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
Conditions: Atrial Fibrillation
Sponsor: Boehringer Ingelheim

ABCD
icTITLE PAGE
0.
TITLE PAGE
Non-interventional Study Protocol
Document Number:
c03518692-01
BI Study Number:
1160.247
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 Prophylaxis in Atrial Fibrillation
Protocol version 
identifier:
01
Date of last version of 
protocol:
17 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 
authorization holder:
Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein, Germany
Joint PASS:
No
Research question and 
objectives:
Primary objective:
Describe the atrial fibrillation patient´s treatment 
perception by using the PACT-Q© (Perception on 
Anticoagulant Treatment Questionnaire).
Secondary objective:
Characterization of patient population (including dosing of 
Pradaxa®) 

Boehringer Ingelheim
Page 2 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Countries of study:
7 European countries (Belgium, Denmark, Greece, 
Norway, Portugal, Sweden and The Netherlands).
Authors:
,
phone: 
 
mobile: 
fax: 
e-mail: 
Medical 
 
mobile: 
e-mail: 
Marketing 
authorization holder:
Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein, Germany
MAH contact person:
Not applicable
EU-QPPV:
Not applicable
Signature of EU-
QPPV:
Not applicable
Date:
17 July 2015
Page 2 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 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
1.
TABLE OF CONTENTS
0.
TITLE PAGE.......................................................................................................... 1
1.
TABLE OF CONTENTS......................................................................................... 3
2.
LIST OF ABBREVIATIONS................................................................................... 5
3.
RESPONSIBLE PARTIES...................................................................................... 7
4.
ABSTRACT............................................................................................................. 8
5.
AMENDMENTS AND UPDATES........................................................................ 11
6.
MILESTONES...................................................................................................... 12
7.
RATIONALE AND BACKGROUND.................................................................... 13
8.
RESEARCH QUESTION AND OBJECTIVES..................................................... 14
9.1
RESEARCH QUESTIONS............................................................................. 14
9.2
OBJECTIVES ................................................................................................. 14
9.
RESEARCH METHODS ...................................................................................... 15
9.1
STUDY DESIGN............................................................................................ 15
9.2
SETTING........................................................................................................ 15
9.2.1
Selection of sites...................................................................................... 15
9.2.2
Inclusion criteria...................................................................................... 16
9.2.3
Exclusion criteria..................................................................................... 16
9.2.4
Removal of patients from the study ........................................................ 17
9.2.5
Visit schedule.......................................................................................... 17
9.2.6
Treatments............................................................................................... 20
9.2.7
Concomitant medications and restrictions .............................................. 21
9.2.8
Representativeness of the study population: ........................................... 21
9.3
VARIABLES .................................................................................................. 21
9.3.1
Variables for objective 1 ......................................................................... 21
9.3.2
Variables for objective 2 ......................................................................... 22
9.4
DATA SOURCES........................................................................................... 22
9.5
STUDY SIZE.................................................................................................. 22
9.6
DATA MANAGEMENT................................................................................ 24
9.7
DATA ANALYSIS......................................................................................... 25
9.7.1
STUDY DESIGN.................................................................................... 25
9.7.2
PLANNED ANALYSES ........................................................................ 25
9.7.2.1
Main Analyses ................................................................................ 25
........................................................................... 26

Boehringer Ingelheim
Page 4 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
9.7.2.3
Safety Analyses............................................................................... 27
9.7.2.4
Schedule of Planned Analyses........................................................ 27
9.7.3
HANDLING OF MISSING DATA ........................................................ 28
9.8
QUALITY CONTROL................................................................................... 28
9.9
LIMITATIONS OF THE RESEARCH METHODS...................................... 28
9.10
OTHER ASPECTS ......................................................................................... 30
9.10.1
INFORMED CONSENT, DATA PROTECTION, STUDY RECORDS30
9.10.1.1
STUDY APPROVAL, PATIENT INFORMATION, AND INFORMED 
CONSENT ......................................................................................................... 30
9.10.1.2
DATA QUALITY ASSURANCE.................................................. 31
9.10.1.3
RECORDS...................................................................................... 31
9.10.1.3.1
Source documents........................................................................... 31
9.10.1.3.2
Direct access to source data and documents................................... 32
9.10.1.4
STATEMENT OF CONFIDENTIALITY...................................... 32
9.10.1.5
COMPLETION OF STUDY .......................................................... 32
10.
PROTECTION OF HUMAN SUBJECTS ............................................................ 33
11.
MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS........................................................................................................ 34
11.1
Definitions of adverse events.......................................................................... 34
11.2
Adverse event and serious adverse event reporting........................................ 35
11.3
Reporting to health Authorities....................................................................... 37
12.
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS. 38
13.
REFERENCES..................................................................................................... 39
13.1
PUBLISHED REFERENCES......................................................................... 39
13.2
UNPUBLISHED REFERENCES................................................................... 40
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS................................................... 41
ANNEX 2. ENCEPP CHECKLIST 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 1160.247
c03518692-01
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), 
Drugs and Alcohol.

Boehringer Ingelheim
Page 6 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
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 1160.247
c03518692-01
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)
Coordinating Investigator (CI)

Boehringer Ingelheim
Page 8 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
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:
17 JUL 2015
1160.247
  01
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 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).
Research question 
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?

Boehringer Ingelheim
Page 9 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
!
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 
assessment.
For Cohort B (newly initiated to VKA or Pradaxa®):
-
Description of PACT-Q1 items at baseline.
Further exploratory outcomes:
-
Variation of PACT-Q2 scores at baseline, during initiation 
period and during the continuation period in respective 
treatment cohorts between countries (both cohorts).
-
Variation of PACT-Q2 scores in different age groups (both 
cohorts).
-
Variation of treatment expectations, measured with PACT-Q1 
items at baseline in different age groups (cohort B).
-
Geographical variation in treatment perception
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)

Boehringer Ingelheim
Page 10 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
-
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:
3.000 patients in 7 European countries
Data analysis:
In this  non-interventional 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.
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: 08-Sep-2015
Planned end of data collection: 05-Oct 2015
Planned final study  report: 10-May-2017

Boehringer Ingelheim
Page 11 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
5.
AMENDMENTS AND UPDATES
None

Boehringer Ingelheim
Page 12 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
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
08-SEP-2015
End of data collection
05-OCT-2016
Registration in the EU PAS register
will be done before study initiation
Final report of study results:
10-MAY-2017

Boehringer Ingelheim
Page 13 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
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 atrial fibrillation cannot be obtained by market 
research.

Boehringer Ingelheim
Page 14 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
8.
RESEARCH QUESTION AND OBJECTIVES
9.1
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.
9.2
OBJECTIVES
Primary objective
!
Describe the 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 15 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
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 (AF) 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 3.000 patients will be collected from approximately 
220 sites in 7 European countries. Planned participating countries are Belgium, Denmark, 
Greece, Norway, Portugal, Sweden and The Netherlands.
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 16 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
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 have been treated 
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 
atrial fibrillation.
3. Current participation in any clinical trial of a drug or device

Boehringer Ingelheim
Page 17 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
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.
The investigator / the study site will be reimbursed for reasonable expenses incurred in case 
of study termination (except in case of the third reason).
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)

Boehringer Ingelheim
Page 18 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Table 9.2.5: 1 Flow Chart / Schedule of Data Collection
Visit
1
2
3
Assessment
Baseline
Initiation period
Continuation period
Day
1
30-45 days
150 – 210 days
Informed Consent1
X
Patient demographics: age, gender
X
Concomitant diseases / co-
morbidities
X
X
X
Concomitant therapies
X
X
X
Healthcare system characteristics2
X
HAS- BLED score (to be calculated 
in the eCRF)
X
CHA2DS2-VASc score (to be 
calculated in the eCRF)
X
Inclusion/exclusion criteria
X
Duration of previous VKA 
treatment (for Cohort A)
X
Reasons for switch to Pradaxa® (for 
Cohort A)
X
Start Pradaxa® or VKA
X
Pradaxa® dosing (110 or 150 mg)
and reasons for dose changes
X
X
X
Creatinine clearance calculation3
X
X
X
Weight4
X
X4
X4
ADR (serious and non-serious), 
fatal AE, pregnancy collection
X
X
Reason for Pradaxa®/VKA 
discontinuation
X
X
PACT-Q1 questionnaire
X (for Cohort B only)
PACT-Q2 questionnaire
X (for Cohort A only)
X (both Cohorts)
X (both Cohorts)
Footnotes: 
1.
Written Informed Consent must be obtained prior to the baseline visit assessments.
2.
The type of hospital/practice and speciality of treating physician must be entered
3.
Creatinine clearance can only be calculated in the eCRF (via Cockroft-Gault Formula) if serum 
creatinine value is available from already existing laboratory reports. No lab assessment must be 
performed for the study at the baseline Visit 1, Visit 2 and/or Visit 3. See also footnote 4.
4.
Weight must be determined at Visit 1. At Visit 2 and/or 3, only if existing serum creatinine value is 
available at Visit 2 and/or 3.

Boehringer Ingelheim
Page 19 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Baseline visit:
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/co-morbidities in the medical history and at 
baseline
!
Collection of current concomitant therapies
!
Weight 
!
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:
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:
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)

Boehringer Ingelheim
Page 20 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
!
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. 
-
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 

Boehringer Ingelheim
Page 21 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
be referred to. The following website, accessed on 16 July 2015, shows the full list of 
products by active substance registered in the EU: 
http://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 current version of Pradaxa® Summary of Product Characteristics (SmPC) can be found 
on the EMA Webpage.
The following link is updated with the most recent version of the approved SmPC:
http://ec.europa.eu/health/documents/community-register/html/h442.htm
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.
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
Variables 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
Further exploratory outcomes:
-
Variation of PACT-Q2 scores at baseline, during initiation period and during the 
continuation period in respective treatment cohorts between countries(both cohorts)

Boehringer Ingelheim
Page 22 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
-
Variation of PACT-Q2 scores in different age groups (both cohorts)
-
Variation of treatment expectations, measured with  PACT-Q1 items at baseline in 
different age groups (cohort B)
-
Geographical variation in treatment perception
9.3.2
Variables 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)
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 3000 patients from 7 European countries will be 
recruited for Cohort A and 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 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 23 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
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 1000 
patients for Cohort A allows this proportion to be estimated with a precision of 5.05% (i.e. 
width of 95% CI). In addition, for a population attribute with a prevalence of 30%, a sample 
size of 500 Pradaxa® patients in a particular subgroup in Cohort B allows this proportion to 
be estimated with a precision of 8.21%.
The planned total sample size of 3000 patients is jointly determined by the following sample 
size assessments and additional non-statistical considerations, including feasibility 
assessments for the participating countries.
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 size assessments are performed using standardized mean differences. In the context of 
this 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 1000 patients will provide over 80% power to detect a standardized mean difference 
of 0.1 in PACT-Q2 scores between two assessments.

Boehringer Ingelheim
Page 24 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
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 2000 patients will provide 
over 80% power to detect a standardized mean difference of 0.11 in PACT-Q2 scores 
between the Pradaxa® and VKA groups at each assessment.
Based on results from the PREFER in AF (R15-1312) registry study, a reasonable expected 
standard deviation for the PACT-Q2 convenience and treatment satisfaction scores is 16. 
Based on this estimate, a standardized mean difference of 0.1 corresponds to an actual mean 
difference of 1.6 in the PACT-Q2 convenience and treatment satisfaction scores.
The PREFER in AF 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.

Boehringer Ingelheim
Page 25 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
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.
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 ANALYSES
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 9.3.2 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®

Boehringer Ingelheim
Page 26 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
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.
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.

Boehringer Ingelheim
Page 27 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
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.
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.

Boehringer Ingelheim
Page 28 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
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:
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 

Boehringer Ingelheim
Page 29 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
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.
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 

Boehringer Ingelheim
Page 30 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
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.
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/ICH GCP.
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 an 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

Boehringer Ingelheim
Page 31 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
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.
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.  The Investigator 
will approve the data using an electronic signature that is 21 CFR Part 11 compliant.
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)

Boehringer Ingelheim
Page 32 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
!
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
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 33 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
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 34 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
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 (SAE) is defined as any AE which
-
results in death, 
-
is life-threatening, 
-
requires in-patient hospitalization, or
-
prolongation of existing hospitalization, 
-
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 hospitalization but might jeopardize 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 hospitalization 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 35 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
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 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 authorization. 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*
-
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 characterized 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 

Boehringer Ingelheim
Page 36 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
•
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.
•
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 a study. Once a subject has been enrolled into the 
study, after having taken Pradaxa®, the investigator must report any drug exposure during 
pregnancy which occurred in a female subject or in a partner to a male subject 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 paper NIS (S)AE form is to be completed and forwarded (by fax/e-mail) to the 
responsible contact (person) for each country as well within the respective timelines. 
Expedited Reporting of 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 37 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
Table 11.2: 1 Report 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 the NIS (S)AE form.
Information required
For each reportable adverse event, the investigator should provide the information requested 
on the appropriate eCRF 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 
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 MAH according to local 
and international regulatory requirements. 

Boehringer Ingelheim
Page 38 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
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. 
In addition, a study specific publication plan will be developed to describe planned 
publications per country and for overall study results.

Boehringer Ingelheim
Page 39 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
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)

Boehringer Ingelheim
Page 40 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
13.2
UNPUBLISHED REFERENCES
None.

Boehringer Ingelheim
Page 41 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS
The following stand-alone documents have not been finalized at the time of protocol 
finalization. The final version of these documents will be archived in the Trial Master File 
(TMF)
!
Statistical and Epidemiological Analysis Plan (SEAP)
!
List of participating investigators

Boehringer Ingelheim
Page 42 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS
Not applicable.

Boehringer Ingelheim
Page 43 of 53
Non-interventional Study Protocol
BI Study Number 1160.247
c03518692-01
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®) will be 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 1160.247
c03518692-01
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 1160.247
c03518692-01
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 1160.247
c03518692-01
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 1160.247
c03518692-01
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 1160.247
c03518692-01
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 1160.247
c03518692-01
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 1160.247
c03518692-01
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 1160.247
c03518692-01
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 1160.247
c03518692-01
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 1160.247
c03518692-01
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

FOLQLFDOWULDOSURWRFRO
1RQLQWHUYHQWLRQDOVWXG\GHVFULELQJSDWLHQWVSHUFHSWLRQRQDQWLFRDJXODQWWUHDWPHQW
DQGWUHDWPHQWFRQYHQLHQFHZKHQWUHDWHGZLWK3UDGD[DRUVWDQGDUGFDUH9.$IRU
63$)
$SSURYDO7HDP0HPEHU0HGLFDO
$IIDLUV
-XO&(67
$SSURYDO
6DIHW\(YDOXDWLRQ
7KHUDSHXWLF$UHD
-XO&(67
$XWKRU7ULDO6WDWLVWLFLDQ
-XO&(67
$SSURYDO2WKHU
-XO&(67
$SSURYDO
RI*OREDO
(SLGHPLRORJ\
-XO&(67
$SSURYDO7KHUDSHXWLF$UHD
-XO&(67
$SSURYDO2WKHU
-XO&(67
$SSURYDO7ULDO&OLQLFDO0RQLWRU
-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
