Use of IPD-based
NMA in
Economic
Models for HTA
Yumi Asukai
ISPOR Milan 2015
Economic Evaluation in HTA
Emphasis on economic evaluation for HTA differ across markets
• Economic Models have varying roles in each country’s national HTA
process.
• Focus on those who regularly utilise cost-effectiveness modelling in
their national HTA.
NICE
TLV
CADTH
INFARMED
PBAC
HIRA
SMC
More Impact
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Less Impact
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Evidence Synthesis in Economic Models
 Use of evidence synthesis
results in CE models are
increasingly more common
 As cost-containment
pressures mount for
governments, payers are
looking to ensure best valuefor-money for the medicines
they reimburse
 This leads to two main
behaviours from the payer
body
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Two major concerns from Payers
Concerns with Uncertainty
•
What sources of uncertainty are
there in the model?
•
How large is the possible error we
will make in supporting this
medicine?
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Looking for “better” value-formoney
• Are there sub-population who have
better cost-effectiveness (and
therefore a smaller budget-impact?)
• This could differ from any identified
population within the regulatory
dossier
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2
Use of IPD-NMA can address both of these concerns
Types of uncertainty
Uncertainty
Variability
• Variability is
observed
differences among
patients due to
chance
Heterogeneity
Parameter
Structural
• Heterogeneity is • Parameter
• Structural
observed
uncertainty is how uncertainty is due
differences due to far the estimated
to different
differences in
parameter value is frameworks that
underlying patient from the true value impose differing
characteristics
assumption in the
model
Briggs et al. Decision Modelling for Health Economic Evaluation.
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How does the use of IPD-NMA address these concerns?
Better subgroup data
• Identify sub-groups of interest =>
reimbursement for a well-defined subpopulation (also with less budget impact)
Quantify impact
of patient
characteristics
• Account for heterogeneity
• Construct better-informed model framework
to reduce structural uncertainty
Increased
precision
• Less parameter uncertainty => reduction in
decision uncertainty
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A few examples of recent technology appraisals from
NICE
Edoxaban in
SPAF
Vedolizumab in
Crohn’s Disease
Aflibercept in
DME
• TA355
• Published
September
2015
• Prevention of
stroke and SE
in non-valvular
atrial fibrillation
• TA352
• Published
August 2015
• Treatment of
moderately to
severely active
Crohn’s
Disease
• TA346
• Published July
2015
• Treatment of
diabetic
macular edema
https://www.nice.org.uk/guidance/published?type=ta
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Edoxaban in SPAF
 RCT conducted with warfarin
 NMA to establish relative treatment effect with novel oral
anti-coagulants (NOAC): dabigatran, rivaroxaban, apixaban,
using aggregate data.
 Primary endpoint was time to first stroke/SE and relative
treatment effect was expressed as a hazard ratio.
 Where HRs were not available from the NMA for patients
with a CHADS2>+2, HRs used from All Patient dataset.
 In the RCT, the ERG determined that proportional hazards
assumption was violated
What issues might have arisen here that could be
overcome with the use of IPD?
https://www.nice.org.uk/guidance/TA355/documents/atrial-fibrillation-nonvalvular-edoxaban-tosylate-id624-committee-papers2
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Vedolizumab in Crohn’s Disease
 RCT conducted with placebo
 NMA to establish relative treatment effect with adalimumab
and infliximab.
 ERG critique of the company NMA included comments on:
 ‘Entire Population’ analysis mixed population with different proportions
of characteristics such as proportion previously failing anti-TNFs,
which is thought to be treatment modifying
 Several studies in the network excluded patients with strictures
 Some studies did not report proportion of patients with fistulising
disease.
Which of these issues might be overcome with the
use of IPD?
https://www.nice.org.uk/guidance/TA352/documents/crohns-disease-moderate-to-severe-vedolizumab-committee-papers-part-22
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Aflibercept in DME
 RCT conducted with laser photocoagulation
 NMA to establish relative treatment effect with ranibizumab
 In a sub-group analysis of patients whose central retinal
thickness (CRT) is at least 400 micrometers, the relative
risks of the NMA from the total population are retained, and
not specific to the sub-group in question.
 NICE ultimately recommended aflibercept for those with a
CRT of >= 400 micrometers.
How did the appraisal committee arrive at this
conclusion?
What might have been done differently?
https://www.nice.org.uk/guidance/TA346/documents/macular-oedema-diabetic-aflibercept-committee-papers4
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Transaction costs of obtaining IPD vs opportunity cost
of ‘guessing’
o IPD usage is generally
considered favourable,
conferring increased precision
and decreased uncertainty
AD
IPD
AD
IPD
o IPD use can also enrich the
underlying economic analysis
itself
o IPD acquisition costs are high
o However, all of these examples
and many more involve
extensive scenario and
sensitivity analyses by the ERG
to attempt simulating ‘what might
have been’, which could be
answered with the use of IPD.
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Key Takeaways
Advantages of using IPD-NMA in an economic evaluation are clear,
but we know there are transaction costs involved in obtaining the data
IPD-NMA
Advantages
IPD-NMA
Disadvantages
What are the issues to consider as a policy or decision maker, and
what practical next steps should they take?
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