Real-World Cost Evaluation of Conbercept vs Ranibizumab for Retinal and Choroidal Vascular Diseases from 2021 to 2024: Evidence from Societal and Medical Insurance Perspectives

Real-World Cost Evaluation of Conbercept vs Ranibizumab for Retinal and Choroidal Vascular Diseases from 2021 to 2024: Evidence from Societal and Medical Insurance Perspectives | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Real-World Cost Evaluation of Conbercept vs Ranibizumab for Retinal and Choroidal Vascular Diseases from 2021 to 2024: Evidence from Societal and Medical Insurance Perspectives Hua Yan, Yuanyuan Liu, Jinhua Zhao, Jinglin Huang, Yawen Qin, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7266099/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Leading blindness causing retinal and choroidal vascular diseases including age-related macular degeneration (AMD), retinal vein occlusion (RVO), diabetic macular edema (DME), and choroidal neovascularization secondary to pathologic myopia (PM) treated with Conbercept and Ranibizumab impose a heavy economic burden. The Markov model was constructed based on best-corrected visual acuity, real-world injection frequencies in Tianjin (2021–2024), costs, utility values, and transition probabilities derived from clinical trials. From both the societal and medical insurance perspectives, conbercept was more cost-effective than ranibizumab in BRVO, CRVO, DME, and PM with Incremental cost-effectiveness ratios (ICER) as 442,423.176, -2,429,628.701, -69,339.384, 410,661.276 RMB/QALY under the societal perspective, and − 370,506.503, -2,491,085.315, -66,253.162, -432,736.475 RMB/QALY under the medical insurance perspective in 2023, respectively. In contrast, ranibizumab consistently showed greater effectiveness for AMD, with conbercept's ICER reaching 53,927.073 RMB/QALY in 2024 under the medical insurance perspective. These findings provide economic evidence to support value-based decision-making anti-VEGF therapy in China. Health sciences/Health care/Health care economics Health sciences/Diseases/Eye diseases/Retinal diseases Conbercept Ranibizumab Cost-effectiveness analysis Markov model Medical insurance perspective Figures Figure 1 Introduction Retinal and choroidal vascular diseases, including age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) and choroidal neovascularization (CNV) secondary to pathologic myopia (PM), represent leading causes of irreversible vision loss in adults globally, imposing a substantial public health burden. By 2040, AMD strongly associated with aging is projected to affect over 288 million people worldwide, with late-stage neovascular AMD contributing to severe vision impairment, particularly in high-income countries and rapidly aging populations like China, where its prevalence is rising sharply alongside demographic shifts 1 . DME affects approximately 5.5% of individuals with diabetes, with China bearing a high prevalence of diabetes 11.9% to 12.4% by WHO and ADA criteria. 2 3 RVO affects about 16 million people globally, and its prevalence in Chinese adults over 40 years of age reaches nearly 1.9%, largely associated with hypertension and cardiovascular comorbidities. 4 5 . PM remains a significant cause of blindness in younger populations, with a rising incidence driven by urbanization and near-work intensity. 6 Anti-vascular endothelial growth factor (anti-VEGF) agents have revolutionized the treatment for the above diseases on vision restoration. Ranibizumab, a monoclonal antibody fragment targeting VEGF-A, has been firstly adopted as a first-line therapy due to its validated efficacy in stabilizing and improving visual acuity 7 .Conbercept, a novel recombinant fusion protein independently developed in China, has emerged as a promising alternative with higher VEGF-binding affinity and broader target specificity (VEGF-A, VEGF-B, and placental growth factor). Since 2017, conbercept has been included in China's National Reimbursement Drug List, it has been demonstrated non-inferiority to ranibizumab in visual improvement and exhibits superior therapeutic responses in certain subtypes, such as PM-related CNV 8 9 . However, evidence comparing the long-term cost-effectiveness of conbercept versus ranibizumab across multiple indications remains sparse, particularly in real-world clinical settings. The cumulative burden of these diseases demanding multiple injections of anti-VEGF agents exacerbates healthcare disparities, particularly in low-resource settings 10 . Costs of anti-VEGF agents is significant aspect of healthcare system expenditures may have an especially large potential economic burden in India and China. The cost of treating all Chinese patients with ranibizumab and conbercept will be projected to 2.0% and 0.64% of the Chinese GDP, respectively 11 . In China alone, vision loss from AMD and DME costs an estimated $7.1 billion annually in direct healthcare expenditures and productivity losses 12 . The economic impact is equally profound, with direct medical costs and productivity losses associated with vision impairment amplifying systemic challenges in healthcare allocation. This study aims to evaluate the cost-effectiveness of conbercept versus ranibizumab for nAMD, DME, RVO, and CNV secondary to PM using real-world injection and cost data from hospitals in Tianjin, China. A Markov model was constructed to simulate long-term disease progression, incorporating local epidemiological, utility, and cost parameters. Importantly, this analysis was conducted from both the societal perspective and the medical insurance perspective to comprehensively capture the economic implications for both patients and the healthcare system. By estimating quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs), the study seeks to inform value-based clinical decisions and reimbursement strategies under China’s evolving healthcare policy landscape. Methods The Markov model was employed in this study to evaluate the cost-effectiveness of conbercept and ranibizumab in the treatment of various retinal diseases, including RVO, DME, PM, and AMD. The model simulated the natural progression of each disease and performed multiple cycles based on the transition probabilities between health states. Each Markov cycle was set to one year, with a total time horizon of 10 years to capture the long-term clinical and economic impacts. Baseline characteristics of the simulated population were informed by previous studies, and model inputs were constructed using real-world data on injection frequency, treatment efficacy, and health utility values for each disease. Health states were defined according to best-corrected visual acuity (BCVA) levels specific to each condition. The structure of health states and transition pathways is illustrated in Figure 1. Definition of Four Disease DME characterized by hard exudates and edema within the macula secondary to damage to retinal microvasculature can be detected by clinical examination or with OCT. Neovasular AMD was defined as retinal hemorrhages or exudates in macular in patients older than 50 years old, with detailed images of retinal structure and fluid offered by OCT, and neovascularization by visualizing dye leakage from retinal blood vessels confirmed on fluorescein angiography 13 . RVO can be defined as a retinal vascular disorder characterized by congestion and dilatation of the retinal veins with subsequent retinal hemorrhages and edema, retinal ischemia including cotton wool spots, retinal exudates and macular edema, classified as CRVO, BRVO, and HRVO depending on the site of occlusion 14 .Myopic Choroidal Neovascularization usually occur subfoveally due to perturbation of the retinal pigment epithelium (RPE)–Bruch membrane complex, especially in patients with PM presenting lacquer cracks and patchy atrophy within one disk diameter of the fovea 15 . Baseline Health States Health states in the model were defined according to BCVA, with disease-specific classification standards applied. The number and boundaries of health states varied slightly across conditions to reflect clinical practice and prior research. The baseline distribution of patients across BCVA health states was derived from the PHOENIX study (AMD), BLOSSOM and CAMELLIA trials (BRVO and CRVO), the SAILING study (DME), and the SHINY study (PM). These data were used to initialize the disease-specific Markov cohorts and are summarized in Table S1(Appendix Part B). Transition Probabilities The transition probabilities represent the conditional likelihood of a patient shifting from one visual acuity state to another over a given time period. In this study, the probabilities reflect transitions over a 1-year Markov cycle and were used to simulate the natural progression or improvement of vision under treatment. The transition probability matrix for each disease—AMD, BRVO, CRVO, DME, and PM—is shown in Table 1. These matrices represent the probabilities of BCVA changes over a 12-month period. The probability estimates for both conbercept and ranibizumab were derived from published clinical trial data and relevant literature to reflect real-world treatment outcomes. Utilities Health utility values were used to reflect the quality of life associated with different levels of visual function. In this study, utility values corresponding to various levels of BCVA impairment were assigned to each health state across the five disease indications. All utility values were obtained from previously published literature. Specifically, utility values for AMD were directly derived from validated sources. For BRVO, CRVO, DME, and PM, utility scores were similarly extracted from published studies that reported utility estimates for corresponding BCVA-defined health states. The utility values ranged from 0.805 to 0.325 for BRVO/CRVO, 0.756 to 0.325 for DME, and 0.756 to 0.325 for PM. A summary of utility values for all indications is provided in Table 2. Costs Costs were evaluated from both the societal perspective and the medical insurance perspective. From the societal perspective, total costs included direct medical costs (such as drug acquisition, injection procedures, outpatient visits, and examinations) as well as indirect costs due to productivity loss. Indirect costs were calculated based on the average number of missed workdays associated with different levels of visual impairment and the corresponding daily wage. The number of missed workdays was derived from published literature, and average wages were adjusted according to 2021 and 2024 data. From the medical insurance perspective, only direct medical costs covered by the insurance system were considered, primarily including drug costs and clinical treatment expenses. Unit prices for conbercept and ranibizumab were obtained from the most recent National Reimbursement Drug List (NRDL). All costs were presented in Chinese Yuan (CNY) and discounted at an annual rate of 3.5%. The model adopted a 1-year cycle length and a 10-year time horizon. Detailed cost parameters are provided in Table S1 (Appendix Part B). Real-World Injection Frequencies The average annual number of intravitreal injections for both conbercept and ranibizumab from 2021 to 2024 was derived from real-world data collected through the medical insurance system of Tianjin, China. These data were based on actual treatment records of patients with AMD, BRVO, CRVO, DME, and PM during the specified period and were used to reflect clinical practice more accurately. The injection frequencies varied by year and disease type, and the average values were applied in the model to estimate annual drug-related costs. Detailed injection frequencies are provided in Table 3. Sensitivity Analysis To assess the robustness of the model outcomes, three types of sensitivity analyses were performed. First, a two-way sensitivity analysis was conducted by simultaneously varying the prices of conbercept and ranibizumab by ±10% to evaluate the impact of drug price fluctuations on cost-effectiveness outcomes. Second, a probabilistic sensitivity analysis was conducted using Monte Carlo simulation with 1,000 iterations. In this analysis, costs were assumed to follow a gamma distribution. Parameters such as drug costs, utilities, and transition probabilities were assigned appropriate probability distributions based on published sources. Cost-effectiveness acceptability curves (CEACs) were generated to illustrate the probability that each treatment strategy would be cost-effective across a range of WTP thresholds. In addition, perform one-way sensitivity analyses on the number of injections for each of the two treatment regimens respectively, with the variation range defined as the minimum and maximum number of injection in the real world, and present the results in tabular form. Results 3.1 Cost-Effectiveness from the Societal Perspective (2021–2024) The cost-effectiveness results of ranibizumab and conbercept for five retinal diseases from 2021 to 2024 are showed in Table 4 to Table 7. In 2021 (see in Table 4), conbercept showed economic advantages in the treatment of BRVO and CRVO, with ICERs of -2,632,799.096 RMB/QALY and -4,982,016.597 RMB/QALY, respectively. For AMD, the ICER was 4,2404.890 RMB/QALY, which was far below the commonly used willingness-to-pay threshold of three times the per capita GDP, indicating acceptable cost-effectiveness. For DME, the ICER was 101,975.929 RMB/QALY, which was far below the commonly used willingness-to-pay threshold of three times the per capita GDP, indicating acceptable cost-effectiveness. However, in PM, the ICER exceeding the willingness-to-pay (WTP) threshold indicates that conbercept lacks cost-effectiveness In 2022 (Table 5), for AMD, although the ICER was positive (5,964.559 RMB/QALY), which was far below the commonly used willingness-to-pay threshold of three times the per capita GDP, indicating acceptable cost-effectiveness. Conbercept continued to demonstrate favorable cost-effectiveness in the treatment of BRVO and CRVO, with ICERs of -480,496.496 RMB/QALY and -7,097,246.654 RMB/QALY, respectively. The ICER for DME was -61,046.505 RMB/QALY, remaining well below the threshold of three times the per capita GDP. In the treatment of PM, conbercept was both less costly and more effective than ranibizumab, with an ICER of -625,677.703 RMB/QALY. In 2023 (see in Table 6), conbercept remained less costly and more effective than ranibizumab in the treatment of BRVO and CRVO, with ICERs of -442,423.176 RMB/QALY and -2,429,628.701 RMB/QALY, respectively. For DME, the ICER was -69,339.384 RMB/QALY, which was below the commonly used cost-effectiveness threshold. In the case of PM, conbercept was also associated with lower cost and better effectiveness, with an ICER of -410,661.276 RMB/QALY. For AMD, the ICER was -3,790.354 RMB/QALY; although the value was negative, the difference in effectiveness between the two treatments was limited, and no significant cost-effectiveness advantage was observed. In 2024 (see in Table 7), conbercept remained less costly and more effective than ranibizumab in the treatment of CRVO and PM, with ICERs of -1,247,442.826 RMB/QALY and -587799.624 RMB/QALY, respectively. For DME, the ICER was -630.846 RMB/QALY, remaining well below the threshold of three times the per capita GDP. In BRVO, the ICER was 214,491.169 RMB/QALY, also within the acceptable range for cost-effectiveness. For AMD, the ICER was 45,236.924 RMB/QALY, indicating that ranibizumab had greater effectiveness than conbercept in that year, albeit at a higher cost. But the ICER was below three times the per capita GDP, suggesting that conbercept was cost-effective in this context. 3.2 Cost-Effectiveness from the Medical Insurance Perspective (2021–2024) From the medical insurance perspective in 2021, ranibizumab incurred higher costs than conbercept for AMD, BRVO, and CRVO (Table 8). Ranibizumab provided only marginal QALY gains over conbercept in AMD, corresponding to incremental cost-effectiveness ratios of approximately ¥40,094.727 gained (Table 8). In BRVO and CRVO, ranibizumab offered no additional effectiveness compared to conbercept but was more costly (Table 8). Conbercept provided only marginal QALY gains over ranibizumab in PM, corresponding to incremental cost-effectiveness ratios of approximately ¥517,369.207 gained, suggesting that conbercept was not cost-effective. For DME, conbercept incurred higher costs than ranibizumab, however, with an incremental cost-effectiveness ratio of ¥77,713.64 gained, conbercept demonstrates a favorable cost-effectiveness profile relative to ranibizumab when treating DME. In 2022, ranibizumab remained more costly than conbercept under the medical insurance perspective across all five indications (Table 9). Small QALY advantages for ranibizumab was still observed in AMD, with corresponding ICERs declining to ¥4,724.899 (Table 9). In BRVO, CRVO, DME, and PM, conbercept continued to achieve comparable effectiveness at a lower cost, so conbercept remained a dominated option in those indications (Table 9). In 2023, conbercept had lower total costs than ranibizumab for RVO、DME and PM from the medical insurance perspective (Table 10). The ICERs for ranibizumab (versus conbercept) in AMD further decreased to ¥ -9,382.256 per QALY, reflecting the reduced cost difference (Table 10). Ranibizumab remained dominated by conbercept in BRVO, CRVO, DME, and PM in 2023, as conbercept provided similar or greater health gains at lower cost in those indications (Table 10). By 2024, ranibizumab’s cost relative to conbercept was further reduced, though conbercept still incurred a lower total cost in each indication (Table 11.). Ranibizumab continued to confer a slight effectiveness benefit in AMD, yielding ICERs of about ¥53,927.073 per QALY gained, when compared to conbercept (Table 11). For BRVO, CRVO, DME and PM, conbercept remained the lower-cost strategy without any loss of effectiveness, and conbercept thus remained dominated in those cases (Table 11). 3.3 Sensitivity Analysis Sensitivity analysis results are presented in Appendix Part B. The two-way sensitivity analysis showed that cost-effectiveness conclusions remained stable under a ±10% variation in drug prices. Probabilistic sensitivity analysis, using Monte Carlo simulation with 1,000 iterations and assuming gamma-distributed costs, further confirmed the robustness of the base-case results. When the price remains and the number of drug injections changes, conbercept has a certain cost-effectiveness in treatment of AMD、RVO、DME and PM with similar number of injections (Appendix Part B). Discussion This study assessed the cost-effectiveness of conbercept compared to ranibizumab for the treatment of four major retinal and choroidal vascular diseases—AMD, DME, BRVO, CRVO and CNV secondary to PM— based on real-world data from Tianjin, China. The analysis incorporated both societal and medical insurance perspectives and revealed that conbercept was more cost-effective in most indications, particularly in DME, RVO, and PM. Although the QALY gains between the two agents were similar, conbercept consistently demonstrated lower total treatment costs and favorable incremental cost-effectiveness ratios (ICERs) across multiple scenarios. These findings support the use of conbercept as a cost-effective therapeutic alternative in clinical settings, especially in resource-limited healthcare systems. Conbercept and ranibizumab have been demonstrate comparable efficacy in improving visual acuity and reducing central retinal thickness (CRT) in retinal vascular diseases such as DME, nAMD and RVO by Multiple RCTs and real-world observational studies. PHOENIX study indicated that conbercept achieved inferior visual gains to ranibizumab in nAMD at same therapeutic regiments as once monthly for the first 3 months, then once quarterly until month 12 (3 + Q3M), with mean BCVA improvements of + 9.98 vs. -0.2 letters at 12 months, respectively 16 . In DME, although patients treated with aflibercept benefited more on BCVA improvement at one year follow up compared to conbercept and ranibizumab, who achieved similar CRT reduction (∼120–150 µm) and vision stabilization at two years 17 18 . Conbercept had higher mean CMT change effects and BCVA improvement at 1month after treatment in patients with RVO compared to ranibizumab, which was comparable after 12 months 19 . As reported, conbercept may require fewer injections due to its longer intraocular half-life and greater bioavailability attributing to an additional antigen-binding fragment (Fab) with specificity for VEGFA as 0.47 ng/ml conbercept detected in retina even 56 days post singe intravitreal injection, but ranibizumab was undetectable since day 45. Hence longer intervals of treatment potentially enhanced patient compliance and lowered costs 20 16 . Although ranibizumab has broader global validation, conbercept offers cost advantages in certain markets, especially in China 8 . By now, the price of conbercept (3452.8RMB/0.5 mg) has been reduced about 10% lower than ranibizumab (࿥3673.5RMB/0.5 mg) in China. From the perspective of medical insurance payment, the economic advantages of conbercept in BRVO, CRVO, DME, and PM are also significant. Among these four indications, conbercept not only has lower direct medical costs but also has clinical effects that are comparable or even superior to Ranibizumab 21 , with the ICER being below the willingness-to-pay threshold in most cases 22 , indicating its clear economic feasibility within the scope of medical insurance payment. In contrast, in the treatment of AMD, although conbercept has relatively lower costs, its therapeutic effects are generally inferior to Ranibizumab, with the ICER mostly being positive, suggesting that it does not have a significant economic advantage under medical insurance in this indication 23 . Therefore, it is recommended that in the formulation of medical insurance policies, different indications should be considered differentially, and conbercept should be prioritized for payment support in indications such as RVO, DME, and PM. However, for AMD, a more cautious approach is needed, and conditional or restricted payment strategies should be established based on actual therapeutic effects and population adaptability. When evaluating the cost-effectiveness of medical treatments, it is crucial to consider different perspectives, including the society and health insurance. From the societal perspective, the analysis not only includes direct medical expenditures but also comprehensively considers self-funded costs and indirect economic losses, i.e. traffic costs, lost wages, which may contribute to reflect the impact of a treatment regimen on the overall allocation of social resources 24 25 . By contrast, the perspective of health insurance mainly focuses on the expenditure of the insurance fund and emphasize the direct cost-effectiveness of the medicine. This difference of perspective may lead to varying conclusions regarding the cost-effectiveness of the treatment regimen 26 , as the economic performance of conbercept in PM (presumably a specific medical condition) in our study. In 2021, it did not demonstrate an advantage from the societal perspective, but it has shown preliminary cost-effectiveness due to lower insurance costs from the health insurance perspective with this advantage gradually strengthening over time. Likewise, in individual year of DME cost, the ICER of conbercept was close to the threshold from the societal perspective, but it remained within the acceptable range from the health insurance perspective. Hence, results of our study strongly suggested that applicability of evaluation perspective should be carefully balanced according to the characteristics of different diseases when formulating payment policies or including medicine in the health insurance catalog 27 28 .Different from previous analysis based on the randomized clinical trials 29 30 , real-world evidence (RWE) can provide crucial data on real-world efficacy, safety, and adherence, which are essential for determining the cost-effectiveness of medicine across diverse patient populations. Accordingly, policymakers also benefit from RWE-informed cost-effectiveness analyses to make more informed reimbursement decisions and ensure medical funding being allocated to interventions patients demanded. There are a few limitations for this study. This retrospective design may lead potential biases in treatment adherence documentation and missing data. Our data from hospitals in Tianjin, which may not generalize to regions with differing healthcare pricing structures (e.g., Europe or North America). Although the data from Tianjin is representative, considering geographical disparities in healthcare services, future economic evaluations based on nationwide multi-center studies or different regional healthcare insurance systems are recommended to enhance the external generalizability of the research. To our knowledge, this is the first cost-effectiveness analysis to incorporate multiple retinal and choroidal vascular diseases using real-world clinical and economic data. By enabling cross-indication comparisons and capturing outcomes under both societal and medical insurance perspectives, this study provides valuable insights for value-based decision-making and indication-specific reimbursement design in ophthalmic care. Conclusion Overall, this study demonstrates that conbercept is a cost-effective alternative to ranibizumab in the treatment of several major retinal and choroidal vascular diseases, particularly DME, RVO, and CNV secondary to PM. By adopting both societal and medical insurance perspectives, our findings provide comprehensive economic evidence to support value-based treatment selection and indication-specific reimbursement decisions in ophthalmic care. Declarations Competing Interest Declaration All authors in this study declare no conflicts of interest. Ethical Approval Statement This study has been approved by the Ethics Committee of Tianjin Medical University General Hospital, China with No. IRB2020-YX-160-01. Author contributions HY conceived this study and take responsibility for its all aspects. YYL and ZC designed the study. YYL, JHZ, YWQ, YMH, WZ, HH and CYY organize the implementation of the project. JHZ, YWQ and HJF were involved in data management and statistical analysis. YYL and JHZ wrote the first and subsequent drafts of the report. HY and ZC were the co-principal investigators of the project, reviewed and commented on drafts of the report. HY and ZC supervised its conduct and data analysis, and provided comments on all drafts. All authors interpreted data, contributed to critical revisions, and approved the final version of the Article. Acknowledgements We appreciated all authors contributed to this work. Fundings This work is supported by Tianjin Science & Technology Foundation (22PTZWHZ00030) and National Natural Science Foundation of China (82330031) to HY, Tianjin Medical University General Hospital Excellent Youth Science Fund (22ZYYYQ05) to YYL, Tianjin Natural Science Foundation Youth Project (23JCQNJC01180) to HH, and Beijing-Tianjin-Hebei Special Project (23JCZXJC00140) to YCY. References Wong WL , et al. 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Supplementary Files supplements.docx Supplements TABLE1Bestcorrectedvisualacuity.docx Table2Healthutilityvalue.docx Table3Thenumberofinjectionsofconberceptandranibizumabinrealworldscenario.docx Table4Thecosteffectivenessanalysesofconberceptandranibizumabfromthesocietalperspectivein2021.docx Table5Thecosteffectivenessanalysesofconberceptandranibizumabfromthesocietalperspectivein2022.docx Table6Thecosteffectivenessanalysesofconberceptandranibizumabfromthesocietalperspectivein2023.docx Table7Thecosteffectivenessanalysesofconberceptandranibizumabfromthesocietalperspectivein2024.docx Table8Thecosteffectivenessanalysesofconberceptandranibizumabfromthemedicalinsuranceperspectivein2021.docx Table9Thecosteffectivenessanalysesofconberceptandranibizumabfromthemedicalinsuranceperspectivein2022.docx Table10Thecosteffectivenessanalysesofconberceptandranibizumabfromthemedicalinsuranceperspectivein2023.docx Table11Thecosteffectivenessanalysesofconberceptandranibizumabfromthemedicalinsuranceperspectivein2024.docx Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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vision loss in adults globally, imposing a substantial public health burden. By 2040, AMD strongly associated with aging is projected to affect over 288 million people worldwide, with late-stage neovascular AMD contributing to severe vision impairment, particularly in high-income countries and rapidly aging populations like China, where its prevalence is rising sharply alongside demographic shifts \u003csup\u003e1\u003c/sup\u003e. DME affects approximately 5.5% of individuals with diabetes, with China bearing a high prevalence of diabetes 11.9% to 12.4% by WHO and ADA criteria. \u003csup\u003e2\u003c/sup\u003e \u003csup\u003e3\u003c/sup\u003e RVO affects about 16 million people globally, and its prevalence in Chinese adults over 40 years of age reaches nearly 1.9%, largely associated with hypertension and cardiovascular comorbidities. \u003csup\u003e4\u003c/sup\u003e \u003csup\u003e5\u003c/sup\u003e. PM remains a significant cause of blindness in younger populations, with a rising incidence driven by urbanization and near-work intensity. \u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eAnti-vascular endothelial growth factor (anti-VEGF) agents have revolutionized the treatment for the above diseases on vision restoration. Ranibizumab, a monoclonal antibody fragment targeting VEGF-A, has been firstly adopted as a first-line therapy due to its validated efficacy in stabilizing and improving visual acuity\u003csup\u003e7\u003c/sup\u003e.Conbercept, a novel recombinant fusion protein independently developed in China, has emerged as a promising alternative with higher VEGF-binding affinity and broader target specificity (VEGF-A, VEGF-B, and placental growth factor). Since 2017, conbercept has been included in China\u0026apos;s National Reimbursement Drug List, it has been demonstrated non-inferiority to ranibizumab in visual improvement and exhibits superior therapeutic responses in certain subtypes, such as PM-related CNV \u003csup\u003e8\u003c/sup\u003e \u003csup\u003e9\u003c/sup\u003e . However, evidence comparing the long-term cost-effectiveness of conbercept versus ranibizumab across multiple indications remains sparse, particularly in real-world clinical settings.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe cumulative burden of these diseases demanding multiple injections of anti-VEGF agents exacerbates healthcare disparities, particularly in low-resource settings \u003csup\u003e10\u003c/sup\u003e. Costs of anti-VEGF agents is significant aspect of healthcare system expenditures may have an especially large potential economic burden in India and China. The cost of treating all Chinese patients with ranibizumab and conbercept will be projected to 2.0% and 0.64% of the Chinese GDP, respectively \u003csup\u003e11\u003c/sup\u003e. In China alone, vision loss from AMD and DME costs an estimated $7.1 billion annually in direct healthcare expenditures and productivity losses \u003csup\u003e12\u003c/sup\u003e. The economic impact is equally profound, with direct medical costs and productivity losses associated with vision impairment amplifying systemic challenges in healthcare allocation.\u003c/p\u003e\n\u003cp\u003eThis study aims to evaluate the cost-effectiveness of conbercept versus ranibizumab for nAMD, DME, RVO, and CNV secondary to PM using real-world injection and cost data from hospitals in Tianjin, China. A Markov model was constructed to simulate long-term disease progression, incorporating local epidemiological, utility, and cost parameters. Importantly, this analysis was conducted from both the societal perspective and the medical insurance perspective to comprehensively capture the economic implications for both patients and the healthcare system. By estimating quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs), the study seeks to inform value-based clinical decisions and reimbursement strategies under China\u0026rsquo;s evolving healthcare policy landscape.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe Markov model was employed in this study to evaluate the cost-effectiveness of conbercept and ranibizumab in the treatment of various retinal diseases, including RVO, DME, PM, and AMD. The model simulated the natural progression of each disease and performed multiple cycles based on the transition probabilities between health states. Each Markov cycle was set to one year, with a total time horizon of 10 years to capture the long-term clinical and economic impacts. Baseline characteristics of the simulated population were informed by previous studies, and model inputs were constructed using real-world data on injection frequency, treatment efficacy, and health utility values for each disease. Health states were defined according to best-corrected visual acuity (BCVA) levels specific to each condition. The structure of health states and transition pathways is illustrated in Figure 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinition of Four Disease\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDME characterized by hard exudates and edema within the macula secondary to damage to retinal microvasculature can be detected by clinical examination or with OCT. Neovasular AMD was defined as retinal hemorrhages or exudates in macular in patients older than 50 years old, with detailed images of retinal structure and fluid offered by OCT, and neovascularization by visualizing dye leakage from retinal blood vessels confirmed on fluorescein angiography \u003csup\u003e13\u003c/sup\u003e. RVO can be defined as a retinal vascular disorder characterized by congestion and dilatation of the retinal veins with subsequent retinal hemorrhages and edema, retinal ischemia including cotton wool spots, retinal exudates and macular edema, classified as CRVO, BRVO, and HRVO depending on the site of occlusion \u003csup\u003e14\u003c/sup\u003e.Myopic Choroidal Neovascularization usually occur subfoveally due to perturbation of the retinal pigment epithelium (RPE)\u0026ndash;Bruch membrane complex, especially in patients with PM presenting lacquer cracks and patchy atrophy within one disk diameter of the fovea \u003csup\u003e15\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline Health States\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHealth states in the model were defined according to BCVA, with disease-specific classification standards applied. The number and boundaries of health states varied slightly across conditions to reflect clinical practice and prior research. The baseline distribution of patients across BCVA health states was derived from the PHOENIX study (AMD), BLOSSOM and CAMELLIA trials (BRVO and CRVO), the SAILING study (DME), and the SHINY study (PM). These data were used to initialize the disease-specific Markov cohorts and are summarized in Table S1(Appendix Part B).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTransition Probabilities\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe transition probabilities represent the conditional likelihood of a patient shifting from one visual acuity state to another over a given time period. In this study, the probabilities reflect transitions over a 1-year Markov cycle and were used to simulate the natural progression or improvement of vision under treatment. The transition probability matrix for each disease\u0026mdash;AMD, BRVO, CRVO, DME, and PM\u0026mdash;is shown in Table 1. These matrices represent the probabilities of BCVA changes over a 12-month period. The probability estimates for both conbercept and ranibizumab were derived from published clinical trial data and relevant literature to reflect real-world treatment outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUtilities\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHealth utility values were used to reflect the quality of life associated with different levels of visual function. In this study, utility values corresponding to various levels of BCVA impairment were assigned to each health state across the five disease indications. All utility values were obtained from previously published literature. Specifically, utility values for AMD were directly derived from validated sources. For BRVO, CRVO, DME, and PM, utility scores were similarly extracted from published studies that reported utility estimates for corresponding BCVA-defined health states. The utility values ranged from 0.805 to 0.325 for BRVO/CRVO, 0.756 to 0.325 for DME, and 0.756 to 0.325 for PM. A summary of utility values for all indications is provided in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCosts\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCosts were evaluated from both the societal perspective and the medical insurance perspective. From the societal perspective, total costs included direct medical costs (such as drug acquisition, injection procedures, outpatient visits, and examinations) as well as indirect costs due to productivity loss. Indirect costs were calculated based on the average number of missed workdays associated with different levels of visual impairment and the corresponding daily wage. The number of missed workdays was derived from published literature, and average wages were adjusted according to 2021 and 2024 data. From the medical insurance perspective, only direct medical costs covered by the insurance system were considered, primarily including drug costs and clinical treatment expenses. Unit prices for conbercept and ranibizumab were obtained from the most recent National Reimbursement Drug List (NRDL). All costs were presented in Chinese Yuan (CNY) and discounted at an annual rate of 3.5%. The model adopted a 1-year cycle length and a 10-year time horizon. Detailed cost parameters are provided in Table S1 (Appendix Part B).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReal-World Injection Frequencies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe average annual number of intravitreal injections for both conbercept and ranibizumab from 2021 to 2024 was derived from real-world data collected through the medical insurance system of Tianjin, China. These data were based on actual treatment records of patients with AMD, BRVO, CRVO, DME, and PM during the specified period and were used to reflect clinical practice more accurately. The injection frequencies varied by year and disease type, and the average values were applied in the model to estimate annual drug-related costs. Detailed injection frequencies are provided in Table 3.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSensitivity Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo assess the robustness of the model outcomes, three types of sensitivity analyses were performed. First, a two-way sensitivity analysis was conducted by simultaneously varying the prices of conbercept and ranibizumab by \u0026plusmn;10% to evaluate the impact of drug price fluctuations on cost-effectiveness outcomes. Second, a probabilistic sensitivity analysis was conducted using Monte Carlo simulation with 1,000 iterations. In this analysis, costs were assumed to follow a gamma distribution. Parameters such as drug costs, utilities, and transition probabilities were assigned appropriate probability distributions based on published sources. Cost-effectiveness acceptability curves (CEACs) were generated to illustrate the probability that each treatment strategy would be cost-effective across a range of WTP thresholds. In addition, perform one-way sensitivity analyses on the number of injections for each of the two treatment regimens respectively, with the variation range defined as the minimum and maximum number of injection in the real world, and present the results in tabular form.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e3.1 Cost-Effectiveness from the Societal Perspective (2021\u0026ndash;2024)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe cost-effectiveness results of ranibizumab and conbercept for five retinal diseases from 2021 to 2024 are showed in Table 4 to Table 7. In 2021 (see in Table 4), conbercept showed economic advantages in the treatment of BRVO and CRVO, with ICERs of -2,632,799.096 RMB/QALY and -4,982,016.597 RMB/QALY, respectively. For AMD, the ICER was 4,2404.890 RMB/QALY, which was far below the commonly used willingness-to-pay threshold of three times the per capita GDP, indicating acceptable cost-effectiveness. For DME, the ICER was 101,975.929 RMB/QALY, which was far below the commonly used willingness-to-pay threshold of three times the per capita GDP, indicating acceptable cost-effectiveness. However, in PM,\u0026nbsp;the ICER exceeding the willingness-to-pay (WTP) threshold indicates that conbercept lacks cost-effectiveness\u003c/p\u003e\n\u003cp\u003eIn 2022 (Table 5), for AMD, although the ICER was positive (5,964.559 RMB/QALY), which was far below the commonly used willingness-to-pay threshold of three times the per capita GDP, indicating acceptable cost-effectiveness. Conbercept continued to demonstrate favorable cost-effectiveness in the treatment of BRVO and CRVO, with ICERs of -480,496.496 RMB/QALY and -7,097,246.654 RMB/QALY, respectively. The ICER for DME was -61,046.505 RMB/QALY, remaining well below the threshold of three times the per capita GDP. In the treatment of PM, conbercept was both less costly and more effective than ranibizumab, with an ICER of -625,677.703 RMB/QALY.\u003c/p\u003e\n\u003cp\u003eIn 2023 (see in Table 6), conbercept remained less costly and more effective than ranibizumab in the treatment of BRVO and CRVO, with ICERs of -442,423.176 RMB/QALY and -2,429,628.701 RMB/QALY, respectively. For DME, the ICER was -69,339.384 RMB/QALY, which was below the commonly used cost-effectiveness threshold. In the case of PM, conbercept was also associated with lower cost and better effectiveness, with an ICER of -410,661.276 RMB/QALY. For AMD, the ICER was -3,790.354 RMB/QALY; although the value was negative, the difference in effectiveness between the two treatments was limited, and no significant cost-effectiveness advantage was observed.\u003c/p\u003e\n\u003cp\u003eIn 2024 (see in Table 7), conbercept remained less costly and more effective than ranibizumab in the treatment of CRVO and PM, with ICERs of -1,247,442.826 RMB/QALY and -587799.624 RMB/QALY, respectively. For DME, the ICER was -630.846 RMB/QALY, remaining well below the threshold of three times the per capita GDP. In BRVO, the ICER was 214,491.169 RMB/QALY, also within the acceptable range for cost-effectiveness. For AMD, the ICER was 45,236.924 RMB/QALY, indicating that ranibizumab had greater effectiveness than conbercept in that year, albeit at a higher cost. But the ICER was below three times the per capita GDP, suggesting that conbercept was cost-effective in this context.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Cost-Effectiveness from the Medical Insurance Perspective (2021\u0026ndash;2024)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom the medical insurance perspective in 2021, ranibizumab incurred higher costs than conbercept for AMD, BRVO, and CRVO (Table 8). Ranibizumab provided only marginal QALY gains over conbercept in AMD, corresponding to incremental cost-effectiveness ratios of approximately \u0026yen;40,094.727 gained (Table 8). In BRVO and CRVO, ranibizumab offered no additional effectiveness compared to conbercept but was more costly (Table 8). Conbercept provided only marginal QALY gains over ranibizumab in PM, corresponding to incremental cost-effectiveness ratios of approximately \u0026yen;517,369.207 gained, suggesting that conbercept was not cost-effective. For DME, conbercept incurred higher costs than ranibizumab, however, with an incremental cost-effectiveness ratio of \u0026yen;77,713.64 gained, conbercept demonstrates a favorable cost-effectiveness profile relative to ranibizumab when treating DME.\u003c/p\u003e\n\u003cp\u003eIn 2022, ranibizumab remained more costly than conbercept under the medical insurance perspective across all five indications (Table 9). Small QALY advantages for ranibizumab was still observed in AMD, with corresponding ICERs declining to \u0026yen;4,724.899 (Table 9). In BRVO, CRVO, DME, and PM, conbercept continued to achieve comparable effectiveness at a lower cost, so conbercept remained a dominated option in those indications (Table 9).\u003c/p\u003e\n\u003cp\u003eIn 2023, conbercept had lower total costs than ranibizumab for RVO、DME and PM from the medical insurance perspective (Table 10). The ICERs for ranibizumab (versus conbercept) in AMD further decreased to \u0026yen; -9,382.256 per QALY, reflecting the reduced cost difference (Table 10). Ranibizumab remained dominated by conbercept in BRVO, CRVO, DME, and PM in 2023, as conbercept provided similar or greater health gains at lower cost in those indications (Table 10).\u003c/p\u003e\n\u003cp\u003eBy 2024, ranibizumab\u0026rsquo;s cost relative to conbercept was further reduced, though conbercept still incurred a lower total cost in each indication (Table 11.). Ranibizumab continued to confer a slight effectiveness benefit in AMD, yielding ICERs of about \u0026yen;53,927.073 per QALY gained, when compared to conbercept (Table 11). For BRVO, CRVO, DME and PM, conbercept remained the lower-cost strategy without any loss of effectiveness, and conbercept thus remained dominated in those cases (Table 11).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Sensitivity Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSensitivity analysis results are presented in Appendix Part B. The two-way sensitivity analysis showed that cost-effectiveness conclusions remained stable under a \u0026plusmn;10% variation in drug prices. Probabilistic sensitivity analysis, using Monte Carlo simulation with 1,000 iterations and assuming gamma-distributed costs, further confirmed the robustness of the base-case results. When the price remains and the number of drug injections changes, conbercept has a certain cost-effectiveness in treatment of AMD、RVO、DME and PM with similar number of injections (Appendix Part B).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study assessed the cost-effectiveness of conbercept compared to ranibizumab for the treatment of four major retinal and choroidal vascular diseases\u0026mdash;AMD, DME, BRVO, CRVO and CNV secondary to PM\u0026mdash; based on real-world data from Tianjin, China. The analysis incorporated both societal and medical insurance perspectives and revealed that conbercept was more cost-effective in most indications, particularly in DME, RVO, and PM. Although the QALY gains between the two agents were similar, conbercept consistently demonstrated lower total treatment costs and favorable incremental cost-effectiveness ratios (ICERs) across multiple scenarios. These findings support the use of conbercept as a cost-effective therapeutic alternative in clinical settings, especially in resource-limited healthcare systems.\u003c/p\u003e\u003cp\u003eConbercept and ranibizumab have been demonstrate comparable efficacy in improving visual acuity and reducing central retinal thickness (CRT) in retinal vascular diseases such as DME, nAMD and RVO by Multiple RCTs and real-world observational studies. PHOENIX study indicated that conbercept achieved inferior visual gains to ranibizumab in nAMD at same therapeutic regiments as once monthly for the first 3 months, then once quarterly until month 12 (3\u0026thinsp;+\u0026thinsp;Q3M), with mean BCVA improvements of +\u0026thinsp;9.98 vs. -0.2 letters at 12 months, respectively \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. In DME, although patients treated with aflibercept benefited more on BCVA improvement at one year follow up compared to conbercept and ranibizumab, who achieved similar CRT reduction (\u0026sim;120\u0026ndash;150 \u0026micro;m) and vision stabilization at two years \u003csup\u003e17 18\u003c/sup\u003e. Conbercept had higher mean CMT change effects and BCVA improvement at 1month after treatment in patients with RVO compared to ranibizumab, which was comparable after 12 months \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. As reported, conbercept may require fewer injections due to its longer intraocular half-life and greater bioavailability attributing to an additional antigen-binding fragment (Fab) with specificity for VEGFA as 0.47 ng/ml conbercept detected in retina even 56 days post singe intravitreal injection, but ranibizumab was undetectable since day 45. Hence longer intervals of treatment potentially enhanced patient compliance and lowered costs \u003csup\u003e20 16\u003c/sup\u003e. Although ranibizumab has broader global validation, conbercept offers cost advantages in certain markets, especially in China\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eBy now, the price of conbercept (3452.8RMB/0.5 mg) has been reduced about 10% lower than ranibizumab (࿥3673.5RMB/0.5 mg) in China. From the perspective of medical insurance payment, the economic advantages of conbercept in BRVO, CRVO, DME, and PM are also significant. Among these four indications, conbercept not only has lower direct medical costs but also has clinical effects that are comparable or even superior to Ranibizumab \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e, with the ICER being below the willingness-to-pay threshold in most cases \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e, indicating its clear economic feasibility within the scope of medical insurance payment. In contrast, in the treatment of AMD, although conbercept has relatively lower costs, its therapeutic effects are generally inferior to Ranibizumab, with the ICER mostly being positive, suggesting that it does not have a significant economic advantage under medical insurance in this indication \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Therefore, it is recommended that in the formulation of medical insurance policies, different indications should be considered differentially, and conbercept should be prioritized for payment support in indications such as RVO, DME, and PM. However, for AMD, a more cautious approach is needed, and conditional or restricted payment strategies should be established based on actual therapeutic effects and population adaptability.\u003c/p\u003e\u003cp\u003eWhen evaluating the cost-effectiveness of medical treatments, it is crucial to consider different perspectives, including the society and health insurance. From the societal perspective, the analysis not only includes direct medical expenditures but also comprehensively considers self-funded costs and indirect economic losses, i.e. traffic costs, lost wages, which may contribute to reflect the impact of a treatment regimen on the overall allocation of social resources \u003csup\u003e24 25\u003c/sup\u003e. By contrast, the perspective of health insurance mainly focuses on the expenditure of the insurance fund and emphasize the direct cost-effectiveness of the medicine. This difference of perspective may lead to varying conclusions regarding the cost-effectiveness of the treatment regimen \u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e, as the economic performance of conbercept in PM (presumably a specific medical condition) in our study. In 2021, it did not demonstrate an advantage from the societal perspective, but it has shown preliminary cost-effectiveness due to lower insurance costs from the health insurance perspective with this advantage gradually strengthening over time. Likewise, in individual year of DME cost, the ICER of conbercept was close to the threshold from the societal perspective, but it remained within the acceptable range from the health insurance perspective. Hence, results of our study strongly suggested that applicability of evaluation perspective should be carefully balanced according to the characteristics of different diseases when formulating payment policies or including medicine in the health insurance catalog \u003csup\u003e27 28\u003c/sup\u003e.Different from previous analysis based on the randomized clinical trials \u003csup\u003e29 30\u003c/sup\u003e, real-world evidence (RWE) can provide crucial data on real-world efficacy, safety, and adherence, which are essential for determining the cost-effectiveness of medicine across diverse patient populations. Accordingly, policymakers also benefit from RWE-informed cost-effectiveness analyses to make more informed reimbursement decisions and ensure medical funding being allocated to interventions patients demanded.\u003c/p\u003e\u003cp\u003eThere are a few limitations for this study. This retrospective design may lead potential biases in treatment adherence documentation and missing data. Our data from hospitals in Tianjin, which may not generalize to regions with differing healthcare pricing structures (e.g., Europe or North America). Although the data from Tianjin is representative, considering geographical disparities in healthcare services, future economic evaluations based on nationwide multi-center studies or different regional healthcare insurance systems are recommended to enhance the external generalizability of the research.\u003c/p\u003e\u003cp\u003eTo our knowledge, this is the first cost-effectiveness analysis to incorporate multiple retinal and choroidal vascular diseases using real-world clinical and economic data. By enabling cross-indication comparisons and capturing outcomes under both societal and medical insurance perspectives, this study provides valuable insights for value-based decision-making and indication-specific reimbursement design in ophthalmic care.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOverall, this study demonstrates that conbercept is a cost-effective alternative to ranibizumab in the treatment of several major retinal and choroidal vascular diseases, particularly DME, RVO, and CNV secondary to PM. By adopting both societal and medical insurance perspectives, our findings provide comprehensive economic evidence to support value-based treatment selection and indication-specific reimbursement decisions in ophthalmic care.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting Interest Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors in this study declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has been approved by the Ethics Committee of Tianjin Medical University General Hospital, China with No. IRB2020-YX-160-01.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHY conceived this study and take responsibility for its all aspects. YYL and ZC designed the study. YYL, JHZ, YWQ, YMH, WZ, HH and CYY organize the implementation of the project. JHZ, YWQ and HJF were involved in data management and statistical analysis. YYL and JHZ wrote the first and subsequent drafts of the report. HY and ZC were the co-principal investigators of the project, reviewed and commented on drafts of the report. HY and ZC supervised its conduct and data analysis, and provided comments on all drafts. All authors interpreted data, contributed to critical revisions, and approved the final version of the Article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciated all authors contributed to this work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFundings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work is supported by Tianjin Science \u0026amp; Technology Foundation (22PTZWHZ00030) and National Natural Science Foundation of China (82330031) to HY, Tianjin Medical University General Hospital Excellent Youth Science Fund (22ZYYYQ05) to YYL, Tianjin Natural Science Foundation Youth Project (23JCQNJC01180) to HH, and Beijing-Tianjin-Hebei Special Project (23JCZXJC00140) to YCY.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWong WL\u003cem\u003e, et al.\u003c/em\u003e Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. \u003cem\u003eThe Lancet Global health\u003c/em\u003e \u003cstrong\u003e2\u003c/strong\u003e, e106-116 (2014).\u003c/li\u003e\n\u003cli\u003eIm JHB, Jin YP, Chow R, Yan P. 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Cost Evaluation of Early Vitrectomy versus Panretinal Photocoagulation and Intravitreal Ranibizumab for Proliferative Diabetic Retinopathy. \u003cem\u003eOphthalmology\u003c/em\u003e \u003cstrong\u003e125\u003c/strong\u003e, 1393-1400 (2018).\u003c/li\u003e\n\u003cli\u003eKymes SM\u003cem\u003e, et al.\u003c/em\u003e Cost-Utility Comparison of Bevacizumab and Aflibercept in the Treatment of Central or Hemiretinal Vein Occlusion in the SCORE2 Trial. \u003cem\u003eJAMA ophthalmology\u003c/em\u003e \u003cstrong\u003e141\u003c/strong\u003e, 554-561 (2023).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 11 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Conbercept, Ranibizumab, Cost-effectiveness analysis, Markov model, Medical insurance perspective","lastPublishedDoi":"10.21203/rs.3.rs-7266099/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7266099/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eLeading blindness causing retinal and choroidal vascular diseases including age-related macular degeneration (AMD), retinal vein occlusion (RVO), diabetic macular edema (DME), and choroidal neovascularization secondary to pathologic myopia (PM) treated with Conbercept and Ranibizumab impose a heavy economic burden. The Markov model was constructed based on best-corrected visual acuity, real-world injection frequencies in Tianjin (2021\u0026ndash;2024), costs, utility values, and transition probabilities derived from clinical trials. From both the societal and medical insurance perspectives, conbercept was more cost-effective than ranibizumab in BRVO, CRVO, DME, and PM with Incremental cost-effectiveness ratios (ICER) as 442,423.176, -2,429,628.701, -69,339.384, 410,661.276 RMB/QALY under the societal perspective, and \u0026minus;\u0026thinsp;370,506.503, -2,491,085.315, -66,253.162, -432,736.475 RMB/QALY under the medical insurance perspective in 2023, respectively. In contrast, ranibizumab consistently showed greater effectiveness for AMD, with conbercept's ICER reaching 53,927.073 RMB/QALY in 2024 under the medical insurance perspective. These findings provide economic evidence to support value-based decision-making anti-VEGF therapy in China.\u003c/p\u003e","manuscriptTitle":"Real-World Cost Evaluation of Conbercept vs Ranibizumab for Retinal and Choroidal Vascular Diseases from 2021 to 2024: Evidence from Societal and Medical Insurance Perspectives","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-31 13:24:59","doi":"10.21203/rs.3.rs-7266099/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"communications-medicine","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"commsmed","sideBox":"Learn more about [Communications Medicine](http://www.nature.com/commsmed)","snPcode":"43856","submissionUrl":"https://mts-commsmed.nature.com/cgi-bin/main.plex","title":"Communications Medicine","twitterHandle":"@commsmedicine","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Communications Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3c00a2b2-6655-4643-af67-aa7fd4ad78e4","owner":[],"postedDate":"October 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":52827008,"name":"Health sciences/Health care/Health care economics"},{"id":52827009,"name":"Health sciences/Diseases/Eye diseases/Retinal diseases"}],"tags":[],"updatedAt":"2025-10-31T13:24:59+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-31 13:24:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7266099","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7266099","identity":"rs-7266099","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}