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 Evidence synthesis Implementation 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 FEV 1 (t)= FEV 1 (t 0 )+(t- t 0 ).(β 1.X 1 +β 2.X 2 + … +u 1.Z 1 + u 2.Z 2 + …)+ε Zafari et al, under review 12 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 review 14 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)

18. 18 Methods Other challenges Discovery Proof of efficacy Proof of efficiency Submission to CADTH Discovery Proof of efficacy Proof of efficiency I have a drug that works, and is good for Canada Show me the proof I have a drug that works, and is good for Canada Show me it works, and I will let you know if we think it is good for Canada

19. 19 Methods Why is it relevant? Efficacy is discovery, efficiency is value demonstration The former is a duty of the innovator Government agencies as Resource Stewarts need to own the latter

20. 20 Methods iKT

21. 21 The Process Evidence Synthesis FEV1 as the hallmark of COPD progression Previous focus on population-average, need for original data analysis to inform DES