CADTH 2015 Symposium

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 / 6-monthly
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. Diabetic retiopathy treatment pathways
• Severe background retinopathy (R3)
– Monitor for progression to R4, and treat DMO if present
• Proliferative retinopathy (R4)
– Pan-retinal photocoagulation
– 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 year 2 years 1 year 2 years
Current grade no DR / 0 0.14 0.39 0.14 0.37
5 0.20 0.64 0.23 0.69
10 0.26 0.90 0.31 1.04
15 0.31 1.13 0.38 1.38
Current grade no DR / Prior
grade no DR
0 0.07 0.25 0.08 0.25
5 0.11 0.43 0.13 0.48
10 0.14 0.61 0.18 0.74
15 0.18 0.78 0.24 1.00
Current grade no DR / Prior
grade mild DR
0 0.42 0.96 0.32 0.68
5 0.82 2.09 0.76 1.80
10 1.24 3.42 1.31 3.40
15 1.61 4.63 1.84 5.04
*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 programme Referred
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
Min Max
1 0.000731 0.000958
2 0.001005 0.001154
3 0.001168 0.0013
4 0.00137 0.00144
5 0.001503 0.001733
6 0.001746 0.002254
7 0.002255 0.008196
8 0.008634 0.026225
9 0.026246 0.051352
10 0.051378 0.360943
Total 0.000731 0.360943

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