1. In Search of Efficiency, Consistency, Fairness, and Impact in HTA: Modelling screening and treatment pathways for diabetic retinopathy Graham Scotland

2. Acknowledgments Dr Helen Looker (University of Dundee) Professor Helen Colhoun (University of Dundee) Professor Paul McKeigue (University of Edinburgh) Professor Graham Leese (NHS Tayside) Dr John Olson (NHS Grampian) Dr Sam Philip (NHS Grampain) The work being presented was funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The author accepts full responsibility for this presentation. I am not aware of any actual or potential conflicts of interest in relation to this presentation

3. Background Diabetic retinopathy / maculopathy – a leading cause of visual loss and blindness – proliferative retinopathy – macular oedema Early signs can be identified on retinal photographs Early identification and treatment can reduce the risk of visual loss Scottish National Screening Programme established in 2006

4. The Scottish diabetic retinopathy screening programme Established in 2006, based on annual screening using digital retinal photography Eligible screening population: 247,017 Number screened 199,268 (8% increase on previous year) Prevalence of diabetes growing by 4% annually ~4% of patients referable in one annual round of screening

5. DR treatment pathways Severe background retinoapthy (R3) – Monitor for progression to R4, and treat DMO if present Proliferative retinopathy (R4) – Pan-retinal photogoagulation – Vitrectomy (for complications of PDR) Maculopathy (M2) / diabetic macular oedema (DMO) – Monitor – Focal laser treatment (prevent moderate visual loss) – Intravitreal Anti-VEGF injections (for symptomatic disease)

6. Cost-effectiveness of risk stratified screening intervals Risk of progression to referable disease associated with: – type of diabetes, duration of diabetes, sex, current observed grade, prior observed grade (Looker et al., 2013)* Large proportion of the current annual screening cohort have progression risk < 1% Scope exists to improve efficiency of screening by adopting risk stratified screening intervals *Looker HC et al. Predicted impact of extending the screening interval for diabetic retinopathy: the Scottish Diabetic Retinopathy Screening programme. Diabetologia. 2013; 56(8):1716-25

7. Progression risks by sex, current/prior grade and duration of Type 2 diabetes Current / prior grade Duration of diabetes (years) Men - probability of any referable disease (%) Women - probability of any referable disease (%) 1 year2 years1 year2 years Current grade no DR / 00.140.390.140.37 50.200.640.230.69 100.260.900.311.04 150.311.130.381.38 Current grade no DR / Prior grade no DR 00.070.250.080.25 50.110.430.130.48 100.140.610.180.74 150.180.780.241.00 Current grade no DR / Prior grade mild DR 00.420.960.320.68 50.822.090.761.80 101.243.421.313.40 151.614.631.845.04 *Looker HC et al. Predicted impact of extending the screening interval for diabetic retinopathy: the Scottish Diabetic Retinopathy Screening programme. Diabetologia. 2013; 56(8):1716-25

8. Aim Model the clinical and cost-effectiveness of adopting extended intervals for groups of patients defined by selected clinical and demographic variables routinely available to screening programmes.

9. Conceptual screening model Starting cohort Non-referable screening participants (age, sex, type of diabetes, duration of diabetes, current / previous grade) In screening programmeReferred M2 R3/R4 R3/R4 +DMO DMO No DMO R3 R4 Monitor Monitor / Treat Monitor Treat/ Monitor Reduced risk of visual loss Non- referable Referable M2 R3/R4 R3/R4 +DMO Treat/ Monitor Visual loss

10. Some preliminary results

11. Risk distribution in the annual screening cohort Risk Decile Range of estimated one year risks of progression MinMax 10.0007310.000958 20.0010050.001154 30.0011680.0013 40.001370.00144 50.0015030.001733 60.0017460.002254 70.0022550.008196 80.0086340.026225 90.0262460.051352 100.0513780.360943 Total0.0007310.360943

12. Cost-effectiveness of biennial versus annual screening by risk decile Progression risk 0.8-2.6% Current practice: annual for all Biennial for all

13. Annual versus biennial screening by current / prior screened grade Biennial for all with no DR / annual for everyone else Biennial if no DR and no history of DR / annual for everyone else Current practice: annual for everyone

14. Summary of preliminary findings Annual screening appears unlikely to be cost- effective against accepted cost per QALY thresholds, if the 1-year forward risk of progression < ~1% Individuals with no retinopathy and no history of retinopathy (55% of the annual screening cohort) have an estimated risk <1% Adoption of biennial intervals in this group could lead to a substantial resource savings for very small QALY losses

15. Further research plans Sub group analysis (by type of diabetes) Further characterisation of uncertainty Interaction between screening approach and variation in downstream treatment pathways Identify more efficient screening/treatment pathway configurations Improve and update the model over time

16. Discussion Benefits Pathway modelling provides a flexible framework to inform changes in clinical pathways over time Individual level simulation can deal with complexity in the pathway and heterogeneity in the cohort – Requires individual patient data Challenges Time consuming to build/debug/analyse Limited availability of causal evidence can lead to many uncertainties – Difficult to pin down precise estimates of cost-effectiveness – Extensive sensitivity analysis required – Difficult to validate Not a substitute for collecting primary randomised data to inform decision problems at different points in the care pathway