1. The PROspective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) Trial: Economic Outcomes
Daniel B. Mark, MD, MPH
Professor of Medicine
Vice Chief for Academic Affairs, Cardiology Division
Duke University Medical Center
Director, Outcomes Research
Duke Clinical Research Institute
Co-Investigators/Econ Team
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

2. 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,  $$
The CON side: CTA would:  non-invasive and invasive testing to clarify ambiguous findings,  radiation exposure,  $$

3. 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
Intervention Arm
Anatomic Testing 64-slice CTA
Usual Care Arm
Pre-selected Functional Testing
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

4. 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

5. PROMISE Primary Endpoint Results: Death, MI, Unstable Angina, Major Procedural Complications
Douglas PS et al
NEJM 2015

6. PROMISE Economic Substudy: Primary Objectives
Measure and compare cumulative total costs as randomized
If CTA outcomes superior, estimate cost effectiveness of anatomic strategy

7. 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

8. 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

9. PROMISE Economic Substudy: Baseline Characteristics
Functional
Anatomic
(N=4,818)
(N=4,831)
Demographics
Age, mean
60.9 ± 8.3
60.7 ± 8.3
Female
54%
52%
Cardiac risk factors
BMI, mean
30.6 ± 6.2
Hypertension
66%
Diabetes
22%
Dyslipidemia
68%
67%
Family history premature CAD
32%
33%
Current or past smoking
51%
Primary symptom chest pain or DOE
 88%
Typical or atypical angina
89%
Pretest probability of CAD
53%

10. PROMISE Economic Substudy: Estimation of Initial Diagnostic Testing Costs
Dx Test
CTA
Echo w/ exercise stress
Echo w/ pharmacologic stress
ECG-only Stress
Nuclear w/ exercise stress
Nuclear w/ pharmacologic stress
Mean Cost*
$285
$428
$415
$137
$829
$1015
MD Fees**
$119
$86
$37
$117
Total
$404
$514
$501
$174
$946
$1132
*based on costs in Premier database
**based on Medicare Fee Schedule

11. (Anatomic – Functional)
PROMISE Economic Substudy: Cumulative Total Costs by ITT and Mean Cost Difference (95%CI)
Difference in Cost
(Anatomic – Functional)
Cumulative Cost
$694
$358
$388
$279

12. PROMISE Secondary Endpoints: 90-Day Catheterization and Revascularization Rates
Invasive cath
Revascularization
No CAD on cath
CTA
(n=4996)
609 (12.2%)
311 (6.2%)
(51% of cath patients)
170 (3.4%)
(28% of cath patients)
Functional
(n=5007)
406 (8.1%)
158 (3.2%)
(39% of cath patients)
213 (4.3%)
(52% of cath patients)

13. 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

14. PROMISE Economic Substudy: Cost Differences by Categories Years 2 and 3
$10
$20
-$35
-$97
$311
$97
$306
$35
-$12
-$69 $7
$15
$53
$29

15. 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

16. PROMISE Economic Substudy: Pre-Randomization MD Choice of Functional Test Subgroups
Months 0-3
Months 0-36
Overall (N= 9,649)
ECG-Only (N= 858)
Echo (N= 2,204)
Nuclear (N= 6,587)
Mean Cost Difference

17. 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

18. 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 non- significant 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