1. The Importance of Decision Analytic Modelling in Evaluating Health Care Interventions Mark Sculpher Professor of Health Economics Centre for Health Economics University of York, UK

2. The requirements of economic evaluation for decision making Objective function Generic measures of health; QALYs Decision problem Clarity about population; full specification of options Appropriate time horizon Time over which options might differ Uncertainty Quantify decision uncertainty; feed in research prioritisation Inclusion of all relevant evidence Evidence base Relevant to specific decision maker(s)Context

3. Is trial-based economic evaluation the answer? What is trial-based economic evaluation? Cost-effectiveness analysis - Costs & effects averaged across trial sample - Time horizon = trial follow-up - External data for valuation only Single RCT Patient level data on: Resource use Health-related events Health care facilities Unit costs (prices) of resources Sample of public ? Utility data to value health events

4. (A selection of) problems with trial-based economic evaluation Time horizon Follow-up often < time horizon Comparison Trials compare selected options not all strategies Evidence base Typically there are other trials and sources Sculpher et al. Whither trial-based economic evaluation for health care decision making? Health Economics 2006;15:677-687. Trials undertaken in multiple locations Context Partial comparison and evidence means uncertainty not appropriately quantified Uncertainty

5. What is the appropriate framework for economic evaluation? Evidence synthesis Systematic review Meta-analysis Mixed treatment comparisons Differing endpoints and follow-up Patient-level and summary data Decision analysis Structure reflecting disease Incorporation of evidence on range of parameters Facilitates extrapolation and separation of baseline and treatment effects Probabilistic methods

6. Case study – Glycoprotein IIb/IIIa antagonists in acute coronary syndrome Strategy 1: GPA as part of initial medical management [7 trials] Strategy 2: GPA in patients with planned percutaneous coronary interventions (PCIs) [1 trial] Strategy 3:GPA as adjunct to PCI [10 trials] Strategy 4:No use of GPA Palmer et al. Management of non-ST-elevation acute coronary syndromes: how cost- effective are glycoprotein IIb/IIIa antagonists in the UK National Health Service? International Journal of Cardiology 2005;100:229-240.

7. Limitations with GPA trials Trial characteristic Partial comparison Non-UK case-mix and clinical practice No resource use data Short-term time horizon Modelling method Pooled relative risks from trials applied to common baseline risks UK-specific baseline risks from observational study. Relationship between baseline risks & treatment effect explored with meta- regression Resource use data from UK observational study attached to clinical events Extrapolation from 6 months based on Markov model populated from UK observational study

8. Decision uncertainty 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00% 90.00% 100.00% 0100002000030000400005000060000700008000090000100000 Maximum willingness to pay for an additional QALY (£) Probability Cost-Effective (%) ICER: £5,738 per QALY 94% at £30,000 Strategy 1 Strategy 4

9. Using uncertainty Relevance of conventional inference? What do we put in its place? –Leave error probabilities to the decision maker –When is it no longer efficient to further information? –What if the decision maker has no control of research?

10. Summary Economic evaluation studies exist to inform decision making Rarely will trial-based studies be sufficient for this purpose Synthesis and models should be seen as the standard framework for economic evaluation