Non-interventional Study Describing Patients´ Perception on Anticoagulant Treatment and Treatment Convenience When Treated With Pradaxa or Vitamine K Antagonist for Stroke Prevention in Non-Valvular Atrial Fibrillation
Conditions: Atrial Fibrillation, Stroke
Sponsor: Boehringer Ingelheim

ABCD
TITLE PAGE
Non-interventional Study Protocol
Document Number:
c03594400-01
BI Study Number:
1160.249
BI Investigational
Product(s):
Dabigatran etexilate (Pradaxa®)
Title:
Non-interventional study describing  patients´ perception 
on anticoagulant treatment and treatment convenience 
when treated with Pradaxa® or Vitamine K Antagonist for 
Stroke Prevention in Non-Valvular Atrial Fibrillation
Protocol version 
identifier:
1.0
Date of last version of 
protocol:
23 July 2015
PASS:
No
EU PAS register 
number:
Not yet available  
(study will be registered in EU PAS Register (ENCePP) 
and clinicaltrials.gov)
Active substance:
B01AE07 - Dabigatran etexilate
Medicinal product:
Dabigatran etexilate
Product reference:
EU/1/08/442 (EMA registration number)
Procedure number:
n.a.
Marketing authorisation 
holder(s):
This study is initiated, managed and financed by:
Boehringer Ingelheim RCV GmbH & Co KG
Division Medicine/Medical Affairs
Dr. Boehringer-Gasse 5-11
A-1121 Wien
Joint PASS:
No
Research question and 
objectives:
Primary objective:
Describe the non-valvular atrial fibrillation patient´s 
treatment perception by using the PACT-Q© (Perception on 
Anticoagulant Treatment Questionnaire).

Boehringer Ingelheim
Page 2 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Secondary objective:
Characterization of patient population (including dosing of 
Pradaxa®)
Country(-ies) of study:
13 countries: Russia, Poland, Romania, Hungary, Austria, 
Czech Republic, Bulgaria, Latvia, Estonia, Slovenia, 
Croatia, Serbia, and Israel
Authors:
 (Trial Clinical Monitor)
Tel: 
Fax:
Mobile:
(Team Member Medicine)
Tel: 
Fax: 
Mobile:
Marketing authorisation 
holder:
Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany
MAH contact person in 
case of PASS:
Not applicable
EU-QPPV in case of 
PASS:
Not applicable
Signature of EU-QPPV
in case of PASS:
Not applicable
Date:
23 July 2015
Page 1 of 53
Proprietary confidential information
© 2015 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

Boehringer Ingelheim
Page 3 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
1.
TABLE OF CONTENTS
1.
TABLE OF CONTENTS....................................................................................... 3
2.
LIST OF ABBREVIATIONS................................................................................ 5
3.
RESPONSIBLE PARTIES.................................................................................... 7
4.
ABSTRACT........................................................................................................... 8
5.
AMENDMENTS AND UPDATES..................................................................... 12
6.
MILESTONES..................................................................................................... 13
7.
RATIONALE AND BACKGROUND................................................................ 14
8.
RESEARCH QUESTION AND OBJECTIVES ................................................. 15
8.1
RESEARCH QUESTIONS............................................................................. 15
8.2
OBJECTIVES ................................................................................................. 15
9.
RESEARCH METHODS .................................................................................... 16
9.1
STUDY DESIGN............................................................................................ 16
9.2
SETTING........................................................................................................ 16
9.2.1
Selection of sites...................................................................................... 16
9.2.2
Inclusion criteria...................................................................................... 17
9.2.3
Exclusion criteria..................................................................................... 17
9.2.4
Removal of patients from the study ........................................................ 18
9.2.5
Visit schedule.......................................................................................... 18
9.2.6
Treatments............................................................................................... 21
9.2.7
Concomitant medications and restrictions .............................................. 21
9.2.8
Representativeness of the study population ............................................ 22
9.3
VARIABLES .................................................................................................. 22
9.3.1
For objective 1......................................................................................... 22
9.3.2
For objective 2......................................................................................... 22
9.4
DATA SOURCES........................................................................................... 23
9.5
STUDY SIZE.................................................................................................. 23
9.6
DATA MANAGEMENT................................................................................ 25
9.7
DATA ANALYSIS......................................................................................... 25
9.7.1
Study Design ........................................................................................... 25
9.7.2
Planned Analysis..................................................................................... 26
9.7.2.1
Main Analyses .................................................................................... 26
9.7.2.3
Safety Analyses................................................................................... 27

Boehringer Ingelheim
Page 4 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
9.7.2.4
Schedule of Planned Analyses............................................................ 28
9.7.3
Handling of missing data......................................................................... 28
9.8
QUALITY CONTROL................................................................................... 28
9.9
LIMITATIONS OF THE RESEARCH METHODS...................................... 29
9.10
OTHER ASPECTS ......................................................................................... 31
9.10.1
Informed Consent, Data Protection, Study Records ............................... 31
9.10.1.1 Study Approval, Patient Information, and Informed Consent............ 31
9.10.1.2 Data Quality Assurance ...................................................................... 32
9.10.1.3 Records ............................................................................................... 32
9.10.1.3.1
Source documents........................................................................... 32
9.10.1.3.2
Direct access to source data and documents................................... 33
9.10.1.4 Statement of Confidentiality............................................................... 33
9.10.1.5 Completion of Study........................................................................... 33
10.
PROTECTION OF HUMAN SUBJECTS .......................................................... 34
11.
MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS....................................................................................................... 35
11.1
DEFINITIONS OF ADVERSE EVENTS...................................................... 35
11.2
ADVERSE EVENT AND SERIOUS ADVERSE EVENT COLLECTION AND
REPORTING .................................................................................................. 36
11.3
REPORTING TO HEALTH AUTHORITIES................................................ 38
12.
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
............................................................................................................................. 39
13.
REFERENCES .................................................................................................... 40
13.1
PUBLISHED REFERENCES......................................................................... 40
13.2
UNPUBLISHED REFERENCES................................................................... 40
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS.............................................. 41
ANNEX 2. ENCEPP CECKLIST FOR STUDY PROTOCOLS ................................. 42
ANNEX 3. ADDITIONAL INFORMATION.............................................................. 43
ANNEX 3.1  Perception of anticoagulant treatment Questionnaire, part 1 (PACT-Q1)44
ANNEX 3.2  Perception of anticoagulant treatment Questionnaire, part 2 (PACT-Q2)47

Boehringer Ingelheim
Page 5 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
2.
LIST OF ABBREVIATIONS
AE
Adverse Event
AF
Atrial Fibrillation
ADR
Adverse Drug Reaction
ANCOVA
Analysis of Covariance
BI
Boehringer Ingelheim
CA
Competent Authority
CHA2DS2-
VASc score
Congestive heart failure, Hypertension, Age (≥75), Diabetes 
mellitus, Stroke/TIA, Vascular disease, Age 65-74, Sex category
CI
Confidence Interval
CML
Local Clinical Monitor
CRA
Clinical Research Associate
CRF
Case Report Form
DMP
Data Management Plan
eCRF
Electronic Case Report Form
DEDP
Drug Exposure During Pregnancy
EC
Ethics Committee
ECG
Electrocardiogram
EDC
Electronic Data Capture
EMA
European Medicine Agency
ENCePP
European Network of Centers for Pharmacoepidemiology and 
Pharmacovigilance
EudraCT
European Clinical Trials Database
EU PAS 
Register
European Post- Authorization Study Register
(current ENCePP electronic register of studies)
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GEP
Good Epidemiological Practice
GPP
Good Pharmacoepidemiology Practice
GPV CTC
Global Pharmacovigilance Clinical Trial Coordinator
HAS-BLED
Hypertension, Abnormal renal and liver function, Stroke (1 point), 
Bleeding history or predisposition, Labile INR, Elderly (>65 years), 

Boehringer Ingelheim
Page 6 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Drugs and Alcohol.
ICH
International Conference of Harmonisation
ICSR
Individual Case Safety Report
IEC
Independent Ethics Committee
INR
International Normalized Ratio
IRB
Institutional Review Board
ISF
Investigator Site File
MAH
Marketing Authorization Holder
n.a.
Not applicable / not available
NVAF
Non valvular atrial fibrillation
OPU
Operative Unit
OAC
Oral anticoagulation
PACT-Q©
Perception of Anticoagulant Treatment Questionnaire
SAE
Serious Adverse Event
SDV
Source Data Verification
SEAP
Statistical and Epidemiological Analysis Plan
SmPC
Summary of Product Characteristics
SOP
Standard Operating Procedure
SPAF
Stroke Prophylaxis (or Prevention) in Atrial Fibrillation
VKA
Vitamin K Antagonist

Boehringer Ingelheim
Page 7 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
3.
RESPONSIBLE PARTIES
Therapeutic Area 
Cardiovascular Medicine (TA
Team Member Medical Affairs (TM MA)
Team Member Epidemiology (TM Epi)
Global Epidemiology (  GEpi)
Therapeutic Area
Risk Management (TA
RM), and
Pharmacovigilance Working Group  (PVWG) 
Trial Clinical Monitor (TCM)
Trial Statistician (TSTAT)

Boehringer Ingelheim
Page 8 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
4.
ABSTRACT
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
Pradaxa® (Dabigatran etexilate), or 
Vitamin K Antagonist (VKA)
Name of active ingredient:
Dabigatran, or VKA
Protocol date:
Study
number:
Version/Revision:
Version/Revision 
date:
23 July 2015
1160.249
1.0
n.a.
Title of study:
Non-interventional study describing patients´ perception on 
anticoagulant treatment and treatment convenience when treated with 
Pradaxa® or Vitamin K Antagonist for Stroke Prophylaxis in Atrial 
Fibrillation.
Rationale and 
background:
Pradaxa® (Dabigatran etexilate) is a direct Thrombin inhibitor 
approved in Europe, USA and many other countries worldwide for the 
prevention of stroke and systemic embolism in adult patients with non-
valvular atrial fibrillation with one or more risk factors. Data on how 
patients perceive Pradaxa® treatment in the context of non-valvular 
atrial fibrillation and anticoagulation management do only exist to a 
limited degree in Europe. (R15-1312).
The decision in clinical practice to use Pradaxa® as the first novel 
anticoagulant or established vitamin K antagonists depends on many 
factors related to the patient and prescribing physician.
The aim of this non-interventional study is to describe patients’ 
perception of anticoagulant treatment when using Pradaxa® to prevent 
stroke and systemic embolism while suffering from non-valvular atrial 
fibrillation (according to its approved indication in the approved 
dosages of 110 mg or 150 mg twice daily) in comparison to using 
Vitamin K Antagonist (VKA).

Boehringer Ingelheim
Page 9 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
Pradaxa® (Dabigatran etexilate), or 
Vitamin K Antagonist (VKA)
Name of active ingredient:
Dabigatran, or VKA
Protocol date:
Study 
number:
Version/Revision:
Version/Revision 
date:
23 July 2015
1160.249
1.0
n.a.
Research 
questions and 
objectives:
!
Objective 1: How do patients perceive anticoagulation treatment with 
Pradaxa® for stroke prevention in non-valvular atrial fibrillation 
(NVAF) in comparison with VKA? 
o
With further exploratory objectives: 
o
Is there a variation of treatment convenience and treatment 
satisfaction among different age groups? Is there a difference 
in treatment convenience and treatment satisfaction between 
switchers and newly initiated patients? 
o
What is treatment expectation of newly diagnosed NVAF 
patients before they start treatment with VKA or Pradaxa®
o
Is there any geographical variation in treatment perception?
!
Objective 2: What are the characteristics of patients receiving 
anticoagulation treatment for stroke prevention regarding 
demographics, physician rated scores, kidney function, treatment 
(choice of treatment, dosing)?
Study design:
Non-interventional study of AF patients in Europe with a current VKA
therapy and subsequent initiation of Pradaxa® OR patients being newly 
diagnosed with AF and initiated on Pradaxa® or VKA.
Population:
Patients diagnosed with non-valvular atrial fibrillation (NVAF) and 
eligible for Pradaxa® or VKA treatment according to Pradaxa® or 
respective VKA label.
Variables:
For objective 1:
Primary outcome 
For Cohort A (NVAF patients on VKA who are switched to 
Pradaxa®)):
-
Mean PACT-Q2 scores at second and last assessment compared to 
baseline assessment.
For Cohort B (newly diagnosed NVAF patients initiated to either 
VKA or Pradaxa®)):
-
Mean PACT-Q2 scores at second and last assessment compared 
between treatment groups.
Secondary outcome 
For Cohort A (switched to Pradaxa®):
-
Mean PACT-Q2 scores at last assessment compared to second 

Boehringer Ingelheim
Page 10 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
Pradaxa® (Dabigatran etexilate), or 
Vitamin K Antagonist (VKA)
Name of active ingredient:
Dabigatran, or VKA
Protocol date:
Study 
number:
Version/Revision:
Version/Revision 
date:
23 July 2015
1160.249
1.0
n.a.
assessment.
For Cohort B (newly initiated to VKA or Pradaxa®):
-
Description of PACT-Q1 items at baseline.
 
 
 
 
For objective 2:
Primary outcome:
Characterization of patients from both cohorts according to
-
Age
-
Gender
-
CHA2DS2-VASc score (R10-5332)
-
HAS-BLED score (modified HAS-BLED for newly initiated 
patients) (R10-6394)
-
Kidney function (creatinine clearance)
-
Co-morbidities
-
Co-medication
-
Dosing of Pradaxa®
-
Duration of previous VKA treatment (for Cohort A)
Data sources:
-
New data collection 
-
Questionnaires completed by patients
-
Patient characteristics completed by physician’s judgement and 
records.
Study size:
Up to 9000 patients in 13 Central & Eastern European countries
Data analysis:
In this  non-interventional study, baseline and longitudinal follow-up data 

Boehringer Ingelheim
Page 11 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
Pradaxa® (Dabigatran etexilate), or 
Vitamin K Antagonist (VKA)
Name of active ingredient:
Dabigatran, or VKA
Protocol date:
Study 
number:
Version/Revision:
Version/Revision 
date:
23 July 2015
1160.249
1.0
n.a.
over 6 months will be collected for non-valvular AF patients with a 
current VKA therapy and subsequent initiation of Pradaxa®  in Cohort A, 
and for newly diagnosed AF patients initiated on Pradaxa® or VKA in 
Cohort B.
Data from baseline and the longitudinal follow-up will be summarized 
descriptively. For Cohort A, mean PACT-Q2 scores between assessments 
will be compared using paired t-tests. For Cohort B, mean PACT-Q2 
scores between Pradaxa® and VKA patients will be compared using 
propensity score matched analysis.
Milestones:
Planned start of data collection: November-2015
Planned end of data collection: December-2016
Planned final study report: May-2017

Boehringer Ingelheim
Page 12 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
5.
AMENDMENTS AND UPDATES
Not applicable

Boehringer Ingelheim
Page 13 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
6.
MILESTONES
Milestone
Planned Date
Start of data collection
November-2015
End of data collection
December-2016
Registration in the EU PAS 
register
Will be registered before study initiation on encepp.eu 
and clinicaltrials.gov
Final report of study results:
May-2017

Boehringer Ingelheim
Page 14 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
7.
RATIONALE AND BACKGROUND
Pradaxa® (Dabigatran etexilate) is a direct Thrombin inhibitor approved in Europe, USA and 
many other countries worldwide for the prevention of stroke and systemic embolism in adult 
patients with non-valvular atrial fibrillation with one or more risk factors. 
Pradaxa® has been studied in the RELY study, one of the largest atrial fibrillation outcome 
studies (P13-05668). Over the course of one year, all anticoagulated patients without outcome 
events (e.g. strokes or major bleedings) had stable HRQoL. Other data on how patients 
perceive Pradaxa® treatment in the context of atrial fibrillation disease management only 
exist to a limited degree in Europe. (R15-1312)
The decision in clinical practice to use Pradaxa® as the first novel anticoagulant or 
established vitamin K antagonists depends on many factors related to:
a) The patient: Level of information, health status, comorbid conditions and 
demographic factors, perception of anticoagulant treatment, understanding of the 
burden of the disease, access to the medication, educational measures informing about 
medications and reimbursement status in a particular country.   
b) The treating physician: Stroke risk assessment, bleeding risk assessment, 
understanding and adherence to guidelines, access and use of medical education, 
interaction with patients and overall local health care system.
It is assumed that these factors in real world clinical practice vary e.g. between countries with 
different health care systems, between patients who start anticoagulation treatment versus 
those who have anticoagulation experience already or between the treatment initiation versus 
the mid-term follow up on Pradaxa® or vitamin K antagonists. 
It is the aim of this non-interventional study to describe the patient perception of 
anticoagulation when treated with Pradaxa® to prevent stroke and systemic embolism while 
suffering from non-valvular atrial fibrillation (according to its approved indication in the 
approved dosages of 110 mg or 150 mg twice daily). To evaluate patient understanding of 
treatment and patient values it is important to assess patient’s perception of the treatment in 
the context of overall disease management as close as possible to the clinical practice. 
Furthermore it is important to anchor the Pradaxa® treatment perception data in different 
ways, in order to determine on how previously and newly diagnosed NVAF patients perceive 
treatment with Pradaxa®, in comparison to vitamin K antagonist treatment (being considered 
the standard anticoagulation treatment for stroke prevention in non-valvular atrial fibrillation 
over decades):
!
Compare the treatment perception data of patients, who are switched to Pradaxa®
treatment, to their perception about their previous anticoagulation (VKA) therapy , and
!
Compare the treatment perception data of patients who are newly initiated Pradaxa®
treatment to the treatment perception data of patients who are newly initiated to VKA
treatment
These real world data are needed to guide the scientific community in designing educational 
efforts for doctors and their patients and to assess the potential values of patient adherence 
programs when using Pradaxa® as the first novel anticoagulant. Also such data, describing 
patient’s perception on Pradaxa® anticoagulation in the context of patient-physician 
interaction managing stroke prevention in non-valvular atrial fibrillation cannot be obtained 
by market research.

Boehringer Ingelheim
Page 15 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
8.
RESEARCH QUESTION AND OBJECTIVES
8.1
RESEARCH QUESTIONS
This non-interventional study will address the following questions:
!
How do patients with non-valvular atrial fibrillation perceive anticoagulation 
treatment for stroke prevention (stratified in cohorts of patients switched from 
previous treatment to Pradaxa®, newly initiated treatment with Pradaxa®, newly 
initiated treatment with VKA)?
!
Is there a variation of treatment convenience and treatment satisfaction among 
different age groups? 
!
Is there a difference in treatment convenience and treatment satisfaction between 
switchers and newly initiated patients? 
!
Is there any geographical variation in treatment expectations?
!
What are the characteristics of patients receiving anticoagulation treatment for stroke 
prevention regarding demographics, physician rated risk scores, kidney function, 
concomitant diseases and concomitant medications, treatment for SPAF (choice of 
treatment, dosing)? 
Two cohorts of patients will be recruited:
Cohort A:
Patients having been treated with VKA and now being switched to Pradaxa®
Cohort B:
Patients newly diagnosed with non-valvular atrial fibrillation and initiated on either Pradaxa®
or VKA.
8.2
OBJECTIVES
Primary objective
!
Describe the non-valvular atrial fibrillation patient´s treatment perception by using the 
PACT-Q at three time-points at baseline, during initiation period and during the 
continuation period.
Secondary objective
!
Characterization of patient population (incl. dosing) in the participating European 
countries.

Boehringer Ingelheim
Page 16 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
9.
RESEARCH METHODS
9.1
STUDY DESIGN
This is a non-interventional multi-national, multi-centre study based on newly collected data. 
The study will enrol consented patients with non-valvular atrial fibrillation in Europe with a 
current VKA therapy and subsequent initiation of Pradaxa® (Cohort A)  OR patients being 
newly diagnosed with AF and initiated on Pradaxa® or VKA (Cohort B).
Patients will be followed over an observation period of 6 months. Data will be collected at 
three time points:
1. At Baseline ( initiation on Pradaxa® or VKA)
2. 30-45 days after initiation on Pradaxa® or VKA (initiation period)
3. 150-210 days after initiation on Pradaxa® or VKA (continuation period)
9.2
SETTING
It is planned that data of approximately 9000 patients from approximately 800 sites in 13
countries will be collected. Planned participating countries are Russia, Poland, Romania, 
Hungary, Austria, Czech Republic, Bulgaria, Latvia, Estonia, Slovenia, Croatia, Serbia, and 
Israel.
9.2.1
Selection of sites
Cardiologists and non-cardiologist sites regularly prescribing Pradaxa® and VKA for stroke 
prevention in atrial fibrillation according to the respective Summary of Product 
Characteristics will participate.
Selected sites within each country should include those physicians (e.g. cardiologists, non-
cardiologists) and facilities (e.g. specialist offices, hospitals, outpatient care centres etc.) that 
reflect the clinical practice in that country. Investigators that are currently participating in the 
BI registry program 1160.136 (GLORIA) are not allowed to participate in this study. 
These site selection criteria will help to ensure that the patients recruited into this study will 
represent the patients treated within that country. After initiation, every site should include 
the first consecutive suitable patients where decision for switch to Pradaxa® (Cohort A) or 
decision for initiation on Pradaxa® or VKA (Cohort B) has been made. In consecutive 
sampling, every eligible patient is selected until the required sample size is enrolled. This 
approach helps to reduce the likelihood of selection bias.
Balance between Cohorts within each country
Within each participating country, the recruitment of patients in Cohort A and Cohort B 
needs to be balanced (A:B = 1:2). Within Cohort B, the patient enrolment will be controlled 
as well, in order to ensure that an equal amount of data will be collected of AF patients newly 
treated with Pradaxa® (sub-Cohort B1) or with VKA (sub-Cohort B2) (Pradaxa®:VKA = 1:1). 
Therefore, the sponsor may have to decide to close the enrolment of patients for one of the 

Boehringer Ingelheim
Page 17 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Cohorts (or sub-Cohorts) during the recruitment period, if the other (sub)Cohort is exceeding 
the maximum number of enrolled patients planned for that country/site.
The decision for therapy has to be taken prior and independently of enrolment into the study. 
Only after the treatment decision for the patient is taken, the investigator can check and 
decide if a patient can be enrolled in Cohort A or Cohort B.
Patients will then have to sign informed consent before they can take part in the non-
interventional study.
A log of all patients included into the study (i.e. having given informed consent) will be 
maintained in the ISF at the investigational site irrespective of whether they complete the 
assessments or not.
9.2.2
Inclusion criteria
Cohort A:
1A.
Written informed consent prior to participation
2A.
Female and male patients ≥ 18 years of age with a diagnosis of non-valvular atrial 
fibrillation.
3A.
At least 3 months of continuous VKA treatment for stroke prevention prior to 
baseline assessment.
4A.
Patients switched to Pradaxa® according Summary of Product Characteristics and 
physician`s discretion.
OR 
Cohort B:
1B.
Written informed consent prior to participation.
2B.
Female and male patients ≥ 18 years of age newly diagnosed with non-valvular 
atrial fibrillation and no previous treatment for stroke prevention (no use of any 
OAC within one year prior to enrolment).
3B.
Stroke prevention treatment initiated with Pradaxa® or VKA according to 
Summary of Product Characteristics and physician`s discretion.
9.2.3
Exclusion criteria
1. Contraindication to the use of Pradaxa® or VKA as described in the Summary of 
Product Characteristics (SmPC)
2. Patients receiving Pradaxa® or VKA for any other condition than stroke prevention in 
non-valvular atrial fibrillation.
3. Current participation in any clinical trial of a drug or device

Boehringer Ingelheim
Page 18 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
4. Current participation in a Registry, e.g. the Gloria registry program, on the use of oral 
anticoagulation in AF
9.2.4
Removal of patients from the study
Every patient has the right to withdraw consent at any time during the study, without the need 
for justification and without any impact on the routine therapy.
A patient is considered permanently discontinued or withdrawn from treatment if the patient 
did not complete the treatment with Pradaxa® or VKA for the entire continuation period until 
Visit 3 and did not perform all visit 3 assessments.
Boehringer Ingelheim reserves the right to discontinue the study overall or at a particular 
study site at any time for the following reasons:
1. Failure to meet expected enrolment goals overall or at a particular study site.
2. Emergence of any efficacy/safety information that could significantly affect continuation 
of the study, or any other administrative reasons.
3. Violation of the protocol, or the contract by a study site or investigator, disturbing the 
appropriate conduct of the study.
9.2.5
Visit schedule
Collection of patient data should be managed during routine practice visits. The time-
schedule below can only be a recommendation; if a patient does not visit the site at these time 
points, data will not be collected (no visits will be conducted solely for study purposes).
Visits must be performed face-to-face and cannot be performed by phone, email or fax, as the 
patient has to complete the self-administered questionnaires.
1. At Baseline (at initiation on Pradaxa® or VKA)
2. 30-45 days after initiation on Pradaxa® or VKA (initiation period)
3. 150-210 days after initiation on Pradaxa® or VKA (continuation period)
Baseline visit (Visit 1):
No data collection for study purposes must be performed unless the patient has consented to 
participate in the study. Once the patient has signed the informed consent form, the patient is 
considered to be enrolled in the study and patient details should be recorded on the enrolment 
log.
The following procedures will be performed at the baseline visit:
!
Sign informed consent form
!
Review of inclusion and exclusion criteria
!
Collection of demographic data: age, gender, 
!
Collection of concomitant diseases/comorbidities  medical history and  at baseline
!
Collection of current concomitant therapies
!
Weight 

Boehringer Ingelheim
Page 19 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
!
Creatinine Clearance: serum creatinine value (if available) to be entered on eCRF, 
Creatinine Clearance according to Cockcroft-Gault formula to be automatically 
calculated
!
CHA2DS2-VASc and HAS-BLED score calculation in eCRF  
!
For Cohort A only: duration of previous treatment with VKA to be documented
!
For Cohort A only: reasons for switch to Pradaxa® to be documented
!
Documentation of Pradaxa® dosing
!
Patient will be asked to complete the following patient related questionnaires:
-
PACT-Q2 (Cohort A only)
-
PACT-Q1 (Cohort B only)
!
Treatment with Pradaxa® or VKA will be initiated
Initiation period (Visit 2):
During a routine practice visit occurring at 30 – 45 days after initiation of treatment, the 
following assessments will be documented:
!
Current dosing of Pradaxa® and reasons for dose change (if applicable)
!
New or changed concomitant diseases/co-morbidities
!
Changes in concomitant therapies
!
Creatinine Clearance: serum creatinine value (if available) to be entered on eCRF, 
Creatinine Clearance according to Cockcroft-Gault formula to be automatically 
calculated 
!
Weight (if needed for creatinine clearance calculation at V2)
!
Collection and reporting of ADR (serious and non-serious), fatal AEs, or pregnancies 
(if applicable)
!
Reasons for Pradaxa® or VKA discontinuation (if applicable)
!
Patients will be asked to complete the PACT-Q2 questionnaire
Continuation period (Visit 3):
During a routine practice visit occurring at 150-210 days after initiation of treatment, the 
following assessments will be documented:
!
Current dosing of Pradaxa® and reasons for dose change (if applicable)
!
New or changed concomitant diseases/co-morbidities
!
Changes in concomitant therapies
!
Creatinine Clearance: serum creatinine value (if available) to be entered on eCRF, 
Creatinine Clearance according to Cockcroft-Gault formula to be automatically 
calculated 
!
Weight (if needed for creatinine clearance calculation at V3)
!
Collection and reporting of ADR (serious and non-serious), fatal AEs, or pregnancies 
(if applicable)
!
Reasons for Pradaxa® or VKA discontinuation (if applicable)
!
Patients will be asked to complete the PACT-Q2 questionnaire
With this visit, the patient´s participation in the study will be completed. 

Boehringer Ingelheim
Page 20 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Table 9.2.5: 1 Visit & Data Collection Schedule
Visit
1
2
3
Assessment
Baseline
Initiation period
Continuation 
period
Day(s)
-
30-45 days after 
baseline
150 – 210 days
after baseline
Informed Consent1
X
Inclusion/exclusion criteria
X
Healthcare System Characteristics2
X
Patient demographics: age, gender
X
HAS- BLED score (to be calculated in 
the eCRF)
X
CHA2DS2-VASc score (to be 
calculated in the eCRF)
X
Duration of previous VKA treatment 
(for Cohort A only)
X
Reasons for switch to Pradaxa®
(for Cohort A only)
X
Start Pradaxa® or VKA treatment
X
Pradaxa® dosing (110 or 150mg) and 
reasons for dose changes if applicable
X
X
X
Weight3
X
X
X
Creatinine clearance calculation4
X
X
X
Concomitant diseases / comorbidities
X
X
X
Concomitant therapies
X
X
X
PACTQ -1 questionnaire
X (for Cohort B only)
PACTQ- 2 questionnaire
X (for Cohort A only)
X (both cohorts)
X (both cohorts)
ADR (serious and non-serious), fatal 
AE, pregnancy collection
X
X
Reason for Pradaxa® or VKA 
discontinuation 
X
X
Footnotes:
1 Written Informed Consent must be obtained prior to the baseline visit assessment.
2 Reimbursement Status (reimbursed, partially reimbursed or private pay), type of hospital or practice, and specialty of 
treating physician
3 Weight must be determined at visit 1 only, and to be entered at visit 2 and 3 only if existing serum creatinine value is 
available.
4 Creatinine clearance can only be calculated in the eCRF (via Cockroft-Gault Formula) if serum creatinine value is available 
from existing laboratory reports. No additional lab assessments must be performed for the study.

Boehringer Ingelheim
Page 21 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Description and justification of patient questionnaires:
PACT-Q© :
The PACT-Q was developed as a means to investigate patients´ satisfaction with 
anticoagulant treatment and treatment convenience in patients with deep venous thrombosis
(DVT), pulmonary embolism (PE) or atrial fibrillation (AF) (R15-1314, R15-1316). The 
PACT-Q is a self-administered questionnaire. It can be completed in about ten minutes. No 
specific training is required to complete this document.
The original PACT-Q consists of two parts and contains 27 items:
! The PACT-Q1 is composed of a single dimension (7 items), covering the expectations 
of patients regarding their anticoagulant treatment, and is to be administered before 
treatment initiation. 
! The PACT-Q2 is composed of three dimensions covering: convenience (11 items),
burden of disease and treatment (2 items), and anticoagulant treatment satisfaction (7 
items). The PACT-Q2 is to be administered to patients once treatment is ongoing. 
9.2.6
Treatments 
Patients will either be switched from VKA treatment to Pradaxa® (cohort A) or newly 
initiated on Pradaxa® or VKA (cohort B).
-
Pradaxa® 110 mg hard capsules
-
Pradaxa® 150 mg hard capsules
-
Vitamin K antagonist
Pradaxa® 110 mg and Pradaxa® 150 mg hard capsules contain Dabigatran etexilate (active 
ingredient: Dabigatran). 
Patients will receive daily dose of Pradaxa® according to the Summary of Product 
characteristics and physician´s discretion.
The choice of vitamin K antagonist and the appropriate dosing is in the discretion of the 
physician. The applicable Summary of Product characteristics of the chosen treatment should 
be referred to. The following website, accessed on 23 July 2015, shows the full list of 
products by active substance registered in the EU. 
Website.ec.europa.eu/health/documents/community-register/html/inn_full_a.htm
Dosing of VKA has to be monitored and individually adapted by regular measurements of 
INR values (International Normalized Ratio). 
The most recent version of the approved Pradaxa® SmPC can be found on the EMA webpage 
under Pradaxa® (debigatran etexilite -- Product information).
9.2.7
Concomitant medications and restrictions
All concomitant medications are prescribed based on the underlying medical condition and 
upon the discretion of the treating physician. No treatment will be withheld from the patients. 
Any prescription is in the responsibility of the treating physician.

Boehringer Ingelheim
Page 22 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
9.2.8
Representativeness of the study population
Inclusion and exclusion criteria have been limited to the respective SmPCs of Pradaxa® and 
VKA. Therefore the patient population recruited in this non-interventional study can be seen
as representative for patients receiving an oral anticoagulation for stroke prevention in non-
valvular atrial fibrillation.
9.3
VARIABLES
9.3.1
For objective 1
Primary outcome 
For Cohort A (switcher):
!
Mean PACT-Q2 scores at second and last assessment compared to baseline 
assessment
For Cohort B (newly initiated):
!
Mean PACT-Q2 scores at second and last assessment between treatment groups
Secondary outcome 
For Cohort A (switcher):
!
Mean PACT-Q2 score at last assessment compared to second assessment
For Cohort B (newly initiated):
!
Description of PACT-Q1 items at baseline
 
9.3.2
For objective 2
Primary outcome:
Characterization of patients from both cohorts according to
-
Age
-
Gender
-
CHA2DS2-VASc score (R10-5332)
-
HAS-BLED score (modified HAS-BLED for newly initiated patients) (R10-6394)
-
Kidney function (creatinine clearance)
-
Stroke- and/or bleeding related risk factors in medical history and at baseline
-
Co-morbidities
-
Concomitant therapies
-
Dosing of Pradaxa®
-
Duration of previous VKA treatment (for Cohort A)

Boehringer Ingelheim
Page 23 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
9.4
DATA SOURCES
Data will be newly collected from the patient by the investigator and recorded as source data 
at the site, i.e. the physicians records,  and entered in the eCRF by the investigator or site 
staff. Patients will be asked to complete the respective questionnaires during their routine 
visits. Patient demographic data, concomitant diseases and concomitant therapies will be 
completed based on the physician´s records. Information on Pradaxa® and/or VKA dosing 
will be collected from physician´s records. Creatinine clearance for assessment of kidney 
function will be calculated within the eCRF, by entering Creatinine values (from existing lab 
reports, if available), and weight (if applicable) to be measured by the physician or delegated 
site staff.
9.5
STUDY SIZE
It is planned that a total of approximately 9000 patients from 13 Central & Eastern European 
countries will be recruited in this study; approximately 3000 patients in cohort A and 
approximately 6000 patients in cohort B.
Baseline demographics and disease characteristics of the patient population will be described 
by estimates and confidence intervals (CIs) overall (for Cohort A), by anticoagulation 
treatment (for Cohort B), and by additional relevant categories as specified in section 9.7.2
and the Statistical and Epidemiological Analysis Plan (SEAP). Categorical attributes will be 
estimated with the precision (i.e. width of descriptive 95% confidence interval) described in 
Table 9.5: 1, according to sample size and prevalence of the attribute.

Boehringer Ingelheim
Page 24 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Table 9.5: 1
Width of 95% confidence interval by sample size and prevalence of attribute
Prevalence of attribute
Sample size (overall or per subgroup)
200
500
1000
2000
3000
10% Expected n
20
50
100
200
300
95% CI width
8.80
5.46
3.82
2.68
2.18
20% Expected n
40
100
200
400
600
95% CI width
11.53
7.20
5.05
3.55
2.90
30% Expected n
60
150
300
600
900
95% CI width
13.13
8.21
5.77
4.06
3.28
40% Expected n
80
200
400
800
1200
95% CI width
13.99
8.77
6.17
4.34
3.54
50% Expected n
100
250
500
1000
1500
95% CI width
14.26
8.94
6.29
4.43
3.61
* Calculations are based on the Clopper-Pearson method.
For example, for a population attribute with a prevalence of 20%, a total sample size of 3000
patients in Cohort A allows this proportion to be estimated with a precision of 2.90% (i.e. 
width of 95% CI). In addition, for a population attribute with a prevalence of 30%, a sample 
size of 1000 Pradaxa® patients in a particular subgroup in Cohort B allows this proportion to 
be estimated with a precision of 5.77%.
The planned total sample size of 9000 patients is jointly determined by the following sample 
size calculations and additional non-statistical considerations, including feasibility 
assessments for each participating country.
Due to the limited number of publications on PACT-Q2 (R15-1314, R15-1316, R15-1359)
and the lack of information regarding the clinical meaning of changes in PACT-Q2 scores, 
sample sizes assessments are performed using standardized mean differences. In the context 
of this non-interventional study, they represent the mean differences in PACT-Q2 scores 
between two assessments (for Cohort A) or between the Pradaxa® and VKA groups (for 
Cohort B) divided by the corresponding standard deviations. In general, a standardized effect 
size of 0.2 is considered a small change, 0.5 a moderate change, and 0.8 a large change.
For Cohort A, assuming a 2-sided alpha of 0.05 and a 20% loss to follow-up, a total sample 
size of 3000 patients will provide over 80% power to detect a standardized mean difference 
of 0.06 in PACT-Q2 scores between two assessments.
For Cohort B, assuming a 2-sided alpha of 0.05, a 1:1 ratio of Pradaxa® and VKA patients, 
and a 30% loss to follow-up and matching, a total sample size of 6000 patients will provide 

Boehringer Ingelheim
Page 25 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
over 80% power to detect a standardized mean difference of 0.065 in PACT-Q2 scores 
between the Pradaxa® and VKA groups at each assessment.
Additional sample size assessments are performed for the planned subgroup analyses at the 
country level based on the same assumptions as described above. For Cohort A, a sample size 
of 250 patients per country will provide 80% power to detect a standardized mean difference 
of 0.2 in PACT-Q2 scores between two assessments. For Cohort B, a sample size of 260
patients per country will provide 80% power to detect a standardized mean difference of 0.3 
in PACT-Q2 scores between the Pradaxa® and VKA groups at each assessment. Therefore, 
no country-level analyses will be performed for countries with a sample size smaller than 250
patients for Cohort A and 260 patients for Cohort B.
Based on results reported in the PREFER in Atrial Fibrillation (R15-1312) registry study, a 
reasonable expected standard deviation for the mean convenience and treatment satisfaction 
scores is 16. Based on this estimate, a standardized mean difference of 0.06 corresponds to an 
actual mean difference of 0.96, respectively, in the PACT-Q2 convenience and treatment 
satisfaction scores.
The PREFER in Atrial Fibrillation study (R15-1312) also reported a mean difference between 
patients receiving novel oral anticoagulants and those receiving VKA of -0.6 for the 
convenience score, and of 1.1 for the treatment satisfaction score. Since the clinical 
meaningfulness of such small mean differences in PACT-Q2 scores is unclear, the current 
study is by design not powered to detect statistically significant differences of such small 
magnitudes.
9.6
DATA MANAGEMENT
A data management plan (DMP) will be created to describe all functions, processes, and 
specifications for data collection, cleaning and validation. The electronic CRFs (eCRFs) will 
include programmable edits to obtain immediate feedback if data are missing, out of range, 
illogical or potentially erroneous. These rules may encompass simple checks such as range 
validation or presence/absence of data, or complex cross-form verifications such as lab result 
deviations across visits. Concurrent manual data review may be performed based on 
parameters dictated by the DMP. Ad hoc queries to the sites may be generated and followed 
up for resolution. A source data quality audit may be initiated to ensure that the data in the 
database is accurate. Source data verification (SDV) will be performed at sites identified by a 
risk-based approach outlined in the monitoring plan, as needed.
The database will be housed in a physically and logically secure computer system maintained 
in accordance with a written security policy. The system will meet the standards of the 
International Committee on Harmonization guideline E6R1 regarding electronic study data 
handling. Patient confidentiality will be strictly maintained.
9.7
DATA ANALYSIS
9.7.1
Study Design
In this non-interventional study, cross-sectional data at study baseline and longitudinal 
follow-up data over 6 months will be collected for non-valvular AF patients with a current 
VKA therapy and subsequent initiation of Pradaxa®  in Cohort A, and for newly diagnosed 
AF patients initiated on Pradaxa® or VKA in Cohort B.

Boehringer Ingelheim
Page 26 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Baseline data will be analyzed using a descriptive approach. Data from the longitudinal 
follow-up will be summarized descriptively. For Cohort A, mean differences in PACT-Q2 
scores between assessments will be assessed using paired t-tests. For Cohort B, mean 
differences in PACT-Q2 scores between Pradaxa® and VKA patients will be assessed using 
propensity score matched analysis.
Due to the nature of this non-interventional study, there is no (confirmatory) hypothesis 
testing foreseen in a strict statistical sense. Analyses are descriptive in nature and confidence 
intervals and p-values from statistical models are used for exploratory purposes.
9.7.2
Planned Analysis
Analyses will be performed by Boehringer Ingelheim or Boehringer Ingelheim’s designees.
The main analysis population will consist of all eligible patients (i.e. all patients fulfilling all 
inclusion criteria and no exclusion criteria) from all participating countries.
Summary statistics for continuous variables will include the N, mean, standard deviation, 
minimum, Q1 (lower quartile), median, Q2 (upper quartile), and maximum value; tabulations 
of categorical variables will present all possible categories and will display the number of 
observations per category as well as percentages. Estimates will be presented with 95% 
confidence intervals.
Additional details of the planned analysis will be provided in the statistical and 
epidemiological analysis plan (SEAP).
9.7.2.1
Main Analyses
Patient demographics and disease characteristics at baseline as described in section 9.3 will 
be summarized descriptively for all eligible patients in Cohort A and by treatment in Cohort 
B. This analysis may be repeated by additional relevant factors (e.g. country) that will be 
specified in the SEAP.
For Cohort A, the mean PACT-Q2 scores at the second and last assessments will be 
compared with the baseline assessment using paired t-tests.
For Cohort B, mean PACT-Q2 scores will be compared between Pradaxa® and VKA patients 
at the second and last assessments. Given the nature of this non-interventional study, patient 
in the two treatment groups may differ with regard to important baseline demographics and 
disease characteristics. When approximately half of the target sample size is reached, 
propensity scores that estimate the probabilities that patients would be initiated on Pradaxa®
will be calculated using a logistic regression model including relevant baseline factors. The 
percentage of Pradaxa® and VKA patients that are matched with a 1:1 ratio and without 
replacement based on propensity scores will be calculated to assess the comparability of the 
two patient populations, and to estimate the loss of patients from the comparative analysis. 
Details of the propensity score model and the matching procedure, such as the choice of 
algorithm and caliper width will be described in the SEAP. If a sufficient percentage of 
matching (e.g. 90%) is achieved, the loss is considered minimal. If the percentage is 
considered not to be sufficient, the target sample size might be raised to increase the power of 
the comparative analysis.

Boehringer Ingelheim
Page 27 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
For the final comparative analysis for Cohort B, Pradaxa® and VKA patients will be matched 
based on propensity scores following the same approach as described above. To assess the 
performance of the propensity score matching procedure, patient demographics and disease 
characteristics at baseline will be descriptively summarized again for the matched patients by 
treatment. Finally, the mean PACT-Q2 scores at each of the second and last assessments will 
be compared between the matched Pradaxa® and VKA patients using a paired t-test.
For both cohorts, the primary analyses will be based on the actual anticoagulation treatment 
the patients receive (i.e. “as treated” analysis). A patient is considered to have permanently 
discontinued initial anticoagulation treatment if other relevant anticoagulation treatment is 
initiated or otherwise dependent on the duration of treatment interruption (details will be 
provided in the SEAP). Patients who have permanently discontinued initial anticoagulation
treatment at the time of an assessment will be excluded from all analyses where data from 
that assessment is included.
 
 
 
 
 
 
 
 
9.7.2.3
Safety Analyses
Safety analyses will be performed separately for Cohort A and B, and will include all 
enrolled patients with an actual follow-up. Statistical analysis and reporting of AEs will be 
descriptive in nature, will be based on BI standards, and will focus on adverse drug reactions 
(ADRs) to Pradaxa® and VKA. No hypothesis testing is planned.

Boehringer Ingelheim
Page 28 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Occurrences of ADRs will be analyzed relative to the number of patients treated as well as 
observed person-years (i.e. time at risk). Safety analysis will be based on the concept of 
treatment emergent ADRs. Patients will be analyzed according to the anticoagulation 
treatment received at the time of the event. If no concurrent anticoagulation treatment is 
administered, then events occurring within a washout period of 3 days (for Pradaxa®) or 6 
days (for VKA) after discontinuation of anticoagulation treatment will be assigned to the last 
treatment given. This washout period will also be included as time at risk for derivation of 
total person-years. ADRs that deteriorate under treatment will also be considered as 
“treatment emergent”. Events occurring prior to first intake of anticoagulation treatment 
prescribed at baseline, during periods without any anticoagulation treatment (excluding 
washout periods), or after the end of the 6 month follow-up (excluding washout periods) will 
not be considered treatment emergent events and will not be included in the summary tables.
The following parameters will be included in the safety analyses:
!
Adverse drug reactions 
!
Adverse drug reactions leading to discontinuation of anticoagulation treatment
!
Serious adverse drug reactions
!
Adverse events leading to deaths
9.7.2.4
Schedule of Planned Analyses
No interim analysis is planned for Cohort A.
For Cohort B, it is planned that an interim analysis that assesses the comparability of patients 
in the Pradaxa® and VKA groups based on propensity scores will be performed when 
approximately half of the target sample size is reached (see details in section 9.7.2.1).
For each cohort, the final analyses as specified in section 9.7.2 will be performed once the 
data collection is completed, the data sets are cleaned, and the database is locked for that 
cohort. The final analysis for both cohorts may be performed together, if their complete data 
becomes available at the same time. One final report will be prepared at the completion of 
both cohorts.
Additional reports (e.g. for country-specific analyses) may be prepared if deemed appropriate 
and will be specified in the SEAP.
9.7.3
Handling of missing data
Every reasonable attempt will be undertaken to ensure completeness of data collection. 
Imputation will be permitted, if deemed appropriate and on a case-by-case basis, depending 
on the extent and distribution of missing values, and will be described in the SEAP.
The percentage of and reason for loss to follow-up will be summarized overall in Cohort A, 
by treatment in Cohort B, and by other relevant factors. In addition, if the proportion of 
patients with loss to follow-up is substantial enough (e.g. ≥ 10%) to warrant further 
investigation, baseline characteristics will be described for patients who were lost to follow-
up in comparison to patients who have completed follow-up.
9.8
QUALITY CONTROL
The following processes will be implemented to ensure data completeness and data quality:

Boehringer Ingelheim
Page 29 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Data Edit Checks:
The electronic CRF (eCRF) will include programmable edit checks to obtain feedback if data 
is missing, out of range, illogical or potentially erroneous.
These checks will be performed once data is entered into the eCRF. 
Thus the data entered in to the eCRF will be validated within the system and the physician 
will receive alerts for missing or inconsistent data. In case any changes of already entered 
data will be required, an audit trail will be available. 
Medical monitoring: 
A review of applicable entered eCRF data will be performed to verify patient eligibility to 
ensure that the analysed patient population corresponds to the protocol–described population.
In addition eCRFs/completed patient related questionnaires will also be reviewed for 
verification that no non reported safety event is present.
Source data verification: 
No regular source data verification is planned in this non-interventional study. However, in 
case of issues (i.e. high amount of missing data, data discrepancies, protocol violations, 
etcetera) detected at a site with the measures described above, a for-cause onsite visit can be 
planned to perform a sample check of source data. 
9.9
LIMITATIONS OF THE RESEARCH METHODS
Consecutive enrolment will be employed to ensure that specific types of patients are not 
selected by site staff to participate. 
VKA has been the mainstay of SPAF for many years. It is widely available, affordable but 
does require regular INR monitoring. Pradaxa® is more expensive, may or may not be 
reimbursed but doesn’t require the continual INR monitoring. There are a number of different 
types of bias that could influence the data collection and analysis from these cohorts such as 
selection bias, information bias and channelling bias.
The study is designed to collect new data. The entry criteria are non-restrictive which will 
permit the enrolment of a broad patient population. The choice of treatment is at the 
discretion of the investigator. Therefore the data collected in this study should reflect the real 
world treatment patterns and patient characteristics.
Selection bias:
Selection bias could occur at both the site (physician) level and the patient level. If sites 
where Pradaxa® is used frequently differ systematically with respect to patient or the routine 
procedures from sites that use Pradaxa® less frequently, the between site difference could 
lead to non-comparability between the patients. To minimize the site level selection bias, the 
goal is to have participating centres that have access to all available treatment options for 
SPAF that are approved for use in that country.

Boehringer Ingelheim
Page 30 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Selection bias at the patient level could occur if sites preferentially enrol specific patients into 
the study. To minimize selection bias at the patient level, consecutive enrolment is 
performed.
• Information / observer bias:
Information or observer bias may occur when information is collected differently between 
two groups. E.g. if the observer/physician has more knowledge about the use of VKA 
treatment, the patients exposure to VKA treatment or the disease status and development 
as compared to Pradaxa®. Also, a VKA patient will be more often seen. Such information 
may result in differences in the way information is collected, measured or interpreted by 
the investigator in each of the treatment groups (cohort A or B (B1, B2)). The use of a 
standardized protocol and eCRF for data collection, but also the use of standardized 
questionnaires (PACT-Q) which have to be completed by the patients themselves, will 
minimize the information/observer bias.
• Loss to follow-up:
All efforts will be made to minimize loss to follow-up in patients who are enrolled. 
Patients who are lost to follow-up will be characterized and compared to the remaining 
patients and the reason and time point of lost to follow-up will be evaluated.
Channelling bias:
Channelling bias can occur due to preferential prescribing in relation to different risks for 
events of interest e.g. if Pradaxa® is prescribed more frequently to high risk patients than to 
other treatments, a high rate of outcome events could be expected in the Pradaxa® group. In 
order to control for potential channelling, an assessment will be conducted to monitor the 
comparability of important patient baseline characteristics. Propensity score matching is 
planned to account for potential differences.
Recall bias:
Recall bias refers to the phenomenon when the outcomes of treatment (either good or bad) 
may colour the patient’s recollection of events prior to or during the treatment. To minimize 
recall bias, patient reported outcomes will be assessed using validated questionnaires within a 
limited period of time to minimize recall bias.
Confounding:
Statistical techniques, such as adjustment for covariates and propensity score matching will 
be used to correct for identified confounders. However unidentified confounders cannot be 
controlled for using statistical analysis. The employed methods are described in the data 
analysis section.
Recall bias:
Recall bias refers to the phenomenon when the outcomes of treatment (either good or bad)
may colour the patient’s recollection of events prior to or during the treatment. To minimize
recall bias, patient reported outcomes and adherence will be assessed using validated scales
within a limited period of time to minimize recall bias.
Confounding:
Statistical techniques, such as adjustment for covariates and propensity score matching will 
be used to correct for identified confounders. However unidentified confounders cannot be 

Boehringer Ingelheim
Page 31 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
controlled for using statistical analysis. The employed methods are described in the data 
analysis section.
9.10
OTHER ASPECTS
9.10.1 Informed Consent, Data Protection, Study Records
The study will be carried out in compliance with the protocol, the principles laid down in the 
Declaration of Helsinki, and as close as possible to the standards of the  International  
Conference of Harmonisation (ICH) Tripartite Guideline, Good Clinical Practice (GCP), 
Guidelines for Good Epidemiological Practice (GEP) (R10-4560), Good 
Pharmacoepidemiology Practice (GPP) (R09-0182) and relevant BI Standard Operating 
Procedures (SOPs). Standard medical care (prophylactic, diagnostic and therapeutic 
procedures) remains in the responsibility of the treating physician of the patient.
The investigator should inform the sponsor immediately of any urgent safety measures taken 
to protect the study subjects against any immediate hazard, and also of any serious breaches 
of the protocol.
The rights of the investigator and of the sponsor with regard to publication of the results of 
this trial are described in the investigator contract. As a general rule, no trial results should be 
published prior to finalization of the Study Report.
Insurance Cover: The requirements for insurance depend on local law and legislations in the 
participating country. If required, the terms and conditions of the insurance cover are made 
available to the investigator and the patients, and the documentation must be archived in the 
Investigator Site File (ISF).
9.10.1.1
Study Approval, Patient Information, and Informed Consent
This study will be initiated only after all required legal documentation has been reviewed and 
approved by the respective Institutional Review Board (IRB) / Independent Ethics Committee 
(IEC) and competent authority (CA) according to national and international regulations. The 
same applies for the implementation of changes introduced by amendments.
Prior to patient participation in the study, written informed consent must be obtained from 
each patient (or the patient’s legally accepted representative) according to ICH GCP and to 
the regulatory and legal requirements of the participating country. Each signature must be 
personally dated by each signatory and the informed consent and any additional patient-
information form retained by the investigator as part of the trial records. A signed copy of the 
informed consent and any additional patient information must be given to each patient or the 
patient’s legally accepted representative. ICH-GCP will be used as guidance where 
applicable.
The patient must be informed that his/her personal study-related data will be used by 
Boehringer Ingelheim in accordance with the local data protection law. The level of 
disclosure must also be explained to the patient.
The patient must be informed that his / her medical records may be examined by authorized 
monitors (CML/CRA) or Clinical Quality Assurance auditors appointed by Boehringer 
Ingelheim, by appropriate IRB / IEC members, and by inspectors from regulatory authorities.

Boehringer Ingelheim
Page 32 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
9.10.1.2
Data Quality Assurance
A quality assurance audit/inspection of this study may be conducted by the sponsor or 
sponsor’s designees or by IRBs/IECs or by regulatory authorities. The quality assurance 
auditor will have access to all medical records, the investigator’s study-related files and 
correspondence, and the informed consent documentation of this study.
9.10.1.3
Records
Case Report Forms (CRFs) for individual patients will be provided by the sponsor via remote 
data capture. All of the clinical data and site/investigator characteristics will be captured via a 
web-based EDC system. The site staff will enter and edit the data via a secure network, with 
secure access features (username, password and secure identification – an electronic 
password system).  A complete electronic audit trail will be maintained.
Patients must not be identified on the eCRF by name.  Appropriately coded identification (i.e. 
Patient numbers) must be used. The Investigator must make a separate confidential record of 
these details (Patient enrolment log) to permit the identification of all patients enrolled in the 
study in case follow-up is required.  Any supporting documentation must be redacted of any 
patient identifying information and the patient ID number must be clearly written on the 
documents.
9.10.1.3.1 Source documents
Source documents provide evidence for the existence of the patient and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data entered in the eCRFs that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may need 
to request previous medical records or transfer records, depending on the trial; also current 
medical records must be available.
For eCRFs all data must be derived from source documents:
!
Patient identification (gender, date of birth)
!
Patient participation in the study (substance, study number, patient number, date 
patient was informed)
!
Dates of Patient’s visits, including prescription of study medication
!
Medical history (including study indication and concomitant diseases, if applicable)
!
Medication history
!
PACT-Q 1 and 2 questionnaires: the original paper questionnaires completed by the 
patients
!
Adverse drug reactions (non-serious) (onset date (mandatory), and end date (if 
available))
!
Serious adverse drug reactions (onset date (mandatory), and end date (if available))
!
Fatal adverse events (onset date (mandatory), and end date (if available))
!
Pregnancy
!
Concomitant therapy (start date, changes)
!
Originals or copies of laboratory results (in validated electronic format, if available)
!
Conclusion of Patient’s Participation in the study

Boehringer Ingelheim
Page 33 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
9.10.1.3.2 Direct access to source data and documents
The investigator / institution will permit study-related monitoring, audits, IRB / IEC review 
and regulatory inspection, providing direct access to all related source data / documents. 
eCRFs and all source documents, including progress notes and copies of laboratory and 
medical test results must be available at all times for review by the sponsor’s clinical study 
monitor, auditor and inspection by health authorities (e.g. FDA). The Clinical Research 
Associate (CRA) / on site monitor and auditor may review all eCRFs, and written informed 
consents. The accuracy of the data will be verified by reviewing the documents described in 
section 9.10.1.3.1.
9.10.1.4
Statement of Confidentiality
Individual patient medical information obtained as a result of this study is considered 
confidential and disclosure to third parties is prohibited with the exceptions noted below. 
Patient confidentiality will be ensured by using patient identification code numbers.
Treatment data may be given to the patient’s personal physician or to other appropriate 
medical personnel responsible for the patient’s welfare. Data generated as a result of the
study need to be available for inspection on request by the participating physicians, the 
sponsor’s representatives, by the IRB / IEC and the regulatory authorities, i.e. the competent 
authority (CA).
9.10.1.5
Completion of Study
The EC/competent authority in each participating EU member state needs to be notified about 
the end of the study (last patient out) or early termination of the study. 

Boehringer Ingelheim
Page 34 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
10.
PROTECTION OF HUMAN SUBJECTS
Please refer to section 9.10.1

Boehringer Ingelheim
Page 35 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
11.
MANAGEMENT AND REPORTING OF ADVERSE 
EVENTS/ADVERSE REACTIONS
11.1
DEFINITIONS OF ADVERSE EVENTS
Adverse event
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a medicinal product and which does not necessarily have a 
causal relationship with this treatment. An adverse event can therefore be any unfavourable 
and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product. 
Adverse drug reaction
An adverse drug reaction (ADR) is defined as a response to a medicinal product which is 
noxious and unintended. Response in this context means that a causal relationship between a 
medicinal product and an adverse event is at least a reasonable possibility. Adverse drug 
reactions may arise from use of the product within or outside the terms of the marketing 
authorization or from occupational exposure. Conditions of use outside the marketing 
authorization include off-label use, overdose, misuse, abuse and medication errors.
Serious adverse event
A serious adverse event is defined as any AE which
-
results in death, 
-
is life-threatening, 
-
requires in-patient hospitalization, or
-
prolongation of existing hospitalisation, 
-
results in persistent or significant disability or incapacity, or 
-
is a congenital anomaly/birth defect 
Life-threatening in this context refers to a reaction in which the patient was at risk of death at 
the time of the reaction; it does not refer to a reaction that hypothetically might have caused 
death if more severe.
Medical and scientific judgement should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life threatening or result in death or hospitalisation but might jeopardise the 
patient or might require intervention to prevent one of the other outcomes listed above. 
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalisation or 
development of dependency or abuse. Any suspected transmission via a medicinal product of 
an infectious agent is also considered a serious adverse reaction.
Adverse Event of Special Interest (AESI)
The term AESI relates to any specific AE that has been identified at the project level as being 
of particular concern for prospective safety monitoring and safety assessment within this 

Boehringer Ingelheim
Page 36 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
study, e.g. the potential for AEs based on knowledge from other compounds in the same 
class.
No AESIs have been defined for this study.
11.2
ADVERSE EVENT AND SERIOUS ADVERSE EVENT COLLECTION AND 
REPORTING
The investigator shall maintain and keep detailed records of all AEs in their patient files. 
Collection of AEs
The study design is of non-interventional nature and the study is conducted within the 
conditions of the approved marketing authorisation. Sufficient data from controlled 
interventional trials are available to support the evidence on the safety and efficacy of the 
studied BI drug. For this reason the following AE collection and reporting requirements have 
been defined.
The following must be collected by the investigator in the eCRF from signing the informed 
consent onwards until the end of the study: 
-
all ADRs (serious and non-serious),
-
all AEs with fatal outcome (serious adverse events),
-
all pregnancies
Note*: For all patients (on Pradaxa® or VKA) these data must be recorded on the AE 
pages in the eCRF. The separate NIS (S)AE form must be used for Pradaxa® patient only 
(see ‘Expedited Reporting’ below).
All ADRs , including those persisting after study completion must be followed up until they 
are resolved, have been sufficiently characterized, or no further information can be obtained.
The investigator carefully assesses whether an AE constitutes an ADR using the information 
below. 
Causal relationship of adverse event
The definition of an adverse reaction implies at least a reasonable possibility of a causal 
relationship between a suspected medicinal product and an adverse event. An adverse 
reaction, in contrast to an adverse event, is characterised by the fact that a causal relationship 
between a medicinal product and an occurrence is suspected. 
Medical judgment should be used to determine the relationship, considering all relevant 
factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, 
confounding factors such as concomitant medication, concomitant diseases and relevant 
history. 
Arguments that may suggest a reasonable causal relationship could be:
•
The event is consistent with the known pharmacology of the drug 
•
The event is known to be caused by or attributed to the drug class.
•
A plausible time to onset of the event relative to the time of drug exposure.

Boehringer Ingelheim
Page 37 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
•
Evidence that the event is reproducible when the drug is re-introduced
•
No medically sound alternative etiologies that could explain the event (e.g. 
preexisting or concomitant diseases, or co-medications).
•
The event is typically drug-related and infrequent in the general population not 
exposed to drugs (e.g. Stevens-Johnson syndrome).
•
An indication of dose-response (i.e. greater effect size if the dose is increased, smaller 
effect size if dose is diminished).
Arguments that may suggest that there is no reasonable possibility of a causal relationship
could be:
•
No plausible time to onset of the event relative to the time of drug exposure is evident 
(e.g. pre-treatment cases, diagnosis of cancer or chronic disease within days/weeks of 
drug administration; an allergic reaction weeks after discontinuation of the drug 
concerned)
•
Continuation of the event despite the withdrawal of the medication, taking into
account the pharmacological properties of the compound (e.g. after 5 half-lives).
Of note, this criterion may not be applicable to events whose time course is prolonged 
despite removing the original trigger.
•
Additional arguments amongst those stated before, like alternative explanation (e.g.
situations where other drugs or underlying diseases appear to provide a more likely
explanation for the observed event than the drug concerned).
•
Disappearance of the event even though the study drug treatment continues or remains 
unchanged.
Intensity of adverse event
The intensity of the AE should be judged based on the following:
Mild:
Awareness of sign(s) or symptom(s) which is/are easily tolerated
Moderate:
Enough discomfort to cause interference with usual activity
Severe:
Incapacitating or causing inability to work or to perform usual activities
Pregnancy:
In rare cases, pregnancy might occur in this study. Once a female subject has been enrolled 
into the study, the investigator must report any drug exposure during pregnancy to the 
Sponsor by means of Part A of the Pregnancy Monitoring Form. The outcome of the 
pregnancy associated with the drug exposure during pregnancy must be followed up and 
reported by means of Part B of the Pregnancy Monitoring Form. 
In the absence of a reportable AE, only the Pregnancy Monitoring Form must be completed, 
otherwise the NIS AE form is to be completed and forwarded (by fax/e-mail) to the 
responsible contact (person) for each country within respective timelines.
Expedited Reporting of ADRs / Fatal AEs and Drug Exposure During Pregnancy
The following must be reported by the investigator on the NIS (S)AE Form from signing the 
informed consent onwards until the end of the study: 

Boehringer Ingelheim
Page 38 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Table 11.2:1 Reporting types and timelines
Type of Report*
Timeline
All SADRs associated with Pradaxa®
immediately within 24 hours
All AEs with fatal outcome in patients exposed to
Pradaxa®
immediately within 24 hours
All non-serious ADRs associated with Pradaxa®
7 calendar days
All pregnancy monitoring forms associated with 
Pradaxa®
7 calendar days
*Note: the NIS (S)AE Form or Pregnancy Monitoring Form is required only for Pradaxa® patients, not for VKA patients.
The same timelines apply if follow-up information becomes available for the respective 
events. In specific occasions the Investigator could inform the Sponsor upfront via telephone. 
This does not replace the requirement to complete and fax/email the NIS (S)AE form.
Information required
For each reportable adverse event, the investigator should provide the information requested 
on the appropriate (e)CRF pages and the NIS (S)AE form.
Reporting of related Adverse Events associated with any other BI drug
The investigator is encouraged to report all adverse events related to any BI drug other than 
the Pradaxa® according to the local regulatory requirements for spontaneous AE reporting at 
the investigator’s discretion by using the locally established routes and AE report forms. The 
term AE includes drug exposure during pregnancy, and, regardless of whether an AE 
occurred or not, any abuse, off-label use, misuse, medication error, occupational exposure, 
lack of effect, and unexpected benefit.
11.3
REPORTING TO HEALTH AUTHORITIES 
Adverse event reporting to regulatory agencies will be done by the Sponsor according to local 
and international regulatory requirements. 

Boehringer Ingelheim
Page 39 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
12.
PLANS FOR DISSEMINATING AND COMMUNICATING 
STUDY RESULTS
Results of this non-interventional study will be disclosed on external websites according to 
BI SOP and a study specific publication plan will be developed to describe planned 
publications per country and for overall study results.

Boehringer Ingelheim
Page 40 of 53
Non-interventional Study Protocol
BI Study Number 1160.249
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
13.
REFERENCES
13.1
PUBLISHED REFERENCES
P13-05668
Monz BU, Connolly SJ, Korhonen M, Noack H, Pooley J Assessing the 
impact of dabigatran and warfarin on health-related quality of life: results 
from an RE-LY sub-study. Int J Cardiol 168 (3), 2540 - 2547 (2013).
R09-0182
Guidelines for Good Pharmacoepidemiology Practices (GPP). 
Pharmacoepidemiology and Drug Safety 17, 200 - 208 (2008).
R10-4560
Good Epidemiological Practice (GEP). IEA Guidelines for Proper Conduct of 
Epidemiological Reseach (2007).
R10-5332
Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM Refining clinical 
risk stratification for predicting stroke and thromboembolism in atrial 
fibrillation using a novel risk factor-based approach: the Euro Heart Survey on 
Atrial Fibrillation. Chest 137 (2), 263 - 272 (2010).
R10-6394
Pisters R, Lane DA, Nieuwlaat R, Vos CB de, Crijns HJGM, Lip GYH A 
novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding 
in patients with atrial fibrillation: the Euro Heart Survey. Chest 138 (5), 1093 -
1100 (2010).
R15-1312
Caterina R de, Brueggenjuergen B, Darius H, Heuzey JY le, Renda G, 
Schilling RJ, Schmitt J, Zamorano JL, Kirchhof P Quality of life and patient 
satisfaction data in atrial fibrillation patients stably treated with a VKA vs 
patients switched from a VKA to NOAC. The PREFER in AF registry. ESC 
2014, 36th Cong of the European Society of Cardiology (ESC), Barcelona, 30 
Aug - 3 Sep 2014 (Poster)
R15-1314
Prins MH, Guillemin I, Gilet H, Gabriel S, Essers B, Raskob G, Kahn SR 
Scoring and psychometric validation of the Perception of Anticoagulant 
Treatment Questionnaire (PACT-Q). Health Qual Life Outcomes 7, 30 (2009)
R15-1316
Prins MH, Marrel A, Carita P, Anerson D, Bousser MG, Crijns H, Consoli S, 
Arnould B. Multinational development of a questionnaire assessing patient 
satisfaction with anticoagulant treatment: the 'Perception of Anticoagulant 
Treatment Questionnaire' (PACT-Q). Health Qual Life Outcomes 7, 9 (2009)
R15-1359
Heidorn K, Haenschke J, Lindner T, Mittelmeier W, Skripitz R. Health 
economic analysis of thromboprophylaxis with rivaroxaban and certoparin-
sodium in patients after total hip or knee replacement. Int J Orthop 1 (1), 15 -
18 (2014)
13.2
UNPUBLISHED REFERENCES
Not applicable

Boehringer Ingelheim
Page 41 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS
The stand-alone documents for this non-interventional study are:
! Informed Consent Form
! Perception of Anticolagulant Treatment Questionnaires (PACT-Q1 & PACT-Q2)
! Statistical and Epidemiological Analysis Plan (SEAP)
! Data Management Plan (DMP)
! Pregnancy Monitoring Form
! Serious Adverse Event Report in Non-Interventional Studies (NIS (S)AE Form)
! Publication Plan
All of the above documents will be archived in the Trial Master File in its original English 
master version.

Boehringer Ingelheim
Page 42 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
ANNEX 2. ENCEPP CECKLIST FOR STUDY PROTOCOLS
Not applicable

Boehringer Ingelheim
Page 43 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
ANNEX 3. ADDITIONAL INFORMATION
The Perception of Anticoagulant Treatment Questionnaires (PACT-Q®) are shown on the 
next pages (in English). Validated translations of these PACT-Q1 and PACT-Q2 
questionnaires will be provided to the patients participating in this study (in their local 
language).

Boehringer Ingelheim
Page 44 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
ANNEX 3.1  PERCEPTION OF ANTICOAGULANT TREATMENT 
QUESTIONNAIRE, PART 1 (PACT-Q1)

Boehringer Ingelheim
Page 45 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies

Boehringer Ingelheim
Page 46 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies

Boehringer Ingelheim
Page 47 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
ANNEX 3.2  PERCEPTION OF ANTICOAGULANT TREATMENT 
QUESTIONNAIRE, PART 2 (PACT-Q2)

Boehringer Ingelheim
Page 48 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies

Boehringer Ingelheim
Page 49 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies

Boehringer Ingelheim
Page 50 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies

Boehringer Ingelheim
Page 51 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies

Boehringer Ingelheim
Page 52 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies

Boehringer Ingelheim
Page 53 of 53
Non-interventional Study Protocol
BI Study Number 1160.249              
                                c03594400-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies

 
 
 
APPROVAL / SIGNATURE PAGE 
Document Number: 
 
Technical Version Number:
Document Name: 
                                                                                                                 
 
Title: 
                                                                                                                   
Signatures (obtained electronically) 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
F

QRQLQWHUYHQWLRQDOVWXG\SURWRFRO
1RQLQWHUYHQWLRQDOVWXG\GHVFULELQJSDWLHQWVSHUFHSWLRQRQDQWLFRDJXODQWWUHDWPHQW
DQGWUHDWPHQWFRQYHQLHQFHZKHQWUHDWHGZLWK3UDGD[DRU9LWDPLQH.$QWDJRQLVWIRU
6WURNH3UHYHQWLRQLQ1RQ9DOYXODU$WULDO)LEULOODWLRQ
$XWKRU&OLQLFDO3URMHFW
-XO&(67
$SSURYDO7KHUDSHXWLF$UHD
-XO&(67
$SSURYDO
6DIHW\(YDOXDWLRQ
7KHUDSHXWLF$UHD
-XO&(67
$SSURYDO2WKHU
-XO&(67
$SSURYDO7HDP0HPEHU0HGLFDO
$IIDLUV
-XO&(67
$SSURYDO
RI*OREDO
(SLGHPLRORJ\
-XO&(67
$XWKRU7ULDO6WDWLVWLFLDQ
-XO&(67

Boehringer Ingelheim 
Page 2 of 2
Document Number: 
Technical Version Number:
(Continued) Signatures (obtained electronically) 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
F
