The Role of Inhaler Device in the Treatment Persistence With Dual Bronchodilators in Patients With COPD
Conditions: Pulmonary Disease, Chronic Obstructive
Sponsor: Boehringer Ingelheim

ABCD
001-MCG-102_RD-02 (1.0) / Saved on: 22 Oct 2015
Protocol for non-interventional studies based on existing data
TITLE PAGE
Document Number:
c30445781-01
BI Study Number:
1237-0090
BI Investigational
Product(s):
Stiolto® Respimat®
Title:
The Role of Inhaler Device in the Treatment Persistence with Dual 
Bronchodilators in Patients with COPD
Protocol version 
identifier:
1.0
Date of last version of 
protocol:
N/A
PASS:
No
EU PAS register 
number:
Study not registered
Active substance:
Olodaterol and Tiotropium Bromide (ATC R03AL06)
Umeclidinium and Vilanterol (ATC R03AL03)
Medicinal product:
Stiolto® Respimat®; Anoro® Ellipta®
Product reference:
N/A
Procedure number:
N/A
Joint PASS:
No
Research question and 
objectives:
The primary objective of the study is to use US data to determine 
relative persistence between Olodaterol/Tiotropium Bromide 
delivered with the Respimat soft mist inhaler and
Umeclidinium/Vilanterol delivered with the Ellipta dry powder
inhaler using a 1:2 propensity score matched analysis.
The secondary objectives of the study are as follows:
-
Characterize new users of Olodaterol/Tiotropium Bromide 
and Umeclidinium/Vilanterol in terms of demographics, 
medication use, comorbidities, and other variables, before 
and after propensity score matching.
-
Determine the incidence rate and proportion of patients 
discontinuing or switching among new users of 
Olodaterol/Tiotropium Bromide and Umeclidinium/
Vilanterol.
-
Determine the relative rate and proportion of patients 
discontinuing between Olodaterol/ Tiotropium Bromide and

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001-MCG-102_RD-02 (1.0) / Saved on: 22 Oct 2015
Umeclidinium/Vilanterol. using a standard multivariate 
analysis (If feasible).
Country(-ies) of study:
United States
Author:
T: 
Email:
T:
Email: 
BI contact person: 
Marketing 
authorisation 
holder(s):
MAH contact person:
In case of PASS, add:
N/A
In case of PASS, add:
N/A
Date:
22 November 2019
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© 2019 Boehringer Ingelheim International GmbH or one or more of its affiliated companies. All rights reserved.
This document may not - in full or in part - be passed on, reproduced, published or otherwise used without prior written permission

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1.
TABLE OF CONTENTS
TITLE PAGE.............................................................................................................................1
1.
TABLE OF CONTENTS...............................................................................................3
2.
LIST OF ABBREVIATIONS........................................................................................5
3.
RESPONSIBLE PARTIES............................................................................................6
4.
ABSTRACT...................................................................................................................7
5.
AMENDMENTS AND UPDATES.............................................................................15
6.
MILESTONES.............................................................................................................15
7.
RATIONALE AND BACKGROUND........................................................................15
8.
RESEARCH QUESTION AND OBJECTIVES..........................................................16
9.
RESEARCH METHODS ............................................................................................17
9.1
STUDY DESIGN..........................................................................................17
9.2
SETTING ......................................................................................................17
9.2.1
Definitions.....................................................................................................17
9.2.2
Study population............................................................................................19
9.3
VARIABLES.................................................................................................20
9.3.1
Exposures ......................................................................................................20
9.3.2
Outcomes.......................................................................................................20
9.3.2.1
Primary outcome..........................................................................................20
9.3.2.2
Secondary outcomes ....................................................................................21
9.3.3
Covariates......................................................................................................21
9.4
DATA SOURCES.........................................................................................23
9.5
STUDY SIZE ................................................................................................23
9.6
DATA MANAGEMENT..............................................................................23
9.7
DATA ANALYSIS .......................................................................................24
9.7.1
Main analysis.................................................................................................24
9.7.1.1
Descriptive Analysis ....................................................................................24
9.7.1.2
Rates and Risks............................................................................................24
9.7.1.3
Comparative Persistence..............................................................................25
9.7.2
Sensitivity Analysis.......................................................................................26
9.8
QUALITY CONTROL .................................................................................27
9.9
LIMITATIONS OF THE RESEARCH METHODS....................................28

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9.10
OTHER ASPECTS........................................................................................28
9.11
SUBJECTS....................................................................................................28
9.11.1
Cases..............................................................................................................28
9.11.2
Controls .........................................................................................................29
9.12
BIAS..............................................................................................................29
10.
PROTECTION OF HUMAN SUBJECTS ..................................................................29
11.
MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ...............................................................................................................30
12.
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS..30
13.
REFERENCES.............................................................................................................31
13.1
PUBLISHED REFERENCES.......................................................................31
13.2
UNPUBLISHED REFERENCES.................................................................32
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS.........................................................33
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS .........................................34
ANNEX 3: LIST OF MEDICATION MEASURE DEFINITIONS........................................35
ANNEX 4. LIST OF COMORBIDITY, SYMPTOMS AND OTHER MEASURE 
DEFINITIONS.............................................................................................................38
ANNEX 5. TABLE SHELLS AND PROPOSED FIGURES .................................................60

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2.
LIST OF ABBREVIATIONS
ACE
Angiotensin Converting Enzyme
AIDS
Acquired Immune Deficiency Syndrome
CCAE
Commercial Claims and Encounters
CDCI
Charlson Deyo Comorbidity Index
CI
Confidence Interval
COB
Coordination of Benefits
COBRA Consolidated Omnibus Budget Reconciliation Act
COPD
Chronic Obstructive Pulmonary Disease
CT
Computed Tomography
DPI
Dry Powder Inhaler
ENCEPP European Network of Centres for Pharmacoepidemiology and Pharmacovigilance
ESRD
End Stage Renal Disease
FDC
Fixed Dose Combination
GLP-1
Glucagon-like Peptide-1
GOLD
Global Initiative for Chronic Obstructive Lung Disease
HIV
Human Immunodeficiency Virus
ICD
International Classification of Diseases
ICS
Inhaled Corticosteroid
IP
Inpatient
IQR
Interquartile Range
IRB
Institutional Review Board
LABA
LAMA
Long-Acting Beta-Agonists
Long-Acting Muscarinic Antagonists
NDC
National Drug Code
NSAID
Nonsteroidal Anti-inflammatory Drug
OCS
Oral Corticosteroid
OP
Outpatient
SABA
Short-acting Beta Agonist
SAMA
Short-acting Muscarinic Antagonist
SD
Standard Deviation
SMI
Soft Mist Inhaler

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3.
RESPONSIBLE PARTIES
T: 
Email: 
Email:
T: 
Email: 
T: 
Email: 

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4.
ABSTRACT
Name of company:
Boehringer Ingelheim International 
GmbH
Name of finished medicinal product:
Stiolto® Respimat®; Anoro® Ellipta®
Name of active ingredient:
Olodaterol and Tiotropium Bromide 
(ATC R03AL06); Umeclidinium and 
Vilanterol (ATC R03AL03)
Protocol date:
Study number:
Version/Revision:
Version/Revision 
date:
22 November 2019
1237-0090
1.0
NA
Title of study:
The Role of Inhalers In Treatment Persistence With Dual 
Bronchodilators In Patients With COPD
Rationale and 
background
Inhaled therapies are the cornerstone of chronic obstructive lung disease 
(COPD) management approaches. The aim of inhaled therapy is to deliver 
therapeutic agents directly to the lungs, optimizing benefits while
minimizing the potential for treatment-related adverse effects (Braido 
2016).
Adherence to COPD therapies involves patients initiating their prescribed 
therapy, implementing it as prescribed (i.e., correctly administering the 
prescribed dose at the physician directed frequency), and persisting with 
treatment (Braido 2016; Mäkelä 2013). Also central to the therapeutic 
benefit of inhaled therapies is their successful administration, which 
requires patients to have knowledge and understanding of (and ability to 
implement) the appropriate inhaler technique required to optimize both the 
dispensed and administered doses (Braido 2016). Inspiratory capabilities 
of patients with COPD are affected by increasing static and dynamic 
hyperinflation and weakening of the respiratory muscles, causing many 
patients to have peak inspiratory flow rates that are suboptimal to use many 
dry-powder inhalers (DPIs) (Sohini 2017). This paradoxical situation may 
lead to improper inhalation that prevents successful drug delivery to the 
lungs, which may affect treatment efficacy. The question if different 
devices, DPI and Soft Mist Inhalers (SMI), played a role in treatment 
persistence remains to be answered. 
In this study we aim to compare the persistence in using two different 
medications from the same drug class (LAMA/LABA FDC) which are 
delivered through different devices, a DPI and an SMI.

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Name of company:
Boehringer Ingelheim International 
GmbH
Name of finished medicinal product:
Stiolto® Respimat®; Anoro® Ellipta®
Name of active ingredient:
Olodaterol and Tiotropium Bromide 
(ATC R03AL06); Umeclidinium and 
Vilanterol (ATC R03AL03)
Protocol date:
Study number:
Version/Revision:
Version/Revision 
date:
22 November 2019
1237-0090
1.0
NA
Research question 
and objectives:
This study seeks to compare the differences in treatment persistence in 
using two combinations of two drugs of the same drug class 
(LAMA/LABA as a fixed dose combination) delivered through different 
devices (a DPI or an SMI) within an administrative claims database in the 
US.
The primary objective of the study is to use US data to determine 
relative treatment persistence between patients prescribed
Olodaterol/Tiotropium Bromide delivered with the Respimat SMI
and Umeclidinium/Vilanterol delivered with the Ellipta DPI using a 
1:2 propensity score matched analysis.
The secondary objectives of the study are as follows:
-
Characterize new users of Olodaterol/Tiotropium Bromide and
Umeclidinium/Vilanterol in terms of demographics, medication 
use, comorbidities, and other variables, before and after propensity 
score matching.
-
Determine the rate and risk (proportion of patients) of 
discontinuation among new users of Olodaterol/Tiotropium
Bromide and Umeclidinium/ Vilanterol in the 1:2 matched cohort.
-
Determine the relative rate and risk of discontinuation between 
Olodaterol/Tiotropium Bromide and Umeclidinium/Vilanterol,
using a standard multivariable analysis (Same variables as 
propensity score model) in the total unmatched cohort.
Study design:
New-user cohort design with propensity scores used to match up to 2
Umeclidinium/Vilanterol initiators to each Olodaterol/Tiotropium Bromide
initiator.
Population:
Patients initiating Olodaterol/Tiotropium Bromide or Umeclidinium/
Vilanterol between 17 November 2015 and 31 March 2018.
Exclusion criteria are:

Aged <40 years.

Enrolment with medical and pharmacy coverage prior to the cohort 
entry < 180 days.

Never had COPD diagnosis on the cohort entry date or prior to 
cohort entry.

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Name of company:
Boehringer Ingelheim International 
GmbH
Name of finished medicinal product:
Stiolto® Respimat®; Anoro® Ellipta®
Name of active ingredient:
Olodaterol and Tiotropium Bromide 
(ATC R03AL06); Umeclidinium and 
Vilanterol (ATC R03AL03)
Protocol date:
Study number:
Version/Revision:
Version/Revision 
date:
22 November 2019
1237-0090
1.0
NA

A record for dispensed Olodaterol/Tiotropium Bromide delivered 
with Respimat inhalator or Umeclidinium/Vilanterol delivered with 
the Ellipta Inhaler during the 180-day baseline prior to cohort 
entry.

Diagnosis of asthma any time prior to cohort entry.

Diagnosis of lung cancer any time prior to cohort entry.

Diagnosis of lung transplant any time prior to cohort entry.

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Name of company:
Boehringer Ingelheim International 
GmbH
Name of finished medicinal product:
Stiolto® Respimat®; Anoro® Ellipta®
Name of active ingredient:
Olodaterol and Tiotropium Bromide 
(ATC R03AL06); Umeclidinium and 
Vilanterol (ATC R03AL03)
Protocol date:
Study number:
Version/Revision:
Version/Revision 
date:
22 November 2019
1237-0090
1.0
NA
Variables:
Exposures

Olodaterol/Tiotropium Bromide (Stiolto®) delivered via Respimat 
inhaler 

Umeclidinium/Vilanterol (Anoro®) delivered via Ellipta Inhaler
Outcome

Discontinuation of index treatment (Olodaterol/Tiotropium 
Bromide or Umeclidinium/Vilanterol), defined as persistence of 
treatment (no refill claim within 60 days (allowable grace period) 
after end of <n> days supply). Addition of another drug will not 
count as a discontinuation.
Covariates
Demographics
●
Age on the cohort entry date
●
Sex (Male, Female)
●
Region (Northeast, North Central, South, West, Unknown, 
Missing)
●
Insurance Type (Commercial, Medicare, Missing)
●
Study Year of Cohort Entry (First Year: 17 Nov 2015-30 Nov
2016, Second Year: 01 Dec 2016-30 Nov 2017, Third Year: 01 
Dec 2017-31 Mar 2018)
Concomitant Medications
●
Oral Corticosteroids (OCS)
●
Short acting muscarinic antagonist (SAMA)
●
Short acting beta agonist (SABA)
●
Long acting muscarinic antagonist (LAMA)
●
Long acting beta agonist (LABA)
●
Inhaled corticosteroid (ICS)
●
LAMA / LABA combination (that is not Stiolto or Anoro)
●
LABA / ICS combination
●
LAMA / LABA / ICS combination
●
NSAIDs
●
Antihistamines

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Name of company:
Boehringer Ingelheim International 
GmbH
Name of finished medicinal product:
Stiolto® Respimat®; Anoro® Ellipta®
Name of active ingredient:
Olodaterol and Tiotropium Bromide 
(ATC R03AL06); Umeclidinium and 
Vilanterol (ATC R03AL03)
Protocol date:
Study number:
Version/Revision:
Version/Revision 
date:
22 November 2019
1237-0090
1.0
NA
●
Opioids
●
Oral antibiotics
●
Antidiabetic Agents (not including insulin)
●
Insulin (basal or mealtime)
●
Methotrexate
●
Statins
●
Antihypertensives
●
Anticoagulants
●
Anti-psychotic/anti-depressives/anxiolytic
●
Oxygen therapy
Comorbidities/Symptoms
●
History of All-Cause Hospitalization
●
History of Emergency Department Visit
●
History of Hospitalization due to Respiratory Condition
●
Acute Myocardial Infarction
●
Angina Pectoris
●
Peripheral Vascular Disease
●
Heart Failure
●
Hypertension
●
Upper Respiratory Infection
●
Lower Respiratory Infection
●
Cardiac Arrhythmias
●
Cerebrovascular Disease
●
All cancers (except non-melanoma skin cancer)
●
Allergic Rhinitis
●
Chronic Sinusitis
●
Bronchiectasis
●
Pneumonia
●
Chronic Bronchitis
●
Exertional Breathlessness
●
Anxiety
●
Dementia
●
Depression
●
Osteoporosis
●
Charlson-Deyo Comorbidity Index 

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Name of company:
Boehringer Ingelheim International 
GmbH
Name of finished medicinal product:
Stiolto® Respimat®; Anoro® Ellipta®
Name of active ingredient:
Olodaterol and Tiotropium Bromide 
(ATC R03AL06); Umeclidinium and 
Vilanterol (ATC R03AL03)
Protocol date:
Study number:
Version/Revision:
Version/Revision 
date:
22 November 2019
1237-0090
1.0
NA
●
Acute Liver Injury or Failure
●
Chronic Kidney Disease (without ESRD)
●
End Stage Renal Disease
●
Rheumatic Disease
●
Peptic Ulcer Disease
●
Gastroesophageal Reflux Disease
●
Type 1 Diabetes Mellitus
●
Type 2 Diabetes Mellitus
●
HIV/AIDS
●
Hemiplegia or Paraplegia
Lifestyle
●
Smoking-related claim
●
Vaccination for Influenza
●
Vaccination for Pneumococcus
Respiratory Function Procedures/Tests Conducted
●
Pulmonary function tests
●
Six-minute walk test
●
Chest X-ray
●
High resolution chest CT

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Name of company:
Boehringer Ingelheim International 
GmbH
Name of finished medicinal product:
Stiolto® Respimat®; Anoro® Ellipta®
Name of active ingredient:
Olodaterol and Tiotropium Bromide 
(ATC R03AL06); Umeclidinium and 
Vilanterol (ATC R03AL03)
Protocol date:
Study number:
Version/Revision:
Version/Revision 
date:
22 November 2019
1237-0090
1.0
NA
Data sources:
Truven MarketScan is a claims database that captures longitudinal, 
individual-level administrative claims data from the United States. 
Study size:
There are 14,751 new users of Olodaterol/Tiotropium Bromide or 
Umeclidinium/Vilanterol between 17 November 2015 and 31 March 2018
who satisfied the inclusion criteria. Among them, 3,889 initiated 
Olodaterol/Tiotropium Bromide and 10,862 initiated Umeclidinium/
Vilanterol).
Data analysis:
For demographic and lifestyle variables, the value recorded on the cohort 
entry date will be reported, otherwise the most recent known value will be 
reported. Presence of comorbidities and use of concomitant medication use 
will be determined based whether they ever occurred within the 180-day 
baseline period preceding the index date.Differences in the confounder 
distributions will be inspected for successful confounder balance of 
measured characteristics.
Patients will be followed up until first occurrence of death, discontinuation, 
disenrollment, end of data, or 365 days.
The data will be displayed in a nonparametric fashion on a persistency 
curve (a Kaplan–Meier curve) with discontinuation considered as 
elimination. 
Unmatched Cohort
Rates and risks (proportion of patients) with the outcomes for each 
exposure group will be reported among the unmatched cohort.
Matched Cohort
Rates and risks (proportion of patients) with the outcomes for each 
exposure group will be reported among the matched cohort.
Logistic regression will be used to calculate the propensity to initiate
Olodaterol/Tiotropium Bromide versus Umeclidinium/Vilanterol. The 
propensity score will then be used to identify up to 2 initiators of 
Umeclidinium/Vilanterol for each initiator of Olodaterol/Tiotropium
Bromide with the same propensity score (± a caliper of 5%) as the 
corresponding initiator of Olodaterol/Tiotropium Bromide.

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Name of company:
Boehringer Ingelheim International 
GmbH
Name of finished medicinal product:
Stiolto® Respimat®; Anoro® Ellipta®
Name of active ingredient:
Olodaterol and Tiotropium Bromide 
(ATC R03AL06); Umeclidinium and 
Vilanterol (ATC R03AL03)
Protocol date:
Study number:
Version/Revision:
Version/Revision 
date:
22 November 2019
1237-0090
1.0
NA
Cox proportional hazard regression model will be used to assess the
relative rate (or hazard) of the outcome in patients treated with
Olodaterol/Tiotropium Bromide compared to patients treated with 
Umeclidinium/Vilanterol during the one-year follow-up. Crude HRs and 
95% CIs will be reported for the matched cohorts.
Among the matched cohort, relative risks with 95% CIs will also be 
reported, as assessed by conditional logistic regression.
Relative rates and risks will also be reported using standard multivariable 
regression.
Sensitivity Analyses

Restrict the 60-day allowable grace period used to define the 
discontinuation outcome to 30 days.

Increase the 60-day allowable grace period used to define the 
discontinuation outcome to 90 days.

Start the patient identification period on 21 May 2015 immediately 
upon FDA approval.

Exclude patients with ACOS. Patients with asthma only but not 
COPD are still excluded from cohort.
Milestones:
-
Feasibility assessment 
Sept 2018 (done)
-    Draft study protocol 
Dec 2018
-    Final study protocol 
Apr 2019
-
Results tables available 
May 2019
-
1st Abstract submitted 
Jun   2019 
(ERS 2019,  ISPOR or AMCP )
   -    Manuscript submitted 
Q2 2019

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5.
AMENDMENTS AND UPDATES
Not Applicable
6.
MILESTONES
Milestone
Planned Date
Draft Protocol
17 December 2018
Protocol Revisions
22 February 2019*
Start of Implementation
01 March 2019
Preliminary Result Tables
15 March 2019
Final Result Tables and 
Documentation of 
Implementation
26 April 2019
*Pending time for approval and suggested changes proposed by BI
7.
RATIONALE AND BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a common disease characterized by airway 
obstruction confirmed by spirometry, often including small airway obstruction, chronic 
bronchitis and emphysema (Barnes 2015). No known medications can reverse COPD, but 
regular maintenance treatments can help manage symptoms, reduce frequency of COPD 
exacerbations and improve health-related quality of life. Inhaled therapies are the cornerstone 
of COPD disease management approaches. The aim of inhaled therapy is to deliver agents 
directly to the lungs, thereby offering benefits while minimizing the potential for treatment-
related adverse effects (Braido 2016).
Adherence to obstructive lung disease therapies involves patients initiating their prescribed 
therapy, implementing it as prescribed (i.e. correctly administering the prescribed dose at the 
physician directed frequency), and persisting with treatment (Braido 2016; Mäkelä 2013). 
Central to the therapeutic benefit of inhaled therapies is their successful administration which 
requires patients to have knowledge and understanding of (and ability to implement) the 
appropriate inhaler technique required to optimize both the dispensed and administered doses 
(Braido 2016). Inspiratory capabilities of patients with COPD are affected by increasing 
static and dynamic hyperinflation and weakening of the respiratory muscles, causing many 
patients to have peak inspiratory flow rates that are suboptimal to use many dry-powder 
inhalers (DPIs) (Sohini 2017). This paradoxical situation may lead to improper inhalation 
that prevents successful drug delivery to the lungs, which may affect treatment effectiveness. 
On the other hand, soft mist inhalers (SMI) force a metered dose of drug solution through a 
precise nozzle to deliver consistent and reliable doses to the lungs with each actuation (Dalby
2004) and may help preserve benefits in patients with diminished peak inspiratory flow rates. 
Stiolto® Respimat®, a combination of Olodaterol and Tiotropium Bromide delivered via soft 
mist inhaler (SMI), was approved in May 2015 in the US and July 2015 in the EU (marketed 

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as Spiolto in the EU). Anoro® Ellipta®, a combination of Umeclidinium and Vilanterol
delivered via dry powder inhaler (DPI), was approved in December 2013 in the US and in 
February 2014 in the EU. Both products are maintenance therapies consisting of a 
combination of long-acting muscarinic antagonists (LAMA) and long-acting beta agonists 
(LABA). However, the question of whether different devices (DPI and SMI) play a role in 
treatment persistence remains to be answered. 
This study seeks to compare the treatment persistence of two drugs in same drug class 
(LAMA/LABA as a fixed dose combination [FDC]) delivered through different devices (a 
DPI and a SMI) within an administrative claims database in the US.
8.
RESEARCH QUESTION AND OBJECTIVES
The primary objective of the study is to use US data to determine relative treatment
persistence in using Olodaterol/Tiotropium Bromide delivered with the Respimat soft mist 
inhaler and Umeclidinium/Vilanterol delivered with the Ellipta dry powder inhaler using a 
1:2 propensity score matched analysis.
The secondary objectives of the study are as follows:
Characterize new users of Olodaterol/Tiotropium Bromide and Umeclidinium/Vilanterol in 
terms of demographics, medication use, comorbidities, and other variables, before and after 
propensity score matching.
Determine the rate and proportion of patients discontinuating among new users of 
Olodaterol/Tiotropium Bromide and Umeclidinium/ Vilanterol.
Determine the relative rate and proportion of patients discontinuing between 
Olodaterol/Tiotropium Bromide and Umeclidinium/Vilanterol, using a standard multivariate 
analysis (If feasible).

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9.
RESEARCH METHODS
9.1
STUDY DESIGN
The proposed study will utilize data from the Truven MarketScan dataset (US).
The Truven MarketScan databases are comprised of two components: the MarketScan
Commercial Claims and Encounters (CCAE) Database and the Medicare Supplemental and 
Coordination of Benefits (COB) Database. These databases capture longitudinal, individual-
level data on healthcare utilization, healthcare expenditures and plan enrollment, and contain 
integrated records for patient demographics, inpatient events, outpatient events, and 
pharmacy dispensing of drugs. The CCAE database is a medical and drug insurance claims 
database on ~150 million patients since from 2008 unique de-identified patients that include 
active employees, dependents, retirees or recipients of the Consolidated Omnibus Budget 
Reconciliation Act (COBRA), and data are drawn from large employers, health plans, and 
public organizations in the United States (Truven Health MarketScan® Research Databases 
2015). The MarketScan Medicare Supplemental and Coordination of Benefits (COB) 
Database contains pooled medical and drug insurance claims data of approximately 13.6 
Million unique de-identified patients (since 1996) that are Medicare-eligible retirees with 
employer-sponsored Medicare Supplemental plans. (Truven Health MarketScan® 
Research Databases 2015). 
In principle, in US when a patient goes to a pharmacy and gets a drug dispensed, the 
pharmacy bills the insurance carrier for the cost of that drug (Strom 2013). For billing 
purposes, the pharmacy has to identify which medication was dispensed along with the 
dosage strength (e.g. the milligrams per tablet) and quantity (e.g., number of tablets, etc.). 
Analogously, when a patient goes to a hospital or to a physician for medical care, the 
providers of care bill the insurance carrier for the cost of the medical care, and have to justify 
the bill with a diagnosis. Using a common patient identification number for both the 
pharmacy and the medical care claims, these elements can be linked, and analyzed as a 
longitudinal medical record (Strom 2013).
9.2
SETTING
9.2.1
Definitions
Study Period: the period of time that includes the exclusion criteria assessment period,
baseline, cohort entry date, and follow-up period for the study population. This period is the 
same for all patients.
The study period will be from 1 January 2008 to 31 March 2018, encompassing date of the 
earliest data availability to the date of the latest data availability.

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Patient Selection Period: the period of time for which patients are eligible to enter the cohort. 
The earliest date of the patient selection period is 17 November 2015, corresponding to 180-
days after US approval date of Stiolto Respimat.
Cohort Entry Date: Date of entry to the initial cohort of Stiolto or Anoro users.
Baseline Period: the 180-day period that ends 1 day prior to the cohort entry date used to 
assess covariate information. The baseline period will vary between patients depending on 
these dates. The earliest start of the baseline period would be 21 May 2015, the date of Stiolto 
approval (i.e. 180 days before November 17, 2015).
Follow-Up Period: the period of time between 1 day after the cohort entry date to the earliest 
occurrence of the outcome (discontinuation of refills), or any censoring criteria (365 days, 
death, disenrollment, or end of data). Addition of another treatment in addition to index 
treatment will not count as discontinuation.
For entry into the study population, patients will be required to have 180 days of continuous 
enrolment with both medical and pharmacy coverage. Data during the baseline period will be 
used to confirm study eligibility and classification of incident COPD. The follow-up period 
will be used for capturing first and second maintenance therapies. This is illustrated in 
Figure 1.
Figure 1
Study timeline for the Primary Study Population

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9.2.2
Study population
The pre-matched study cohort will consist of patients initiating Olodaterol/Tiotropium 
Bromide or Umeclidinium/Vilanterol between 17 November 2015 and 31 March 2018. 
The following exclusion criteria will then be applied:
Aged <40 years.
Enrolment with medical and pharmacy coverage prior to the cohort entry < 180 days.
Never had COPD diagnosis on the cohort entry date or prior to cohort entry.
A record for dispensed Olodaterol/Tiotropium Bromide delivered with Respimat inhalator or 
Umeclidinium/Vilanterol delivered with the Ellipta Inhaler during the 180-day baseline prior 
to cohort entry.
Diagnosis of asthma any time prior to cohort entry.
Diagnosis of lung cancer any time prior to cohort entry.
Diagnosis of lung transplant any time prior to cohort entry.
Figure 2
Below depicts the flow diagram of patients.

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Diagnosis of COPD (ICD-9: 491.*, 492.*, 496.*; ICD-10: J41.0, J41.1, J41.8, J42.*, J43.0, 
J43.1, J43.2, J43.8, J43.9, J44.0, J44.1, J44.9) will be defined as the presence of an inpatient 
or outpatient claim.
Diagnosis of asthma (ICD-9: 493.*; ICD-10: J45, J45.20, J45.21, J45.22, J45.90*, J45.99*) 
will be defined as either 1 inpatient claim or 2 outpatient events 30-365 days apart.
Diagnosis of lung cancer (ICD-9: 162.2, 162.3, 162.4, 162.5, 162.8, 162.9, 231.2; ICD-10: 
C34.00, C34.01, C34.02, C34.10, C34.11, C34.12, C34.2, C34.30, C34.31, C34.32, C34.80, 
C34.81, C34.82, C34.90, C34.91, C34.92, C7A.090, D02.20, D02.21, D02.22, Z85.118) will 
be defined as either 1 inpatient claim or 2 outpatient events 30-365 days apart.
Matched Cohort
A matched propensity score analysis will be used to assess comparative persistence between 
the two exposure comparison groups. Logistic regression will be used to calculate the 
propensity to initiate Olodaterol/Tiotropium Bromide versus Umeclidinium/Vilanterol given 
all covariates (except components of the Charlson Comorbidity index) listed in section 9.3.3, 
according to the following model:
Logit (Treatment | X1, X2, … , Xn) =  β0 + β1*X1 + β2*X2 + … + βn*Xn
Any covariates which are collinear with each other will be dropped from the analysis (if it 
causes failure of model to converge). The propensity score will then be used to identify up to 
2 initiators of Umeclidinium/Vilanterol for each initiator of Olodaterol/Tiotropium Bromide 
with the same propensity score (± a caliper of 5%) as the corresponding initiator of 
Olodaterol/Tiotropium Bromide (Austin 2011). 
9.3
VARIABLES
9.3.1
Exposures

Exposure: Olodaterol/Tiotropium Bromide (Stiolto®) delivered with Respimat 
inhalator 

Active Comparator: Umeclidinium/Vilanterol (Anoro®) delivered with the Ellipta 
Inhaler
Both exposures will be identified via NDC Generic Name and NDC Brand Name.
9.3.2
Outcomes
9.3.2.1
Primary outcome
Discontinuation
The primary outcome of interest is discontinuation of index treatment (Olodaterol/Tiotropium 
Bromide or Umeclidinium/Vilanterol), defined as persistence (i.e. no refill claim within 60 

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days [not involving treatment switch, nor death] (allowable grace period) after end of <n> 
days supply) during follow-up.
Censoring
Patients will be censoring if they did not discontinue their index treatment but had an 
occurrence of any of the following: 365 days of follow-up without discontinuation, death, 
disenrollment, end of data.
9.3.2.2
Secondary outcomes
Not applicable.
9.3.3
Covariates
Covariates will be identified based on data recorded within 180 days prior to or on the index 
date (date of dispensing/initiation of the exposure), unless otherwise specified. If multiple 
measurements are made in the baseline period, then the most recent measurement will be 
used. 
Covariates will be used to predict propensity scores in later analyses. Absolute and relative 
frequencies of each covariate will also be reported in Table Shells 1 and 2 (see Annex 5).
Detailed descriptions of the listed covariates can be found in Annex 3 and 4.
Demographics

Age on index date

Sex (Male, Female)

Region (Northeast, North Central, South, West, Unknown, Missing

Insurance Type (Commercial, Medicare, Missing)

Year of Cohort Entry (First Year, Second Year)
Concomitant Medications

Oral Corticosteroids

Short acting muscarinic antagonist (SAMA)

Short acting beta agonist (SABA)

Long acting muscarinic antagonist (LAMA)

Long acting beta agonist (LABA)

Inhaled corticosteroid (ICS)

LAMA / LABA combination (that is not Stiolto or Anoro)

LABA / ICS combination

LAMA / LABA / ICS combination

NSAIDs

Antihistamines

Opioids

Oral antibiotics

Antidiabetic Agents (not including insulin)

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
Insulin (basal or mealtime)

Methotrexate

Statins

Antihypertensives

Anticoagulants

Anti-psychotic/anti-depressives/anxiolytic

Oxygen therapy
Comorbidities/Symptoms

History of All-Cause Hospitalization

History of Emergency Department Visit

History of Hospitalization due to Respiratory Condition

Acute Myocardial Infarction

Angina Pectoris

Peripheral Vascular Disease

Heart Failure

Hypertension

Upper Respiratory Infection

Lower Respiratory Infection

Cardiac Arrhythmias

Cerebrovascular Disease

All Cancers (except nonmelanoma skin cancer)

Allergic Rhinitis

Chronic Sinusitis

Bronchiectasis

Pneumonia

Chronic Bronchitis

Exertional Breathlessness

Anxiety

Dementia

Depression

Osteoporosis

Charlson Deyo Comorbidity Index

Acute Liver Injury or Failure

Chronic Kidney Disease (without ESRD)

End Stage Renal Disease

Rheumatic Disease

Peptic Ulcer Disease

Gastroesophageal Reflux Disease

Type 1 Diabetes Mellitus

Type 2 Diabetes Mellitus

HIV/AIDS

Hemiplegia or Paraplegia

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Lifestyle

Smoking-related claim

Vaccination for Influenza

Vaccination for Pneumococcus
Respiratory Function Procedures/Tests

Pulmonary function tests

Six-minute walk test

Chest X-ray

High resolution chest CT
9.4
DATA SOURCES
The proposed study will utilize data from Truven MarketScan data (US).
The Truven MarketScan databases capture longitudinal, individual-level administrative 
claims data from the United States. The data available for the study includes three 
components of MarketScan: the Commercial Claims and Encounters (CCAE) Database, the 
Medicare Supplemental and Coordination of Benefits Database (MDCR), and the Medicaid 
Database. Patients in the databases include active employees, dependents, retirees, COBRA 
recipients, and Medicare or Medicaid enrollees. Data were drawn from large employers, 
health plans, and public organizations in the United States. The following tables of the 
MarketScan databases were available for analysis: Enrollment Detail, Inpatient Admissions, 
Inpatient Services, Outpatient Services, Outpatient Pharmaceutical Claims, and Long Term 
Care. These tables provide information on plan enrollment, healthcare utilization and 
expenditures, demographics, and integrated records for inpatient events, outpatient events, 
and pharmacy dispensings. Data are available from January 1, 2008 to March 31, 2018, and 
represent approximately 162 million patients.
9.5
STUDY SIZE
There are 14,751 new users of Olodaterol/Tiotropium Bromide or Umeclidinium/Vilanterol 
between 17 November 2015 and 31 March 2018 who satisfied the inclusion criteria. Among 
them, 3,889 initiated Olodaterol/Tiotropium Bromide and 10,862 initiated 
Umeclidinium/Vilanterol).
9.6
DATA MANAGEMENT
Dataset
The Truven Health MarketScan database is comprised of fully adjudicated and paid claims 
records of integrated longitudinal enrolment, inpatient, outpatient and drug data from 
multiple payors that has been standardized and de-identified prior to use for the analysis. The 
statistical analysis will be conducted using the 
 Evidence Platform.

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Drug Duration
Unless otherwise noted, drug event duration was calculated from the “Day’s Supply” field, 
and in cases where this field was 0, the duration was assumed to be 1 day. 
Handling of Missing Data
Missing data that occurs in covariates or descriptive variables will be classified as its own 
level. In addition, a feasibility assessment before beginning the analyses will be done, and 
variables with >75 % missing values will be excluded from all analyses, other than baseline 
characteristics. If a variable is left with only one level other than missing, the variable will be 
excluded completely from all analyses.
9.7
DATA ANALYSIS
9.7.1
Main analysis
For all analyses, variables will be reported as follows:

Continuous variables (e.g., age) will be presented as means (with standard deviation, 
SD) and/or medians (with interquartile range, IQR).

Categorical variables (e.g., sex) will be presented as absolute and relative frequencies.

All results will have two digits following the decimal point.
9.7.1.1
Descriptive Analysis
All variables specified in section 9.3.3 will be reported. For demographic and lifestyle 
variables, the value recorded on the cohort entry date will be reported, otherwise the most 
recent known value will be reported. Presence of comorbidities and use of concomitant 
medication use will be determined based whether they ever occurred within the 180-day 
baseline period preceding the index date. Differences in the confounder distributions were 
inspected for successful confounder balance of measured characteristics.
9.7.1.2
Rates and Risks

Rate of Discontinuation of Olodaterol/Tiotropium Bromide or
Umeclidinium/Vilanterol in the Pre-matched Cohort
Among the pre-matched cohort, rates of discontinuation of Olodaterol/Tiotropium Bromide 
or Umeclidinium/Vilanterol will be reported as the number of events divided by the number 
of person-years at risk.

Risk of Discontinuation of Olodaterol/Tiotropium Bromide or 
Umeclidinium/Vilanterol in the Pre-matched Cohort
Among the pre-matched cohort, risk (proportion of patients) of discontinuation of 
Olodaterol/Tiotropium Bromide or Umeclidinium/Vilanterol will be reported as the number 
of events divided by the number of eligible patients at cohort entry date. 

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
Discontinuation of Olodaterol/Tiotropium Bromide or Umeclidinium/Vilanterol in the 
Post-matched Cohort
Among the post-matched cohort, rates of discontinuation of Olodaterol/Tiotropium Bromide 
or Umeclidinium/Vilanterol will be reported as the number of events divided by the number 
of person-years at risk.

Discontinuation of Olodaterol/Tiotropium Bromide or Umeclidinium/Vilanterol in the 
Post-matched Cohort
Among the post-matched cohort, risk (proportion of patients) of discontinuation of 
Olodaterol/Tiotropium Bromide or Umeclidinium/Vilanterol will be reported as the number 
of events divided by the number of eligible patients at cohort entry date. 
9.7.1.3
Comparative Persistence

Relative Rate of Discontinuation of Olodaterol/Tiotropium Bromide vs 
Umeclidinium/Vilanterol in the Unmatched Cohort
Multivariable Cox proportional hazards models with all variables (except components of the 
Charlson Comorbidity index) in section 9.3.3. will be used to estimate the hazard ratios 
(HRs) and 95% CIs for Olodaterol/Tiotropium Bromide compared to patients treated with 
Umeclidinium/Vilanterol during follow-up for incident discontinuations, according to the 
following model:
h(t | Treatment, X1, … , Xn) = h(t0)*exp(β1*Treatment + β1*X2 + … + βn*Xn+1)
Where treatment can be 1=Stiolto or 0=Anoro and t = time to discontinuation

Relative Risk of Discontinuation of Olodaterol/Tiotropium Bromide vs 
Umeclidinium/Vilanterol in the Unmatched Cohort
Multivariable logistic regression will be used to assess relative risk of discontinuation and 
95% CIs for Olodaterol/Tiotropium Bromide compared to patients treated with 
Umeclidinium/Vilanterol during follow-up for incident discontinuations, according to the 
following model using all covariates (except components of the Charlson Comorbidity index) 
in section 9.3.3.:
Logit (Discontinuation=1 | Treatment, X1, X2, … , Xn) = β0 + β1*Treatment + β1*X2 + … + 
βn*Xn+1

Relative Rate of Discontinuation of Olodaterol/Tiotropium Bromide vs 
Umeclidinium/Vilanterol in the Matched Cohort
Cox proportional hazards models with treatment as the only independent variable will be 
used to estimate the hazard ratios (HRs) and 95% CIs for Olodaterol/Tiotropium Bromide 

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compared to patients treated with Umeclidinium/Vilanterol during follow-up for incident 
discontinuations, according to the following model:
h(t |Treatment, X) = h0(t)*exp(β1*Treatment)
Where treatment can be 1=Stiolto or 0=Anoro and t = time to discontinuation

Relative Risk of Discontinuation of Olodaterol/Tiotropium Bromide vs 
Umeclidinium/Vilanterol in the Matched Cohort
Logistic regression will be used to assess relative risk of discontinuation and 95% CIs for
Olodaterol/Tiotropium Bromide compared to patients treated with Umeclidinium/Vilanterol 
during follow-up for incident discontinuations, according to the following model:
Logit (Discontinuation=1 | Matched set) = β1*Treatment + stratum(i)
Where treatment can be 1=Stiolto or 0=Anoro and t = time to discontinuation
9.7.2
Sensitivity Analysis
Four sensitivity analyses will be conducted. For these analyses, in the interest of reducing the 
number of additional tables, only the descriptive statistics for the matched population (Annex 
Table 2), and primary results (Annex Tables 4 and 5) will be reported.
Two sensitivity analyses will be conducted to evaluate the robustness of the outcome 
definition:
1. Use of a 30-day Grace Period
Restrict the 60-day allowable grace period used to define the discontinuation outcome to 30
days to allow a gap of one month. This sensitivity analysis may be useful if the 60-day grace 
period is too lenient, as the usual day’s supply of Stiolto is 30 days.
2. Use of a 90-day Grace Period
Since neither the Olodaterol/Tiotropium Bromide or Umeclidinium/Vilanterol drug products 
are available as generic formulations, the relatively high price of these medications may lead 
some patients to space out their doses to greater than the recommended dosing schedule or 
use one puff instead of two to prolong their medication supply. Patients may also neglect to 
take their medications due to forgetfulness or because they become less symptomatic. Thus, 
we will also increase the 60-day allowable grace period used to define the discontinuation 
outcome, to 90 days.
Two sensitivity analyses will be conducted in an attempt to increase the sample size:
3. Start Patient Identification Period in 21 May 2015

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The primary identification period starts 180 days after Stiolto Respimat was approved by 
FDA for use in the US (21 May 2015) on 17 November 2015. This sensitivity cohort will 
start the patient identification period immediately upon FDA approval on 21 May 2015.
4. Do Not Exclude Patients with Diagnosis of ACOS from the Cohort
Patients in the primary analysis with diagnosis of asthma (regardless of whether or not they 
have COPD) will be excluded to restrict to patients with only COPD. It is possible that some 
patients with COPD may have a claim for asthma prior to their COPD diagnosis as part of 
their COPD diagnostic work-up, rather than an ongoing asthma diagnosis. Therefore, this 
sensitivity cohort will not exclude patients with a previous diagnosis of asthma. Note that 
patients with only asthma but no COPD will still be excluded from this cohort.
9.8
QUALITY CONTROL
will build measures for cohort inclusion, outcomes and covariates. Some of the 
measure algorithms will be based on those collaboratively developed for another respiratory-
related protocol with clinical input from external pulmonology experts. When available, 
algorithms that have been validated in administrative databases will be used. When validated 
algorithms are not available, coding criteria will be based on clinical input and through 
searches of medical claim coding systems.
All measures created, cohorts developed, statistical analyses implemented, and tables 
completed will undergo quality control review by at least 1 additional analyst or scientist 
under the supervision of the senior scientist.
This protocol will be strictly followed in the study. However, measure definitions may 
undergo modification if determined to be scientifically sensible. All changes to this protocol 
will be documented in protocol amendments.
The study protocol has been written following the Code of Conduct by the European Network 
of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) [R15-4870] that 
provides a set of rules and principles for post-authorisation studies with regard to the best 
practices and transparency, thereby promoting scientific independence of such studies. The 
study will be registered to the ENCePP’s E-register and the results will also be published on 
the same site.
The study protocol also follows the key elements of the Guideline for Good 
Pharmacoepidemiology Practices (GPP) by International Society for Pharmacoepidemiology 
[R11-4318], and the recent draft Guidance for Industry and FDA Staff “Best Practices for 
Conducting and Reporting Pharmacoepidemiologic Safety Studies Using Electronic 
Healthcare Data Sets” [R15-4859].
Quality controls include checks for the validity and logical content of codes and checks for 
missing values and variables. In order to control for potential inconsistencies and errors, all 

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variables will be tabulated. In addition, the distribution of each variable will be examined. 
Extreme observations with values larger than ± 3 standard deviations (SD) will be examined 
as potential outliers and consequently excluded from the dataset.
9.9
LIMITATIONS OF THE RESEARCH METHODS
This study will be conducted using data from insurance claims and is subject to certain 
limitations. One limitation is that these are based on a large, non-random convenience 
sample, which may contain biases or lack generalizability to other populations. Data also 
come mostly from large employers, and although the database also includes a large amount of 
data from health plans, data from medium and small firms may be underrepresented.
Additionally, the MarketScan database also poses some limitations inherent to administrative 
claims data. Electronic outpatient pharmacy dispensing records are considered accurate 
because pharmacists fill prescriptions with little room for interpretation and are reimbursed 
by insurers on the basis of detailed, complete, and accurate claims submitted electronically 
(Stergachi 1988, Levy 2003). Pharmacy dispensing information is usually seen as the gold 
standard of drug exposure information compared to self-reported information (West 1995) or 
prescribing records in outpatient medical records (West 1994). However, drugs used during 
hospital stays are not recorded in this data source. Claims data are subject to certain 
limitations. The presence of a claim for a filled prescription does not indicate that the 
medication was consumed or that it was taken as prescribed, and any medications filled over-
the-counter or provided as samples by the physician will not be observed in the claims data. 
Furthermore, as with all claims-based analyses, study results may not be generalizable to the 
overall population as patients who have commercial health insurance may be different from 
those with non-commercial or without (commercial) health insurance. Finally, patients are 
required not to have a claim for Olodaterol/Tiotropium Bromide or Umeclidinium/Vilanterol
during the baseline period, but use of these medications may have occurred prior to the start 
of the baseline period.
In the analytical portion of this protocol, propensity score matching will be used to estimate 
relative persistence between the two exposures of interest. Various covariates are included in 
the prediction model of the propensity scores, but as with all non-interventional studies, the 
potential for unmeasured and residual confounding cannot be ruled out. 
9.10
OTHER ASPECTS
Not applicable.
9.11
SUBJECTS
9.11.1
Cases
See Section 9.2.2.

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9.11.2
Controls
Not applicable.
9.12
BIAS
In principle, electronic outpatient pharmacy dispensing records are considered accurate 
because pharmacists fill prescriptions with little room for interpretation, and are reimbursed 
by insurers based on detailed, complete, and accurate claims submitted electronically (Levy 
2003; Stergachis 1988). Pharmacy dispensing information is usually seen as the gold 
standard of drug exposure information compared to self-reported information or prescribing 
records in outpatient medical records.
The population-based nature of the database will avoid selection bias and ensure external 
validity. Confounding bias through observable covariates will be controlled for by the design, 
which includes propensity score matching.
To minimize misclassification of the recorded patient characteristics, previously validated 
algorithms or code lists will be used whenever available. Code lists will be reviewed by the 
qualified medical reviewers prior to implementation. Basic plausibility checks will be 
implemented for continuous variables (e.g. age, etc.).
While this analysis is designed to assess non-persistence as an endpoint. Whether or not the 
patient actually complied with the prescription cannot be known. For example, a patient may 
fill a 30-day prescription, but may only comply with the medication for a few days before 
truly discontinuing, leading to an overestimation of persistence when using claims data. 
Furthermore, even if a patient did comply, they may administer the doses incorrectly. 
The covariates chosen in section 9.3.3. are hypothesized to be confounders in the relationship 
between exposure and outcome. The range and quantity of variables selected are aimed to 
make the two exposure groups more comparable so that the interpretation of effect estimates 
may be more meaningful. 
10.
PROTECTION OF HUMAN SUBJECTS
As the present study is a non-interventional retrospective cohort study, the most significant 
potential impact on the participants would be the potential for individual identification and 
loss of privacy. Patients in the MarketScan dataset are de-identified, such that names are not 
linked to patient IDs. Thus, the risks to participants are expected to be minimal.

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11.
MANAGEMENT AND REPORTING OF ADVERSE 
EVENTS/ADVERSE REACTIONS
Data is anonymized and extracted, analyzed, validated and reported in aggregate. 
There is no potential that any employee of BI or agent working on behalf of BI will access 
individual patient data in which the patient may be identified during data compilation, data 
reporting or data analysis.
Based on current guidelines from the International Society for Pharmacoepidemiology 
[R11-4318] and the EMA [R13-1970], non-interventional studies such as the one described in 
this protocol, conducted using health care records, do not require expedited reporting of 
suspected adverse events/reactions. Specifically, as stated in section VI.C.1.2.1 of Guideline 
on Good Pharmacovigilance Practices (GVP), Module VI – Management and Reporting of 
Adverse Reactions to Medicinal Products, for non-interventional study designs, which are 
based on use of secondary data, reporting of adverse reactions is not required.
12.
PLANS FOR DISSEMINATING AND COMMUNICATING 
STUDY RESULTS
The results of the study will primarily serve internal decision making for future studies on 
comparative effectiveness. These baseline results will be published as an abstract and/or 
manuscript. Conference and Journal to be decided.

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13.
REFERENCES
13.1
PUBLISHED REFERENCES
P04-12446
Dalby R, Spallek M, Voshaar T. A review of the development of Respimat 
Soft Mist Inhaler. Int J Pharm. 2004 Sep 28;283(1–2):1–9.
P13-03077
West SL, Strom BL, Freundlich B, Normand E, Koch G, Savitz DA. 
Completeness of prescription recording in outpatient medical records from a 
health maintenance organization. Journal of clinical epidemiology. 
1994;47(2):165–71.
P13-03078
West SL, Savitz DA, Koch G, Strom BL, Guess HA, Hartzema A. Recall 
accuracy for prescription medications: self-report compared with database 
information. Am J Epidemiol. 1995 Nov 15;142(10):1103–12
P19-09366
Braido F, Chrystyn H, Baiardini I, Bosnic-Anticevich S, van der Molen T, 
Dandurand RJ, et al. “Trying, But Failing” - The Role of Inhaler Technique 
and Mode of Delivery in Respiratory Medication Adherence. J Allergy Clin 
Immunol Pract. 2016 Oct;4(5):823–32.
P19-09661
Barnes PJ, Burney PGJ, Silverman EK, Celli BR, Vestbo J, Wedzicha JA, et 
al. Chronic obstructive pulmonary disease. Nat Rev Dis Primers. 2015 Dec 
3;1:15076.
R11-4318
Guidelines for Good Pharmacoepidemiology Practices (GPP) (revision 2: 
April 2007). http://www.pharmacoepi.org/resources/guidelines_08027.cfm 
(access date: 13 September 2011) ; Bethesda: International Society for 
Pharmacoepidemiology (ISPE) (2007)
R13-1970
European Medicines Agency (EMA), Heads of Medicines Agencies (HMA)
Guideline on good pharmacovigilance practices (GVP): module VI -
management and reporting of adverse reactions to medicinal products (22 June 
2012,EMA/873138/2011).http://www.ema.europa.eu/docs/en_GB/document_l
ibrary/Scientific_guideline/2012/0 6/WC500129135.pdf (access date: 7 May 
2013) ; European Medicines Agency (EMA), Heads of Medicines Agencies 
(HMA) (2012) 
R13-2804
Stergachis AS. Record linkage studies for postmarketing drug surveillance: 
data quality and validity considerations. Drug Intell Clin Pharm. 1988 
Feb;22(2):157–61.
R13-2806
Levy AR, O’Brien BJ, Sellors C, Grootendorst P, Willison D. Coding 
accuracy of administrative drug claims in the Ontario Drug Benefit database. 
Can J Clin Pharmacol. 2003 Summer;10(2):67–71.
R15-4859 
Guidance for industry and FDA staff: best practices for conducting and 
reporting pharmacoepidemiologic safety studies using electronic healthcare 
data (May 2013, drug safety). 
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformati
on/guida nces/ucm243537.pdf (access date: 28 August 2015) ; U.S. 
Department of Health and Human Services, Food and Drug Administration, 

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Center for Drug Evaluation and Research (CDER), Center for Biologics 
Evaluation and Research (CBER) (2013)
R15-4870
European Medicines Agency (EMA)The ENCePP code of conduct for 
scientific independence and transparency in the conduct of 
pharmacoepidemiological and pharmacovigilance studies (London, 21 
November 2011, EMA/929209/2011).
http://www.encepp.eu/code_of_conduct/documents/CodeofConduct_Rev2.pdf 
(access date: 28 August 2015) ; London: European Medicines Agency (EMA), 
European Network of Centres for Pharmacoepidemiology and 
Pharmacovigilance (ENCePP) (2011)
R18-2599
Austin PC. An Introduction to Propensity Score Methods for Reducing the 
Effects of Confounding in Observational Studies. Multivariate behavioral 
research. 2011 May;46(3):399–424.
R18-2765
Makela MJ, Backer V, Hedegaard M, Larsson K. Adherence to inhaled 
therapies, health outcomes and costs in patients with asthma and COPD. 
Respir Med. 2013 Oct;107(10):1481–90.
R19-3352
Ghosh S, Ohar JA, Drummond MB. Peak Inspiratory Flow Rate in Chronic 
Obstructive Pulmonary Disease: Implications for Dry Powder Inhalers. Journal 
of Aerosol Medicine and Pulmonary Drug Delivery. 2017 Sep 21;30(6):381–7
R19-3355
Truven Health MarketScan Research Databases. Commercial claims and 
encounters Medicare Supplemental and Coordination of Benefits [Internet]. 
2015. Available from: https://www.entnet.org/content/marketscan-
commerical-claims-and-encountersmarketscan-medicare-supplemental-and-
coordination.
R19-3476
Strom BL. Overview of automated databases in pharmacoepidemiology. In a 
Book Strom BL, Kimmel SE, Hennessy S, editors. Pharmacoepidemiology. 
Hoboken: John Wiley & Sons, Incorporated.
13.2
UNPUBLISHED REFERENCES
Not Applicable

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ANNEX 1. LIST OF STAND-ALONE DOCUMENTS
Number
Document 
Reference 
Number
Date
Title
1
Annex 1
19 April 2019
List of stand-alone documents
2
Annex 2
19 April 2019
ENCEPP Checklist for study protocols
3
Annex 3
19 April 2019
List of medication measure definitions
4
Annex 4
19 April 2019
List of comorbidity and other measure 
definitions
5
Annex 5
19 April 2019
Table shells and proposed figures

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ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS
Not Applicable

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ANNEX 3. LIST OF MEDICATION MEASURE DEFINITIONS
Name
Components
Corticosteroids
Betamethasone, *beclometasone (beclomethasone), cortisone acetate, dexamethasone, hydrocortisone, 
methylprednisolone, prednisolone, prednisone, triamcinolone, deflazacort, fludrocortisone
Short Acting Beta Agonist 
Albuterol, metaproterenol, levalbuterol, pirbuterol, terbutaline
Short Acting Muscarinic 
Antagonist
Ipratropium
Long Acting Muscarinic 
Antagonist (LAMA)
Umeclidinium, glycopyrrolate, tiotropium, aclidinium, Incruse, Seebri, Spiriva, Tudorza
Long Acting Beta Agonist 
(LABA)
Indacaterol, arformoterol, formoterol, salmeterol, olodaterol, Arcapta, Atimos, Brovana, Perforomist, Serevent, 
Striverdi, Foradil
Inhaled Corticosteroids
Flunisolide, budesonide, mometasone, ciclesonide, fluticasone, beclomethasone, Aerobid, Aerospan, Alvesco, 
Armonair, Arnuity, Asmanex, Azmacort, Flixotide, Flovent, Pulmicort, Qvar
LAMA / LABA combination
indacaterol/glycopyrrolate, glycopyrrolate/formoterol, Utibron, Bevespi
LABA / ICS combination
Fluticasone/vilanterol, budesonide/formoterol, fluticasone/salmeterol, mometasone/formoterol, Advair, Symbicort, 
Breo, Dulera
LAMA / LABA / ICS 
combination
Fluticasone/umeclidinium/vilanterol, Trelegy
NSAIDs
Phenylbutazone, sulindac, tolmetin, diclofenac, etodolac, ketorolac, piroxicam, meloxicam, ibuprofen, naproxen, 
ketoprofen, fenoprofen, suprofen, flurbiprofen, oxaprozin, mefanamic acid, meclofenamic acid, celecoxib, rofecoxib, 
valdecoxib, nabumetone, glucosamine sulfate

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Opioids
Morphine, hydromorphone, oxycodone, dihydrocodeine, fentanyl, pentazocine, buprenorphine, butorphanol, nalbuphine, 
tramadol, tapentadol, hydrocodone, codeine
Antihistamines/Antiallergenic
s
Diphenhydramine, clemastine, carbinoxamine, doxylamine, brompheniramine, dexchlorpheniramine, pheniramine, 
tripelennamine, promethazine, thiethylperazine, cyclizine, chlorcyclizine, cetirizine, cyproheptadine, phenindamine, 
triprolidine, azatadine, astemizole, terfenadine, loratadine, ketotifen, azelastine, levocabastine, epinastine, fexofenadine, 
desloratadine, ephedrine, phenylephrine, oxymetazoline, xylometazoline, naphazoline, nedocromil
Oral Antibiotics
Demeclocycline, doxycycline, chlortetracycline, oxytetracycline, tetracycline, minocycline, tigecycline, 
chloramphenicol, ampicillin, carbenicillin, amoxicillin, bacampicillin, mezlocillin, piperacillin, ticarcillin, dicloxacillin, 
cloxacillin, oxacillin, flucloxacillin, nafcillin, sulbactam, tazobactam, cefazolin, cefadroxil, cefoxitin, cefuroxime, 
cefamandole, cefaclor, cefotetan, loracarbef, cefprozil, cefotaxime, ceftazidime, ceftriaxone, ceftizoxime, cefixime, 
cefoperazone, cefpodoxime, ceftibuten, cefdinir, cefditoren, cefepime, aztreonam, meropenem, ertapenem, doripenem, 
trimethoprim, sulfapyridine, sulfanilamide, sulfathiazole, sulfamethoxazole, sulfadiazine, sulfamerazine, sulfapyridine, 
sulfanilamide, sulfathiazole, sulfadiazine, sulfamethoxazole, sulfachlorpyridazine, sulfamerazine, sulfacetamide, 
erythromycin, troleandomycin, clarithromycin, azithromycin, dirithromycin, telithromycin, clindamycin, lincomycin, 
quinupristin/dalfopristin, streptomycin, tobramycin, gentamicin, kanamycin, neomycin, amikacin, netilmicin, 
paromomycin, ofloxacin, ciprofloxacin, enoxacin, norfloxacin, lomefloxacin, sparfloxacin, grepafloxacin, levofloxacin, 
trovafloxacin, moxifloxacin, gemifloxacin, gatifloxacin, delafloxacin, cinoxacin, vancomycin, telavancin, dalbavancin, 
oritavancin, colistin, polymyxin b, metronidazole, tinidazole, nitrofurantoin, fosfomycin, spectinomycin, methenamine, 
mandelic acid, linezolid, daptomycin, bacitracin, tedizolid, novobiocin
Diabetes Mellitus Medications
Sulfonylureas (chlorpropamide, tolbutamide, tolazamide, glipizide, gliquidone, acetohexamide), biguanides (metformin), 
thiazolidinediones (troglitazone, rosiglitazone, pioglitazone), alpha-glucosidase inhibitors (acarbose, miglitol), 
meglitinides (repaglinide, nateglinide, mitiglinide), DPP-4 inhibitors (gitagliptin, vildagliptin, saxagliptin, alogliptin, 
linagliptin), GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide), SGLT-2 
inhibitors (dapagliflozin, canagliflozin, empagliflozin)
Insulin
Rapid-acting insulin, short-acting insulin, intermediate-acting insulin, long-acting insulin
Methotrexate
Methotrexate
Anticoagulants
Vitamin K antagonists (phenindione, warfarin), heparins (heparin, antithrombin III, dalteparin, enoxaparin, danaparoid, 
tinzaparin), platelet aggregation inhibitors (clopidogrel, ticlopidine, dipyridamole, epoprostenol, iloprost, abciximab, 
eptifibatide, tirofiban, treprostinil, prasugrel, cilostazol, ticagrelor, cangrelor, vorapaxar, selexipag), direct thrombin 

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inhibitors (desirudin, lepirudin, argatroban, bivalirudin, dabigatran etexilate), direct factor Xa inhibitors (rivaroxaban, 
apixaban, edoxaban), anticoagulant enzymes (anistreplase, urokinase, reteplase, drotrecogin alfa, tenecteplase), 
defibrotide, fondaparinux)
Statins
Atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin, pitavastatin, cerivastatin
Antihypertensives
Angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel 
blockers, diuretics, alpha-blockers, alpha-beta blockers, vasiodilators
Anti-psychotics/
Anti-depressives/Anxiolytics
Desipramine, clomipramine, trimipramine, amitriptyline, nortriptyline, protriptyline, doxepin, amoxapine, maprotiline, 
fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine, escitalopram, isocarboxazid, phenelzine, tranylcypromine, 
tryptophan, trazodone, nefazodone, minaprine, mirtazapine, bupropion, venlafaxine, milnacipran, duloxetine, 
desvenlafaxine, vilazodone, vortioxetine, selegiline, chlorpromazine, promazine, acepromazine, triflupromazine, 
fluphenazine, perphenazine, prochlorperazine, trifluoperazine, thioridazine, mesoridazine, pipotiazine, haloperidol, 
droperidol, molindone, ziprasidone, lurasidone, thiothixene, pimozide, loxapine, clozapine, olanzapine, quetiapine, 
asenapine, lithium, risperidone, aripiprazole, paliperidone, iloperidone, cariprazine, brexpiprazole, pimavanserin, 
diazepam, chlordiazepoxide, oxazepam, lorazepam, clobazam, alprazolam, halazepam, hydroxyzine, meprobamate, 
buspirone
Oxygen Therapy
Oxygen

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ANNEX 4. LIST OF COMORBIDITY, SYMPTOMS AND OTHER MEASURE DEFINITIONS
Name
Definition
Comorbidities/Symptoms
History of All-Cause 
Hospitalization
All inpatient events
History of 
Emergency 
Department Visit
1 Outpatient

Place of Service is any of:
o
Emergency Room - Hospital
o
Urgent Care Facility
History of 
Hospitalization due to 
Respiratory 
Condition
1 Inpatient
Diagnosis Code (Principal), ICD-9 is any of: { “415.1”, “415.11”, “415.12”, “415.13”, “415.19”, “465”, “465.0”, “465.8”, 
“465.9”, “466”, “466.0”, “466.1”, “466.11”, “466.19”, “480.0”, “480.1”, “480.2”, “480.3”, “480.8”, “480.9”, “481”, “482.0”, 
“482.1”, “482.2”, “482.30”, “482.31”, “482.32”, “482.39”, “482.40”, “482.41”, “482.42”, “483.0”, “483.1”, “483.8”, “484.1”, 
“484.3”, “484.5”, “484.6”, “484.7”, “484.8”, “486”, “487.0”, “488.01”, “488.11”, “488.81”, “490”, “491”, “491.0”, “491.1”, 
“491.2”, “491.20”, “491.21”, “491.22”, “491.8”, “491.9”, “492.0”, “492.8”, “493.0”, “493.00”, “493.01”, “493.02”, “493.1”, 
“493.10”, “493.11”, “493.12”, “496”, “515”, “516.3”, “516.30”, “516.31”, “516.32”, “516.8”, “516.9”, “518.81”, “518.83”, 
“518.84” }
Diagnosis Code (Principal), ICD-10 is any of: { “A01.03”, “A02.22”,  “A37.01”,  “A37.11”, “A37.81”,  “A37.91”, “A40.3”, 
“A50.04”, “A54.84”, “B01.2”, “B05.2”, “B06.81”, “B77.81”, “B95.3”, “B96.0”, “B96.1”, “I26.9”, “I26.90”, “I26.92”, “I26.99”, 
“J06”, “J06.0”, “J06.9”, “J09.X1”, “J09.X2”, “J10.0”, “J10.00”, “J10.01”, “J10.08”, “J10.1”, “J11.0”, “J11.00”, “J11.08”, “J11.1”, 
“J12”, “J12.0”, “J12.1”, “J12.2”, “J12.3”, “J12.8”, “J12.81”, “J12.89”, “J12.9”, “J13”, “J14”, “J15”, “J15.0”, “J15.1”, “J15.2”, 
“J15.20”, “J15.21”, “J15.211”, “J15.212”, “J15.29”, “J15.3”, “J15.4”, “J15.5”, “J15.6”, “J15.7”, “J15.8”, “J15.9”, “J16”, “J16.0”, 
“J16.8”, “J17”, “J18”, “J18.0”, “J18.1”, “J18.2”, “J18.8”, “J18.9”, “J20”, “J20.0”, “J20.1”, “J20.2”, “J20.3”, “J20.4”, “J20.5”, 
“J20.6”, “J20.7”, “J20.8”, “J20.9”, “J21.0”, “J22”, “J39”, “J39.3”, “J39.8”, “J39.9”, “J40”, “J41”, “J41.0”, “J41.1”, “J41.8”, “J42”, 
“J43”, “J43.0”, “J43.1”, “J43.2”, “J43.8”, “J43.9”, “J44.0”, “J45”, “J45.2”, “J45.20”, “J45.21”, “J45.22”, “J45.3”, “J45.30”,
“J45.31”, “J45.32”, “J45.4”, “J45.40”, “J45.41”, “J45.42”, “J45.5”, “J45.50”, “J45.51”, “J45.52”, “J45.9”, “J45.90”, “J45.901”, 
“J45.902”, “J45.909”, “J45.99”, “J45.991”, “J45.998”, “J47.0”, “J68.0”, “J84.11”, “J84.111”, “J84.116”, “J84.117”, “J84.2”, 

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“J85.1”, "J96", "J96.9", "J96.90", "J96.91", "J96.92", “J96.0”, “J96.00”, “J96.01”, “J96.02”, “J96.1”, “J96.10”, “J96.11”, 
“J96.12”, “J96.2”, “J96.20”, “J96.21”, “J96.22”, “J98”, “J98.2”, “J98.3”, “J98.8” }
Acute Myocardial 
Infarction
1 Inpatient or 1 Outpatient
Diagnosis Code (Position 1), ICD-9 is any of: { “410”, “410.0”, “410.00”, “410.01”, “410.1”, “410.10”, “410.11”, “410.2”, 
“410.20”, “410.21”, “410.3”, “410.30”, “410.31”, “410.4”, “410.40”, “410.41”, “410.5”, “410.50”, “410.51”, “410.6”, “410.60”,
“410.61”, “410.7”, “410.70”, “410.71”, “410.8”, “410.80”, “410.81”, “410.9”, “410.90”, “410.91” }
Diagnosis Code (Principal), ICD-10 is any of: { “I21.09”, “I21.11”, “I21.19”, “I21.29”, “I21.3”, “I21.4”, “I22.0”, “I22.1”, 
“I22.2”, “I22.8”, “I22.9” }
Angina Pectoris
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “413”, “413.0”, “413.1”, “413.9” }
Diagnosis Code (Any Position), ICD-10 is any of: { “I20.1”, “I20.8”, “I20.9” }
Peripheral Vascular 
Disease
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “440”, “440.0”, “440.1”, “440.2”, “440.20”, “440.21”, “440.22”, “440.23”, 
“440.24”, “440.29”, “440.3”, “440.30”, “440.31”, “440.32”, “440.4”, “440.8”, “440.9”, “441”, “441.0”, “441.00”, “441.01”, 
“441.02”, “441.03”, “441.1”, “441.2”, “441.3”, “441.4”, “441.5”, “441.6”, “441.7”, “441.9”, “442”, “442.0”, “442.1”, “442.2”,
“442.3”, “442.8”, “442.81”, “442.82”, “442.83”, “442.84”, “442.89”, “442.9”, “443.1”, “443.2”, “443.21”, “443.22”, “443.23”, 
“443.24”, “443.29”, “443.8”, “443.81”, “443.82”, “443.89”, “443.9”, “447.1”, “785.4”, “38.13”, “38.14”, “38.16”, “38.18”, 
“38.33”, “38.34”, “38.36”, “38.38”, “38.43”, “38.44”, “38.46”, “38.48”, “39.22”, “39.23”, “39.24”, “39.25”, “39.26”, “39.29” }
Diagnosis Code (Any Position), ICD-10 is any of: { “I70.0”, “I70.1”, “I70.209”, “I70.219”, “I70.229”, “I70.25”, “I70.269”, 
“I70.299”, “I70.399”, “I70.499”, “I70.599”, “I70.8”, “I70.90”, “I70.91”, “I70.92”, “I71.00”, “I71.01”, “I71.02”, “I71.03”, “I71.1”,
“I71.2”, “I71.3”, “I71.4”, “I71.5”, “I71.6”, “I71.8”, “I71.9”, “I72.0”, “I72.1”, “I72.2”, “I72.3”, “I72.4”, “I72.8”, “I72.9”, “I73.1”, 
“I73.81”, “I73.89”, “I73.9”, “I77.1”, “I77.71”, “I77.72”, “I77.73”, “I77.74”, “I77.79”, “I79.8”, “I96” }

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Heart Failure
1 Inpatient
Diagnosis Code (Any Position), ICD-9 is any of: { “428”, “428.0”, “428.1”, “428.2”, “428.20”, “428.21”, “428.22”, 
“428.23”, “428.3”, “428.30”, “428.31”, “428.32”, “428.33”, “428.4”, “428.40”, “428.41”, “428.42”, “428.43”, “428.9” 
}
Diagnosis Code (Any Position), ICD-10 is any of: { “I50”, “I50.9”, “I50.2”, “I50.20”, “I50.21”, “I50.22”, “I50.23”, 
“I50.3”, “I50.30”, “I50.31”, “I50.32”, “I50.33”, “I50.4”, “I50.40”, “I50.41”, “I50.42”, “I50.43” }
Hypertension
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “401”, “401.0”, “401.1”, “401.9”, “402”, “402.0”, “402.00”, 
“402.1”, “402.10”, “402.9”, “402.90”, “403”, “403.0”, “403.00”, “403.01”, “403.1”, “403.10”, “403.11”, “403.9”, 
“403.90”, “403.91”, “404”, “404.0”, “404.00”, “404.01”, “404.02”, “404.03”, “404.1”, “404.10”, “404.11”, “404.12”, 
“404.13”, “404.9”, “404.90”, “404.91”, “404.92”, “404.93”, “405”, “405.0”, “405.01”, “405.09”, “405.1”, “405.11”, 
“405.19”, “405.9”, “405.91”, “405.99” }
Diagnosis Code (Any Position), ICD-10 is any of: { “I10”, “I11.9”, “I12.0”, “I12.9”, “I13.0”, “I13.10”, “I13.11”, 
“I13.2”, “I15.0”, “I15.8” }
Upper Respiratory 
Infection (with no 
sinusitis)
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “034”, “034.0”, “034.1”, “460”, “461”, “461.0”, “461.1”, “461.2”, 
“461.3”, “461.8”, “461.9”, “462”, “463”, “464”, “464.0”, “464.00”, “464.01”, “464.1”, “464.10”, “464.11”, “464.2”, 
“464.20”, “464.21”, “464.3”, “464.30”, “464.31”, “464.4”, “464.5”, “464.50”, “464.51”, “465”, “465.0”, “465.8”, 
“465.9”, “487”, “487.1”, “487.8” }
Diagnosis Code (Any Position), ICD-10 is any of: { “J03.00”, “J03.01”, “A38”, “A38.8”, “A38.9”, “J00”, “J01”, 
“J01.9”, “J01.90”, “J01.8”, “J01.80”, “J01.0”, “J01.00”, “J01.01”, “J32.0”, “J01.1”, “J01.10”, “J01.11”, “J32.1”, 
“J01.2”, “J01.20”, “J01.21”, “J32.2”, “J01.3”, “J01.30”, “J01.31”, “J32.3”, “J02”, “J02.8”, “J02.9”, “J04”, “J04.0”, 
“J05”, “J05.0”, “J04.1”, “J04.10”, “J04.11”, “J04.2”, “J05.1”, “J05.10”, “J05.11”, “J04.3”, “J04.30”, “J04.31”, “J06”, 
“J06.9”, “J11.89”, “J11.8”, “J11.1”, “J11”, “J10.89”, “J10.8”, “J10.1”, “J10.00”, “J10.0”, “J10”, “J09.X2”, “J09.X9”, 

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“J09.X”, “J09” }
Lower Respiratory 
Infection
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “466”, “466.0”, “466.1”, “466.11”, “466.19” }
Diagnosis Code (Any Position), ICD-10 is any of: { “J20.9”, “J21.0”, “J21.8”, “J22” }
Cardiac Arrhythmias
1 Inpatient or 1 Outpatient
Diagnosis Code (Principal), ICD-9 is any of: { “427”, “427.0”, “427.1”, “427.2”, “427.3”, “427.31”, “427.32”, 
“427.4”, “427.41”, “427.42”, “427.5”, “427.6”, “427.60”, “427.61”, “427.69”, “427.8”, “427.81”, “427.89”, “427.9” }
Diagnosis Code (Position 1), ICD-10 is any of: { “I46.9”, “I47.1”, “I47.2”, “I47.9”, “I48.91”, “I48.92”, “I49.01”, 
“I49.02”, “I49.1”, “I49.3”, “I49.40”, “I49.49”, “I49.5”, “I49.8”, “I49.9”, “R00.1” }
Cerebrovascular 
Disease
1 Inpatient
Diagnosis Code (Any Position), ICD-9 is any of: { “430”, “431”, “432”, “432.0”, “432.1”, “432.9”, “433”, “433.0”, 
“433.01”, “433.1”, “433.11”, “433.2”, “433.21”, “433.3”, “433.31”, “433.8”, “433.81”, “433.9”, “433.91”, “434”, 
“434.0”, “434.01”, “434.1”, “434.11”, “434.9”, “434.90”, “434.91”, “435”, “435.8”, “435.9”, “436” }
Diagnosis Code (Any Position), ICD-10 is any of: { “G45”, “G45.8”, “G45.9”, “I60”, “I60.0”, “I60.00”, “I60.01”, 
“I60.02”, “I60.1”, “I60.10”, “I60.11”, “I60.12”, “I60.2”, “I60.20”, “I60.21”, “I60.22”, “I60.3”, “I60.30”, “I60.31”, 
“I60.32”, “I60.4”, “I60.5”, “I60.50”, “I60.51”, “I60.52”, “I60.6”, “I60.7”, “I60.8”, “I60.9”, “I61”, “I61.0”, “I61.1”, 
“I61.2”, “I61.3”, “I61.4”, “I61.5”, “I61.6”, “I61.8”, “I61.9”, “I62”, “I62.0”, “I62.00”, “I62.01”, “I62.02”, “I62.03”, 
“I62.1”, “I62.9”, “I63”, “I63.0”, “I63.00”, “I63.01”, “I63.011”, “I63.012”, “I63.019”, “I63.02”, “I63.03”, “I63.031”, 
“I63.032”, “I63.039”, “I63.09”, “I63.1”, “I63.10”, “I63.11”, “I63.111”, “I63.112”, “I63.119”, “I63.12”, “I63.13”, 
“I63.131”, “I63.132”, “I63.139”, “I63.19”, “I63.2”, “I63.20”, “I63.21”, “I63.211”, “I63.212”, “I63.219”, “I63.22”, 
“I63.23”, “I63.231”, “I63.232”, “I63.239”, “I63.29”, “I63.3”, “I63.30”, “I63.31”, “I63.311”, “I63.312”, “I63.319”, 
“I63.32”, “I63.321”, “I63.322”, “I63.329”, “I63.33”, “I63.331”, “I63.332”, “I63.339”, “I63.34”, “I63.341”, “I63.342”, 
“I63.349”, “I63.39”, “I63.4”, “I63.40”, “I63.41”, “I63.411”, “I63.412”, “I63.419”, “I63.42”, “I63.421”, “I63.422”, 

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“I63.429”, “I63.43”, “I63.431”, “I63.432”, “I63.439”, “I63.44”, “I63.441”, “I63.442”, “I63.449”, “I63.49”, “I63.5”, 
“I63.50”, “I63.51”, “I63.511”, “I63.512”, “I63.519”, “I63.52”, “I63.521”, “I63.522”, “I63.529”, “I63.53”, “I63.531”, 
“I63.532”, “I63.539”, “I63.54”, “I63.541”, “I63.542”, “I63.549”, “I63.59”, “I63.6”, “I63.8”, “I63.9”, “I65”, “I65.0”, 
“I65.01”, “I65.02”, “I65.03”, “I65.09”, “I65.1”, “I65.2”, “I65.21”, “I65.22”, “I65.23”, “I65.29”, “I65.8”, “I65.9”, 
“I66”, “I66.0”, “I66.01”, “I66.02”, “I66.03”, “I66.09”, “I66.1”, “I66.11”, “I66.12”, “I66.13”, “I66.19”, “I66.2”, 
“I66.21”, “I66.22”, “I66.23”, “I66.29”, “I66.3”, “I66.8”, “I66.9” }
All Cancers (except 
nonmelanoma skin 
cancer)
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “140”, “140.0”, “140.1”, “140.3”, “140.4”, “140.5”, “140.6”, 
“140.8”, “140.9”, “141”, “141.0”, “141.1”, “141.2”, “141.3”, “141.4”, “141.5”, “141.6”, “141.8”, “141.9”, “142”, 
“142.0”, “142.1”, “142.2”, “142.8”, “142.9”, “143”, “143.0”, “143.1”, “143.8”, “143.9”, “144”, “144.0”, “144.1”, 
“144.8”, “144.9”, “145”, “145.0”, “145.1”, “145.2”, “145.3”, “145.4”, “145.5”, “145.6”, “145.8”, “145.9”, “146”, 
“146.0”, “146.1”, “146.2”, “146.3”, “146.4”, “146.5”, “146.6”, “146.7”, “146.8”, “146.9”, “147”, “147.0”, “147.1”, 
“147.2”, “147.3”, “147.8”, “147.9”, “148”, “148.0”, “148.1”, “148.2”, “148.3”, “148.8”, “148.9”, “149”, “149.0”, 
“149.1”, “149.8”, “149.9”, “150”, “150.0”, “150.1”, “150.2”, “150.3”, “150.4”, “150.5”, “150.8”, “150.9”, “151”, 
“151.0”, “151.1”, “151.2”, “151.3”, “151.4”, “151.5”, “151.6”, “151.8”, “151.9”, “152”, “152.0”, “152.1”, “152.2”, 
“152.3”, “152.8”, “152.9”, “153”, “153.0”, “153.1”, “153.2”, “153.3”, “153.4”, “153.5”, “153.6”, “153.7”, “153.8”, 
“153.9”, “154”, “154.0”, “154.1”, “154.2”, “154.3”, “154.8”, “155”, “155.0”, “155.1”, “155.2”, “156”, “156.0”, 
“156.1”, “156.2”, “156.8”, “156.9”, “157”, “157.0”, “157.1”, “157.2”, “157.3”, “157.4”, “157.8”, “157.9”, “158”, 
“158.0”, “158.8”, “158.9”, “159”, “159.0”, “159.1”, “159.8”, “159.9”, “160”, “160.0”, “160.1”, “160.2”, “160.3”, 
“160.4”, “160.5”, “160.8”, “160.9”, “161”, “161.0”, “161.1”, “161.2”, “161.3”, “161.8”, “161.9”, “162”, “162.0”, 
“162.2”, “162.3”, “162.4”, “162.5”, “162.8”, “162.9”, “163”, “163.0”, “163.1”, “163.8”, “163.9”, “164”, “164.0”, 
“164.1”, “164.2”, “164.3”, “164.8”, “164.9”, “165”, “165.0”, “165.8”, “165.9”, “170”, “170.0”, “170.1”, “170.2”, 
“170.3”, “170.4”, “170.5”, “170.6”, “170.7”, “170.8”, “170.9”, “171”, “171.0”, “171.2”, “171.3”, “171.4”, “171.5”, 
“171.6”, “171.7”, “171.8”, “171.9”, “174”, “174.0”, “174.1”, “174.2”, “174.3”, “174.4”, “174.5”, “174.6”, “174.8”, 
“174.9”, “175”, “175.0”, “175.9”, “176”, “176.0”, “176.1”, “176.2”, “176.3”, “176.4”, “176.5”, “176.8”, “176.9”, 
“179”, “180”, “180.0”, “180.1”, “180.8”, “180.9”, “181”, “182”, “182.0”, “182.1”, “182.8”, “183”, “183.0”, “183.2”, 
“183.3”, “183.4”, “183.5”, “183.8”, “183.9”, “184”, “184.0”, “184.1”, “184.2”, “184.3”, “184.4”, “184.8”, “184.9”, 
“185”, “186”, “186.0”, “186.9”, “187”, “187.1”, “187.2”, “187.3”, “187.4”, “187.5”, “187.6”, “187.7”, “187.8”, 
“187.9”, “188”, “188.0”, “188.1”, “188.2”, “188.3”, “188.4”, “188.5”, “188.6”, “188.7”, “188.8”, “188.9”, “189”, 

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“189.0”, “189.1”, “189.2”, “189.3”, “189.4”, “189.8”, “189.9”, “190”, “190.0”, “190.1”, “190.2”, “190.3”, “190.4”, 
“190.5”, “190.6”, “190.7”, “190.8”, “190.9”, “191”, “191.0”, “191.1”, “191.2”, “191.3”, “191.4”, “191.5”, “191.6”, 
“191.7”, “191.8”, “191.9”, “192”, “192.0”, “192.1”, “192.2”, “192.3”, “192.8”, “192.9”, “193”, “194”, “194.0”, 
“194.1”, “194.3”, “194.4”, “194.5”, “194.6”, “194.8”, “194.9”, “195”, “195.0”, “195.1”, “195.2”, “195.3”, “195.4”, 
“195.5”, “195.8”, “172”, “172.0”, “172.1”, “172.2”, “172.3”, “172.4”, “172.5”, “172.6”, “172.7”, “172.8”, “172.9”, 
“196”, “196.0”, “196.1”, “196.2”, “196.3”, “196.5”, “196.6”, “196.8”, “196.9”, “197”, “197.0”, “197.1”, “197.2”, 
“197.3”, “197.4”, “197.5”, “197.6”, “197.7”, “197.8”, “198”, “198.0”, “198.1”, “198.2”, “198.3”, “198.4”, “198.5”, 
“198.6”, “198.7”, “198.8”, “198.81”, “198.82”, “198.89”, “199”, “199.0”, “199.1”, “199.2”, “200”, “200.0”, “200.00”, 
“200.01”, “200.02”, “200.03”, “200.04”, “200.05”, “200.06”, “200.07”, “200.08”, “200.1”, “200.10”, “200.11”, 
“200.12”, “200.13”, “200.14”, “200.15”, “200.16”, “200.17”, “200.18”, “200.2”, “200.20”, “200.21”, “200.22”, 
“200.23”, “200.24”, “200.25”, “200.26”, “200.27”, “200.28”, “200.3”, “200.30”, “200.31”, “200.32”, “200.33”, 
“200.34”, “200.35”, “200.36”, “200.37”, “200.38”, “200.4”, “200.40”, “200.41”, “200.42”, “200.43”, “200.44”, 
“200.45”, “200.46”, “200.47”, “200.48”, “200.5”, “200.50”, “200.51”, “200.52”, “200.53”, “200.54”, “200.55”, 
“200.56”, “200.57”, “200.58”, “200.6”, “200.60”, “200.61”, “200.62”, “200.63”, “200.64”, “200.65”, “200.66”, 
“200.67”, “200.68”, “200.7”, “200.70”, “200.71”, “200.72”, “200.73”, “200.74”, “200.75”, “200.76”, “200.77”, 
“200.78”, “200.8”, “200.80”, “200.81”, “200.82”, “200.83”, “200.84”, “200.85”, “200.86”, “200.87”, “200.88”, “201”, 
“201.0”, “201.00”, “201.01”, “201.02”, “201.03”, “201.04”, “201.05”, “201.06”, “201.07”, “201.08”, “201.1”, 
“201.10”, “201.11”, “201.12”, “201.13”, “201.14”, “201.15”, “201.16”, “201.17”, “201.18”, “201.2”, “201.20”, 
“201.21”, “201.22”, “201.23”, “201.24”, “201.25”, “201.26”, “201.27”, “201.28”, “201.4”, “201.40”, “201.41”, 
“201.42”, “201.43”, “201.44”, “201.45”, “201.46”, “201.47”, “201.48”, “201.5”, “201.50”, “201.51”, “201.52”, 
“201.53”, “201.54”, “201.55”, “201.56”, “201.57”, “201.58”, “201.6”, “201.60”, “201.61”, “201.62”, “201.63”, 
“201.64”, “201.65”, “201.66”, “201.67”, “201.68”, “201.7”, “201.70”, “201.71”, “201.72”, “201.73”, “201.74”, 
“201.75”, “201.76”, “201.77”, “201.78”, “201.9”, “201.90”, “201.91”, “201.92”, “201.93”, “201.94”, “201.95”, 
“201.96”, “201.97”, “201.98”, “202”, “202.0”, “202.00”, “202.01”, “202.02”, “202.03”, “202.04”, “202.05”, “202.06”, 
“202.07”, “202.08”, “202.1”, “202.10”, “202.11”, “202.12”, “202.13”, “202.14”, “202.15”, “202.16”, “202.17”, 
“202.18”, “202.2”, “202.20”, “202.21”, “202.22”, “202.23”, “202.24”, “202.25”, “202.26”, “202.27”, “202.28”, 
“202.3”, “202.30”, “202.31”, “202.32”, “202.33”, “202.34”, “202.35”, “202.36”, “202.37”, “202.38”, “202.4”, 
“202.40”, “202.41”, “202.42”, “202.43”, “202.44”, “202.45”, “202.46”, “202.47”, “202.48”, “202.5”, “202.50”, 
“202.51”, “202.52”, “202.53”, “202.54”, “202.55”, “202.56”, “202.57”, “202.58”, “202.6”, “202.60”, “202.61”, 
“202.62”, “202.63”, “202.64”, “202.65”, “202.66”, “202.67”, “202.68”, “202.7”, “202.70”, “202.71”, “202.72”, 
“202.73”, “202.74”, “202.75”, “202.76”, “202.77”, “202.78”, “202.8”, “202.80”, “202.81”, “202.82”, “202.83”, 

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“202.84”, “202.85”, “202.86”, “202.87”, “202.88”, “202.9”, “202.90”, “202.91”, “202.92”, “202.93”, “202.94”, 
“202.95”, “202.96”, “202.97”, “202.98”, “203”, “203.0”, “203.00”, “203.01”, “203.02”, “203.1”, “203.10”, “203.11”, 
“203.12”, “203.8”, “203.80”, “203.81”, “203.82”, “204”, “204.0”, “204.00”, “204.01”, “204.02”, “204.1”, “204.10”, 
“204.11”, “204.12”, “204.2”, “204.20”, “204.21”, “204.22”, “204.8”, “204.80”, “204.81”, “204.82”, “204.9”, 
“204.90”, “204.91”, “204.92”, “205”, “205.0”, “205.00”, “205.01”, “205.02”, “205.1”, “205.10”, “205.11”, “205.12”, 
“205.2”, “205.20”, “205.21”, “205.22”, “205.3”, “205.30”, “205.31”, “205.32”, “205.8”, “205.80”, “205.81”, 
“205.82”, “205.9”, “205.90”, “205.91”, “205.92”, “206”, “206.0”, “206.00”, “206.01”, “206.02”, “206.1”, “206.10”, 
“206.11”, “206.12”, “206.2”, “206.20”, “206.21”, “206.22”, “206.8”, “206.80”, “206.81”, “206.82”, “206.9”, 
“206.90”, “206.91”, “206.92”, “207”, “207.0”, “207.00”, “207.01”, “207.02”, “207.1”, “207.10”, “207.11”, “207.12”, 
“207.2”, “207.20”, “207.21”, “207.22”, “207.8”, “207.80”, “207.81”, “207.82”, “208”, “208.0”, “208.00”, “208.01”, 
“208.02”, “208.1”, “208.10”, “208.11”, “208.12”, “208.2”, “208.20”, “208.21”, “208.22”, “208.8”, “208.80”, 
“208.81”, “208.82”, “208.9”, “208.90”, “208.91”, “208.92”, “V10.82” }
Diagnosis Code (Any Position), ICD-10 is any of: { “C00.0”, “C00.1”, “C00.2”, “C00.3”, “C00.4”, “C00.5”, 
“C00.6”, “C00.8”, “C01”, “C02.0”, “C02.1”, “C02.2”, “C02.3”, “C02.4”, “C02.8”, “C02.9”, “C03.0”, “C03.1”, 
“C03.9”, “C04.0”, “C04.1”, “C04.8”, “C04.9”, “C05.0”, “C05.1”, “C05.2”, “C05.9”, “C06.0”, “C06.1”, “C06.2”, 
“C06.89”, “C06.9”, “C07”, “C08.0”, “C08.1”, “C08.9”, “C09.0”, “C09.1”, “C09.9”, “C10.0”, “C10.1”, “C10.2”, 
“C10.3”, “C10.4”, “C10.8”, “C10.9”, “C11.0”, “C11.1”, “C11.2”, “C11.3”, “C11.8”, “C11.9”, “C12”, “C13.0”, 
“C13.1”, “C13.2”, “C13.8”, “C13.9”, “C14.0”, “C14.2”, “C14.8”, “C15.3”, “C15.4”, “C15.5”, “C15.8”, “C15.9”, 
“C16.0”, “C16.1”, “C16.2”, “C16.3”, “C16.4”, “C16.5”, “C16.6”, “C16.8”, “C16.9”, “C17.0”, “C17.1”, “C17.2”, 
“C17.3”, “C17.8”, “C17.9”, “C18.0”, “C18.1”, “C18.2”, “C18.3”, “C18.4”, “C18.5”, “C18.6”, “C18.7”, “C18.8”, 
“C18.9”, “C19”, “C20”, “C21.0”, “C21.1”, “C21.8”, “C22.0”, “C22.1”, “C22.2”, “C22.7”, “C22.8”, “C22.9”, “C23”, 
“C24.0”, “C24.1”, “C24.8”, “C24.9”, “C25.0”, “C25.1”, “C25.2”, “C25.3”, “C25.4”, “C25.7”, “C25.8”, “C25.9”, 
“C26.0”, “C26.1”, “C26.9”, “C30.0”, “C30.1”, “C31.0”, “C31.1”, “C31.2”, “C31.3”, “C31.8”, “C31.9”, “C32.0”, 
“C32.1”, “C32.2”, “C32.3”, “C32.8”, “C32.9”, “C33”, “C34.00”, “C34.10”, “C34.2”, “C34.30”, “C34.80”, “C34.90”, 
“C37”, “C38.0”, “C38.1”, “C38.2”, “C38.3”, “C38.4”, “C38.8”, “C39.0”, “C39.9”, “C40.00”, “C40.10”, “C40.20”, 
“C40.30”, “C41.0”, “C41.1”, “C41.2”, “C41.3”, “C41.4”, “C41.9”, “C43.0”, “C43.10”, “C43.20”, “C43.30”, 
“C43.31”, “C43.39”, “C43.4”, “C43.59”, “C43.60”, “C43.70”, “C43.8”, “C43.9”, “C46.0”, “C46.1”, “C46.2”, 
“C46.3”, “C46.4”, “C46.50”, “C46.7”, “C46.9”, “C47.8”, “C48.0”, “C48.1”, “C48.2”, “C48.8”, “C49.0”, “C49.10”, 
“C49.20”, “C49.3”, “C49.4”, “C49.5”, “C49.6”, “C49.8”, “C49.9”, “C50.019”, “C50.029”, “C50.119”, “C50.219”, 
“C50.319”, “C50.419”, “C50.519”, “C50.619”, “C50.819”, “C50.919”, “C50.929”, “C51.0”, “C51.1”, “C51.2”, 

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“C51.9”, “C52”, “C53.0”, “C53.1”, “C53.8”, “C53.9”, “C54.0”, “C54.1”, “C54.2”, “C54.3”, “C54.8”, “C54.9”, “C55”, 
“C56.9”, “C57.00”, “C57.10”, “C57.20”, “C57.3”, “C57.4”, “C57.7”, “C57.8”, “C57.9”, “C58”, “C60.0”, “C60.1”, 
“C60.2”, “C60.8”, “C60.9”, “C61”, “C62.00”, “C62.10”, “C62.90”, “C63.00”, “C63.10”, “C63.2”, “C63.7”, “C63.8”, 
“C63.9”, “C64.9”, “C65.9”, “C66.9”, “C67.0”, “C67.1”, “C67.2”, “C67.3”, “C67.4”, “C67.5”, “C67.6”, “C67.7”, 
“C67.8”, “C67.9”, “C68.0”, “C68.1”, “C68.8”, “C68.9”, “C69.00”, “C69.10”, “C69.20”, “C69.30”, “C69.40”, 
“C69.50”, “C69.60”, “C69.80”, “C69.90”, “C70.0”, “C70.1”, “C70.9”, “C71.0”, “C71.1”, “C71.2”, “C71.3”, “C71.4”, 
“C71.5”, “C71.6”, “C71.7”, “C71.8”, “C71.9”, “C72.0”, “C72.1”, “C72.50”, “C72.9”, “C73”, “C74.90”, “C75.0”, 
“C75.1”, “C75.2”, “C75.3”, “C75.4”, “C75.5”, “C75.8”, “C75.9”, “C76.0”, “C76.1”, “C76.2”, “C76.3”, “C76.40”, 
“C76.50”, “C76.8”, “C77.0”, “C77.1”, “C77.2”, “C77.3”, “C77.4”, “C77.5”, “C77.8”, “C77.9”, “C78.00”, “C78.1”, 
“C78.2”, “C78.39”, “C78.4”, “C78.5”, “C78.6”, “C78.7”, “C78.89”, “C79.00”, “C79.11”, “C79.19”, “C79.2”, 
“C79.31”, “C79.32”, “C79.49”, “C79.51”, “C79.52”, “C79.60”, “C79.70”, “C79.81”, “C79.82”, “C79.89”, “C80.0”, 
“C80.1”, “C80.2”, “C81.00”, “C81.01”, “C81.02”, “C81.03”, “C81.04”, “C81.05”, “C81.06”, “C81.07”, “C81.08”, 
“C81.09”, “C81.10”, “C81.11”, “C81.12”, “C81.13”, “C81.14”, “C81.15”, “C81.16”, “C81.17”, “C81.18”, “C81.19”, 
“C81.20”, “C81.21”, “C81.22”, “C81.23”, “C81.24”, “C81.25”, “C81.26”, “C81.27”, “C81.28”, “C81.29”, “C81.30”, 
“C81.31”, “C81.32”, “C81.33”, “C81.34”, “C81.35”, “C81.36”, “C81.37”, “C81.38”, “C81.39”, “C81.40”, “C81.41”, 
“C81.42”, “C81.43”, “C81.44”, “C81.45”, “C81.46”, “C81.47”, “C81.48”, “C81.49”, “C81.70”, “C81.71”, “C81.72”, 
“C81.73”, “C81.74”, “C81.75”, “C81.76”, “C81.77”, “C81.78”, “C81.79”, “C81.90”, “C81.91”, “C81.92”, “C81.93”, 
“C81.94”, “C81.95”, “C81.96”, “C81.97”, “C81.98”, “C81.99”, “C82.90”, “C82.91”, “C82.92”, “C82.93”, “C82.94”, 
“C82.95”, “C82.96”, “C82.97”, “C82.98”, “C82.99”, “C83.10”, “C83.11”, “C83.12”, “C83.13”, “C83.14”, “C83.15”, 
“C83.16”, “C83.17”, “C83.18”, “C83.19”, “C83.30”, “C83.31”, “C83.32”, “C83.33”, “C83.34”, “C83.35”, “C83.36”, 
“C83.37”, “C83.38”, “C83.39”, “C83.50”, “C83.51”, “C83.52”, “C83.53”, “C83.54”, “C83.55”, “C83.56”, “C83.57”, 
“C83.58”, “C83.59”, “C83.70”, “C83.71”, “C83.72”, “C83.73”, “C83.74”, “C83.75”, “C83.76”, “C83.77”, “C83.78”, 
“C83.79”, “C83.80”, “C83.81”, “C83.82”, “C83.83”, “C83.84”, “C83.85”, “C83.86”, “C83.87”, “C83.88”, “C83.89”, 
“C84.00”, “C84.01”, “C84.02”, “C84.03”, “C84.04”, “C84.05”, “C84.06”, “C84.07”, “C84.08”, “C84.09”, “C84.10”, 
“C84.11”, “C84.12”, “C84.13”, “C84.14”, “C84.15”, “C84.16”, “C84.17”, “C84.18”, “C84.19”, “C84.40”, “C84.41”, 
“C84.42”, “C84.43”, “C84.44”, “C84.45”, “C84.46”, “C84.47”, “C84.48”, “C84.49”, “C84.60”, “C84.61”, “C84.62”, 
“C84.63”, “C84.64”, “C84.65”, “C84.66”, “C84.67”, “C84.68”, “C84.69”, “C84.70”, “C84.71”, “C84.72”, “C84.73”, 
“C84.74”, “C84.75”, “C84.76”, “C84.77”, “C84.78”, “C84.79”, “C84.93”, “C85.80”, “C85.81”, “C85.82”, “C85.83”, 
“C85.84”, “C85.85”, “C85.86”, “C85.87”, “C85.88”, “C85.89”, “C88.8”, “C90.00”, “C90.01”, “C90.02”, “C90.10”, 
“C90.11”, “C90.12”, “C90.20”, “C90.21”, “C90.22”, “C90.30”, “C90.31”, “C90.32”, “C91.00”, “C91.01”, “C91.02”, 
“C91.10”, “C91.11”, “C91.12”, “C91.40”, “C91.41”, “C91.90”, “C91.91”, “C91.92”, “C91.Z0”, “C91.Z1”, “C91.Z2”, 

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“C92.00”, “C92.01”, “C92.02”, “C92.10”, “C92.11”, “C92.12”, “C92.20”, “C92.21”, “C92.22”, “C92.30”, “C92.31”, 
“C92.32”, “C92.40”, “C92.41”, “C92.42”, “C92.50”, “C92.51”, “C92.52”, “C92.90”, “C92.91”, “C92.92”, “C92.Z0”, 
“C92.Z1”, “C92.Z2”, “C93.00”, “C93.01”, “C93.02”, “C93.10”, “C93.11”, “C93.12”, “C93.90”, “C93.91”, “C93.92”, 
“C93.Z0”, “C93.Z1”, “C93.Z2”, “C94.00”, “C94.01”, “C94.02”, “C94.20”, “C94.21”, “C94.22”, “C94.30”, “C94.31”, 
“C94.32”, “C94.80”, “C94.81”, “C94.82”, “C95.00”, “C95.01”, “C95.02”, “C95.10”, “C95.11”, “C95.12”, “C95.90”, 
“C95.91”, “C95.92”, “C96.0”, “C96.4”, “C96.9”, “C96.A”, “C96.Z”, “D03.0”, “D03.10”, “D03.11”, “D03.12”, 
“D03.20”, “D03.21”, “D03.22”, “D03.30”, “D03.39”, “D03.4”, “D03.51”, “D03.52”, “D03.59”, “D03.60”, “D03.61”, 
“D03.62”, “D03.70”, “D03.71”, “D03.72”, “D03.8”, “D03.9”, “D45”, “D03”, “D03.1”, “D03.2”, “D03.3”, “D03.5”, 
“D03.6”, “D03.7”, “C43”, “C43.1”, “C43.11”, “C43.12”, “C43.2”, “C43.21”, “C43.22”, “C43.3”, “C43.5”, “C43.51”, 
“C43.52”, “C43.6”, “C43.61”, “C43.62”, “C43.7”, “C43.71”, “C43.72”, “Z85.820” }
Allergic Rhinitis
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “477”, “477.0”, “477.1”, “477.2”, “477.8”, “477.9” }
Diagnosis Code (Any Position), ICD-10 is any of: { “J30”, “J30.1”, “J30.2”, “J30.5”, “J30.8”, “J30.81”, “J30.89”, 
“J30.9” }
Chronic Sinusitis
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “473”, “473.0”, “473.1”, “473.2”, “473.3”, “473.8”, “473.9” }
Diagnosis Code (Any Position), ICD-10 is any of: { “J32”, “J32.0”, “J32.1”, “J32.2”, “J32.3”, “J32.4”, “J32.8”, 
“J32.9” }
Bronchiectasis
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “011.5”, “011.50”, “011.51”, “011.52”, “011.53”, “011.54”, 
“011.55”, “011.56”, “494”, “494.0”, “494.1”, “748.61” }
Diagnosis Code (Any Position), ICD-10 is any of: { “J47.1”, “J47.9”, “Q33.4”, “J47”, “J47.0” }

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Pneumonia
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “003.22”, “020.3”, “020.4”, “020.5”, “021.2”, “022.1”, “031.0”, 
“039.1”, “052.1”, “055.1”, “073.0”, “083.0”, “112.4”, “114.0”, “114.4”, “114.5”, “115.05”, “115.15”, “115.95”, 
“130.4”, “136.3”, “480.0”, “480.1”, “480.2”, “480.3”, “480.8”, “480.9”, “481”, “482”, “482.0”, “482.1”, “482.2”, 
“482.3”, “482.30”, “482.31”, “482.32”, “482.39”, “482.4”, “482.40”, “482.41”, “482.42”, “482.49”, “482.8”, 
“482.81”, “482.82”, “482.83”, “482.84”, “482.89”, “482.9”, “483”, “483.0”, “483.1”, “483.8”, “484”, “484.1”, 
“484.3”, “484.5”, “484.6”, “484.7”, “484.8”, “485”, “486”, “487”, “487.0”, “487.1”, “487.8”, “517.1” }
Diagnosis Code (Any Position), ICD-10 is any of: { “A01.03”, “A02.22”, “A20.2”, “A21.2”, “A22.1”, “A31.0”, 
“A37.01”, “A37.11”, “A37.91”, “A43.0”, “A49.2”, “B01.2”, “B05.2”, “B06.81”, “B25.0”, “B37.1”, “B38.0”, “B38.1”, 
“B38.2”, “B39.0”, “B39.1”, “B39.2”, “B44.0”, “B58.3”, “B59”, “B77.81”, “J09”, “J09.X”, “J09.X1”, “J09.X2”, 
“J09.X9”, “J10”, “J10.0”, “J10.00”, “J10.01”, “J10.08”, “J10.1”, “J10.8”, “J10.89”, “J11”, “J11.0”, “J11.00”, 
“J11.08”, “J11.8”, “J11.89”, “J12.0”, “J12.1”, “J12.2”, “J12.3”, “J12.81”, “J12.89”, “J12.9”, “J13”, “J14”, “J15.0”, 
“J15.1”, “J15.20”, “J15.211”, “J15.212”, “J15.29”, “J15.3”, “J15.4”, “J15.5”, “J15.6”, “J15.7”, “J15.8”, “J15.9”, 
“J16.0”, “J16.8”, “J17”, “J18.0”, “J18.1”, “J18.8”, “J18.9” }
Chronic Bronchitis
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “491”, “491.0”, “491.1”, “491.2”, “491.20”, “491.21”, “491.22”, 
“491.8”, “491.9” }
Diagnosis Code (Any Position), ICD-10 is any of: { “J41”, “J41.0”, “J41.1”, “J41.8”, “J42” }
Exertional 
Breathlessness
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-10 is any of: { “R06.0*” }
Diagnosis Code (Any Position), ICD-9 is any of: { “786.0” }

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Anxiety
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “293.84”, “300.0”, “300.00”, “300.02”, “300.09”, “309.21”, 
“309.24”, “309.28”, “313.0” }
Diagnosis Code (Any Position), ICD-10 is any of: { “F06.4”, “F41.1”, “F41.8”, “F41.9”, “F43.22”, “F43.23”, 
“F93.0”, “F93.8”, "F40", "F40.8", "F40.9", "F41", "F41.0", "F41.3" }
Dementia
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “290.0”, “290.1”, “290.10”, “290.11”, “290.12”, “290.13”, 
“290.2”, “290.20”, “290.21”, “290.3”, “290.4”, “290.40”, “290.41”, “290.42”, “290.43”, “291.2”, “292.82”, “294.0”, 
“294.1”, “294.10”, “294.11”, “294.8”, “331.0”, “331.1”, “331.11”, “331.19”, “331.2”, “331.7”, “331.8”, “331.81”, 
“331.82”, “331.83”, “331.89”, “331.9”, “797” }
Diagnosis Code (Any Position), ICD-10 is any of: { “F01.50”, “F01.51”, “F02.80”, “F02.81”, “F03.90”, “F04”, 
“F05”, “F06.0”, “F06.8”, “F10.27”, “F19.97”, “G30.9”, “G31.01”, “G31.09”, “G31.1”, “G31.83”, “G31.84”, 
“G31.89”, “G31.9”, “G93.7”, “G94”, “R41.81”, "F32", "F32.8", "F33", "F33.8" }
Generic Name is any of: { “DONEPEZIL HCL”, “GALANTAMINE HBR”, “RIVASTIGMINE”, “MEMANTINE 
HCL” }
Depression
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “296.2”, “296.20”, “296.21”, “296.22”, “296.23”, “296.24”, 
“296.25”, “296.26”, “296.3”, “296.30”, “296.31”, “296.32”, “296.33”, “296.34”, “296.35”, “296.36”, “298.0”, 
“300.4”, “309.0”, “309.1”, “309.28”, “311” }
Diagnosis Code (Any Position), ICD-10 is any of: { “F32.0”, “F32.1”, “F32.2”, “F32.3”, “F32.4”, “F32.5”, “F32.9”, 
“F33.0”, “F33.1”, “F33.2”, “F33.3”, “F33.41”, “F33.42”, “F33.9”, “F34.1”, “F43.21”, “F43.23” }
Osteoporosis
1 Inpatient or 2 Outpatient (30 – 365 days apart)

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Diagnosis Code (Any Position), ICD-9 is any of: { “733.0”, “733.00”, “733.01”, “733.02”, “733.03”, “733.09”, 
“733.1”, “733.10”, “733.11”, “733.12”, “733.13”, “733.14”, “733.15”, “733.16”, “733.19” }
Diagnosis Code (Any Position), ICD-10 is any of: { “M80”, “M80.0”, “M80.00”, “M80.00XA”, “M80.00XD”, 
“M80.00XG”, “M80.00XK”, “M80.00XP”, “M80.00XS”, “M80.01”, “M80.011”, “M80.011A”, “M80.011D”, 
“M80.011G”, “M80.011K”, “M80.011P”, “M80.011S”, “M80.012”, “M80.012A”, “M80.012D”, “M80.012G”, 
“M80.012K”, “M80.012P”, “M80.012S”, “M80.019”, “M80.019A”, “M80.019D”, “M80.019G”, “M80.019K”, 
“M80.019P”, “M80.019S”, “M80.02”, “M80.021”, “M80.021A”, “M80.021D”, “M80.021G”, “M80.021K”, 
“M80.021P”, “M80.021S”, “M80.022”, “M80.022A”, “M80.022D”, “M80.022G”, “M80.022K”, “M80.022P”, 
“M80.022S”, “M80.029”, “M80.029A”, “M80.029D”, “M80.029G”, “M80.029K”, “M80.029P”, “M80.029S”, 
“M80.03”, “M80.031”, “M80.031A”, “M80.031D”, “M80.031G”, “M80.031K”, “M80.031P”, “M80.031S”, 
“M80.032”, “M80.032A”, “M80.032D”, “M80.032G”, “M80.032K”, “M80.032P”, “M80.032S”, “M80.039”, 
“M80.039A”, “M80.039D”, “M80.039G”, “M80.039K”, “M80.039P”, “M80.039S”, “M80.04”, “M80.041”, 
“M80.041A”, “M80.041D”, “M80.041G”, “M80.041K”, “M80.041P”, “M80.041S”, “M80.042”, “M80.042A”, 
“M80.042D”, “M80.042G”, “M80.042K”, “M80.042P”, “M80.042S”, “M80.049”, “M80.049A”, “M80.049D”, 
“M80.049G”, “M80.049K”, “M80.049P”, “M80.049S”, “M80.05”, “M80.051”, “M80.051A”, “M80.051D”, 
“M80.051G”, “M80.051K”, “M80.051P”, “M80.051S”, “M80.052”, “M80.052A”, “M80.052D”, “M80.052G”, 
“M80.052K”, “M80.052P”, “M80.052S”, “M80.059”, “M80.059A”, “M80.059D”, “M80.059G”, “M80.059K”, 
“M80.059P”, “M80.059S”, “M80.06”, “M80.061”, “M80.061A”, “M80.061D”, “M80.061G”, “M80.061K”, 
“M80.061P”, “M80.061S”, “M80.062”, “M80.062A”, “M80.062D”, “M80.062G”, “M80.062K”, “M80.062P”, 
“M80.062S”, “M80.069”, “M80.069A”, “M80.069D”, “M80.069G”, “M80.069K”, “M80.069P”, “M80.069S”, 
“M80.07”, “M80.071”, “M80.071A”, “M80.071D”, “M80.071G”, “M80.071K”, “M80.071P”, “M80.071S”, 
“M80.072”, “M80.072A”, “M80.072D”, “M80.072G”, “M80.072K”, “M80.072P”, “M80.072S”, “M80.079”, 
“M80.079A”, “M80.079D”, “M80.079G”, “M80.079K”, “M80.079P”, “M80.079S”, “M80.08”, “M80.08XA”, 
“M80.08XD”, “M80.08XG”, “M80.08XK”, “M80.08XP”, “M80.08XS”, “M80.8”, “M80.80”, “M80.80XA”, 
“M80.80XD”, “M80.80XG”, “M80.80XK”, “M80.80XP”, “M80.80XS”, “M80.81”, “M80.811”, “M80.811A”, 
“M80.811D”, “M80.811G”, “M80.811K”, “M80.811P”, “M80.811S”, “M80.812”, “M80.812A”, “M80.812D”, 
“M80.812G”, “M80.812K”, “M80.812P”, “M80.812S”, “M80.819”, “M80.819A”, “M80.819D”, “M80.819G”, 
“M80.819K”, “M80.819P”, “M80.819S”, “M80.82”, “M80.821”, “M80.821A”, “M80.821D”, “M80.821G”, 
“M80.821K”, “M80.821P”, “M80.821S”, “M80.822”, “M80.822A”, “M80.822D”, “M80.822G”, “M80.822K”, 

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“M80.822P”, “M80.822S”, “M80.829”, “M80.829A”, “M80.829D”, “M80.829G”, “M80.829K”, “M80.829P”, 
“M80.829S”, “M80.83”, “M80.831”, “M80.831A”, “M80.831D”, “M80.831G”, “M80.831K”, “M80.831P”, 
“M80.831S”, “M80.832”, “M80.832A”, “M80.832D”, “M80.832G”, “M80.832K”, “M80.832P”, “M80.832S”, 
“M80.839”, “M80.839A”, “M80.839D”, “M80.839G”, “M80.839K”, “M80.839P”, “M80.839S”, “M80.84”, 
“M80.841”, “M80.841A”, “M80.841D”, “M80.841G”, “M80.841K”, “M80.841P”, “M80.841S”, “M80.842”, 
“M80.842A”, “M80.842D”, “M80.842G”, “M80.842K”, “M80.842P”, “M80.842S”, “M80.849”, “M80.849A”, 
“M80.849D”, “M80.849G”, “M80.849K”, “M80.849P”, “M80.849S”, “M80.85”, “M80.851”, “M80.851A”, 
“M80.851D”, “M80.851G”, “M80.851K”, “M80.851P”, “M80.851S”, “M80.852”, “M80.852A”, “M80.852D”, 
“M80.852G”, “M80.852K”, “M80.852P”, “M80.852S”, “M80.859”, “M80.859A”, “M80.859D”, “M80.859G”, 
“M80.859K”, “M80.859P”, “M80.859S”, “M80.86”, “M80.861”, “M80.861A”, “M80.861D”, “M80.861G”, 
“M80.861K”, “M80.861P”, “M80.861S”, “M80.862”, “M80.862A”, “M80.862D”, “M80.862G”, “M80.862K”, 
“M80.862P”, “M80.862S”, “M80.869”, “M80.869A”, “M80.869D”, “M80.869G”, “M80.869K”, “M80.869P”, 
“M80.869S”, “M80.87”, “M80.871”, “M80.871A”, “M80.871D”, “M80.871G”, “M80.871K”, “M80.871P”, 
“M80.871S”, “M80.872”, “M80.872A”, “M80.872D”, “M80.872G”, “M80.872K”, “M80.872P”, “M80.872S”, 
“M80.879”, “M80.879A”, “M80.879D”, “M80.879G”, “M80.879K”, “M80.879P”, “M80.879S”, “M80.88”, 
“M80.88XA”, “M80.88XD”, “M80.88XG”, “M80.88XK”, “M80.88XP”, “M80.88XS”, “M81”, “M81.0”, “M81.6”, 
“M81.8” }

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Charlson-Deyo 
Comorbidity Index
This measure computes a score by summing over the following components:
· If the event Acute Myocardial Infarction Occurs within 180 days, set the score to 1.0 Otherwise, set the score to 0.0 
· If the event Heart Failure Occurs within 180 days, set the score to 1.0 Otherwise, set the score to 0.0 
· If the event Peripheral Vascular Disease Occurs within 180 days, set the score to 1.0 Otherwise, set the score to 0.0
· If the event Cerebrovascular Disease Occurs within 180 days, set the score to 1.0 Otherwise, set the score to 0.0 
· If the event Dementia Occurs within 180 days, set the score to 1.0 Otherwise, set the score to 0.0 
· If the event Chronic Obstructive Pulmonary Disease Occurs within 180 days, set the score to 1.0 Otherwise, set the 
score to 0.0 
· If the event Rheumatologic Disease Occurs within 180 days, set the score to 1.0 Otherwise, set the score to 0.0 
· If the event Peptic Ulcer Disease Occurs within 180 days, set the score to 1.0 Otherwise, set the score to 0.0 
· If the event Hemiplegia or Paraplegia Occurs within 180 days, set the score to 2.0 Otherwise, set the score to 0.0 
· If the event Renal Disease Occurs within 180 days, set the score to 2.0 Otherwise, set the score to 0.0 
· If the event HIV/AIDS Occurs within 180 days, set the score to 6.0 Otherwise, set the score to 0.0 
· For the measure Cancer use the value of the measure as the score multiplied by weight 1.0 If the value is missing, set 
the score to 0.0 
· For the measure Diabetes use the value of the measure as the score multiplied by weight 1.0 If the value is missing, 
set the score to 0.0 
· For the measure Liver Disease use the value of the measure as the score multiplied by weight 1.0 If the value is 
missing, set the score to 0.0
Acute Liver Injury or 
Failure
1 Inpatient or 1 Outpatient
Diagnosis Code (Any Position), ICD-9 is any of: { “570”, “864.0”, “864.00”, “864.01”, “864.02”, “864.03”, 
“864.04”, “864.05”, “864.09”, “864.1”, “864.10”, “864.11”, “864.12”, “864.13”, “864.14”, “864.15”, “864.19” }
Diagnosis Code (Any Position), ICD-10 is any of: { “K72.0”, “K72.00”, “K72.01”, “K72.9”, “K72.90”, “K72.91”, 
“S36.11”, “S36.112”, “S36.112A”, “S36.112D”, “S36.112S”, “S36.113”, “S36.113A”, “S36.113D”, “S36.113S”, 
“S36.114”, “S36.114A”, “S36.114D”, “S36.114S”, “S36.115”, “S36.115A”, “S36.115D”, “S36.115S”, “S36.116”, 
“S36.116A”, “S36.116D”, “S36.116S”, “S36.118”, “S36.118A”, “S36.118D”, “S36.118S”, “S36.119”, “S36.119A”, 
“S36.119D”, “S36.119S” }
Chronic Kidney 
1 Inpatient or 2 Outpatient (30 – 365 days apart)

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Disease (without 
ESRD)
Diagnosis Code (Any Position), ICD-9 is any of: { “585.1”, “585.2”, “585.3”, “585.4” }
Diagnosis Code (Any Position), ICD-10 is any of: { “N18.1”, “N18.2”, “N18.3”, “N18.4” }
Procedure Code (Any Position), CPT and HCPC is any of: { “G0420”, “G0421”, “G8487”, “G8771” }
End Stage Renal 
Disease
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “403.01”, “403.91”, “458.21”, “585.5”, “585.6”, “996.56”, 
“996.68”, “996.73”, “V42.0”, “V45.1”, “V45.11”, “V45.12”, “V56”, “V56.0”, “V56.1”, “V56.2”, “V56.3”, “V56.31”, 
“V56.32”, “V56.8” }
Diagnosis Code (Any Position), ICD-10 is any of: { “I12.0”, “N18.5”, “N18.6”, “T86.10”, “T86.11”, “T86.12”, 
“Z49.01”, “Z49.02”, “Z49.31”, “Z49.32”, “Z91.15”, “Z94.0”, “Z99.2” }
Procedure Code (Any Position), ICD-9 is any of: { “55.69”, “55.6”, “38.95”, “39.27”, “39.42”, “39.43”, “39.95”, 
“54.98” }
Procedure Code (Any Position), ICD-10 is any of: { “05HY33Z”, “06HY33Z”, “0TS00ZZ”, “0TS10ZZ”, 
“0TY00Z0”, “0TY00Z1”, “0TY00Z2”, “0TY10Z0”, “0TY10Z1”, “0TY10Z2”, “3E1M39Z”, “5A1D00Z”, 
“5A1D60Z” }
Procedure Code (Any Position), CPT and HCPC is any of: { “36145”, “36800”, “36810”, “36815”, “36825”, 
“36830”, “36831”, “36832”, “36833”, “50323”, “50325”, “50327”, “50328”, “50329”, “50340”, “50360”, “50365”, 
“90918”, “90919”, “90920”, “90921”, “90922”, “90923”, “90924”, “90925”, “90935”, “90937”, “90939”, “90940”, 
“90945”, “90947”, “90951”, “90952”, “90953”, “90954”, “90955”, “90956”, “90957”, “90958”, “90959”, “90960”, 
“90961”, “90962”, “90963”, “90964”, “90965”, “90966”, “90967”, “90968”, “90969”, “90970”, “90989”, “90993”, 
“90997”, “90999”, “93990”, “99512”, “A4653”, “A4656”, “A4657”, “A4670”, “A4671”, “A4672”, “A4673”, 
“A4674”, “A4680”, “A4706”, “A4707”, “A4708”, “A4709”, “A4712”, “A4714”, “A4719”, “A4720”, “A4721”, 
“A4722”, “A4723”, “A4724”, “A4725”, “A4726”, “A4728”, “A4730”, “A4736”, “A4737”, “A4740”, “A4750”, 
“A4755”, “A4760”, “A4765”, “A4766”, “A4770”, “A4771”, “A4773”, “A4774”, “A4802”, “A4860”, “A4870”, 
“A4890”, “A4911”, “A4913”, “A4918”, “A4928”, “A4929”, “C1881”, “E1500”, “E1520”, “E1530”, “E1540”, 
“E1550”, “E1560”, “E1570”, “E1575”, “E1580”, “E1600”, “E1610”, “E1615”, “E1620”, “E1625”, “E1634”, 

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“E1635”, “E1636”, “E1637”, “E1639”, “E1699”, “G0257”, “G0308”, “G0309”, “G0310”, “G0311”, “G0312”, 
“G0313”, “G0314”, “G0315”, “G0316”, “G0317”, “G0318”, “G0319”, “G0320”, “G0321”, “G0323”, “G0324”, 
“G0325”, “G0326”, “G0327”, “G8727”, “G9013”, “G9014”, “J0635”, “J0636”, “S2065”, “S9335”, “S9339”, 
“E1638”, “G0322” }
Rheumatologic 
Disease
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “135”, “183.0”, “274.9”, “275.49”, “279.49”, “443.0”, “448.9”, 
“530.5”, “555.9”, “571.42”, “571.6”, “576.1”, “579.0”, “696.0”, “696.1”, “710.0”, “710.1”, “710.2”, “710.3”, “710.9”, 
“711.90”, “712.19”, “714.0”, “714.30”, “715.09”, “715.11”, “715.12”, “715.13”, “715.14”, “715.15”, “715.17”, 
“715.18”, “715.96”, “719.42”, “719.44”, “719.45”, “719.47”, “719.49”, “720.0”, “721.90”, “725”, “729.1”, “729.5”, 
“795.79” }
Diagnosis Code (Any Position), ICD-10 is any of: { “D59.0”, “D59.1”, “D86.9”, “D89.89”, “E83.59”, “I73.00”,
“I73.01”, “I78.9”, “K22.4”, “K50.90”, “K74.3”, “K74.4”, “K74.5”, “K75.4”, “K83.0”, “K90.0”, “L40.0”, “L40.1”, 
“L40.2”, “L40.50”, “L40.54”, “L40.59”, “L40.8”, “M00.9”, “M06.9”, “M08.00”, “M10.9”, “M11.9”, “M15.0”, 
“M16.0”, “M16.10”, “M16.11”, “M16.12”, “M17.9”, “M19.019”, “M19.029”, “M19.039”, “M19.049”, “M19.079”, 
“M19.91”, “M25.50”, “M25.529”, “M25.559”, “M25.579”, “M32.10”, “M33.90”, “M34.0”, “M34.1”, “M34.2”, 
“M34.81”, “M34.82”, “M34.83”, “M34.89”, “M34.9”, “M35.00”, “M35.01”, “M35.02”, “M35.03”, “M35.04”, 
“M35.09”, “M35.3”, “M35.9”, “M45.9”, “M47.819”, “M60.9”, “M76.0”, “M76.11”, “M76.12”, “M76.8”, “M76.9”, 
“M79”, “M79.1”, “M79.609”, “M79.646” }

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Peptic Ulcer Disease
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “531”, “531.0”, “531.00”, “531.01”, “531.1”, “531.10”, “531.11”, 
“531.2”, “531.20”, “531.21”, “531.3”, “531.30”, “531.31”, “531.4”, “531.40”, “531.41”, “531.5”, “531.50”, “531.51”, 
“531.6”, “531.60”, “531.61”, “531.7”, “531.70”, “531.71”, “531.9”, “531.90”, “531.91”, “532”, “532.0”, “532.00”, 
“532.01”, “532.1”, “532.10”, “532.11”, “532.2”, “532.20”, “532.21”, “532.3”, “532.30”, “532.31”, “532.4”, “532.40”, 
“532.41”, “532.5”, “532.50”, “532.51”, “532.6”, “532.60”, “532.61”, “532.7”, “532.70”, “532.71”, “532.9”, “532.90”, 
“532.91”, “533”, “533.0”, “533.00”, “533.01”, “533.1”, “533.10”, “533.11”, “533.2”, “533.20”, “533.21”, “533.3”, 
“533.30”, “533.31”, “533.4”, “533.40”, “533.41”, “533.5”, “533.50”, “533.51”, “533.6”, “533.60”, “533.61”, “533.7”,
“533.70”, “533.71”, “533.9”, “533.90”, “533.91”, “534”, “534.0”, “534.00”, “534.01”, “534.1”, “534.10”, “534.11”, 
“534.2”, “534.20”, “534.21”, “534.3”, “534.30”, “534.31”, “534.4”, “534.40”, “534.41”, “534.5”, “534.50”, “534.51”, 
“534.6”, “534.60”, “534.61”, “534.7”, “534.70”, “534.71”, “534.9”, “534.90”, “534.91” }
Diagnosis Code (Any Position), ICD-10 is any of: { “K25.0”, “K25.1”, “K25.2”, “K25.3”, “K25.4”, “K25.5”, 
“K25.6”, “K25.7”, “K25.9”, “K26.0”, “K26.1”, “K26.2”, “K26.3”, “K26.4”, “K26.5”, “K26.6”, “K26.7”, “K26.9”, 
“K27.0”, “K27.1”, “K27.2”, “K27.3”, “K27.4”, “K27.5”, “K27.6”, “K27.7”, “K27.9”, “K28.0”, “K28.1”, “K28.2”, 
“K28.3”, “K28.4”, “K28.5”, “K28.6”, “K28.7”, “K28.9” }
Gastroesophageal 
Reflux Disease
Any of the following criteria:
≥2 medical claims with a primary or secondary ICD-9-CM code for reflux esophagitis (530.11), esophageal reflux 
(530.81) or heartburn (787.1) or primary or secondary ICD-10-CM code for GERD (K21, K21.0, K21.9) or Heartburn 
(R12); ≥1 medical claim with a primary or secondary ICD-9-CM 530.11, 530.81 or 787.1 and either (a) ≥1 pharmacy 
claim for a PPI (esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole), an H2RA (cimetidine, 
famotidine, nizatidine, or ranitidine) or “other” GERD agent (bethanechol, metoclopramide, sucralfate) or (b) ≥1 
medical claim with a primary or secondary ICD-9-CM code for esophageal stricture (530.3) Barrett’s esophagus 
(530.85), esophageal ulcer (530.2x) or esophagitis (530.1x).
Type 1 Diabetes 
Mellitus
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “250.11”, “250.13”, “250.21”, “250.23”, “250.31”, “250.33”, 
“250.41”, “250.43”, “250.51”, “250.53”, “250.61”, “250.63”, “250.71”, “250.73”, “250.81”, “250.83”, “250.91”, 

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“250.93”, “250.01”, “250.03” }
Diagnosis Code (Any Position), ICD-10 is any of: { “E10”, “E10.1”, “E10.10”, “E10.11”, “E10.2”, “E10.21”, 
“E10.22”, “E10.29”, “E10.3”, “E10.31”, “E10.311”, “E10.319”, “E10.32”, “E10.321”, “E10.329”, “E10.33”, 
“E10.331”, “E10.339”, “E10.34”, “E10.341”, “E10.349”, “E10.35”, “E10.351”, “E10.359”, “E10.36”, “E10.39”, 
“E10.4”, “E10.40”, “E10.41”, “E10.42”, “E10.43”, “E10.44”, “E10.49”, “E10.5”, “E10.51”, “E10.52”, “E10.59”, 
“E10.6”, “E10.61”, “E10.610”, “E10.618”, “E10.62”, “E10.620”, “E10.621”, “E10.622”, “E10.628”, “E10.63”, 
“E10.630”, “E10.638”, “E10.64”, “E10.641”, “E10.649”, “E10.65”, “E10.69”, “E10.8”, “E10.9” }
Type 2 Diabetes 
Mellitus
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “250.00”, “250.02”, “250.10”, “250.12”, “250.20”, “250.22”, 
“250.30”, “250.32”, “250.40”, “250.42”, “250.50”, “250.52”, “250.60”, “250.62”, “250.70”, “250.72”, “250.80”, 
“250.82”, “250.90”, “250.92” }
Diagnosis Code (Any Position), ICD-10 is any of: { “E11.00”, “E11.01”, “E11.21”, “E11.29”, “E11.311”, 
“E11.319”, “E11.36”, “E11.39”, “E11.40”, “E11.51”, “E11.618”, “E11.620”, “E11.621”, “E11.622”, “E11.628”, 
“E11.630”, “E11.638”, “E11.641”, “E11.649”, “E11.65”, “E11.69”, “E11.8”, “E11.9”, “E13.10” }
Type 1 or Type 2 
Diabetes without 
Complications
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “250.0”, “250.00”, “250.01”, “250.02”, “250.03”, “250.1”, 
“250.10”, “250.11”, “250.12”, “250.13”, “250.2”, “250.20”, “250.21”, “250.22”, “250.23”, “250.3”, “250.7”, 
“250.70”, “250.71”, “250.72”, “250.73”, “249.0”, “249.00”, “249.01” }
Diagnosis Code (Any Position), ICD-10 is any of: { “E10.1”, “E10.6”, “E10.8”, “E10.9”, “E11.0”, “E11.6”, 
“E11.8”, “E11.9”, “E13.0”, “E13.1”, “E13.6”, “E13.8”, “E13.9” }

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Type 1 or Type 2 
Diabetes with 
Complications
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “250.4”, “250.40”, “250.41”, “250.42”, “250.43”, “250.5”, 
“250.50”, “250.51”, “250.52”, “250.53”, “250.6”, “250.60”, “250.61”, “250.62”, “250.63”, “250.3”, “250.30”, 
“250.31”, “250.32”, “250.33” }
Diagnosis Code (Any Position), ICD-10 is any of: { “E10.2”, “E10.21”, “E10.22”, “E10.29”, “E10.3”, “E10.31”, 
“E10.311”, “E10.319”, “E10.32”, “E10.321”, “E10.329”, “E10.33”, “E10.331”, “E10.339”, “E10.34”, “E10.341”, 
“E10.349”, “E10.35”, “E10.351”, “E10.359”, “E10.36”, “E10.39”, “E10.4”, “E10.40”, “E10.41”, “E10.42”, 
“E10.43”, “E10.44”, “E10.49”, “E10.5”, “E11.2”, “E11.21”, “E11.22”, “E11.29”, “E11.3”, “E11.31”, “E11.311”, 
“E11.319”, “E11.32”, “E11.321”, “E11.329”, “E11.33”, “E11.331”, “E11.339”, “E11.34”, “E11.341”, “E11.349”, 
“E11.35”, “E11.351”, “E11.359”, “E11.36”, “E11.39”, “E11.4”, “E11.40”, “E11.41”, “E11.42”, “E11.43”, “E11.44”, 
“E11.49”, “E11.5”, “E13.4”, “E13.40”, “E13.41”, “E13.42”, “E13.43”, “E13.44”, “E13.49”, “E13.5” }
Mild Liver Disease
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “571.2”, “571.4”, “571.40”, “571.41”, “571.42”, “571.49”, 
“571.5”, “571.6” }
Diagnosis Code (Any Position), ICD-10 is any of: { “B18.0”, “B18.1”, “B18.2”, “B18.8”, “B18.9”, “K70.0”, 
“K70.1”, “K70.10”, “K70.11”, “K70.2”, “K70.3”, “K70.9”, “K71.3”, “K71.4”, “K71.5”, “K71.7”, “K73.0”, “K73.1”, 
“K73.2”, “K73.8”, “K73.9”, “K74.0”, “K74.1”, “K74.2”, “K74.3”, “K74.4”, “K74.5”, “K74.6”, “K74.60”, “K74.69”, 
“K76.0”, “K76.2”, “K76.3”, “K76.4”, “K76.8”, “K76.9”, “Z94.4” }
Moderate/Severe 
Liver Disease
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “456.0”, “456.1”, “456.2”, “456.20”, “456.21”, “572.2”, 
“572.3”, “572.4”, “572.8” }
Diagnosis Code (Any Position), ICD-10 is any of: { “I85.0”, “I86.4”, “K70.4”, “K71.1”, “K72.1”, “K72.9”, 
“K76.5”, “K76.6”, “K76.7” }

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Renal Disease
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “582”, “582.0”, “582.1”, “582.2”, “582.4”, “582.8”, “582.81”, 
“582.89”, “582.9”, “583”, “583.0”, “583.1”, “583.2”, “583.4”, “583.6”, “583.7”, “585”, “585.1”, “585.2”, “585.3”, 
“585.4”, “585.5”, “585.6”, “585.9”, “586”, “588”, “588.0”, “588.1”, “588.8”, “588.81”, “588.89”, “588.9” }
Diagnosis Code (Any Position), ICD-10 is any of: { “I12.0”, “I13.1”, “N03.2”, “N03.3”, “N03.4”, “N03.5”, 
“N03.6”, “N03.7”, “N05.2”, “N05.3”, “N05.4”, “N05.5”, “N05.6”, “N05.7”, “N18.1”, “N18.2”, “N18.3”, “N18.4”, 
“N18.5”, “N18.6”, “N18.9”, “N25.0”, “Z49.0”, “Z49.01”, “Z49.02”, “Z94.0”, “Z99.2” }
Metastatic Solid 
Tumors
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “196”, “196.0”, “196.1”, “196.2”, “196.3”, “196.5”, “196.6”, 
“196.8”, “196.9”, “197”, “197.0”, “197.1”, “197.2”, “197.3”, “197.4”, “197.5”, “197.6”, “197.7”, “197.8”, “198”, 
“198.0”, “198.1”, “198.2”, “198.3”, “198.4”, “198.5”, “198.6”, “198.7”, “198.8”, “198.81”, “198.82”, “198.89”, 
“199”, “199.0”, “199.1” }
Diagnosis Code (Any Position), ICD-10 is any of: { “C77.0”, “C77.1”, “C77.2”, “C77.3”, “C77.4”, “C77.5”, 
“C77.8”, “C77.9”, “C78”, “C78.0”, “C78.00”, “C78.01”, “C78.02”, “C78.1”, “C78.2”, “C78.3”, “C78.30”, “C78.39”, 
“C78.4”, “C78.5”, “C78.6”, “C78.7”, “C78.8”, “C78.80”, “C78.89”, “C79”, “C79.0”, “C79.00”, “C79.01”, “C79.02”, 
“C79.1”, “C79.10”, “C79.11”, “C79.19”, “C79.2”, “C79.3”, “C79.31”, “C79.32”, “C79.4”, “C79.40”, “C79.49”, 
“C79.5”, “C79.51”, “C79.52”, “C79.6”, “C79.60”, “C79.61”, “C79.62”, “C79.7”, “C79.70”, “C79.71”, “C79.72”, 
“C79.8”, “C79.81”, “C79.82”, “C79.89”, “C79.9”, “C80”, “C80.0”, “C80.1”, “C80.2” }
HIV/AIDS
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “042”, “795.71”, “V08”, “V65.44”, “079.53” }
Diagnosis Code (Any Position), ICD-10 is any of: { “B20”, “Z21”, “B97.35”, “O98.7*”, “Z71.7” }
Hemiplegia or 
Paraplegia
1 Inpatient or 2 Outpatient (30 – 365 days apart)
Diagnosis Code (Any Position), ICD-9 is any of: { “342”, “342.0”, “342.00”, “342.01”, “342.02”, “342.1”, “342.10”, 

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“342.11”, “342.12”, “342.8”, “342.80”, “342.81”, “342.82”, “342.9”, “342.90”, “342.91”, “342.92”, “344.1” }
Diagnosis Code (Any Position), ICD-10 is any of: { “G81.00”, “G81.01”, “G81.02”, “G81.03”, “G81.04”, “G81.10”, 
“G81.11”, “G81.12”, “G81.13”, “G81.14”, “G81.90”, “G81.91”, “G81.92”, “G81.93”, “G81.94”, “G82.20”, “G81”, 
“G81.9”, “I69.05”, “I69.051”, “I69.052”, “I69.053”, “I69.054”, “I69.059”, “I69.15”, “I69.151”, “I69.152”, “I69.153”, 
“I69.154”, “I69.159”, “I69.25”, “I69.251”, “I69.252”, “I69.253”, “I69.254”, “I69.259”, “I69.35”, “I69.351”, 
“I69.352”, “I69.353”, “I69.354”, “I69.359”, “I69.85”, “I69.851”, “I69.852”, “I69.853”, “I69.854”, “I69.859”, 
“I69.95”, “I69.951”, “I69.952”, “I69.953”, “I69.954”, “I69.959”, “G81.0”, “G81.1”, “G82.2”, “G82”, “G82.21”, 
“G82.22”, “G04.1”, “G11.4” }
Lifestyle
Smoking-related 
claim
1 Inpatient or 1 Outpatient
Diagnosis Code (Any Position), ICD-9 is any of: { “305.1”, “V15.82, “989.84”, “649.0x” }
Diagnosis Code (Any Position), ICD-10 is any of: { “F17.2”, “T65.2”, “Z71.6”, “O99.33”, “O99.330”, “O99.331”, 
“O99.332”, “O99.333”, “O99.334”, “O99.335”, “Z72.0”, “Z81.2” }
Procedure Code (Any Position), CPT and HCPC is any of: { “99406”, “99407”, “G0436”, “G0437”, “G9016”, 
“S9453”, “S4995”, “G9276”, “G9458”, “1034F”, “4004F”, “4001F”}
Vaccination for 
Influenza/Pneumococ
cus
1 Inpatient Service or 1 Outpatient
Procedure Code (Position 1), CPT and HCPC is any of: { “4040F”, “90630”, “90653”, “90654”, “90655”, “90656”, 
“90657”, “90658”, “90659”, “90660”, “90661”, “90662”, “90663”, “90664”, “90665”, “90666”, “90667”, “90668”, 
“90669”, “90670”, “90672”, “90673”, “90685”, “90686”, “90687”, “90688”, “90732”, “G0008”, “G0009”, “G0919”, 
“G8108”, “G8115”, “G8864”, “G9279”, “Q0034”, “Q2033”, “Q2034”, “Q2035”, “Q2036”, “Q2037”, “Q2038”, 
“Q2039”, “S0195” }

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Respiratory Function Procedures/Tests
Pulmonary function 
tests
1 Inpatient or 1 Outpatient
Procedure Code (Any Position), CPT and HCPC is any of: { “3038F”, “94010”, “94014”, “94015”, “94060”, 
“94621”, “94720”, “94725”, “94726”, “94727”, “94728”, “94729”, “94750”, “94770”, “94799” }
Procedure Code (Any Position), ICD-9 is any of: { “89.37” }
Procedure Code (Any Position), ICD-10 is any of: { “4A0971Z”, “4A0981Z”, “4A09X1Z”, “4A1971Z”, 
“4A19X1Z” }
Six-minute walk test
1 Inpatient or 1 Outpatient
Legacy Attribute - Procedure Code (Any Position) is any of: { “94620” }
Chest X-ray
1 Inpatient or 1 Outpatient
Procedure Code (Any Position), CPT and HCPC is any of: { “71010”, “71020”, “71021”, “71022”, “71023”, 
“71030”, “71034”, “71035” }
High Resolution 
Chest CT
1 Inpatient or 1 Outpatient
Procedure Code (Any Position), CPT and HCPC is any of: { “71250”, “71270” }

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ANNEX 5. TABLE SHELLS AND PROPOSED FIGURES
Table 1. Cohort Selection 
Excluded
Remaining
Eligible Population
Did not meet cohort entry criteria (use of Tio/Olo or Umec/Vi)
< 180 days of continuous enrollment
Prior use of Umec/Vi during 180d washout
Prior use of Tio/Olo during 180d washout
Tio/Olo and Umec/Vi both occurring on cohort entry date
Age <40 years
No prior diagnosis of COPD any time prior using all available data
Diagnosis of Asthma any time prior using all available data
Diagnosis of Lung Cancer any time prior using all available data
Lung Transplant any time prior using all available data
Final cohort

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Table 2. Patient Characteristics of the Study Population (Unmatched/ Matched)
Tio/Olo
Umec/Vi
Standardized Difference (95% CI)
N
Median Follow-up Time [IQR]
Demographics
Age on index date
Mean (SD)
Median [IQR]
Gender
Male; n (%)
Female; n (%)
Region
Northeast; n (%)
North Central; n (%)
South; n (%)
West; n (%)
Missing/Unknown; n (%)
Insurance Type
Commercial; n (%)
Medicare; n (%)
Missing; n (%)
Year of Cohort Entry, n (%)
First Year (November 17, 2015 – November 30, 2016); n (%)
Second Year (December 1, 2016 – November 30, 2017); n (%)
Third Year (December 1, 2017 to March 31, 2018)
Concomitant Medications

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Tio/Olo
Umec/Vi
Standardized Difference (95% CI)
Oral Corticosteroids; n (%)
Short acting muscarinic antagonist (SAMA), n (%)
Short acting beta agonist (SABA), n (%)
Long acting muscarinic antagonist (LAMA), n (%)
Long acting beta agonist (LABA), n (%)
Inhaled corticosteroid (ICS), n (%)
LAMA / LABA combination (not Tio/Olo or Umec/Vi), n (%)
LABA / ICS combination, n (%)
LAMA / LABA / ICS combination, n (%)
NSAIDs, n (%)
Antihistamines, n (%)
Opioids, n (%)
Oral antibiotics, n (%)
Antidiabetic Agents (not including insulin), n (%)
Insulin (basal or mealtime), n (%)
Methotrexate, n (%)
Statins; n (%)
Antihypertensives; n (%)
Anticoagulants; n (%)
Anti-psychotic/anti-depressives/anxiolytic, n (%)
Oxygen therapy, n (%)
Comorbidities/Symptoms
History of All-Cause Hospitalization; n (%)
History of Emergency Department Visit; n (%)
History of Hospitalization due to Respiratory Condition; n (%)
Acute Myocardial Infarction; n (%)
Angina Pectoris; n (%)
Peripheral Vascular Disease; n (%)

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Tio/Olo
Umec/Vi
Standardized Difference (95% CI)
Heart Failure; n (%)
Hypertension; n (%)
Upper Respiratory Tract Infection; n (%)
Lower Respiratory Tract Infection; n (%)
Cardiac Arrhythmias; n (%)
Cerebrovascular Disease; n (%)
All Cancers (except non-melanoma skin cancer); n (%)
Allergic Rhinitis; n (%)
Chronic Sinusitis; n (%)
Bronchietasis; n (%)
Pneumonia; n (%)
Chronic Bronchitis; n (%)
Exertional Breathlessness; n (%)
Anxiety; n (%)
Dementia; n (%)
Depression; n (%)
Osteoporosis; n (%)
Charlson-Deyo Comorbidity Index, continuous
mean (sd)
median [IQR]
Charlson-Deyo Comorbidity Index, categorical
0; n (%)
1; n (%)
2; n (%)
3+; n (%)
Acute Liver Injury or Failure; n (%)
Chronic Kidney Disease (without ESRD); n (%)
End Stage Renal Disease; n (%)
Rheumatologic Disease; n (%)

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Tio/Olo
Umec/Vi
Standardized Difference (95% CI)
Peptic Ulcer Disease; n (%)
Gastroesophageal reflux disease (GERD); n (%)
Type 1 Diabetes Mellitus; n (%)
Type 2 Diabetes Mellitus; n (%)
Type 1 or Type 2 Diabetes with no chronic complications; n (%)
Type 1 or Type 2 Diabetes with chronic complications; n (%)
Mild Liver Disease; n (%)
Moderate to Severe Liver Disease; n (%)
Renal Disease; n (%)
Metastatic Solid Tumor; n (%)
HIV/AIDS; n (%)
Hemiplegia or Paraplegia; n (%)
Lifestyle
Smoking Related Claim or Intervention; n (%)
Vaccination for Influenza; n (%)
Vaccination for Pneumococcus; n (%)
Respiratory Function Procedures/Tests
Pulmonary function tests; n (%)
Six-minute walk test; n (%)
Chest X-ray; n (%)
Chest HRCT; n (%)
Tio/Olo, tiotropium/olodaterol; Umec/Vi, umeclidinium, vilanterol.

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Table 3. Absolute Standardized Differences as Measured in the Unmatched vs. Matched Cohorts
Abs. Std. Diff. 
(Unmatched)
Abs. Std. Diff. 
(Matched)
Change
Change (%)
Demographics
Age on index date
Gender
Region
Insurance Type
Year of Cohort Entry
Oral Corticosteroids; n (%)
Short acting muscarinic antagonist (SAMA), n (%)
Short acting beta agonist (SABA), n (%)
Long acting muscarinic antagonist (LAMA), n (%)
Long acting beta agonist (LABA), n (%)
Inhaled corticosteroid (ICS), n (%)
LAMA / LABA combination (not Tio/Olo or 
Umec/Vi), n (%)
LABA / ICS combination, n (%)
LAMA / LABA / ICS combination, n (%)
NSAIDs, n (%)
Antihistamines, n (%)
Opioids, n (%)
Oral antibiotics, n (%)
Antidiabetic Agents (not including insulin), n (%)
Insulin (basal or mealtime), n (%)
Methotrexate, n (%)
Statins; n (%)
Antihypertensives; n (%)
Anticoagulants; n (%)

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Abs. Std. Diff. 
(Unmatched)
Abs. Std. Diff. 
(Matched)
Change
Change (%)
Anti-psychotic/anti-depressives/anxiolytic, n (%)
Oxygen therapy, n (%)
Comorbidities/Symptoms
History of All-Cause Hospitalization; n (%)
History of Emergency Department Visit; n (%)
History of Hospitalization due to Respiratory 
Condition; n (%)
Acute Myocardial Infarction; n (%)
Angina Pectoris; n (%)
Peripheral Vascular Disease; n (%)
Heart Failure; n (%)
Hypertension; n (%)
Upper Respiratory Tract Infection; n (%)
Lower Respiratory Tract Infection; n (%)
Cardiac Arrhythmias; n (%)
Cerebrovascular Disease; n (%)
All Cancers (except non-melanoma skin cancer); n 
(%)
Allergic Rhinitis; n (%)
Chronic Sinusitis; n (%)
Bronchietasis; n (%)
Pneumonia; n (%)
Chronic Bronchitis; n (%)
Exertional Breathlessness; n (%)
Anxiety; n (%)
Dementia; n (%)
Depression; n (%)
Osteoporosis; n (%)

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Abs. Std. Diff. 
(Unmatched)
Abs. Std. Diff. 
(Matched)
Change
Change (%)
Charlson-Deyo Comorbidity Index, continuous
Charlson-Deyo Comorbidity Index, categorical
Acute Liver Injury or Failure; n (%)
Chronic Kidney Disease (without ESRD); n (%)
End Stage Renal Disease; n (%)
Rheumatologic Disease; n (%)
Peptic Ulcer Disease; n (%)
Gastroesophageal reflux disease (GERD); n (%)
Type 1 Diabetes Mellitus; n (%)
Type 2 Diabetes Mellitus; n (%)
Type 1 or Type 2 Diabetes with no chronic 
complications; n (%)
Type 1 or Type 2 Diabetes with chronic 
complications; n (%)
Mild Liver Disease; n (%)
Moderate to Severe Liver Disease; n (%)
Renal Disease; n (%)
Metastatic Solid Tumor; n (%)
HIV/AIDS; n (%)
Hemiplegia or Paraplegia; n (%)
Vaccination for Influenza / Pneumococcus; n (%)
Respiratory Function Procedures/Tests
Pulmonary function tests; n (%)
Six-minute walk test; n (%)
Chest X-ray; n (%)
Chest HRCT; n (%)
Tio/Olo, tiotropium/olodaterol; Umec/Vi, umeclidinium, vilanterol.

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Table 4. Unmatched Cohort Discontinuation Rates and Risks for Tio/Olo vs. Umec/Vi.
Parameter
Tio/Olo
Umec/Vi
Number of patients
Number of person-years
Number of events (discontinuations)
Rate
Rate per 1,000 person-years
Rate Difference per 1,000 person-years (95% CI)
1.0 (Reference)
Rate Ratio (95% CI)
1.0 (Reference)
Risk
Risk per 1,000 patients
Risk Difference per 1,000 person-years (95% CI)
1.0 (Reference)
Risk Ratio (95% CI)
1.0 (Reference)
Primary Estimates
Unadjusted Hazard Ratio (95% CI) 
1.0 (Reference)
Fully adjusted Hazard Ratio (95% CI)
1.0 (Reference)
Tio/Olo, tiotropium/olodaterol; Umec/Vi, umeclidinium, vilanterol.

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Table 5. 1:2 Matched Cohort Discontinuation Risk for Tio/Olo vs. Umec/Vi.
Parameter
Tio/Olo
Umec/Vi
Number of patients
Number of person-years
Number of events (discontinuations)
Rate
Rate per 1,000 person-years
Rate Difference per 1,000 person-years (95% CI)
1.0 (Reference)
Rate Ratio (95% CI)
1.0 (Reference)
Risk
Risk per 1,000 patients
Risk Difference per 1,000 person-years (95% CI)
1.0 (Reference)
Risk Ratio (95% CI)
1.0 (Reference)
Primary Estimates
Matched Hazard Ratio (95% CI)
1.0 (Reference)
Tio/Olo, tiotropium/olodaterol; Umec/Vi, umeclidinium, vilanterol.

 
 
 
 
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