How to integrate external evidence into within trial economic evaluations?

Mohsen Sadatsafavi MD, PhDUniversity of British Columbia

2015.04.13

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Conflict of Interest

No apparent or perceived conflict of interest

Received CIHR fellow-ship award for this work

All interpretations are my own

Our TeamCarlo Marra, Shawn Aaron, Stirling Bryan

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Outline

• A novel method for incorporating external evidence in economic evaluations

• Context in which it is applicable• What it does• A running example• Pros + Cons + conclusions

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Economic trialsas vehicles for evaluations

• Model-based evaluations• Evidence is ‘parameterized’ and fed into a computer

program (mathematical function)

• simulation

• Trial-based evaluations• Individuals are assigned to competing treatments and

their experiences is represented through cost and effectiveness values

• (bivariate) statistical inference• bootstrap as s popular paradigm

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Issues with trial-based CEAs

Failure to compare all available options

A truncated time horizon

Lack of relevance to the jurisdiction of interest

Failure to incorporate all evidence the most damning criticism

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ContextAn example: OPTIMAL trial in COPD

• Mono, double, and triple inhaler therapy in COPD (T1, T2, T3)

• N=442• Follow-up 1 year• Primary outcome: exacerbation rate• Prospective economic evaluation component• Results

– RR of T2 v. T1: 1.01 (0.59 – 0.73)– RR of T3 v. T1: 0.84 (0.47 – 1.49)

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ContextOPTIMAL CEA

• Sequence of imputation, regression, outcome calculations within a bootstrap envelope

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Trialist versus economist

Treatment effects (RR=0.84, NS) ICER=243K

Pooled estimate

Regression-based methods Bootstrap methods

OPTIMAL trial

Trialist Economist

Decision maker

Welte et. al. T3 v. T1

RR=0.38 (0.28 – 0.57)

Meta-analyst

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CONTEXTReconciling external evidence in RCT-based CEAs

Desist RCT-based CEA and resort to model-based evaluation Paradigm shift

Switch to parametric Bayesian evidence synthesisMCMC using WinBUGS (technical, lots of programing, model

convergence etc) Off-putting

Stay with the bootstrap-based methods, incorporate external evidence

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MethodsRCT-CEA without external evidence

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MethodsRCT-CEA with external evidence

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ResultsCase study in COPD

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ResultsCase study in COPD

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Conclusions

• Theoretically, possible to use trials as ‘vehicle’ for evidence synthesis, yet avoid the ‘most damning criticism’

• Practically, with too many parameters, it can be computationally prohibitive

• Best use is in sensitivity and secondary analyses• What if we incorporate the results of the study by xyz?

• The experts in our team believe it is almost impossible that chemo+radiation increases the risk of metastasis ->half-flat priors

FacultyMohsen SadatsafaviJ Mark FitzGeraldStirling BryanLarry Lynd

Research StaffHamid TavakoliTania ConteRoxanne Rousseau

StudentsZafar ZafariWenjia Chen

Thank You!

msafavi@mail.ubc.ca

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