Transcript The Duke Stroke Policy Model (SPM)

Validation / citations
Validation
 Expert
review of model structure
 Expert review of basic code
implementation
 Reproduce original inputs
 Correctly respond to changes in
parameters
 Consistent with other analyses
 Consistent across versions
Documentation specifications
Validation requires adequate
documentation to…
Describe clinical model
Describe programming algorithms
Describe inputs (sources / values /
data quality)
Describe validation strategy
Citations
Basic rationale and structure -- Matchar et
al., Annals of Internal Medicine (1997)
 Bootstrapped sensitivity analysis -Parmigiani et al., Medical Decision Making
(1997)
 Application to acute stroke trial -- Samsa et
al., Journal of Clinical Epidemiology (in
press)

Outline
Rationale
for modeling
Stroke model described
Applying the SPM to a
randomized trial (*)
Extensions
Applying the SPM to an RCT
Basic idea: After the short follow-up period
typical of an RCT, we are likely to observe
that the intervention induces small shifts in
the distribution of morality / disability
(measured at the conclusion of follow-up).
Modeling can be used to account for the
effects of these shifts on long-term
outcomes.
Disability measure
 Disability
could be measured by the
Rankin Scale (RS), Barthel Index (BI), or
a number of other instruments.
 For concreteness, we use the RS with 5
categories. The analysis easily extends
to other scales and/or cut-points.
Risk (hazard) ratios for disability
on subsequent outcomes*
RS Utility h(IS) h(MI) h(DT) Cost
0-1
2
3
4
5
.80
.65
.50
.35
.20
1.00
1.05
1.12
1.24
1.30
1.00
1.07
1.14
1.26
1.31
1.00
1.11
1.27
1.71
2.37
1.00
1.27
1.94
3.98
6.01
*As derived by an expert panel, supported by
published and unpublished literature
Rationale
The utilities for RS of 0-1 and 5 were
obtained from the PORT’s patient survey.
• Other values obtained by interpolation
• Consistent with unpublished RCT data
 Increased hazard of death results from
sequelae of inactivity such as aspiration
pneumonia, etc.
 Daily costs greatly increase when disability
level implies high likelihood of
institutionalization.

SPM results by Rankin*
RS
0-1
2
3
4
5
Survival
10.60
9.99
9.28
8.22
7.09
QALY Cost
6.07
143,820
4.70
167,602
3.37
217,039
2.13
328,895
1.09
403,911
*Beginning 6 months after IS, for patients
with mean age 70 years
Thought experiment -- typical
RCT results (6 month follow-up)
Intervention
QALY
0.25
Cost
27,000
Placebo
0.23
24,000
That is, little difference in QALY in absolute
terms. For cost, we assume equivalent
utilization plus the cost of the drug.
Typical RCT results (cont’d)
RS
0-1
2
3
4
5
Died
Intervention
31%
21%
11%
6%
11%
20%
Placebo
25%
15%
10%
10%
15%
25%
Typical results (cont’d)
The previous results describe a
“break-through drug”, but the
ICER based upon 6 months of
follow-up is only (27,000-24,000) /
(0.25-0.23) = 150,000 $/QALY.
Combining short- and
long-term outcomes
For each patient, we assign long-term
outcomes (cost and QALYs) based
upon RS at 6 months. For example,
total costs then become 6-month
costs (observed) + expected longterm costs (simulated).
Long-term QALYs by group
 Intervention:
(.31)(6.07) + (.21)(4.70) + (.11)(3.37)
+ (.06)(2.13) + (.11)(1.09) + (.20)(0) = 3.49 QALY
 Placebo: (.25)(6.07) + (.15)(4.70) + (.10)(3.37) +
(.10)(2.13) + (.15)(1.09) + (.25)(0) = 2.94 QALY
– Identical multipliers -- groups only differ in
proportion of patients in each RS category
– Same weighted average calculations for cost
Comprehensive CEA
 Intervention
QALY = 0.25+3.49 = 3.74
 Intervention cost = 27,000+167,818 =
194,818
 Placebo QALY = 0.23+2.94 = 3.17
 Placebo cost = 24,000 + 176,275 =
200,275
 ICER = (194,818-200,275)/(3.74-3.17) =
-9,573 $/QALY
Conclusion
By considering its long-term
effects, the intervention moves
from “not cost effective” to “cost
saving,” even if the price of the
drug is increased substantially.
This result holds across a wide
range of sensitivity analyses.
Outline
Rationale
for modeling
Stroke model described
Applying the SPM to a
randomized trial
Extensions (*)
Extensions
International
applications
Planning trials
International applications
 Basic
idea: Use the same SPM but change
the inputs.
 In theory, every component of the input
data (e.g., natural history, effect of
covariates, effect of interventions, QOL,
cost) could differ by nation.
 In practice, the biggest differences will
involve utilization patterns (and thus cost).
Comment
The size of the task depends upon the
difficulty in estimating the relevant
parameters.
This, in turn, depends what we are
willing to assume versus what will
require additional data collection.
Once new estimates have been derived,
inserting them into the SPM is
straightforward.
International costs
Costs are affected by
Different utilization patterns
Different unit prices
Different payment mechanisms
/ perspectives (affecting which
components of cost to include
in the calculation)
Recommendation
 Begin
with US data on utilization and unit
prices.
 Then use expert judgement (supported by the
literature as available) to posit any changes in
utilization patterns.
 Attach country-specific unit prices.
 Limit the analysis to the cost categories and
time periods of interest to decision-makers in
that country.
Planning trials
 The
SPM can help to determine the
(minimum) clinically important
difference in short-term disability.
 This, in turn, would be the basis for
the trial’s sample size calculations.
Observation
 Many
stroke trials have been underpowered.
 That is, the size of the effect which
is significant from the perspective of
public health / CEA is much smaller
than that suggested by clinical
intuition (Samsa et al, Journal of
Clinical Epidemiology, in press).
Observation
Many RCTs of acute stroke
treatments have had other
sources of statistical inefficiency - for example, pertaining to the
choice of target population, the
choice of measure, and so forth.
Summation
 Because
most benefits of stroke
treatments accrue in the long-term,
modeling is necessary.
 The SPM is a well-validated model which
can be helpful in both the planning and
analysis of trials.
 Planned extensions include international
practice patterns and user-friendly
software.