Replication of the D58 Asthma Trial in Healthcare Claims Data
Conditions: Asthma
Sponsor: Brigham and Women's Hospital

Replication of the D58 Asthma Trial in Healthcare Claims Data 
DUPLICATE-D58 
September 14, 2021 
NCT04892732 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
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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
A 26 Week, Randomized, Double-blind, Parallel-group, Active Controlled, Multicenter, Multinational Safety Study 
Evaluating the Risk of Serious Asthma-related Events During Treatment With Symbicort®, a Fixed Combination of Inhaled 
Corticosteroid (ICS) (Budesonide) and a Long Acting β2-agonist (LABA) (Formoterol) as Compared to Treatment With ICS 
(Budesonide) Alone in Adult and Adolescent (≥12 Years of Age) Patients With Asthma (D5896C00027 Study 
NCT01444430)  
1.2 Intended aim(s) 
To assess the effects of 26 weeks treatment with budesonide-formoterol compared with budesonide alone on the incidence of 
first serious asthma-related event (a composite of adjudicated death, intubation, and hospitalization) in patients who had 
persistent asthma.  
1.3 Primary endpoint for replication 
First serious asthma-related event (a composite of adjudicated death, intubation, and hospitalization. 
1.4 Required power for primary endpoint and noninferiority margin (if applicable) 
To meet the prespecified noninferiority margin, the upper limit of the two-sided 95% confidence interval of the hazard ratio 
for the first serious asthma-related event with budesonide-formoterol versus budesonide had to be less than 2.0.  The 
incidence rate of serious asthma-related events in the budesonide-only treatment group was predicted to be 0.0075 over a 26-
week period.  It was calculated that 87 events would have to occur for the study to have 90% power to rule out an event rate 
with budesonide-formoterol that was twice as high as the rate with budesonide alone.   
1.5 Secondary endpoint for replication (assay sensitivity) and RCT finding 
Individual components of the primary outcome 1) Asthma-related hospitalization 
2) Asthma-related intubation
3) Asthma-related death

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1.6 Trial estimate 
Hazard Ratio, HR = 1.07 (95% CI, 0.70 to 1.65) comparing budesonide-formoterol versus budesonide during a 26-week 
period (Peters et al., 2016).  
 
2. Person responsible for implementation of replication in Aetion 
Hemin Lee, MD, MPH, implemented the study design in the Aetion Evidence Platform. She is 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. 
 
3. Data Source(s) 
Optum CDM, IBM® MarketScan® 
 
4. Study Design Diagram 
The study design diagram visualizes key aspects of the longitudinal study design for expedited review. 
 
Figure 1. Design Diagram – D5896C00027 (NCT 01444430) TRIAL REPLICATION 

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5. Cohort Identification  
 
5.1 Cohort Summary 
This study will involve a new user, parallel group, propensity score-matched, retrospective cohort design comparing budesonide-
formoterol versus budesonide alone. The patients will be required to have continuous enrollment during a baseline period of 180 
days before initiation of budesonide-formoterol or budesonide.  
 
5.2 Important steps for cohort formation 
New use of budesonide-formoterol (exposure) is defined as no use of the exposure drug within the 180 days prior to index date. 
This will emulate the trial requirement for which treatment with budesonide-formoterol was not allowed any time before 
randomization. New use of budesonide (comparator) is defined as no use of the comparator drug within the 180 days prior to index 
date. New users of budesonide are not allowed to receive of budesonide-formoterol within the 180 days prior to index date, and 
new users of budesonide-formoterol are not allowed to receive budesonide within the 180 days prior to index date. 
 
5.2.1 Eligible cohort entry dates 
Budesonide-formoterol was approved by FDA on July 21, 2006 for management of asthma.  The initial eligible cohort 
entry date was the first date after July 21, 2006 for both the databases investigated (IBM® MarketScan®, Optum CDM). 
The last date eligible as cohort entry date was the end of available data for IBM® MarketScan® and Optum CDM. The 
following eligible cohort entry dates were included: 
• IBM® MarketScan®: July 21, 2006 – December 31, 2018 (end of available data)  
• Optum CDM: July 21, 2006 – June 30, 2020 (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 A and are summarized in the flowcharts below.  
 
 
 
 
 
 
 

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5.3 Flowchart of the study cohort assembly 
For Budesonide-formoterol vs. Budesonide 
 
  
Optum CDM 
IBM® MarketScan® 
Less Excluded Patients 
Remaining 
Patients 
Remaining 
Patients 
Less 
Excluded 
Patients 
Remaining 
Patients 
All patients 
  
78,202,636   
200,203,908 
Did not meet cohort entry criteria 
-
77,464,646 737,990 
-
198,996,061 1,207,847 
Excluded due to insufficient enrollment 
-114,685 
623,305 
-157,484 
1,050,363 
Excluded due to prior use of referent 
-27,092 
596,213 
-80,459 
969,904 
Excluded due to prior use of exposure 
-292,949 
303,264 
-398,899 
571,005 
Excluded because patient qualified in >1 exposure category 
-40 
303,224 
-139 
570,866 
Excluded based on Age : exclude missing 
-3 
303,221 
0 
570,866 
Excluded based on Gender : exclude missing 
0 
303,221 
0 
570,866 
Excluded based on INCLUSION: Age >=12 
-14,027 
289,194 
-38,285 
532,581 
Excluded based on Inclusion 2 - Asthma >=1 year prior to CED 
-167,426 
121,768 
-316,772 
215,809 
Excluded based on Inclusion 3 - Asthma exacerbation (combination) [-365,-30] 
-59,930 
61,838 
-150,606 
65,203 
Excluded based on Inclusion 4 - Asthma Therapy [-365,-30] 
-10,146 
51,692 
-8,560 
56,643 
Excluded based on Exclusion 1 - Acute respiratory failure - intubation/nivs (combination) 
-4,103 
47,589 
-3,423 
53,220 
Excluded based on Exclusion 2b - Asthma exacerbation (combination) >4 in 365 days 
-5,195 
42,394 
-3,857 
49,363 
Excluded based on Exclusion 2C - Asthma exacerbation (inpatient primary) >2 times in 365 days 
-4,020 
38,374 
-109 
49,254 
Excluded based on Exclusion 3 - Use of oral corticosteroids (-30, 0] 
-3,222 
35,152 
-6,184 
43,070 
Excluded based on Exclusion 4 - Asthma exacerbation (combination) [-7,0] 
-196 
34,956 
-483 
42,587 
Excluded based on Exclusion 7 - Respiratory disease (combination) 
-540 
34,416 
-609 
41,978 
Excluded based on Exclusion 8 - Smoking 
-931 
33,485 
-657 
41,321 
Excluded based on Exclusion 9 - Acute upper or lower respiratory infections 
-2,527 
30,958 
-4,278 
37,043 
Excluded based on Exclusion 10 - Pregnancy 
-66 
30,892 
-85 
36,958 
Excluded based on Exclusion 11 - Malignancy 
-308 
30,584 
-367 
36,591 
Excluded based on Exclusion 14 - Use of omalizumab 
-1 
30,583 
-103 
36,488 

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Excluded based on Exclusion 15 - Use of Beta-blocker 
-150 
30,433 
-161 
36,327 
Excluded based on Exclusion 19 - Drug/alcohol abuse 
-49 
30,384 
-31 
36,296 
Final cohort 
  
30,384 
  
36,296 
 
 
6. Variables  
 
6.1 Exposure-related variables:  
 
Study drug:  
New initiation of Budesonide-formoterol (80/4.5 ug or 160/4.5 ug twice daily). New initiation is defined as no use of Budesonide-
formoterol in the prior 180 days before treatment initiation (washout period). New users of Budesonide-formoterol are not allowed to 
receive budesonide within the 180 days prior to treatment initiation. 
 
Comparator agent: 
New initiation of Budesonide alone. New initiation is defined as no use of budesonide in the prior 180 days before treatment initiation 
(washout period). New users of budesonide are not allowed to receive Budesonide-formoterol within the 180 days prior to treatment 
initiation. 
 
6.2 Preliminary Covariates: 
• Age 
• Gender 
• Combined Comorbidity Index (CCI), measured over the baseline covariate assessment period, defined as 180 days prior to and 
including index date. 
 
Covariates listed above represent only a small subset of covariates that will ultimately be controlled for in the design and analysis. 
We use the covariates 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).  
 
6.3 Outcome variables and study follow-up:  
 
6.3.1 Outcome variables 

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Effectiveness outcome variables of interest (definitions provided in Appendix A): 
§ Primary outcome: First serious asthma-related event (a composite of adjudicated death, intubation, and hospitalization 
  Secondary outcome: Individual components of the primary outcome 1) Asthma-related hospitalization  
                                                                                       
 
         2) Asthma-related intubation 
                                                                                        
 
         3) Asthma-related death  
 
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 the day of 
cohort entry. Because adherence in the real-world databases is expected to be much worse than in the trial, the AT analysis is the 
primary analysis, as it targets the relative hazard of outcomes on treatment. 
For the AT analyses, the follow-up will start the day after initiation of Budesonide-formoterol and Budesonide 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, 
§ Discontinuation of the index drugs, 
§ End of the study period, 
§ Measured death event occurs, 
§ Nursing home admission 
o Nursing home admissions are considered a censoring event because the data sources utilized typically provide little to 
no data on a patient, particularly on drug utilization, after admission. We will utilize this as an exclusion reason for 
cohorts for the same reason. 
• The date of drug discontinuation, defined as the date of the last continuous treatment episode of the index drug (Budesonide-
formoterol or a comparator) plus a defined grace period (i.e., 60 days after the end of the last prescription’s days’ supply in 
main analyses). 
• The date of augmentation or switching from exposure to comparator or vice versa or augmentation 
§ A dosage change on the index treatment does not fulfill this criterion 
 
7. Initial Feasibility Analysis  
Aetion report name: 

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For Budesonide-formoterol vs. budesonide 
Optum CDM - https://bwh-dope.aetion.com/projects/details/1657/results/67114/result/0 
IBM® MarketScan®- https://bwh-dope.aetion.com/projects/details/1656/results/67113/result/0 
 
Date conducted: 03/16/2021 
 
Complete Aetion feasibility analysis using age and CCI as the only covariates and the primary endpoint (Section 6.3.1) as the 
outcome. No measures of association will be computed nor will incidence rates stratified by treatment group. 
 
8. Initial Power Assessment 
 
Aetion report name: 
§ 
For Budesonide-formoterol vs. budesonide 
§ 
Optum CDM - https://bwh-dope.aetion.com/projects/details/1657/rwrs/67089 
IBM® MarketScan®- https://bwh-dope.aetion.com/projects/details/1656/rwrs/67108 
 
Date conducted:  03/17/2021 
 
In order to complete the initial power analysis, the dummy outcome of 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. Complete a 1:1 
PS-matched comparative analysis using this outcome. PS should include only 3 covariates: age, gender, and combined comorbidity 
index. Power calculations are based on the formulas 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. 
 
• 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: 
3/19/2021 
Reviewed by FDA: 
Ken Quinto 
Date reviewed: 
4/2/2021 
Reasons for stopping 
analysis (if required): 
 

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9. Balance Assessment 
For Budesonide-formoterol vs. budesonide 
Optum CDM:  https://bwh-dope.aetion.com/projects/details/1657/rwrs/68456 
IBM® MarketScan®: https://bwh-dope.aetion.com/projects/details/1656/rwrs/68455 
 
Date conducted: 4/14/2021 
 
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 B.  
 
• Report covariate balance after matching. 
Note- For Table 1, please refer to Appendix B.  
 
 
 
• Report reasons for censoring by treatment group. 
 
Overall 
Referent 
Exposure 
Dummy outcome 
0 (0.00%) 
0 (0.00%) 
0 (0.00%) 
Death 
14 (0.06%) 
5 (0.02%) 
9 (0.04%) 
Start of an additional exposure 
291 (1.20%) 
242 (1.00%) 
49 (0.20%) 
End of index exposure 
20257 (83.31%) 
10172 (41.84%) 
10085 (41.48%) 
Specified date reached 
486 (2.00%) 
227 (0.93%) 
259 (1.07%) 
End of patient data 
0 (0.00%) 
0 (0.00%) 
0 (0.00%) 
End of patient enrollment 
3159 (12.99%) 
1463 (6.02%) 
1696 (6.98%) 
Nursing home admission, pharmacy disenrollment 
107 (0.44%) 
48 (0.20%) 
59 (0.24%) 
 

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• Report follow-up time by treatment group. 
Median Follow-Up Time (Days) [IQR] 
Patient Group 
Optum 
Marketscan 
Overall Patient Population 
88 [88,148] 
107 [88,163] 
Referent –  
88 [88,148] 
93 [88, 148] 
Exposure 
88 [88, 158] 
116 [88, 177] 
 
• Report overall risk of the primary outcome.  
  
Optum CDM 
IBM® MarketScan® 
Pooled 
Risk per 1,000 patients 
3.7 
4.7  
4.2 
 
10. Final Power Assessment 
 
Date conducted: 4/15/2021 
 
• 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. 
 
o Pooled 

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o Optum CDM 
 
o IBM® MarketScan® 
Non-inferiority Analysis
Number of patients matched
24,314
Reference
12,157
Exposed
12,157
Risk per 1,000 patients
4.2
Assumed HR from RCT
1.07
Alpha (2-sided)
0.05
Non-inferiority margin
2
Number of events expected
102.1188
Power
0.885015194
Non-inferiority Analysis
Number of patients matched
10,396
Reference
5,198
Exposed
5,198
Risk per 1,000 patients
3.7
Assumed HR from RCT
1.07
Alpha (2-sided)
0.05
Non-inferiority margin
2
Number of events expected
38.4652
Power
0.491896419

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• Stop analyses until balance and final power assessment are reviewed by primary investigators, FDA, and assigned members of 
advisory board. 
Reviewed by PI: 
Shirley Wang 
Date reviewed: 
4/16/2021 
Reviewed by FDA: 
Ken Quinto 
Date reviewed: 
4/30/2021 
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. 
• 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 
Non-inferiority Analysis
Number of patients matched
13,918
Reference
6,959
Exposed
6,959
Risk per 1,000 patients
4.7
Assumed HR from RCT
1.07
Alpha (2-sided)
0.05
Non-inferiority margin
2
Number of events expected
65.4146
Power
0.71548801

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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 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
14.2 
Table 2: Follow-up time 
 

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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. 
 
14.5 
Table 5: Results from secondary analyses. 
 
 
 
 

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15. References 
 
 
Chow S, Shao J, Wang H. 2008.  Sample Size Calculations in Clinical Research. 2nd Ed. Chapman & Hall/CRC Biostatistics 
Series. page 177. 
 
 

#
NCT01444430 trial definitions
Implementation in routine care
Reference/Rationale 
Exposure) Budesonide-formoterol 
Referent) Budesonide
Exposure : Budesonide- formoterol
Two actuations of 80 ug of budesonide plus 4.5 ug of formoterol or 
160 ug of budesonide plus 4.5 ug of formoterol)
NDC code:
00186037020 - budesonide/formoterol fumarate
00186037028 - budesonide/formoterol fumarate
00186037220 - budesonide/formoterol fumarate
00186037228 - budesonide/formoterol fumarate
54569646600 - budesonide/formoterol fumarate
54868593600 - budesonide/formoterol fumarate
54868593700 - budesonide/formoterol fumarate
Referent: Budsonide alone
Two actuations of 80 ug or 160 ug in trial 
90 ug or 180 ug will be used in replication (market available doses) 
NDC code:
00186091612 (180 ug)
00186091706 (90 ug) 
First Serious asthma-related events 
(Composite of asthma-related deaths, intubations, and hospitalizations) 
Measured 1 day after drug initiationo in inpatient setting 
Asthma-related death: 
Inpatient death with primary discharge code of asthma (Optum, Marketscan) +
 Patient attribute for death  (Optum) 
Asthma related -Intubations: 
Diagnosis code for asthma in primary position plus CPT procedure code, 
31500: Endotracheal intubation, emergency in inpatient or Emergency room setting
Asthma-related Hospitalizations: 
Inpatient discharge diagnosis for asthma in primary position
1 ≥12 years of age
Measured on the day of drug initiation 
Age >=12 
2 Documented clinical diagnosis of asthma for ≥1 year prior to randomization
Measured between [-∞, 365] days prior to drug initiation in any position/any setting
Asthma:
ICD-9: 493.x
 ICD-10 : J45.*
Larsson K, Ställberg B, Lisspers K, Telg G, Johansson G, Thuresson M, Janson C. Prevalence and 
management of severe asthma in primary care: an observational cohort study in Sweden 
(PACEHR). Respir Res. 2018 Jan 18;19(1):12. doi: 10.1186/s12931-018-0719-x. PMID: 
29347939; PMCID: PMC5774144.
3
History of at least one asthma exacerbation in the previous year (but none in the 4 weeks prior to randomization. An asthma exacerbation was 
defined as an event requiring treatment with systemic corticosteroids or requiring hospitalization (i.e. an inpatient stay or >24-hour stay in 
the observation area of an emergency room or local equivalent)
Measured between 30 to 365 days prior to drug initiation in defined position and 
setting
1) Asthma diagnosis code in inpatient primary diagnosis position
2) Asthma diagnosis code in inpatient any position or outpatient setting PLUS a prescription 
claim for systemic steroids 14 days before and after the diagnosis code 
Asthma:
ICD-9: 493.x
 ICD-10 : J45.*
4 Receiving:
4a
A stable dose of ICS alone or in combination with a LABA, leukotriene receptor antagonist or other maintenance therapy/therapies for ≥4 
weeks prior to randomization (any patient maintained on a stable high-dose ICS with or without a LABA or LTRA or other maintenance 
therapy/therapies was required to have an ACQ6 total score of <1.5 at screening) or
4b
A stable dose of LTRA or xanthine monotherapy (for ≥4 weeks prior to randomization) or daily SABA (in the 4 weeks before randomization but 
≤8 puffs a day on two consecutive days, or ≥25 puffs in one day, in the 7 days prior to screening).
Patients on LTRAs, xanthines, or daily SABA, were eligible only if they recorded an ACQ6 total score of ≥1.5, and in the investigator’s clinical 
judgment, the patient’s asthma severity could have justified treatment with ICS or ICS/LABA combination
5 Provided signed informed consent/pediatric assent prior to the study
N/A
EXCLUSION CRITERIA
PRIMARY OUTCOME
Measured between 30 to 365 days prior to drug initiation in defined position and 
setting
A prescription claim for one of the following asthma maintenance medications: 
ICS monotherapy
ICS/LABA combination: 
Xanthines
Leukotriene receptor antagonist
Note) Did not incorporate SABA as it is difficult to capture daily use
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
Please see the following Google Drive for further details or any missing information: 
https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV?usp=sharing
Trial details- clinicaltrial.gov NCT01444430
EXPOSURE vs. COMPARISON
INCLUSION CRITERIA
Appendix A

1 A history of life-threatening asthma (defined as an asthma episode that required intubation and/or was associated with hypercapnia requiring 
non-invasive ventilatory support)
Measured  any time prior to and including drug initiation date in any setting
Acute respiratory failure/insufficiency/arrest
ICD-9: “517.3”, “518.5”, “518.81”, “518.82”, “518.83”, “518.84”, “799.1”, “V46.1”, 
“V46.11”, “V46.12”, “V46.13”, “V46.14”, “V46.2”
ICD-10: “J80”, “J96.00”, “J96.01”, “J96.02”, “J96.10”, “J96.11”, “J96.12”, “J96.20”, 
“J96.21”, “J96.22”, “J96.90”, “J96.91”, “J96.92”, “R09.01”, “R09.2”, “Z99.11”, “Z99.12”, 
“Z99.81” }
Intubation/Non-invasive ventilatory support:  
ICD-9 Procedure code: “93.90”, “93.92”, “96.01”, “96.02”, “96.03”, “96.04”, “96.05”, 
“96.70”, “96.71”, “96.72” 
ICD-10 procedure codes: “09HN7BZ”, “09HN8BZ”, “0BH13EZ”, “0BH17EZ”, “0BH18EZ”, 
“0CHY7BZ”, “0CHY8BZ”, “0DH57BZ”, “0DH58BZ”, “0WHQ73Z”, “0WHQ7YZ”, “5A09357”, 
“5A09457”, “5A09557”, “5A1935Z”, “5A1945Z”, “5A1955Z” }
Walkey AJ, Wiener RS. Use of noninvasive ventilation in patients with acute respiratory failure, 
2000-2009: a population-based study. Ann Am Thorac Soc. 2013 Feb;10(1):10-7. doi: 
10.1513/AnnalsATS.201206-034OC. PMID: 23509327; PMCID: PMC3780971.
2
2a) Any asthma exacerbation requiring systemic corticosteroids within 4 weeks prior to randomization 
or
2b) >4 separate exacerbations 
or 
2c) >2 hospitalizations (an inpatient stay or >24- hour stay in the observation area of an emergency room or local equivalent) due to asthma in 
the previous year
Note: 2a) Exclusion due to systemic corticosteroid use is applied for exclusion 3
2b) Asthma exacerbation, measured >4 times, 365 days prior to drug initiation 
Defined as 
a) Asthma diagnosis code in inpatient primary diagnosis position
b) Asthma diagnosis code in inpatient any position or outpatient setting PLUS a prescription 
claim for systemic steroids 14 days before and after the diagnosis code 
2c) Asthma hospitalization, measured >2 times, 365 days prior to drug initiation
Asthma:
ICD-9: 493.x
 ICD-10 : J45.*
http://mchp-appserv.cpe.umanitoba.ca/concept/asthma_table1.html
3 Received systemic corticosteroids for any reason in the 4 weeks prior to randomization
Measured 30 days prior to and including the day of drug initiation 
Cortisone, hydrocortisone, prednisone, prednisolone, methylprednisolone, triamcinolone, 
dexamethasone, betamethasone 
4 Had an ongoing asthma exacerbation requiring systemic corticosteroids
Measured 7 days prior to aind including the day of drug initiation 
Asthma exacerbation
Defined as 
a) Asthma diagnosis code in inpatient primary diagnosis position
b) Asthma diagnosis code in inpatient any position or outpatient setting PLUS a prescription 
claim for systemic steroids 14 days before and after the diagnosis code 
Asthma:
ICD-9: 493.x
 ICD-10 : J45.*
5
Unstable asthma within 7 days prior to randomization (defined as asthma symptoms that persisted throughout the day on two consecutive 
days, night-time awakening due to asthma during ≥3 nights, rescue medication use for the acute worsening of asthma symptoms of >8 
inhalations a day over two consecutive days or ≥25 inhalations in one day, and asthma symptoms so severe that the patient was limited in 
their ability to perform normal daily activity)
N/A 
6 Peak expiratory flow (pre- or post-bronchodilatory) <50% of predicted normal
N/A
7 Concurrent respiratory disease (chronic obstructive pulmonary disease, chronic bronchitis, emphysema, idiopathic pulmonary fibrosis,
bronchiectasis, and/or any pulmonary disease)
Measured 180 days prior to drug initiation in any care setting and position
COPD : 
“491.0”, “491.1”, “491.2”, “491.21”, “491.22”, “491.8”, “491.9”, “492.0”, “J41.8”, “J43.1”, “J43.8”, 
“J47.0”, “491.20”, “492.8”, “494.0”, “494.1”, “506.4”, “J41.0”, “J41.1”, “J43.0”, “J43.2”, “J43.9”, 
“J44.0”, “J44.1”, “J47.1”, “J47.9” 
Tuberculosis: 
ICD-9:  010.x - 018.x 
ICD-10:  A15.x - A19.x
Lung cancer
ICD-9: 162.2x, 162.3x, 162.4x, 162.5x, 162.8x, 162.9x 
ICD-10:  C34.0x, C34.1x, C34.2x, C34.3x, C34.8x, C34.9x
Bronchiectasis:
ICD-9: 494.x
ICD-10: J47.x 
8 A smoking history of >10 pack-years
Measured 180 days prior at least 1 inpatient or outpatient code for.
V15.82, 305.1x, 649.0x, 989.84
OR
CPT code
99406, 99407, G0436, G0437, G9016, S9075, S9453, S4995, G9276, G9458, 1034F, 4004F, 
4001F
OR
use of varenicline tartrate or nicotine replacement therapy (“Nicotine”, “Nicotine Bitartrate”, 
and “NicotinePolacrilex”)
9 Respiratory infection or other viral/bacterial illness
Measured 180 days prior to drug initiation in any position/any setting
Acute upper /lower respiratory infections 
ICD-10: J00.x, J01.x, J02.x, J03.x, J04.x, J05.x, J06.x 
J20.x, J21.x, J22.x
ICD-9: 460.x, 461.x, 462.x, 463.x, 464.x, 461
10 Pregnancy (current/planned) and lactation
Measured 180 days prior to drug initiation in any position/any setting
See tab [Pregnancy]
Appendix A

11 Malignancy (with the exception of basal cell carcinoma) within the 5 years prior to study commencement
Measured 180 days prior to drug initiation in any position/any setting
See tab [Malignancy]
12 Known or suspected hypersensitivity to study medications or their excipients
N/A
13 Participation in a concurrent LABA safety study or other interventional or investigational drug study
N/A
14 Omalizumab or any other monoclonal/polyclonal antibody use in the 6 months prior to randomization
Measured 180 days prior to drug initiation 
Drug generic name: omalizumab 
15 Concomitant β-blocker use
Measured 30 days prior to drug initiation 
Drug generic name: 
Propranolol, bucindolol, carteolol, carvedilol, labetalol, nadolol, Oxprenolol, penbutolol, 
pindolol, sotalol, timolol, Acebutolol, Atenolol, Betaxolol, bisoprolol, Celiprolol, metoprolol, 
nebivolol, esmolol, butaxamine, nebivolol
16 Any other significant disease/disorder that, in the opinion of the investigator, could have either put the patient at risk, or influence the 
results of the study or the patient’s ability to participate in the study
N/A
17 Clinically relevant abnormal findings in physical examination/vital signs at randomization
N/A
18 Risk of non-compliance
N/A
19 Drug/alcohol abuse
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or 
outpatient care setting:
Alcohol abuse or dependence:
291.xx, 303.xx, 305.0x, 571.0x, 571.1x, 571.2x, 571.3x, 357.5x, 425.5x, E860.0x, V11.3x
Drug abuse or dependence:
292.xx, 304.xx, 305.2x-305.9x, 648.3x
20 Planned blood donation during the study
N/A
21 Affiliation with study sponsor and/or investigator
N/A
Appendix A

Pregnancy 
Diagnosis codes 
650   NORMAL DELIVERY
660   OBSTRUCTED LABOR
661   ABNORMALITY OF FORCES OF LABOR
662   LONG LABOR
663   UMBILICAL CORD COMPLICATIONS DURING LABOR AND DELIVERY
664   TRAUMA TO PERINEUM AND VULVA DURING DELIVERY
665   OTHER OBSTETRICAL TRAUMA
667   RETAINED PLACENTA OR MEMBRANES WITHOUT HEMORRHAGE
668   COMPLICATIONS OF THE ADMINISTRATION OF ANESTHETIC OR OTHER SEDATION IN LABOR AND DELIVERY
669.94   UNSPECIFIED COMPLICATION OF LABOR AND DELIVERY POSTPARTUM CONDITION OR COMPLICATION
V24   POSTPARTUM CARE AND EXAMINATION
V24.0   POSTPARTUM CARE AND EXAMINATION IMMEDIATELY AFTER DELIVERY
V24.1   POSTPARTUM CARE AND EXAMINATION OF LACTATING MOTHER
V24.2   ROUTINE POSTPARTUM FOLLOW
V27   OUTCOME OF DELIVERY
V27.0   MOTHER WITH SINGLE LIVEBORN
V27.1   MOTHER WITH SINGLE STILLBORN+A2:J81
V27.2   MOTHER WITH TWINS BOTH LIVEBORN
V27.3   MOTHER WITH TWINS ONE LIVEBORN AND ONE STILLBORN
V27.4   MOTHER WITH TWINS BOTH STILLBORN
V27.5   MOTHER WITH OTHER MULTIPLE BIRTH ALL LIVEBORN
V27.6   MOTHER WITH OTHER MULTIPLE BIRTH SOME LIVEBORN
V27.7   MOTHER WITH OTHER MULTIPLE BIRTH ALL STILLBORN
V27.9   MOTHER WITH UNSPECIFIED OUTCOME OF DELIVERY
Procedure codes 
72.0   LOW FORCEPS OPERATION
72.1   LOW FORCEPS OPERATION WITH EPISIOTOMY
72.2   MID FORCEPS OPERATION
72.21   MID FORCEPS OPERATION WITH EPISIOTOMY
72.29   OTHER MID FORCEPS OPERATION
72.3   HIGH FORCEPS OPERATION
72.31   HIGH FORCEPS OPERATION WITH EPISIOTOMY
72.39   OTHER HIGH FORCEPS OPERATION
72.4   FORCEPS ROTATION OF FETAL HEAD
72.5   BREECH EXTRACTION
72.51   PARTIAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD
72.52   OTHER PARTIAL BREECH EXTRACTION
Appendix A

72.53   TOTAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD
72.54   OTHER TOTAL BREECH EXTRACTION
72.6   FORCEPS APPLICATION TO AFTERCOMING HEAD
72.7   VACUUM EXTRACTION
72.71   VACUUM EXTRACTION WITH EPISIOTOMY
72.79   OTHER VACUUM EXTRACTION
72.8   OTHER SPECIFIED INSTRUMENTAL DELIVERY
72.9   UNSPECIFIED INSTRUMENTAL DELIVERY
73.0   ARTIFICIAL RUPTURE OF MEMBRANES
73.01   INDUCTION OF LABOR BY ARTIFICIAL RUPTURE OF MEMBRANES
73.09   OTHER ARTIFICIAL RUPTURE OF MEMBRANES
73.1   OTHER SURGICAL INDUCTION OF LABOR
73.2   INTERNAL AND COMBINED VERSION AND EXTRACTION
73.21   INTERNAL AND COMBINED VERSION WITHOUT EXTRACTION
73.22   INTERNAL AND COMBINED VERSION WITH EXTRACTION
73.3   FAILED FORCEPS
73.4   MEDICAL INDUCTION OF LABOR
73.5   MANUALLY ASSISTED DELIVERY
73.51   MANUAL ROTATION OF FETAL HEAD
73.59   OTHER MANUALLY ASSISTED DELIVERY
73.6   EPISIOTOMY
73.8   OPERATIONS ON FETUS TO FACILITATE DELIVERY
73.9   OTHER OPERATIONS ASSISTING DELIVERY
73.91   EXTERNAL VERSION ASSISTING DELIVERY
73.92   REPLACEMENT OF PROLAPSED UMBILICAL CORD
73.93   INCISION OF CERVIX TO ASSIST DELIVERY
73.94   PUBIOTOMY TO ASSIST DELIVERY
73.99   OTHER OPERATIONS ASSISTING DELIVERY
74.0   CLASSICAL CESAREAN SECTION
74.1   LOW CERVICAL CESAREAN SECTION
74.2   EXTRAPERITONEAL CESAREAN SECTION
74.3   REMOVAL OF EXTRATUBAL ECTOPIC PREGNANCY
74.4   CESAREAN SECTION OF OTHER SPECIFIED TYPE
74.9   CESAREAN SECTION OF UNSPECIFIED TYPE
74.91   HYSTEROTOMY TO TERMINATE PREGNANCY
74.99   OTHER CESAREAN SECTION OF UNSPECIFIED TYPE
75.4   MANUAL REMOVAL OF RETAINED PLACENTA
75.5   REPAIR OF CURRENT OBSTETRIC LACERATION OF UTERUS
75.6   REPAIR OF OTHER CURRENT OBSTETRIC LACERATION
75.7   MANUAL EXPLORATION OF UTERINE CAVITY, POSTPARTUM
75.9   OTHER OBSTETRIC OPERATIONS
Appendix A

Malignancy
140 - MALIGNANT NEOPLASM OF LIP
140.0 - MALIGNANT NEOPLASM OF UPPER LIP VERMILION BORDER
140.1 - MALIGNANT NEOPLASM OF LOWER LIP VERMILION BORDER
140.3 - MALIGNANT NEOPLASM OF UPPER LIP INNER ASPECT
140.4 - MALIGNANT NEOPLASM OF LOWER LIP INNER ASPECT
140.5 - MALIGNANT NEOPLASM OF LIP UNSPECIFIED INNER ASPECT
140.6 - MALIGNANT NEOPLASM OF COMMISSURE OF LIP
140.8 - MALIGNANT NEOPLASM OF OTHER SITES OF LIP
140.9 - MALIGNANT NEOPLASM OF LIP UNSPECIFIED VERMILION BORDER
141 - MALIGNANT NEOPLASM OF TONGUE
141.0 - MALIGNANT NEOPLASM OF BASE OF TONGUE
141.1 - MALIGNANT NEOPLASM OF DORSAL SURFACE OF TONGUE
141.2 - MALIGNANT NEOPLASM OF TIP AND LATERAL BORDER OF TONGUE
141.3 - MALIGNANT NEOPLASM OF VENTRAL SURFACE OF TONGUE
141.4 - MALIGNANT NEOPLASM OF ANTERIOR TWO-THIRDS OF TONGUE PART UNSPECIFIED
141.5 - MALIGNANT NEOPLASM OF JUNCTIONAL ZONE OF TONGUE
141.6 - MALIGNANT NEOPLASM OF LINGUAL TONSIL
141.8 - MALIGNANT NEOPLASM OF OTHER SITES OF TONGUE
141.9 - MALIGNANT NEOPLASM OF TONGUE UNSPECIFIED
142 - MALIGNANT NEOPLASM OF MAJOR SALIVARY GLANDS
142.0 - MALIGNANT NEOPLASM OF PAROTID GLAND
142.1 - MALIGNANT NEOPLASM OF SUBMANDIBULAR GLAND
142.2 - MALIGNANT NEOPLASM OF SUBLINGUAL GLAND
142.8 - MALIGNANT NEOPLASM OF OTHER MAJOR SALIVARY GLANDS
142.9 - MALIGNANT NEOPLASM OF SALIVARY GLAND UNSPECIFIED
143 - MALIGNANT NEOPLASM OF GUM
143.0 - MALIGNANT NEOPLASM OF UPPER GUM
143.1 - MALIGNANT NEOPLASM OF LOWER GUM
143.8 - MALIGNANT NEOPLASM OF OTHER SITES OF GUM
143.9 - MALIGNANT NEOPLASM OF GUM UNSPECIFIED
144 - MALIGNANT NEOPLASM OF FLOOR OF MOUTH
144.0 - MALIGNANT NEOPLASM OF ANTERIOR PORTION OF FLOOR OF MOUTH
144.1 - MALIGNANT NEOPLASM OF LATERAL PORTION OF FLOOR OF MOUTH
144.8 - MALIGNANT NEOPLASM OF OTHER SITES OF FLOOR OF MOUTH
144.9 - MALIGNANT NEOPLASM OF FLOOR OF MOUTH PART UNSPECIFIED
145 - MALIGNANT NEOPLASM OF OTHER AND UNSPECIFIED PARTS OF MOUTH
145.0 - MALIGNANT NEOPLASM OF CHEEK MUCOSA
145.1 - MALIGNANT NEOPLASM OF VESTIBULE OF MOUTH
145.2 - MALIGNANT NEOPLASM OF HARD PALATE
145.3 - MALIGNANT NEOPLASM OF SOFT PALATE
145.4 - MALIGNANT NEOPLASM OF UVULA
145.5 - MALIGNANT NEOPLASM OF PALATE UNSPECIFIED
145.6 - MALIGNANT NEOPLASM OF RETROMOLAR AREA
145.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED PARTS OF MOUTH
145.9 - MALIGNANT NEOPLASM OF MOUTH UNSPECIFIED
Appendix A

146 - MALIGNANT NEOPLASM OF OROPHARYNX
146.0 - MALIGNANT NEOPLASM OF TONSIL
146.1 - MALIGNANT NEOPLASM OF TONSILLAR FOSSA
146.2 - MALIGNANT NEOPLASM OF TONSILLAR PILLARS (ANTERIOR) (POSTERIOR)
146.3 - MALIGNANT NEOPLASM OF VALLECULA EPIGLOTTICA
146.4 - MALIGNANT NEOPLASM OF ANTERIOR ASPECT OF EPIGLOTTIS
146.5 - MALIGNANT NEOPLASM OF JUNCTIONAL REGION OF OROPHARYNX
146.6 - MALIGNANT NEOPLASM OF LATERAL WALL OF OROPHARYNX
146.7 - MALIGNANT NEOPLASM OF POSTERIOR WALL OF OROPHARYNX
146.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF OROPHARYNX
146.9 - MALIGNANT NEOPLASM OF OROPHARYNX UNSPECIFIED SITE
147 - MALIGNANT NEOPLASM OF NASOPHARYNX
147.0 - MALIGNANT NEOPLASM OF SUPERIOR WALL OF NASOPHARYNX
147.1 - MALIGNANT NEOPLASM OF POSTERIOR WALL OF NASOPHARYNX
147.2 - MALIGNANT NEOPLASM OF LATERAL WALL OF NASOPHARYNX
147.3 - MALIGNANT NEOPLASM OF ANTERIOR WALL OF NASOPHARYNX
147.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF NASOPHARYNX
147.9 - MALIGNANT NEOPLASM OF NASOPHARYNX UNSPECIFIED SITE
148 - MALIGNANT NEOPLASM OF HYPOPHARYNX
148.0 - MALIGNANT NEOPLASM OF POSTCRICOID REGION OF HYPOPHARYNX
148.1 - MALIGNANT NEOPLASM OF PYRIFORM SINUS
148.2 - MALIGNANT NEOPLASM OF ARYEPIGLOTTIC FOLD HYPOPHARYNGEAL ASPECT
148.3 - MALIGNANT NEOPLASM OF POSTERIOR HYPOPHARYNGEAL WALL
148.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF HYPOPHARYNX
148.9 - MALIGNANT NEOPLASM OF HYPOPHARYNX UNSPECIFIED SITE
149 - MALIGNANT NEOPLASM OF OTHER AND ILL-DEFINED SITES WITHIN THE LIP ORAL CAVITY AND PHARYNX
149.0 - MALIGNANT NEOPLASM OF PHARYNX UNSPECIFIED
149.1 - MALIGNANT NEOPLASM OF WALDEYER'S RING
149.8 - MALIGNANT NEOPLASM OF OTHER SITES WITHIN THE LIP AND ORAL CAVITY
149.9 - MALIGNANT NEOPLASM OF ILL-DEFINED SITES WITHIN THE LIP AND ORAL CAVITY
150 - MALIGNANT NEOPLASM OF ESOPHAGUS
150.0 - MALIGNANT NEOPLASM OF CERVICAL ESOPHAGUS
150.1 - MALIGNANT NEOPLASM OF THORACIC ESOPHAGUS
150.2 - MALIGNANT NEOPLASM OF ABDOMINAL ESOPHAGUS
150.3 - MALIGNANT NEOPLASM OF UPPER THIRD OF ESOPHAGUS
150.4 - MALIGNANT NEOPLASM OF MIDDLE THIRD OF ESOPHAGUS
150.5 - MALIGNANT NEOPLASM OF LOWER THIRD OF ESOPHAGUS
150.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED PART OF ESOPHAGUS
150.9 - MALIGNANT NEOPLASM OF ESOPHAGUS UNSPECIFIED SITE
151 - MALIGNANT NEOPLASM OF STOMACH
151.0 - MALIGNANT NEOPLASM OF CARDIA
151.1 - MALIGNANT NEOPLASM OF PYLORUS
151.2 - MALIGNANT NEOPLASM OF PYLORIC ANTRUM
151.3 - MALIGNANT NEOPLASM OF FUNDUS OF STOMACH
151.4 - MALIGNANT NEOPLASM OF BODY OF STOMACH
151.5 - MALIGNANT NEOPLASM OF LESSER CURVATURE OF STOMACH UNSPECIFIED
Appendix A

151.6 - MALIGNANT NEOPLASM OF GREATER CURVATURE OF STOMACH UNSPECIFIED
151.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF STOMACH
151.9 - MALIGNANT NEOPLASM OF STOMACH UNSPECIFIED SITE
152 - MALIGNANT NEOPLASM OF SMALL INTESTINE INCLUDING DUODENUM
152.0 - MALIGNANT NEOPLASM OF DUODENUM
152.1 - MALIGNANT NEOPLASM OF JEJUNUM
152.2 - MALIGNANT NEOPLASM OF ILEUM
152.3 - MALIGNANT NEOPLASM OF MECKEL'S DIVERTICULUM
152.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF SMALL INTESTINE
152.9 - MALIGNANT NEOPLASM OF SMALL INTESTINE UNSPECIFIED SITE
153 - MALIGNANT NEOPLASM OF COLON
153.0 - MALIGNANT NEOPLASM OF HEPATIC FLEXURE
153.1 - MALIGNANT NEOPLASM OF TRANSVERSE COLON
153.2 - MALIGNANT NEOPLASM OF DESCENDING COLON
153.3 - MALIGNANT NEOPLASM OF SIGMOID COLON
153.4 - MALIGNANT NEOPLASM OF CECUM
153.5 - MALIGNANT NEOPLASM OF APPENDIX VERMIFORMIS
153.6 - MALIGNANT NEOPLASM OF ASCENDING COLON
153.7 - MALIGNANT NEOPLASM OF SPLENIC FLEXURE
153.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF LARGE INTESTINE
153.9 - MALIGNANT NEOPLASM OF COLON UNSPECIFIED SITE
154 - MALIGNANT NEOPLASM OF RECTUM RECTOSIGMOID JUNCTION AND ANUS
154.0 - MALIGNANT NEOPLASM OF RECTOSIGMOID JUNCTION
154.1 - MALIGNANT NEOPLASM OF RECTUM
154.2 - MALIGNANT NEOPLASM OF ANAL CANAL
154.3 - MALIGNANT NEOPLASM OF ANUS UNSPECIFIED SITE
154.8 - MALIGNANT NEOPLASM OF OTHER SITES OF RECTUM RECTOSIGMOID JUNCTION AND ANUS
155 - MALIGNANT NEOPLASM OF LIVER AND INTRAHEPATIC BILE DUCTS
155.0 - MALIGNANT NEOPLASM OF LIVER PRIMARY
155.1 - MALIGNANT NEOPLASM OF INTRAHEPATIC BILE DUCTS
155.2 - MALIGNANT NEOPLASM OF LIVER NOT SPECIFIED AS PRIMARY OR SECONDARY
156 - MALIGNANT NEOPLASM OF GALLBLADDER AND EXTRAHEPATIC BILE DUCTS
156.0 - MALIGNANT NEOPLASM OF GALLBLADDER
156.1 - MALIGNANT NEOPLASM OF EXTRAHEPATIC BILE DUCTS
156.2 - MALIGNANT NEOPLASM OF AMPULLA OF VATER
156.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF GALLBLADDER AND EXTRAHEPATIC BILE DUCTS
156.9 - MALIGNANT NEOPLASM OF BILIARY TRACT PART UNSPECIFIED SITE
157 - MALIGNANT NEOPLASM OF PANCREAS
157.0 - MALIGNANT NEOPLASM OF HEAD OF PANCREAS
157.1 - MALIGNANT NEOPLASM OF BODY OF PANCREAS
157.2 - MALIGNANT NEOPLASM OF TAIL OF PANCREAS
157.3 - MALIGNANT NEOPLASM OF PANCREATIC DUCT
157.4 - MALIGNANT NEOPLASM OF ISLETS OF LANGERHANS
157.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF PANCREAS
157.9 - MALIGNANT NEOPLASM OF PANCREAS PART UNSPECIFIED
158 - MALIGNANT NEOPLASM OF RETROPERITONEUM AND PERITONEUM
Appendix A

158.0 - MALIGNANT NEOPLASM OF RETROPERITONEUM
158.8 - MALIGNANT NEOPLASM OF SPECIFIED PARTS OF PERITONEUM
158.9 - MALIGNANT NEOPLASM OF PERITONEUM UNSPECIFIED
159 - MALIGNANT NEOPLASM OF OTHER AND ILL-DEFINED SITES WITHIN THE DIGESTIVE ORGANS AND PERITONEUM
159.0 - MALIGNANT NEOPLASM OF INTESTINAL TRACT PART UNSPECIFIED
159.1 - MALIGNANT NEOPLASM OF SPLEEN NOT ELSEWHERE CLASSIFIED
159.8 - MALIGNANT NEOPLASM OF OTHER SITES OF DIGESTIVE SYSTEM AND INTRA-ABDOMINAL ORGANS
159.9 - MALIGNANT NEOPLASM OF ILL-DEFINED SITES WITHIN THE DIGESTIVE ORGANS AND PERITONEUM
160 - MALIGNANT NEOPLASM OF NASAL CAVITIES MIDDLE EAR AND ACCESSORY SINUSES
160.0 - MALIGNANT NEOPLASM OF NASAL CAVITIES
160.1 - MALIGNANT NEOPLASM OF AUDITORY TUBE MIDDLE EAR AND MASTOID AIR CELLS
160.2 - MALIGNANT NEOPLASM OF MAXILLARY SINUS
160.3 - MALIGNANT NEOPLASM OF ETHMOIDAL SINUS
160.4 - MALIGNANT NEOPLASM OF FRONTAL SINUS
160.5 - MALIGNANT NEOPLASM OF SPHENOIDAL SINUS
160.8 - MALIGNANT NEOPLASM OF OTHER ACCESSORY SINUSES
160.9 - MALIGNANT NEOPLASM OF ACCESSORY SINUS UNSPECIFIED
161 - MALIGNANT NEOPLASM OF LARYNX
161.0 - MALIGNANT NEOPLASM OF GLOTTIS
161.1 - MALIGNANT NEOPLASM OF SUPRAGLOTTIS
161.2 - MALIGNANT NEOPLASM OF SUBGLOTTIS
161.3 - MALIGNANT NEOPLASM OF LARYNGEAL CARTILAGES
161.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF LARYNX
161.9 - MALIGNANT NEOPLASM OF LARYNX UNSPECIFIED
162 - MALIGNANT NEOPLASM OF TRACHEA BRONCHUS AND LUNG
162.0 - MALIGNANT NEOPLASM OF TRACHEA
162.2 - MALIGNANT NEOPLASM OF MAIN BRONCHUS
162.3 - MALIGNANT NEOPLASM OF UPPER LOBE BRONCHUS OR LUNG
162.4 - MALIGNANT NEOPLASM OF MIDDLE LOBE BRONCHUS OR LUNG
162.5 - MALIGNANT NEOPLASM OF LOWER LOBE BRONCHUS OR LUNG
162.8 - MALIGNANT NEOPLASM OF OTHER PARTS OF BRONCHUS OR LUNG
162.9 - MALIGNANT NEOPLASM OF BRONCHUS AND LUNG UNSPECIFIED
163 - MALIGNANT NEOPLASM OF PLEURA
163.0 - MALIGNANT NEOPLASM OF PARIETAL PLEURA
163.1 - MALIGNANT NEOPLASM OF VISCERAL PLEURA
163.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF PLEURA
163.9 - MALIGNANT NEOPLASM OF PLEURA UNSPECIFIED
164 - MALIGNANT NEOPLASM OF THYMUS HEART AND MEDIASTINUM
164.0 - MALIGNANT NEOPLASM OF THYMUS
164.1 - MALIGNANT NEOPLASM OF HEART
164.2 - MALIGNANT NEOPLASM OF ANTERIOR MEDIASTINUM
164.3 - MALIGNANT NEOPLASM OF POSTERIOR MEDIASTINUM
164.8 - MALIGNANT NEOPLASM OF OTHER PARTS OF MEDIASTINUM
164.9 - MALIGNANT NEOPLASM OF MEDIASTINUM PART UNSPECIFIED
165 - MALIGNANT NEOPLASM OF OTHER AND ILL-DEFINED SITES WITHIN THE RESPIRATORY SYSTEM AND INTRATHORACIC ORGANS
165.0 - MALIGNANT NEOPLASM OF UPPER RESPIRATORY TRACT PART UNSPECIFIED
Appendix A

165.8 - MALIGNANT NEOPLASM OF OTHER SITES WITHIN THE RESPIRATORY SYSTEM AND INTRATHORACIC ORGANS
165.9 - MALIGNANT NEOPLASM OF ILL-DEFINED SITES WITHIN THE RESPIRATORY SYSTEM
170 - MALIGNANT NEOPLASM OF BONE AND ARTICULAR CARTILAGE
170.0 - MALIGNANT NEOPLASM OF BONES OF SKULL AND FACE EXCEPT MANDIBLE
170.1 - MALIGNANT NEOPLASM OF MANDIBLE
170.2 - MALIGNANT NEOPLASM OF VERTEBRAL COLUMN EXCLUDING SACRUM AND COCCYX
170.3 - MALIGNANT NEOPLASM OF RIBS STERNUM AND CLAVICLE
170.4 - MALIGNANT NEOPLASM OF SCAPULA AND LONG BONES OF UPPER LIMB
170.5 - MALIGNANT NEOPLASM OF SHORT BONES OF UPPER LIMB
170.6 - MALIGNANT NEOPLASM OF PELVIC BONES SACRUM AND COCCYX
170.7 - MALIGNANT NEOPLASM OF LONG BONES OF LOWER LIMB
170.8 - MALIGNANT NEOPLASM OF SHORT BONES OF LOWER LIMB
170.9 - MALIGNANT NEOPLASM OF BONE AND ARTICULAR CARTILAGE SITE UNSPECIFIED
171 - MALIGNANT NEOPLASM OF CONNECTIVE AND OTHER SOFT TISSUE
171.0 - MALIGNANT NEOPLASM OF CONNECTIVE AND OTHER SOFT TISSUE OF HEAD FACE AND NECK
171.2 - MALIGNANT NEOPLASM OF CONNECTIVE AND OTHER SOFT TISSUE OF UPPER LIMB INCLUDING SHOULDER
171.3 - MALIGNANT NEOPLASM OF CONNECTIVE AND OTHER SOFT TISSUE OF LOWER LIMB INCLUDING HIP
171.4 - MALIGNANT NEOPLASM OF CONNECTIVE AND OTHER SOFT TISSUE OF THORAX
171.5 - MALIGNANT NEOPLASM OF CONNECTIVE AND OTHER SOFT TISSUE OF ABDOMEN
171.6 - MALIGNANT NEOPLASM OF CONNECTIVE AND OTHER SOFT TISSUE OF PELVIS
171.7 - MALIGNANT NEOPLASM OF CONNECTIVE AND OTHER SOFT TISSUE OF TRUNK UNSPECIFIED
171.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF CONNECTIVE AND OTHER SOFT TISSUE
171.9 - MALIGNANT NEOPLASM OF CONNECTIVE AND OTHER SOFT TISSUE SITE UNSPECIFIED
172 - MALIGNANT MELANOMA OF SKIN
172.0 - MALIGNANT MELANOMA OF SKIN OF LIP
172.1 - MALIGNANT MELANOMA OF SKIN OF EYELID INCLUDING CANTHUS
172.2 - MALIGNANT MELANOMA OF SKIN OF EAR AND EXTERNAL AUDITORY CANAL
172.3 - MALIGNANT MELANOMA OF SKIN OF OTHER AND UNSPECIFIED PARTS OF FACE
172.4 - MALIGNANT MELANOMA OF SKIN OF SCALP AND NECK
172.5 - MALIGNANT MELANOMA OF SKIN OF TRUNK EXCEPT SCROTUM
172.6 - MALIGNANT MELANOMA OF SKIN OF UPPER LIMB INCLUDING SHOULDER
172.7 - MALIGNANT MELANOMA OF SKIN OF LOWER LIMB INCLUDING HIP
172.8 - MALIGNANT MELANOMA OF OTHER SPECIFIED SITES OF SKIN
172.9 - MELANOMA OF SKIN SITE UNSPECIFIED
174 - MALIGNANT NEOPLASM OF FEMALE BREAST
174.0 - MALIGNANT NEOPLASM OF NIPPLE AND AREOLA OF FEMALE BREAST
174.1 - MALIGNANT NEOPLASM OF CENTRAL PORTION OF FEMALE BREAST
174.2 - MALIGNANT NEOPLASM OF UPPER-INNER QUADRANT OF FEMALE BREAST
174.3 - MALIGNANT NEOPLASM OF LOWER-INNER QUADRANT OF FEMALE BREAST
174.4 - MALIGNANT NEOPLASM OF UPPER-OUTER QUADRANT OF FEMALE BREAST
174.5 - MALIGNANT NEOPLASM OF LOWER-OUTER QUADRANT OF FEMALE BREAST
174.6 - MALIGNANT NEOPLASM OF AXILLARY TAIL OF FEMALE BREAST
174.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF FEMALE BREAST
174.9 - MALIGNANT NEOPLASM OF BREAST (FEMALE) UNSPECIFIED SITE
175 - MALIGNANT NEOPLASM OF MALE BREAST
175.0 - MALIGNANT NEOPLASM OF NIPPLE AND AREOLA OF MALE BREAST
Appendix A

175.9 - MALIGNANT NEOPLASM OF OTHER AND UNSPECIFIED SITES OF MALE BREAST
176 - KAPOSI'S SARCOMA
176.0 - KAPOSI'S SARCOMA SKIN
176.1 - KAPOSI'S SARCOMA SOFT TISSUE
176.2 - KAPOSI'S SARCOMA PALATE
176.3 - KAPOSI'S SARCOMA GASTROINTESTINAL SITES
176.4 - KAPOSI'S SARCOMA LUNG
176.5 - KAPOSI'S SARCOMA LYMPH NODES
176.8 - KAPOSI'S SARCOMA OTHER SPECIFIED SITES
176.9 - KAPOSI'S SARCOMA UNSPECIFIED SITE
179 - MALIGNANT NEOPLASM OF UTERUS-PART UNS
180 - MALIGNANT NEOPLASM OF CERVIX UTERI
180.0 - MALIGNANT NEOPLASM OF ENDOCERVIX
180.1 - MALIGNANT NEOPLASM OF EXOCERVIX
180.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF CERVIX
180.9 - MALIGNANT NEOPLASM OF CERVIX UTERI UNSPECIFIED SITE
181 - MALIGNANT NEOPLASM OF PLACENTA
182 - MALIGNANT NEOPLASM OF BODY OF UTERUS
182.0 - MALIGNANT NEOPLASM OF CORPUS UTERI EXCEPT ISTHMUS
182.1 - MALIGNANT NEOPLASM OF ISTHMUS
182.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF BODY OF UTERUS
183 - MALIGNANT NEOPLASM OF OVARY AND OTHER UTERINE ADNEXA
183.0 - MALIGNANT NEOPLASM OF OVARY
183.2 - MALIGNANT NEOPLASM OF FALLOPIAN TUBE
183.3 - MALIGNANT NEOPLASM OF BROAD LIGAMENT OF UTERUS
183.4 - MALIGNANT NEOPLASM OF PARAMETRIUM
183.5 - MALIGNANT NEOPLASM OF ROUND LIGAMENT OF UTERUS
183.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF UTERINE ADNEXA
183.9 - MALIGNANT NEOPLASM OF UTERINE ADNEXA UNSPECIFIED SITE
184 - MALIGNANT NEOPLASM OF OTHER AND UNSPECIFIED FEMALE GENITAL ORGANS
184.0 - MALIGNANT NEOPLASM OF VAGINA
184.1 - MALIGNANT NEOPLASM OF LABIA MAJORA
184.2 - MALIGNANT NEOPLASM OF LABIA MINORA
184.3 - MALIGNANT NEOPLASM OF CLITORIS
184.4 - MALIGNANT NEOPLASM OF VULVA UNSPECIFIED SITE
184.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF FEMALE GENITAL ORGANS
184.9 - MALIGNANT NEOPLASM OF FEMALE GENITAL ORGAN SITE UNSPECIFIED
185 - MALIGNANT NEOPLASM OF PROSTATE
186 - MALIGNANT NEOPLASM OF TESTIS
186.0 - MALIGNANT NEOPLASM OF UNDESCENDED TESTIS
186.9 - MALIGNANT NEOPLASM OF OTHER AND UNSPECIFIED TESTIS
187 - MALIGNANT NEOPLASM OF PENIS AND OTHER MALE GENITAL ORGANS
187.1 - MALIGNANT NEOPLASM OF PREPUCE
187.2 - MALIGNANT NEOPLASM OF GLANS PENIS
187.3 - MALIGNANT NEOPLASM OF BODY OF PENIS
187.4 - MALIGNANT NEOPLASM OF PENIS PART UNSPECIFIED
Appendix A

187.5 - MALIGNANT NEOPLASM OF EPIDIDYMIS
187.6 - MALIGNANT NEOPLASM OF SPERMATIC CORD
187.7 - MALIGNANT NEOPLASM OF SCROTUM
187.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF MALE GENITAL ORGANS
187.9 - MALIGNANT NEOPLASM OF MALE GENITAL ORGAN SITE UNSPECIFIED
188 - MALIGNANT NEOPLASM OF BLADDER
188.0 - MALIGNANT NEOPLASM OF TRIGONE OF URINARY BLADDER
188.1 - MALIGNANT NEOPLASM OF DOME OF URINARY BLADDER
188.2 - MALIGNANT NEOPLASM OF LATERAL WALL OF URINARY BLADDER
188.3 - MALIGNANT NEOPLASM OF ANTERIOR WALL OF URINARY BLADDER
188.4 - MALIGNANT NEOPLASM OF POSTERIOR WALL OF URINARY BLADDER
188.5 - MALIGNANT NEOPLASM OF BLADDER NECK
188.6 - MALIGNANT NEOPLASM OF URETERIC ORIFICE
188.7 - MALIGNANT NEOPLASM OF URACHUS
188.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF BLADDER
188.9 - MALIGNANT NEOPLASM OF BLADDER PART UNSPECIFIED
189 - MALIGNANT NEOPLASM OF KIDNEY AND OTHER AND UNSPECIFIED URINARY ORGANS
189.0 - MALIGNANT NEOPLASM OF KIDNEY EXCEPT PELVIS
189.1 - MALIGNANT NEOPLASM OF RENAL PELVIS
189.2 - MALIGNANT NEOPLASM OF URETER
189.3 - MALIGNANT NEOPLASM OF URETHRA
189.4 - MALIGNANT NEOPLASM OF PARAURETHRAL GLANDS
189.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF URINARY ORGANS
189.9 - MALIGNANT NEOPLASM OF URINARY ORGAN SITE UNSPECIFIED
190 - MALIGNANT NEOPLASM OF EYE
190.0 - MALIGNANT NEOPLASM OF EYEBALL EXCEPT CONJUNCTIVA CORNEA RETINA AND CHOROID
190.1 - MALIGNANT NEOPLASM OF ORBIT
190.2 - MALIGNANT NEOPLASM OF LACRIMAL GLAND
190.3 - MALIGNANT NEOPLASM OF CONJUNCTIVA
190.4 - MALIGNANT NEOPLASM OF CORNEA
190.5 - MALIGNANT NEOPLASM OF RETINA
190.6 - MALIGNANT NEOPLASM OF CHOROID
190.7 - MALIGNANT NEOPLASM OF LACRIMAL DUCT
190.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF EYE
190.9 - MALIGNANT NEOPLASM OF EYE PART UNSPECIFIED
191 - MALIGNANT NEOPLASM OF BRAIN
191.0 - MALIGNANT NEOPLASM OF CEREBRUM EXCEPT LOBES AND VENTRICLES
191.1 - MALIGNANT NEOPLASM OF FRONTAL LOBE
191.2 - MALIGNANT NEOPLASM OF TEMPORAL LOBE
191.3 - MALIGNANT NEOPLASM OF PARIETAL LOBE
191.4 - MALIGNANT NEOPLASM OF OCCIPITAL LOBE
191.5 - MALIGNANT NEOPLASM OF VENTRICLES
191.6 - MALIGNANT NEOPLASM OF CEREBELLUM NOT OTHERWISE SPECIFIED
191.7 - MALIGNANT NEOPLASM OF BRAIN STEM
191.8 - MALIGNANT NEOPLASM OF OTHER PARTS OF BRAIN
191.9 - MALIGNANT NEOPLASM OF BRAIN UNSPECIFIED SITE
Appendix A

192 - MALIGNANT NEOPLASM OF OTHER AND UNSPECIFIED PARTS OF NERVOUS SYSTEM
192.0 - MALIGNANT NEOPLASM OF CRANIAL NERVES
192.1 - MALIGNANT NEOPLASM OF CEREBRAL MENINGES
192.2 - MALIGNANT NEOPLASM OF SPINAL CORD
192.3 - MALIGNANT NEOPLASM OF SPINAL MENINGES
192.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF NERVOUS SYSTEM
192.9 - MALIGNANT NEOPLASM OF NERVOUS SYSTEM PART UNSPECIFIED
193 - MALIGNANT NEOPLASM OF THYROID GLAND
194 - MALIGNANT NEOPLASM OF OTHER ENDOCRINE GLANDS AND RELATED STRUCTURES
194.0 - MALIGNANT NEOPLASM OF ADRENAL GLAND
194.1 - MALIGNANT NEOPLASM OF PARATHYROID GLAND
194.3 - MALIGNANT NEOPLASM OF PITUITARY GLAND AND CRANIOPHARYNGEAL DUCT
194.4 - MALIGNANT NEOPLASM OF PINEAL GLAND
194.5 - MALIGNANT NEOPLASM OF CAROTID BODY
194.6 - MALIGNANT NEOPLASM OF AORTIC BODY AND OTHER PARAGANGLIA
194.8 - MALIGNANT NEOPLASM OF OTHER ENDOCRINE GLANDS AND RELATED STRUCTURES
194.9 - MALIGNANT NEOPLASM OF ENDOCRINE GLAND SITE UNSPECIFIED
195 - MALIGNANT NEOPLASM OF OTHER AND ILL-DEFINED SITES
195.0 - MALIGNANT NEOPLASM OF HEAD FACE AND NECK
195.1 - MALIGNANT NEOPLASM OF THORAX
195.2 - MALIGNANT NEOPLASM OF ABDOMEN
195.3 - MALIGNANT NEOPLASM OF PELVIS
195.4 - MALIGNANT NEOPLASM OF UPPER LIMB
195.5 - MALIGNANT NEOPLASM OF LOWER LIMB
195.8 - MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES
196 - SECONDARY AND UNSPECIFIED MALIGNANT NEOPLASM OF LYMPH NODES
196.0 - SECONDARY AND UNSPECIFIED MALIGNANT NEOPLASM OF LYMPH NODES OF HEAD FACE AND NECK
196.1 - SECONDARY AND UNSPECIFIED MALIGNANT NEOPLASM OF INTRATHORACIC LYMPH NODES
196.2 - SECONDARY AND UNSPECIFIED MALIGNANT NEOPLASM OF INTRA-ABDOMINAL LYMPH NODES
196.3 - SECONDARY AND UNSPECIFIED MALIGNANT NEOPLASM OF LYMPH NODES OF AXILLA AND UPPER LIMB
196.5 - SECONDARY AND UNSPECIFIED MALIGNANT NEOPLASM OF LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
196.6 - SECONDARY AND UNSPECIFIED MALIGNANT NEOPLASM OF INTRAPELVIC LYMPH NODES
196.8 - SECONDARY AND UNSPECIFIED MALIGNANT NEOPLASM OF LYMPH NODES OF MULTIPLE SITES
196.9 - SECONDARY AND UNSPECIFIED MALIGNANT NEOPLASM OF LYMPH NODES SITE UNSPECIFIED
197 - SECONDARY MALIGNANT NEOPLASM OF RESPIRATORY AND DIGESTIVE SYSTEMS
197.0 - SECONDARY MALIGNANT NEOPLASM OF LUNG
197.1 - SECONDARY MALIGNANT NEOPLASM OF MEDIASTINUM
197.2 - SECONDARY MALIGNANT NEOPLASM OF PLEURA
197.3 - SECONDARY MALIGNANT NEOPLASM OF OTHER RESPIRATORY ORGANS
197.4 - SECONDARY MALIGNANT NEOPLASM OF SMALL INTESTINE INCLUDING DUODENUM
197.5 - SECONDARY MALIGNANT NEOPLASM OF LARGE INTESTINE AND RECTUM
197.6 - SECONDARY MALIGNANT NEOPLASM OF RETROPERITONEUM AND PERITONEUM
197.7 - MALIGNANT NEOPLASM OF LIVER SECONDARY
197.8 - SECONDARY MALIGNANT NEOPLASM OF OTHER DIGESTIVE ORGANS AND SPLEEN
198 - SECONDARY MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES
198.0 - SECONDARY MALIGNANT NEOPLASM OF KIDNEY
Appendix A

198.1 - SECONDARY MALIGNANT NEOPLASM OF OTHER URINARY ORGANS
198.2 - SECONDARY MALIGNANT NEOPLASM OF SKIN
198.3 - SECONDARY MALIGNANT NEOPLASM OF BRAIN AND SPINAL CORD
198.4 - SECONDARY MALIGNANT NEOPLASM OF OTHER PARTS OF NERVOUS SYSTEM
198.5 - SECONDARY MALIGNANT NEOPLASM OF BONE AND BONE MARROW
198.6 - SECONDARY MALIGNANT NEOPLASM OF OVARY
198.7 - SECONDARY MALIGNANT NEOPLASM OF ADRENAL GLAND
198.8 - SECONDARY MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES
198.81 - SECONDARY MALIGNANT NEOPLASM OF BREAST
198.82 - SECONDARY MALIGNANT NEOPLASM OF GENITAL ORGANS
198.89 - SECONDARY MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES
199 - MALIGNANT NEOPLASM WITHOUT SPECIFICATION OF SITE
199.0 - DISSEMINATED MALIGNANT NEOPLASM
199.1 - OTHER MALIGNANT NEOPLASM OF UNSPECIFIED SITE
199.2 - MALIGNANT NEOPLASM ASSOCIATED WITH TRANSPLANTED ORGAN
200 - LYMPHOSARCOMA AND RETICULOSARCOMA AND OTHER SPECIFIED MALIGNANT TUMORS OF LYMPHATIC TISSUE
200.0 - RETICULOSARCOMA
200.00 - RETICULOSARCOMA UNSPECIFIED SITE
200.01 - RETICULOSARCOMA INVOLVING LYMPH NODES OF HEAD FACE AND NECK
200.02 - RETICULOSARCOMA INVOLVING INTRATHORACIC LYMPH NODES
200.03 - RETICULOSARCOMA INVOLVING INTRA-ABDOMINAL LYMPH NODES
200.04 - RETICULOSARCOMA INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
200.05 - RETICULOSARCOMA INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
200.06 - RETICULOSARCOMA INVOLVING INTRAPELVIC LYMPH NODES
200.07 - RETICULOSARCOMA INVOLVING SPLEEN
200.08 - RETICULOSARCOMA INVOLVING LYMPH NODES OF MULTIPLE SITES
200.1 - LYMPHOSARCOMA
200.10 - LYMPHOSARCOMA UNSPECIFIED SITE
200.11 - LYMPHOSARCOMA INVOLVING LYMPH NODES OF HEAD FACE AND NECK
200.12 - LYMPHOSARCOMA INVOLVING INTRATHORACIC LYMPH NODES
200.13 - LYMPHOSARCOMA INVOLVING INTRA-ABDOMINAL LYMPH NODES
200.14 - LYMPHOSARCOMA INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
200.15 - LYMPHOSARCOMA INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
200.16 - LYMPHOSARCOMA INVOLVING INTRAPELVIC LYMPH NODES
200.17 - LYMPHOSARCOMA INVOLVING SPLEEN
200.18 - LYMPHOSARCOMA INVOLVING LYMPH NODES OF MULTIPLE SITES
200.2 - BURKITT'S TUMOR OR LYMPHOMA
200.20 - BURKITT'S TUMOR OR LYMPHOMA UNSPECIFIED SITE
200.21 - BURKITT'S TUMOR OR LYMPHOMA INVOLVING LYMPH NODES OF HEAD FACE AND NECK
200.22 - BURKITT'S TUMOR OR LYMPHOMA INVOLVING INTRATHORACIC LYMPH NODES
200.23 - BURKITT'S TUMOR OR LYMPHOMA INVOLVING INTRA-ABDOMINAL LYMPH NODES
200.24 - BURKITT'S TUMOR OR LYMPHOMA INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
200.25 - BURKITT'S TUMOR OR LYMPHOMA INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
200.26 - BURKITT'S TUMOR OR LYMPHOMA INVOLVING INTRAPELVIC LYMPH NODES
200.27 - BURKITT'S TUMOR OR LYMPHOMA INVOLVING SPLEEN
200.28 - BURKITT'S TUMOR OR LYMPHOMA INVOLVING LYMPH NODES OF MULTIPLE SITES
Appendix A

200.3 - MARGINAL ZONE LYMPHOMA
200.30 - MARGINAL ZONE LYMPHOMA UNSPECIFIED SITE
200.31 - MARGINAL ZONE LYMPHOMA INVOLVING LYMPH NODES OF HEAD FACE AND NECK
200.32 - MARGINAL ZONE LYMPHOMA INVOLVING INTRATHORACIC LYMPH NODES
200.33 - MARGINAL ZONE LYMPHOMA INVOLVING INTRA-ABDOMINAL LYMPH NODES
200.34 - MARGINAL ZONE LYMPHOMA INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
200.35 - MARGINAL ZONE LYMPHOMA INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
200.36 - MARGINAL ZONE LYMPHOMA INVOLVING INTRAPELVIC LYMPH NODES
200.37 - MARGINAL ZONE LYMPHOMA INVOLVING SPLEEN
200.38 - MARGINAL ZONE LYMPHOMA INVOLVING LYMPH NODES OF MULTIPLE SITES
200.4 - MANTLE CELL LYMPHOMA
200.40 - MANTLE CELL LYMPHOMA UNSPECIFIED SITE
200.41 - MANTLE CELL LYMPHOMA INVOLVING LYMPH NODES OF HEAD FACE AND NECK
200.42 - MANTLE CELL LYMPHOMA INVOLVING INTRATHORACIC LYMPH NODES
200.43 - MANTLE CELL LYMPHOMA INVOLVING INTRA-ABDOMINAL LYMPH NODES
200.44 - MANTLE CELL LYMPHOMA INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
200.45 - MANTLE CELL LYMPHOMA INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
200.46 - MANTLE CELL LYMPHOMA INVOLVING INTRAPELVIC LYMPH NODES
200.47 - MANTLE CELL LYMPHOMA INVOLVING SPLEEN
200.48 - MANTLE CELL LYMPHOMA INVOLVING LYMPH NODES OF MULTIPLE SITES
200.5 - PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
200.50 - PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA UNSPECIFIED SITE
200.51 - PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA INVOLVING LYMPH NODES OF HEAD FACE AND NECK
200.52 - PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA INVOLVING INTRATHORACIC LYMPH NODES
200.53 - PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA INVOLVING INTRA-ABDOMINAL LYMPH NODES
200.54 - PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
200.55 - PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
200.56 - PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA INVOLVING INTRAPELVIC LYMPH NODES
200.57 - PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA INVOLVING SPLEEN
200.58 - PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA INVOLVING LYMPH NODES OF MULTIPLE SITES
200.6 - ANAPLASTIC LARGE CELL LYMPHOMA
200.60 - ANAPLASTIC LARGE CELL LYMPHOMA UNSPECIFIED SITE
200.61 - ANAPLASTIC LARGE CELL LYMPHOMA INVOLVING LYMPH NODES OF HEAD FACE AND NECK
200.62 - ANAPLASTIC LARGE CELL LYMPHOMA INVOLVING INTRATHORACIC LYMPH NODES
200.63 - ANAPLASTIC LARGE CELL LYMPHOMA INVOLVING INTRA-ABDOMINAL LYMPH NODES
200.64 - ANAPLASTIC LARGE CELL LYMPHOMA INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
200.65 - ANAPLASTIC LARGE CELL LYMPHOMA INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
200.66 - ANAPLASTIC LARGE CELL LYMPHOMA INVOLVING INTRAPELVIC LYMPH NODES
200.67 - ANAPLASTIC LARGE CELL LYMPHOMA INVOLVING SPLEEN
200.68 - ANAPLASTIC LARGE CELL LYMPHOMA INVOLVING LYMPH NODES OF MULTIPLE SITES
200.7 - LARGE CELL LYMPHOMA
200.70 - LARGE CELL LYMPHOMA UNSPECIFIED SITE
200.71 - LARGE CELL LYMPHOMA INVOLVING LYMPH NODES OF HEAD FACE AND NECK
200.72 - LARGE CELL LYMPHOMA INVOLVING INTRATHORACIC LYMPH NODES
200.73 - LARGE CELL LYMPHOMA INVOLVING INTRA-ABDOMINAL LYMPH NODES
200.74 - LARGE CELL LYMPHOMA INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
Appendix A

200.75 - LARGE CELL LYMPHOMA INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
200.76 - LARGE CELL LYMPHOMA INVOLVING INTRAPELVIC LYMPH NODES
200.77 - LARGE CELL LYMPHOMA INVOLVING SPLEEN
200.78 - LARGE CELL LYMPHOMA INVOLVING LYMPH NODES OF MULTIPLE SITES
200.8 - OTHER NAMED VARIANTS OF LYMPHOSARCOMA AND RETICULOSARCOMA
200.80 - OTHER NAMED VARIANTS OF LYMPHOSARCOMA AND RETICULOSARCOMA UNSPECIFIED SITE
200.81 - OTHER NAMED VARIANTS OF LYMPHOSARCOMA AND RETICULOSARCOMA INVOLVING LYMPH NODES OF HEAD FACE AND NECK
200.82 - OTHER NAMED VARIANTS OF LYMPHOSARCOMA AND RETICULOSARCOMA INVOLVING INTRATHORACIC LYMPH NODES
200.83 - OTHER NAMED VARIANTS OF LYMPHOSARCOMA AND RETICULOSARCOMA INVOLVING INTRA-ABDOMINAL LYMPH NODES
200.84 - OTHER NAMED VARIANTS OF LYMPHOSARCOMA AND RETICULOSARCOMA INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
200.85 - OTHER NAMED VARIANTS OF LYMPHOSARCOMA AND RETICULOSARCOMA INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
200.86 - OTHER NAMED VARIANTS OF LYMPHOSARCOMA AND RETICULOSARCOMA INVOLVING INTRAPELVIC LYMPH NODES
200.87 - OTHER NAMED VARIANTS OF LYMPHOSARCOMA AND RETICULOSARCOMA INVOLVING SPLEEN
200.88 - OTHER NAMED VARIANTS OF LYMPHOSARCOMA AND RETICULOSARCOMA INVOLVING LYMPH NODES OF MULTIPLE SITES
201 - HODGKIN'S DISEASE
201.0 - HODGKIN'S PARAGRANULOMA
201.00 - HODGKIN'S PARAGRANULOMA UNSPECIFIED SITE
201.01 - HODGKIN'S PARAGRANULOMA INVOLVING LYMPH NODES OF HEAD FACE AND NECK
201.02 - HODGKIN'S PARAGRANULOMA INVOLVING INTRATHORACIC LYMPH NODES
201.03 - HODGKIN'S PARAGRANULOMA INVOLVING INTRA-ABDOMINAL LYMPH NODES
201.04 - HODGKIN'S PARAGRANULOMA INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
201.05 - HODGKIN'S PARAGRANULOMA INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
201.06 - HODGKIN'S PARAGRANULOMA INVOLVING INTRAPELVIC LYMPH NODES
201.07 - HODGKIN'S PARAGRANULOMA INVOLVING SPLEEN
201.08 - HODGKIN'S PARAGRANULOMA INVOLVING LYMPH NODES OF MULTIPLE SITES
201.1 - HODGKIN'S GRANULOMA
201.10 - HODGKIN'S GRANULOMA UNSPECIFIED SITE
201.11 - HODGKIN'S GRANULOMA INVOLVING LYMPH NODES OF HEAD FACE AND NECK
201.12 - HODGKIN'S GRANULOMA INVOLVING INTRATHORACIC LYMPH NODES
201.13 - HODGKIN'S GRANULOMA INVOLVING INTRA-ABDOMINAL LYMPH NODES
201.14 - HODGKIN'S GRANULOMA INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
201.15 - HODGKIN'S GRANULOMA INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
201.16 - HODGKIN'S GRANULOMA INVOLVING INTRAPELVIC LYMPH NODES
201.17 - HODGKIN'S GRANULOMA INVOLVING SPLEEN
201.18 - HODGKIN'S GRANULOMA INVOLVING LYMPH NODES OF MULTIPLE SITES
201.2 - HODGKIN'S SARCOMA
201.20 - HODGKIN'S SARCOMA UNSPECIFIED SITE
201.21 - HODGKIN'S SARCOMA INVOLVING LYMPH NODES OF HEAD FACE AND NECK
201.22 - HODGKIN'S SARCOMA INVOLVING INTRATHORACIC LYMPH NODES
201.23 - HODGKIN'S SARCOMA INVOLVING INTRA-ABDOMINAL LYMPH NODES
201.24 - HODGKIN'S SARCOMA INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
201.25 - HODGKIN'S SARCOMA INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
201.26 - HODGKIN'S SARCOMA INVOLVING INTRAPELVIC LYMPH NODES
201.27 - HODGKIN'S SARCOMA INVOLVING SPLEEN
201.28 - HODGKIN'S SARCOMA INVOLVING LYMPH NODES OF MULTIPLE SITES
201.4 - HODGKIN'S DISEASE LYMPHOCYTIC-HISTIOCYTIC PREDOMINANCE
Appendix A

201.40 - HODGKIN'S DISEASE LYMPHOCYTIC-HISTIOCYTIC PREDOMINANCE UNSPECIFIED SITE
201.41 - HODGKIN'S DISEASE LYMPHOCYTIC-HISTIOCYTIC PREDOMINANCE INVOLVING LYMPH NODES OF HEAD FACE AND NECK
201.42 - HODGKIN'S DISEASE LYMPHOCYTIC-HISTIOCYTIC PREDOMINANCE INVOLVING INTRATHORACIC LYMPH NODES
201.43 - HODGKIN'S DISEASE LYMPHOCYTIC-HISTIOCYTIC PREDOMINANCE INVOLVING INTRA-ABDOMINAL LYMPH NODES
201.44 - HODGKIN'S DISEASE LYMPHOCYTIC-HISTIOCYTIC PREDOMINANCE INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
201.45 - HODGKIN'S DISEASE LYMPHOCYTIC-HISTIOCYTIC PREDOMINANCE INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
201.46 - HODGKIN'S DISEASE LYMPHOCYTIC-HISTIOCYTIC PREDOMINANCE INVOLVING INTRAPELVIC LYMPH NODES
201.47 - HODGKIN'S DISEASE LYMPHOCYTIC-HISTIOCYTIC PREDOMINANCE INVOLVING SPLEEN
201.48 - HODGKIN'S DISEASE LYMPHOCYTIC-HISTIOCYTIC PREDOMINANCE INVOLVING LYMPH NODES OF MULTIPLE SITES
201.5 - HODGKIN'S DISEASE NODULAR SCLEROSIS
201.50 - HODGKIN'S DISEASE NODULAR SCLEROSIS UNSPECIFIED SITE
201.51 - HODGKIN'S DISEASE NODULAR SCLEROSIS INVOLVING LYMPH NODES OF HEAD FACE AND NECK
201.52 - HODGKIN'S DISEASE NODULAR SCLEROSIS INVOLVING INTRATHORACIC LYMPH NODES
201.53 - HODGKIN'S DISEASE NODULAR SCLEROSIS INVOLVING INTRA-ABDOMINAL LYMPH NODES
201.54 - HODGKIN'S DISEASE NODULAR SCLEROSIS INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
201.55 - HODGKIN'S DISEASE NODULAR SCLEROSIS INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
201.56 - HODGKIN'S DISEASE NODULAR SCLEROSIS INVOLVING INTRAPELVIC LYMPH NODES
201.57 - HODGKIN'S DISEASE NODULAR SCLEROSIS INVOLVING SPLEEN
201.58 - HODGKIN'S DISEASE NODULAR SCLEROSIS INVOLVING LYMPH NODES OF MULTIPLE SITES
201.6 - HODGKIN'S DISEASE MIXED CELLULARITY
201.60 - HODGKIN'S DISEASE MIXED CELLULARITY UNSPECIFIED SITE
201.61 - HODGKIN'S DISEASE MIXED CELLULARITY INVOLVING LYMPH NODES OF HEAD FACE AND NECK
201.62 - HODGKIN'S DISEASE MIXED CELLULARITY INVOLVING INTRATHORACIC LYMPH NODES
201.63 - HODGKIN'S DISEASE MIXED CELLULARITY INVOLVING INTRA-ABDOMINAL LYMPH NODES
201.64 - HODGKIN'S DISEASE MIXED CELLULARITY INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
201.65 - HODGKIN'S DISEASE MIXED CELLULARITY INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
201.66 - HODGKIN'S DISEASE MIXED CELLULARITY INVOLVING INTRAPELVIC LYMPH NODES
201.67 - HODGKIN'S DISEASE MIXED CELLULARITY INVOLVING SPLEEN
201.68 - HODGKIN'S DISEASE MIXED CELLULARITY INVOLVING LYMPH NODES OF MULTIPLE SITES
201.7 - HODGKIN'S DISEASE LYMPHOCYTIC DEPLETION
201.70 - HODGKIN'S DISEASE LYMPHOCYTIC DEPLETION UNSPECIFIED SITE
201.71 - HODGKIN'S DISEASE LYMPHOCYTIC DEPLETION INVOLVING LYMPH NODES OF HEAD FACE AND NECK
201.72 - HODGKIN'S DISEASE LYMPHOCYTIC DEPLETION INVOLVING INTRATHORACIC LYMPH NODES
201.73 - HODGKIN'S DISEASE LYMPHOCYTIC DEPLETION INVOLVING INTRA-ABDOMINAL LYMPH NODES
201.74 - HODGKIN'S DISEASE LYMPHOCYTIC DEPLETION INVOLVING LYMPH NODES OF AXILLA AND UPPER LIMB
201.75 - HODGKIN'S DISEASE LYMPHOCYTIC DEPLETION INVOLVING LYMPH NODES OF INGUINAL REGION AND LOWER LIMB
201.76 - HODGKIN'S DISEASE LYMPHOCYTIC DEPLETION INVOLVING INTRAPELVIC LYMPH NODES
201.77 - HODGKIN'S DISEASE LYMPHOCYTIC DEPLETION INVOLVING SPLEEN
201.78 - HODGKIN'S DISEASE LYMPHOCYTIC DEPLETION INVOLVING LYMPH NODES OF MULTIPLE SITES
201.9 - HODGKIN'S DISEASE UNSPECIFIED TYPE
201.90 - HODGKIN'S DISEASE UNSPECIFIED TYPE UNSPECIFIED SITE
201.91 - HODGKIN'S DISEASE, UNSPECIFIED TYPE, LYMPH NODES OF HEAD, FACE, AND NECK
Appendix A

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Appendix B

Variable
Budesonide alone 
Budesonide-
formoterol
St. Diff.
Budesonide alone 
Budesonide-
formoterol
St. Diff.
Budesonide alone 
Budesonide-
formoterol
St. Diff.
Number of patients
6,337
24,000
7,380
28,864
13,717                      52,864 
Year of Cohort Entry Date
6,812 
5,344 
6,691 
13,208 
13,503                      18,552 
...2007; n (%)
1,064 (16.8%)
255 (1.1%)
0.053
690 (9.3%)
366 (1.3%)
0.035
1,754 (12.8%)
621 (1.2%)
0.467
...2008; n (%)
841 (13.3%)
968 (4.0%)
0.032
559 (7.6%)
1,296 (4.5%)
0.013
1,400 (10.2%)
2,264 (4.3%)
0.229
...2009; n (%)
699 (11.0%)
1,427 (5.9%)
0.018
663 (9.0%)
2,025 (7.0%)
0.007
1,362 (9.9%)
3,452 (6.5%)
0.124
...2010; n (%)
651 (10.3%)
1,868 (7.8%)
0.008
686 (9.3%)
2,777 (9.6%)
-0.001
1,337 (9.7%)
4,645 (8.8%)
0.031
...2011; n (%)
568 (9.0%)
1,747 (7.3%)
0.006
688 (9.3%)
2,691 (9.3%)
0.000
1,256 (9.2%)
4,438 (8.4%)
0.028
...2012; n (%)
497 (7.8%)
1,832 (7.6%)
0.001
763 (10.3%)
3,144 (10.9%)
-0.002
1,260 (9.2%)
4,976 (9.4%)
-0.007
...2013; n (%)
497 (7.8%)
2,017 (8.4%)
-0.002
723 (9.8%)
3,125 (10.8%)
-0.003
1,220 (8.9%)
5,142 (9.7%)
-0.028
...2014; n (%)
439 (6.9%)
1,485 (6.2%)
0.003
784 (10.6%)
4,332 (15.0%)
-0.012
1,223 (8.9%)
5,817 (11.0%)
-0.070
...2015; n (%)
393 (6.2%)
1,076 (4.5%)
0.007
642 (8.7%)
2,723 (9.4%)
-0.002
1,035 (7.5%)
3,799 (7.2%)
0.011
...2016; n (%)
250 (3.9%)
2,197 (9.2%)
-0.021
493 (6.7%)
2,082 (7.2%)
-0.002
743 (5.4%)
4,279 (8.1%)
-0.108
...2017; n (%)
143 (2.3%)
2,112 (8.8%)
-0.028
379 (5.1%)
1,780 (6.2%)
-0.005
522 (3.8%)
3,892 (7.4%)
-0.157
...2018; n (%)
130 (2.1%)
2,606 (10.9%)
-0.035
310 (4.2%)
2,523 (8.7%)
-0.018
440 (3.2%)
5,129 (9.7%)
-0.267
...2019; n (%)
121 (1.9%)
2,779 (11.6%)
-0.037
NA
NA
NA
NA
NA
NA
...2020; n (%)
44 (0.7%)
1,631 (6.8%)
-0.032
NA
NA
NA
NA
NA
NA
Age
...mean (sd)
42.71 (20.00)
51.86 (19.19)
-0.467
43.92 (20.01)
48.36 (17.11)
-0.238
43.36 (20.01)
49.95 (18.08)
-0.346
...median [IQR]
43.00 [27.00, 58.00]
54.00 [39.00, 67.00]
-0.561
47.00 [27.00, 59.00]
51.00 [39.00, 60.00]
-0.215
45.15 (20.01)
52.36 (18.08)
-0.378
Age categories
...12-17; n (%)
1,167 (18.4%)
1,752 (7.3%)
0.031
1,275 (17.3%)
2,255 (7.8%)
0.027
2,442 (17.8%)
4,007 (7.6%)
0.310
...18-39; n (%)
1,616 (25.5%)
4,397 (18.3%)
0.015
1,641 (22.2%)
5,370 (18.6%)
0.008
3,257 (23.7%)
9,767 (18.5%)
0.128
...40 - 64; n (%)
2,590 (40.9%)
10,603 (44.2%)
-0.005
3,478 (47.1%)
17,391 (60.3%)
-0.018
6,068 (44.2%)
27,994 (53.0%)
-0.177
...>= 65; n (%)
964 (15.2%)
7,248 (30.2%)
-0.032
986 (13.4%)
3,848 (13.3%)
0.000
1,950 (14.2%)
11,096 (21.0%)
-0.179
Geographic Region
...Northeast; n (%)
916 (14.5%)
2,632 (11.0%)
0.010
1,649 (22.3%)
5,792 (20.1%)
0.005
2,565 (18.7%)
8,424 (15.9%)
0.074
...South; n (%)
2,191 (34.6%)
10,968 (45.7%)
-0.018
2,151 (29.1%)
11,533 (40.0%)
-0.019
4,342 (31.7%)
22,501 (42.6%)
-0.227
...Midwest; n (%)
1,960 (30.9%)
5,075 (21.1%)
0.019
2,404 (32.6%)
7,125 (24.7%)
0.015
4,364 (31.8%)
12,200 (23.1%)
0.196
...West; n (%)
1,270 (20.0%)
5,325 (22.2%)
-0.005
1,118 (15.1%)
4,153 (14.4%)
0.002
2,388 (17.4%)
9,478 (17.9%)
-0.013
...Unknown/Missing; n (%)
NA
NA
NA
58 (0.8%)
261 (0.9%)
-0.001
NA
NA
NA
Metropolitan Statistical Area
...Urban; n (%)
NA
NA
NA
6,069 (82.2%)
22,803 (79.0%)
0.004
NA
NA
NA
...Rural; n (%)
NA
NA
NA
108 (1.5%)
705 (2.4%)
-0.006
NA
NA
NA
...Unknown/Missing; n (%)
NA
NA
NA
1,203 (16.3%)
5,356 (18.6%)
-0.006
NA
NA
NA
General Health Related Measures
Alcohol/Drug abuse or dependence ; n (%)
12 (0.2%)
216 (0.9%)
-0.009
30 (0.4%)
127 (0.4%)
0.000
042 (0.3%)
343 (0.6%)
-0.045
Obesity or Overweight; n (%)
333 (5.3%)
3,464 (14.4%)
-0.029
440 (6.0%)
2,772 (9.6%)
-0.013
773 (5.6%)
6,236 (11.8%)
-0.221
Obesity; n (%)
269 (4.2%)
2,786 (11.6%)
-0.026
376 (5.1%)
2,344 (8.1%)
-0.012
645 (4.7%)
5,130 (9.7%)
-0.194
Overweight; n (%)
66 (1.0%)
798 (3.3%)
-0.016
74 (1.0%)
511 (1.8%)
-0.007
140 (1.0%)
1,309 (2.5%)
-0.115
Cardiovascular Measures
Hypertension; n (%)
1,467 (23.1%)
9,667 (40.3%)
-0.031
1,708 (23.1%)
9,051 (31.4%)
-0.016
3,175 (23.1%)
18,718 (35.4%)
-0.273
Hyperlipidemia; n (%)
1,280 (20.2%)
7,113 (29.6%)
-0.019
1,309 (17.7%)
6,483 (22.5%)
-0.011
2,589 (18.9%)
13,596 (25.7%)
-0.164
MI, angina, Coronary atherosclerosis and other forms of chronic 
ischemic heart disease; n (%)
199 (3.1%)
1,404 (5.9%)
-0.013
243 (3.3%)
1,231 (4.3%)
-0.005
442 (3.2%)
2,635 (5.0%)
-0.091
Old MI; n (%)
22 (0.3%)
140 (0.6%)
-0.004
20 (0.3%)
78 (0.3%)
0.000
042 (0.3%)
218 (0.4%)
-0.017
Acute MI; n (%)
8 (0.1%)
51 (0.2%)
-0.003
11 (0.1%)
48 (0.2%)
-0.003
019 (0.1%)
099 (0.2%)
-0.026
Stable angina; n (%)
27 (0.4%)
277 (1.2%)
-0.009
29 (0.4%)
207 (0.7%)
-0.004
056 (0.4%)
484 (0.9%)
-0.062
Coronary atherosclerosis and other forms of chronic ischemic 
heart disease; n (%)
179 (2.8%)
1,219 (5.1%)
-0.012
204 (2.8%)
1,045 (3.6%)
-0.004
383 (2.8%)
2,264 (4.3%)
-0.081
History of CABG or PTCA; n (%)
32 (0.5%)
250 (1.0%)
-0.006
20 (0.3%)
124 (0.4%)
-0.002
052 (0.4%)
374 (0.7%)
-0.041
Marketscan
POOLED
Unmatched
Optum
Appendix B

Cerebrovascular disease (Stroke, TIA, Late effects); n (%)
38 (0.6%)
321 (1.3%)
-0.007
62 (0.8%)
270 (0.9%)
-0.001
100 (0.7%)
591 (1.1%)
-0.042
Stroke (Ischemic or hemorrhagic); n (%)
19 (0.3%)
157 (0.7%)
-0.006
26 (0.4%)
148 (0.5%)
-0.001
045 (0.3%)
305 (0.6%)
-0.045
TIA; n (%)
14 (0.2%)
127 (0.5%)
-0.005
33 (0.4%)
113 (0.4%)
0.000
047 (0.3%)
240 (0.5%)
-0.032
Late effects of cerebrovascular disease; n (%)
10 (0.2%)
102 (0.4%)
-0.004
12 (0.2%)
62 (0.2%)
0.000
022 (0.2%)
164 (0.3%)
-0.020
Atrial fibrillation and Other cardiac dysrhythmia; n (%)
229 (3.6%)
1,188 (5.0%)
-0.007
337 (4.6%)
1,045 (3.6%)
0.005
566 (4.1%)
2,233 (4.2%)
-0.005
Atrial fibrillation; n (%)
108 (1.7%)
639 (2.7%)
-0.007
169 (2.3%)
460 (1.6%)
0.005
277 (2.0%)
1,099 (2.1%)
-0.007
Other cardiac dysrhythmia; n (%)
155 (2.4%)
978 (4.1%)
-0.009
223 (3.0%)
776 (2.7%)
0.002
378 (2.8%)
1,754 (3.3%)
-0.029
Diabetes Related Measures
Diabetes with or w/o complications; n (%)
447 (7.1%)
3,349 (14.0%)
-0.021
520 (7.0%)
3,147 (10.9%)
-0.013
967 (7.0%)
6,496 (12.3%)
-0.180
Diabetes mellitus without mention of complications; n (%)
430 (6.8%)
3,099 (12.9%)
-0.019
485 (6.6%)
2,986 (10.3%)
-0.013
915 (6.7%)
6,085 (11.5%)
-0.167
Diabetes with specified complications; n (%)
75 (1.2%)
814 (3.4%)
-0.015
87 (1.2%)
489 (1.7%)
-0.004
162 (1.2%)
1,303 (2.5%)
-0.097
Diabetes with unspecified complications; n (%)
17 (0.3%)
151 (0.6%)
-0.004
17 (0.2%)
126 (0.4%)
-0.004
034 (0.2%)
277 (0.5%)
-0.051
GI Conditions
GERD; n (%)
559 (8.8%)
3,512 (14.6%)
-0.017
606 (8.2%)
3,258 (11.3%)
-0.010
1,165 (8.5%)
6,770 (12.8%)
-0.140
Upper GI (Diseases of esophagus, stomach and duodenum including 
GERD) ; n (%)
698 (11.0%)
4,098 (17.1%)
-0.016
788 (10.7%)
4,062 (14.1%)
-0.010
1,486 (10.8%)
8,160 (15.4%)
-0.137
GI bleeding; n (%)
78 (1.2%)
339 (1.4%)
-0.002
84 (1.1%)
392 (1.4%)
-0.003
162 (1.2%)
731 (1.4%)
-0.018
Non-infective enteritis and colitis; n (%)
189 (3.0%)
757 (3.2%)
-0.001
238 (3.2%)
952 (3.3%)
-0.001
427 (3.1%)
1,709 (3.2%)
-0.006
Intraoperative and postprocedural complications and disorders of 
digestive system; n (%)
86 (1.4%)
297 (1.2%)
0.002
80 (1.1%)
361 (1.3%)
-0.002
166 (1.2%)
658 (1.2%)
0.000
Disorders of gallbladder, biliary tract and pancreas; n (%)
50 (0.8%)
264 (1.1%)
-0.003
61 (0.8%)
283 (1.0%)
-0.002
111 (0.8%)
547 (1.0%)
-0.021
Rheumatic Conditions
Rheumatoid arthritis and other inflammatory polyarthropathies; n 
(%)
68 (1.1%)
405 (1.7%)
-0.005
108 (1.5%)
414 (1.4%)
0.001
176 (1.3%)
819 (1.5%)
-0.017
Osteoarthrosis; n (%)
405 (6.4%)
2,814 (11.7%)
-0.018
562 (7.6%)
2,559 (8.9%)
-0.005
967 (7.0%)
5,373 (10.2%)
-0.114
Other rheumatic disorders (including gout); n (%)
1,177 (18.6%)
6,074 (25.3%)
-0.014
1,481 (20.1%)
6,665 (23.1%)
-0.006
2,658 (19.4%)
12,739 (24.1%)
-0.114
Gout and other crystal arthropathies; n (%)
37 (0.6%)
359 (1.5%)
-0.009
40 (0.5%)
294 (1.0%)
-0.006
077 (0.6%)
653 (1.2%)
-0.064
Other rheumatic disorders; n (%)
1,156 (18.2%)
5,834 (24.3%)
-0.013
1,455 (19.7%)
6,470 (22.4%)
-0.006
2,611 (19.0%)
12,304 (23.3%)
-0.105
Neuro Conditions
Alzheimer and other Dementia Disease ; n (%)
37 (0.6%)
276 (1.1%)
-0.005
34 (0.5%)
141 (0.5%)
0.000
071 (0.5%)
417 (0.8%)
-0.037
Seizure disorders (epilepsy); n (%)
30 (0.5%)
158 (0.7%)
-0.003
40 (0.5%)
164 (0.6%)
-0.001
070 (0.5%)
322 (0.6%)
-0.014
Delirium/Psychosis; n (%)
50 (0.8%)
228 (0.9%)
-0.001
46 (0.6%)
175 (0.6%)
0.000
096 (0.7%)
403 (0.8%)
-0.012
Other Conditions
Hypothyroidism; n (%)
550 (8.7%)
2,811 (11.7%)
-0.009
552 (7.5%)
2,594 (9.0%)
-0.005
1,102 (8.0%)
5,405 (10.2%)
-0.077
Chronic kidney disease stages I-III; n (%)
100 (1.6%)
1,021 (4.3%)
-0.016
61 (0.8%)
422 (1.5%)
-0.007
161 (1.2%)
1,443 (2.7%)
-0.109
Chronic kidney disease stages IV-V, ESRD; n (%)
31 (0.5%)
229 (1.0%)
-0.006
20 (0.3%)
121 (0.4%)
-0.002
051 (0.4%)
350 (0.7%)
-0.041
COPD; n (%)
283 (4.5%)
2,954 (12.3%)
-0.027
381 (5.2%)
2,608 (9.0%)
-0.014
664 (4.8%)
5,562 (10.5%)
-0.216
Obstructive sleep apnea; n (%)
302 (4.8%)
2,390 (10.0%)
-0.019
378 (5.1%)
2,438 (8.4%)
-0.013
680 (5.0%)
4,828 (9.1%)
-0.161
Syncope; n (%)
67 (1.1%)
319 (1.3%)
-0.002
75 (1.0%)
315 (1.1%)
-0.001
142 (1.0%)
634 (1.2%)
-0.019
Falls; n (%)
67 (1.1%)
422 (1.8%)
-0.006
39 (0.5%)
174 (0.6%)
-0.001
106 (0.8%)
596 (1.1%)
-0.031
VTE; n (%)
35 (0.6%)
200 (0.8%)
-0.002
61 (0.8%)
266 (0.9%)
-0.001
096 (0.7%)
466 (0.9%)
-0.022
Combined comorbidity score, 365 days
...mean (sd)
1.14 (0.91)
1.38 (1.37)
-0.206
1.15 (0.89)
1.14 (0.97)
0.011
1.15 (0.90)
1.25 (1.17)
-0.096
...median [IQR]
1.00 [1.00, 1.00]
1.00 [1.00, 2.00]
0.000
1.00 [1.00, 1.00]
1.00 [1.00, 1.00]
0.000
1.00 (0.90)
1.00 (1.17)
0.000
Frailty Score: Empirical Version 365 days as Categories
...< 0.1 non frail; n (%)
4,334 (68.4%)
16,797 (70.0%)
-0.002
4,405 (59.7%)
15,841 (54.9%)
0.006
8,739 (63.7%)
32,638 (61.7%)
0.041
...0.1 - < 0.2 prefrail; n (%)
1,342 (21.2%)
4,099 (17.1%)
0.009
1,854 (25.1%)
7,413 (25.7%)
-0.001
3,196 (23.3%)
11,512 (21.8%)
0.036
… > 0.2 frail; n (%)
661 (10.4%)
3,104 (12.9%)
-0.007
1,121 (15.2%)
5,610 (19.4%)
-0.010
1,782 (13.0%)
8,714 (16.5%)
-0.099
Medication Use
Use of oral corticosteroids; n (%)
2,830 (44.7%)
13,878 (57.8%)
-0.018
7,014 (95.0%)
27,411 (95.0%)
0.000
9,844 (71.8%)
41,289 (78.1%)
-0.146
Use of antidepressants; n (%)
1,161 (18.3%)
6,021 (25.1%)
-0.015
1,607 (21.8%)
7,480 (25.9%)
-0.008
2,768 (20.2%)
13,501 (25.5%)
-0.126
Use of anticonvulsants; n (%)
339 (5.3%)
2,529 (10.5%)
-0.019
536 (7.3%)
2,666 (9.2%)
-0.007
875 (6.4%)
5,195 (9.8%)
-0.125
Use of beta blocker OR calcium channel blocker; n (%)
579 (9.1%)
3,575 (14.9%)
-0.017
803 (10.9%)
3,549 (12.3%)
-0.004
1,382 (10.1%)
7,124 (13.5%)
-0.106
Use of PPIs; n (%)
870 (13.7%)
5,203 (21.7%)
-0.019
1,526 (20.7%)
7,048 (24.4%)
-0.008
2,396 (17.5%)
12,251 (23.2%)
-0.142
Use of opioids; n (%)
937 (14.8%)
4,912 (20.5%)
-0.014
1,378 (18.7%)
7,123 (24.7%)
-0.013
2,315 (16.9%)
12,035 (22.8%)
-0.148
Appendix B

Use of antipsychotics; n (%)
83 (1.3%)
527 (2.2%)
-0.007
107 (1.4%)
534 (1.9%)
-0.004
190 (1.4%)
1,061 (2.0%)
-0.046
Use of anxiolytics/hypnotics; n (%)
329 (5.2%)
1,814 (7.6%)
-0.009
486 (6.6%)
2,517 (8.7%)
-0.008
815 (5.9%)
4,331 (8.2%)
-0.090
Use of dementia meds; n (%)
23 (0.4%)
220 (0.9%)
-0.006
26 (0.4%)
122 (0.4%)
0.000
049 (0.4%)
342 (0.6%)
-0.028
Use of antiparkinsonian meds; n (%)
58 (0.9%)
448 (1.9%)
-0.008
104 (1.4%)
519 (1.8%)
-0.003
162 (1.2%)
967 (1.8%)
-0.049
Use of Benzodiazepine; n (%)
541 (8.5%)
2,733 (11.4%)
-0.009
880 (11.9%)
3,889 (13.5%)
-0.004
1,421 (10.4%)
6,622 (12.5%)
-0.066
All antidiabetic medications; n (%)
351 (5.5%)
2,778 (11.6%)
-0.021
499 (6.8%)
2,817 (9.8%)
-0.010
850 (6.2%)
5,595 (10.6%)
-0.159
ACEI/ARB; n (%)
996 (15.7%)
6,682 (27.8%)
-0.026
1,410 (19.1%)
7,124 (24.7%)
-0.012
2,406 (17.5%)
13,806 (26.1%)
-0.209
Use of Anticoagulants; n (%)
116 (1.8%)
674 (2.8%)
-0.007
165 (2.2%)
608 (2.1%)
0.001
281 (2.0%)
1,282 (2.4%)
-0.027
Use of Amiodarone; n (%)
11 (0.2%)
55 (0.2%)
0.000
17 (0.2%)
44 (0.2%)
0.000
028 (0.2%)
099 (0.2%)
0.000
Digoxin; n (%)
26 (0.4%)
100 (0.4%)
0.000
45 (0.6%)
114 (0.4%)
0.003
071 (0.5%)
214 (0.4%)
0.015
Use of Diuretics; n (%)
813 (12.8%)
5,229 (21.8%)
-0.022
1,183 (16.0%)
5,938 (20.6%)
-0.011
1,996 (14.6%)
11,167 (21.1%)
-0.170
Use of Aspirin; n (%)
21 (0.3%)
110 (0.5%)
-0.003
26 (0.4%)
144 (0.5%)
-0.001
047 (0.3%)
254 (0.5%)
-0.032
NSAIDs (NOT including aspirin); n (%)
533 (8.4%)
3,311 (13.8%)
-0.016
861 (11.7%)
4,372 (15.1%)
-0.009
1,394 (10.2%)
7,683 (14.5%)
-0.131
HRT (Use of estrogens, progestins, androgens); n (%)
889 (14.0%)
2,782 (11.6%)
0.007
1,178 (16.0%)
4,006 (13.9%)
0.005
2,067 (15.1%)
6,788 (12.8%)
0.066
Use of Statins ; n (%)
1,037 (16.4%)
6,365 (26.5%)
-0.022
1,290 (17.5%)
6,323 (21.9%)
-0.010
2,327 (17.0%)
12,688 (24.0%)
-0.174
Healthcare Utilization Measures
Use of any drugs claims
...mean (sd)
22.04 (17.13)
26.38 (19.37)
-0.237
24.69 (17.07)
27.04 (18.47)
-0.132
23.47 (17.10)
26.74 (18.88)
-0.182
...median [IQR]
18.00 [10.00, 29.00]
22.00 [12.00, 35.00]
-0.219
21.00 [12.00, 33.00]
23.00 [14.00, 36.00]
-0.112
19.61 (17.10)
22.55 (18.88)
-0.163
Number of office visits 
...mean (sd)
9.78 (7.99)
11.67 (9.61)
-0.214
11.12 (8.19)
11.44 (7.91)
-0.040
10.50 (8.10)
11.54 (8.72)
-0.124
...median [IQR]
8.00 [5.00, 12.00]
9.00 [5.00, 15.00]
-0.113
9.00 [6.00, 14.00]
10.00 [6.00, 15.00]
-0.124
8.54 (8.10)
9.55 (8.72)
-0.120
Number of ED visits
...mean (sd)
0.31 (0.75)
0.45 (1.08)
-0.151
0.52 (1.14)
0.56 (1.20)
-0.034
0.42 (0.98)
0.51 (1.15)
-0.084
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.000
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.000
0.00 (0.98)
0.00 (1.15)
0.000
Number of hospitalizations
...mean (sd)
0.02 (0.19)
0.04 (0.27)
-0.086
0.16 (1.28)
0.17 (1.23)
-0.008
0.10 (0.95)
0.11 (0.93)
-0.011
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.000
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.000
0.00 (0.95)
0.00 (0.93)
0.000
Recent hospitalization (-30 days to Index Rx date); n (%)
14 (0.2%)
152 (0.6%)
-0.006
40 (0.5%)
186 (0.6%)
-0.001
054 (0.4%)
338 (0.6%)
-0.028
Old hospitalizations (-365 to -31 days); n (%)
354 (5.6%)
1,508 (6.3%)
-0.003
503 (6.8%)
1,972 (6.8%)
0.000
857 (6.2%)
3,480 (6.6%)
-0.016
Number of Pulmonologist/Allergist visits
...mean (sd)
0.02 (0.23)
0.04 (0.43)
-0.058
1.37 (3.61)
1.35 (3.58)
0.006
0.75 (2.65)
0.76 (2.66)
-0.004
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.000
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.000
0.00 (2.65)
0.00 (2.66)
0.000
Pulmonologist /allergist on CED; n (%)
3 (0.0%)
61 (0.3%)
-0.008
465 (6.3%)
2,178 (7.5%)
-0.005
468 (3.4%)
2,239 (4.2%)
-0.042
Number of hospital days
...mean (sd)
0.18 (2.69)
0.28 (2.91)
-0.036
0.16 (1.28)
0.17 (1.23)
-0.008
0.17 (2.06)
0.22 (2.16)
-0.024
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.000
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.000
0.00 (2.06)
0.00 (2.16)
0.000
Occurrence of basic or comprehensive metabolic blood chemistry 
test; n (%)
1,597 (25.2%)
9,025 (37.6%)
-0.022
1,762 (23.9%)
8,401 (29.1%)
-0.010
3,359 (24.5%)
17,426 (33.0%)
-0.189
Number of HbA1C test ordered
...mean (sd)
0.29 (0.82)
0.62 (1.17)
-0.327
0.28 (0.77)
0.40 (0.94)
-0.140
0.28 (0.79)
0.50 (1.05)
-0.237
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.000
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.000
0.00 (0.79)
0.00 (1.05)
0.000
Flexible Sigmoidoscopy or colonoscopy or CT virtual colonoscopy; 
n (%)
194 (3.1%)
890 (3.7%)
-0.003
250 (3.4%)
1,119 (3.9%)
-0.003
444 (3.2%)
2,009 (3.8%)
-0.033
Number of Mammograms (Breast cancer screening); n (%)
849 (13.4%)
3,434 (14.3%)
-0.002
993 (13.5%)
3,999 (13.9%)
-0.001
1,842 (13.4%)
7,433 (14.1%)
-0.020
Number of Pap smear (Cervical cancer screening); n (%)
898 (14.2%)
2,170 (9.0%)
0.015
1,035 (14.0%)
3,178 (11.0%)
0.008
1,933 (14.1%)
5,348 (10.1%)
0.123
Flu vaccine; n (%)
1,130 (17.8%)
4,320 (18.0%)
0.000
1,247 (16.9%)
4,546 (15.7%)
0.003
2,377 (17.3%)
8,866 (16.8%)
0.013
Pneumococcal vaccine; n (%)
325 (5.1%)
3,234 (13.5%)
-0.028
449 (6.1%)
2,077 (7.2%)
-0.004
774 (5.6%)
5,311 (10.0%)
-0.165
Copay for pharmacy cost (charges in U.S. $)
...mean (sd)
35.24 (31.61)
35.92 (35.15)
-0.020
25.32 (23.84)
25.69 (25.62)
-0.015
29.90 (27.70)
30.33 (30.32)
-0.015
...median [IQR]
29.02 [16.72, 45.16]
29.15 [15.10, 46.93]
-0.004
21.25 [9.74, 34.71]
20.90 [10.28, 34.52]
0.014
24.84 (27.70)
24.65 (30.32)
0.007
Business Type
...Commercial; n (%)
5,566 (87.8%)
16,395 (68.3%)
0.022
NA
NA
NA
NA
NA
NA
...Medicare; n (%)
771 (12.2%)
7,605 (31.7%)
-0.042
NA
NA
NA
NA
NA
NA
Insurance Plan Type
Appendix B

...Comprehensive; n (%)
NA
NA
NA
601 (8.1%)
2,299 (8.0%)
0.000
NA
NA
NA
...HMO; n (%)
NA
NA
NA
978 (13.3%)
3,421 (11.9%)
0.004
NA
NA
NA
...PPO; n (%)
NA
NA
NA
4,270 (57.9%)
16,728 (58.0%)
0.000
NA
NA
NA
...Others; n (%)
NA
NA
NA
1,531 (20.7%)
6,416 (22.2%)
-0.003
NA
NA
NA
SABA; n (%)
3,308 (52.2%)
12,697 (52.9%)
-0.001
4,699 (63.7%)
18,511 (64.1%)
-0.001
8,007 (58.4%)
31,208 (59.0%)
-0.012
SAMA; n (%)
95 (1.5%)
450 (1.9%)
-0.003
204 (2.8%)
744 (2.6%)
0.001
299 (2.2%)
1,194 (2.3%)
-0.007
SABA/SAMA; n (%)
116 (1.8%)
835 (3.5%)
-0.010
269 (3.6%)
1,517 (5.3%)
-0.008
385 (2.8%)
2,352 (4.4%)
-0.086
ICS without budesonide; n (%)
1,922 (30.3%)
6,879 (28.7%)
0.003
2,746 (37.2%)
10,504 (36.4%)
0.001
4,668 (34.0%)
17,383 (32.9%)
0.023
LABA; n (%)
493 (7.8%)
240 (1.0%)
0.032
502 (6.8%)
447 (1.5%)
0.026
995 (7.3%)
687 (1.3%)
0.299
LAMA; n (%)
126 (2.0%)
1,049 (4.4%)
-0.013
248 (3.4%)
1,685 (5.8%)
-0.011
374 (2.7%)
2,734 (5.2%)
-0.129
ICS/LABA (without budesonide-formoterol); n (%)
635 (10.0%)
3,591 (15.0%)
-0.014
825 (11.2%)
5,565 (19.3%)
-0.021
1,460 (10.6%)
9,156 (17.3%)
-0.194
Blood eosinophilia test ; n (%)
26 (0.4%)
53 (0.2%)
0.004
14 (0.2%)
88 (0.3%)
-0.002
040 (0.3%)
141 (0.3%)
0.000
Serum immunoglobulin E (IgE) level test; n (%)
72 (1.1%)
346 (1.4%)
-0.003
121 (1.6%)
659 (2.3%)
-0.005
193 (1.4%)
1,005 (1.9%)
-0.039
H2 blocker; n (%)
59 (0.9%)
649 (2.7%)
-0.013
233 (3.2%)
982 (3.4%)
-0.001
292 (2.1%)
1,631 (3.1%)
-0.063
Oxygen codes; n (%)
15 (0.2%)
156 (0.7%)
-0.007
37 (0.5%)
226 (0.8%)
-0.004
052 (0.4%)
382 (0.7%)
-0.041
Respiratory arrest/dependence on oxygen; n (%)
1 (0.0%)
6 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
001 (0.0%)
006 (0.0%)
#DIV/0!
Aetion link to Optum results: https://bwh-dope.aetion.com/projects/details/1657/rwrs/68456
Aetion link to Marketscan results: https://bwh-dope.aetion.com/projects/details/1656/rwrs/68455
Appendix B

Variable
Budesonide alone 
Budesonide-
formoterol
St. Diff.
Budesonide alone 
Budesonide-
formoterol
St. Diff.
Budesonide 
alone 
Budesonide-
formoterol
St. Diff.
Number of patients
5,198
5,198
6,959
6,959
12,157 
12,157 
Year of Cohort Entry Date
...2007; n (%)
250 (4.8%)
245 (4.7%)
0.0005
336 (4.8%)
330 (4.7%)
0.0005
586 (4.8%)
575 (4.7%)
0.005
...2008; n (%)
627 (12.1%)
656 (12.6%)
-0.0014
521 (7.5%)
529 (7.6%)
-0.0004
1,148 (9.4%)
1,185 (9.7%)
-0.010
...2009; n (%)
647 (12.4%)
658 (12.7%)
-0.0008
648 (9.3%)
668 (9.6%)
-0.0010
1,295 (10.7%)
1,326 (10.9%)
-0.006
...2010; n (%)
636 (12.2%)
625 (12.0%)
0.0006
680 (9.8%)
692 (9.9%)
-0.0003
1,316 (10.8%)
1,317 (10.8%)
0.000
...2011; n (%)
552 (10.6%)
538 (10.4%)
0.0006
687 (9.9%)
711 (10.2%)
-0.0009
1,239 (10.2%)
1,249 (10.3%)
-0.003
...2012; n (%)
494 (9.5%)
518 (10.0%)
-0.0016
761 (10.9%)
756 (10.9%)
0.0000
1,255 (10.3%)
1,274 (10.5%)
-0.007
...2013; n (%)
496 (9.5%)
463 (8.9%)
0.0020
723 (10.4%)
685 (9.8%)
0.0019
1,219 (10.0%)
1,148 (9.4%)
0.020
...2014; n (%)
435 (8.4%)
444 (8.5%)
-0.0003
783 (11.3%)
793 (11.4%)
-0.0003
1,218 (10.0%)
1,237 (10.2%)
-0.007
...2015; n (%)
373 (7.2%)
356 (6.8%)
0.0015
641 (9.2%)
644 (9.3%)
-0.0003
1,014 (8.3%)
1,000 (8.2%)
0.004
...2016; n (%)
250 (4.8%)
242 (4.7%)
0.0005
491 (7.1%)
469 (6.7%)
0.0015
741 (6.1%)
711 (5.8%)
0.013
...2017; n (%)
143 (2.8%)
151 (2.9%)
-0.0006
378 (5.4%)
397 (5.7%)
-0.0013
521 (4.3%)
548 (4.5%)
-0.010
...2018; n (%)
130 (2.5%)
146 (2.8%)
-0.0018
310 (4.5%)
285 (4.1%)
0.0019
440 (3.6%)
431 (3.5%)
0.005
...2019; n (%)
121 (2.3%)
117 (2.3%)
0.0000
NA
NA
NA
NA
NA
NA
...2020; n (%)
44 (0.8%)
39 (0.8%)
0.0000
NA
NA
NA
NA
NA
NA
Age*
...mean (sd)
43.68 (20.21)
43.29 (19.29)
0.0197
43.76 (19.95)
43.63 (18.37)
0.0068
43.73 (20.06)
43.48 (18.77)
0.013
...median [IQR]
44.00 [28.00, 59.00]
44.00 [28.00, 58.00] 0.0000
47.00 [27.00, 59.00]
46.00 [29.00, 58.00]
0.0521
45.72 (20.06)
45.14 (18.77)
0.030
Age categories
...12-17; n (%)
901 (17.3%)
757 (14.6%)
0.0068
1,206 (17.3%)
938 (13.5%)
0.0097
2,107 (17.3%)
1,695 (13.9%)
0.094
...18-39; n (%)
1,308 (25.2%)
1,394 (26.8%)
-0.0031
1,566 (22.5%)
1,677 (24.1%)
-0.0033
2,874 (23.6%)
3,071 (25.3%)
-0.040
...40 - 64; n (%)
2,107 (40.5%)
2,267 (43.6%)
-0.0048
3,281 (47.1%)
3,660 (52.6%)
-0.0078
5,388 (44.3%)
5,927 (48.8%)
-0.090
...>= 65; n (%)
882 (17.0%)
780 (15.0%)
0.0050
906 (13.0%)
684 (9.8%)
0.0095
1,788 (14.7%)
1,464 (12.0%)
0.079
Geographic Region*
...Northeast; n (%)
715 (13.8%)
748 (14.4%)
-0.0016
1,576 (22.6%)
1,560 (22.4%)
0.0004
2,291 (18.8%)
2,308 (19.0%)
-0.005
...South; n (%)
1,950 (37.5%)
1,928 (37.1%)
0.0007
2,066 (29.7%)
2,040 (29.3%)
0.0007
4,016 (33.0%)
3,968 (32.6%)
0.009
...Midwest; n (%)
1,445 (27.8%)
1,455 (28.0%)
-0.0004
2,220 (31.9%)
2,261 (32.5%)
-0.0011
3,665 (30.1%)
3,716 (30.6%)
-0.011
...West; n (%)
1,088 (20.9%)
1,067 (20.5%)
0.0009
1,042 (15.0%)
1,031 (14.8%)
0.0005
2,130 (17.5%)
2,098 (17.3%)
0.005
...Unknown/Missing; n (%)
NA
NA
NA
55 (0.8%)
67 (1.0%)
-0.0021
NA
NA
NA
Metropolitan Statistical Area*
...Urban; n (%)
NA
NA
NA
5,712 (82.1%)
5,672 (81.5%)
0.0007
NA
NA
NA
...Rural; n (%)
NA
NA
NA
108 (1.6%)
104 (1.5%)
0.0008
NA
NA
NA
...Unknown/Missing; n (%)
NA
NA
NA
1,139 (16.4%)
1,183 (17.0%)
-0.0015
NA
NA
NA
General Health Related Measures
Alcohol/Drug abuse or dependence ; n (%)
12 (0.2%)
26 (0.5%)
-0.0051
29 (0.4%)
20 (0.3%)
0.0017
041 (0.3%)
046 (0.4%)
-0.017
Obesity or Overweight; n (%)*
319 (6.1%)
293 (5.6%)
0.0021
436 (6.3%)
427 (6.1%)
0.0008
755 (6.2%)
720 (5.9%)
0.013
Obesity; n (%)
258 (5.0%)
251 (4.8%)
0.0009
372 (5.3%)
353 (5.1%)
0.0009
630 (5.2%)
604 (5.0%)
0.009
Overweight; n (%)
63 (1.2%)
50 (1.0%)
0.0019
73 (1.0%)
83 (1.2%)
-0.0019
136 (1.1%)
133 (1.1%)
0.000
Cardiovascular Measures
Hypertension; n (%)*
1,300 (25.0%)
1,268 (24.4%)
0.0012
1,630 (23.4%)
1,621 (23.3%)
0.0002
2,930 (24.1%)
2,889 (23.8%)
0.007
Hyperlipidemia; n (%)*
1,109 (21.3%)
1,050 (20.2%)
0.0024
1,252 (18.0%)
1,235 (17.7%)
0.0007
2,361 (19.4%)
2,285 (18.8%)
0.015
MI, angina, Coronary atherosclerosis and other forms of chronic 
ischemic heart disease; n (%)*
176 (3.4%)
159 (3.1%)
0.0017
224 (3.2%)
215 (3.1%)
0.0006
400 (3.3%)
374 (3.1%)
0.011
Old MI; n (%)
17 (0.3%)
15 (0.3%)
0.0000
19 (0.3%)
14 (0.2%)
0.0020
036 (0.3%)
029 (0.2%)
0.020
Acute MI; n (%)
7 (0.1%)
6 (0.1%)
0.0000
11 (0.2%)
4 (0.1%)
0.0026
018 (0.1%)
010 (0.1%)
0.000
Stable angina; n (%)
25 (0.5%)
31 (0.6%)
-0.0013
28 (0.4%)
25 (0.4%)
0.0000
053 (0.4%)
056 (0.5%)
-0.015
Coronary atherosclerosis and other forms of chronic ischemic 
heart disease; n (%)
159 (3.1%)
134 (2.6%)
0.0030
186 (2.7%)
192 (2.8%)
-0.0006
345 (2.8%)
326 (2.7%)
0.006
History of CABG or PTCA; n (%)
29 (0.6%)
26 (0.5%)
0.0013
20 (0.3%)
24 (0.3%)
0.0000
049 (0.4%)
050 (0.4%)
0.000
PS-matched
Optum
Marketscan
POOLED
Appendix B

Cerebrovascular disease (Stroke, TIA, Late effects); n (%)*
31 (0.6%)
37 (0.7%)
-0.0012
58 (0.8%)
58 (0.8%)
0.0000
089 (0.7%)
095 (0.8%)
-0.012
Stroke (Ischemic or hemorrhagic); n (%)
17 (0.3%)
20 (0.4%)
-0.0017
23 (0.3%)
35 (0.5%)
-0.0032
040 (0.3%)
055 (0.5%)
-0.032
TIA; n (%)
11 (0.2%)
14 (0.3%)
-0.0020
32 (0.5%)
26 (0.4%)
0.0015
043 (0.4%)
040 (0.3%)
0.017
Late effects of cerebrovascular disease; n (%)
8 (0.2%)
9 (0.2%)
0.0000
12 (0.2%)
13 (0.2%)
0.0000
020 (0.2%)
022 (0.2%)
0.000
Atrial fibrillation and Other cardiac dysrhythmia; n (%)*
200 (3.8%)
191 (3.7%)
0.0005
312 (4.5%)
312 (4.5%)
0.0000
512 (4.2%)
503 (4.1%)
0.005
Atrial fibrillation; n (%)
96 (1.8%)
89 (1.7%)
0.0008
158 (2.3%)
123 (1.8%)
0.0035
254 (2.1%)
212 (1.7%)
0.029
Other cardiac dysrhythmia; n (%)
136 (2.6%)
138 (2.7%)
-0.0006
209 (3.0%)
242 (3.5%)
-0.0028
345 (2.8%)
380 (3.1%)
-0.018
Diabetes Related Measures
Diabetes with or w/o complications; n (%)*
411 (7.9%)
354 (6.8%)
0.0041
496 (7.1%)
503 (7.2%)
-0.0004
907 (7.5%)
857 (7.0%)
0.019
Diabetes mellitus without mention of complications; n (%)
395 (7.6%)
329 (6.3%)
0.0049
463 (6.7%)
481 (6.9%)
-0.0008
858 (7.1%)
810 (6.7%)
0.016
Diabetes with specified complications; n (%)
73 (1.4%)
57 (1.1%)
0.0027
83 (1.2%)
66 (0.9%)
0.0029
156 (1.3%)
123 (1.0%)
0.028
Diabetes with unspecified complications; n (%)
16 (0.3%)
13 (0.3%)
0.0000
17 (0.2%)
14 (0.2%)
0.0000
033 (0.3%)
027 (0.2%)
0.020
GI Conditions
GERD; n (%)*
492 (9.5%)
467 (9.0%)
0.0016
591 (8.5%)
611 (8.8%)
-0.0010
1,083 (8.9%)
1,078 (8.9%)
0.000
Upper GI (Diseases of esophagus, stomach and duodenum including 
GERD) ; n (%)
611 (11.8%)
597 (11.5%)
0.0009
763 (11.0%)
783 (11.3%)
-0.0009
1,374 (11.3%)
1,380 (11.4%)
-0.003
GI bleeding; n (%)*
71 (1.4%)
63 (1.2%)
0.0018
77 (1.1%)
94 (1.4%)
-0.0027
148 (1.2%)
157 (1.3%)
-0.009
Non-infective enteritis and colitis; n (%)
153 (2.9%)
164 (3.2%)
-0.0017
229 (3.3%)
215 (3.1%)
0.0011
382 (3.1%)
379 (3.1%)
0.000
Intraoperative and postprocedural complications and disorders of 
digestive system; n (%)
75 (1.4%)
55 (1.1%)
0.0027
71 (1.0%)
70 (1.0%)
0.0000
146 (1.2%)
125 (1.0%)
0.019
Disorders of gallbladder, biliary tract and pancreas; n (%)*
42 (0.8%)
40 (0.8%)
0.0000
56 (0.8%)
57 (0.8%)
0.0000
098 (0.8%)
097 (0.8%)
0.000
Rheumatic Conditions
Rheumatoid arthritis and other inflammatory polyarthropathies; n 
(%)*
59 (1.1%)
52 (1.0%)
0.0010
100 (1.4%)
108 (1.6%)
-0.0016
159 (1.3%)
160 (1.3%)
0.000
Osteoarthrosis; n (%)*
366 (7.0%)
347 (6.7%)
0.0011
525 (7.5%)
498 (7.2%)
0.0011
891 (7.3%)
845 (7.0%)
0.012
Other rheumatic disorders (including gout); n (%)*
1,007 (19.4%)
989 (19.0%)
0.0009
1,405 (20.2%)
1,420 (20.4%)
-0.0004
2,412 (19.8%)
2,409 (19.8%)
0.000
Gout and other crystal arthropathies; n (%)
35 (0.7%)
41 (0.8%)
-0.0012
35 (0.5%)
55 (0.8%)
-0.0037
070 (0.6%)
096 (0.8%)
-0.024
Other rheumatic disorders; n (%)
988 (19.0%)
960 (18.5%)
0.0012
1,382 (19.9%)
1,381 (19.8%)
0.0002
2,370 (19.5%)
2,341 (19.3%)
0.005
Neuro Conditions*
Alzheimer and other Dementia Disease ; n (%)
35 (0.7%)
31 (0.6%)
0.0012
30 (0.4%)
37 (0.5%)
-0.0015
065 (0.5%)
068 (0.6%)
-0.014
Seizure disorders (epilepsy); n (%)
26 (0.5%)
28 (0.5%)
0.0000
40 (0.6%)
41 (0.6%)
0.0000
066 (0.5%)
069 (0.6%)
-0.014
Delirium/Psychosis; n (%)
44 (0.8%)
43 (0.8%)
0.0000
43 (0.6%)
46 (0.7%)
-0.0012
087 (0.7%)
089 (0.7%)
0.000
Other Conditions
Hypothyroidism; n (%)*
484 (9.3%)
484 (9.3%)
0.0000
531 (7.6%)
512 (7.4%)
0.0007
1,015 (8.3%)
996 (8.2%)
0.004
Chronic kidney disease stages I-III; n (%)*
100 (1.9%)
101 (1.9%)
0.0000
59 (0.8%)
60 (0.9%)
-0.0011
159 (1.3%)
161 (1.3%)
0.000
Chronic kidney disease stages IV-V, ESRD; n (%)
31 (0.6%)
25 (0.5%)
0.0013
17 (0.2%)
16 (0.2%)
0.0000
048 (0.4%)
041 (0.3%)
0.017
COPD; n (%)*
261 (5.0%)
258 (5.0%)
0.0000
352 (5.1%)
347 (5.0%)
0.0004
613 (5.0%)
605 (5.0%)
0.000
Obstructive sleep apnea; n (%)*
274 (5.3%)
263 (5.1%)
0.0009
372 (5.3%)
378 (5.4%)
-0.0004
646 (5.3%)
641 (5.3%)
0.000
Syncope; n (%)
62 (1.2%)
50 (1.0%)
0.0019
72 (1.0%)
86 (1.2%)
-0.0019
134 (1.1%)
136 (1.1%)
0.000
Falls; n (%)
58 (1.1%)
42 (0.8%)
0.0031
39 (0.6%)
30 (0.4%)
0.0028
097 (0.8%)
072 (0.6%)
0.024
VTE; n (%)*
32 (0.6%)
36 (0.7%)
-0.0012
57 (0.8%)
59 (0.8%)
0.0000
089 (0.7%)
095 (0.8%)
-0.012
Combined comorbidity score, 365 days*
...mean (sd)
1.17 (0.96)
1.15 (0.97)
0.0207
1.15 (0.89)
1.13 (0.86)
0.0229
1.16 (0.92)
1.14 (0.91)
0.022
...median [IQR]
1.00 [1.00, 1.00]
1.00 [1.00, 1.00]
0.0000
1.00 [1.00, 1.00]
1.00 [1.00, 1.00]
0.0000
1.00 (0.92)
1.00 (0.91)
0.000
Frailty Score: Empirical Version 365 days as Categories*
...< 0.1 non frail; n (%)
3,483 (67.0%)
3,450 (66.4%)
0.0007
4,163 (59.8%)
4,169 (59.9%)
-0.0001
7,646 (62.9%)
7,619 (62.7%)
0.004
...0.1 - < 0.2 prefrail; n (%)
1,118 (21.5%)
1,168 (22.5%)
-0.0021
1,741 (25.0%)
1,748 (25.1%)
-0.0002
2,859 (23.5%)
2,916 (24.0%)
-0.012
… > 0.2 frail; n (%)
597 (11.5%)
580 (11.2%)
0.0009
1,055 (15.2%)
1,042 (15.0%)
0.0005
1,652 (13.6%)
1,622 (13.3%)
0.009
Medication Use
Use of oral corticosteroids; n (%)*
2,474 (47.6%)
2,528 (48.6%)
-0.0014
6,612 (95.0%)
6,635 (95.3%)
-0.0003
9,086 (74.7%)
9,163 (75.4%)
-0.016
Use of antidepressants; n (%)*
981 (18.9%)
984 (18.9%)
0.0000
1,520 (21.8%)
1,525 (21.9%)
-0.0002
2,501 (20.6%)
2,509 (20.6%)
0.000
Use of anticonvulsants; n (%)*
297 (5.7%)
284 (5.5%)
0.0008
509 (7.3%)
487 (7.0%)
0.0011
806 (6.6%)
771 (6.3%)
0.012
Use of beta blocker OR calcium channel blocker; n (%)*
505 (9.7%)
474 (9.1%)
0.0020
751 (10.8%)
732 (10.5%)
0.0009
1,256 (10.3%)
1,206 (9.9%)
0.013
Use of PPIs; n (%)*
744 (14.3%)
734 (14.1%)
0.0005
1,413 (20.3%)
1,430 (20.5%)
-0.0004
2,157 (17.7%)
2,164 (17.8%)
-0.003
Appendix B

Use of opioids; n (%)*
808 (15.5%)
781 (15.0%)
0.0013
1,307 (18.8%)
1,308 (18.8%)
0.0000
2,115 (17.4%)
2,089 (17.2%)
0.005
Use of antipsychotics; n (%)*
73 (1.4%)
73 (1.4%)
0.0000
101 (1.5%)
99 (1.4%)
0.0008
174 (1.4%)
172 (1.4%)
0.000
Use of anxiolytics/hypnotics; n (%)*
289 (5.6%)
285 (5.5%)
0.0004
457 (6.6%)
489 (7.0%)
-0.0015
746 (6.1%)
774 (6.4%)
-0.012
Use of dementia meds; n (%)*
23 (0.4%)
23 (0.4%)
0.0000
21 (0.3%)
23 (0.3%)
0.0000
044 (0.4%)
046 (0.4%)
0.000
Use of antiparkinsonian meds; n (%)*
53 (1.0%)
51 (1.0%)
0.0000
98 (1.4%)
103 (1.5%)
-0.0008
151 (1.2%)
154 (1.3%)
-0.009
Use of Benzodiazepine; n (%)*
467 (9.0%)
454 (8.7%)
0.0010
822 (11.8%)
839 (12.1%)
-0.0009
1,289 (10.6%)
1,293 (10.6%)
0.000
All antidiabetic medications; n (%)*
328 (6.3%)
286 (5.5%)
0.0033
474 (6.8%)
491 (7.1%)
-0.0011
802 (6.6%)
777 (6.4%)
0.008
ACEI/ARB; n (%)8
875 (16.8%)
865 (16.6%)
0.0005
1,316 (18.9%)
1,334 (19.2%)
-0.0007
2,191 (18.0%)
2,199 (18.1%)
-0.003
Use of Anticoagulants; n (%)*
104 (2.0%)
91 (1.8%)
0.0015
154 (2.2%)
150 (2.2%)
0.0000
258 (2.1%)
241 (2.0%)
0.007
Use of Amiodarone; n (%)
9 (0.2%)
10 (0.2%)
0.0000
16 (0.2%)
9 (0.1%)
0.0026
025 (0.2%)
019 (0.2%)
0.000
Digoxin; n (%)
22 (0.4%)
17 (0.3%)
0.0017
41 (0.6%)
30 (0.4%)
0.0028
063 (0.5%)
047 (0.4%)
0.015
Use of Diuretics; n (%)*
705 (13.6%)
689 (13.3%)
0.0008
1,104 (15.9%)
1,108 (15.9%)
0.0000
1,809 (14.9%)
1,797 (14.8%)
0.003
Use of Aspirin; n (%)
16 (0.3%)
17 (0.3%)
0.0000
25 (0.4%)
27 (0.4%)
0.0000
041 (0.3%)
044 (0.4%)
-0.017
NSAIDs (NOT including aspirin); n (%)
463 (8.9%)
523 (10.1%)
-0.0039
811 (11.7%)
929 (13.3%)
-0.0045
1,274 (10.5%)
1,452 (11.9%)
-0.044
HRT (Use of estrogens, progestins, androgens); n (%)*
716 (13.8%)
735 (14.1%)
-0.0008
1,088 (15.6%)
1,111 (16.0%)
-0.0010
1,804 (14.8%)
1,846 (15.2%)
-0.011
Use of Statins ; n (%)*
909 (17.5%)
870 (16.7%)
0.0019
1,203 (17.3%)
1,188 (17.1%)
0.0005
2,112 (17.4%)
2,058 (16.9%)
0.013
Healthcare Utilization Measures
Use of any drugs claims*
...mean (sd)
22.17 (17.48)
22.00 (16.75)
0.0099
24.51 (16.99)
24.60 (17.10)
-0.0053
23.51 (17.20)
23.49 (16.95)
0.001
...median [IQR]
18.00 [10.00, 29.00]
18.00 [10.00, 29.00] 0.0000
20.00 [12.00, 32.00]
21.00 [12.00, 32.00]
-0.0587
19.14 (17.20)
19.72 (16.95)
-0.034
Number of office visits*
...mean (sd)
10.07 (8.28)
10.04 (8.68)
0.0035
11.05 (8.13)
11.08 (7.78)
-0.0038
10.63 (8.19)
10.64 (8.18)
-0.001
...median [IQR]
8.00 [5.00, 13.00]
8.00 [5.00, 12.25]
0.0000
9.00 [6.00, 14.00]
9.00 [6.00, 14.00]
0.0000
8.57 (8.19)
8.57 (8.18)
0.000
Number of ED visits*
...mean (sd)
0.33 (0.77)
0.32 (0.76)
0.0131
0.52 (1.15)
0.52 (1.07)
0.0000
0.44 (1.01)
0.43 (0.95)
0.010
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.0000
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.0000
0.00 (1.01)
0.00 (0.95)
0.000
Number of hospitalizations*
...mean (sd)
0.03 (0.20)
0.03 (0.25)
0.0000
0.16 (1.29)
0.14 (1.09)
0.0167
0.10 (0.98)
0.09 (0.84)
0.011
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.0000
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.0000
0.00 (0.98)
0.00 (0.84)
0.000
Recent hospitalization (-30 days to Index Rx date); n (%)*
14 (0.3%)
8 (0.2%)
0.0020
38 (0.5%)
40 (0.6%)
-0.0013
052 (0.4%)
048 (0.4%)
0.000
Old hospitalizations (-365 to -31 days); n (%)*
295 (5.7%)
303 (5.8%)
-0.0004
468 (6.7%)
482 (6.9%)
-0.0008
763 (6.3%)
785 (6.5%)
-0.008
Number of Pulmonologist/Allergist visits*
...mean (sd)
0.02 (0.26)
0.02 (0.27)
0.0000
1.38 (3.64)
1.39 (3.52)
-0.0028
0.80 (2.76)
0.80 (2.67)
0.000
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.0000
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.0000
0.00 (2.76)
0.00 (2.67)
0.000
Pulmonologist /allergist on CED; n (%)*
3 (0.1%)
2 (0.0%)
0.0045
456 (6.6%)
466 (6.7%)
-0.0004
459 (3.8%)
468 (3.8%)
0.000
Number of hospital days*
...mean (sd)
0.21 (2.95)
0.19 (2.73)
0.0070
0.16 (1.29)
0.14 (1.09)
0.0167
0.18 (2.16)
0.16 (1.97)
0.010
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.0000
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.0000
0.00 (2.16)
0.00 (1.97)
0.000
Occurrence of basic or comprehensive metabolic blood chemistry 
test; n (%)*
1,406 (27.0%)
1,348 (25.9%)
0.0021
1,693 (24.3%)
1,679 (24.1%)
0.0004
3,099 (25.5%)
3,027 (24.9%)
0.014
Number of HbA1C test ordered*
...mean (sd)
0.33 (0.88)
0.29 (0.80)
0.0476
0.29 (0.78)
0.29 (0.78)
0.0000
0.31 (0.82)
0.29 (0.79)
0.025
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.0000
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.0000
0.00 (0.82)
0.00 (0.79)
0.000
Flexible Sigmoidoscopy or colonoscopy or CT virtual colonoscopy; 
n (%)*
162 (3.1%)
159 (3.1%)
0.0000
236 (3.4%)
244 (3.5%)
-0.0005
398 (3.3%)
403 (3.3%)
0.000
Number of Mammograms (Breast cancer screening); n (%)*
687 (13.2%)
669 (12.9%)
0.0008
918 (13.2%)
918 (13.2%)
0.0000
1,605 (13.2%)
1,587 (13.1%)
0.003
Number of Pap smear (Cervical cancer screening); n (%)*
690 (13.3%)
707 (13.6%)
-0.0008
961 (13.8%)
954 (13.7%)
0.0003
1,651 (13.6%)
1,661 (13.7%)
-0.003
Flu vaccine; n (%)*
973 (18.7%)
982 (18.9%)
-0.0005
1,201 (17.3%)
1,155 (16.6%)
0.0017
2,174 (17.9%)
2,137 (17.6%)
0.008
Pneumococcal vaccine; n (%)*
307 (5.9%)
306 (5.9%)
0.0000
443 (6.4%)
448 (6.4%)
0.0000
750 (6.2%)
754 (6.2%)
0.000
Copay for pharmacy cost (charges in U.S. $)*
...mean (sd)
35.89 (33.14)
36.20 (29.55)
-0.0099
25.00 (23.64)
24.90 (23.97)
0.0042
29.66 (28.10)
29.73 (26.50)
-0.003
...median [IQR]
29.37 [16.66, 46.02]
31.05 [18.46, 47.50] -0.0535
21.00 [9.54, 34.19]
20.80 [10.00, 34.36]
0.0084
24.58 (28.10)
25.18 (26.50)
-0.022
Business Type*
...Commercial; n (%)
4,456 (85.7%)
4,494 (86.5%)
-0.0009
NA
NA
NA
NA
NA
NA
Appendix B

...Medicare; n (%)
742 (14.3%)
704 (13.5%)
0.0021
NA
NA
NA
NA
NA
NA
Insurance Plan Type*
...Comprehensive; n (%)
NA
NA
NA
547 (7.9%)
554 (8.0%)
-0.0004
NA
NA
NA
...HMO; n (%)
NA
NA
NA
902 (13.0%)
896 (12.9%)
0.0003
NA
NA
NA
...PPO; n (%)
NA
NA
NA
4,037 (58.0%)
4,052 (58.2%)
-0.0003
NA
NA
NA
...Others; n (%)
NA
NA
NA
1,473 (21.2%)
1,457 (20.9%)
0.0007
NA
NA
NA
SABA; n (%)*
2,756 (53.0%)
2,770 (53.3%)
-0.0004
4,454 (64.0%)
4,477 (64.3%)
-0.0004
7,210 (59.3%)
7,247 (59.6%)
-0.006
SAMA; n (%)*
79 (1.5%)
66 (1.3%)
0.0017
182 (2.6%)
187 (2.7%)
-0.0006
261 (2.1%)
253 (2.1%)
0.000
SABA/SAMA; n (%)*
101 (1.9%)
100 (1.9%)
0.0000
255 (3.7%)
265 (3.8%)
-0.0005
356 (2.9%)
365 (3.0%)
-0.006
ICS without budesonide; n (%)*
1,600 (30.8%)
1,649 (31.7%)
-0.0016
2,596 (37.3%)
2,705 (38.9%)
-0.0026
4,196 (34.5%)
4,354 (35.8%)
-0.027
LABA; n (%)*
209 (4.0%)
191 (3.7%)
0.0015
340 (4.9%)
349 (5.0%)
-0.0004
549 (4.5%)
540 (4.4%)
0.005
LAMA; n (%)*
111 (2.1%)
115 (2.2%)
-0.0007
228 (3.3%)
243 (3.5%)
-0.0011
339 (2.8%)
358 (2.9%)
-0.006
ICS/LABA (without budesonide-formoterol); n (%)*
546 (10.5%)
568 (10.9%)
-0.0012
813 (11.7%)
857 (12.3%)
-0.0017
1,359 (11.2%)
1,425 (11.7%)
-0.016
Blood eosinophilia test ; n (%)*
15 (0.3%)
16 (0.3%)
0.0000
13 (0.2%)
15 (0.2%)
0.0000
028 (0.2%)
031 (0.3%)
-0.020
Serum immunoglobulin E (IgE) level test; n (%)*
62 (1.2%)
72 (1.4%)
-0.0018
119 (1.7%)
119 (1.7%)
0.0000
181 (1.5%)
191 (1.6%)
-0.008
H2 blocker; n (%)*
56 (1.1%)
60 (1.2%)
-0.0009
213 (3.1%)
193 (2.8%)
0.0017
269 (2.2%)
253 (2.1%)
0.007
Oxygen codes; n (%)*
14 (0.3%)
7 (0.1%)
0.0045
32 (0.5%)
29 (0.4%)
0.0015
046 (0.4%)
036 (0.3%)
0.017
Respiratory arrest/dependence on oxygen; n (%)*
1 (0.0%)
0 (0.0%)
#DIV/0!
0 (0.0%)
0 (0.0%)
#DIV/0!
001 (0.0%)
000 (0.0%)
#DIV/0!
*Included in the 1:1 PS matching model
Appendix B