Model Input Parameters

The baseline prevalence of the disease severity was obtained from our previous studies [11]. The transition probabilities were derived from the literature [11, 12]. The proportion of patients with bilateral DR was estimated at 75% in the model [29]. Since the relative risk of mortality of patients with diabetes and blindness had not yet been reported and the main causes of blindness in patients with DR were from STDR [30], we therefore applied the relative risk of mortality in patients with STDR. The compliance to follow-up treatment after true positive screening results had not yet been systematically quantified in the Thai health system. We therefore used 60% for both screening modalities at baseline based on random sampling from a few screening sites.

We used 50% as the screening uptake according to data from the Ministry of Public Health in the base case analysis. The age-specific all-cause mortality, derived from the Thai population’s life table data, was used and integrated with relative risks of mortality among patients in the different health states.

Direct medical costs of the screenings included the costs of fundus cameras, CFP capture, and image interpretation. The first two costs were the same in both arms. The average direct medical cost for image interpretation by HG was estimated at 56 Thai baht (THB) (~ US$ 1.7) per patient. Additional costs included setting up certified training courses. The cost for image interpretation and other related practice expenses using DL was set at the price of 32 THB (~ US$ 1) per patient, a pricing estimate comparable with HG interpretation. We probed this price per patient further in threshold analyses.

Total annual cost related to screening at primary health centers using DL, HG, and confirmation of referrals at tertiary health centers by retinal specialists were 375 (~ US$ 11.7), 399 (~ US$ 12.5), and 535 (~ US$ 16.7) THB, respectively. The details of these costs, including the cost of outpatient service, fundus photography, and visual acuity measurement, are given in Fig. 2.

Summary of details of screening and treatment costs. BB bilateral blindness, DL deep learning, DR diabetic retinopathy, DME diabetic macular edema, HG trained human graders, STDR sight-threatening diabetic retinopathy, THB Thai baht. Unit cost of treatment of DME includes cost of bevacizumab and intravitreal administration listed in Table ​Table1.1. Unit cost of treatment of STDR includes cost of laser photocoagulation and vitrectomy (not shown in this figure but shown in Table ​Table1).1). Treatment for DME includes cost of outpatient service, bevacizumab, intravitreal injection, and macular imaging by optical coherence tomography. Treatment for STDR in the first year covers the cost of outpatient service and cost of laser photocoagulation, or cost of vitrectomy and inpatient service

Cost of treatment for STDR without DME included the cost of pan-retinal photocoagulation (PRP), at the average of two sessions, at 7000 THB per patient. For PDR, the cost was the weighted average between a proportion of patients (two-third) treated with PRP and another proportion (one-third) treated with surgery [31], which was vitrectomy, at an average of 30,000 THB per patient. Patients with DME were treated with 17 doses of bevacizumab, the number of intravitreal injections during the first 5 years of treatment derived from clinical trials [22]. Total cost of treatment for DME was 59,503 THB in the first year, 11,388 THB in the second year, and 619 THB for subsequent years. The cost of bevacizumab was used since this medication is listed on Thailand’s National Essential List of Medicines and used as the first-line treatment for DME in the country.

Direct non-medical costs comprised costs of food, transportation, accommodation, equipment and facilities for patients, and productivity loss of caregivers, which was calculated based on gross national income per capita, assuming caregiving time at 4 h per day. These costs per patient are the same for both arms.

Indirect costs were omitted to avoid double counting in the CUA according to the recommendation from the Thai Health Technology Assessment guideline. All incurred costs were converted to 2020 values using the consumer price index for Thailand and were converted to US$ using the exchange rate as of 1 July 2021 of 32.02 THB per US$. The cost of blindness is comprised primarily of visual rehabilitation aids and services, including residential and community care [32]. In Thailand, visual rehabilitation clinics are operated only in a few training centers with low patient volumes [33]. Therefore, this cost is minimal compared to the treatment costs and is not considered in the health provider perspective. Disaggregated costs from both societal and provider perspectives are shown in Fig. 3.

Total and disaggregated costs for the two screening strategies (HG and DL). The costs are for the cost-utility analysis at base case from both societal and provider perspectives. BB bilateral blindness, DL deep learning, DME diabetic macular edema, HG trained human graders, STDR sight-threatening diabetic retinopathy. Costs of treatment of DME and STDR without DME are presented separately. We assumed no direct medical costs for bilateral blindness; all the values are Thai baht in 2020

Since the health utility weights for patients with DR in Thailand or Asia are not available, we applied those from the next closest match, i.e., those associated with patients with DR at a primary care service in Brazil, another MIC [34]. In that study, the utility values were estimated using the Brazilian EuroQol five dimension (EQ-5D) tariffs from patients without DR, with non-STDR, STDR, and bilateral blindness. Since DME was not considered in that model, we assumed that those who progressed into STDR with and without DME had the same utility values.

All these input parameters are shown in detail in Table ​Table11 and Fig. 2.