Patients Assessment of Satisfaction for Stroke Prevention in Atrial Fibrillation Impact of Conventional Oral Anticoagulant (OAC) Compared With Novel Oral Anticoagulant (NOAC)
Conditions: Atrial Fibrillation
Sponsor: Boehringer Ingelheim

 
 
Protocol version 1.0 
Date: 15 March 2017 
 
001-MCS-90-118_RD-01 (7.0) / Saved on: 09 Nov 2015 
 
TITLE PAGE 
Non-interventional Study Protocol 
Document Number: 
c15931948-04 
BI Study Number: 
1160-0286 
BI Investigational 
Product(s): 
Dabigatran etexilate (Pradaxa) 
Title: 
Patients’ Assessment of Satisfaction for Stroke Prevention in 
Atrial FibrillationImpact of Conventional Oral Anticoagulant 
(OAC) Compared with Novel Oral Anticoagulant (NOAC) 
Brief lay title 
PASSION  
Protocol version 
identifier: 
1.0 
Date of last version of 
protocol: 
15 March 2017 
PASS: 
No 
EU PAS register 
number: 
To be decided 
Active substance: 
B01AE07-Dabigatran etexilate 
Medicinal product: 
Dabigatran etexilate 
Product reference: 
EU/1/08/442 (EMA registration number) 
Procedure number: 
Not applicable 
Marketing authorisation 
holder(s): 
This study is initiated, managed, and financed by: 
Boehringer Ingelheim 
Division Medicine/Medical Affairs 
Joint PASS: 
No 
Research question and 
objectives: 
Objective 1 
To describe the treatment perception from patients with non-
valvular atrial fibrillation (NVAF) receiving Pradaxa® or VKA 
for stroke prevention by using the self-estimation questionnaire 
of PACT-Q during a 6-month study period. 
Objective 2 
To investigate the patient’s characteristics. 

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Country(-ies) of study: 
Taiwan 
Author: 
 
Title: 
 of Medical Affairs 
Name: 
 
Tel: 
 
Direct Line: 
 
Fax:
 
Marketing authorisation 
holder(s): 
 
Title: 
 of Medical Affairs 
Name: 
 
Tel: 
 
Direct Line: 
 
Fax:
 
Address: 
 
 
 
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: 
15 March 2017 
 
Page 2 of 49 
 
Proprietary confidential information 
© 2017 Boehringer Ingelheim International GmbH or one or more of its affiliated companies. All rights reserved. 
This document may not - in full or in part - be passed on, reproduced, published or otherwise used without prior written permission 
 

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1. 
TABLE OF CONTENTS 
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 ................................................. 16 
9. 
RESEARCH METHODS .................................................................................... 17 
9.1 
STUDY DESIGN ............................................................................................ 17 
9.2 
SETTING ........................................................................................................ 17 
9.2.1 
Study sites ............................................................................................... 17 
9.2.2 
Study population ..................................................................................... 18 
9.2.3 
Study visits .............................................................................................. 19 
9.2.4 
Study discontinuation .............................................................................. 24 
9.3 
VARIABLES .................................................................................................. 24 
9.3.1 
Exposures ................................................................................................ 24 
9.3.2 
Outcomes ................................................................................................. 25 
9.3.3 
Covariates ................................................................................................ 25 
9.3.4 
Baseline characteristics and general information .................................... 26 
9.3.5 
Description and justification of patient questionnaires (PACT-Q©) ....... 28 
9.4 
DATA SOURCES ........................................................................................... 29 
9.5 
STUDY SIZE .................................................................................................. 29 
9.6 
DATA MANAGEMENT ................................................................................ 30 
9.7 
DATA ANALYSIS ......................................................................................... 30 
9.7.1 
Main analysis ........................................................................................... 30 
9.7.3 
Safety analysis ......................................................................................... 31 
9.7.4 
Handling of missing data ......................................................................... 32 
9.8 
QUALITY CONTROL ................................................................................... 32 
9.9 
LIMITATIONS OF THE RESEARCH METHODS ...................................... 33 
9.10 
OTHER ASPECTS ......................................................................................... 34 

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9.10.1 
Data quality assurance ............................................................................. 34 
9.10.2 
Study records ........................................................................................... 34 
10. 
PROTECTION OF HUMAN SUBJECTS .......................................................... 36 
10.1 
Study approval, patient information, and informed consent ........................... 36 
10.2 
Statement of confidentiality ............................................................................ 37 
11. 
MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ....................................................................................................... 38 
11.1 
Definitions of adverse events .......................................................................... 38 
11.2 
Adverse event and serious adverse event collection and reporting................. 39 
11.3 
Reporting to health Authorities ....................................................................... 42 
12. 
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
 ............................................................................................................................. 43 
13. 
REFERENCES .................................................................................................... 44 
13.1 
PUBLISHED REFERENCE ........................................................................... 44 
13.2 
UNPUBLISHED REFERENCES ................................................................... 46 
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS .............................................. 47 
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS .............................. 48 
ANNEX 3. ADDITIONAL INFORMATION .............................................................. 49 
 
 

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2. 
LIST OF ABBREVIATIONS 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
AF 
Atrial Fibrillation 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
AP 
Alkaline Phosphatase 
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 
Clinical Monitor Local 
CRA 
Clinical Research Associate 
CrCl 
Creatinine Clearance 
CRF 
Case Report Form 
DMP 
Data Management Plan 
EC 
Ethics Committee 
ENCePP  
European Network of Centres for Pharmacoepidemiology and 
Pharmacovigilance  
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 
HAS-BLED 
Hypertension, Abnormal renal and liver function, Stroke (1 point), 
Bleeding history or predisposition, Labile INR, Elderly (> 65 years), 
Drugs and Alcohol 
HRQoL 
Health-Related Quality of Life 
ICH 
International Conference of Harmonisation 
IEC 
Independent Ethics Committee 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
MAH 
Marketing Authorisation Holder 
NHI 
National Health Insurance 
NIS 
Non-Interventional Study 
NSAID 
Non-Steroidal Anti-Inflammatory Drug 
NVAF 
Non-Valvular Atrial Fibrillation 
OAC 
Oral Anticoagulation 
PACT-Q© 
Perception of Anticoagulant Treatment Questionnaire 
PASS 
Post-Authorization Safety Study 
PT 
Prothrombin Time 
RWE 
Real World Experience 

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SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SDV 
Source Data Verification 
SmPC 
Summary of Product Characteristics 
SOP 
Standard Operating Procedure 
SPAF 
Stroke Prophylaxis (or Prevention) in Atrial Fibrillation 
VKA 
Vitamin K Antagonist 
 
 

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3. 
RESPONSIBLE PARTIES 
Title 
Name 
Boehringer Ingelheim Taiwan 
 
 of Medical Affairs 
 
Medical Affairs Coordinator 
 
 
 
 
 
Data 
/Biostatistician 
 
 
Clinical Research 
 
 
 

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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: 
15 March 2017 
1160-0286 
1.0 
15 March 2017 
Title of study: 
Patients’ Assessment of Satisfaction for Stroke Prevention in Atrial 
FibrillationImpact of Conventional Oral Anticoagulant (OAC) 
Compared with Novel Oral Anticoagulant (NOAC) 
Rationale and 
background: 
Non-interventional studies (NIS) observing patients treated with 
Pradaxa for stroke prevention in atrial fibrillation (SPAF) to assess 
treatment satisfaction have not been conducted in Taiwan. Due to the 
limited data on patients’ perception of conventional Vitamin K 
antagonist (VKA) or Pradaxa treatment in real world experience 
(RWE), it remains an interesting topic to address. Therefore, the 
observational study is proposed to describe the perception of 
anticoagulant treatment according to the questionnairePACT-Q in 
the cohorts of patients switching from VKAs to Pradaxa or newly 
initiating Pradaxa/VKAs. 
Research question 
and objectives: 
Objective 1 
To describe the treatment perception from patients with non-valvular 
atrial fibrillation (NVAF) receiving Pradaxa® or VKA for stroke 
prevention by using the self-estimation questionnaire of PACT-Q 
during a 6-month study period. 
Objective 2 
To investigate the patient’s characteristics. 
Study design: 
This non-interventional study enrolling patients in Taiwan with a 
previous VKA therapy, followed by switching to Pradaxa® OR patients 
being newly diagnosed with NVAF and initiated on Pradaxa® or VKA. 
The study is primarily based on questionnairePACT-Q. 
Population: 
Inclusion criteria: 
Cohort A (patients switched from VKA to Pradaxa) 
1.A. Written informed consent prior to participation. 
2.A. Female or male patients ≥ 20 years of age with a diagnosis of 
non-valvular atrial fibrillation (NVAF). 
3.A. At least 3 months of continuous VKA treatment for stroke 

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prevention prior to baseline assessment. 
4.A. Patients switched to Pradaxa prior to baseline assessment 
according to the physician’s discretion and the Summary of 
Product Characteristics (SmPCs)/reimbursement criteria. 
OR 
Cohort B (patients newly initiated Pradaxa or VKA) 
1.B. Written informed consent prior to participation. 
2.B. Female or male patients ≥ 20 years of age, newly diagnosed 
with NVAF, and no previous treatment for stroke prevention 
(no use of any OAC within 1 year prior to enrolment). 
3.B. Patients initiated stroke prevention treatment with Pradaxa® 
or VKA according to the physician’s discretion and the 
SmPCs/reimbursement criteria. 
Exclusion criteria: 
1. 
Contraindication to the use of Pradaxa® or VKA as described 
in the SmPCs. 
2. 
Patients receiving Pradaxa® or VKA for any other condition 
than stroke prevention in NVAF. 
3. 
Current participation in any clinical trial of a drug or device.  
4. 
Current participation in an AF-related registry, e.g. the Gloria 
AF program. 
Withdrawal Criteria: 
1. 
Patients withdraw informed consent. 
2. 
Patients lost to follow-up. 
3. 
Any pathological event, adverse event, or any change in the 
patient’s status giving an indication to the physicians that 
further participation in the study may not be the best interest 
of the patient. 
Variables: 
Primary outcome: 
Cohort A (patients switched from VKA to Pradaxa) 
 
Mean PACT-Q2 scores at the second (30-45 days) and the last 
assessment (150-210 days) compared to baseline assessment. 
Cohort B (patients newly initiated Pradaxa or VKA) 
 
Mean PACT-Q2 scores at the second (30-45 days) and the last 
assessment (150-210 days) compared between 2 treatment 
groups. 
Secondary outcome: 
Cohort A (patients switched from VKA to Pradaxa) 
 
Mean PACT-Q2 score at the last assessment (150-210 days) 
compared to the second assessment (30-45 days). 
Cohort B (patients newly initiated Pradaxa or VKA) 
 
Description of mean PACT-Q1 score at baseline. 

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Characterization of patients from both cohorts according to: 
 
Demographics: Age, gender, race, education level, height, weight, 
and BMI 
 
Co-morbidities 
 
Concomitant therapies 
 
Stroke- and/or bleeding related risk factors in the medical history 
 
CHA2DS2-VASc score 
 
HAS-BLED score 
 
Kidney function (creatinine clearance) 
 
Dosing of Pradaxa® and the reasons for dose change 
 
Duration of previous VKA treatment (for Cohort A only) 
Data sources: 
Source data are collected from medical charts and the questionnaires 
(PACT-Q) completed by the enrolled subjects at approximately 20 
medical centers or regional hospitals. A case report form will be 
designed for data collection. 
Study size: 
It is planned that approximately total 1000 patients from around 20 
medical centers or regional hospitals will be recruited in the study. An 
estimated sub-group allocation basing on real-world practice in Taiwan 
includes approximately 300 patients in Cohort A (patients switched 
from VKA to Pradaxa) and around 700 patients in Cohort B (patients 
newly initiated Pradaxa or VKA), with about 500 patients receiving 
Pradaxa® and 200 patients receiving VKA. Consecutive enrolment will 
be performed to minimize selection bias. The actual number of patients 
in each cohort will be according to the patient distribution in the real-
world practice. 
Total number 
1000 
Estimated 
number in 
sub-grouping 
Cohort AVKA switches to Pradaxa 
300 
Cohort BNewly initiator 
Pradaxa 
500 
VKA 
200 
 
 
 
 

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Data analysis: 
A Data Management Plan (DMP) and Statistical Analysis Plan (SAP) 
will be prepared to describe all processes, variables, and specifications 
for data collection, cleaning, validation, and analyses. 
The study is essentially descriptive. All patients who have signed the 
informed consent and fulfilled study criteria will be included in the 
main analysis. 
Baseline demographic and clinical characteristics 
Descriptive summary will be presented for all patients enrolled in 
Cohort A, Cohort B Pradaxa® initiators, and Cohort B VKA initiators, 
respectively. For continuous variables, number of patients, mean, 
standard deviation, median, lower quartile, upper quartile, minimum, 
and maximum will be presented. For categorical variables, frequency 
and percentage will be presented for each category. 
Primary outcomes 
For Cohort A, the PACT-Q2 score at Visit 2 and Visit 3 will be 
compared with the PACT-Q2 score at baseline visit, respectively, 
using paired t-test or Wilcoxon signed-rank test. 
For Cohort B, the patients newly initiated Pradaxa or VKA will be 
matched with a ratio of 1:1 based on the propensity score. The 
covariates will be included in the propensity score model if available. 
Descriptive summary of the baseline characteristics will be compared 
between the matched patients to check the balance of baseline 
characteristics between the two sub-groups of Cohort B after 
propensity score matching (PSM). Standardized difference will be 
calculated as a measure of the balance of baseline characteristics after 
PSM. Analyses of PACT-Q2 score will be performed on propensity 
score matched Pradaxa initiators and VKA initiators. PACT-Q2 score 
will be compared between matched Pradaxa initiators and VKA 
initiators using paired t-test or Wilcoxon signed-rank test.  
Secondary outcomes 
For Cohort A, the PACT-Q2 score at Visit 2 and Visit 3 will be 
compared using paired t-test or Wilcoxon signed-rank test based on the 
distribution of the data. 
For Cohort B, descriptive summary will be presented for PACT-Q1 
score at baseline visit on all patients in Cohort B and by treatment 
(Pradaxa or VKA). 
Milestones: 
 
IRB/IEC approval: 17 July 2017 
 
Start of data collection: 07 August 2017 
 
End of data collection: 27 September 2018 
 
Final report of study results: 20 December 2018 
 

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5. 
AMENDMENTS AND UPDATES 
None. 

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6. 
MILESTONES 
Milestone 
Planned Date 
IRB/IEC approval 
17 July 2017 
Start of data collection 
07 August 2017 
End of data collection 
27 September 2018 
Final report of study results 
20 December 2018 

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7. 
RATIONALE AND BACKGROUND 
Pradaxa® (dabigatran etexilate), one of the novel oral anticoagulants (NOACs), is a direct 
thrombin inhibitor first approved in Europe in 2008 for the prevention of stroke and 
systemic embolism in adult patients suffering from non-valvular atrial fibrillation (NVAF) 
with one or more risk factors. In 2010, the Food and Drug Administration (FDA) confirmed 
the findings of the RE-LY study in 18,000 patients, which led to the approval of Pradaxa® 
for stroke prevention in AF worldwide.1,2,3 In 2014, the FDA reported the study results 
comparing Pradaxa® to warfarin in 134,000 patients, and concluded that Pradaxa® was 
associated with a significantly reduced risk of ischaemic stroke and intracranial bleeding 
and a significant survival benefit compared with warfarin in elderly patients with NVAF.1 
Similar results were found in other observational studies, showing Pradaxa® was effective 
and safe with low rates of cardiovascular or major bleeding events.4,5,6 
According to the previous study results, the decision in clinical practice to use Pradaxa® or 
established vitamin K antagonists (VKAs) depends on many factors related to: (a) The 
patient: health status, comorbid and demographic conditions, perception of anticoagulant 
treatment, understanding of the burden of the disease, access to the medication, educational 
measures informing about medications, and reimbursement status. (b) The treating physician: 
stroke risk assessment, bleeding risk assessment, adherence to guidelines, access and use of 
medical education, and overall local health care system. These factors in the real-world 
clinical practice vary in countries with different health care systems; patients who newly 
start anticoagulation treatment versus those have had anticoagulation experience already; 
and the initiation versus the mid-term follow-up on Pradaxa®. According to National Health 
Insurance (NHI) in Taiwan, Pradaxa® is prescribed to a newly diagnosed NVAF patient with 
stroke or systemic embolism, left ventricular ejection fraction < 40%, symptomatic heart 
failure (New York Heart Association Class ≥ 2), age ≥ 75 years, or age ≥ 65 years with one 
of the following risk factors: diabetes mellitus, coronary artery disease (CAD), or 
hypertension. Pradaxa® should not be considered if the patient has valvular heart disease, 
stroke within 14 days, serious stroke within 6 months, the risk of increasing ischemia, 
creatinine clearance (CrCl) < 30 mL/min, active liver disease, or pregnant. 
Although the clinical practice guide on the dosing and management of Pradaxa® is well 
established, the data on how patients perceive Pradaxa® treatment in the context of atrial 
fibrillation disease management only exist to a limited degree.7 In the RE-LY study, over 
the course of one year, all the anticoagulated patients without outcome events (e.g. strokes 
or major bleedings) had stable results in Health-Related Quality of Life (HRQoL). To 
further describe patient's perception of anticoagulant treatment when using Pradaxa® to 
prevent stroke and systemic embolism while suffering from NVAF in comparison to 
standard care using VKA, some patient convenience studies are conducted in Europe 
(
 and 
 and Asia 
 at present. However, such a 
non-interventional study (NIS) observing patients treated with Pradaxa for stroke 
prevention in atrial fibrillation (SPAF) to assess treatment satisfaction has not been 
conducted in Taiwan. Due to the limited data on patients’ perception of conventional VKA 
or Pradaxa treatment in real world experience (RWE), it remains an interesting topic to 
address. Therefore, the observational study is proposed to describe the perception of 

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anticoagulant treatment according to the questionnairePACT-Q in the cohorts of patients 
switching from VKAs to Pradaxa or newly initiating Pradaxa/VKAs. 

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8. 
RESEARCH QUESTION AND OBJECTIVES 
Objective 1 
To describe the treatment perception from patients with non-valvular atrial fibrillation 
(NVAF) receiving Pradaxa® or VKA for stroke prevention by using the self-estimation 
questionnaire of PACT-Q during a 6-month study period. 
Objective 2 
To investigate the patient’s characteristics. 
 
Two cohorts of patients will be recruited: 
Cohort A: 
Patients who had been treated with VKA and have switched to Pradaxa®. 
Cohort B: 
Patients who are newly diagnosed with NVAF and initiated on either Pradaxa® or VKA. 

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9. 
RESEARCH METHODS 
9.1 
STUDY DESIGN 
This is a non-interventional, single-country, multi-center study based on newly collected 
data. The study will enroll consented patients with NVAF in Taiwan with a previous VKA 
therapy, followed by switching to Pradaxa® (Cohort A) OR patients being newly diagnosed 
with NVAF and initiated on Pradaxa® or VKA (Cohort B). Patients will be followed up over 
an observation period of 6 months. Data will be collected at 3 time points: 
1. 
Baseline (e.g., the enrolment date for Cohort A; the date of initiation on Pradaxa® or 
VKA for Cohort B). 
2. 
30 to 45 days after baseline (initiation period). 
3. 
150 to 210 days after baseline (continuation period). 
 
9.2 
SETTING 
It is planned that data of approximately 1000 patients will be collected from approximately 
20 medical centers or regional hospitals in Taiwan where Pradaxa taken as one 110/150 mg 
capsule twice a day is listed as a prescription of SPAF in hospital formulary. Patients 
diagnosed with NVAF before the patient’s baseline (inclusion) visit will be consecutively 
enrolled in the study. Selected subjects must meet all of the eligibility criteria described in 
Section 9.2.2. 
After study initiation, the sites will include suitable patients where the decision for 
switching from VKA to Pradaxa® (Cohort A) or decision for initiation with Pradaxa® or 
VKA (Cohort B) has been made. Consecutive enrolment will be performed during whole 
recruitment period to minimize selection bias in the real-world practice. 
The decision for therapy has to be made prior to and independently of enrolment into the 
study. Only after the treatment decision for the patient is made, the investigator can check 
and decide if a patient can be enrolled in Cohort A or Cohort B. Patients will then have to 
sign the informed consent before they can take part in the non-interventional study. 
 
9.2.1 
Study sites 
Cardiologist and non-cardiologist sites regularly prescribing Pradaxa® and VKA for stroke 
prevention in NVAF according to the respective Summary of Product Characteristics 
(SmPCs) will participate. 
Selected sites include around 20 medical centers or regional hospitals in Taiwan, from 
Northern to Southern area, with physicians and facilities that reflect the locally clinical 
practice. The site selection criteria will help to ensure that the patients recruited into this 
study will represent the population with NVAF receiving Pradaxa® or VKA for stroke 
prevention in Taiwan. 

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9.2.2 
Study population 
Inclusion criteria 
Cohort A (patients switched from VKA to Pradaxa) 
1.A. 
Written informed consent prior to participation. 
2.A. 
Female or male patients ≥ 20 years of age with a diagnosis of non-valvular atrial 
fibrillation (NVAF). 
3.A. 
At least 3 months of continuous VKA treatment for stroke prevention prior to 
baseline assessment. 
4.A. 
Patients switched to Pradaxa prior to baseline assessment according to the 
physician’s 
discretion 
and 
the 
Summary 
of 
Product 
Characteristics 
(SmPCs)/reimbursement criteria. 
OR 
 
Cohort B (patients newly initiated Pradaxa or VKA) 
1.B. 
Written informed consent prior to participation. 
2.B. 
Female or male patients ≥ 20 years of age, newly diagnosed with NVAF, and no 
previous treatment for stroke prevention (no use of any OAC within 1 year prior 
to enrolment). 
3.B. 
Patients initiated stroke prevention treatment with Pradaxa® or VKA according 
to the physician’s discretion and the SmPCs/reimbursement criteria. 
 
Exclusion criteria 
1. 
Contraindication to the use of Pradaxa® or VKA as described in the SmPCs. 
2. 
Patients receiving Pradaxa® or VKA for any other condition than stroke 
prevention in NVAF. 
3. 
Current participation in any clinical trial of a drug or device.  
4. 
Current participation in an AF-related registry, e.g. the Gloria AF program. 
 
Withdrawal criteria 
Every patient has the right to withdraw consent at any time during the study, without the 
need for justification or any impact on the routine therapy. A patient is considered 
permanently discontinued or withdrawn from treatment if he/she does not complete the 
treatment with Pradaxa® or VKA in the 6-month study period or did not perform all three 
assessments. Withdrawal criteria includes: 
1. 
Patients withdraw informed consent. 
2. 
Patients lost to follow-up. 
3. 
Any pathological event, adverse event, or any change in the patient’s status 
giving an indication to the physicians that further participation in the study may 
not be the best interest of the patient. 

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9.2.3 
Study visits 
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, no visit 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 (PACT-Q). The planned collection time points are as 
follows: 
1. 
Baseline (e.g., the enrolment date for Cohort A; the date of initiation on Pradaxa® or 
VKA for Cohort B) 
2. 
30 to 45 days after baseline (initiation period) 
3. 
150 to 210 days after baseline (continuation period) 
 
Data will be collected and recorded on the CRF at baseline and follow-up visits according to 
Table 1, if available. 
 
Remark: This is a non-interventional, observational study, all the tests collected at 
baseline and subsequent visits will be performed as judged appropriate by the treating 
physicians, and the results of interest will be recorded only if they are available. This 
study does not require additional tests or examinations to be performed throughout 
the entire study 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, and data will be collected 
from the medical chart and recorded on the CRF, if available: 
 
Sign informed consent form. 
 
Review of inclusion and exclusion criteria, and record date of inclusion. 
 
Collection of reimbursement status (reimbursed, partially reimbursed, or private pay). 
 
Collection of demographic data: age, gender, race, education level, height, weight&, and 
BMI. 
&Weight will be used to calculate BMI and creatinine clearance (CrCl). 
 
Collection of concomitant diseases/comorbidities in the medical history and at baseline. 
 
Collection of concomitant diseases/comorbidities,8 risk factors,9,10 and medical history 
related to NVAF prior to enrolment, including diabetes mellitus, hypertension, 
ischaemic heart disease, congestive heart failure, left ventricular dysfunction, stroke, 
transient ischaemic attack, thromboembolism, vascular disease (myocardial infarction, 
peripheral artery disease, and complex aortic plaque), abnormal renal function, 

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abnormal liver function (e.g. cirrhosis), bleeding (e.g. prior major bleeding, 
predisposition to bleeding/anemia), and alcohol usage. These data will be used to 
calculate CHA2DS2-VASc score and HAS-BLED score#. 
 
Collection of current concomitant therapies within 1 month prior to enrolment. Detail 
information (e.g. indication, start/stop date or ongoing, dosage, route, unit, and 
frequency etc.) will be recorded if available. 
- 
For the concomitant therapy as an element for CHA2DS2-VASc score or HAS-
BLED score calculation,9,10 including chronic dialysis or renal transplant due to 
abnormal renal function and medication usage predisposing to bleeding (antiplatelet 
agents or nonsteroidal anti-inflammatory drugs (NSAIDs)), information prior to 
enrolment will only be collected as active/past or never occurred. 
 
Collection of serum creatinine, if available, to calculate creatinine clearance (CrCl). 
The most updated data of serum creatinine assessed prior to enrolment will be collected. 
CrCl will be calculated according to Cockcroft-Gault formula (using weight collected 
at the baseline visit and the most updated serum creatinine assessed prior to enrolment). 
 
Collect the most updated data of lab assessment assessed prior to enrolment for 
CHA2DS2-VASc score and HAS-BLED score calculation.9,10 The lab assessments 
include renal function test (CrCl, as described above), liver function tests (bilirubin, 
aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline 
phosphatase (AP)), and international normalized ratio (INR), including prothrombin 
time (PT). 
 
For Cohort A only: Collect duration of previous treatment with VKA. 
 
For Cohort A only: Collect reasons for switching from VKA to Pradaxa®. 
 
Document the dosing of Pradaxa®. 
 
Patients will be asked to complete the following patient related questionnaires: 
- 
PACT-Q1 (Cohort B only) 
- 
PACT-Q2 (Cohort A only) 
 
Conduct safety reporting for Pradaxa® relevant adverse drug reaction (serious, non-
serious), fatal AEs, and pregnancies; and record them on corresponding ADR forms 
and CRF pages. 
 
Complete the screening log for all patients that do not qualify at baseline*. 
 
Complete required CRFs. 
 
#Information to be collected, whenever available, for CHA2DS2-VASc score and HAS-BLED 
score calculation 
Age, gender, and part of concomitant diseases/comorbidities, risk factors, medical history, 
concomitant therapies, and lab assessments will be collected for the CHA2DS2-VASc score 
and HAS-BLED score calculation, if available. The data time frame on medical chart is 
defined as below: 
- Demographics (age and gender): at the baseline visit. 
- Comorbidities, risk factors, medical history, and concomitant therapies: prior to enrolment. 

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- Lab assessment: the most updated data conducted prior to enrolment, if regular practice 
available. 
The description of scoring CHA2DS2-VASc and HAS-BLED is summarized in Section 9.3.4. 
*Information to be collected on screening failures 
The screening log entry with demographic information and the primary reason for not 
continuing or ineligibility must be completed for all screened patients that do not qualify for 
baseline visit (Visit 1). No CRF other than the screening log will be collected for these 
patients. The subject number of these ineligible patients should be kept, and the following 
enrolments will be numbered in sequence. 
 
Initiation period (Visit 2): 
During a routine practice visit occurring at 30 to 45 days after baseline, the following 
assessments will be documented, if available: 
 
Weight will be recorded to calculate creatinine clearance (CrCl). 
 
New or changed concomitant diseases/comorbidities. 
 
Changes in concomitant therapies. 
 
Collection of serum creatinine, if available, to calculate creatinine clearance (CrCl). 
Serum creatinine assessed within 30 to 45 days after enrolment will be collected. CrCl 
will be calculated according to Cockcroft-Gault formula (using weight collected at 
Visit 2 and serum creatinine assessed within 30 to 45 days after enrolment). 
 
Collect dosing of Pradaxa® and reasons for dose change (if applicable). 
 
Patients will be asked to complete the PACT-Q2 questionnaire. 
 
Reasons for Pradaxa® or VKA discontinuation (if applicable). 
 
Conduct safety reporting for Pradaxa® relevant ADR (serious, non-serious), fatal AEs, 
and pregnancies; and record them on corresponding ADR forms and CRF pages. 
 
Complete required CRFs. 
 
Continuation period (Visit 3): 
During a routine practice visit occurring at 150 to 210 days after baseline, the following 
assessments will be documented, if available: 
 
Weight will be recorded to calculate creatinine clearance (CrCl). 
 
New or changed concomitant diseases/comorbidities. 
 
Changes in concomitant therapies. 
 
Collection of serum creatinine, if available, to calculate creatinine clearance (CrCl). 
Serum creatinine assessed within 150 to 210 days after enrolment will be collected. 
CrCl will be calculated according to Cockcroft-Gault formula (using weight collected 
at Visit 3 and serum creatinine assessed within 150 to 210 days after enrolment). 
 
Collect dosing of Pradaxa® and reasons for dose change (if applicable). 
 
Patients will be asked to complete the PACT-Q2 questionnaire. 

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 
Reasons for Pradaxa® or VKA discontinuation (if applicable). 
 
Conduct safety reporting for Pradaxa® relevant ADR (serious, non-serious), fatal AEs, 
and pregnancies; and record them on corresponding ADR forms and CRF pages. 
 
Complete required CRFs. 
With this visit, the patient’s participation in the study will be completed. 
 
 

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Table 1 is the recommended data collection schedule that most likely mirrors the patterns of 
routine clinical care of most NVAF patients for stroke prevention. The sign “X” indicates 
when the data will be collected if available. 
 
Table 1  Data Collection Schedule 
Visit 
1 
2 
3 
Assessment 
Baseline 
Initiation period 
Continuation period 
Day(s) and allowed window* 
1 
30 to 45 
150 to 210 
Informed consent1 
X 
 
 
Inclusion/exclusion criteria 
X 
 
 
Reimbursement status2 
X 
 
 
Patient demographics3 
X 
 
 
Weight4 
X 
X 
X 
Concomitant diseases/comorbidities 
X 
X 
X 
Comorbidities, risk factors, and 
medical history related to NVAF5 
X 
 
 
Concomitant therapies6 
X 
X 
X 
Concomitant therapies related to 
CHA2DS2-VASc and HAS-BLED7 
X 
 
 
Collection of serum creatinine to 
calculate creatinine clearance8 
X 
X 
X 
Collection of lab data related to 
CHA2DS2-VASc and HAS-BLED9 
X 
 
 
CHA2DS2-VASc score 
X 
 
 
HAS-BLED score 
X 
 
 
Duration of previous VKA 
treatment (Cohort A only) 
X 
 
 
Reasons for switching from VKA 
to Pradaxa® (Cohort A only) 
X 
 
 
Record Pradaxa® dosing (110 or 
150mg) and reasons for dose 
changes if applicable 
 
 
 
PACT-Q1 questionnaire 
X (Cohort B only) 
 
 
PACT-Q2 questionnaire 
X (Cohort A only) 
X (both cohorts) 
X  (both cohorts) 
Reason for Pradaxa® or VKA 
discontinuation 
 
 
 
Safety reporting10 
 
 
 

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*Only lab data assessed within the following allowed window and according to regular practice will be 
collected: 
-Baseline: the most updated data conducted prior to enrolment 
-Visit 2: within 30-45 days after baseline 
-Visit 3: within 150-210 days after baseline 
1. Written informed consent must be obtained prior to the baseline visit assessment. 
2. Reimbursement status includes reimbursed, partially reimbursed, or private pay. 
3. Age, gender, race, education level, height, weight, and BMI. 
4. Weight will be recorded at each visit if possible to calculate BMI (baseline only) and creatinine clearance. 
5. Comorbidities, risk factors, and medical history related to NVAF include: diabetes mellitus, hypertension, 
ischaemic heart disease, congestive heart failure, left ventricular dysfunction, stroke, transient ischaemic 
attack, thromboembolism, vascular disease (myocardial infarction, peripheral artery disease, and complex 
aortic plaque), abnormal renal function, abnormal liver function (e.g. cirrhosis), bleeding (e.g. prior major 
bleeding, predisposition to bleeding/anemia), and alcohol usage. The data prior to enrolment will be collected. 
6. The current concomitant therapies within 1 month prior to enrolment will be collected. Changes in 
concomitant therapies will be collected at Visit 2 and Visit 3. 
7. The concomitant therapies related to CHA2DS2-VASc and HAS-BLED score prior to enrolment will be 
collected, including chronic dialysis or renal transplant due to abnormal renal function, and medication usage 
predisposing to bleeding (antiplatelet agents or nonsteroidal anti-inflammatory drugs (NSAIDs)). 
8. Serum creatinine assessment conducted within the allowed window of lab assessment* will be collected to 
calculate CrCl according to Cockcroft-Gault formula. 
9. The lab assessments include: renal function test (serum creatinine, same as the collection of CrCl at baseline 
described in #8), liver function tests (bilirubin, aspartate aminotransferase (AST), alanine aminotransferase 
(ALT), and alkaline phosphatase (AP)), and international normalized ratio (INR, including prothrombin time 
(PT)). Only the most updated results of assessments conducted prior to enrolment will be collected. 
10. Pradaxa® relevant ADR (serious and non-serious), fatal AEs, and pregnancies. 
 
9.2.4 
Study discontinuation 
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 the 
continuation of the study, or any other administrative reasons. 
3. 
Violation of Good Clinical Practice (GCP) (as applicable), the study 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). 
 
9.3 
VARIABLES 
9.3.1 
Exposures 
Currently, Pradaxa and VKA have been approved for treating NVAF patients for stroke 
prevention. The use of Pradaxa and VKA will be according to the SmPCs and physician´s 
discretion. Prescription of Pradaxa will be collected and recorded on the CRF during the 

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observational period, if available, including start/end date, dose, and the reason for dose 
adjustment or interruption. 
 
9.3.2 
Outcomes 
9.3.2.1 
Primary outcomes 
Cohort A (patients switched from VKA to Pradaxa) 
 
Mean PACT-Q2 scores at the second (30-45 days) and the last assessment (150-210 
days) compared to baseline assessment. 
Cohort B (patients newly initiated Pradaxa or VKA) 
 
Mean PACT-Q2 scores at the second (30-45 days) and the last assessment (150-210 
days) compared between 2 treatment groups. 
 
9.3.2.2 
Secondary outcome 
Cohort A (patients switched from VKA to Pradaxa) 
 
Mean PACT-Q2 score at the last assessment (150-210 days) compared to the second 
assessment (30-45 days). 
Cohort B (patients newly initiated Pradaxa or VKA) 
 
Description of mean PACT-Q1 score at baseline. 
 
9.3.3 
Covariates 
Demographic and clinical characteristics, including age, gender, body weight, CHA2DS2-
VASc score, HAS-BLED score, kidney function (creatinine clearance), stroke and/or 
bleeding related risk factors, co-morbidities, and/or concomitant therapies will be collected 
if available. If any covariates or confounding/interacting variables that may be possibly 
predictive of the outcome under study are noted, additional analyses may be carried out to 
identify its effect. Details of handling covariates will be given in the statistical analysis plan 
(SAP), if any covariates of interest are detected. 
 
 

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9.3.4 
Baseline characteristics and general information 
Baseline characteristics of patients include: 
 
Demographics: Age, gender, race, education level, height, weight, and BMI 
 
Comorbidities 
 
Concomitant therapies 
 
Stroke- and/or bleeding related risk factors in the medical history 
 
CHA2DS2-VASc score 
 
HAS-BLED score 
 
Kidney function (creatinine clearance) 
 
Dosing of Pradaxa® and the reasons for dose change 
 
Duration of previous VKA treatment (for Cohort A only) 
 
For the following 6 sections, data collection detail is described in Section 9.2.3. 
1. 
Concomitant diseases/comorbidities 
All the concomitant diseases/comorbidities in the medical history will be collected at 
Baseline visit (Visit 1). Newly occurred or changed concomitant diseases/comorbidities 
compared with the previous visit will be collected at the initiation period (Visit 2) and the 
continuation period (Visit 3). 
2. 
Comorbidities/Risk factors/Medical history related to NVAF8 
For the comorbidities/risk factors/medical history related to NVAF, the status (active/past or 
never occurred, no retrospective time limit is set) should be documented at enrolment, if 
available. The comorbidities/risk factors/medical history related to NVAF include diabetes 
mellitus, hypertension, ischaemic heart disease, heart failure, stroke, transient ischaemic 
attack, and thromboembolism. 
3. 
Concomitant therapies 
Current concomitant therapies within 1 month prior to enrolment will be collected. Changes 
in concomitant therapies compared with the previous visit will be collected at the initiation 
period (Visit 2) and the continuation period (Visit 3). Data of interest include start/stop date 
or ongoing, dose, unit, and frequency. 
For the concomitant therapy as an element for the CHA2DS2-VASc score or HAS-BLED 
score calculation, including chronic dialysis or renal transplant due to abnormal renal 
function and medication usage predisposing to bleeding (antiplatelet agents or nonsteroidal 
anti-inflammatory drugs (NSAIDs)), information will only be collected as active/past or 
never occurred prior to enrolment (no retrospective time limit is set). 
4. 
Calculation of CHA2DS2-VASc score9 
The CHA2DS2-VASc score is a clinical prediction rule for estimating the risk of stroke in 
patients with non-rheumatic AF. The CHA2DS2-VASc score is composed of 8 items with a 
maximum score of 9. Among all the items, 2 of them have extra weight with 2 points, 

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including “age 75 and above” and “stroke, transient ischemic attack, and thromboembolism”, 
while the other 6 items are counted as 1 point of each. A higher score corresponds to a 
greater risk of stroke. The available information for verifying the items in CHA2DS2-VASc 
score will be collected from source data and will be recorded on the CRFs. The CHA2DS2-
VASc score will be calculated according to Table 2. 
Table 2  The 2009 Birmingham Schema Expressed as a Point-Based Scoring System, 
With the Acronym CHA2DS2-VASc 
Letter 
Clinical Characteristic 
Score 
C 
Congestive heart failure or left ventricular dysfunction 
1 
H 
Hypertension 
1 
A2 
Age ≥ 75 years 
2 
D 
Diabetes Mellitus 
1 
S2 
Previous stroke, transient ischemic attack, or thromboembolism 
2 
V 
Vascular disease (prior myocardial infarction, peripheral artery disease, or 
aortic plaque) 
1 
A 
Age 65–74 years 
1 
Sc 
Sex category (i.e. female sex) 
1 
 
5. 
Calculation of HAS-BLED score10 
HAS-BLED is a scoring system developed to assess 1-year risk of major bleeding in 
patients with AF. The HAS-BLED score is composed of 7 items with a maximum score of 9. 
Among all the items, 2 of them will be scored with 1 or 2 points depending on the number 
of corresponded description, including “abnormal renal and liver function” and “drugs or 
alcohol”, while the other 5 items are counted as 1 point of each. A higher score corresponds 
to a greater risk of bleeding, and a score of ≥ 3 points indicates "high risk". The available 
information for verifying the items in HAS-BLED score will be collected from source data 
and will be recorded on the CRFs. The HAS-BLED score will be calculated according to 
Table 3. 
Table 3  Clinical Characteristics Composing the HAS-BLED Bleeding Risk Score 
Letter 
Clinical Characteristic 
Score 
H 
Hypertension1 
1 
A 
Abnormal renal function2 and abnormal liver function3 (1 point each) 
1 or 2 
S 
Stroke4 
1 
B 
Bleeding5 
1 
L 
Labile INRs6 
1 
E 
Elderly, age > 65 years 
1 

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D 
Drugs or alcohol (1 point each)7 
1 or 2 
1. Hypertension should be uncontrolled, with systolic blood pressure > 160 mmHg. 
2. Abnormal kidney function is classified as a presence of chronic dialysis, renal transplantation, or serum 
creatinine ≥ 200 µmol/L. 
3. Abnormal liver function is deﬁned as the chronic hepatic disease (e.g., cirrhosis) or biochemical evidence of 
signiﬁcant hepatic derangement (e.g., bilirubin > 2 × upper limit of normal, in association with 
AST/ALT/AP > 3 × upper limit normal, and so forth.) 
4. Previous history, particularly lacunar. 
5. Bleeding history, such as prior major bleeding or predisposition to bleeding (e.g., anemia). 
6. Labile international normalized ratio (INR, e.g., therapeutic time in range < 60%). 
7. Drugs are medication usage predisposing to bleeding (e.g. antiplatelet agents or NSAIDs). 
Ethanol abuse is classiﬁed as ≥ 8 units of alcoholic consumption per week. 
 
6. 
Calculation of creatinine clearance (CrCl) 
Kidney function will be evaluated according to creatinine clearance (CrCl). Serum 
creatinine available from medical chart and weight assessed according to the visit schedule 
will be collected to calculate the CrCl value by Cockcroft-Gault formula*. In addition, only 
serum creatinine data assessed within the allowed window will be collected. The allowed 
window at each visit is listed as below: 
- Baseline: the most updated data assessed prior to enrolment 
- Visit 2 (initiation period): within 30-45 days after baseline 
- Visit 3 (continuation period): within 150-210 days after baseline 
 
*Cockcroft-Gault formula: 
If the information of serum creatinine and weight are both collected and recorded on the 
CRFs, the CrCl will be calculated via Cockcroft-Gault formula which could be measured in 
different serum creatinine units (mg/dL or µmol/L):11,12 
 
When serum creatinine is measured in mg/dL: 
The resulting value is multiplied by a constant of 0.85 if the patient is female. 
 
When serum creatinine is measured in µmol/L: 
Constant is 1.23 for male and 1.04 for female. 
 
9.3.5 
Description and justification of patient questionnaires (PACT-Q©) 
The Perception of Anticoagulant Treatment Questionnaire (PACT-Q) was developed as a 
means to investigate patients’ satisfaction with anticoagulant treatment and treatment 

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convenience in patients with deep venous thrombosis (DVT), pulmonary embolism (PE), or 
atrial fibrillation (AF). 13, 14 The PACT-Q is a self-administered questionnaire. It can be 
completed in about 10 minutes. No specific training is required to complete this document. 
The original PACT-Q consists of 2 parts and contains 27 items: 
1. 
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. Only patients in Cohort B (newly initiator) will receive the PACT-
Q1 questionnaire at baseline. 
2. 
The PACT-Q2 is composed of 3 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. The patients 
in Cohort A (switchers) will receive PACT-Q2 at all the 3 visits, while the ones in 
Cohort B (initiators) will receive the questionnaire at Visit 2 and Visit 3. 
 
9.4 
DATA SOURCES 
As this is a non-interventional study, no diagnostic or monitoring procedures additional to 
the standard of care and routine practice will be applied to the patients. All the assessment 
will be performed by the investigator if they are deemed necessary for the medical treatment 
procedure. 
This non-interventional study will collect the data onto the designed paper case report form 
(CRF) if available by the investigators or delegated site staffs. Data source includes patient 
questionnaires (PACT-Q), hospital discharge files, abstracts of primary clinical records, 
electronic medical records, ad hoc clinical databases, administrative records such as 
eligibility files, prescription drug files, biological measurements, exposure/work history 
record reviews, etc. during the routine clinical practice.  
Each patient is identified by a unique central patient identification code, which is only used 
for study purposes. 
 
9.5 
STUDY SIZE 
It is planned that approximately 1000 patients from around 20 medical centers or regional 
hospitals will be recruited in the study. An estimated sub-group allocation basing on real-
world practice in Taiwan includes approximately 300 patients in Cohort A (patients 
switched from VKA to Pradaxa) and around 700 patients in Cohort B (patients newly 
initiated Pradaxa or VKA), with about 500 patients receiving Pradaxa® and 200 patients 
receiving VKA. Consecutive enrolment will be performed during whole recruitment period 
to minimize selection bias. The actual number of patients in each cohort will be according to 
the patient distribution in the real-world practice. 
  
 

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Total number 
1000 
Estimated 
number in 
sub-grouping 
Cohort AVKA switches to Pradaxa 
300 
Cohort BNewly initiator 
Pradaxa 
500 
VKA 
200 
 
9.6 
DATA MANAGEMENT 
The data from enrolled patients in this study will be recorded on a CRF or other applicable 
forms. The designated CRO will capture, check, store and analyze the data. The designated 
CRO will follow Boehringer Ingelheim standard operating procedures (SOPs) and their own 
internal SOPs. 
A data management plan (DMP) will be created to describe all functions, processes, and 
specifications for data collection, cleaning, and validation. 
Data will be transferred to Boehringer Ingelheim after the closure of the study. 
 
9.7 
DATA ANALYSIS 
Analyses will be performed by a designated CRO. The main analysis population will consist 
of all eligible patients (i.e. all patients who have signed the informed consent and fulfilled 
all inclusion criteria and no exclusion criteria). In addition, all eligible patients will be 
categorized into Cohort A (patients switched from VKA to Pradaxa) and Cohort B 
(patients newly initiated Pradaxa or VKA). Cohort B will be further classified into 2 
groups, the Pradaxa initiators or the VKA initiators. The 2 cohorts and the 2 subgroups will 
be used in corresponding PACT-Q analyses. 
Analytic specifications, including tables and listings, will be detailed in the statistical 
analysis plan (SAP) that is separate from the full study protocol. 
Statistical analysis of all data will be performed using the latest version of SAS® statistical 
software (SAS Institute, Cary, NC, USA). All statistical tests are two sided and statistical 
significance level of 0.05 will be used. 
 
9.7.1 
Main analysis 
Baseline demographic and clinical characteristics 
Descriptive summary will be presented for baseline demographic and clinical characteristics 
of all patients enrolled in Cohort A, Cohort B Pradaxa® initiators, and Cohort B VKA 
initiators, respectively. For continuous variables, number of patients, mean, standard 
deviation (SD), median, Q1 (lower quartile), Q3 (upper quartile), minimum, and maximum 
will be presented. For categorical variables, frequency and percentage will be presented for 
each category. 
 

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Primary outcomes 
For Cohort A, descriptive summary will be presented for PACT-Q2 score at baseline visit 
(Visit 1), Visit 2, and Visit 3 using measure of central tendency and variation (mean ± SD, 
or median with inter-quartile range (IQR)). The PACT-Q2 score at Visit 2 and Visit 3 will 
be compared with the PACT-Q2 score at baseline visit, respectively, using paired t-test or 
Wilcoxon signed-rank test based on the distribution of the data. 
For Cohort B, the patients newly initiated Pradaxa or VKA will be matched with a ratio of 
1:1 based on the propensity score. The covariates age, gender, body weight, CHA2DS2-
VASc score, HAS-BLED score, kidney function (creatinine clearance), stroke and/or 
bleeding related risk factors, co-morbidities, and/or concomitant therapies, if available, will 
be included in the propensity score model. Details of the propensity score model and the 
matching procedure, such as the choice of algorithm and caliper width will be specified in 
the SAP. Descriptive summary of the baseline characteristics will be presented for and 
compared between the matched patients to check the balance of baseline characteristics 
between the two groups of Cohort B after propensity score matching. Moreover, 
standardized difference will be calculated as a measure of the balance of baseline 
characteristics after propensity score matching. Analyses of PACT-Q2 score will be 
performed on propensity score matched Pradaxa initiators and VKA initiators. Descriptive 
summary will be presented for PACT-Q2 score at Visit 2 and Visit 3 using mean ± SD, or 
median with IQR. PACT-Q2 score will be compared between matched Pradaxa initiators 
and VKA initiators using paired t-test or Wilcoxon signed-rank test. 
Secondary outcomes 
For Cohort A, the PACT-Q2 score at Visit 2 and Visit 3 will be compared using paired t-
test or Wilcoxon signed-rank test based on the distribution of the data. 
For Cohort B, descriptive summary will be presented for PACT-Q1score at baseline visit 
using mean ± standard deviation, or median with IQR, and will be performed on all patients 
in Cohort B and by treatment (Pradaxa or VKA). 
 
9.7.3 
Safety analysis 
Safety analyses will be performed separately for Cohort A and Cohort B, and will include all 
enrolled patients with an actual follow-up. Statistical analysis and reporting of AEs (i.e. 
Pradaxa® relevant ADR (serious and non-serious), fatal AEs, and pregnancies) will be 
descriptive in nature and based on BI standards. No hypothesis testing is planned. The 
assessment of safety will be based mainly on the frequency of adverse events, which includes 

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all serious adverse events. All adverse events will be summarized with the coding term, 
severity, and relationship to study drug by frequency tables with the counts and percentage. 
In addition, occurrences of Pradaxa® relevant ADRs will be analyzed relative to the number 
of patients treated as well as observed person-years (i.e. time at risk). If no concurrent 
Pradaxa® treatment is administered, then events occurring within a washout period of 3 days 
after discontinuation of Pradaxa® 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 Pradaxa® treatment prescribed at baseline, during 
periods without Pradaxa® 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. 
Furthermore, serious adverse events will be listed with event narration. Adverse events will 
be coded using the latest version of Medical dictionary for regulatory activities (MedDRA) 
terminology. 
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 
 
9.7.4 
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 SAP. 
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 are lost to follow-up 
in comparison to patients who have completed follow-up. 
 
9.8 
QUALITY CONTROL 
Before the study launch, participating physicians will be trained on the protocol, safety 
reporting (as described in Section 11) and study conduct procedures by Boehringer 
Ingelheim (or designee). 
In keeping with the non-interventional design employed in this study, site interaction (e.g., 
direct contact between site study staff or patients and representatives of the call center or the 
Study Coordinating Center) is minimized. 

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Twenty percent source data verification is planned in this study. At any time during the 
course of the study, the site study staff may contact designated personnel for clarification of 
study conduct. All information will be kept confidential. 
During the study, the occurrence of any protocol violations will be determined. After these 
actions have been completed and the clinical database has been declared to be complete and 
accurate, it will be locked. 
To ensure the data accuracy, completeness, and reliability, quality control will be the 
ongoing, concurrent review of data collection forms for completion and logic. The research 
staffs will preserve documented data from all sources on CRF, including lab test results, 
chart records, treatment conditions, physical examination, concomitant medication, and any 
safety information. 
Boehringer Ingelheim or designated CRO will assure database quality processes are 
followed including the review of the data entered into the CRFs by investigational staffs for 
completeness and accuracy, and in accordance with the data validation plan. 
 
9.9 
LIMITATIONS OF THE RESEARCH METHODS 
A non-interventional study is the most suitable design for obtaining information about the 
use of medicines in everyday therapeutic practice and thus for clarifying questions in 
everyday therapeutic practice. However, observational methodology inherits the limitation 
of selection bias and generalizability. In addition, the observational design intends to collect 
available data that are recorded on medical charts. The lack of data of interest may be one of 
the limitations. 
A number of different types of bias that could influence the data collection and analysis 
from these cohorts are summarized below. Consecutive enrolment will be employed to 
minimize selection bias. The entry criteria are non-restrictive and will permit the enrolment 
of a broad patient population. The choice of treatment is at the discretion of the investigator. 
Missing data will be handled as appropriate (see Section 9.7.4) to lower the effect of missing 
values. All efforts will be made to minimize loss to follow-up in patients who are enrolled. 
Adjustment for covariates and propensity score matching (PSM) will be used to correct for 
identified confounders and channeling bias which could 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). Patient reported outcomes will be assessed using 
validated questionnaires within a limited period of time to minimize recall bias which 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. 
 

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9.10 
OTHER ASPECTS 
9.10.1 
Data quality assurance 
A quality assurance audit/inspection of this study may be conducted by the sponsor or 
sponsor’s designees or by Institutional Review Board (IRBs)/Independent Ethics Committee 
(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. 
 
9.10.2 
Study records 
Case Report Forms (CRFs) for individual patients will be provided by the sponsor via paper. 
All paper CRFs should be typed or filled out with a black ball-point pen and must be legible.  
 
Corrections to paper forms will be made by a single line stroke through the error and 
insertion of the correction above or beside the error. The change must be initialed 
and dated by the investigator or a member of the study staff authorized by the 
investigator on the Authority Form. No erasers, correction fluid, or tape may be used. 
 
The principal investigator will sign and date the indicated places on the CRFs. These 
signatures will indicate that the principal investigator inspected or reviewed the data 
on the CRF, the data queries, and the site notifications, and agrees with the content. 
 
9.10.2.1 
Source documents 
Source documents are original documents, data, and records from which the subject’s CRF 
data are obtained. These include but are not limited to hospital records, clinical and office 
charts, laboratory and pharmacy records, diaries, microfiches, radiographs, and 
correspondence. Case report form entries may be considered source data if the CRF is the 
site of the original recording (i.e., there is no other written or electronic record of data). 
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 reported on the CRFs 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 study; also 
current medical records must be available. 
For paper CRFs, the following data need to be derived from source documents: 
 
Patient identification (gender, date of birth, etc.) 
 
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 concomitant diseases and concomitant, if applicable) 

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 
Adverse drug reactions and outcome events (onset date [mandatory], and end date [if 
available]) 
 
fatal adverse events (SAEs) (onset date (mandatory), and end date (if available)) 
 
Pregnancy record 
 
Originals or copies of laboratory results or examinations (in validated electronic 
format, if available) 
 
Conclusion of Patient’s Participation in the study 
The physician must keep the original informed consent form signed by the patient (a signed 
copy is given to the patient). 
The investigator should maintain a list of appropriately qualified persons to whom he/she 
has delegated trial duties. All persons authorized to make entries and/or corrections on CRFs 
will be included on the Authority Form. 
No information in source documents about the identity of the patients will be disclosed. No 
study document should be destroyed without prior written agreement between Boehringer 
Ingelheim and the investigator. Should the investigator wish to assign the study records to 
another party or move them to another location, he/she must notify Boehringer Ingelheim in 
advance. 
 
9.10.2.2 
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. 
CRFs and all source documents, including progress notes, 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. US Food and Drug Administration [FDA]). 
The Clinical Research Associate (CRA)/Clinical Monitor Local (CML) and the auditor may 
review all CRFs and written informed consents. The accuracy of the data will be verified by 
reviewing the documents described in Section 9.10.2.1. 

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10. 
PROTECTION OF HUMAN SUBJECTS 
The study will be carried out in compliance with the protocol, the principles laid down in the 
Declaration of Helsinki, in accordance with the ICH Harmonized Tripartite Guideline for 
Good Clinical Practice (GCP) (to the extent applicable to the NIS setting and required by 
local regulations), Good Epidemiological Practice (GEP), Guidelines for Good 
Pharmacoepidemiology Practice (GPP), 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 study are described in the investigator contract. As a general rule, no study results 
should be published prior to finalization of the Study Report and consent from sponsor. 
Insurance Cover: The requirements for insurance depend on local law and legislations. 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). 
 
10.1 
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 to 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 study 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. 
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. Eligible patients may only be included in 
the study after providing written (witnessed, where required by law or regulation), IRB/EC-
approved informed consent, or, if incapable of doing so, after such consent has been 
provided by a legally acceptable representative of the patient. In cases where the patient’s 
representative gives consent, the patient should be informed about the study to the extent 
possible given his/her understanding. If the patient is capable of doing so, he/she should 
assent by personally signing and dating the written informed consent document or a separate 

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assent form. Informed consent must be obtained before any data are collected. The process 
of obtaining informed consent should be documented in the patient source documents. 
The patient must be informed that his/her medical records may be examined by authorized 
monitors (CML/CRA) or Quality Medicine auditors appointed by Boehringer Ingelheim, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
 
10.2 
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. 
No subject names will be supplied to Boehringer Ingelheim or other responsible parties. 
Only the subject number and subject initials will be recorded on the CRF, and if the 
subject’s name appears on any other document (e.g., laboratory report), it must be 
obliterated before a copy of the document is supplied to Boehringer Ingelheim or other 
responsible parties. Study findings stored on a computer will be stored in accordance with 
local data protection laws.  
The investigator will maintain a personal subject identification list (subject numbers with 
the corresponding subject names) to enable records to be identified. 
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. All personal 
information made available for inspection will be handled in strictest confidence and in 
accordance with local data protection laws. 

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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 unfavorable 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 reaction 
An adverse reaction is defined as a response to a medicinal product which is noxious and 
unintended. The response in this context means that a causal relationship between a 
medicinal product and an adverse event is at least a reasonable possibility. Adverse 
reactions may arise from the 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 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 judgment 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 

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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 Adverse Event of Special Interest (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 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 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 CRF from signing the informed 
consent onwards until the end of the study:  
 
All adverse drug reaction (ADRs) (serious and non-serious), 
 
All AEs with fatal outcome, 
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 should carefully assess 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 the pattern of reaction, temporal relationship, de-challenge or re-challenge, 
and confounding factors such as concomitant medication, concomitant diseases, and 
relevant history.  
Arguments that may suggest a reasonable causal relationship could be: 

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 
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. 
 
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 the 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 

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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 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 AE form from signing the 
informed consent onwards until the end of the study:  
 
Type of Report 
Timeline 
All serious ADRs 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 
7 calendar days 
 
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 AE form. 
 
Information required 
For each reportable adverse event, the investigator should provide the information requested 
on the appropriate CRF pages and the NIS 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. 
 

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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. 
 

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12. 
PLANS FOR DISSEMINATING AND COMMUNICATING 
STUDY RESULTS 
Results of this non-interventional study will be disclosed on external websites according to 
BI SOP. The rights of the investigator and of the sponsor with regard to publication of the 
results of this study are described in the investigator contract. As a general rule, no study 
results should be published prior to finalization of the study report. 
 

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13. 
REFERENCES 
13.1 
PUBLISHED REFERENCE 
                                                 
1 Graham J. et al. Cardiovascular, bleeding, and mortality risks in elderly medicare patients 
treated with dabigatran or warfarin for non-valvular atrial fibrillation. Circulation. 2014. 
doi: 10.1161/CIRCULATIONAHA.114.012061 Published online October 30, 2014. 
2 Connolly SJ. et al. The Long Term Multi-Center Extension of Dabigatran Treatment in 
Patients with Atrial Fibrillation (RELY-ABLE) study. Circulation. 2013;128:237-43. 
3 Connolly SJ. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J 
Med. 2009;361:1139-51. 
4 J. Beyer-Westendorf, F. Ebertz, V. Gelbricht, K. Foerster, L. Tittl, S. Werth, C. Koehler. 
Real life efficacy and safety of dabigatran for stroke prevention in atrial fibrillation: 
updated results of the prospective NOAC registry. European Heart Journal. 1 August 
2013. DOI: http://dx.doi.org/10.1093/eurheartj/eht310.P4871. 
5 Urooj F, Kulkarni A, Stapleton D, Kaluski E. New Oral Anticoagulants in Nonvalvular 
Atrial Fibrillation. Clin Cardiol. 2016 Dec;39(12):739-746. doi: 10.1002/clc.22582. 
Epub 2016 Oct 7. 
6 Kailas SD, Thambuluru SR. Efficacy and Safety of Direct Oral Anticoagulants Compared to 
Warfarin in Prevention of Thromboembolic Events Among Elderly Patients with Atrial 
Fibrillation. 
Muacevic 
A, 
Adler 
JR, 
eds. 
Cureus. 
2016;8(10):e836. 
doi:10.7759/cureus.836. 
7 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) 
8 Carroll K, Majeed A. Comorbidity associated with atrial fibrillation: a general practice-
based study. The British Journal of General Practice. 2001;51(472):884-891. 
9  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). 
10 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). 
11 Cockcroft D, W, Gault M, H, Prediction of Creatinine Clearance from Serum Creatinine. 
Nephron 1976;16:31-41 
12 Gault M, H, Longerich L, L, Harnett J, D, Wesolowski C, Predicting Glomerular Function 
from Adjusted Serum Creatinine. Nephron 1992;62:249-256 
13 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) 
14 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 

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anticoagulant treatment: the 'Perception of Anticoagulant Treatment Questionnaire' 
(PACT-Q). Health Qual Life Outcomes 7, 9 (2009) 

 
 
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13.2 
UNPUBLISHED REFERENCES 
None. 

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ANNEX 1. LIST OF STAND-ALONE DOCUMENTS 
Number 
Document 
Reference Number 
Date 
Title 
1 
Not applicable 
23 September 2016 
PACT-Q1 - 
Taiwan/Mandarin 
2 
Not applicable 
23 September 2016 
PACT-Q2 - 
Taiwan/Mandarin 
 

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Protocol version 1.0 
Date: 15 March 2017 
 
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ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS 
As attached. 

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ANNEX 3. ADDITIONAL INFORMATION 
None.