1. Sensitivity in Cost Effectiveness Analyses Sensitivity of a CEA on prevention strategies against Neural Tube Defects using DPL software. Radboud Duintjer Tebbens

2. Contents • Objectives • Problem Description • The Model • Implementation and Deterministic Results • Sensitivity Analysis • Probabilistic Model • Conclusions Sensitivity in CEA's

3. Objectives • Exploring the possibilities of DPL for sensitivity analyses • Getting familiar with Cost Effectiveness Analyses • How can sensitivity analyses on CEA’s be improved? Sensitivity in CEA's

4. Problem Description • What is a Cost Effectiveness Analysis? Analysis that compares health interventions using C/E ratio C/E ratio = Incremental Cost/Incremental Effectiveness = Incremental Cost / Incremental QALY’s QALY: Quality-Adjusted Life Year 1 QALY = 1 year in full health 0 QALY = 1 year dead Sensitivity in CEA's

5. Problem Description (2) • The CEA on Neural Tube Defects (NTD’s) considers 5 health programs for prevention of NTD’s on newborns: 1. No Program (baseline) 2. Supplementation: education program to stimulate women aged 15-45 to take Vitamin Supplements 3,4&5. Fortification with folic acid: a rule that forces food producers to fortify cereals with folic acid, 0.14 , 0.35 or 0.70 mg per 100g of cereals • The CEA on neural tube defects is described in the appendix of the book: Cost-effectiveness in Health and Medicine, M.R. Gold et. al, Oxford University Press 1996 Sensitivity in CEA's

6. Problem Description (3) • Adverse Effect in Fortification Programs: intakes of more than 1.0 mg of folic acid can cause delayed diagnosis of vitamin B12 deficiency which can lead to neurological complications, mostly by elderly persons Sensitivity in CEA's

7. The Model Simple deterministic model that: • Calculates the number of babies born with NTD with each program • Calculates the number of Adverse Effects caused by any of the programs • Adds costs of the various programs and their health outcomes • Uses expert judgment outcomes to evaluate the number of QALY’s gained compared to the baseline case ‘no program’. Sensitivity in CEA's

8. Important Uncertain Parameters: parameter value sensitivity range QALY’s per NTD 12.591 5 -20 Costs per NTD 180972.8 160 000 - 200 000 QALY’s per Adverse Effect 0.31 0.20 - 0.40 Costs per Adverse Effect 3897.38 3500 - 4300 pNTD0.4+ 0.000035 0.000021-0.000049 pNTD0.4- 0.000085 -- pOAdvEff 0.000023 0.000007-0.000047 pBegSupp 0.15 0.0 -1.0 The Model (2) Sensitivity in CEA's

9. Model (3) • pNTD0.4+ is the probability that a women aged 15-45 who consumes at least 0.4 mg of folic acid daily will have an NTD affected pregnancy. • pNTD0.4+ is the probability that a women aged 15-45 who consumes less than 0.4 mg of folic acid daily will have an NTD affected pregnancy. • The difference between these variable accounts for the number of prevented NTD’s by the health intervention. • pOAdveff, the probability that someone who is not a woman aged 15-45 and who consumes more than 1.0 mg of folic acid daily, eventually quantifies the occurrence of neurological complications Sensitivity in CEA's

10. Implementation and Deterministic Results Straightforward Influence Diagram with • 1 Decision Node: Program • Many Value Nodes containing all model parameters • Objective function to be minimized: Incremental C/E = Costs/QALY’s Gained NB: I used Costs instead of Incremental Costs Sensitivity in CEA's

11. Implementation and Deterministic Results (2) • Deterministic Results: Program Costs(M$) QALY’s lost Incremental C/E No Program 710 49 398 - Suppl. 724 45 642 195 089 Fort. 0.14 706 48 373 688 821 Fort. 0.35 636 43 119 101 333 Fort. 0.70 503 32 144 31 106 Sensitivity in CEA's

12. Sensitivity Analysis • Univariate: Rainbow Diagrams or Tornado Diagrams • Many Univariate Sensitivity Analyses at once: Tornado Diagrams • Multivariate? • (See accompanying DPL file: NTDdeterm.da) Sensitivity in CEA's

13. Probabilistic Model • Not conceptually very clear • Use of Risk Profiles and probability distributions, but very basic • No improvement for sensitivity visualization • (See accompanying DPL file: NTDprob.da) Sensitivity in CEA's

14. Conclusions • DPL is good for a first look at sensitivity of a model on its parameters. • First look at CEA on NTD prevention shows that the decision based on the C/E ratio is very little sensitive to most uncertain parameters, even though the cost and health outcomes are quite sensitive to them. Sensitivity in CEA's

15. Conclusions (2) • Multivariate sensitivity analyses for CEA’s? • It would be interesting to look at uncertainty analysis for CEA’s, taking into consideration the (joint) probability distribution of the uncertain parameters (but is it necessary?) Sensitivity in CEA's