Summary
Background
To assess the cost-effectiveness and cost-utility of a population-level traditional and telemedicine combined age-related macular degeneration (AMD) and diabetic retinopathy (DR) screening program in rural and urban China.
Methods
Decision-analytic Markov models were conducted to evaluate the costs and benefits of traditional and telemedicine combined AMD and DR screening from a societal perspective. A cohort of all participants aged 50 years old and above was followed through a total of 30 1-year Markov cycles. Separate analyses were performed for rural and urban settings. Relevant parameters such as the prevalence of AMD and DR, transition probability, compliance with screening and treatment, screening sensitivity, specificity, utility, and mortality were collected from published studies specific to China, other Asian counties’ studies, or unpublished data sources such as the National Committee for the Prevention of Blindness. Costs of screening, full examination, and treatment come from the real medical environments and unified pricing of Beijing Municipal Medical Insurance Bureau. Primary outcomes were incremental cost-utility ratios (ICURs) using quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) using years of blindness avoided. One-way deterministic and simulated probabilistic sensitivity analyses were conducted to reflect uncertainty.
Findings
Under the status quo, the total expected medical costs for a 50-year-old patient with AMD or DR were $869·59 and $1,514·18 in rural and urban settings, respectively. Both traditional and telemedicine screening were highly cost-effective. In rural settings, ICURs were $191 (95% confidence interval [CI]: $66 to $239) and $199 (95% CI: $-12 to $217), and ICERs were $2,436 (95% CI: $1,089 to $3,254) and $2,441 (95% CI: $1,452 to $3,900) for traditional and telemedicine screening separately. Even more surprising, both screening strategies dominated no screening in urban settings. Our results were insensitive and robust to extensive sensitivity analyses. Among all acceptable screening intervals (from 1 to 5 years), annual screening could not only produce biggest benefits but also keep ICERs less than three times and one time the per capita gross domestic product (GDP) in rural and urban settings separately. When compared with traditional screening, ICERs of telescreening were less than three times the per capita GDP in rural settings ($2,559 to $8,809) and less than one time the per capita GDP in urban settings (less than $5,564), annual telescreening produced the biggest benefits, it could avert 119 and 270 years of blindness in rural and urban areas separately when 100,000 people were screened.
Interpretation
We performed decision-analytic Markov models for combined AMD and DR screening in rural and urban China, and the results showed that population-level combined screening for AMD and DR is likely to be highly cost-effective in both rural and urban China for people over 50 years old. Optimal screening may have an interval of every year based on teleophthalmology platforms. In the future, China should pay more attention to chronic eye diseases and the government should establish a sound chronic disease management system and make every patient enjoy equal medical services.
Funding
National Natural Science Foundation of China, NSFC (82171051); the Major Innovation Platform of Public Health & Disease Control and Prevention, Renmin University of China and Beijing Nova program (Z191100001119072).
Introduction
Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the global burden of disease study.
As the world’s most populous country, China is home to a large population with age-related eye diseases.
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In 2019, the number of patients with blindness caused by AMD and DR in China was 0·32 and 0·23 million respectively.
Currently, the burden of chronic eye diseases continues to increase as a result of population aging and increases in the prevalence of metabolic diseases
; moreover, the slow natural progression and asymptomatic early stages of AMD and DR make patients unaware of their vision changes until they have had the disease for a long time,
,
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which also imposes a significant economic burden on both individuals and society.
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Real-world DR screening program has been also recommended and nationally conducted among diabetes mellitus (DM) patients in China. Notably, the “Health Express-Diabetic Retinopathy Screening Project” and “China Diabetic Retinopathy Screening and Prevention Project” have helped a large number of undiagnosed DR patients to get screening and timely treatment. However, previous DR screening programs were mostly single-center studies targeted at the diabetic population and there is still a lack of population-based national DR screening program in China. As for AMD screening, there is limited evidence of real-world screening programs and cost-effectiveness analyses of AMD worldwide.
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Not to mention the combination of AMD and DR screening. We believe that combined screening may be a cost-effective option because it can not only detect a large number of patients with AMD or DR at early stage and enable them to receive early treatment, but also do not require additional medical costs. Although there have been implications that combined AMD and DR screening could be potentially cost-effective, there are also many challenges and barriers to carry out population-based large-scale screening programs across the country. It takes a lot of workforces of manpower and time to organize a nationwide screening program. Given the country’s complex national conditions such as large population, vast territory and uneven distribution of medical resources, it is difficult to carry out large-scale face-to-face screening programs in China. However, the rapid development of telemedicine has made it possible to achieve large-scale population-based screening. To date, the economic studies of combined traditional or telemedicine-based AMD and DR screening, which health care providers and policymakers required to consider, were inadequate. Our study evaluated the cost-effectiveness of population-based combined AMD and DR screening among Chinese participants aged 50 years and older in rural and urban settings separately, and compared the cost-effectiveness between traditional face-to-face screening and telemedicine-based screening. The results of our study may provide a reference for policy makers in planning eye disease screening programs.
Methods
Model overview
We built Markov models using TreeAge Pro (TreeAge Software; Williamstown, MA, USA) to evaluate the economic effects of traditional and telemedicine screening, and the primary results were incremental cost-effectiveness ratios (ICERs) and incremental cost-utility ratios (ICURs). To minimize the influence of the environment on the results, we set up Markov models for rural and urban areas and described the results separately.
Individuals were allowed to enter the model as either healthy (free of AMD and DR) or unhealthy (affected by AMD or DR) and could transition to death from any health state. The classifications of AMD and DR were based on international classification systems and were appropriately modified to fit our model (The Markov models for AMD and DR are shown in Appendix Figure 11). The Markov model for AMD was based on The Age-Related Eye Disease Study, which comprised 4 stages (from level 1 to 4).
In our study, level 1 and 2 were considered early AMD, level 3 was considered geographic atrophy (GA), and level 4 was considered NVAMD.
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Similarly, the Markov model for DR was modified according to the English National Screening Programme for Diabetic Retinopathy, which included non-sight-threatening DR (non-STDR), sight-threatening DR (STDR) and DME.
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Notably, because of incomplete data regarding unilateral and bilateral blindness, we combined the two stages, and defined blindness as presenting visual acuity
During each cycle, an individual either stayed in the same state or transitioned to a more severe phase. Treatment could reduce the risk of progressing from one state to another. Relevant parameters such as the prevalence of AMD and DR, transition probability, compliance with screening and treatment, screening sensitivity, specificity, utility, and mortality were collected from published studies specific to China, other Asian counties’ studies, or unpublished data sources (such as the National Committee for the Prevention of Blindness and the China Diabetic Retinopathy Screening and Prevention Project). Costs of screening, full examination, and treatment come from real-world eye disease screening programs, Beijing Tongren Hospital and unified pricing of Beijing Municipal Medical Insurance Bureau. The basic parameters and detailed ranges of fluctuations for the sensitivity analyses are listed in Appendix Tables 1–4.
Overview of screening strategies
No screening program. Patients did not receive a routine ophthalmic screening examination but might be opportunistically diagnosed and treated upon presenting at a hospital for another concern.
patients with NVAMD or DME were treated with anti-VEGF drugs,
scatter or panretinal photocoagulation was recommended for patients with STDR.
Telemedicine screening. Residents aged 50 years or older were invited to participate in a combined AMD and DR telescreening program in primary medical institutions (local medical examination centers or community hospitals). All examination programs were performed by primary eye care staff (nurses or medical assistants). It included auto-optometry, intraocular pressure measurement, and anterior segment and fundus photography using a digital nonmydriatic retinal camera. When all the tests were done, data were timely transmitted to a high-level hospital telemedicine platform via a secured network system (in line with the standards of Health Insurance Portability or Accountability Act or Privacy Information Management System Certification). Then two trained graders assessed the severity of the retinal images. Subsequently, one ophthalmologist made final diagnosis and sent the assessment report back to the primary care settings. Participants usually came back to collect their assessment report in two days. The further management of positive subjects was the same as that described for traditional screening programs. Under telescreening system, ophthalmologists did not come to the community and examine the participants face to face, which greatly saved time and money. Therefore, we assumed that more participants could be detected during the same time span than traditional screening.
Prevalence and transition probabilities
Most transition data were obtained from published studies specific to China (including Hong Kong); however, few data are available on the transition probabilities from one stage to the next stage for Chinese patients, several parameters were obtained from other Asian countries or unpublished data sources (the National Committee for the Prevention of Blindness and the China Diabetic Retinopathy Screening and Prevention Project).
Screening and intervention costs
Table 1Costs of AMD and DR related screening, full examination and treatment in rural and urban settings.
AMD=age related degeneration. DR=diabetic retinopathy. NVAMD=neovascular AMD. STDR=sight-threatening DR. DME= diabetic macular edema. NA=not applicable.
a=same with the rural setting.
Costs are given in US dollars.
According to “Handan Eye and General Health Study” and “Beijing Tongren Eye Centre Ocular Reading Centre and China Intelligent Ophthalmology Big Data Research Center”, the procedures of traditional and telemedicine screening were defined. Screening costs included equipment purchase and maintenance costs, labour costs for medical personnel, and residents’ costs for transportation. The annualized cost for fixed assets was calculated by assuming a life span of 5 years and no salvage value and they were collected from the Finance Department and Procurement Center of Beijing Tongren Hospital. The construction and maintenance cost of the telemedicine platform came from Beijing Tongren Eye Centre Ocular Reading Centre and China Intelligent Ophthalmology Big Data Research Center. We assumed that under traditional screening mode, each patient’s visit time was 20 min, eye care professionals worked 8 h a day for 250 days a year, so about 20,000 patients were screened annually. In telescreening mode, each patient was examined for 5 min by primary eye care staff, and a total of about 30,000 patients were screened annually. Since the participants were older than 50 years old, we assumed that they did not produce wage loss. Furthermore, the wage loss for accompanying family members were also not included in screening costs. The total costs per person for traditional screening were $2·79 and $2·64 in rural and urban settings, respectively, and the cost of telescreening in both settings was $1·52. The detailed compositions of Screening costs are provided in Appendix Table 6.
For further thorough examination, direct medical costs included the costs of ophthalmic examinations, equipment and wage for medical personnel; direct non-medical costs included costs of transposition, food, accommodation associated with the visits; indirect costs consisted of one accompanying family member’s wage loss according to time spent and per capita daily income in rural and urban areas. The costs of full examination were collected from unified pricing of Beijing Municipal Medical Insurance Bureau and the health care costs were under the Chinese government’s control and varied little from institution to institution. Due to the different examination items, the costs for AMD and DR patients were slightly different. What’s more, we assumed that rural patients needed to spend more time and transportation costs to go to tertiary hospitals or specialized ophthalmic hospitals for examination than urban patients. The detailed compositions of hospital-based examination costs are provided in Appendix Table 7.
Since we considered the societal costs of medical care, specific reimbursement rates were not relevant. The detailed compositions of treatment costs are provided in Appendix Tables 8 and 9.
Utilities and quality-adjusted life-years
0·97 for those with early AMD,
0·85 for those with GA,
and 0·57 for those with NVAMD.
Patients with non-STDR were assumed to have a utility value of 0·87,
and patients with DME and STDR were assumed to have utility values of 0·83 and 0·7,
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respectively. Patients with blindness were assumed to have a utility value of 0·26.
All of the values for the base and sensitivity analyses are shown in Appendix Table 3.
Other parameters
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We first used data from studies conducted in China and then considered data from other countries with similar conditions to China. A recent Chinese study suggested that telescreening could improve patients’ satisfaction and compliance to screening.
Since compliance with traditional community screening was 90·7% in rural settings and 82·5% in urban settings,
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we assumed increases in compliance with telemedicine screening to 95% and 90% in rural and urban settings, respectively. Since the role of telescreening was to widely screen patients who may have diseases in the population, the sensitivities of telescreening were the same as or higher than those of face-to-face screening but that the specificity was still lower than that of traditional screening. Natural mortality could occur at any stage in our model, and we used natural age-specific mortality rates.
Moreover, we considered the increased odds of mortality for patients with severe disease.
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We calculated the per capita GDP for rural ($7,000) and urban ($12,000) China in 2020 according to the overall per capita national GDP ($10,137·98), urbanization rate (0·61), and urban-rural ratio (2·64) of per capita disposable income (The detailed calculations are shown in Appendix Figure 13). We assumed a willingness to pay (WTP) of $21,000 per QALY gained for rural settings and $36,000 per QALY gained for urban settings.
Main outcomes
Sensitivity analysis
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The widths of the bars in the tornado diagrams represent the 5 factors that had the greatest influence on ICURs. A probabilistic sensitivity analysis enabled uncertainty across all of the variables to vary simultaneously. It was evaluated by taking 10,000 random draws from the probability distribution of each parameter, and the upper and lower bounds used in the 1-way probabilistic sensitivity analysis were used to define the distribution parameters. The reporting of methods and results conformed to the Consolidated Health Economic Evaluation Reporting Standards (Appendix Table 10).
Role of the funding source
The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Results
Table 2Base-case cost-utility and cost-effectiveness results from AMD and DR combined screening programs.
AMD=age-related macular degeneration. DR= diabetic retinopathy. QALY=quality-adjusted life-year. ICUR=incremental cost-utility ratio. ICER=incremental cost-effectiveness ratio. CI=confidence interval.
Costs are given in US dollars. Costs, QALYs, and years of blindness are defined as lifetime values per person, whereas incremental costs, incremental QALYs, ICURs, years of blindness avoided, and ICERs are defined as values per 100,000 people. ICURs and ICERs of traditional screening and telemedicine screening are calculated against no screening for rural and urban settings respectively. Negative ICURs and ICERs are regarded as dominating.
Figure 1Deterministic 1-way sensitivity analysis. Costs are given in US dollars. The top 5 parameters that caused the greatest impact on ICURs are shown in above figures. We did 1-way sensitivity analyses for rural (a-b) and urban (c-d) settings respectively, and for traditional (a and c) and telemedicine (b and d) screening respectively. The intervention was defined as cost-effective if it cost less than $21,000 in rural areas (per-capita GDP $7,000) and less than $36,000 in urban areas (per-capita GDP $12,000). GDP=gross domestic product. ICUR=incremental cost-utility ratio. QALY=quality-adjusted life-years. STDR= sight-threatening diabetic retinopathy. AMD= age related degeneration. GA= geographic atrophy. NVAMD= neovascular AMD. DME= diabetic macular edema.
Figure 2Probabilistic sensitivity analysis of the incremental costs and incremental QALYs. Costs are given in US dollars. Incremental benefits are defined as incremental QALYs. We did probabilistic sensitivity analyses for rural (a-b) and urban (c-d) settings respectively, and for traditional (a and c) and telemedicine (b and d) screening respectively. Dashed and solid lines represent one-time and three-times GDP, respectively. QALY= quality-adjusted life-year. GDP= gross domestic product.
Figure 3Cost-effectiveness acceptability curve of AMD and DR combined screening. Costs are given in US dollars. These curves show the cost-effective probabilities of no screening (green), traditional screening (purple) and telemedicine screening (pink) in rural (a) and urban (b) settings respectively. The threshold for cost-effective assumed for this analysis is labeled at $21,000 in rural setting and $36,000 in urban setting. GDP= gross domestic product. AMD=age-related macular degeneration. DR= diabetic retinopathy.
Table 3Cost-effectiveness of different screening intervals in rural and urban settings.
ICER=incremental cost-effectiveness ratio. Costs are given in US dollars. Costs and years of blindness are defined as lifetime values per person, whereas years of blindness avoided and ICERs are defined as values per 100,000 people. ICERs are calculated per 100,000 people screened against the previous screening interval scenario.
To determine the optimal screening strategies, we also evaluated the costs and benefits of telemedicine screening versus traditional screening. For all acceptable screening intervals, telemedicine screening resulted in greater decreases in the number of years of blindness, and annual telescreening avoided the most years of blindness per 100,000 people screened than traditional screening (119 and 270 years in rural and urban settings, respectively). Since the ICERs were always less than three times the per capita GDP in rural areas (between $2,559 and $8,809) and one time the per capita GDP in urban areas (less than $5,564), annual telescreening was the best screening strategy in both rural and urban China (Appendix Table 12).
Discussion
The results of our study show that population-based combined AMD and DR screening using either a traditional or telemedicine approach was highly cost-effective in rural and urban China, and annual screening avoided the most years of blindness. Since telescreening yielded the most effectiveness compared with traditional screening, it was the best option under the current WTP threshold. In broad sensitivity analyses, our results were robust and insensitive to a wide range of changes in parameters.
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A recent economic study in China also confirmed that DR screening for patients with newly diagnosed type 2 DM was cost-effective at an ICER of $7,312 per QALY.
However, it is difficult to determine whether screening for AMD would be cost-effective. Studies in the United Kingdom, South Korea and Hong Kong have concluded that AMD screening was cost-effective.
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But one study in Japan pointed that although AMD screening was highly effective in reducing the total number of patients with blindness, and early screening programs were more effective than complementary therapy, AMD screening was still not cost-effective because the ICER exceeded the WTP threshold in Japan.
In addition, few studies have explored the cost-effectiveness of AMD screening or combined screening for different eye diseases in mainland China.
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Secondly, due to the low detection rate and high blindness rate of AMD and DR, early detection and timely treatment can delay the development of the disease to the severe stage and reduce the economic burden on the government and individuals.
Third, although foreign studies generally believe that early AMD screening is not cost-effective, combined AMD and DR screening does not add additional costs, which means that combined screening may be cost-effective in China. Forth, combined screening might be cheaper in China, largely because China’s labor costs are lower than those of high-income countries.
The guidelines of many countries recommend annual ophthalmic examinations for patients with DM.
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Many developed countries, such as the United Kingdom, found that annual screening or more frequent screening for those with background DR could save up to 50% of the potential sight years lost.
In contrast, a recent study in mainland China demonstrated that screening every 4 years produced the greatest increase in QALYs, while the marginal cost resulted in ICERs of annual screening exceeding the WTP threshold.
Similarly, another cost-effectiveness analysis of DR screening in the United States suggested that the marginal benefit offered by annual screening for the entire United States population was so small that annual screening may be overzealous and unnecessary.
Considering the current situation, Wu et al.
and Vijan et al.
recommended that screening strategies should be adjusted according to the patient’s risk factors, such as the age at DM diagnosis and glycemic control. When patients were diagnosed with DM at an age
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For instance, real-time video consultations between hospital-based ophthalmologists and emergency physicians or other specialists can help emergency patients get timely evaluations and referrals, improving diagnostic accuracy.
What’s more, the development of self-screening and home monitoring based on smartphones is a convenient and real-time telescreening mode that can improve patient compliance and achieve regular monitoring of disease progression.
In recent years, China has gradually implemented some DR screening programs. For example, the telemedicine-based “China Diabetic Retinopathy Screening and Prevention Project”, organized by the National Committee for the Prevention of Blindness and the Chinese Society of Microcirculation, has covered 577 hospitals in 29 provinces and screened more than 800,000 diabetes patients. Actually, the Chinese government not only pays attention to eye disease screening, but also strives to build a complete chronic eye disease management system. Chronic eye disease management is a patient-centered chronic disease management system that follows timely, coordinated, continuous, safe and effective mode. However, there are still many deficiencies in the management of chronic eye diseases in China. One the one hand, the working mechanism of chronic eye disease prevention and control led by the government and participated of the whole society has not been completely established. On the other hand, the implementation of the national basic medical insurance policy in different provinces is not equal. In the future, it is necessary to establish a complete telemedicine-based chronic eye diseases diagnosis and treatment system that includes screening, referral, treatment and follow-up, and promote equitable distribution of health resources. We referred to the relevant literature and proposed a process for telemedicine-based chronic eye disease management system in the future
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(Appendix Figure 14).
Therefore, the government needs to constantly improve network security protection system and related policies to ensure residents’ information security well protected.
This study has various strengths. First, to the best of our knowledge, this is the first study to analyze the costs and effectiveness of AMD and DR combined screening programs and compare the cost-effectiveness of traditional face-to-face community screening and telemedicine screening using a Markov model. Second, all of the parameters used in the models were from reliable real-world studies. As such, our findings provide practical recommendations for governments and policy makers in China and might also be applicable to other low- and middle-income countries where blindness-causing eye diseases are prevalent and regular screening programs are lacking. Third, considering the uneven distribution of the population and medical resources in China and the different incidences of diseases in rural and urban areas, we developed models and analyzed the cost-effectiveness for rural and urban settings separately. Fourth, due to the rapid aging of the population and changes in people’s living habits, metabolic and age-related eye diseases are gradually becoming the main source of eye disease burden in China. Therefore, we extended the target population to all Chinese residents over 50 years old, not just those with DM, with the aim of detecting not only eye diseases but also improving the timely diagnosis and treatment of metabolic diseases.
Second, to better describe the disease progression more clearly, we simplified the national disease grading system according to the actual situation. Third, the additional benefits of combined screening, such as detection and treatment of other common blindness-causing diseases, were not considered in our study. Fourth, due to gaps in the existing literature, we used some parameters from non-Chinese studies or expert advice from the National Committee for the Prevention of Blindness. However, extensive sensitivity analyses showed that our results were robust and insensitive to wide range fluctuation of parameters.
We believe that combined screening for multiple blindness-causing eye diseases might be more cost-effective and ideal for clinical application, and it has the potential to become the main trend of eye disease screening programs in the future. Therefore, health economic studies should be conducted to evaluate the cost-effectiveness of multimodal screening for common blindness-causing eye diseases (i.e., glaucoma, DR, AMD, retinal detachment and other retinal diseases), which could provide adequate evidence for health care providers and policymakers. In addition, the impact of gender, age groups, economic and medical level in different regions on cost-effectiveness should also be taken into consideration.
Contributors
Conception and design: Hanruo Liu,Ningli Wang, Jianjun Tang.
Acquisition or interpretation of data: Ruyue Li, Ziwei Yang, Yue Zhang, Weiling Bai. Runzhou Sun, Yifan Du.
Drafting of the manuscript: Ruyue Li.
Critical revision of the manuscript for important intellectual content: Hanruo Liu, Ningli Wang, Jianjun Tang.
Statistical analysis: Ruyue Li, Ziwei Yang.
Obtained funding: Hanruo Liu.
Supervision: Hanruo Liu, Ningli Wang, and Jianjun Tang had accessed and verified data. Hanruo Liu, Ningli Wang, and Jianjun Tang were responsible for the decision to submit the manuscript.
