Real World Cost-Effectiveness of Cancer Drugs ISPOR...

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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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

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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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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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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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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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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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Real-world outcomes9

Population-based retrospective analysis

of cancer drugs

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Outline10

Overview & Objectives

Rituximab Study• Cohort Selection• Survival• Costs• Cost-effectiveness

Conclusion

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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

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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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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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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)

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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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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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Thank you

Contact us:

Sara KhorEmail: sara.khor@cancercare.on.ca

Websites: http://healtheconomics.utoronto.cahttp://www.cc-arcc.ca

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