This document summarizes the Evaluation Platform in COPD (EPIC) project. The project aims to create the first Canadian outcomes model of COPD to evaluate case detection strategies and support policy, practice, and research. It will use a whole disease modeling approach with discrete event simulation to model the natural history of COPD. The model will incorporate demographics, smoking behaviors, lung function decline, comorbidities, costs and quality of life. Evidence from studies like the Lung Health Study will be synthesized to parameterize the model. It will be implemented on a dedicated platform to enable probabilistic sensitivity analysis and evaluation of various screening strategies. An expert advisory committee and engagement with patients and stakeholders will ensure the model is calibrated, validated and

1. In search of equity, efficiency and impact in HTA:
the case for Evaluation Platform in COPD
(EPIC)
Mohsen Sadatsafavi MD, PhD
University of British Columbia
2015.04.13

2. 2
Disclosures and Acknowledgements
• I am not aware of any actual or potential conflicts of
interest
• Have received funding for this work
– The Canadian Respiratory Research Network
– Genome Canada
• Team
– Core development team: Zafar Zafari & Amir Khakban
– Co-investigators: Don Sin, J Mark FitzGerald, Stirling Bryan

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Outline
• The Need
– COPD as an escalating public health challenge
– Research community’s need for a framework to attach value to the
research pipeline
• Objectives
– Overall & specific
• The approach
– Whole Disease Modeling as the conceptual framework
– Conceptualization -> Evidence synthesis ->Implementation
– iKT
• Challenges & Rewards

4. 4
The Need
COPD, undefeated!
Canadian Lung Association – 2010, Khakban et. al. under reivew
• The fourth common cause of death, to be the third by
2020
• The only common chronic disease whose burden is
increasing
• Under-diagnosis epidemic: for every 2 diagnosed
COPD patients, 3 remain undiagnosed

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The Need
The Canadian Respiratory Research Network
• First CIHR-funded national respiratory network in
Canada
• 13 research platforms (including Health Economics)
• Major focus on health policy and public health
research on chronic airway diseases
• Burden and relevance of unidentified obstructive
lung disease a major focus of the network
www.respiratoryresearchnetwork.ca/

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The Need
Explicit health economic studies & evaluations
• Environmental Health platform
– Attributable burden of air pollution
• Population Health platform
– Attributable burden of asthma-COPD overlap syndrome
• Biomarker Discovery platform
– Cost-effectiveness and budget impact of
diagnostic and prognostic biomarkers
• Health Services Research platform
– Cost-effectiveness of screening/case detection of
COPD at community level

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The Need
Our response
One model to rule them all

8. 8
Evaluation Platform in COPD
Objectives
• Specific objective
– To evaluate COPD case detection strategies (in
different at-risk subgroups) in terms of
epidemiological consequences, cost-effectiveness,
and budget impact.
• General objective
– To create the first Canadian outcomes model of
COPD to support policy, practice, and research.

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The Process
Conceptual framework
• Whole Disease Modeling
1: Modeling the complete natural history of COPD
2: Capturing subgroups/pathways of care
3: Transferability of decision node
4: Enabling evaluation of disinvestment options
– Individual-level simulation
• Discrete Event Simulation
– Metric for modeling natural history of disease
• FEV1, FVC
– Open population
Tappenden et. al. Value in Health, 2012

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The Process
Conceptualizations
EvidencesynthesisImplementation
Calibration/Validation
Expert Advisory
Committee

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The Process
Conceptualization
• Demographics
– Agent creation, dynamic risk factors (e.g., weight)
• Smoking
– Incidence, remission, and relapse
• Lung Function
– Representing the core natural history component
• Co-morbidities
– As important determinants of burden ofCOPD
• Payoffs
– Costs, quality of life, life years, number of exacerbations

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The Process
Evidence Synthesis(A)
(B)
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FEV1(L)
Time (years)
95% coverage interval
Mean FEV1 decline
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1
1.5
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0 1 2 3 4 5 6 7 8 9 10 11
FEV1(L)
Time (years)
Chart Title
95% coverage interval
Mean FEV1 decline
FEV1(t)= FEV1(t0)+(t- t0).(β1.X1+β2.X2+ …
+u1.Z1+ u 2.Z2+ …)+ε
Zafari et al, under review1
Web App:
http://resp.med.ubc.ca/software/ipress/epic/fev1pred/
Mixed-effects regression using the
Lung Health Study Data

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The Process
Implementation
• Scalable platform, ready to accommodate
future questions
• Enable PSA and even EVI
– Require two-level Monte Carlo simulation
• Fast platform is required as the number of
simulation runs will be enormous
– Dedicated implementation platform

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The Process
Calibration/Validation
Zafari et al, under review1
Internal validity External validity
LHS EUROSCOPE
Plans:
- An external study for validation of exacerbation equations
- Validation of model outputs against BC administrative health data

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Integrated Knowledge
Translation
• Require constant engagement of
– Expert to supply the ‘science’ behind the model
– Stakeholders to navigate overall development process
– Patients to prioritize outcomes, characterize real-world
experience of care
• To be impactful, the product should be
– Available to all relevant stakeholders
– Transparent in structure and assumptions
Careful documentation of structure and associations
 Interactive, free to use, Web Interface (iPRESS)
http://resp.med.ubc.ca/software/ipress/epic/

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Challenges and Rewards
• Soliciting clinical input in a meaningful way difficult
• Significant time and resources required, in the era of
publish yet still perish
• Is it possible to have a model that only needs to be
‘tweaked’ for new evaluations?
• Sustainability?
• Conceptualization forces us to think -> better
understanding of the disease process
• Tremendous support (scientific and logistical)
• CONSISTENCY
• Transferability of methodology/technology

17. Faculty
Mohsen Sadatsafavi
J Mark FitzGerald
Stirling Bryan
Larry Lynd
Research Staff
Hamid Tavakoli
Tania Conte
Roxanne Rousseau
Amir Khakban
Students
Zafar Zafari
Wenjia Chen
Thank You!
msafavi@mail.ubc.ca
Respiratory Evaluation Sciences Program (resp.med.ubc.ca)