Transcript Mark_PROMISEecon - Clinical Trial Results

The PROspective Multicenter Imaging Study for Evaluation of Chest
Pain (PROMISE) Trial: Economic Outcomes
Daniel B. Mark, MD, MPH
Co-Investigators/Econ Team
Professor of Medicine
Vice Chief for Academic Affairs, Cardiology Division
Duke University Medical Center
Director, Outcomes Research
Duke Clinical Research Institute
Kevin Anstrom
Patricia Cowper
Linda Davidson Ray
Udo Hoffmann
Manesh Patel
Lawton Cooper
Kerry Lee
Pamela Douglas
Jeff Federspiel
Melanie Daniels
Financial Disclosures
Consulting
Milestone
Medtronic
CardioDx
St Jude Medical
Research Grants
NIH
Eli Lilly & Company
AstraZeneca
Gilead
AGA Medical
Bristol Myers Squibb
March 15, 2015
PROMISE Trial Background:
Moving From Controversy to Evidence
• Noninvasive ability to directly visualize the coronary arteries of
patients with chest pain has long been on Cardiology’s Wish List
• As coronary CT angiography evolved into a test that might actually be
able to fulfill this wish, controversy broke out
• The PRO side: CTA would allow precision care - only the patients who
needed revascularization would actually go to cath and the rest would
avoid it –  invasive testing,  unneeded revascularization,  false
positives,  $$
• The CON side: CTA would:  non-invasive and invasive testing to
clarify ambiguous findings,  radiation exposure,  $$
PROMISE: Design Overview
10,003 patients with symptoms of CAD
•New or worsening chest pain or symptoms w/out known CAD
•Low to intermediate risk
•Planned noninvasive testing for diagnosis
193 sites
(US, CA)
1:1 Randomization
Stratified by site and intended
functional test
Usual Care Arm
Intervention Arm
Pre-selected Functional Testing
Anatomic Testing 64-slice CTA
Median study follow-up 25.2 months
1° endpoint: composite of death, MI, UA hosp, or major procedural complication
2° aims incl.: cost and cost effectiveness
PROMISE Trial:
CTA Patient Outcomes Not Superior to Functional Testing
“Strategy of initial CTA, as compared with
functional testing, did not improve clinical
outcomes over a median follow-up of 2 years.”
Douglas PS et al
NEJM 2015
PROMISE Primary Endpoint Results:
Death, MI, Unstable Angina, Major Procedural Complications
Douglas PS et al
NEJM 2015
PROMISE Economic Substudy:
Primary Objectives
• Measure and compare cumulative total costs as
randomized
• If CTA outcomes superior, estimate cost effectiveness
of anatomic strategy
PROMISE Economic Substudy:
Calculation of Medical Costs
• 96% (9649) of PROMISE cohort in Economic Substudy
• Initial diagnostic test technical fees
- Bottom up estimate (resource-based cost accounting methods) from
large proprietary registry (Premier Research Database)
• Hospital-based facility costs
- UB 04 bill forms provide hospital charges by department
- Department-specific ratios of costs to charges (RCCs) used to convert
charges to estimates of cost
• MD professional fees for testing and hospital services
- Medicare Fee Schedule
PROMISE Economic Substudy:
Analysis Methods
• Comparisons by intention to treat principle
• Costs to 3 years estimated, accounting for censoring using
inverse probability weighting methods
• Bootstrapped confidence intervals: 1000 replications (500
in subgroup analyses), 95% confidence intervals
PROMISE Economic Substudy:
Baseline Characteristics
Demographics
Age, mean
Female
Cardiac risk factors
BMI, mean
Hypertension
Diabetes
Dyslipidemia
Family history premature CAD
Current or past smoking
Primary symptom chest pain or DOE
Typical or atypical angina
Pretest probability of CAD
Functional
(N=4,831)
Anatomic
(N=4,818)
60.9 ± 8.3
54%
60.7 ± 8.3
52%
30.6 ± 6.2
66%
22%
68%
32%
51%
88%
89%
53%
30.6 ± 6.2
66%
22%
67%
33%
51%
88%
89%
54%
PROMISE Economic Substudy:
Estimation of Initial Diagnostic Testing Costs
Mean Cost*
MD Fees**
Total
CTA
$285
$119
$404
Echo w/ exercise stress
Echo w/ pharmacologic stress
$428
$415
$86
$86
$514
$501
ECG-only Stress
$137
$37
$174
Nuclear w/ exercise stress
Nuclear w/ pharmacologic stress
$829
$1015
$117
$117
$946
$1132
Dx Test
*based on costs in Premier database
**based on Medicare Fee Schedule
PROMISE Economic Substudy:
Cumulative Total Costs by ITT and Mean Cost Difference (95%CI)
Difference in Cost
(Anatomic – Functional)
Cumulative Cost
$694
$279
$358
$388
PROMISE Secondary Endpoints:
90-Day Catheterization and Revascularization Rates
CTA
(n=4996)
Functional
(n=5007)
609 (12.2%)
406 (8.1%)
Revascularization
311 (6.2%)
(51% of cath patients)
158 (3.2%)
(39% of cath patients)
No CAD on cath
170 (3.4%)
(28% of cath patients)
213 (4.3%)
(52% of cath patients)
Invasive cath
PROMISE Economic Substudy:
Cost Differences by Categories 0-3 and 4-12 Months
-$378
$68
$357
$203
$17
$12
$279
-$17
$49
$43
-$10
$8
$8
$81
PROMISE Economic Substudy:
Cost Differences by Categories Years 2 and 3
$35
-$12
-$69
$7
$15
$53
$29
$10
$20
-$35
-$97 $311
$97
$306
PROMISE Economic Substudy:
2-Year Cost Difference Thresholds From Bootstrap Analysis
Cumulative
distribution of
mean cost
difference
[CTA-FXN]
from 1000
bootstrap
replications
out to 24
months
Cost difference:
< $500 – 62% of samples
< $750 – 81% of samples
< $1000 – 93% of samples
PROMISE Economic Substudy:
Pre-Randomization MD Choice of Functional Test Subgroups
Overall (N= 9,649)
ECG-Only (N= 858)
Echo (N= 2,204)
Nuclear (N= 6,587)
Months 0-3
Months 0-36
Mean Cost Difference
Mean Cost Difference
PROMISE Economic Substudy:
Caveats
• Costs of initial testing from external data source
• Significant deviations by centers from testing costs
used in this analysis might alter relative cost
positions of the two strategies
• Outpatient medications not counted
• QOL and employment status still being analyzed
PROMISE Economic Substudy:
Summary
• In stable patients with new chest pain, CTA strategy improved efficiency of use of
invasive cath (fewer normal caths, higher proportion of caths also getting revasc)
• But despite lower testing costs for CTA compared with stress echo (~$100 less) and
stress nuclear (~$630 less), net effect was to drive a small (<$500), statistically nonsignificant increase in cost
• After 90 days, very little test strategy-related differences in costs out to 3 years
• Coronary CTA may not be the “holy grail” of diagnostic testing once hoped for, but its
more liberal use following PROMISE standards will improve some aspects of care
without causing a major new economic burden on the health care system