Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Sara Khor, MAScPharmacoeconomics Research Unit, Cancer Care OntarioLi Ka Shing Knowledge Institute, St. Michael’s HospitalCanadian Centre for Applied Research in Cancer Control
May 23rd, 2011ISPOR 16th Annual International Meeting
Real World Cost-Effectiveness of Cancer Drugs:
Comparative effectiveness research using retrospective Canadian registry data before and after drug approval
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Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Acknowledgements
Ministry of Health Drug Innovation Fund
Dr. Jeffrey HochDr. Murray Krahn
Dr. David HodgsonDr. Jin LuoKaren BremnerDr. Linda LeeDr. Michael Crump
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Dr. Chaim BellScott GavuraDr. Paul GrootendorstDr. Muhammad MamdaniDr. Stuart Peacock Dr. Carol SawkaDr. Terry SullivanDr. Maureen Trudeau
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Outline3
Overview & Objectives
Rituximab Study• Cohort Selection• Survival• Costs• Cost-effectiveness
Conclusion
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
The need of evidence-based data in CER
Healthcare payers, providers, pharmaceutical manufacturers rely on the use of evidence-based data to evaluate the effectiveness and “value for money” of innovative therapies relative to current standard-of-care practices
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Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Evidence to evaluate clinical outcomes
Randomized controlled trials is the golden standard:
Challenging to conduct Costly, require a lot resources, restricted to short time frames
Might not reflect the real-worldSelected group of patients, specific procedures, ethical issues
Might not reflect how the drug is used in practiceToxicities/side effects may not be determined
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Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Why real-world cost-effectiveness analysis?
Accurate information about how a drug is actually used or how much it actually costs is only available after a drug is funded
Allows us to evaluate real benefits or harms and value for money of new agents, especially expensive ones
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Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Our study
First study in Ontario that evaluates population-based post-market effectiveness and cost-effectiveness of very expensive cancer drugs
First study in Canada incorporating recently developed statistical methods for analyzing incomplete costs and cost-effectiveness of cancer treatments
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Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Overall Objectives
To determine whether it is feasible to conduct post-market evaluation of cancer drugs using Ontario’s administrative databases.
To compare survival benefits and costs from the real-world to what is being reported in RCTs and economic models.
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Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Real-world outcomes9
Population-based retrospective analysis
of cancer drugs
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Outline10
Overview & Objectives
Rituximab Study• Cohort Selection• Survival• Costs• Cost-effectiveness
Conclusion
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Diffuse-large-B-cell lymphoma
3000 new cases of non-Hodgkin lymphoma in Ontario in 20101300 deaths attributed to the diseaseDiffuse-large-B-cell lymphoma is the most common form, represents approx. 25% of new cases
Standard treatment: CHOP*New treatment: Rituximab + CHOP (RCHOP)
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*cyclophosphamide, doxorubicin, vincristine and prednisone
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
In Ontario
Rituximab approved for funding via the New Drug Funding Program in Ontario:
Jan 10th, 2001 – 60-80 years oldApril 2nd, 2001 – ≥80 years oldJuly 1st, 2004 – <60 years old
Based on efficacy results from out-of-province trials and theoretical economic models
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Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Outline13
Overview & Objectives
Rituximab Study• Cohort Selection• Survival• Costs• Cost-effectiveness
Conclusion
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Historical cohort selection14
Jan,
200
1
Apr
il, 2
001
July,
200
4
t
Jan
1, 1
997
Dec
31,
200
7
60-80
≥80
<60
≥80
60-80
<60
Pre-era CHOP
Post -era RCHOP
Mar
31,
200
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Characteristics
Before matchingPre-era CHOP
Post-era RCHOP
Std. diff
P value
N = 1196 N =2825Age Mean ± SD 56.7± 16 65.5 ± 14 0.62 <.001
Age Group
0-19 1% <1% 0.09 <.00120-59 56% 25% 0.6760-69 19% 30% 0.2570-79 20% 33% 0.3080+ 5% 12% 0.22
Female 47% 48% 0.01 0.74
ACG* Group
0 <1% <1% 0.09 <.0011-3 7% 5% 0.104-6 24% 17% 0.187-9 28% 31% 0.0510 + 40% 47% 0.16
Income Quintile
1 16% 17% 0.02 0.182 20% 21% 0.023 20% 19% 0.024 24% 21% 0.085 20% 22% 0.06
missing <1% <1% 0.02
Treatment intensity
Low 32% 30% 0.04 0.04High 54% 58% 0.08
Unclassifiable 15% 12% 0.07
Primary Histology
Code
9590 16% 20% 0.11 <.0019591 3% 3% 0.029640 80% 69% 0.259680 2% 9% 0.29
Hard-matched on age groupPropensity score-matched on:
SexAdjusted clinical group (ACG) scoreIncome quintileTreatment intensityPrimary histology diagnosis code
*ACG – adjusted clinical group scores
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Characteristics
Before matching After matchingPre-era CHOP
Post-era RCHOP
Std. diff
P value
Pre-era CHOP
Post-era RCHOP
Std. diff
P value
N = 1196 N =2825 N = 1131 N = 1131Age Mean ± SD 56.7± 16 65.5 ± 14 0.62 <.001 57.4 ± 15 58.9 ± 15 0.03 0.47
Age Group
0-19 1% <1% 0.09 <.001 <1% <1% 0.00 1.0020-59 56% 25% 0.67 54% 54% 0.0060-69 19% 30% 0.25 19% 19% 0.0070-79 20% 33% 0.30 21% 21% 0.0080+ 5% 12% 0.22 6% 6% 0.00
Female 47% 48% 0.01 0.74 47% 47% 0.00 0.93
ACG Group
0 <1% <1% 0.09 <.001 <1% <1% 0.02 0.561-3 7% 5% 0.10 7% 7% 0.014-6 24% 17% 0.18 23% 23% 0.007-9 28% 31% 0.05 29% 31% 0.0610 + 40% 47% 0.16 41% 38% 0.06
Income Quintile
1 16% 17% 0.02 0.18 16% 15% 0.03 0.912 20% 21% 0.02 20% 20% 0.023 20% 19% 0.02 20% 21% 0.014 24% 21% 0.08 23% 24% 0.025 20% 22% 0.06 20% 20% 0.01
missing <1% <1% 0.02 <1% <1% 0.03
Treatment intensity
Low 32% 30% 0.04 0.04 31% 32% 0.03 0.16High 54% 58% 0.08 55% 56% 0.03
Unclassifiable 15% 12% 0.07 15% 12% 0.08
Primary Histology
Code
9590 16% 20% 0.11 <.001 16% 17% 0.02 0.779591 3% 3% 0.02 3% 2% 0.049640 80% 69% 0.25 79% 79% 0.019680 2% 9% 0.29 2% 2% 0.00
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Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Outline17
Overview & Objectives
Rituximab Study• Cohort Selection• Survival• Costs• Cost-effectiveness
Conclusion
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Kaplan-Meier Survival Curves18
3-year: 10%↑5-year: 8%↑
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Outline19
Overview & Objectives
Rituximab Study• Cohort Selection• Survival• Costs• Cost-effectiveness
Conclusion
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Cost analysis
Perspective: Payer – Ministry of Health
Adjusted for incomplete cost data (due to not enough follow-up time) by using Bang and Tsiatis’ estimator (2000)
Fixed time-frames: 3-year and 5-year
Discounted by 3%
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Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
5-year costs21
$71,
639
$71,
640
$79,
668
$88,
536
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Cost drivers22
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Outline23
Overview & Objectives
Rituximab Study• Cohort Selection• Survival• Costs• Cost-effectiveness
Conclusion
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Incremental Cost-effectiveness Ratios
3% discounted
Incremental cost
(CAD$)
Incremental survival(Years)
ICER ($/LYG)
3 year 15,032 0.16 96,764
5 year 16,785 0.33 51,587
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Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Cost-effectiveness acceptability curve25
020
4060
8010
0P
erce
ntag
e
0 50000 100000 150000 200000 250000Willingness-to-pay ($/LYG)
3 Year 5 Year
Bootstrap ICERs vs WTP
23%
92%91%
99.7%
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Outline26
Overview & Objectives
Rituximab Study• Cohort Selection• Survival• Costs• Cost-effectiveness
Conclusion
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
How do we compare?27
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13
8
0 10 20 30
BC observationalstudy
Europe GELA Trial
Our study
Survival %
2-year Absolute Survival Benefit
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
How do we compare?28
7900
9700
12740
16785
0 5000 10000 15000 20000
BC microsimulation
BC microsimulation
US model
Our study
Cost ($)
5-yr Incremental Cost
(High)
(Low)
Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Key methodological findings
Using appropriate methods to adjust for confounding variables is important
Adjusting for incomplete cost data is essential
Selection of timeframe has a big effect on cost-effectiveness results
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Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Overall Conclusions
It is feasible to perform real-world cost-effectiveness analysis with Ontario’s administrative data
Cost-effectiveness results in a real-world analysis differ from those from clinical trials and economic models
Healthcare payers, providers and pharmaceutical manufacturers should be cautious about conclusions from results of trials/models
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Pharmacoeconomics Research Unit RESEARCH. DECISION SUPPORT. KNOWLEDGE TRANSLATION. CAPACITY BUILDING
Thank you
Contact us:
Sara KhorEmail: [email protected]
Websites: http://healtheconomics.utoronto.cahttp://www.cc-arcc.ca
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