Post on 19-Dec-2015
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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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)