CADTH 2015 Symposium

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

3. 3
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

5. 5
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/

6. 6
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

7. 7
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.

9. 9
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

10. 10
The Process
Conceptualizations
EvidencesynthesisImplementation
Calibration/Validation
Expert Advisory
Committee

11. 11
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

12. 12
The Process
Evidence Synthesis(A)
(B)
0
0.5
1
1.5
2
2.5
3
3.5
0 1 2 3 4 5 6 7 8 9 10 11
FEV1(L)
Time (years)
95% coverage interval
Mean FEV1 decline
0
0.5
1
1.5
2
2.5
3
3.5
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

13. 13
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

14. 14
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

15. 15
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/

16. 16
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)