA1c) level (US $484 for HbA1c <7 to US $1936 for HbA1c >9).
      When combining costs to obtain an overall estimate, costs similarly varied. A number of studies [
      • Kumpatla S.
      • Kothandan H.
      • Tharkar S.
      The costs of treating long term diabetic complications in a developing country: a study from India.
      ,
      • Satyavani K.
      • Kothandan H.
      • Jayaraman M.
      • et al.
      Direct costs associated with chronic kidney disease among type 2 diabetic patients in India.
      ,
      • Tharkar S.
      • Satyavani K.
      • Viswanathan V.
      Cost of medical care among type 2 diabetic patients with a co-morbid condition—hypertension in India.
      ] modeled 2-year expenditure estimates on the basis of their data for total direct costs (medical and nonmedical), which included data for serious complications of DM. The range of these 2-year costs was US $2,420 to US $40,331 (or annual costs of US $1,210–US $20,166). Estimates from studies that additionally included indirect costs (to direct costs) tended to have much lower estimates because they were outpatient only or mixed outpatient and inpatient samples with fewer complications and so attracted lower costs. The range of total annual (direct and indirect) costs for these studies [
      • Kapur A.
      Economic analysis of diabetes care.
      ,
      • Rayappa P.
      • Raju K.
      • Kapur A.
      • et al.
      The economic cost of diabetes care: the Bangalore urban district diabetes study.
      ,
      • Khowaja L.A.
      • Khuwaja A.K.
      • Cosgrove P.
      Cost of diabetes care in out-patient clinics of Karachi, Pakistan.
      ,
      • Shrestha N.
      • Lohani S.P.
      • Angdembe M.R.
      • et al.
      Cost of diabetes mellitus care among patients attending selected outpatient clinics.
      ,
      • Akari S.
      • Mateti U.V.
      • Kunduru B.R.
      Health-care cost of diabetes in South India: a cost of illness study.
      ] was US $483 to US $2637. The study [
      • Tharkar S.
      • Devarajan A.
      • Kumpatla S.
      • et al.
      The socioeconomics of diabetes from a developing country: a population based cost of illness study.
      ] that estimated costs incorporating direct, indirect, and intangible costs estimated annual total costs of US $2048 (Table 3).

      Discussion

      Our review found broadly similar estimates of annual direct medical costs per person in South Asia for routine management of CVD compared with routine management of DM, with costs of US $386 for hypertension, US $563 for CVD, and US $463 to US $951 for DM outpatient care and US $575 to US $1216 for all DM care (Table 4). Importantly, when complications (such as stroke, severe foot ulcers, amputations, and coronary events) of these diseases occurred and required treatment, there was a substantial increase in costs. For severe complications of DM, the direct medical costs rose to US $2087 to US $4597. For the occurrence of each stroke, direct medical costs were estimated to be US $3,890 to US $28,451. These findings indicate that the financial burden of treating the complications of CVD and DM in South Asia form a significant proportion of the overall financial burden of these diseases. Total annual direct costs for CVD in India have been modeled at US $14.4 billion in 2016, which is set to increase to US $16.6 billion by 2020. An economic imperative therefore clearly exists for policymakers in South Asia to increase preventative approaches, both to decrease the incidence of DM and CVD and to increase early detection as well as provide access to evidence-based treatments to reduce the prevalence of costly complications.
      Table 4Summary of annual costs for cardiovascular disease (CVD) and diabetes mellitus (DM) in South Asia (US$ 2015)
      CVD
      Direct medical costsHypertension outpatient careUS$ 386
      Hypertension drugsUS$ 79 - 231
      All CVD care per patientUS$ 563
      All CVD drugsUS$ 415
      CVD Hospitalisation costsUS$ 677 - 1,523
      Per StrokeUS$ 3,890 - 28,451
      Direct non-medical costsPer StrokeUS$ 357 - 1,552
      Indirect costsPer StrokeUS$ 872 – 1,719
      Loss of (national) productivity due to CVDIndia US$ 1.96 billion
      Pakistan US$ 0.21 billion
      Bangladesh US$ 0.14 billion
      Total societal costsPer stroke (First 12 months)US$ 5,966 - 32,927
      DM
      Direct medical costsOutpatient careUS$ 463 - 951
      Including hospitalisationUS$ 575 - 1216
      Minor complicationsUS$ 246 – 502
      Major complicationsUS$ 2,087 – 4,597
      Direct non-medical costsOutpatient careUS$ 12 – 21
      Including hospitalisationUS$ 258
      Complications per admissionUS$ 50 – 470
      Indirect costsAll patientsUS$ 9 - 2,803
      Intangible costsWillingness to pay to stay wellUS$ 1,936
      The economic burden of these considerable direct costs borne by the patient as out-of-pocket expenditure (and increasingly by social insurance schemes) in the region is compounded by the indirect costs to individuals and families. Our review has identified total annual costs (direct and indirect) of US $1,210 to US $20,166 per person for DM and US $ 5,966 to US $32,927 for each patient suffering a stroke. At the national level, an estimate of total economic burden of DM in India was US $99.2 billion to US $148.2 billion. This economic burden at the societal level is set to grow considerably across South Asia as the rapid epidemiological transition is set to continue. The recent increases in rates of smoking among the young, sedentary lifestyles, and the consumption of added sugars and processed carbohydrates are projected to continue, increasing the prevalence of CVD and DM [
      • O’Keefe E.L.
      • DiNicolantonio J.J.
      • Patil H.
      • et al.
      Lifestyle choices fuel epidemics of diabetes and cardiovascular disease among Asian Indians.
      ,
      • Prabhakaran D.
      • Jeemon P.
      • Roy A.
      Cardiovascular diseases in India: current epidemiology and future directions.
      ]. The ability of countries in the region to address this rising burden will depend on their commitment to preventative economic and health policies such as taxation, education, food labeling, and health promotion in schools [
      • Moran A.
      • Vedanthan R.
      Cardiovascular disease prevention in South Asia: gathering the evidence.
      ,
      • Regmi P.
      • Kurmi O.
      • Aryal N.
      • et al.
      Diabetes prevention and management in South Asia: a call for action.
      ].
      The quality checklist that we developed for this study provided a wide range of quality scores for the included studies in our review. Studies with higher quality scores (>70%) tended to be those using more sophisticated research methods such as macroeconomic modeling, multicountry data collection, or estimation of indirect or intangible costs. Conversely, cost-of-illness studies had a wide range of quality scores, with some scoring very poorly. The findings from our quality checklist support the criticism of cost-of-illness studies, concerning their variable results and lack of reliability due to the heterogeneity of methods used [
      • Akobundu E.
      • Ju J.
      • Blatt L.
      • et al.
      Cost-of-illness studies: a review of current methods.
      ]. To improve the value of cost-of-illness studies, researchers should ensure that they use a robust methodological approach and follow recognized reporting standards (such as the Consolidated Health Economic Evaluation Reporting Standards statement [
      • Husereau D.
      • Drummond M.
      • Petrou S.
      • et al.
      Consolidated Health Economic Evaluation Reporting Standards (CHEERS)—explanation and elaboration: a report of the ISPOR Health Economic Evaluation Publication Guidelines Good Reporting Practices Task Force.
      ]). The main limitations of studies were the inadequate description of the study population and therefore uncertainty about their representativeness; a lack of categorization into commonly used economic categories (direct medical, direct nonmedical, indirect and intangible costs); the unit costs and the sources of cost data were often not stated; the quantity of resource utilization was not usually reported separately to the cost data; the perspective taken for the study was not often specified; and there was a lack of clarity about who bore the payment for costs identified.
      The time horizon for most studies was a single year. No studies presented longitudinal costs. Given the chronicity of CVD and DM, this is an important consideration. As life expectancy increases across South Asia [
      The World Bank
      ], patients can expect to live longer with these diseases with increasing risks of developing associated complications and therefore an escalation of related health care costs. It is unclear how accurate these annual estimates are for cumulative costs for patients and society over the individual’s life. Studies that calculate costs of CVD and DM over the medium to long-term in South Asia would be welcome.

       Study Limitations

      There are several limitations to our review. First, the results are dominated by studies from India. No studies provided data for Sri Lanka, Maldives, Afghanistan, and Bhutan, so the findings cannot easily be generalized to the region as a whole. Second, we only reviewed published literature and therefore some relevant data in gray literature (including nonindexed regional journals) may have been missed, limiting the comprehensiveness of our review. Third, we did not contact authors to obtain clarifying information, which may have enriched the included data and subsequent findings. Last, we did not exclude studies from our review on the basis of a low quality score from our checklist, so the internal validity of some studies is questionable. However, we have presented the quality scores to allow readers to interpret results accordingly. We recognize the limitations of using a checklist scoring system to assess the risk of bias and the fact that all criteria carried equal weight. Further research to explore weighting these criteria and to validate the scoring system could improve this tool.

      Conclusions

      This systematic review of the economic costs of CVD, DM, and their associated complications in South Asia has identified significant costs to individuals and families who bear the brunt of this financial burden currently. Marked increases in costs have been identified when complications of these chronic diseases occur, underlining the importance of secondary prevention approaches in chronic disease management. This review has summarized the current available evidence. However, given the variable quality of cost-of- illness studies included, the findings of this review are tentative. Higher quality studies from every country across the region, especially those that include longitudinal costs, are required to establish more robust cost estimates.

      Acknowledgments

      Source of financial support: This study was funded by COMDIS-HSD, a research consortium funded by UK aid from the UK government; however, the views expressed do not necessarily reflect the UK government’s official policies.

      Appendix A. Supplementary material

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