1. How to integrate external evidence into within trial economic evaluations? Mohsen Sadatsafavi MD, PhD University of British Columbia 2015.04.13

2. 2 Conflict of Interest No apparent or perceived conflict of interest Received CIHR fellow-ship award for this work All interpretations are my own Our Team Carlo Marra, Shawn Aaron, Stirling Bryan

3. 3 Outline A novel method for incorporating external evidence in economic evaluations Context in which it is applicable What it does A running example Pros + Cons + conclusions

4. 4 Economic trials as vehicles for evaluations Model-based evaluations Evidence is ‘parameterized’ and fed into a computer program (mathematical function) simulation Trial-based evaluations Individuals are assigned to competing treatments and their experiences is represented through cost and effectiveness values (bivariate) statistical inference bootstrap as s popular paradigm

5. 5 Issues with trial-based CEAs  Failure to compare all available options  A truncated time horizon  Lack of relevance to the jurisdiction of interest  Failure to incorporate all evidence  the most damning criticism

6. 6 Context An example: OPTIMAL trial in COPD Mono, double, and triple inhaler therapy in COPD (T1,T2, T3) N=442 Follow-up 1 year Primary outcome: exacerbation rate Prospective economic evaluation component Results – RR of T2 v. T1: 1.01 (0.59 – 0.73) – RR of T3 v. T1: 0.84 (0.47 – 1.49)

7. 7 Context OPTIMAL CEA Sequence of imputation, regression, outcome calculationswithin a bootstrap envelope

8. 8 Trialist versus economist Treatment effects (RR=0.84, NS) ICER=243K Pooled estimate Regression-based methods Bootstrap methods OPTIMAL trial Trialist Economist Decision maker Welte et. al. T3 v. T1 RR=0.38 (0.28 – 0.57) Meta-analyst

9. 9 CONTEXT Reconciling external evidence in RCT-based CEAs Desist RCT-based CEA and resort to model-based evaluation Switch to parametric Bayesian evidence synthesis MCMC using WinBUGS (technical, lots of programing, model convergence etc) Stay with the bootstrap-based methods, incorporate external evidence

10. 10 Methods RCT-CEA without external evidence

11. 11 Methods RCT-CEA with external evidence

12. 12 Results Case study in COPD

13. 13 Results Case study in COPD

14. 14 Conclusions Theoretically, possible to use trials as ‘vehicle’ for evidence synthesis, yet avoid the ‘most damning criticism’ Practically, with too many parameters, it can be computationally prohibitive Best use is in sensitivity and secondary analyses What if we incorporate the results of the study by xyz? The experts in our team believe it is almost impossible that chemo+radiation increases the risk of metastasis ->half-flat priors

15. Faculty Mohsen Sadatsafavi J Mark FitzGerald Stirling Bryan Larry Lynd Research Staff Hamid Tavakoli Tania Conte Roxanne Rousseau Students Zafar Zafari Wenjia Chen Thank You! msafavi@mail.ubc.ca Respiratory Evaluation Sciences Program (resp.med.ubc.ca)