Comparative Effectiveness of Triple Therapy in COPD: A New-user Cohort Study
Conditions: Pulmonary Disease, Chronic Obstructive
Sponsor: Boehringer Ingelheim



Boehringer Ingelheim  
Page 27 of 33 
Protocol for observational studies based on existing data 
1237-0078 
<Document Number> 
Proprietary confidential information © 2019 Boehringer Ingelheim International GmbH or one or more of its affiliated companies 
ANNEX 2: ENCEPP CHECKLIST FOR STUDY PROTOCOLS 
ENCePP Checklist for Study Protocols (Revision 2, amended) 
Adopted by the ENCePP Steering Group on 14/01/2013 
 
Study title:  
Comparative effectiveness of triple therapy in COPD: A new-user cohort study 
 
Study reference number: 
205.526 
 
Section 1: Milestones 
 
Yes 
No 
N/A 
Page 
Number(s) 
1.1 Does the protocol specify timelines for  
1.1.1 Start of data collection1 
1.1.2 End of data collection2 
1.1.3 Study progress report(s)  
1.1.4 Interim progress report(s) 
1.1.5 Registration in the EU PAS register 
1.1.6 Final report of study results. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
16 
16 
13 
13 
      
13 
Comments: 
      
 
Section 2: Research question 
 
Yes 
No 
N/A 
Page 
Number(s) 
2.1 Does the formulation of the research question 
and objectives clearly explain:  
 
2.1.1 Why the study is conducted? (e.g. to address 
an important public health concern, a risk identified in the 
risk management plan, an emerging safety issue) 
 
2.1.2 The objective(s) of the study? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
14 
 
15 
 
2.1.3 The target population? (i.e. population or 
subgroup to whom the study results are intended to be 
generalised) 
 
2.1.4 Which formal hypothesis(-es) is (are) to 
be tested?  
 
2.1.5 If applicable, that there is no a priori 
hypothesis? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
16 
 
15 
 
      
Comments: 
      
 
 
                                                 
1 Date from which information on the first study is first recorded in the study dataset or, in the case of 
secondary use of data, the date from which data extraction starts. 
2 Date from which the analytical dataset is completely available. 

Boehringer Ingelheim  
Page 28 of 33 
Protocol for observational studies based on existing data 
1237-0078 
<Document Number> 
Proprietary confidential information © 2019 Boehringer Ingelheim International GmbH or one or more of its affiliated companies 
Section 3: Study design 
 
Yes 
No 
N/A 
Page 
Number(s) 
3.1 Is the study design described? (e.g. cohort, case-
control, randomised controlled trial, new or alternative 
design)  
 
 
 
16 
3.2 Does the protocol specify the primary and 
secondary (if applicable) endpoint(s) to be 
investigated? 
 
 
 
17-18 
3.3 Does the protocol describe the measure(s) of 
effect? (e.g. relative risk, odds ratio, deaths per 1000 
person-years, absolute risk, excess risk, incidence rate ratio, 
hazard ratio, number needed to harm (NNH) per year) 
 
 
 
20 
Comments: 
      
 
Section 4: Source and study populations 
 
Yes 
No 
N/A 
Page 
Number(s) 
4.1 Is the source population described? 
 
 
 
16 
4.2 Is the planned study population defined in terms 
of: 
4.2.1 Study time period? 
4.2.2 Age and sex? 
4.2.3 Country of origin? 
4.2.4 Disease/indication?  
4.2.5 Co-morbidity? 
4.2.6 Seasonality? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
16 
16 
16 
16 
      
      
4.3 Does the protocol define how the study 
population will be sampled from the source 
population? (e.g. event or inclusion/exclusion criteria)   
 
 
 
 
 
 
 
16 
Comments: 
      
 
Section 5: Exposure definition and 
measurement 
 
Yes 
No 
N/A 
Page 
Number(s) 
5.1 Does the protocol describe how exposure is 
defined and measured? (e.g. operational details for 
defining and categorising exposure)  
 
 
 
 
 
 
 
17 
5.2 Does the protocol discuss the validity of 
exposure measurement? (e.g. precision, accuracy, 
prospective ascertainment, exposure information recorded 
before the outcome occurred, use of validation sub-study) 
 
 
 
 
 
 
 
19 
5.3 Is exposure classified according to time 
windows? (e.g. current user, former user, non-use) 
 
 
 
 
 
 
 
17 
5.4 Is exposure classified based on biological 
mechanism of action and taking into account the 
 
 
 
 
 
 
 
      

Boehringer Ingelheim  
Page 29 of 33 
Protocol for observational studies based on existing data 
1237-0078 
<Document Number> 
Proprietary confidential information © 2019 Boehringer Ingelheim International GmbH or one or more of its affiliated companies 
Section 5: Exposure definition and 
measurement 
 
Yes 
No 
N/A 
Page 
Number(s) 
pharmacokinetics and pharmacodynamics of the 
drug? 
5.5 Does the protocol specify whether a dose-
dependent or duration-dependent response is 
measured? 
 
 
 
20 
Comments: 
      
 
Section 6: Endpoint definition and 
measurement 
 
Yes 
No 
N/A 
Page 
Number(s) 
6.1 Does the protocol describe how the endpoints 
are defined and measured?  
 
 
 
 
 
 
 
17-18 
6.2 Does the protocol discuss the validity of 
endpoint measurement? (e.g. precision, accuracy, 
sensitivity, specificity, positive predictive value, prospective 
or retrospective ascertainment, use of validation sub-study) 
 
 
 
 
 
 
 
19 
Comments: 
      
 
Section 7: Confounders and effect modifiers 
 
Yes 
No 
N/A 
Page 
Number(s) 
7.1 Does the protocol address known confounders? 
(e.g. collection of data on known confounders, methods of 
controlling for known confounders) 
 
 
 
 
 
 
 
18 
7.2 Does the protocol address known effect 
modifiers? (e.g. collection of data on known effect 
modifiers, anticipated direction of effect) 
 
 
 
 
 
 
 
21 
Comments: 
      
 
Section 8: Data sources 
Yes 
No 
N/A 
Page 
Number(s) 
8.1 Does the protocol describe the data source(s) 
used in the study for the ascertainment of: 
8.1.1 Exposure? (e.g. pharmacy dispensing, general 
practice prescribing, claims data, self-report, face-to-face 
interview, etc.)  
8.1.2 Endpoints? (e.g. clinical records, laboratory 
markers or values, claims data, self-report, patient interview 
including scales and questionnaires, vital statistics, etc.) 
8.1.3 Covariates?  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
19 
 
19 
 
19 
8.2 Does the protocol describe the information 
available from the data source(s) on: 
8.2.1 Exposure? (e.g. date of dispensing, drug quantity, 
dose,  number of days of supply prescription, daily dosage,  
prescriber)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
19 
 

Boehringer Ingelheim  
Page 30 of 33 
Protocol for observational studies based on existing data 
1237-0078 
<Document Number> 
Proprietary confidential information © 2019 Boehringer Ingelheim International GmbH or one or more of its affiliated companies 
Section 8: Data sources 
Yes 
No 
N/A 
Page 
Number(s) 
8.2.2 Endpoints? (e.g. date of occurrence, multiple 
event, severity measures related to event)  
8.2.3 Covariates? (e.g. age, sex, clinical and drug use 
history, co-morbidity, co-medications, life style, etc.) 
 
 
 
 
 
 
 
 
 
19 
 
19 
8.3 Is a coding system described for: 
8.3.1 Diseases? (e.g. International Classification of 
Diseases (ICD)-10) 
8.3.2 Endpoints? (e.g. Medical Dictionary for Regulatory 
Activities (MedDRA) for adverse events) 
8.3.3 Exposure? (e.g. WHO Drug Dictionary, Anatomical 
Therapeutic Chemical (ATC)Classification System) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
19 
 
19 
 
19 
8.4 Is the linkage method between data sources 
described? (e.g. based on a unique identifier or other)  
 
 
 
 
 
 
 
19 
Comments: 
      
 
Section 9: Study size and power 
 
Yes 
No 
N/A 
Page 
Number(s) 
9.1 Is sample size and/or statistical power 
calculated?  
 
 
 
19-20 
Comments: 
      
 
Section 10: Analysis plan 
 
Yes 
No 
N/A 
Page 
Number(s) 
10.1 Does the plan include measurement of excess 
risks? 
 
 
 
20-21 
10.2 Is the choice of statistical techniques 
described?  
 
 
 
20-21 
10.3 Are descriptive analyses included? 
 
 
 
20-21 
10.4 Are stratified analyses included? 
 
 
 
21 
10.5 Does the plan describe methods for adjusting 
for confounding? 
 
 
 
 
 
 
 
20-21 
10.6 Does the plan describe methods addressing 
effect modification? 
 
 
 
 
 
 
 
21 
Comments: 
      
 
Section 11: Data management and quality 
control 
 
Yes 
No 
N/A 
Page 
Number(s) 
11.1 Is information provided on the management of 
missing data? 
 
 
 
21 

Boehringer Ingelheim  
Page 31 of 33 
Protocol for observational studies based on existing data 
1237-0078 
<Document Number> 
Proprietary confidential information © 2019 Boehringer Ingelheim International GmbH or one or more of its affiliated companies 
Section 11: Data management and quality 
control 
 
Yes 
No 
N/A 
Page 
Number(s) 
11.2 Does the protocol provide information on data 
storage? (e.g. software and IT environment, database 
maintenance and anti-fraud protection, archiving) 
 
 
 
22 
11.3 Are methods of quality assurance described? 
 
 
 
22 
11.4  Does the protocol describe possible quality 
issues related to the data source(s)? 
 
 
 
22 
11.5 Is there a system in place for independent 
review of study results?  
 
 
 
25 
Comments: 
      
 
Section 12: Limitations 
 
Yes 
No 
N/A 
Page 
Number(s) 
12.1 Does the protocol discuss: 
12.1.1 Selection biases? 
12.1.2 Information biases? 
(e.g. anticipated direction and magnitude of such biases, 
validation sub-study, use of validation and external data, 
analytical methods) 
 
 
 
 
 
 
 
 
 
 
 
 
 
      
 
19-22 
12.2 Does the protocol discuss study feasibility? (e.g. 
sample size, anticipated exposure, duration of follow-up in 
a cohort study, patient recruitment) 
 
 
 
19 
12.3 Does the protocol address other limitations?  
 
 
 
19-22 
Comments: 
      
 
Section 13: Ethical issues 
 
Yes 
No 
N/A 
Page 
Number(s) 
13.1 Have requirements of Ethics 
Committee/Institutional Review Board approval 
been described? 
 
 
 
23 
13.2 Has any outcome of an ethical review 
procedure been addressed? 
 
 
 
      
13.3 Have data protection requirements been 
described? 
 
 
 
23 
Comments: 
      
 
Section 14: Amendments and deviations 
 
Yes 
No 
N/A 
Page 
Number(s) 
14.1 Does the protocol include a section to 
document future amendments and deviations?  
 
 
 
12 
Comments: 
      

Boehringer Ingelheim  
Page 32 of 33 
Protocol for observational studies based on existing data 
1237-0078 
<Document Number> 
Proprietary confidential information © 2019 Boehringer Ingelheim International GmbH or one or more of its affiliated companies 
 
 
 
Section 15: Plans for communication of study 
results 
 
Yes 
No 
N/A 
Page 
Number(s) 
15.1 Are plans described for communicating study 
results (e.g. to regulatory authorities)?  
 
 
 
      
15.2 Are plans described for disseminating study 
results externally, including publication? 
 
 
 
25 
 
Comments: 
      
 
Name of the main author of the protocol: 
 
Date: 23/02/2017 
 
Signature: ___________________________ 
 
 
 

Boehringer Ingelheim  
Page 33 of 33 
Protocol for observational studies based on existing data 
1237-0078 
<Document Number> 
Proprietary confidential information © 2019 Boehringer Ingelheim International GmbH or one or more of its affiliated companies 
ANNEX 3: ADDITIONAL INFORMATION 
Additional annexes may be included if necessary. 
ANNEX 3.1: DEFINITION OF STUDY EXPOSURES 
See section 7.4.1.  Complete list of drug codes will be finalized and supplied to BI in the 
course of the study 
ANNEX 3.2: DEFINITIONS OF STUDY OUTCOMES  
See section 7.4.2.  Complete list of READ and ICD-10 codes will be finalized and supplied to 
BI in the course of the study 
ANNEX 3.3: DEFINITIONS OF STUDY COVARIATES 
See section 7.4.3.  Complete list of READ and drug codes will be finalized and supplied to BI 
in the course of the study 
 
ANNEX 3.4: STATISTICAL CONSIDERATIONS 
See section 7.9.