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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
• 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
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
• 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
• To estimate the incremental cost-effectiveness of bevas a systemic therapy treatment for mCRC, accounting for the differences in costs and health outcomes associated with bevand standard of care treatments
• BUT: Cannot directly compare costs and outcomes for patients treated vs. not treated with bevacizumab because of selection bias
Goal
• 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 bevamong the subset of patients receiving “doublet” chemotherapy (5-FU plus irinotecan or oxaliplatin)
Approach and Objectives
Stage IV Diagnosis
1st Line Chemo
No Chemo
3rd Line Chemo
2nd Line Chemo
Alive
Dead
Markov Model Schema
• 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
• Survival: derived based on Weibull models
• Chemotherapy: derived based on Exponential models
Transition Probabilities
Chemotherapy Death
No Chemotherapy Death
1st-line 2nd-line
2nd-line 3rd-line
Pre- Post Pre Post Pre Post Pre Post
0.059 0.054 0.093 0.075 0.060 0.086 0.068 0.096
Expense Source Average Cost Per Patient
Pre (n=611) Post (n=332)
Diagnosis &
staging
StatsCan POHEM modeling$2115.38 $2115.38
Day surgeryOntario Case Costing Initiative
$ 1,046.01 $ 1,136.00
InpatientOntario 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 $ 3,843.40
Costs
State Base-Case Value * Range*
Healthy 1.00 NA
No chemotherapy 0.25 0.20-0.31
Clinical CRC Stage 4 – 1st line chemo 0.25 0.20-0.31
Clinical CRC Stage 4 – 2nd line chemo 0.25 0.20-0.31
Clinical CRC Stage 4 – 3rd line chemo 0.25 0.20-0.31
Dead 0.00 0.00
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
Survival for individuals who initiated chemotherapy
0 10 20 30 40
0.0
0.2
0.4
0.6
0.8
1.0
Overall survival time for individuals initiating chemotherapy
Time (months)
Pro
porti
on s
urvi
ving
Pre-Bev: Median = 17.2 months
Bev: Median = 20.1 months
Era Cost / patient Median OS Utilities per patient
Pre$ 34,972 15.6 months 0.34
Post$ 38,764 19.5 months 0.40
Cost/QALY $ 62,468 / QALY Cost/LYG $ 15,617/ LYG
Era-Based Base-Case Results
Sensitivity Analysis
QALY difference
Cos
t diff
eren
ce (t
hous
and
$)
0.000 0.025 0.050 0.075 0.100
-3-1
13
57
• Subset of era-based analysis:
– 1) Diagnosed before age 70
– 2) Treated with first-line doublet chemotherapy
• Intent: include only patients who wereorwould have been eligible for a bev-based protocol
Restricted Analysis
Era Cost per
patient
Median OS Utilities per patient
Pre$ 43,305 18.7 months 0.37
Post$ 45,199 23.1 months 0.41
Cost/QALY $ 43,058 / QALY Cost/LYG $ 10,764 / LYG
Restricted Cohort Base-Case Results
• 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
• 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)
• As a 1st or 2nd line treatment for mCRC, bevmay 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
Acknowledgements
• Project team:
– Dr. Stuart Peacock
– Dr. Diego Villa
– Dr. Hagen Kennecke
• Funding sources:
– CIHR Partnerships in Health Systems Improvement