Prediction of the PRONOUNCE Prostate Cancer Trial in Healthcare Claims Data
Conditions: Prostate Cancer
Sponsor: Brigham and Women's Hospital

Prediction of Findings From the Ongoing PRONOUNCE Trial Using Healthcare 
Database Analyses  
DUPLICATE - PRONOUNCE 
September 9, 2021 
NCT04897958 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
1 
1. RCT Details 
This section provides a high-level overview of a published RCT that the described real-world evidence study is trying to replicate 
as closely as possible given the remaining limitations inherent in the healthcare databases. 
 
1.1 Title 
Cardiovascular Safety of Degarelix Versus Leuprolide for Advanced Prostate Cancer (PRONOUNCE Trial)  
 
1.2 Intended aim(s) 
To compare the incidence of major cardiovascular events (MACE) among advanced prostate cancer subjects treated with 
degarelix versus leuprolide. 
 
1.3 Primary endpoint for replication  
Time from randomization to the first confirmed, adjudicated occurrence of a MACE, which is defined as a composite of all-
cause death, nonfatal myocardial infarction, or nonfatal stroke through 12 months of ADT treatment. 
 
1.4 Required power for primary endpoint and noninferiority margin (if applicable) 
Based on prior literature, it was determined that 66 MACE events and 876 subjects would be required to reject a two-sided 
null hypothesis of equal hazards with 80% power at a 5% type I error rate. A hazard ratio of 0.49 with absolute event rates 
of 5.1% and 10.2% (degarelix vs leuprolide) were hypothesized. 
 
1.5 Secondary endpoint for replication (assay sensitivity) and RCT finding 
Secondary cardiovascular objectives: To assess 1) the frequency of MACE components individually (i.e., nonfatal myocardial 
infarction, nonfatal stroke, and all-cause mortality) 
 
1.6 Trial estimate 
The trial is ongoing and scheduled to complete in April 2021. 
 
2. Person responsible for implementation of replication in Aetion 
David Merola, PharmD, SM and Sushama Kattinakere Sreedhara, MBBS, MSPH, implemented the study design in the Aetion Evidence 
Platform. They are not responsible for the validity of the design and analytic choices. All implementation steps are recorded, and the 
implementation history is archived in the platform. 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
2 
 
3. Data Source(s) 
Optum CDM, IBM® MarketScan®, Medicare Diabetes 
 
4. Study Design Diagram 
 
The study design diagram visualizes key aspects of the longitudinal study design for expedited review. 
 
Figure 1. 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
3 
 
5. Cohort Identification  
 
5.1 Cohort Summary 
An active-comparator, incident-user design will be employed to compare patients that received degarelix vs. leuprolide. Subjects will 
be selected on the basis of having at least one diagnosis code indicating prostate cancer, male sex, and a history of atherosclerotic 
cardiovascular disease. Subjects will be excluded if they were not treatment-naïve with respect to prostate cancer, had a record of 
uncontrolled diabetes or hypertension within 30 days prior to treatment initiation, had a history of long QT syndrome or risk factors 
thereof (i.e., heart failure, hypokalemia, or medications known to prolong the QT interval), or an acute myocardial infarction, stroke, 
or revascularization procedure within 30 days prior to treatment initiation. In contrast to the PRONOUNCE trial, patients cannot be 
required to have had established tumor staging information, angiography-verified stenosis/occlusion of vessels, and a lack of planned 
cardiac surgery at the time of treatment initiation due to poor capture of this information in administrative data. All patients were 
required to have continuous enrollment for 365 days prior to cohort entry to ensure incident use of the study drugs. 
 
5.2 Important steps for cohort formation 
Incident use of the exposure (leuprolide or degarelix) is defined as no use of the exposure drug in the 365 days prior to meeting 
all eligibility criteria and initiation of exposure.  
 
5.2.1 Eligible cohort entry dates 
The degarelix indication for treatment of prostate cancer was approved by the FDA on Dec 24, 2008. Leuprolide was 
initially approved for the same indication prior to Dec 24, 2008. 
§ IBM® MarketScan®: Dec 24, 2008 – December 31, 2018 (end of available data)  
§ Optum CDM: Dec 24, 2008 – June 30, 2020 (end of available data)  
§ CMS Diabetes: Dec 24, 2008 – Dec 31, 2017 (end of available data) 
 
5.2.2 Specify inclusion/exclusion criteria for cohort entry and define the index date 
Inclusion and exclusion criteria were adapted from the trial as closely as possible. Definitions for all inclusion/exclusion are 
provided in Appendix and are summarized in the flowcharts below.  
 
5.3 Flowchart of the study cohort assembly 
For Degarelix vs Leuprolide 
 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
4 
 
 
IBM® MarketScan® 
Optum CDM 
CMS - Diabetes 
 
Less Excluded 
Patients 
Remaining 
Patients 
Less 
Excluded 
Patients 
Remaining 
Patients 
Less 
Excluded 
Patients 
Remaining 
Patients 
All patients in our database 
 
200,203,908 
 
78,202,636 
 
23,466,175 
Patients with Degarelix/Leuprolide [measured 
between Dec 24, 2008 and Dec 31, 2019.] 
-199,937,514 
266,394 
-78,046,787 
155,849 
-23,212,628 
253,547 
Excluded due to insufficient enrollment [-365, 
0] 
-94,870 
171,524 
-36,242 
119,607 
-125,589 
127,958 
After wash-out for prior use of reference 
(Leuprolide) [-365, -1] 
-106,281 
65,243 
-77,869 
41,738 
-96,813 
31,145 
After wash-out for prior use of exposure 
(Degarelix) [-365, -1] and Excluded because 
patient qualified in >1 exposure category 
-1,961 
63,282 
-2,153 
39,585 
-3,397 
27,748 
Inclusion only Male gender [-365, 0] 
-43,683 
19,599 
-17,401 
22,184 
-183 
27,565 
Inclusion Prostate Cancer [start of all available 
data, 0] 
-784 
18,815 
-502 
21,682 
-210 
27,355 
Inclusion Pre-existing ASCVD [start of all 
available data, -30] 
-14,187 
4,628 
-15,729 
5,953 
-16,099 
11,256 
Exclusion Androgen deprivation therapy 
(GnRH agonists/antagonists) [-365, 0] 
-145 
4,483 
-106 
5,847 
-465 
10,791 
Exclusion Androgen deprivation therapy 
(hormonal therapy) [-365, -14] and Exclusion 
Androgen deprivation therapy (Orchiectomy) 
[start of all available data, 0] 
-575 
3,908 
-748 
5,099 
 
 
-1,768 
 
 
 
9,023 
Exclusion Uncontrolled Diabetes [-30, 0] 
0 
3,908 
0 
5,099 
0 
9,023 
Exclusion Uncontrolled Hypertension  
[-30, 0] 
-28 
3,880 
-19 
5,080 
-97 
8,926 
Exclusion Heart failure [starts of all available 
data, 0] 
-285 
3,595 
-556 
4,524 
-1,602 
7,324 
Exclusion QT syndrome [starts of all available 
data, 0] 
-7 
3,588 
-9 
4,515 
-19 
7,305 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
5 
Exclusion Hypokalemia [-90, 0] 
-3 
3,585 
-14 
4,501 
-37 
7,268 
Exclusion Hypomagnesemia [-90, 0] 
-9 
3,576 
-7 
4,494 
-12 
7,256 
Exclusion QT prolonging medicines [0, 0] 
-192 
3,384 
-191 
4,303 
-446 
6,810 
Exclusion Acute MI [-29, 0] 
-6 
3,378 
-9 
4,294 
-11 
6,799 
Exclusion Stroke [-29, 0] and Exclusion 
Revascularization [-29,0] 
-9 
3,369 
-16 
4,278 
-29 
6,770 
Final cohort 
 
3,369 
 
4,278 
 
6,770 
 
**Certain exclusion criteria are in collapsed form to maintain compliance with CMS’ cell suppression policy** 
 
6. Variables  
 
6.1 Exposure-related variables:  
 
Study drug:  
The study exposure of interest is defined by a HCPCS/CPT code or outpatient prescription drug claim indicating degarelix 
administration or dispensation, respectively. New initiation will be defined by no such records of degarelix in the prior 365 days 
before treatment initiation (washout period) and fulfillment of study eligibility criteria.  
 
Comparator agent: 
The comparator is defined by an HCPCS/CPT code or outpatient prescription drug claim indicating leuprolide administration or 
dispensation, respectively. New initiation will be defined by no such records of leuprolide in the prior 365 days before treatment 
initiation (washout period) and fulfillment of study eligibility criteria. 
 
6.2 Preliminary Covariates: 
• Age 
 
The covariate listed above represents only a small subset of the covariate vector that will ultimately be controlled for in the 
design and analysis. We use the covariate above only for initial feasibility analyses to judge whether there is likely to be sufficient 
overlap between treatment groups to proceed with the study. Remaining covariates are defined only after the study has passed 
the initial feasibility analysis and the initial power assessment and are listed in Table 1 (Appendix B). Gender is not included since 
the study is already restricted to male subjects. 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
6 
 
6.3 Outcome variables and study follow-up:  
 
6.3.1 Outcome variables 
 
Effectiveness outcome variables of interest (definitions provided in Appendix): 
§ Primary outcome: MACE (all-cause death, nonfatal myocardial infarction, or nonfatal stroke through 12 months of 
primary treatment with leuprolide or degarelix)  
§ Secondary outcomes:  
o Secondary cardiovascular objectives: To assess 1) the frequency of MACE components individually (i.e., nonfatal 
myocardial infarction, nonfatal stroke, and all-cause mortality) 
 
6.3.2 Study follow-up 
Both as-treated (AT) and intention-to-treat (ITT) analyses will be conducted with treatment defined as the index drug on day of 
cohort entry. An allowable gap of 90 days between records indicating each treatment will qualify as “continuous therapy” with 
respect to follow-up in the as-treated analysis.  
The follow-up will start the day after drug initiation (i.e., cohort entry date), and will continue until the earliest date of the following 
events: 
• The first occurrence of the outcome of interest, 
• The date of end of continuous registration in the database, 
• End of the study period, 
• Measured death event occurs, 
• 365 days 
• Switch  
• Discontinuation (90 days allowable grace period and risk window) 
 
In the secondary ITT analysis, we will not censor for discontinuation or switching among study drugs 
 
  

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
7 
 
7. Initial Feasibility Analysis  
Aetion report name: 
For degarelix vs. leuprolide  
Optum CDM- https://bwh-dope.aetion.com/projects/details/1636/rwrs/67085  
IBM® MarketScan®- https://bwh-dope.aetion.com/projects/details/1323/rwrs/67083  
CMS Diabetes - https://bwh-dope.aetion.com/projects/details/1637/rwrs/67081  
 
Date conducted: 03/06/2021 
 
Complete Aetion feasibility analysis using age as the only covariate and the primary endpoint (Section 6.3.1) as the outcome. No 
measures of association will be computed, nor will incidence rates be stratified by treatment group. 
 
• Report patient characteristics by treatment group 
§ 
Degarelix vs Leuprolide 
 
  
Optum CDM 
IBM® MarketScan® 
CMS - Diabetes 
Variable 
Leuprolide - 
Comparator 
Degarelix - 
Exposure 
Difference 
Leuprolide - 
Comparator 
Degarelix - 
Exposure 
Difference 
Leuprolide - 
Comparator 
Degarelix - 
Exposure 
Difference 
Number of 
patients 
3,676 
596 
 
2,936 
431 
 
5,828 
941 
 
Age 
 
 
 
 
 
 
 
 
 
...mean 
(sd) 
75.71 (7.42) 
75.93 (7.66) 
-0.22 (-0.88, 
0.44) 
74.38 (9.05) 
74.49 (9.12) 
-0.11 (-1.03, 
0.82) 
76.85 (6.58) 
76.94 (6.49) 
-0.09 (-0.53, 
0.36) 
...median 
[IQR] 
76.00 [71.00, 
81.00] 
76.00 
[71.00, 
82.00] 
 
75.00 [68.00, 
81.00] 
75.00 
[68.00, 
82.00] 
 
76.00 [72.00, 
81.00] 
77.00 
[72.00, 
81.87] 
 
 
• Report summary parameters of study population FEASIBILITY- FOR STUDY OUTCOME 
§ 
For Degarelix vs Leuprolide 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
8 
 
FEASIBILITY FOR STUDY OUTCOME 
 
Optum CDM 
IBM® MarketScan® 
CMS - Diabetes 
Number of patients in full cohort 
4,278 
3,369 
6,770 
Number of patients dropped as incomplete cases 
0 
0 
0 
Number of patients that did not begin follow-up 
6 
2 
1 
Number of patients in analytic cohort 
4,272 
3,367 
6,769 
Number of events 
108 
43 
211 
Number of person-years 
1,259.68 
1,001.03 
2,031.94 
Number of patients in group: Leuprolide - Comparator 
3,676 
2,936 
5,828 
Number of patients in group: Degarelix - Exposure 
596 
431 
941 
Risk per 1,000 patients 
25.28 
12.77 
31.17 
Rate per 1,000 person-years 
85.74 
42.96 
103.84 
 
• Report median follow-up time by treatment group 
§ 
For Degarelix vs Leuprolide 
 
FOLLOW-UP TIME FOR STUDY OUTCOME 
Median Follow-Up Time (Days) [IQR] – At 90 days gap 
Patient Group 
Optum CDM IBM® MarketScan® CMS - Diabetes 
Overall Patient Population 
89 [89, 89] 
89 [89, 89] 
89 [89, 89] 
Referent - Leuprolide 
89 [89, 89] 
89 [89, 89] 
89 [89, 89] 
Exposure - Degarelix 
82 [33, 132] 
68 [31, 126] 
67 [32, 124] 
 
• Report reasons for censoring in the overall study population 
§ 
For Degarelix vs Leuprolide 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
9 
CENSORING REASONS FOR STUDY OUTCOME 
Reasons  
Optum CDM 
IBM® MarketScan® CMS - Diabetes 
Outcome 
108 (2.5%) 
43 (1.3%) 
211 (3.1%) 
Start of an additional exposure 351 (8.2%) 
256 (7.6%) 
584 (8.6%) 
End of index exposure 
3,344 (78.3%) 2,674 (79.4%) 
5,277 (78.0%) 
Maximum follow-up time 
118 (2.8%) 
94 (2.8%) 
205 (3.0%) 
Specified date reached 
182 (4.3%) 
52 (1.5%) 
270 (4.0%) 
End of patient data 
0 (0.0%) 
0 (0.0%) 
0 (0.0%) 
End of patient enrollment 
169 (4.0%) 
248 (7.4%) 
222 (3.3%) 
 
• Report overall risk of the primary outcome. 
 
  
Optum CDM 
IBM® MarketScan® 
CMS - Diabetes 
Pooled 
Risk per 1,000 patients 
25.28 
12.77 
31.17 
25.12 
 
 
8. Initial Power Assessment 
 
Aetion report name: 
§ 
For Degarelix vs Leuprolide 
• 
Optum CDM- https://bwh-dope.aetion.com/projects/details/1636/rwrs/67086  
• IBM® MarketScan®- https://bwh-dope.aetion.com/projects/details/1323/rwrs/67084  
• CMS Diabetes - https://bwh-dope.aetion.com/projects/details/1637/rwrs/67082  
 
Date conducted:   
 
In order to complete the initial power analysis, a dummy outcome indicating a 90-day gap in database enrollment will be used. This 
outcome is used to ensure that no information on the comparative risks of the outcomes of interest are available at this stage. A 1:1 
PS-matched comparative analysis was performed, including age as the only covariate. Power calculations are based on the formulas 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
10 
from Chow et al. (2008). 
 
• Stop analyses until feasibility and power are reviewed by primary investigators and FDA. Reviewers evaluate the results of the 
analyses described above in Sections 7 and 8, including numbers of patients, patient characteristics, follow-up time, and reasons 
for censoring by treatment group, as well as overall rates of outcomes and study power. These parameters are re-evaluated and 
reported in the subsequent sections, after incorporating feedback and refining the protocol. 
 
• 
Pooled 
 
 
• 
Optum CDM 
Superiority Analysis
Number of patients matched
3,934
Reference
1,967
Exposed
1,967
Risk per 1,000 patients
25.12
Desired HR from RCT
0.49
Alpha (2-sided)
0.05
Number of events expected
98.82208
Power
0.943598201

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
11 
 
 
• 
IBM® MarketScan® 
 
 
Superiority Analysis
Number of patients matched
1,192
Reference
596
Exposed
596
Risk per 1,000 patients
25.28
Desired HR from RCT
0.49
Alpha (2-sided)
0.05
Number of events expected
30.13376
Power
0.499237002
Superiority Analysis
Number of patients matched
862
Reference
431
Exposed
431
Risk per 1,000 patients
12.77
Desired HR from RCT
0.49
Alpha (2-sided)
0.05
Number of events expected
11.00774
Power
0.21953525

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
12 
 
• 
CMS - Diabetes 
 
 
 
Stop analyses until feasibility and power are reviewed by primary investigators, FDA, and assigned members of advisory board. 
Reviewed by PI: 
Shirley Wang 
Date reviewed: 
3/17/2021 
Reviewed by FDA: 
Ken 
Date reviewed: 
4/3/2021 
Reasons for stopping 
analysis (if required): 
 
 
 
9. Balance Assessment 
 
Aetion report name: 
For Degarelix vs. leuprolide  
Optum CDM- https://bwh-dope.aetion.com/projects/details/1636/rwrs/68435 
IBM® MarketScan®- https://bwh-dope.aetion.com/projects/details/1323/rwrs/68424  
Superiority Analysis
Number of patients matched
1,880
Reference
940
Exposed
940
Risk per 1,000 patients
31.17
Desired HR from RCT
0.49
Alpha (2-sided)
0.05
Number of events expected
58.5996
Power
0.779468883

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
13 
CMS Diabetes - https://bwh-dope.aetion.com/projects/details/1637/rwrs/68434   
 
Date conducted: 04/14/2021 
 
After review of initial feasibility and power analyses, complete creation of the remaining covariates from Section 6.2. Again, using the 
dummy outcome of a 90-day gap in database enrollment, complete a 1:1 PS-matched analysis. The PS should include the complete 
list of covariates. 
• Provide plot of PS distributions stratified by treatment group. 
Note- Please refer to Appendix_Table1_PRONOUNCE_v1 (worksheet named ‘PS matching’). 
• Report covariate balance after matching. 
Note- Please refer to Appendix_Table1_PRONOUNCE_v1 (worksheet named ‘Table 1’). 
 
• Report reasons for censoring by treatment group. 
 
Overall 
Referent 
Exposure 
Start of an additional exposure 
1147 (30.39%) 
1 (0.05%) 
1146 (60.73%) 
End of index exposure 
2084 (55.22%) 
1645 (87.18%) 
439 (23.26%) 
Specified date reached 
157 (4.16%) 
78 (4.13%) 
79 (4.19%) 
Maximum follow-up reached (365 days) 
142 (3.76) 
42 (2.23%) 
100 (5.30%) 
End of patient enrollment 
244 (6.46%) 
121 (6.41%) 
123 (6.52%) 
 
• Report follow-up time by treatment group. 
Median Follow-Up Time (Days) [IQR] 
Patient Group 
Optum CDM 
IBM® MarketScan® 
CMS - Diabetes 
Overall Patient Population 
89 [64, 116] 
89 [55, 118] 
89 [61, 109] 
Referent 
89 [89, 89] 
89 [89, 89] 
89 [89, 89] 
Exposure 
82 [33, 140] 
67 [31, 126] 
68 [33, 125] 
 
10. Final Power Assessment 
 
Date conducted: 4/15/2021 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
14 
 
Re-calculate power in the appropriate excel table, using the revised number of matched patients from the PS-match in Section 9. All 
other parameters in the table should be the same as in Section 8. 
 
• 
Pooled 
 
 
• 
Optum CDM 
Superiority Analysis
Number of patients matched
3,774
Reference
1,887
Exposed
1,887
Risk per 1,000 patients
25.12
Desired HR from RCT
0.49
Alpha (2-sided)
0.05
Number of events expected
94.80288
Power
0.93484302

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
15 
 
 
• 
IBM® MarketScan® 
 
 
Superiority Analysis
Number of patients matched
1,092
Reference
546
Exposed
546
Risk per 1,000 patients
25.28
Desired HR from RCT
0.49
Alpha (2-sided)
0.05
Number of events expected
27.60576
Power
0.465815489
Superiority Analysis
Number of patients matched
830
Reference
415
Exposed
415
Risk per 1,000 patients
12.77
Desired HR from RCT
0.49
Alpha (2-sided)
0.05
Number of events expected
10.5991
Power
0.21311438

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
16 
 
• 
CMS - Diabetes 
 
 
 
 
• Stop analyses until balance and final power assessment are reviewed by primary investigators, FDA, and assigned members of 
advisory board. 
Reviewed by PI: 
 
Date reviewed: 
 
Reviewed by FDA: 
 
Date reviewed: 
 
Reasons for stopping 
analysis (if required): 
 
 
11. Study Confidence and Concerns 
 
Deadline for voting on study confidence and listing concerns: 
Date votes and concerns are summarized:    
 
• If final feasibility and power analyses are reviewed and approved, proceed to the remaining protocol steps. 
Superiority Analysis
Number of patients matched
1,852
Reference
926
Exposed
926
Risk per 1,000 patients
31.17
Desired HR from RCT
0.49
Alpha (2-sided)
0.05
Number of events expected
57.72684
Power
0.773370349

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
17 
• All study team and advisory board members that review this protocol should at this stage provide their level of confidence for the 
success of the RWD study in the Google Form. This form also provides space for reviewers to list any concerns that they feel may 
contribute to a failure to replicate the findings of the RCT, including differences in study populations, poor measurement of study 
variables, or residual confounding. All responses will be kept confidential and individual-level results will only be shared with the 
individual respondent. 
• After the deadline for voting has passed, provide the distribution of responses and summarize all concerns here. 
 
12. Register study protocol on clinicalTrials.gov 
 
Date conducted:    
 
• Register the study on clinicalTrials.gov and upload this document. 
 
13. Comparative Analyses 
 
Aetion report name: 
Date conducted:    
 
13.1 
For primary analysis:  
 
13.2 
For sensitivity analyses: 
 
 
14.  Requested Results  
 
14.1 
Table 1: Baseline characteristics before and after adjustment 
 
Variable 
 
Before adjustment 
After adjustment 
Referent 
Exposure 
Std. diff. 
Referent 
Exposure 
Std. diff. 
Number of patients 
 
 
- 
 
 
- 
Age categories 
 
 
 
 
 
 
… 
 
 
 
 
 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
18 
 
 
14.2 
Table 2: Follow-up time 
 
Patient Group 
Median Follow-Up Time (Days) [IQR] 
Overall Patient Population 
 
Referent 
 
Exposure 
 
 
14.3 
Table 3: Censoring events 
 
 
Overall 
Referent 
Exposure 
Outcome 
 
 
 
Death 
 
 
 
Start of an additional exposure 
 
 
 
End of index exposure 
 
 
 
Specified date reached 
 
 
 
End of patient data 
 
 
 
End of patient enrollment 
 
 
 
… 
 
 
 
 
14.4 
Table 4: Results from primary analyses; 
 
Analysis 
No. exposed events 
No. referent events 
Exposed rate 
Referent rate 
HR (95% CI) 
Crude 
 
 
 
 
 
Analysis 1 
 
 
 
 
 
Analysis 2 
 
 
 
 
 
... 
 
 
 
 
 
HR, Hazard Ratio; CI, Confidence Interval. 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
19 
14.5 
Table 5: Results from secondary analyses; 
 
 
15. References 
 
Chow S, Shao J, Wang H. 2008.  Sample Size Calculations in Clinical Research. 2nd Ed. Chapman & Hall/CRC Biostatistics Series. page 
177 

Information from Trial
Trial Name: PRONOUNCE https://www.clinicaltrials.gov/ct2/show/NCT02663908
NCT: NCT02663908
Therapeutic Area: Oncology
RCT Category: Equivalence/Superiority
Brand Name: Firmagon
Generic Name: Degarelix
Sponsor: Ferring Pharmaceuticals 
Year: 2016 - Present
Measurable Endpoint: MACE
Exposure: Degarelix
Comparator: Leuprolide
Populuation: Men of any age with with advance prostate cancer and predefined CV disease
No. of Patients: TBD 
Power: TBD
Appendix A

#
PRONOUNCE  trial definitions 
Implementation in routine care
References/Rationale
Color coding
Please see the following Google Drive for further details or any missing information: 
https://drive.google.com/open?id=1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV
Criteria
ICD-10 codes are not listed in this document because of excel cell size limitations and excessive number of ICD-10 codes. 
Full ICD-10 code lists will be available in the above Google Drive Folder (link above). ICD-9 to ICD-10 code conversions 
were completed using a SAS macro that implements forward/ backward mapping based on the CMS ICD-9 to ICD-10 
mapping: https://www.nber.org/data/icd9-icd-10-cm-and-pcs-crosswalk-general-equivalence-mapping.html
Can be replicated in claims
Degarelix 240mg SC q mt x 1 month, Degarelix 80mg SC q mt x 11 months thereafter
vs.
Leuprolide IM 22.5mg q 3 months x 12 months
Degarelix Arm: Generic name: Degarelix Acetate; HCPCS/CPT: J9155 (inpatient and outpatient)
vs.
Leuprolide Arm: Generic name: Leuprolide Acetate; HCPCS/CPT: J1950, C9430, J9219,  J9218, J9217 (inpatient and outpatient)
Using dummy definitions for measuring in claims
Can't be measured in claims
MACE (All-cause death, nonfatal myocardial infarction, nonfatal stroke)
Measured from first day following exposure initiation
Death: inpatient death indicated by discharge date
Nonfatal MI: ICD-9 diagnosis: 410.xx EXCEPT 410.x2
ICD-10 diagnosis: I21.01, I21.02, I21.09, I21.11, I21.19, I21.21, I21.29, I21.3, I21.4, I22.0, I22.1, I22.2, I22.8, I22.9
Nonfatal Stroke: Stroke (ischemic/hemorrhagic): ICD-9 diagnosis: “430”, “431”, “433.01”, “433.11”, “433.21”, “433.31”, “433.81”, “433.91”, “434.01”, “434.11”, “434.91”, “436.xx”, 
ICD-10 diagnosis: I60.00 I60.01 I60.02 I60.10 I60.11 I60.12 I60.2 I60.30  I60.31 I60.32 I60.4 I60.50 I60.51 I60.52 I60.6 I60.7 I60.8 I60.9 I61.0 I61.1 I61.2 I61.3 I61.4 I61.5 I61.6 I61.8 I61.9 I63.00 I63.011 I63.012 
I63.019 I63.02 I63.031 I63.032 I63.039 I63.09 I63.10 I63.111 I63.112 I63.119 I63.12 I63.131 I63.132 I63.139 I63.19 I63.20 I63.211 I63.212 I63.219 I63.22 I63.231 I63.232 I63.239 I63.29 I63.30 I63.311 I63.312 
I63.319 I63.321 I63.322 I63.329 I63.331 I63.332 I63.339 I63.341 I63.342 I63.349 I63.39 I63.40 I63.411 I63.412 I63.419  I63.421 I63.422 I63.429 I63.431 I63.432 I63.439 I63.441 I63.442 I63.449 I63.49 I63.50 
I63.511 I63.512 I63.519 I63.521 I63.522 I63.529 I63.531 I63.532 I63.539 I63.541 I63.542 I63.549 I63.59 I63.6 I63.8 I63.9  I67.89 (primary inpatient)
Source: CANVAS trial (https://bwh-dope.aetion.com/measures/details/92945/661/0/basics)
Can't be measured in claims but not important for the analysis
1
Histologically confirmed adenocarcinoma of the prostate
Measured from [start of all available data, 0]. Must have both, diagnosis code and male gender for inclusion.
Malignant Neoplasm of the Prostate: 
ICD-9 diagnosis: 185.xx 
ICD-10 diagnosis: C61.x  (inpatient and outpatient)
Sex: Male
Male patients with 1 dx code + an exposure provides enough information to confirm diagnosis, as the 
exposures have very few or no indications outside of advanced PC
Necessitating code for biopsy may exclude subjects with prevalent prostate cancer if they were initially 
diagnosed prior to database enrollment with early stage disease
Lupron is indicated in females for endometriosis. Restricting to males helps ensure indication of interest.
2
Tumor, node, metastasis staging available before treatment start (bone scan and/or CT scan and/or MRI) <12 weeks before 
study start
3
Investigator judgement to initiate continued ADT therapy with intended duration of 12 months or longer 
     -Patients with metastatic prostate cancer at time of diagnosis
     -Patients with prostate cancer who develop metastases after local therapy
     -Patients with prostate cancer with very high-risk, high-risk, or intermediate risk disease with feature of unfavorable 
prognosis who will be treated with definitive radiation therapy in combination with at least 12 months of 
neoadjuvant/adjuvant ADT
4
Pre-existing ASCVD (confirmed diagnosis, documented) according to at least 1 of the following criteria 
     -Previous myocardial infarction >=30 days before randomization
     -Previous revascularization procedure >=30 days before randomization
     -Coronary artery: stent placement/balloon angioplasty or coronary artery bypass graft surgery 
     -Carotid artery: stent placement/balloon angioplasty or endarterectomy surgery 
     -Iliac, femoral, popliteal arteries: stent placement/balloon angioplasty or vascular bypass surgery
Measured from [start of all available data , -30] in an inpatient or outpatient care setting in any diagnosis position
Acute or old MI: 
ICD-9 diagnosis: 410.xx , 412.xx 
ICD-10 diagnosis: I21.01, I21.02, I21.09, I21.11, I21.19, I21.21, I21.29, I21.3, I21.4, I22.0, I22.1, I22.2, I22.8, I22.9, I25.2
Coronary, Carotid, Illiac, Femoral, Popliteal revascularization (Angioplasty/Stent/CABG/Vascular bypass/endarterectomy): 
ICD-9 procedure: “00.66”, “36.03”, “36.06”, “36.07”, “36.09”, “36.31”, “36.32”, “36.33”, “36.34”, “36.1”, “36.10”, “36.11”, “36.12”, “36.13”, “36.14”, “36.15”, “36.16”, “36.17”, “36.19”, “36.2”; 
ICD-10 procedure: see Appendix
HCPCS/CPT: “35302”, “35355”, “35363”, “35371”, “35372”, “35381”, “35483”, “35493”, “35521”, “35533”, “35539”, “35540”, “35546”, “35548”, “35549”, “35551”, “35556”, “35558”, “35565”, “35621”, 
“35646”, “35647”, “35651”, “35654”, “35656”, “35661”, “35665”, “35666”, “34201”, “34203”, “34421”, “34451”, “35303”, “35571”, “35623”, “35671” 
Sources: DUPLICATE  Standard Measures ("MI (Inc3 HF Algorithm)", "Old MI with ICD 10 Copy")
DUPLICATE Standard Measures ("Old MI with ICD 10 Copy", "Information on Outcome- Coronary 
revascularization (PTCA, stenting, CABG) v5 -WITH ICD-10 CODES")
5
At least 1 vascular stenosis >=50% at any time point before randomization by angiography or CT angiography
     -Coronary artery
     -Carotid artery
     -Iliac, femoral, or popliteal arteries
     -Carotid ultrasound results that documented a vascular stenosis >=50% at any time point before randomization 
     -Ankle brachial pressure index <0.9 at any time point before randomization
1
Patients must be treatment-naive (ADT) 
     -If patients received previous ADT for neoadjuvant or adjuvant therapy, then the last dose of therapy must be at least 12 
months before randomization
     -Any additional hormonal therapy upfront (i.e., abiraterone) is prohibited in the study; however, anti-androgen use for 
initial flare protection is allowed for a maximum period of up to 28 days after randomization
Measured [-365, 0] in an inpatient or oupatient care setting in any diagnosis position
GnRH Agonists: generic name: goserelin, triptorelin, histrelin
 HCPCS/CPT:  goserelin: J9202 S9560; triptorelin: J3315 J3316 histrelin: J1675 J9225 J9226 Q2020 S0133 (inpatient and outpatient)
Measured [-365, -14] 
Hormonal Therapy: generic name: abiraterone, ketoconazole, flutamide, bicalutamide, nilutamide, enzalutamide, apalutamide, finasteride, dutasteride
HCPCS/CPT: flutamide: S0175 finasteride: S0138
Source:https://jamanetwork.com/journals/jamaoncology/article-abstract/2476248
Patients may fill prescription and initiate androgen blockade ~1-2 weeks prior to start of LHRH agonist for flare 
protection
2
Previous or current hormonal management of prostate cancer 
     -Surgical castration
     -Any hormonal manipulation
     -Any previous neoadjuvant/adjuvant hormonal therapy, unless treatment terminated >12 months before study start
Measured from [start of all available data , 0] in an inpatient and outpatient care setting in any diagnosis position:
Orchiectomy: HCPCS/CPT: 54520, 54522, 54530, 54535, 54690 (54521 not found in databases)
ICD-9 procedure: 62.3x, 62.4x  (inpatient and outpatient)
ICD-10 procedure:  “0VT90ZZ”, “0VT94ZZ”, “0VTB0ZZ”, “0VTB4ZZ”, "0VTC4ZZ", "0VTC0ZZ"
Measured [-365, 0]:
GnRH Agonists: generic name: goserelin, triptorelin, histrelin
HCPCS/CPT: goserelin: J9202 S9560; triptorelin: J3315 J3316 histrelin: J1675 J9225 J9226 Q2020 S0133 (inpatient and outpatient)
Measured [-365, -14]:
Hormonal Therapy: generic name: abiraterone, ketoconazole, flutamide, bicalutamide, nilutamide, enzalutamide, apalutamide, finasteride, dutasteride
HCPCS/CPT: flutamide: S0175 finasteride: S0138
Source:https://jamanetwork.com/journals/jamaoncology/article-abstract/2476248
patients may initiate androgen blockade for flare within 14 days of initial treatment, which is permissible per 
PRONOUNCE selection criteria
Abarelix was not included, as it was only on the market for a short  period of time prior to the span of our data 
resources. Cetrorelix and ganirelix are also excluded from this analysis since they're not indicated for prostate 
cancer.
3
Uncontrolled type 1 or type 2 diabetes mellitus (defined as HbA1c >10%) at time of randomization
Measured [-30, 0]  in an inpatient care setting in a primary diagnosis position 
Uncontrolled Diabetes
 ICD-9: 790.29 
 ICD-10: R73.09, R73.9
Source: Codes from Duplicate standard measure library (https://bwh-
dope.aetion.com/measures/details/306630/0/0/templates/simpleEventSet?tab=3)
An inpatient, primary diagnosis of hyperglycemia is thought to be a good proxy for uncontrolled diabetes based 
on the investigators' substantive knowledge. 
4
Uncontrolled hypertension (SBP >180 mm Hg or DBP >110 mm Hg) at time of randomization
Measured [-30, 0] ICD-10 meausred in either an inpatient or outpatient care setting in any diagnosis position. . ICD-9 measured in an inpatient care setting or ED setting in a primary diagnosis position: 
Malignant hypertension/Hypertensive crisis: 
ICD-9 diagnosis: 401.9, 362.11,  401.0, 402.0x, 403.0x, 404.0x, 405.0x, 403.9x, 437.2, 796.2
ICD-10 diagnosis: I16.x 
Source: DUPLICATE Team (EMPEROR-Preserved trial)
Malignant HTN clinically defined as SBP>180mmHg
5
A history of congenital long QT syndrome or risk factors for Torsade de pointes ventricular arrhythmias (e.g., heart failure, 
hypokalemia, concomitant medication known to cause QT prolongation)
Measured [start of all available data, 0] in an inpatient or outpatient care setting in any diagnosis position
Long QT Syndrome: 
ICD-9 diagnosis: 426.82
ICD-10 diagnosis: I45.81
Measured [-365, 0] in an 1 inpatient code or 2 outpatient codes in any diagnosis position
Heart failure:  
ICD-9 diagnosis: 428.x, 398.91, 402.01, 402.11, 402.91, 404.01, 404.11, 404.91, 404.03, 404.13, 404.93; 
ICD-10 Diagnosis: "I11.0”, “I13.0”, “I13.2”, “I50.1”, “I50.20”, “I50.21”, “I50.22”, “I50.23”, “I50.30”, “I50.31”, “I50.32”, “I50.33”, “I50.40”, “I50.41”, “I50.42”, “I50.43”, “I50.9” 
Measured [-90, 0] in an inpatient or outpatient care setting in any diagnosis position
Hypokalemia:
ICD-9 diagnosis: 276.8 
ICD-10 diagnosis: E87.6
Hypomagnesemia:  
ICD-9 diagnosis: 275.2x 
ICD-10 diagnosis: E83.42
Measured [0,0] 
QT-prolonging medications: generic name: amiodarone, anagrelide, azithromycin, chloroquine, atovaquone/proguanil, chlorpromazine, cilostazol, ciprofloxacin, citalopram, clarithromycin, disopyramide, 
donepezil, dronedarone, droperidol, erythromycin, escitalopram, flecainide, fluconazole, haloperidol, levofloxacin, methadone, moxifloxacin, ondansetron, oxaliplatin, pentamidine, pimozide, procainamide, 
propofol, quinidine, sevoflurane, sotalol, thioridazine, ibutilide, dofetilide, cabozantinib, ceritinib, dexmedetomidine, eliglustat, encorafenib, eribulin, ezogabine, fluorouracil (5-FU), gemifloxacin, glasdegib, 
hydrocodone, iloperidone, melipramine, lopinavir, ritonavir, necitumumab, norfloxacin, panobinostat, pimavanserin, ribociclib, telavancin, vorinostat
Souces: DUPLICATE Standard Measure ("Heart Failure (CHF) Ever Lookback"); CPRD Measure Library 
("REPEAT_Redact_135_QT Prolonging drugs"); Aetion Search; Aetion Search
Electrolyte imbalances and QT-prolonging medicines from >90 days are irrelevant, while heart failure and 
congenital long QT are chronic  conditions that will persist despite occurrence from long ago
PRIMARY OUTCOME
TRIAL DETAILS
EXPOSURE vs. COMPARISON
INCLUSION CRITERIA
EXCLUSION CRITERIA
Appendix A

6
Within 30 days before randomization:
     -Myocardial Infarction
     -stroke (hemorrhagic/ischemic)
     -coronary, carotid, or peripheral artery revascularization
Measured [-29, 0] in an inpatient or outpatien care setting in any diagnosis position
Acute MI: ICD-9 diagnosis: 410.xx;  
ICD-10 diagnosis: I21.01, I21.02, I21.09, I21.11, I21.19, I21.21, I21.29, I21.3, I21.4, I22.0, I22.1, I22.2, I22.8, I22.9  (inpatient and outpatient)
Stroke (ischemic/hemorrhagic): ICD-9 diagnosis: “430”, “431”, “433.01”, “433.11”, “433.21”, “433.31”, “433.81”, “433.91”, “434.01”, “434.11”, “434.91”, “436.xx”, 
ICD-10 diagnosis: I60.00 I60.01 I60.02 I60.10 I60.11 I60.12 I60.2 I60.30  I60.31 I60.32 I60.4 I60.50 I60.51 I60.52 I60.6 I60.7 I60.8 I60.9 I61.0 I61.1 I61.2 I61.3 I61.4 I61.5 I61.6 I61.8 I61.9 I63.00 I63.011 I63.012 
I63.019 I63.02 I63.031 I63.032 I63.039 I63.09 I63.10 I63.111 I63.112 I63.119 I63.12 I63.131 I63.132 I63.139 I63.19 I63.20 I63.211 I63.212 I63.219 I63.22 I63.231 I63.232 I63.239 I63.29 I63.30 I63.311 I63.312 
I63.319 I63.321 I63.322 I63.329 I63.331 I63.332 I63.339 I63.341 I63.342 I63.349 I63.39 I63.40 I63.411 I63.412 I63.419  I63.421 I63.422 I63.429 I63.431 I63.432 I63.439 I63.441 I63.442 I63.449 I63.49 I63.50 
I63.511 I63.512 I63.519 I63.521 I63.522 I63.529 I63.531 I63.532 I63.539 I63.541 I63.542 I63.549 I63.59 I63.6 I63.8 I63.9  I67.89 (inpatient and outpatient)
Coronary, Carotid, Illiac, Femoral, Popliteal revascularization (Angioplasty/Stent/CABG): ICD-9 procedure: “00.66”, “36.03”, “36.06”, “36.07”, “36.09”, “36.31”, “36.32”, “36.33”, “36.34”, “36.1”, “36.10”, 
“36.11”, “36.12”, “36.13”, “36.14”, “36.15”, “36.16”, “36.17”, “36.19”, “36.2”; 
ICD-10 procedure: see Appendix; 
HCPCS/CPT: “35302”, “35355”, “35363”, “35371”, “35372”, “35381”, “35483”, “35493”, “35521”, “35533”, “35539”, “35540”, “35546”, “35548”, “35549”, “35551”, “35556”, “35558”, “35565”, “35621”, 
“35646”, “35647”, “35651”, “35654”, “35656”, “35661”, “35665”, “35666”, “34201”, “34203”, “34421”, “34451”, “35303”, “35571”, “35623”, “35671” (inpatient and outpatient)
DUPLICATE  Standard Measure ("Information on Outcome - Stroke WITH ICD-10 CODES [inpatient, PRIMARY]", 
"Acute MI [EVER LOOKBACK]")
7
Planned or scheduled cardiac surgery or PCI procedure that is known at the time of randomization
Appendix A

Variable
Leuprolide
Degarelix
St. Diff
Leuprolide
Degarelix
St. Diff
Leuprolide
Degarelix
St. Diff
Leuprolide
Degarelix
St. Diff
Number of patients
3,681
597
2,938
431
5,829
941
12,448
1,969
              
Year of Cohort Entry Date
...2008-2009; n (%)
262 (7.1%)
0 (0.0%)
0.39 312 (10.6%)
0 (0.0%)
0.49 353 (6.1%)
0 (0.0%)
0.36 927 (7.4%)
0 (0.0%)
0.40
...2010; n (%)
265 (7.2%)
21 (3.5%)
0.16 358 (12.2%)
24 (5.6%)
0.23 427 (7.3%)
37 (3.9%)
0.15 1,050 (8.4%) 82 (4.2%)
0.17
...2011; n (%)
263 (7.1%)
25 (4.2%)
0.13 421 (14.3%)
45 (10.4%)
0.12 467 (8.0%)
49 (5.2%)
0.11 1,151 (9.2%) 119 (6.0%)
0.12
...2012; n (%)
245 (6.7%)
41 (6.9%)
-0.01 377 (12.8%)
50 (11.6%)
0.04 485 (8.3%)
69 (7.3%)
0.04 1,107 (8.9%) 160 (8.1%)
0.03
...2013; n (%)
241 (6.5%)
54 (9.0%)
-0.09 357 (12.2%)
56 (13.0%)
-0.02 757 (13.0%)
121 (12.9%)
0.00 1,355 (10.9%)231 (11.7%)
-0.03
...2014; n (%)
247 (6.7%)
38 (6.4%)
0.01 268 (9.1%)
48 (11.1%)
-0.07 888 (15.2%)
177 (18.8%)
-0.10 1,403 (11.3%)263 (13.4%)
-0.06
...2015; n (%)
258 (7.0%)
44 (7.4%)
-0.02 257 (8.7%)
66 (15.3%)
-0.20 1,009 (17.3%)171 (18.2%)
-0.02 1,524 (12.2%)281 (14.3%)
-0.06
...2016; n (%)
322 (8.7%)
67 (11.2%)
-0.08 281 (9.6%)
65 (15.1%)
-0.17 784 (13.4%)
148 (15.7%)
-0.07 1,387 (11.1%)280 (14.2%)
-0.09
...2017; n (%)
399 (10.8%)
78 (13.1%)
-0.07 193 (6.6%)
50 (11.6%)
-0.17 659 (11.3%)
169 (18.0%)
-0.19 1,251 (10.0%)297 (15.1%)
-0.15
...2018; n (%)
435 (11.8%)
86 (14.4%)
-0.08 114 (3.9%)
27 (6.3%)
-0.11 ------
------
...2019; n (%)
479 (13.0%)
103 (17.3%)
-0.12 ------
------
------
------
...2020; n (%)
265 (7.2%)
40 (6.7%)
0.02 ------
------
------
------
Age
...mean (sd)
75.71 (7.42)
75.93 (7.65)
-0.03 74.38 (9.05) 74.49 (9.12)
-0.01 76.85 (6.58) 76.94 (6.49)
-0.01 75.93 (7.48) 76.10 (7.49)
-0.02
...median [IQR]
76.00 [71.00, 76.00 [71.00, 
0.00 75.00 [68.00, 75.00 [68.00, 
0.00 76.00 [72.00, 77.00 [72.00, 
-0.15 75.76 (8.66) 76.26 (8.81)
-0.06
Region
...1 - Northeast; n (%)
366 (9.9%)
99 (16.6%)
-0.20 423 (14.4%)
95 (22.0%)
-0.20 1,018 (17.5%)194 (20.6%)
-0.08 1,807 (14.5%)388 (19.7%)
-0.14
...2 - North Central; n (%)
1,037 (28.2%) 143 (24.0%)
0.10 1,176 (40.0%)150 (34.8%)
0.11 1,482 (25.4%)225 (23.9%)
0.03 3,695 (29.7%)518 (26.3%)
0.08
...3 - South; n (%)
1,352 (36.7%) 221 (37.0%)
-0.01 914 (31.1%)
137 (31.8%)
-0.02 2,336 (40.1%)375 (39.9%)
0.00 4,602 (37.0%)733 (37.2%)
0.00
...4 - West; n (%)
925 (25.1%)
131 (21.9%)
0.08 420 (14.3%)
49 (11.4%)
0.09 988 (16.9%)
147 (15.6%)
0.04 2,333 (18.7%)327 (16.6%)
0.06
Race
...White; n (%)
2,727 (74.1%) 448 (75.0%)
-0.02 ------
------
4,818 (82.7%)806 (85.7%)
-0.08 7,545 (60.6%)1,254 (63.7%)
-0.06
...Asian; n (%)
75 (2.0%)
11 (1.8%)
0.01 ------
------
N/A
N/A
N/A
N/A
N/A
N/A
...Black; n (%)
346 (9.4%)
62 (10.4%)
-0.03 ------
------
628 (10.8%)
86 (9.1%)
0.06 974 (7.8%)
148 (7.5%)
0.01
...Hispanic; n (%)
228 (6.2%)
39 (6.5%)
-0.01 ------
------
N/A
N/A
N/A
N/A
N/A
N/A
...North American Native; n (%)
------
------
------
------
N/A
N/A
N/A
N/A
N/A
N/A
...Other; n (%)
------
------
------
------
108 (1.9%)
16 (1.7%)
0.02 108 (1.9%)
16 (1.7%)
0.02
Cardiovascular event prognosticators
Acute or Old MI; n (%)
1,428 (38.8%) 232 (38.9%)
0.00 713 (24.3%)
97 (22.5%)
0.04 2,039 (35.0%)354 (37.6%)
-0.05 4,180 (33.6%)683 (34.7%)
-0.02
Anxiety; n (%)
228 (6.2%)
37 (6.2%)
0.00 125 (4.3%)
24 (5.6%)
-0.06 399 (6.8%)
58 (6.2%)
0.02 752 (6.0%)
119 (6.0%)
0.00
Atrial Fibrillation; n (%)
633 (17.2%)
101 (16.9%)
0.01 387 (13.2%)
73 (16.9%)
-0.10 1,148 (19.7%)207 (22.0%)
-0.06 2,168 (17.4%)381 (19.3%)
-0.05
Coronary Atherosclerosis; n (%)
2,781 (75.6%) 475 (79.6%)
-0.10 2,116 (72.0%)316 (73.3%)
-0.03 4,790 (82.2%)776 (82.5%)
-0.01 9,687 (77.8%)1,567 (79.6%)
-0.04
Coronary, Carotid, Illiac, Femoral, and Popliteal Revascularization (Angioplasty/Stent/CABG); n 358 (9.7%)
50 (8.4%)
0.05 269 (9.2%)
35 (8.1%)
0.04 611 (10.5%)
71 (7.5%)
0.10 1,238 (9.9%) 156 (7.9%)
0.07
Diabetes with Complications; n (%)
1,297 (35.2%) 208 (34.8%)
0.01 357 (12.2%)
63 (14.6%)
-0.07 4,642 (79.6%)736 (78.2%)
0.03 6,296 (50.6%)1,007 (51.1%)
-0.01
Diabetes without Complications; n (%)
747 (20.3%)
131 (21.9%)
-0.04 945 (32.2%)
143 (33.2%)
-0.02 2,203 (37.8%)355 (37.7%)
0.00 3,895 (31.3%)629 (31.9%)
-0.01
DVT; n (%)
150 (4.1%)
27 (4.5%)
-0.02 108 (3.7%)
6 (1.4%)
0.15 257 (4.4%)
43 (4.6%)
-0.01 515 (4.1%)
76 (3.9%)
0.01
Edema; n (%)
344 (9.3%)
68 (11.4%)
-0.07 178 (6.1%)
30 (7.0%)
-0.04 721 (12.4%)
138 (14.7%)
-0.07 1,243 (10.0%)236 (12.0%)
-0.06
Erectile dysfunction; n (%)
455 (12.4%)
82 (13.7%)
-0.04 265 (9.0%)
44 (10.2%)
-0.04 705 (12.1%)
123 (13.1%)
-0.03 1,425 (11.4%)249 (12.6%)
-0.04
Foot ulcer; n (%)
90 (2.4%)
23 (3.9%)
-0.09 52 (1.8%)
10 (2.3%)
-0.04 262 (4.5%)
49 (5.2%)
-0.03 404 (3.2%)
82 (4.2%)
-0.05
Hyperlipidemia; n (%)
3,088 (83.9%) 511 (85.6%)
-0.05 1,865 (63.5%)302 (70.1%)
-0.14 5,283 (90.6%)858 (91.2%)
-0.02 10,236 (82.2%1,671 (84.9%)
-0.07
Hypertension; n (%)
3,188 (86.6%) 522 (87.4%)
-0.02 2,192 (74.6%)331 (76.8%)
-0.05 5,428 (93.1%)880 (93.5%)
-0.02 10,808 (86.8%1,733 (88.0%)
-0.04
Intracranial or Retroperitoneal Hemorrhage ; n (%)
54 (1.5%)
5 (0.8%)
0.07 20 (0.7%)
5 (1.2%)
-0.05 N/A
N/A
N/A
N/A
N/A
N/A
Ischemic Heart Disease; n (%)
3,026 (82.2%) 504 (84.4%)
-0.06 2,250 (76.6%)333 (77.3%)
-0.02 5,000 (85.8%)806 (85.7%)
0.00 10,276 (82.6%1,643 (83.4%)
-0.02
Ischemic Stroke; n (%)
644 (17.5%)
119 (19.9%)
-0.06 497 (16.9%)
79 (18.3%)
-0.04 1,510 (25.9%)232 (24.7%)
0.03 2,651 (21.3%)430 (21.8%)
-0.01
Major Trauma; n (%)
196 (5.3%)
30 (5.0%)
0.01 117 (4.0%)
21 (4.9%)
-0.04 410 (7.0%)
56 (6.0%)
0.04 723 (5.8%)
107 (5.4%)
0.02
Obesity; n (%)
524 (14.2%)
68 (11.4%)
0.08 252 (8.6%)
47 (10.9%)
-0.08 976 (16.7%)
164 (17.4%)
-0.02 1,752 (14.1%)279 (14.2%)
0.00
Other Disorders of Thyroid Gland; n (%)
112 (3.0%)
18 (3.0%)
0.00 69 (2.3%)
13 (3.0%)
-0.04 262 (4.5%)
38 (4.0%)
0.02 443 (3.6%)
69 (3.5%)
0.01
Overweight; n (%)
294 (8.0%)
46 (7.7%)
0.01 83 (2.8%)
13 (3.0%)
-0.01 208 (3.6%)
42 (4.5%)
-0.05 585 (4.7%)
101 (5.1%)
-0.02
PE; n (%)
59 (1.6%)
10 (1.7%)
-0.01 39 (1.3%)
2 (0.5%)
0.08 99 (1.7%)
14 (1.5%)
0.02 197 (1.6%)
26 (1.3%)
0.03
Peripheral Vascular Disease; n (%)
1,234 (33.5%) 205 (34.3%)
-0.02 705 (24.0%)
117 (27.1%)
-0.07 1,798 (30.8%)277 (29.4%)
0.03 3,737 (30.0%)599 (30.4%)
-0.01
Stable Angina; n (%)
490 (13.3%)
83 (13.9%)
-0.02 276 (9.4%)
37 (8.6%)
0.03 769 (13.2%)
115 (12.2%)
0.03 1,535 (12.3%)235 (11.9%)
0.01
Systemic Embolism; n (%)
60 (1.6%)
11 (1.8%)
-0.02 49 (1.7%)
10 (2.3%)
-0.04 N/A
N/A
N/A
N/A
N/A
N/A
TIA; n (%)
90 (2.4%)
22 (3.7%)
-0.08 63 (2.1%)
10 (2.3%)
-0.01 266 (4.6%)
36 (3.8%)
0.04 419 (3.4%)
68 (3.5%)
-0.01
General Health/Mortality Prognosticators
Abnormal liver function; n (%)
333 (9.0%)
55 (9.2%)
-0.01 189 (6.4%)
28 (6.5%)
0.00 574 (9.8%)
97 (10.3%)
-0.02 1,096 (8.8%) 180 (9.1%)
-0.01
Alcohol Abuse/Dependence; n (%)
72 (2.0%)
17 (2.8%)
-0.05 33 (1.1%)
5 (1.2%)
-0.01 108 (1.9%)
19 (2.0%)
-0.01 213 (1.7%)
41 (2.1%)
-0.03
Anemias (Sickle-Cell, G6PD Deficiency, Nutrient Deficiency); n (%)
840 (22.8%)
157 (26.3%)
-0.08 492 (16.7%)
72 (16.7%)
0.00 1,970 (33.8%)286 (30.4%)
0.07 3,302 (26.5%)515 (26.2%)
0.01
Asthma; n (%)
150 (4.1%)
22 (3.7%)
0.02 106 (3.6%)
22 (5.1%)
-0.07 351 (6.0%)
58 (6.2%)
-0.01 607 (4.9%)
102 (5.2%)
-0.01
COPD; n (%)
859 (23.3%)
137 (22.9%)
0.01 502 (17.1%)
79 (18.3%)
-0.03 1,421 (24.4%)223 (23.7%)
0.02 2,782 (22.3%)439 (22.3%)
0.00
Delirium; n (%)
69 (1.9%)
16 (2.7%)
-0.05 50 (1.7%)
5 (1.2%)
0.04 177 (3.0%)
36 (3.8%)
-0.04 296 (2.4%)
57 (2.9%)
-0.03
UNMATCHED
Marketscan
Medicare
Pooled
Optum
Table 1 Unmatched

Dementia; n (%)
101 (2.7%)
18 (3.0%)
-0.02 56 (1.9%)
10 (2.3%)
-0.03 222 (3.8%)
31 (3.3%)
0.03 379 (3.0%)
59 (3.0%)
0.00
Depression ; n (%)
318 (8.6%)
48 (8.0%)
0.02 157 (5.3%)
25 (5.8%)
-0.02 561 (9.6%)
77 (8.2%)
0.05 1,036 (8.3%) 150 (7.6%)
0.03
Falls; n (%)
229 (6.2%)
42 (7.0%)
-0.03 68 (2.3%)
13 (3.0%)
-0.04 351 (6.0%)
72 (7.7%)
-0.07 648 (5.2%)
127 (6.4%)
-0.05
Fractures; n (%)
226 (6.1%)
32 (5.4%)
0.03 147 (5.0%)
22 (5.1%)
0.00 341 (5.9%)
47 (5.0%)
0.04 714 (5.7%)
101 (5.1%)
0.03
HIV/AIDS; n (%)
6 (0.2%)
2 (0.3%)
-0.02 1 (0.0%)
0 (0.0%)
N/A
N/A
N/A
N/A
N/A
N/A
Organ Transplant; n (%)
16 (0.4%)
5 (0.8%)
-0.05 20 (0.7%)
4 (0.9%)
-0.02 N/A
N/A
N/A
N/A
N/A
N/A
Osteoporosis; n (%)
201 (5.5%)
27 (4.5%)
0.05 134 (4.6%)
14 (3.2%)
0.07 399 (6.8%)
56 (6.0%)
0.03 734 (5.9%)
97 (4.9%)
0.04
Peptic Ulcer Disease; n (%)
892 (24.2%)
154 (25.8%)
-0.04 437 (14.9%)
80 (18.6%)
-0.10 1,593 (27.3%)259 (27.5%)
0.00 2,922 (23.5%)493 (25.0%)
-0.04
Pneumonia; n (%)
72 (2.0%)
17 (2.8%)
-0.05 134 (4.6%)
17 (3.9%)
0.03 108 (1.9%)
19 (2.0%)
-0.01 314 (2.5%)
53 (2.7%)
-0.01
Renal Failure; n (%)
775 (21.1%)
142 (23.8%)
-0.06 393 (13.4%)
57 (13.2%)
0.01 1,467 (25.2%)252 (26.8%)
-0.04 2,635 (21.2%)451 (22.9%)
-0.04
Renal Failure (CKD Stage 4 or higher); n (%)
128 (3.5%)
20 (3.4%)
0.01 95 (3.2%)
12 (2.8%)
0.02 311 (5.3%)
50 (5.3%)
0.00 534 (4.3%)
82 (4.2%)
0.00
Sleep Apnea; n (%)
432 (11.7%)
57 (9.5%)
0.07 317 (10.8%)
44 (10.2%)
0.02 741 (12.7%)
109 (11.6%)
0.03 1,490 (12.0%)210 (10.7%)
0.04
Sleep Disorder; n (%)
295 (8.0%)
29 (4.9%)
0.13 307 (10.4%)
39 (9.0%)
0.05 760 (13.0%)
104 (11.1%)
0.06 1,362 (10.9%)172 (8.7%)
0.07
Smoking; n (%)
1,015 (27.6%) 194 (32.5%)
-0.11 352 (12.0%)
71 (16.5%)
-0.13 1,758 (30.2%)296 (31.5%)
-0.03 3,125 (25.1%)561 (28.5%)
-0.08
Frailty Score: Empirical Version 365 days (ICD-9 and ICD-10) v2
...mean (sd)
0.17 (0.05)
0.17 (0.05)
0.00 0.16 (0.05)
0.16 (0.05)
0.00 0.20 (0.06)
0.19 (0.06)
0.17 0.18 (0.05)
0.18 (0.06)
0.00
...median [IQR]
0.16 [0.13, 0.10.16 [0.13, 0.1
0.00 0.15 [0.13, 0.10.15 [0.13, 0.1
0.00 0.19 [0.16, 0.20.18 [0.15, 0.2
0.17 0.17 (0.06)
0.17 (0.06)
0.00
Healthcare utilization
Any hospitalization; n (%)
905 (24.6%)
155 (26.0%)
-0.03 786 (26.8%)
95 (22.0%)
0.11 1,691 (29.0%)250 (26.6%)
0.05 3,382 (27.2%)500 (25.4%)
0.04
Bone mineral density; n (%)
162 (4.4%)
23 (3.9%)
0.03 78 (2.7%)
10 (2.3%)
0.03 245 (4.2%)
43 (4.6%)
-0.02 485 (3.9%)
76 (3.9%)
0.00
BUN tests; n (%)
502 (13.6%)
89 (14.9%)
-0.04 281 (9.6%)
48 (11.1%)
-0.05 1,151 (19.7%)184 (19.6%)
0.00 1,934 (15.5%)321 (16.3%)
-0.02
Cardiologist visit
0
1,492 (40.5%) 205 (34.3%)
0.13 1,317 (44.8%)193 (44.8%)
0.00 1,338 (23.0%)195 (20.7%)
0.06 4,147 (33.3%)593 (30.1%)
0.07
1-2
1,101 (29.9%) 175 (29.3%)
0.01 744 (25.3%)
115 (26.7%)
-0.03 1,920 (32.9%)325 (34.5%)
-0.03 3,765 (30.2%)615 (31.2%)
-0.02
3-5
665 (18.1%)
146 (24.5%)
-0.16 536 (18.2%)
76 (17.6%)
0.02 1,567 (26.9%)254 (27.0%)
0.00 2,768 (22.2%)476 (24.2%)
-0.05
>=6
423 (11.5%)
71 (11.9%)
-0.01 341 (11.6%)
47 (10.9%)
0.02 1,004 (17.2%)167 (17.7%)
-0.01 1,768 (14.2%)285 (14.5%)
-0.01
Colonoscopy; n (%)
412 (11.2%)
69 (11.6%)
-0.01 330 (11.2%)
43 (10.0%)
0.04 632 (10.8%)
109 (11.6%)
-0.03 1,374 (11.0%)221 (11.2%)
-0.01
Endocrinologist Visit; n (%)
178 (4.8%)
20 (3.4%)
0.07 83 (2.8%)
15 (3.5%)
-0.04 563 (9.7%)
93 (9.9%)
-0.01 824 (6.6%)
128 (6.5%)
0.00
Fecal occult blood (FOB) test; n (%)
300 (8.1%)
52 (8.7%)
-0.02 127 (4.3%)
20 (4.6%)
-0.01 401 (6.9%)
64 (6.8%)
0.00 828 (6.7%)
136 (6.9%)
-0.01
Flu vaccine; n (%)
1,333 (36.2%) 218 (36.5%)
-0.01 588 (20.0%)
82 (19.0%)
0.03 3,495 (60.0%)617 (65.6%)
-0.12 5,416 (43.5%)917 (46.6%)
-0.06
Glucose test strips; n (%)
86 (2.3%)
14 (2.3%)
0.00 45 (1.5%)
8 (1.9%)
-0.03 357 (6.1%)
63 (6.7%)
-0.02 488 (3.9%)
85 (4.3%)
-0.02
Glucose tests; n (%)
578 (15.7%)
101 (16.9%)
-0.03 336 (11.4%)
59 (13.7%)
-0.07 1,837 (31.5%)276 (29.3%)
0.05 2,751 (22.1%)436 (22.1%)
0.00
HbA1c tests ; n (%)
1,554 (42.2%) 280 (46.9%)
-0.09 570 (19.4%)
97 (22.5%)
-0.08 4,510 (77.4%)724 (76.9%)
0.01 6,634 (53.3%)1,101 (55.9%)
-0.05
Imaging/Diagnostics Used in Prostate Cancer
0
1,717 (46.6%) 197 (33.0%)
0.28 1,366 (46.5%)132 (30.6%)
0.33 2,879 (49.4%)355 (37.7%)
0.24 5,962 (47.9%)684 (34.7%)
0.27
1-3
1,620 (44.0%) 323 (54.1%)
-0.20 1,243 (42.3%)217 (50.3%)
-0.16 2,248 (38.6%)438 (46.5%)
-0.16 5,111 (41.1%)978 (49.7%)
-0.17
>=4
344 (9.3%)
77 (12.9%)
-0.11 329 (11.2%)
82 (19.0%)
-0.22 702 (12.0%)
148 (15.7%)
-0.11 1,375 (11.0%)307 (15.6%)
-0.14
Internal Medicine/Family Medicine Visits; n (%)
3,489 (94.8%) 568 (95.1%)
-0.01 2,513 (85.5%)377 (87.5%)
-0.06 5,219 (89.5%)838 (89.1%)
0.01 11,221 (90.1%1,783 (90.6%)
-0.02
Lipid tests; n (%)
2,689 (73.1%) 439 (73.5%)
-0.01 1,011 (34.4%)152 (35.3%)
-0.02 5,013 (86.0%)789 (83.8%)
0.06 8,713 (70.0%)1,380 (70.1%)
0.00
Microalbuminuria tests; n (%)
921 (25.0%)
150 (25.1%)
0.00 404 (13.8%)
72 (16.7%)
-0.08 2,428 (41.7%)425 (45.2%)
-0.07 3,753 (30.1%)647 (32.9%)
-0.06
Number of different/distinct medication prescriptions
...mean (sd)
8.01 (6.17)
8.27 (6.02)
-0.04 10.22 (5.52) 10.55 (5.10)
-0.06 11.92 (5.24) 11.69 (4.90)
0.05 10.36 (5.60) 10.40 (5.31)
-0.01
...median [IQR]
8.00 [3.00, 12 8.00 [4.00, 12
0.00 9.00 [6.00, 1310.00 [7.00, 1
-0.19 11.00 [8.00, 111.00 [8.00, 1
0.00 9.64 (6.20)
9.87 (5.91)
-0.04
Office Visits (outpatient setting only)
...mean (sd)
12.48 (6.80)
12.44 (6.38)
0.01 12.31 (7.03) 12.46 (6.32)
-0.02 14.62 (7.67) 14.29 (6.95)
0.05 13.44 (7.27) 13.33 (6.65)
0.02
...median [IQR]
11.00 [8.00, 1 11.00 [8.00, 15.00]
11.00 [8.00, 111.00 [8.00, 1
0.00 13.00 [9.00, 113.00 [9.00, 1
0.00 11.94 (8.02) 11.96 (7.38)
0.00
Oncology Specialist Visit
0
2,571 (69.8%) 409 (68.5%)
0.03 2,668 (90.8%)390 (90.5%)
0.01 3,246 (55.7%)552 (58.7%)
-0.06 8,485 (68.2%)1,351 (68.6%)
-0.01
1-5
455 (12.4%)
77 (12.9%)
-0.02 112 (3.8%)
16 (3.7%)
0.01 1,059 (18.2%)185 (19.7%)
-0.04 1,626 (13.1%)278 (14.1%)
-0.03
>=6
655 (17.8%)
111 (18.6%)
-0.02 158 (5.4%)
25 (5.8%)
-0.02 1,524 (26.1%)204 (21.7%)
0.10 2,337 (18.8%)340 (17.3%)
0.04
Pneumonia vaccine; n (%)
958 (26.0%)
183 (30.7%)
-0.10 276 (9.4%)
49 (11.4%)
-0.07 1,445 (24.8%)281 (29.9%)
-0.11 2,679 (21.5%)513 (26.1%)
-0.11
Prostate cancer prognosticators
Radiation Therapies Used in Prostate Cancer; n (%)
18 (0.5%)
1 (0.2%)
0.05 7 (0.2%)
0 (0.0%)
0.06 N/A
N/A
N/A
N/A
N/A
N/A
PSA Test
...mean (sd)
2.42 (1.78)
2.40 (1.74)
0.01 1.19 (3.39)
1.00 (1.51)
0.12 2.59 (1.58)
2.41 (1.43)
0.12 2.21 (2.20)
2.10 (1.55)
0.06
...median [IQR]
2.00 [1.00, 3.02.00 [1.00, 3.0
0.00 0.00 [0.00, 2.00.00 [0.00, 2.0
0.00 2.00 [2.00, 3.02.00 [1.00, 3.0
-1.33 1.53 (2.74)
1.56 (1.73)
-0.01
Prostatectomy; n (%)
146 (4.0%)
18 (3.0%)
0.05 117 (4.0%)
11 (2.6%)
0.08 132 (2.3%)
22 (2.3%)
0.00 395 (3.2%)
51 (2.6%)
0.04
Prostate exam for DRE
...mean (sd)
1.19 (3.27)
1.18 (2.90)
0.00 0.31 (1.48)
0.31 (1.42)
0.17 0.38 (0.81)
0.42 (0.82)
-0.05
...median [IQR]
0.00 [0.00, 0.00.00 [0.00, 0.0
0.00 0.00 [0.00, 0.00.00 [0.00, 0.0
0.17 0.00 [0.00, 0.00.00 [0.00, 1.0
0.00
Prostate Cancer Comorbidity Index (PCCI)
...mean (sd)
35.65 (6.07)
36.68 (6.34)
-0.17 33.34 (4.90) 34.65 (5.37)
-0.02 36.36 (6.00) 36.99 (6.37)
-0.10 35.44 (5.78) 36.38 (6.16)
-0.16
...median [IQR]
35.00 [31.00, 36.00 [32.00, 
0.00 33.00 [30.00, 34.00 [30.00, 
-0.02 35.00 [32.00, 36.00 [33.00, 
-0.16 34.53 (6.24) 35.56 (6.74)
-0.16
Medications
ACE inhibitors; n (%)
1,263 (34.3%) 190 (31.8%)
0.05 1,161 (39.5%)181 (42.0%)
-0.05 2,704 (46.4%)461 (49.0%)
-0.05 5,128 (41.2%)832 (42.3%)
-0.02
Table 1 Unmatched

Anti-arrhythmics; n (%)
54 (1.5%)
12 (2.0%)
-0.04 55 (1.9%)
5 (1.2%)
0.06 136 (2.3%)
20 (2.1%)
0.01 245 (2.0%)
37 (1.9%)
0.01
Anti-diabetic Drugs; n (%)
747 (20.3%)
131 (21.9%)
-0.04 752 (25.6%)
118 (27.4%)
-0.04 3,789 (65.0%)582 (61.8%)
0.07 5,288 (42.5%)831 (42.2%)
0.01
Chemotherapies Used in Prostate Cancer; n (%)
18 (0.5%)
1 (0.2%)
0.05 10 (0.3%)
0 (0.0%)
0.08 N/A
N/A
N/A
N/A
N/A
N/A
Metformin; n (%)
486 (13.2%)
87 (14.6%)
-0.04 388 (13.2%)
68 (15.8%)
-0.07 2,144 (36.8%)346 (36.8%)
0.00 3,018 (24.2%)501 (25.4%)
-0.03
Use of anticonvulsants; n (%)
354 (9.6%)
52 (8.7%)
0.03 293 (10.0%)
44 (10.2%)
-0.01 901 (15.5%)
138 (14.7%)
0.02 1,548 (12.4%)234 (11.9%)
0.02
Use of antidepressants; n (%)
426 (11.6%)
70 (11.7%)
0.00 379 (12.9%)
58 (13.5%)
-0.02 1,015 (17.4%)144 (15.3%)
0.06 1,820 (14.6%)272 (13.8%)
0.02
Use of Antiparkinsonian Meds; n (%)
51 (1.4%)
13 (2.2%)
-0.06 69 (2.3%)
7 (1.6%)
0.05 207 (3.6%)
18 (1.9%)
0.10 327 (2.6%)
38 (1.9%)
0.05
Use of antiplatelet agents; n (%)
985 (26.8%)
161 (27.0%)
0.00 1,135 (38.6%)162 (37.6%)
0.02 2,276 (39.0%)356 (37.8%)
0.02 4,396 (35.3%)679 (34.5%)
0.02
Use of antipsychotics; n (%)
25 (0.7%)
7 (1.2%)
-0.05 35 (1.2%)
8 (1.9%)
-0.06 N/A
N/A
N/A
N/A
N/A
N/A
Use of anxiolytics/hypnotics; n (%)
137 (3.7%)
25 (4.2%)
-0.03 176 (6.0%)
25 (5.8%)
0.01 428 (7.3%)
62 (6.6%)
0.03 741 (6.0%)
112 (5.7%)
0.01
Use of ARBs; n (%)
573 (15.6%)
100 (16.8%)
-0.03 627 (21.3%)
88 (20.4%)
0.02 1,403 (24.1%)230 (24.4%)
-0.01 2,603 (20.9%)418 (21.2%)
-0.01
Use of Benzos; n (%)
355 (9.6%)
60 (10.1%)
-0.02 409 (13.9%)
45 (10.4%)
0.11 594 (10.2%)
108 (11.5%)
-0.04 1,358 (10.9%)213 (10.8%)
0.00
Use of beta blockers; n (%)
1,806 (49.1%) 305 (51.1%)
-0.04 1,879 (64.0%)286 (66.4%)
-0.05 3,987 (68.4%)689 (73.2%)
-0.11 7,672 (61.6%)1,280 (65.0%)
-0.07
Use of bisphosphonate; n (%)
105 (2.9%)
9 (1.5%)
0.10 82 (2.8%)
5 (1.2%)
0.11 175 (3.0%)
18 (1.9%)
0.07 362 (2.9%)
32 (1.6%)
0.09
Use of calcium channel blockers; n (%)
837 (22.7%)
154 (25.8%)
-0.07 889 (30.3%)
113 (26.2%)
0.09 1,955 (33.5%)294 (31.2%)
0.05 3,681 (29.6%)561 (28.5%)
0.02
Use of COPD/asthma meds; n (%)
468 (12.7%)
82 (13.7%)
-0.03 513 (17.5%)
89 (20.6%)
-0.08 1,128 (19.4%)166 (17.6%)
0.05 2,109 (16.9%)337 (17.1%)
-0.01
Use of Dementia Meds; n (%)
30 (0.8%)
10 (1.7%)
-0.08 63 (2.1%)
8 (1.9%)
0.01 153 (2.6%)
19 (2.0%)
0.04 246 (2.0%)
37 (1.9%)
0.01
Use of digoxin; n (%)
53 (1.4%)
12 (2.0%)
-0.05 93 (3.2%)
12 (2.8%)
0.02 211 (3.6%)
43 (4.6%)
-0.05 357 (2.9%)
67 (3.4%)
-0.03
Use of heparin and other low-molecular weight heparins; n (%)
40 (1.1%)
8 (1.3%)
-0.02 62 (2.1%)
7 (1.6%)
0.04 107 (1.8%)
25 (2.7%)
-0.06 209 (1.7%)
40 (2.0%)
-0.02
Use of Insulin; n (%)
214 (5.8%)
34 (5.7%)
0.00 223 (7.6%)
34 (7.9%)
-0.01 1,154 (19.8%)186 (19.8%)
0.00 1,591 (12.8%)254 (12.9%)
0.00
Use of Lithium; n (%)
6 (0.2%)
0 (0.0%)
0.06 2 (0.1%)
0 (0.0%)
0.04 N/A
N/A
N/A
N/A
N/A
N/A
Use of Loop Diuretics; n (%)
338 (9.2%)
59 (9.9%)
-0.02 395 (13.4%)
61 (14.2%)
-0.02 1,199 (20.6%)197 (20.9%)
-0.01 1,932 (15.5%)317 (16.1%)
-0.02
Use of nitrates; n (%)
524 (14.2%)
75 (12.6%)
0.05 630 (21.4%)
82 (19.0%)
0.06 1,348 (23.1%)205 (21.8%)
0.03 2,502 (20.1%)362 (18.4%)
0.04
Use of NSAIDs; n (%)
405 (11.0%)
74 (12.4%)
-0.04 402 (13.7%)
57 (13.2%)
0.01 1,015 (17.4%)132 (14.0%)
0.09 1,822 (14.6%)263 (13.4%)
0.03
Use of opioids; n (%)
1,034 (28.1%) 173 (29.0%)
-0.02 1,087 (37.0%)171 (39.7%)
-0.06 2,338 (40.1%)369 (39.2%)
0.02 4,459 (35.8%)713 (36.2%)
-0.01
Use of oral anticoagulants (Dabigatran, Rivaroxaban, Apixaban, Warfarin); n (%)
326 (8.9%)
52 (8.7%)
0.01 350 (11.9%)
53 (12.3%)
-0.01 822 (14.1%)
147 (15.6%)
-0.04 1,498 (12.0%)252 (12.8%)
-0.02
Use of oral corticosteroids; n (%)
700 (19.0%)
134 (22.4%)
-0.08 710 (24.2%)
103 (23.9%)
0.01 1,538 (26.4%)252 (26.8%)
-0.01 2,948 (23.7%)489 (24.8%)
-0.03
Use of other antiplatelet agents; n (%)
33 (0.9%)
8 (1.3%)
-0.04 50 (1.7%)
3 (0.7%)
0.09 N/A
N/A
N/A
N/A
N/A
N/A
Use of other diuretics; n (%)
100 (2.7%)
16 (2.7%)
0.00 122 (4.2%)
22 (5.1%)
-0.04 289 (5.0%)
52 (5.5%)
-0.02 511 (4.1%)
90 (4.6%)
-0.02
Use of other hypertension drugs; n (%)
274 (7.4%)
49 (8.2%)
-0.03 266 (9.1%)
32 (7.4%)
0.06 661 (11.3%)
91 (9.7%)
0.05 1,201 (9.6%) 172 (8.7%)
0.03
Use of other lipid-lowering drugs; n (%)
329 (8.9%)
45 (7.5%)
0.05 477 (16.2%)
55 (12.8%)
0.10 910 (15.6%)
135 (14.3%)
0.04 1,716 (13.8%)235 (11.9%)
0.06
Use of statins; n (%)
2,231 (60.6%) 374 (62.6%)
-0.04 2,230 (75.9%)342 (79.4%)
-0.08 4,610 (79.1%)766 (81.4%)
-0.06 9,071 (72.9%)1,482 (75.3%)
-0.05
Use of thiazide; n (%)
321 (8.7%)
46 (7.7%)
0.04 315 (10.7%)
45 (10.4%)
0.01 730 (12.5%)
113 (12.0%)
0.02 1,366 (11.0%)204 (10.4%)
0.02
Table 1 Unmatched

Variable
Leuprolide
Degarelix
St. Diff
Leuprolide
Degarelix
St. Diff
Leuprolide
Degarelix
St. Diff
Leuprolide
Degarelix
St. Diff
Number of patients
546
546
415
415
926
926
1,887
1,887
Year of Cohort Entry Date
...2008-2009; n (%)
------
------
------
------
------
------
...2010; n (%)
18 (3.3%)
20 (3.7%)
-0.02 28 (6.7%)
24 (5.8%)
0.04 46 (5.0%)
37 (4.0%)
0.05 92 (4.9%)
81 (4.3%)
0.03
...2011; n (%)
26 (4.8%)
23 (4.2%)
0.03 42 (10.1%)
45 (10.8%)
-0.02 53 (5.7%)
49 (5.3%)
0.02 121 (6.4%)
117 (6.2%)
0.01
...2012; n (%)
42 (7.7%)
40 (7.3%)
0.02 44 (10.6%)
50 (12.0%)
-0.04 92 (9.9%)
69 (7.5%)
0.09 178 (9.4%)
159 (8.4%)
0.04
...2013; n (%)
50 (9.2%)
50 (9.2%)
0.00 61 (14.7%)
56 (13.5%)
0.03 116 (12.5%)
121 (13.1%)
-0.02 227 (12.0%)
227 (12.0%)
0.00
...2014; n (%)
39 (7.1%)
35 (6.4%)
0.03 42 (10.1%)
46 (11.1%)
-0.03 143 (15.4%)
170 (18.4%)
-0.08 224 (11.9%)
251 (13.3%)
-0.04
...2015; n (%)
39 (7.1%)
42 (7.7%)
-0.02 58 (14.0%)
60 (14.5%)
-0.01 182 (19.7%)
171 (18.5%)
0.03 279 (14.8%)
273 (14.5%)
0.01
...2016; n (%)
67 (12.3%)
62 (11.4%)
0.03 63 (15.2%)
63 (15.2%)
0.00 130 (14.0%)
144 (15.6%)
-0.05 260 (13.8%)
269 (14.3%)
-0.01
...2017; n (%)
65 (11.9%)
74 (13.6%)
-0.05 53 (12.8%)
47 (11.3%)
0.05 164 (17.7%)
165 (17.8%)
0.00 282 (14.9%)
286 (15.2%)
-0.01
...2018; n (%)
72 (13.2%)
76 (13.9%)
-0.02 24 (5.8%)
24 (5.8%)
0.00 ------
------
...2019; n (%)
89 (16.3%)
91 (16.7%)
-0.01 ------
------
------
------
...2020; n (%)
39 (7.1%)
33 (6.0%)
0.04 ------
------
------
------
Age
...mean (sd)
76.19 (6.92)
76.04 (7.59)
0.02 74.65 (9.34)
74.49 (9.17)
0.02 76.99 (6.56)
77.02 (6.47)
0.00 76.24 (6.74)
76.18 (6.87)
0.01
...median [IQR]
77.00 [72.00, 81.00]
76.00 [71.00, 82.00]
0.14 75.00 [67.00, 82.00]
75.00 [68.00, 82.00]
0.00 76.00 [72.00, 82.00]
77.00 [72.00, 82.00]
-0.15 76.07 (7.36)
76.27 (7.46)
-0.03
Region
...1 - Northeast; n (%)
86 (15.8%)
85 (15.6%)
0.01 94 (22.7%)
92 (22.2%)
0.01 194 (21.0%)
189 (20.4%)
0.01 374 (19.8%)
366 (19.4%)
0.01
...2 - North Central; n (%)
131 (24.0%)
131 (24.0%)
0.00 145 (34.9%)
144 (34.7%)
0.00 208 (22.5%)
223 (24.1%)
-0.04 484 (25.6%)
498 (26.4%)
-0.02
...3 - South; n (%)
209 (38.3%)
205 (37.5%)
0.02 139 (33.5%)
130 (31.3%)
0.05 373 (40.3%)
368 (39.7%)
0.01 721 (38.2%)
703 (37.3%)
0.02
...4 - West; n (%)
120 (22.0%)
125 (22.9%)
-0.02 37 (8.9%)
49 (11.8%)
-0.10 151 (16.3%)
146 (15.8%)
0.01 308 (16.3%)
320 (17.0%)
-0.02
Race
...White; n (%)
437 (80.0%)
438 (80.2%)
-0.01 ------
------
796 (86.0%)
803 (86.7%)
-0.02 1,233 (65.3%)
1,241 (65.8%)
-0.01
...Asian; n (%)
8 (1.5%)
11 (2.0%)
-0.04 ------
------
N/A
N/A
N/A
N/A
N/A
N/A
...Black; n (%)
66 (12.1%)
61 (11.2%)
0.03 ------
------
93 (10.0%)
85 (9.2%)
0.03 159 (8.4%)
146 (7.7%)
0.03
...Hispanic; n (%)
35 (6.4%)
36 (6.6%)
-0.01 ------
------
N/A
N/A
N/A
N/A
N/A
N/A
...North American Native; n (%)
------
------
------
------
N/A
N/A
N/A
N/A
N/A
N/A
...Other; n (%)
------
------
------
------
18 (1.9%)
16 (1.7%)
0.02 18 (1.9%)
16 (1.7%)
0.02
Cardiovascular event prognosticators
Acute or Old MI; n (%)
204 (37.4%)
212 (38.8%)
-0.03 97 (23.4%)
94 (22.7%)
0.02 357 (38.6%)
348 (37.6%)
0.02 658 (34.9%)
654 (34.7%)
0.00
Anxiety; n (%)
32 (5.9%)
33 (6.0%)
0.00 20 (4.8%)
22 (5.3%)
-0.02 60 (6.5%)
57 (6.2%)
0.01 112 (5.9%)
112 (5.9%)
0.00
Atrial Fibrillation; n (%)
84 (15.4%)
90 (16.5%)
-0.03 62 (14.9%)
70 (16.9%)
-0.05 187 (20.2%)
206 (22.2%)
-0.05 333 (17.6%)
366 (19.4%)
-0.05
Coronary Atherosclerosis; n (%)
436 (79.9%)
432 (79.1%)
0.02 305 (73.5%)
302 (72.8%)
0.02 764 (82.5%)
762 (82.3%)
0.01 1,505 (79.8%)
1,496 (79.3%)
0.01
Coronary, Carotid, Illiac, Femoral, and Popliteal Revascularization (Angioplasty/Stent/CABG); n (%)
30 (5.5%)
43 (7.9%)
-0.10 40 (9.6%)
32 (7.7%)
0.07 63 (6.8%)
70 (7.6%)
-0.03 133 (7.0%)
145 (7.7%)
-0.03
Diabetes with Complications; n (%)
181 (33.2%)
186 (34.1%)
-0.02 62 (14.9%)
58 (14.0%)
0.03 745 (80.5%)
724 (78.2%)
0.06 988 (52.4%)
968 (51.3%)
0.02
Diabetes without Complications; n (%)
98 (17.9%)
116 (21.2%)
-0.08 149 (35.9%)
134 (32.3%)
0.08 340 (36.7%)
351 (37.9%)
-0.02 587 (31.1%)
601 (31.8%)
-0.02
DVT; n (%)
24 (4.4%)
23 (4.2%)
0.01 7 (1.7%)
6 (1.4%)
0.02 45 (4.9%)
42 (4.5%)
0.02 76 (4.0%)
71 (3.8%)
0.01
Edema; n (%)
60 (11.0%)
60 (11.0%)
0.00 30 (7.2%)
28 (6.7%)
0.02 136 (14.7%)
135 (14.6%)
0.00 226 (12.0%)
223 (11.8%)
0.01
Erectile dysfunction; n (%)
79 (14.5%)
77 (14.1%)
0.01 39 (9.4%)
42 (10.1%)
-0.02 121 (13.1%)
121 (13.1%)
0.00 239 (12.7%)
240 (12.7%)
0.00
Foot ulcer; n (%)
12 (2.2%)
18 (3.3%)
-0.07 9 (2.2%)
10 (2.4%)
-0.01 48 (5.2%)
48 (5.2%)
0.00 69 (3.7%)
76 (4.0%)
-0.02
Hyperlipidemia; n (%)
459 (84.1%)
467 (85.5%)
-0.04 300 (72.3%)
290 (69.9%)
0.05 837 (90.4%)
843 (91.0%)
-0.02 1,596 (84.6%)
1,600 (84.8%)
-0.01
Hypertension; n (%)
477 (87.4%)
479 (87.7%)
-0.01 313 (75.4%)
318 (76.6%)
-0.03 862 (93.1%)
867 (93.6%)
-0.02 1,652 (87.5%)
1,664 (88.2%)
-0.02
Intracranial or Retroperitoneal Hemorrhage ; n (%)
7 (1.3%)
5 (0.9%)
0.04 4 (1.0%)
3 (0.7%)
0.03 12 (1.3%)
17 (1.8%)
-0.04 23 (1.2%)
25 (1.3%)
-0.01
Ischemic Heart Disease; n (%)
461 (84.4%)
457 (83.7%)
0.02 325 (78.3%)
319 (76.9%)
0.03 795 (85.9%)
791 (85.4%)
0.01 1,581 (83.8%)
1,567 (83.0%)
0.02
Ischemic Stroke; n (%)
101 (18.5%)
101 (18.5%)
0.00 77 (18.6%)
76 (18.3%)
0.01 228 (24.6%)
229 (24.7%)
0.00 406 (21.5%)
406 (21.5%)
0.00
Major Trauma; n (%)
21 (3.8%)
27 (4.9%)
-0.05 22 (5.3%)
18 (4.3%)
0.05 65 (7.0%)
55 (5.9%)
0.04 108 (5.7%)
100 (5.3%)
0.02
Obesity; n (%)
66 (12.1%)
59 (10.8%)
0.04 55 (13.3%)
45 (10.8%)
0.08 147 (15.9%)
159 (17.2%)
-0.03 268 (14.2%)
263 (13.9%)
0.01
Other Disorders of Thyroid Gland; n (%)
12 (2.2%)
16 (2.9%)
-0.04 16 (3.9%)
13 (3.1%)
0.04 34 (3.7%)
38 (4.1%)
-0.02 62 (3.3%)
67 (3.6%)
-0.02
Overweight; n (%)
38 (7.0%)
40 (7.3%)
-0.01 10 (2.4%)
13 (3.1%)
-0.04 41 (4.4%)
42 (4.5%)
0.00 89 (4.7%)
95 (5.0%)
-0.01
PE; n (%)
10 (1.8%)
8 (1.5%)
0.02 2 (0.5%)
2 (0.5%)
0.00 N/A
N/A
N/A
N/A
N/A
N/A
Peripheral Vascular Disease; n (%)
191 (35.0%)
185 (33.9%)
0.02 109 (26.3%)
111 (26.7%)
-0.01 284 (30.7%)
272 (29.4%)
0.03 584 (30.9%)
568 (30.1%)
0.02
Stable Angina; n (%)
62 (11.4%)
75 (13.7%)
-0.07 38 (9.2%)
34 (8.2%)
0.04 107 (11.6%)
112 (12.1%)
-0.02 207 (11.0%)
221 (11.7%)
-0.02
Systemic Embolism; n (%)
9 (1.6%)
8 (1.5%)
0.01 9 (2.2%)
9 (2.2%)
0.00 N/A
N/A
N/A
N/A
N/A
N/A
TIA; n (%)
19 (3.5%)
19 (3.5%)
0.00 8 (1.9%)
10 (2.4%)
-0.03 35 (3.8%)
36 (3.9%)
-0.01 62 (3.3%)
65 (3.4%)
-0.01
General Health/Mortality Prognosticators
Abnormal liver function; n (%)
57 (10.4%)
53 (9.7%)
0.02 31 (7.5%)
27 (6.5%)
0.04 103 (11.1%)
97 (10.5%)
0.02 191 (10.1%)
177 (9.4%)
0.02
Alcohol Abuse/Dependence; n (%)
19 (3.5%)
15 (2.7%)
0.05 5 (1.2%)
5 (1.2%)
0.00 18 (1.9%)
19 (2.1%)
-0.01 42 (2.2%)
39 (2.1%)
0.01
Anemias (Sickle-Cell, G6PD Deficiency, Nutrient Deficiency); n (%)
129 (23.6%)
141 (25.8%)
-0.05 81 (19.5%)
68 (16.4%)
0.08 282 (30.5%)
280 (30.2%)
0.01 492 (26.1%)
489 (25.9%)
0.00
Asthma; n (%)
23 (4.2%)
21 (3.8%)
0.02 21 (5.1%)
21 (5.1%)
0.00 60 (6.5%)
58 (6.3%)
0.01 104 (5.5%)
100 (5.3%)
0.01
COPD; n (%)
127 (23.3%)
125 (22.9%)
0.01 84 (20.2%)
74 (17.8%)
0.06 236 (25.5%)
221 (23.9%)
0.04 447 (23.7%)
420 (22.3%)
0.03
Delirium; n (%)
15 (2.7%)
14 (2.6%)
0.01 4 (1.0%)
4 (1.0%)
0.00 34 (3.7%)
34 (3.7%)
0.00 53 (2.8%)
52 (2.8%)
0.00
Dementia; n (%)
17 (3.1%)
18 (3.3%)
-0.01 11 (2.7%)
9 (2.2%)
0.03 24 (2.6%)
30 (3.2%)
-0.04 52 (2.8%)
57 (3.0%)
-0.01
Depression ; n (%)
49 (9.0%)
45 (8.2%)
0.03 23 (5.5%)
22 (5.3%)
0.01 72 (7.8%)
76 (8.2%)
-0.01 144 (7.6%)
143 (7.6%)
0.00
Falls; n (%)
31 (5.7%)
38 (7.0%)
-0.05 10 (2.4%)
10 (2.4%)
0.00 60 (6.5%)
71 (7.7%)
-0.05 101 (5.4%)
119 (6.3%)
-0.04
Fractures; n (%)
35 (6.4%)
29 (5.3%)
0.05 22 (5.3%)
21 (5.1%)
0.01 44 (4.8%)
45 (4.9%)
0.00 101 (5.4%)
95 (5.0%)
0.02
HIV/AIDS; n (%)
0 (0.0%)
2 (0.4%)
-0.09 0 (0.0%)
0 (0.0%)
N/A
N/A
N/A
N/A
N/A
N/A
N/A
Organ Transplant; n (%)
1 (0.2%)
3 (0.5%)
-0.05 4 (1.0%)
4 (1.0%)
0.00 N/A
N/A
N/A
N/A
N/A
N/A
Osteoporosis; n (%)
29 (5.3%)
23 (4.2%)
0.05 14 (3.4%)
12 (2.9%)
0.03 48 (5.2%)
54 (5.8%)
-0.03 91 (4.8%)
89 (4.7%)
0.00
Peptic Ulcer Disease; n (%)
142 (26.0%)
141 (25.8%)
0.00 73 (17.6%)
72 (17.3%)
0.01 249 (26.9%)
254 (27.4%)
-0.01 464 (24.6%)
467 (24.7%)
0.00
Pneumonia; n (%)
19 (3.5%)
15 (2.7%)
0.05 11 (2.7%)
15 (3.6%)
-0.05 18 (1.9%)
19 (2.1%)
-0.01 48 (2.5%)
49 (2.6%)
-0.01
Renal Failure; n (%)
123 (22.5%)
127 (23.3%)
-0.02 56 (13.5%)
56 (13.5%)
0.00 246 (26.6%)
246 (26.6%)
0.00 425 (22.5%)
429 (22.7%)
0.00
Renal Failure (CKD Stage 4 or higher); n (%)
17 (3.1%)
17 (3.1%)
0.00 10 (2.4%)
12 (2.9%)
-0.03 47 (5.1%)
49 (5.3%)
-0.01 74 (3.9%)
78 (4.1%)
-0.01
Sleep Apnea; n (%)
46 (8.4%)
52 (9.5%)
-0.04 42 (10.1%)
43 (10.4%)
-0.01 96 (10.4%)
106 (11.4%)
-0.03 184 (9.8%)
201 (10.7%)
-0.03
Sleep Disorder; n (%)
27 (4.9%)
29 (5.3%)
-0.02 26 (6.3%)
38 (9.2%)
-0.11 82 (8.9%)
101 (10.9%)
-0.07 135 (7.2%)
168 (8.9%)
-0.06
Smoking; n (%)
184 (33.7%)
178 (32.6%)
0.02 73 (17.6%)
66 (15.9%)
0.05 270 (29.2%)
290 (31.3%)
-0.05 527 (27.9%)
534 (28.3%)
-0.01
Frailty Score: Empirical Version 365 days (ICD-9 and ICD-10) v2
...mean (sd)
0.16 (0.05)
0.16 (0.05)
0.00 0.16 (0.05)
0.16 (0.05)
0.00 0.19 (0.06)
0.19 (0.06)
0.00 0.17 (0.05)
0.17 (0.05)
0.00
...median [IQR]
0.15 [0.13, 0.19]
0.16 [0.13, 0.19]
-0.20 0.15 [0.13, 0.18]
0.15 [0.13, 0.19]
0.00 0.18 [0.15, 0.22]
0.18 [0.15, 0.22]
0.00 0.16 (0.06)
0.17 (0.06)
-0.17
Healthcare utilization
Any hospitalization; n (%)
109 (20.0%)
133 (24.4%)
-0.11 89 (21.4%)
90 (21.7%)
-0.01 242 (26.1%)
244 (26.3%)
0.00 440 (23.3%)
467 (24.7%)
-0.03
Bone mineral density; n (%)
23 (4.2%)
20 (3.7%)
0.03 11 (2.7%)
9 (2.2%)
0.03 41 (4.4%)
41 (4.4%)
0.00 75 (4.0%)
70 (3.7%)
0.02
BUN tests; n (%)
82 (15.0%)
82 (15.0%)
0.00 55 (13.3%)
45 (10.8%)
0.08 181 (19.5%)
183 (19.8%)
-0.01 318 (16.9%)
310 (16.4%)
0.01
Cardiologist visit
0
203 (37.2%)
189 (34.6%)
0.05 181 (43.6%)
187 (45.1%)
-0.03 200 (21.6%)
194 (21.0%)
0.01 584 (30.9%)
570 (30.2%)
0.02
1-2
160 (29.3%)
164 (30.0%)
-0.02 114 (27.5%)
108 (26.0%)
0.03 336 (36.3%)
320 (34.6%)
0.04 610 (32.3%)
592 (31.4%)
0.02
3-5
132 (24.2%)
131 (24.0%)
0.00 75 (18.1%)
75 (18.1%)
0.00 241 (26.0%)
249 (26.9%)
-0.02 448 (23.7%)
455 (24.1%)
-0.01
>=6
51 (9.3%)
62 (11.4%)
-0.07 45 (10.8%)
45 (10.8%)
0.00 149 (16.1%)
163 (17.6%)
-0.04 245 (13.0%)
270 (14.3%)
-0.04
Colonoscopy; n (%)
67 (12.3%)
65 (11.9%)
0.01 44 (10.6%)
41 (9.9%)
0.02 91 (9.8%)
108 (11.7%)
-0.06 202 (10.7%)
214 (11.3%)
-0.02
Endocrinologist Visit; n (%)
17 (3.1%)
19 (3.5%)
-0.02 13 (3.1%)
15 (3.6%)
-0.03 70 (7.6%)
90 (9.7%)
-0.07 100 (5.3%)
124 (6.6%)
-0.05
Fecal occult blood (FOB) test; n (%)
53 (9.7%)
47 (8.6%)
0.04 16 (3.9%)
19 (4.6%)
-0.03 62 (6.7%)
64 (6.9%)
-0.01 131 (6.9%)
130 (6.9%)
0.00
MATCHED
Optum
Marketscan
Pooled
Medicare
Table 1 Matched

Flu vaccine; n (%)
222 (40.7%)
204 (37.4%)
0.07 84 (20.2%)
79 (19.0%)
0.03 599 (64.7%)
605 (65.3%)
-0.01 905 (48.0%)
888 (47.1%)
0.02
Glucose test strips; n (%)
6 (1.1%)
12 (2.2%)
-0.09 8 (1.9%)
8 (1.9%)
0.00 59 (6.4%)
63 (6.8%)
-0.02 73 (3.9%)
83 (4.4%)
-0.03
Glucose tests; n (%)
74 (13.6%)
91 (16.7%)
-0.09 73 (17.6%)
54 (13.0%)
0.13 268 (28.9%)
271 (29.3%)
-0.01 415 (22.0%)
416 (22.0%)
0.00
HbA1c tests ; n (%)
246 (45.1%)
249 (45.6%)
-0.01 101 (24.3%)
92 (22.2%)
0.05 712 (76.9%)
712 (76.9%)
0.00 1,059 (56.1%)
1,053 (55.8%)
0.01
Imaging/Diagnostics Used in Prostate Cancer
0
177 (32.4%)
181 (33.2%)
-0.02 128 (30.8%)
132 (31.8%)
-0.02 332 (35.9%)
348 (37.6%)
-0.04 637 (33.8%)
661 (35.0%)
-0.03
1-3
304 (55.7%)
296 (54.2%)
0.03 209 (50.4%)
208 (50.1%)
0.01 449 (48.5%)
433 (46.8%)
0.03 962 (51.0%)
937 (49.7%)
0.03
>=4
65 (11.9%)
69 (12.6%)
-0.02 78 (18.8%)
75 (18.1%)
0.02 145 (15.7%)
145 (15.7%)
0.00 288 (15.3%)
289 (15.3%)
0.00
Internal Medicine/Family Medicine Visits; n (%)
512 (93.8%)
521 (95.4%)
-0.07 368 (88.7%)
364 (87.7%)
0.03 827 (89.3%)
824 (89.0%)
0.01 1,707 (90.5%)
1,709 (90.6%)
0.00
Lipid tests; n (%)
407 (74.5%)
402 (73.6%)
0.02 151 (36.4%)
146 (35.2%)
0.03 770 (83.2%)
775 (83.7%)
-0.01 1,328 (70.4%)
1,323 (70.1%)
0.01
Microalbuminuria tests; n (%)
129 (23.6%)
138 (25.3%)
-0.04 70 (16.9%)
66 (15.9%)
0.03 423 (45.7%)
419 (45.2%)
0.01 622 (33.0%)
623 (33.0%)
0.00
Number of different/distinct medication prescriptions
...mean (sd)
8.05 (5.80)
8.22 (6.03)
-0.03 10.77 (5.60)
10.45 (5.00)
0.06 11.62 (4.86)
11.67 (4.91)
-0.01 10.40 (4.84)
10.40 (4.79)
0.00
...median [IQR]
8.00 [4.00, 12.00]
8.00 [4.00, 12.00]
0.00 10.00 [7.00, 14.00]
10.00 [7.00, 13.00]
0.00 11.00 [8.00, 15.00]
11.00 [8.00, 15.00]
0.00 9.91 (5.31)
9.91 (5.28)
0.00
Office Visits (outpatient setting only)
...mean (sd)
12.19 (6.15)
12.35 (6.28)
-0.03 13.06 (6.91)
12.48 (6.36)
0.09 13.78 (6.87)
14.30 (6.98)
-0.08 13.16 (5.92)
13.34 (5.86)
-0.03
...median [IQR]
11.00 [8.00, 15.00]
11.00 [8.00, 15.00]
0.00 12.00 [8.00, 16.00]
11.00 [8.00, 16.00]
0.15 13.00 [9.00, 17.00]
13.00 [9.00, 18.00]
0.00 12.20 (6.68)
11.98 (6.65)
0.03
Oncology Specialist Visit
0
370 (67.8%)
370 (67.8%)
0.00 368 (88.7%)
375 (90.4%)
-0.06 565 (61.0%)
546 (59.0%)
0.04 1,303 (69.1%)
1,291 (68.4%)
0.02
1-5
73 (13.4%)
72 (13.2%)
0.01 18 (4.3%)
16 (3.9%)
0.02 166 (17.9%)
181 (19.5%)
-0.04 257 (13.6%)
269 (14.3%)
-0.02
>=6
103 (18.9%)
104 (19.0%)
0.00 29 (7.0%)
24 (5.8%)
0.05 195 (21.1%)
199 (21.5%)
-0.01 327 (17.3%)
327 (17.3%)
0.00
Pneumonia vaccine; n (%)
174 (31.9%)
174 (31.9%)
0.00 45 (10.8%)
48 (11.6%)
-0.03 257 (27.8%)
275 (29.7%)
-0.04 476 (25.2%)
497 (26.3%)
-0.03
Prostate cancer prognosticators
Radiation Therapies Used in Prostate Cancer; n (%)
3 (0.5%)
1 (0.2%)
0.05 1 (0.2%)
0 (0.0%)
0.06 N/A
N/A
N/A
N/A
N/A
N/A
PSA Test
...mean (sd)
2.38 (1.80)
2.41 (1.75)
-0.02 0.94 (1.45)
1.01 (1.53)
-0.05 2.33 (1.40)
2.40 (1.42)
-0.05 2.04 (1.40)
2.10 (1.41)
0.00
...median [IQR]
2.00 [1.00, 3.00]
2.00 [1.00, 3.25]
0.00 0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 2.00 [1.00, 3.00]
2.00 [1.00, 3.00]
0.00 1.56 (1.54)
1.56 (1.55)
0.00
Prostatectomy; n (%)
14 (2.6%)
17 (3.1%)
-0.03 16 (3.9%)
11 (2.7%)
-0.24 22 (2.4%)
21 (2.3%)
-0.22 52 (2.8%)
49 (2.6%)
0.01
Prostate exam for DRE
...mean (sd)
1.27 (3.29)
1.17 (2.84)
0.03 0.33 (1.34)
0.30 (1.42)
0.02 0.45 (0.90)
0.42 (0.82)
0.03 0.66 (1.94)
0.61 (1.72)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 0.00 (1.98)
0.00 (1.76)
0.00
Prostate Cancer Comorbidity Index (PCCI)
...mean (sd)
36.39 (6.41)
36.50 (6.31)
-0.02 34.75 (5.72)
34.42 (5.19)
0.06 37.00 (6.38)
36.99 (6.21)
0.00 36.33 (5.55)
36.28 (5.35)
0.00
...median [IQR]
35.00 [32.00, 40.00]
35.00 [32.00, 40.00]
0.00 34.00 [30.00, 38.00]
34.00 [30.00, 37.00]
0.00 36.00 [32.00, 41.00]
36.00 [33.00, 41.00]
0.00 35.27 (6.25)
35.27 (6.03)
0.00
Medications
ACE inhibitors; n (%)
179 (32.8%)
178 (32.6%)
0.00 162 (39.0%)
173 (41.7%)
-0.06 446 (48.2%)
453 (48.9%)
-0.01 787 (41.7%)
804 (42.6%)
-0.02
Anti-arrhythmics; n (%)
9 (1.6%)
11 (2.0%)
-0.03 7 (1.7%)
5 (1.2%)
0.04 11 (1.2%)
19 (2.1%)
-0.07 27 (1.4%)
35 (1.9%)
-0.04
Anti-diabetic Drugs; n (%)
116 (21.2%)
114 (20.9%)
0.01 114 (27.5%)
111 (26.7%)
0.02 582 (62.9%)
574 (62.0%)
0.02 812 (43.0%)
799 (42.3%)
0.01
Chemotherapies Used in Prostate Cancer; n (%)
3 (0.5%)
1 (0.2%)
0.05 1 (0.2%)
0 (0.0%)
0.06 N/A
N/A
N/A
N/A
N/A
N/A
Metformin; n (%)
73 (13.4%)
77 (14.1%)
-0.02 76 (18.3%)
62 (14.9%)
0.09 320 (34.6%)
341 (36.8%)
-0.05 469 (24.9%)
480 (25.4%)
-0.01
Use of anticonvulsants; n (%)
46 (8.4%)
49 (9.0%)
-0.02 44 (10.6%)
41 (9.9%)
0.02 128 (13.8%)
135 (14.6%)
-0.02 218 (11.6%)
225 (11.9%)
-0.01
Use of antidepressants; n (%)
67 (12.3%)
64 (11.7%)
0.02 46 (11.1%)
53 (12.8%)
-0.05 144 (15.6%)
142 (15.3%)
0.01 257 (13.6%)
259 (13.7%)
0.00
Use of Antiparkinsonian Meds; n (%)
10 (1.8%)
10 (1.8%)
0.00 6 (1.4%)
7 (1.7%)
-0.02 20 (2.2%)
18 (1.9%)
0.02 36 (1.9%)
35 (1.9%)
0.00
Use of antiplatelet agents; n (%)
143 (26.2%)
142 (26.0%)
0.00 164 (39.5%)
153 (36.9%)
0.05 358 (38.7%)
348 (37.6%)
0.02 665 (35.2%)
643 (34.1%)
0.02
Use of antipsychotics; n (%)
6 (1.1%)
6 (1.1%)
0.00 4 (1.0%)
7 (1.7%)
-0.06 N/A
N/A
N/A
N/A
N/A
N/A
Use of anxiolytics/hypnotics; n (%)
24 (4.4%)
23 (4.2%)
0.01 22 (5.3%)
24 (5.8%)
-0.02 57 (6.2%)
62 (6.7%)
-0.02 103 (5.5%)
109 (5.8%)
-0.01
Use of ARBs; n (%)
81 (14.8%)
87 (15.9%)
-0.03 90 (21.7%)
86 (20.7%)
0.02 248 (26.8%)
228 (24.6%)
0.05 419 (22.2%)
401 (21.3%)
0.02
Use of Benzos; n (%)
51 (9.3%)
54 (9.9%)
-0.02 48 (11.6%)
44 (10.6%)
0.03 98 (10.6%)
103 (11.1%)
-0.02 197 (10.4%)
201 (10.7%)
-0.01
Use of beta blockers; n (%)
273 (50.0%)
278 (50.9%)
-0.02 268 (64.6%)
276 (66.5%)
-0.04 668 (72.1%)
675 (72.9%)
-0.02 1,209 (64.1%)
1,229 (65.1%)
-0.02
Use of bisphosphonate; n (%)
12 (2.2%)
9 (1.6%)
0.04 11 (2.7%)
5 (1.2%)
0.11 18 (1.9%)
18 (1.9%)
0.00 41 (2.2%)
32 (1.7%)
0.04
Use of calcium channel blockers; n (%)
144 (26.4%)
144 (26.4%)
0.00 110 (26.5%)
108 (26.0%)
0.01 288 (31.1%)
291 (31.4%)
-0.01 542 (28.7%)
543 (28.8%)
0.00
Use of COPD/asthma meds; n (%)
75 (13.7%)
78 (14.3%)
-0.02 93 (22.4%)
82 (19.8%)
0.06 172 (18.6%)
163 (17.6%)
0.03 340 (18.0%)
323 (17.1%)
0.02
Use of Dementia Meds; n (%)
6 (1.1%)
8 (1.5%)
-0.04 11 (2.7%)
8 (1.9%)
0.05 20 (2.2%)
19 (2.1%)
0.01 37 (2.0%)
35 (1.9%)
0.01
Use of digoxin; n (%)
9 (1.6%)
10 (1.8%)
-0.02 11 (2.7%)
12 (2.9%)
-0.01 31 (3.3%)
43 (4.6%)
-0.07 51 (2.7%)
65 (3.4%)
-0.04
Use of heparin and other low-molecular weight heparins; n (%)
4 (0.7%)
6 (1.1%)
-0.04 9 (2.2%)
6 (1.4%)
0.06 26 (2.8%)
25 (2.7%)
0.01 39 (2.1%)
37 (2.0%)
0.01
Use of Insulin; n (%)
23 (4.2%)
28 (5.1%)
-0.04 30 (7.2%)
32 (7.7%)
-0.02 174 (18.8%)
184 (19.9%)
-0.03 227 (12.0%)
244 (12.9%)
-0.03
Use of Lithium; n (%)
1 (0.2%)
0 (0.0%)
0.06 0 (0.0%)
0 (0.0%)
N/A
N/A
N/A
N/A
N/A
N/A
N/A
Use of Loop Diuretics; n (%)
45 (8.2%)
52 (9.5%)
-0.05 51 (12.3%)
58 (14.0%)
-0.05 186 (20.1%)
195 (21.1%)
-0.02 282 (14.9%)
305 (16.2%)
-0.04
Use of nitrates; n (%)
74 (13.6%)
69 (12.6%)
0.03 74 (17.8%)
77 (18.6%)
-0.02 198 (21.4%)
201 (21.7%)
-0.01 346 (18.3%)
347 (18.4%)
0.00
Use of NSAIDs; n (%)
71 (13.0%)
69 (12.6%)
0.01 62 (14.9%)
57 (13.7%)
0.03 141 (15.2%)
128 (13.8%)
0.04 274 (14.5%)
254 (13.5%)
0.03
Use of opioids; n (%)
169 (31.0%)
159 (29.1%)
0.04 158 (38.1%)
162 (39.0%)
-0.02 376 (40.6%)
361 (39.0%)
0.03 703 (37.3%)
682 (36.1%)
0.02
Use of oral anticoagulants (Dabigatran, Rivaroxaban, Apixaban, Warfarin); n (%)
46 (8.4%)
46 (8.4%)
0.00 51 (12.3%)
51 (12.3%)
0.00 138 (14.9%)
147 (15.9%)
-0.03 235 (12.5%)
244 (12.9%)
-0.01
Use of oral corticosteroids; n (%)
126 (23.1%)
124 (22.7%)
0.01 110 (26.5%)
100 (24.1%)
0.06 277 (29.9%)
246 (26.6%)
0.07 513 (27.2%)
470 (24.9%)
0.05
Use of other antiplatelet agents; n (%)
8 (1.5%)
5 (0.9%)
0.06 4 (1.0%)
3 (0.7%)
0.03 N/A
N/A
N/A
N/A
N/A
N/A
Use of other diuretics; n (%)
16 (2.9%)
16 (2.9%)
0.00 29 (7.0%)
21 (5.1%)
0.08 48 (5.2%)
51 (5.5%)
-0.01 93 (4.9%)
88 (4.7%)
0.01
Use of other hypertension drugs; n (%)
44 (8.1%)
47 (8.6%)
-0.02 28 (6.7%)
31 (7.5%)
-0.03 96 (10.4%)
90 (9.7%)
0.02 168 (8.9%)
168 (8.9%)
0.00
Use of other lipid-lowering drugs; n (%)
37 (6.8%)
41 (7.5%)
-0.03 45 (10.8%)
51 (12.3%)
-0.05 131 (14.1%)
132 (14.3%)
-0.01 213 (11.3%)
224 (11.9%)
-0.02
Use of statins; n (%)
347 (63.6%)
341 (62.5%)
0.02 324 (78.1%)
327 (78.8%)
-0.02 743 (80.2%)
752 (81.2%)
-0.03 1,414 (74.9%)
1,420 (75.3%)
-0.01
Use of thiazide; n (%)
42 (7.7%)
41 (7.5%)
0.01 40 (9.6%)
43 (10.4%)
-0.03 106 (11.4%)
112 (12.1%)
-0.02 188 (10.0%)
196 (10.4%)
-0.01
Table 1 Matched