In search of equity, efficiency and impact in HTA: the case for Evaluation Platform in COPD

(EPIC)

Mohsen Sadatsafavi MD, PhDUniversity of British Columbia

2015.04.13

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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

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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 NeedThe 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 NeedExplicit 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 NeedOur response

One model to rule them all

Prevention (smoking session)

Environmental contribution

Early diagnosis (screening/case

finding/diagnostic biomarkers)

Early intervention (CEA,EVI)

Optimal pharmacotherapy

Biomarkers for exacerbation

Optimal treatment of exacerbations

Readmissions

Self management

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Evaluation Platform in COPDObjectives

• 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 ProcessConceptual framework

• Whole Disease Modeling 1: Modeling the complete natural history of COPD2: Capturing subgroups/pathways of care3: Transferability of decision node4: 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

Evidence synthesis

Implementation

Calibration/Validation

Expert Advisory Committee

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The ProcessConceptualization

• 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 ProcessEvidence Synthesis

(A)

(B)

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1.5

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3.5

0 1 2 3 4 5 6 7 8 9 10 11

FEV1

(L)

Time (years)

95% coverage interval

Mean FEV1 decline

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0.5

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1.5

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2.5

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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 review12

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 ProcessImplementation

• 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 ProcessCalibration/Validation

Zafari et al, under review14

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

FacultyMohsen SadatsafaviJ Mark FitzGeraldStirling BryanLarry Lynd

Research StaffHamid TavakoliTania ConteRoxanne RousseauAmir Khakban

StudentsZafar ZafariWenjia Chen

Thank You!

msafavi@mail.ubc.ca

Respiratory Evaluation Sciences Program (resp.med.ubc.ca)

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MethodsOther 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 CanadaShow me the proof

I have a drug that works, and is good for CanadaShow me it works, and I will let you know if we think it is good for Canada

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MethodsWhy 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

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MethodsiKT

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The ProcessEvidence Synthesis

• FEV1 as the hallmark of COPD progression

• Previous focus on population-average, need for original data analysis to inform DES