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Frameworks to Assess Value for Cancer Treatments

April 11, 2016

© 2016 Canadian Agency for Drugs and Technologies in Health

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• Alexandra Chambers• Dolly Han• Jessa Letargo• Kelley-Anne Sabarre

Authors of This Presentation


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• Overview of pCODR• What are Values frameworks? And Why Now?• Comparison of 3 Frameworks:

ASCO – Value Framework ESMO – Magnitude of Clinical Benefit Scale pCODR Expert Review Committee’s (pERC)

Deliberative Framework

Outline


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Overview of pCODR• What is pCODR?

The pan-Canadian Oncology Drug Review is an evidence-based, cancer drug review process

Assesses cancer drugs by reviewing clinical evidence, cost-effectiveness, and patient perspectives

Designed to bring consistency and clarity to the assessment of

• Why was it created? To bring consistency and clarity to the assessment of cancer drugs

• Who informs the process? Clinicians Ministries of Health/Cancer agencies Patients Health Economists Industry


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• Who makes the drug funding recommendations?• pCODR Expert Review Committee (pERC)

• How does pERC make their recommendations?• Information package:

Systematic review Patient input Jurisdiction input Clinical interpretation Economic evaluation

Overview of pCODR Cont’d…


pERC's Deliberative Framework for drug funding recommendations focuses on four main criteria:

CLINICAL BENEFIT

PATIENT-BASED

VALUES

ECONOMIC

EVALUATION

ADOPTION FEASIBILITY

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• What? Processes to evaluate drugs in a consistent,

reproducible way e.g. ASCO, ESMO, NCCN, ICER

• Why now? Escalating costs of drugs—pressure for health

systems, patients, caregivers Identify ways to objectively compare/prioritize

drugs in the overall cancer landscape

What are Value Frameworks? And Why Now?


Understanding the Frameworks

7© 2016 Canadian Agency for Drugs and Technologies in Health

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• pERC Deliberative Framework The provide an outline of all of the elements that should

be considered by pERC during its review. No single element overrides another, rather pERC uses the sum of all elements to formulate a funding recommendation

• ASCO Framework To compare the relative clinical benefit, toxicity, and cost

of treatment in the medical oncology setting

• ESMO Framework To provide an objective and reproducible approach that

allows comparisons of the magnitude of benefit

Comparison of the Frameworks


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Mapping the ASCO and ESMO Frameworks to pERC’s Deliberative Framework

* Please note: Effect includes quality of life data

Clinical Benefit

ASCO ESMO

Effect* ü ü-

Safety ü ü

Patient-Based Values

ASCO ESMO

Experience with

Disease

Experience with drug

û û

û û

EconomicEvaluation

ASCO ESMO

CostEffective-ness

Drug Cost

û û

ü û -

Adoption Feasibility

ASCO ESMO

Budget Impact

Implementation

û û

û ûBurden of Illness

û ûNeed û û


pERC’s Deliberative Framework

Provides a quantitative score to allow for comparison across drugs

A catalyst to begin the discussion on how new expensive cancer drugs are valued and their comparative values (for a cancer type and across cancer types)

Only includes clinical trial, excludes: Patient values Burden of Illness Need Feasibility Cost-effectiveness Budget impact

Doesn’t apply to non-comparative studies

Doesn’t address issues of cross trial comparisons

Not population focused ESMO excludes hematology

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Strengths and Limitations of ASCO and ESMO Frameworks


Case Studies

11© 2016 Canadian Agency for Drugs and Technologies in Health

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• 2 RCTs- CORRECT – regorafenib monotherapy vs placebo

(multicenter/international)- CONCUR – regorafenib monotherapy vs placebo (Asian

patients)• pERC Recommendation

- The pCODR Expert Review Committee (pERC) does not recommend funding regorafenib for patients with mCRC

- …because regorafenib plus best supportive care had only a very modest progression-free survival and overall survival benefit, moderate but not insignificant toxicities, and a similar decline in quality of life.

Regorafenib for Metastatic Colorectal Cancer


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ASCO Value Framework

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Outcome 1 2 3 4 5 MultiplierImprovement

in median overall survival

>0-24% 25-49% 50-75% 76-100%Double

the median OS

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Improvement in median

progression-free survival

>0-24% 25-49% 50-75% 76-100%Double

the median

PFS11

Response Rate >0-20% 21-40% 41-60% 61-80% 81-100% 8

ASCO – Step 1 Clinical Benefit

Median OS:6.4 months (treatment) vs 5.0 months (control) – 28% (CORRECT)8.8 months (treatment) vs 6.3 months (control) – 40% (CONCUR)

Clinical Benefit Score: 2 * 16 = 32

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Enzalutamide =8 rows with >1Placebo =6 rows with >1

=(8-6)/6 =33%

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Toxicity -20 -10 0 10 20Does the new

regimen represent an improvement in

toxicity over the standard of

care/comparator?

75-100% increase in grade 3-5 toxicities

50-74% increase in grade 3-5 toxicities

<49% increase to

<49% decrease in grade 3-5 toxicities

50-74% decrease in grade 3-5 toxicities

75-100% decrease in grade 3-5 toxicities

ASCO – Step 2 Toxicity

Treatment n=21 vs control n=10 – 110% (CORRECT)Treatment n=12 vs control n=5 – 140% (CONCUR)

Toxicity score = -20

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• Palliation bonus – 10 points• Treatment-free interval bonus – up to 20 points

ASCO – Step 3 Bonus Points

ASCO – Step 4 Calculate Net Health Benefit Score

Combine clinical benefit + toxicity + bonus points= 32 (clinical benefit) + (-20) (toxicity) + 0 bonus points= 12/130

NOTE: Drug acquisition cost is also included in the ASCO framework

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Regorafenib for Metastatic Colorectal Cancer – ESMO

CORRECTΔ 1.4 months & HR=0.77

Note: CONCURΔ 2.5 months & HR=0.55 Grade 3

X

X


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Regorafenib for Metastatic Colorectal Cancer – ESMO

No similar decline

No grade 3/4 54% vs. 16%

X

CORRECT study final adjusted magnitude of clinical benefit grade is 1 out of 5CONCUR study final adjusted magnitude of clinical benefit grade is 3 out of 5


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Case Studies – Summary Table

*pERC reviewed two trials. Here, one trial is scored.

Drug pERC Rec ASCO Score ESMO Score Gaps Regorafenib Negative 12 out of 130 1out of 5 2 trials, varying

scores12 out of 130 3 out of 5

or Ibrutinib Positive

(conditional) 24 of out 130

• Median OS PFS not reached

• Clinical benefit scored using RR

N/A hematology Medians not reached, risk of diluting clinical benefit or no assessment

Bevacizumab +capecitabine

Positive* (conditional)

44 out of 130 for PFS16 out of 130for OS

3 out of 4 for PFS

2 out of 5 for OS

Scores variesbased on outcome

Aldesleukin Positive* (unconditional)

Undetermined

• Single arm trial, unable to assess toxicity

Undetermined

• Framework not applicable

No assessment for non-comparative

studies


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• The ASCO and ESMO frameworks have been designed for different jurisdictions and audiences (i.e. different context)

• They are not a “magic bullet” solutions to drug funding prioritization

• The frameworks do not explicitly consider any information beyond the clinical trial (and drug cost—ASCO)• Other issues such as need and equity will always be a

part of cancer drug funding decisions

What Have We Learned?


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• Identify if components of the value frameworks could be used in addition to pERC’s Deliberative Framework

• Consider options for adapting and implementing the frameworks and assess if there are practical, reproducible methods to address some of the limitations

Next Steps


Healthcare

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