1. Advancing Health Economics, Services, Policy and Ethics An Application of Evidence-Based Marginal Analysis: Assessing the Incremental Cost Effectiveness of Eras of Metastatic Colorectal Cancer Therapy in British Columbia, Canada: Pre- and Post-Bevacizumab Introduction Lindsay Hedden Priorities 2010, Boston, MA

2. This bevacizumab study is part of a larger program of research into Evidence Based Marginal Analysis –Goal: to develop and pilot novel evidence-based methods for priority setting and resource allocation within the context of cancer control and care in British Columbia A key objective: evaluate the effectiveness of priority setting decisions using utilization, mortality, and quality of life data Priority Setting and Resource Allocation at BCCA

3. STEERING COMMITTEE –Established and refined decision criteria –Identified three areas for potential resource reallocation –Reviewed results of cost-effectiveness analyses –Made recommendations for resource reallocation PROGRAM PANELS –Provide clinical and data expertise on model building –Validate results EMBA Study Structure

4. Bevacizumab (bev): given as a first- or second-line systemic therapy in combination with other regimens to treat metastatic colorectal cancer (mCRC) –2.8 month average improvement in overall survival –2.6 months average improvement in progression-free survival National Institute for Health and Clinical Excellence (UK) –£62,857-£88,436 per QALY gained –Use of bev as first-line therapy is NOT recommended Bevacizumab (Avastin): Background

5. To estimate the incremental cost- effectiveness of bev as a systemic therapy treatment for mCRC, accounting for the differences in costs and health outcomes associated with bev and standard of care treatments BUT: Cannot directly compare costs and outcomes for patients treated vs. not treated with bevacizumab because of selection bias Goal

6. Compare eras of treatment for mCRC: –pre-bevacizumab introduction and post- bevacizumab introduction –secondary pseudo case-control comparison Objectives –1) To assess the cost-effectiveness of the era of bev protocols in the treatment of mCRC compared with the pre-bev era –2) to evaluate the incremental cost-effectiveness of a first- and second-line bev among the subset of patients receiving “doublet” chemotherapy (5-FU plus irinotecan or oxaliplatin) Approach and Objectives

7. Markov Model Schema

8. Complete cohort of patients presenting with mCRC at diagnosis, identified using BCCA’s Information Service (CAIS) –Pre-era: Diagnosed Jan 1, 2003-Dec 31, 2004; followed to death, censoring, or Oct 31, 2005 –Bev-era: Diagnosed Jan 1, 2006-Dec 31, 2006; followed to death, censoring, or Oct 31, 2008 611 cases in pre-era & 332 in the post-era Sample

9. Survival: derived based on Weibull models Chemotherapy: derived based on Exponential models Transition Probabilities Chemotherapy  Death No Chemotherapy  Death 1 st -line  2 nd -line 2 nd -line  3 rd -line Pre-PostPrePostPrePostPrePost 0.0590.0540.0930.0750.0600.0860.0680.096

10. ExpenseSourceAverage Cost Per Patient Pre (n=611)Post (n=332) Diagnosis & staging StatsCan POHEM modeling $2115.38 Day surgery Ontario Case Costing Initiative $ 1,046.01$ 1,136.00 Inpatient Ontario Case Costing Initiative $ 11,115.13$ 14,718.00 Systemic Therapy BCCA provincial pharmacy database $ 20,672.62$ 24,464.53 Radiation therapy BCCA radiation oncology database $ 3,843.40 Costs

11. StateBase-Case Value *Range* Healthy1.00NA No chemotherapy0.250.20-0.31 Clinical CRC Stage 4 – 1 st line chemo0.250.20-0.31 Clinical CRC Stage 4 – 2 nd line chemo0.250.20-0.31 Clinical CRC Stage 4 – 3 rd line chemo0.250.20-0.31 Dead0.00 Utility Values *Source: Ness, R.M., et al., Outcome states of colorectal cancer: identification and description using patient focus groups. The American Journal of Gastroenterology, 1998. 93(9): p. 1491-1497

12. Survival for individuals who initiated chemotherapy

13. EraCost / patientMedian OSUtilities per patient Pre $ 34,97215.6 months0.34 Post $ 38,76419.5 months0.40 Cost/QALY$ 62,468 / QALY Cost/LYG$ 15,617/ LYG Era-Based Base-Case Results

14. Sensitivity Analysis

15. Subset of era-based analysis: –1) Diagnosed before age 70 –2) Treated with first-line doublet chemotherapy Intent: include only patients who were or would have been eligible for a bev-based protocol Restricted Analysis

16. Era Cost per patient Median OSUtilities per patient Pre $ 43,30518.7 months0.37 Post $ 45,19923.1 months0.41 Cost/QALY$ 43,058 / QALY Cost/LYG$ 10,764 / LYG Restricted Cohort Base-Case Results

17. Era-based: $62,468.68/QALY or $15,617/LYG  3.9 month/patient improvement in survival & $3,791/patient increase in cost –Not directly inferred as cost-effectiveness of bev Other factors my have led to improvements in survival, increases in cost Interpretation

18. Restricted Analysis: $43,058/QALY or $10,764/LYG  4.4 month/patient improvement in survival & $1,894/patient increase in cost –Closer to a true incremental cost-effectiveness comparing bev with standard of care, but not perfect Both methods produced ICERs demonstrating better cost-effectiveness than estimated by NICE Interpretation (2)

19. As a 1 st or 2 nd line treatment for mCRC, bev may be relatively cost-effective, considered as part of a suite of available treatments –the era-based ICER of $62,468 is well in-line with cost-effectiveness ratios reported for other therapies for metastatic cancer therapies Implications

20. Acknowledgements Project team: –Dr. Stuart Peacock –Dr. Diego Villa –Dr. Hagen Kennecke Funding sources: –CIHR Partnerships in Health Systems Improvement