Post Marketing Surveillance Program of Praxbind Use in India.
Conditions: Thromboembolism
Sponsor: Boehringer Ingelheim

ABCD
001-MCS-90-118_RD-01 (7.0) / Saved on: 09 Nov 2015
TITLE PAG
Non-interventional Study Protocol
1.
TITLE PAGE
Document Number:
c17261390-04
BI Study Number:
1321-0023
BI Investigational
Product(s):
PraxbindTM
Title:
Post marketing surveillance program of PraxbindTM use in 
India.
Brief lay title
PraxbindTM India PMS program
Protocol version 
identifier:
3.0
Date of last version of 
protocol:
13 Sep 2017
PASS:
Yes
EU PAS register 
number:
EUPAS21619
Active substance:
Idarucizumab
Medicinal product:
1 vial of 50 ml contains 2.5 g Idarucizumab (50 mg/ml); 
Total recommended dose of 5g.
Product reference:
Not Applicable
Procedure number:
Not Applicable
Marketing 
authorisation 
holder(s):
Joint PASS:
No
Research question and 
objectives:
The main objective of the PraxbindTM administration 
surveillance program is to evaluate the prescription patterns 
of use of PraxbindTM in a clinical practice setting, with 
special focus on ADRs and fatal AEs.

Boehringer Ingelheim
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001-MCS-90-118_RD-01 (7.0) / Saved on: 09 Nov 2015
Country(-ies) of 
study:
India
Author:
Marketing 
authorisation 
holder(s):
In case of PASS, add:
MAH contact person:
In case of PASS, add:
<EU-QPPV:>
In case of PASS, add:
<Signature of EU-
QPPV:>
Signature of EU-QPPV is added at the end of the Protocol 
in the signature page.
Date:
23 Mar 2018
Page 2 of 41
Proprietary confidential information
© 2018 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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2.
TABLE OF CONTENTS
1.
TITLE PAGE......................................................................................................... 1
2.
TABLE OF CONTENTS....................................................................................... 3
3.
LIST OF ABBREVIATIONS................................................................................ 5
4.
RESPONSIBLE PARTIES.................................................................................... 6
5.
ABSTRACT........................................................................................................... 7
6.
AMENDMENTS AND UPDATES..................................................................... 13
7.
MILESTONES..................................................................................................... 16
8.
RATIONALE AND BACKGROUND................................................................ 17
9.
RESEARCH QUESTION AND OBJECTIVES ................................................. 18
10.
RESEARCH METHODS .................................................................................... 19
10.1
STUDY DESIGN............................................................................................ 19
10.1.1
Study sites ............................................................................................... 19
10.1.2
Study population ..................................................................................... 19
10.1.3
Study discontinuation.............................................................................. 20
10.2
VARIABLES .................................................................................................. 20
10.2.1
Exposures ................................................................................................ 22
10.2.2
Outcomes................................................................................................. 22
10.2.2.1
Primary outcomes............................................................................. 22
10.2.2.2
Secondary outcomes......................................................................... 22
10.2.3
Covariates................................................................................................ 22
10.3
DATA SOURCES........................................................................................... 22
10.4
STUDY SIZE.................................................................................................. 22
10.5
DATA MANAGEMENT................................................................................ 22
10.6
DATA ANALYSIS......................................................................................... 23
10.6.1
Main analysis........................................................................................... 23
10.7
QUALITY CONTROL................................................................................... 23
10.8
LIMITATIONS OF THE RESEARCH METHODS...................................... 23
10.9
OTHER ASPECTS ......................................................................................... 23
10.9.1
Data quality assurance............................................................................. 23

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10.9.2
Study records........................................................................................... 23
10.9.2.1
Source documents ............................................................................ 23
10.9.2.2
Direct access to source data and documents .................................... 24
11.
PROTECTION OF HUMAN SUBJECTS .......................................................... 25
11.1
Study approval, patient information, and informed consent........................... 25
11.2
Statement of confidentiality............................................................................ 26
12.
MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS....................................................................................................... 27
12.1
Definitions of adverse events.......................................................................... 27
12.2
Adverse event and serious adverse event collection and reporting................. 28
12.3
Reporting to health Authorities....................................................................... 31
13.
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
............................................................................................................................. 31
14.
REFERENCES .................................................................................................... 32
14.1
PUBLISHED REFERENCES......................................................................... 32
14.2
UNPUBLISHED REFERENCES................................................................... 32
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS.............................................. 33
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS .............................. 34
ANNEX 3. ADDITIONAL INFORMATION.............................................................. 41

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3.
LIST OF ABBREVIATIONS
ADR
Adverse Drug Reaction
AE
Adverse Event
AESI
Adverse Event of Special interest
CA
Competent Authority
CCDS
Company Core Data Sheet
CI
Confidence Interval
CML
Local Clinical Monitor 
CRA
Clinical Research Associate
CRF
Case Report Form
CTCAE
Common Terminology Criteria for Adverse Events
CTP
Clinical Trial Protocol
EMA
ENCePP 
EU
European Medicines Agency
European Network of Centers for Pharmacoepidemiology and 
Pharmacovigilance 
European Union
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GEP
Good Epidemiological Practice
GPP
Good Pharmacoepidemiology Practice
GVP
Good Pharmacovigilance Practices
IB
ICF
Investigator’s Brochure
Informed Consent Form
IEC
Independent Ethics Committee
IRB
Institutional Review Board
MAH
Marketing Authorisation Holder
Activities
NIS
Non-Interventional Study
SAE
Serious Adverse Event

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4.
RESPONSIBLE PARTIES
Contact details and the list of all investigators will be kept in a stand-alone document.

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5.
ABSTRACT
Name of company:
Boehringer Ingelheim India Pvt 
Ltd
Name of finished medicinal 
product:
PraxbindTM
Name of active ingredient:
Idarucizumab
Protocol date:
Study
number:
Version/Revision:
Version/Revision 
date:
12 Jul 2017
1321-0023
3.0
23 Mar 2018
Title of study:
Post marketing surveillance program of PraxbindTM use in India.
Rationale and 
background:
PraxbindTM (Idarucizumab) is a humanized monoclonal antibody 
fragment (Fab) that binds to dabigatran with very high affinity. 
PraxbindTM potently and specifically binds to dabigatran and its 
metabolites and neutralises its anticoagulant effect. PraxbindTM is 
a specific reversal agent for dabigatran and is indicated in 
patients treated with dabigatran etexilate when rapid reversal of 
the anticoagulant effects of dabigatran is required:

for emergency surgery/urgent procedures
OR

in life-threatening or uncontrolled bleeding.
The aim of this PraxbindTM drug administration surveillance 
program is to collect data on PraxbindTM prescription patterns in a 
clinical practice setting in India.
Research 
question and 
objectives:
The main objective of the PraxbindTM drug administration 
surveillance program is to evaluate the prescription patterns of use 
of PraxbindTM in a clinical practice setting, with special focus on 
ADRs and fatal AEs.
Study design:
This drug administration surveillance program is designed as an 
Indian multi-Center program enrolling patients administered with 
PraxbindTM after launch. There are no protocol mandated follow-
up visits or procedures associated with the program. No 
interference with usual medical care is involved, and thus it will 
not affect the treatment of patients.
The program will apply to all participating Centers where the 
PraxbindTM is   prescribed   depending   on   market   country 
regulations and requirements.

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Name of company:
Boehringer Ingelheim India Pvt 
Ltd
Name of finished medicinal 
product:
PraxbindTM
Name of active ingredient:
Idarucizumab
Protocol date:
Study 
number:
Version/Revision:
Version/Revision 
date:
12 Jul 2017
1321-0023
3.0
23 Mar 2018
PraxbindTM
is prescribed depending on market country 
regulations and requirements.
Population:
Hospital (sites)
with access to PraxbindTM
will receive 
information material about the drug administration surveillance 
program. The target population will be all patients, who receive 
PraxbindTM as prescribed by the treating physician.
This program will be initiated after the commercial availability of 
PraxbindTM in India. It will include up to 25 patients who require 
PraxbindTMas prescribed according to the approved Indian label or 
the patients included in 2 years at selected Centers approved by 
the regulatory authority, whichever is earlier. 
The patients who participate in 1160.189 and 1160.248 study and 
have a requirement for PraxbindTM will also be part of this 
protocol.
Inclusion criteria:
1. Patients treated with Pradaxa (dabigatran etexilate) 
capsules with requirement of rapid reversal of the 
anticoagulant effects of dabigatran:

For emergency surgery/urgent procedures
(or)

In life-threatening or uncontrolled bleeding
2.
Written 
informed 
consent 
in 
accordance 
with 
International Conference on Harmonization Good 
Clinical Practice (GCP) guidelines and local legislation 
and/or regulations. 
Exclusion criteria:

Participation in an PraxbindTM clinical trial

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Name of company:
Boehringer Ingelheim India Pvt 
Ltd
Name of finished medicinal 
product:
PraxbindTM
Name of active ingredient:
Idarucizumab
Protocol date:
Study 
number:
Version/Revision:
Version/Revision 
date:
12 Jul 2017
1321-0023
3.0
23 Mar 2018
Variables:
Information on basic patient characteristics and use of PraxbindTM
will be entered into the PraxbindTM drug administration record. 
The following anonymized data will be collected from the 
PraxbindTM administration records upon availability:
1. Site characteristics

Multi-specialty hospitals with emergency management 
facilities and having access to PraxbindTM.

Practice 
type 
(academic, 
non-academic, 
private, 
Government);

Availability of prescription/medical records at the site.
2. Patient data

Year of birth

Gender: Male or Female 

Vital Signs

Physical Examination

Laboratory data

Pregnancy status in case of female patient
3. Medical History 

Name, dose and last intake of previous anticoagulant 
medications (Dabigatran);

Pertaining to haemorrhagic risk factors or impact on safety 
outcomes (e.g. renal impairment, congenital or acquired 
coagulation disorders, thrombocytopenia or functional

Boehringer Ingelheim
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001-MCS-90-118_RD-01 (7.0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim India Pvt 
Ltd
Name of finished medicinal 
product:
PraxbindTM
Name of active ingredient:
Idarucizumab
Protocol date:
Study 
number:
Version/Revision:
Version/Revision 
date:
12 Jul 2017
1321-0023
3.0
23 Mar 2018
Platelet defects, recent biopsy, recent surgery, major 
trauma, 
bacterial 
endocarditis, 
esophagitis, 
gastritis, 
gastroesophageal 
reflux, 
hepatic 
disorders, 
vascular 
disorders, neoplasms/cancer, inherited vascular disorder 
(aneurysms, arteriovenous malformation, microangiopathy) 
and the HAS-BLED score).

Concomitant treatment pertaining to haemorrhagic risk 
factors or impact on safety outcomes (e.g. acetylsalicylic 
acid, non-steroidal anti-inflammatory drugs, clopidogrel, 
selective serotonin reuptake inhibitors
or serotonin–
norepinephrine reuptake inhibitors, sStrong P-Gp inhibitors 
(e.g. 
ketoconazole, 
clarithromycin, 
ticagrelor), 
chemotherapy, radiation therapy.
3. PraxbindTM utilization

Department (emergency, operating room, ICU, other patient 
setting);

Type of surgery / procedure if applicable;

Information on bleeding event (pre and post PraxbindTM
administration) including location (Gastrointestinal tract; 
Intracranial; 
Skin, 
Urogenital 
tract, 
Intramuscular, 
Retroperitoneal, 
Undefined 
location, 
Other 
defined
location) if applicable, and if bleeding was life threatening 
(yes/no);

Indication: 
life-threatening 
or 
uncontrolled 
bleeding 
requiring urgent medical intervention, emergency surgery 
or other urgent medical procedure necessitating rapid 
reversal of the anticoagulant effect of dabigatran prior to 
surgery/procedure, scheduled or planned surgery/procedure, 

Boehringer Ingelheim
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001-MCS-90-118_RD-01 (7.0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim India Pvt 
Ltd
Name of finished medicinal 
product:
PraxbindTM
Name of active ingredient:
Idarucizumab
Protocol date:
Study 
number:
Version/Revision:
Version/Revision 
date:
12 Jul 2017
1321-0023
3.0
23 Mar 2018

Dosage and administration (total dose administered and 
time interval between the administration of the two vials;
vials to be taken one after the other, immediate 
administration of the second vial is mandatory).

Premature 
PraxbindTM
administration 
discontinuation 
(yes/no).

In case if the patient requires an additional 5 g dose for the 
following conditions as per the label:

recurrence of clinically relevant bleeding together with 
prolonged clotting times, or

if potential re-bleeding would be life-threatening and 
prolonged clotting times are observed, or

patients require a second emergency surgery/urgent 
procedure and have prolonged clotting times.

Information on restart of anticoagulation therapy (which 
anticoagulation treatment including dose and when was it 
restarted).

All adverse drug reactions (ADRs, serious and non-serious) 
associated with PraxbindTM,

All AEs with fatal outcome in patients exposed to 
PraxbindTM

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Name of company:
Boehringer Ingelheim India Pvt 
Ltd
Name of finished medicinal 
product:
PraxbindTM
Name of active ingredient:
Idarucizumab
Protocol date:
Study number:
Version/Revision:
Version/Revision 
date:
12 Jul 2017
1321-0023
3.0
23 Mar 2018
Outcomes
Primary Outcome:-
Any suspected ADRs and fatal AEs; with special focus on 
hypersensitivity and thrombotic event, occurred within 7 days after 
PraxbindTM administration.
Secondary Outcome:-
Percentage of patients who either received PraxbindTM for emergency 
surgery/urgent procedures or in life-threatening or uncontrolled 
bleeding at the end of 2 years.
Data sources:
Data collected will be entered by the site using electronic CRF forms.
It is the doctor’s responsibility to ensure the accuracy of the data 
provided to the program by any site staff that is trained for the 
program data collection.
Study size:
This program will be initiated after the commercial availability of 
PraxbindTM in India. It will include up to 25 consecutive patients who 
may require PraxbindTM prescribed according to the approved Indian 
label or the patients included in 2 years at selected Centers approved 
by the regulatory authority, whichever is earlier. 
Data analysis:
A detailed analysis plan will be prepared prior to First Patient In.
All variables will be presented using descriptive statistics (absolute 
and relative frequencies, means, standard deviations, medians, 
quartiles, minimum and maximum values, 95% CIs) as appropriate 
for the nature of the variables (i.e. categorical or continuous).
Milestones:
Start of data collection: Currently planned for Q2 2018 (Depending 
on start time of commercial availability and necessary regulatory 
approvals). End of data collection: Currently planned for Q2 2020
(As per the DCGI approval of marketing authorization).
Final report: Currently planned for Q3 2020 (Depending on 
completion of data collection).

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6.
AMENDMENTS AND UPDATES
Following administrative were performed throughout the document:-
Sr No
Section
Page
no.
Protocol V 3.0 dated 23 Mar 2018
1
Title Page
  1
EU PAS Register Number added (EUPAS21619)
2
Abstract: 
Milestones
13
Start of data collection: Currently planned for Q4
Q2 2018 (Depending on start time of commercial 
availability and necessary regulatory approvals).
End of data collection: Currently planned for Q4
Q2 202019 (Depending on start of market 
authorisation and PraxbindTM usage. As per the 
DCGI approval of marketing authorization).
Final report: Currently planned for Q31 2020
(Depending on start of market authorisation and
PraxbindTM usage completion of data collection).
3
Section 7:-
Milestones
16
Final Protocol 13 Sep 2017 (Revision) 12 Jul 2017
Start of data collection:
15 Dec 2017 Q 2 2018
End of data collection:
15 Dec 2019  Q 2 
2020
Final report of study results: 30 Feb 2020 Q 3 
2020
Added:-
Revision 1.0 (Version 2.0)13 Sep 2017
Revision 2.0 (Version 3.0) 23 Mar 2018
4
Abstract:-
Population; 
Section 10.1.2:-
Study Population
8; 19
The patients who participate in 1160.189 and
1160.248 study and have a requirement for
PraxbindTM will also be part of this protocol.
5
ENCePP
Checklist for 
Study Protocols: 
Section 1. 
Milestones
37
Comment deleted:-
1.1.5 EU PAS Registration will be completed after 
the Protocol is finalized.
Updated:- EU PAS registration completed and 
number added in the title page.
Typographical errors corrected throughout the document.

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The following additions have been made to the Protocol based on the recommendations of the 
Drug Controller General India, DCG(I):-
Sr. No
Section
Page 
no.
Protocol V 2.0 dated 13 Sep 2017
1
Title Page; Abstract 
and
Section 9:-Research 
question and objectives
1, 7 and 
17
The main objective of the Praxbind® 
administration surveillance program is to 
evaluate the prescription patterns of use of 
Praxbind® in a clinical practice setting, with 
special focus on ADRs and fatal AEs.
2
Abstract:-Outcomes;
Section 10.2.2.1:-
Primary Outcomes
12 and 
21
Any suspected ADRs and fatal AEs; with 
special focus on hypersensitivity and 
thrombotic event, occurred within 7 days 
after Praxbind® administration.
3
Abstract:-Outcomes;
Section 10.2.2.2:-
Secondary Outcomes
12 and 
21
Percentage of patients who either received 
Praxbind® for emergency surgery/urgent 
procedures or in life-threatening or 
uncontrolled bleeding at the end of 2 
years.
Following administrative and typographical corrections were performed throughout the 
document:-
Sr No
Section
Page 
no.
Protocol V 2.0 dated 13 Sep 2017
1
Medicinal Product
1
1 vial of 50 ml contains 2.5 g Idarucizumab 
(50 mg/ml); Total recommended dose of 
5g.
2
Section 7:- Milestones
18
Updated as per the new planned dates
3
Abstract:- Population;
Section:-10.1.2 Study 
population
8, 18
The target population will be all patients, 
who receive Praxbind® as prescribed by 
the treating physician.
It will include up to 25 consecutive patients 
who require Praxbind®
as prescribed 
according to the approved Indian label or 
the patients included in 2 years at selected 
Centers 
approved 
by 
the 
regulatory 
authority, whichever is earlier.
4
Abstract:-Variables;
Section 10.2:- Variables
9, 19
Availability    of prescription/medical 
records at the pharmacy site.
5
Abstract:-Variables;
Section 10.2:- Variables
9, 19

Pregnancy status in case of female 
patient.

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6
Abstract:-Variables;
Section 10.2:- Variables
11, 20

All adverse drug reactions 
(ADRs, serious and non-
serious) associated with 
PraxbindTM,

All AEs with fatal outcome in 
patients exposed to 
PraxbindTM
7
Section 10.1 Study Design
18
This is a post marketing surveillance 
study wherein patients will be eligible 
for the study if they are prescribed 
Praxbind® as per the approved label.
The drug administration surveillance 
program is designed as a multi-center 
program enrolling patients administered 
with Praxbind®.
8
10.1.2 Study population
18
The target population will be all 
patients, who receive Praxbind® 
prescribed as per the approved label.
9
10.1.3 Study 
discontinuation
19
The investigator / the study site will be 
reimbursed for reasonable expenses 
incurred in case of study termination 
(except in case of the third reason).
10
10.9.2. Study Records
22
Case Report Forms (CRFs) for 
individual patients will be provided by 
the sponsor electronically.
11
10.7 Quality Control
22
It is the responsibility of the pharmacist
Investigator to ensure that the data are 
as accurate and complete as possible. 
The Pharmacist Investigator and 
delegate will be trained on data entry.
12
12.1. Definition of adverse 
events
26
Any suspected transmission via a 
medicinal product of an infectious agent 
is also considered a serious adverse 
reaction.

Name of study drug changed from Idarucizumab to PraxbindTM across the entire 
Protocol.

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7.
MILESTONES
Milestone
Planned Date
Final Protocol
12 Jul 2017
Revision 1.0 (Version 2.0)
13 Sep 2017
Revision 2.0 (Version 3.0)
23 Mar 2018
Start of data collection
Q2 2018
End of data collection
Q2 2020
Final report of study results:
Q3 2020

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8.
RATIONALE AND BACKGROUND
A clinical development program is ongoing to support marketing authorisation submissions 
for PraxbindTM indicated in patients treated with dabigatran who require emergency 
surgery/urgent procedures or who have a life-threatening or uncontrolled bleeding when rapid 
reversal of the anticoagulant effects of dabigatran is required.
The aim of this drug administration surveillance program is to capture a large proportion of 
the patients treated with PraxbindTM in order to collect data on PraxbindTM prescription 
patterns in a clinical practice setting in India.
PraxbindTM (Idarucizumab) is a humanized monoclonal antibody fragment (Fab) that binds to 
Dabigatran with very high affinity. PraxbindTM potently and specifically binds to dabigatran 
and its metabolites and neutralises its anticoagulant effect. PraxbindTM is a specific reversal 
agent for dabigatran and is indicated in patients treated with dabigatran etexilate when rapid 
reversal of the anticoagulant effects of dabigatran is required:

for emergency surgery/urgent procedures
(or)

in life-threatening or uncontrolled bleeding
Dabigatran etexilate (Pradaxa) is an oral pro-drug of dabigatran, a direct-acting thrombin 
inhibitor that has been shown to be effective in the prevention or reduction of thrombotic 
events in:

patients with non-valvular atrial fibrillation

patients with deep vein thrombosis or pulmonary embolism who have been treated 
with a parenteral anticoagulant for 5-10 days

patients who have previously received anticoagulant therapy for treatment of venous 
thromboembolism

in orthopedic surgery patients at risk for post-operative DVT
Anticoagulation therapy is a mainstay of treatment and prevention of pathologic thrombosis 
in these different clinical settings. However, as with all anticoagulants, bleeding is a potential 
side effect. The risk of bleeding in dabigatran-treated patients during emergency surgery or 
other urgent invasive procedures is also a consideration.

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9.
RESEARCH QUESTION AND OBJECTIVES
The main objective of the PraxbindTM drug administration surveillance program is to evaluate 
the prescription patterns of use of PraxbindTM in a clinical practice setting, with special focus 
on ADRs and fatal AEs.

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10.
RESEARCH METHODS
This program will be initiated after the commercial availability of PraxbindTM in India. It will 
include patients administered with PraxbindTM
into the surveillance program after 
commercial availability in 2 years at selected centers approved by the regulatory authority.
10.1
STUDY DESIGN
This is a post marketing surveillance study wherein patients will be eligible for the study if 
they are prescribed PraxbindTM as per the approved label. The drug administration 
surveillance program is designed as a multi-center program enrolling patients administered 
with PraxbindTM. Data will be collected for patients who have been treated with PraxbindTM
within 2 years. There are no protocol mandated follow-up visits or procedures associated with 
the program. No interference with usual medical care is involved, and thus it will not affect 
the treatment of patients.
10.1.1
Study sites
The program will be available to select hospitals approved by Indian regulatory authority 
with access to PraxbindTM.
Hospital (sites) having access to PraxbindTM will receive information material about 
PraxbindTM administration surveillance program.
10.1.2
Study population
The target population will be all patients, who receive PraxbindTM prescribed as per the 
approved label.
The patients who participate in 1160.189 and 1160.248 study and have a requirement for 
PraxbindTM will also be part of this protocol.
Inclusion criteria:
1. Patients treated with Pradaxa (dabigatran etexilate) capsules with requirement of 
rapid reversal of the anticoagulant effects of dabigatran:

For emergency surgery/urgent procedures
(or)

In life-threatening or uncontrolled bleeding
2. Written informed consent in accordance with International Conference on 
Harmonization Good Clinical Practice (GCP) guidelines and local legislation 
and/or regulations.
Exclusion criteria:

Participation in a PraxbindTM clinical trial.

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10.1.3
Study discontinuation
A log of all patients included into the drug surveillance study will be maintained at the
Investigational sites.
Boehringer Ingelheim reserves the right to discontinue the study overall or at a particular 
study site at any time for the following reasons:
1. Emergence of any efficacy/safety information of PraxbindTM that could significantly 
affect continuation of the study.
2.
Violation of 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.
10.2
VARIABLES
1.
Site characteristics:
To evaluate the diversity of sites the following information will be collected for each 
participating site:

Multi-specialty hospitals with emergency management facilities and having access to 
PraxbindTM

Practice type (academic, non-academic, private, Government)

Availability of prescription/medical records at the site.
Patient characteristics and PraxbindTM use:-
The following anonymized data will be collected from the PraxbindTM administration records 
upon availability:
2.
Patient Data:

Year of Birth 

Gender: Male or Female 

Vital Signs

Physical Examination

Laboratory data (Data would be collected of lab results performed as a routine 
practice. No additional lab tests should be performed specifically for this study 
purpose)

Pregnancy status in case of female patient
3.
Medical History: 

Name, dose and last intake of previous anticoagulant medications (Dabigatran);

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
Pertaining to haemorrhagic risk factors or impact on safety outcomes (e.g. renal 
impairment, congenital or acquired coagulation disorders, thrombocytopenia or 
functional platelet defects, recent biopsy, recent surgery, major trauma, bacterial 
endocarditis, esophagitis, gastritis, gastroesophageal reflux, hepatic disorders, 
vascular disorders, neoplasms/cancer, inherited vascular disorder (aneurysms, 
arteriovenous malformation, microangiopathy) and the HAS-BLED score).

Concomitant treatment pertaining to haemorrhagic risk factors or impact on safety 
outcomes 
(e.g. 
acetylsalicylic 
acid, 
non-steroidal 
anti-inflammatory 
drugs, 
clopidogrel, selective serotonin reuptake inhibitors or serotonin–norepinephrine 
reuptake inhibitors, Strong P-Gp inhibitors (e.g. ketoconazol, clarithromycin, 
ticagrelor), chemotherapy, radiation therapy.
4.
PraxbindTM utilization:

Department (emergency, operating room, ICU, other patient setting);

Type of surgery /procedure if applicable;

Information on bleeding event including location (Gastrointestinal tract; Intracranial; 
Skin, Urogenital tract, Intramuscular, Retroperitoneal, Undefined location, Other 
(defined location) if applicable, and if bleeding was life-threatening (yes/no);

Indication: life-threatening or uncontrolled bleeding requiring urgent medical 
intervention, emergency surgery or other urgent medical procedure necessitating rapid 
reversal of the anticoagulant effect of dabigatran prior to surgery/procedure, 
scheduled or planned surgery/procedure, other;

Dosage and administration (total dose administered and time interval between the 
administration of the two vials; vials to be taken one after the  other, immediate 
administration of the second vial is mandatory);

Premature PraxbindTM administration discontinuation (yes/no).

In case if the patient requires an additional 5 g dose for the following conditions as 
per the label:
i.
recurrence of clinically relevant bleeding together with prolonged clotting 
times, or
ii.
if potential re-bleeding would be life-threatening and prolonged clotting 
times are observed, or
iii.
patients require a second emergency surgery/urgent procedure and have 
prolonged clotting times.

Information on restart of anticoagulation therapy (which anticoagulation treatment
including dose and when was it restarted).

All adverse drug reactions (ADRs, serious and non-serious) associated with 
PraxbindTM.

All AEs with fatal outcome in patients exposed to PraxbindTM. 

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10.2.1
Exposures
Not Applicable
10.2.2
Outcomes
10.2.2.1
Primary outcomes
Any suspected ADRs and fatal AEs; with special focus on hypersensitivity and thrombotic 
event, occurred within 7 days after PraxbindTM administration.
10.2.2.2
Secondary outcomes
Percentage of patients who either received PraxbindTM for emergency surgery/urgent 
procedures or in life-threatening or uncontrolled bleeding at the end of 2 years.
10.2.3
Covariates
Not Applicable
10.3
DATA SOURCES
Data collected from patient's medical notes and hospital records will be entered by the site 
directly in the paper based forms. All sites will be fully trained for using the CRF forms. It is 
the site’s responsibility to ensure the accuracy of the data provided to the program by any site 
staff that is trained for the program data collection. The program does not entail any change 
in prescribing pattern or management policies which are left to the discretion of the treating 
physician. No special evaluation procedure is required. The data to be entered in the e-CRFs 
is part of the information that should be generally available during routine medical practice.
Data will be transferred to the Sponsor after closure of the program.
10.4
STUDY SIZE
This program will be initiated after the commercial availability of PraxbindTM in India. It will 
include up to 25 patients who require PraxbindTM according to the approved Indian label or 
the patients included in 2 years at selected Centers approved by the regulatory authority, 
whichever is earlier.
10.5
DATA MANAGEMENT
A data management plan will be created before data collection begins and will describe all 
functions, processes, and specifications for data collection and validation. 

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10.6
DATA ANALYSIS
10.6.1
Main analysis
A detailed analysis plan will be prepared prior to First Patient In.
All variables will be presented using descriptive statistics (absolute and relative frequencies, 
means, standard deviations, medians, quartiles, minimum and maximum values, 95% CIs) as 
appropriate for the nature of the variables (i.e. categorical or continuous).
10.7
QUALITY CONTROL
It is the responsibility of the Investigator to ensure that the data are as accurate and complete 
as possible. The Investigator and delegate will be trained on data entry. 
Data will be recorded by local site staff directly into the e-CRF’s. Data quality will be 
ensured by implementation of validations and edit checks.
No patient identifying information will be available to non-study staff except Ethics 
Committee and regulatory agencies during inspections.
10.8
LIMITATIONS OF THE RESEARCH METHODS
This study will include only up to 25 consecutive patients who require PraxbindTM. The data 
analysis will be done using descriptive statistics with no formal statistical hypothesis.
10.9
OTHER ASPECTS
10.9.1
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.
10.9.2
Study records
Case Report Forms (CRFs) for individual patients will be provided by the sponsor 
electronically. 
10.9.2.1
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.

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Data reported on the e-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 e-CRFs, the following data need to be derived from source documents:

Patient identification (gender, date of birth)

Patient participation in the study (product, study number, patient number, date patient 
was informed)

Dates of Patient’s visit, (including PraxbindTM administration & Hospital Admission 
details)

Medical history (including indication and concomitant diseases, if applicable)

Medication history

Adverse events (onset date (mandatory), and end date (if available))

Serious adverse events (SAEs) (onset date (mandatory), and end date (if available))

Concomitant therapy (start date, changes)

Laboratory results 

Conclusion of Patient’s Participation in the study
10.9.2.2
Direct access to source data and documents
The Investigator / institution will permit active surveillance study related monitoring, audits, 
IRB/IEC review and regulatory inspection, providing direct access to all related source 
data/documents.
e-CRF and all source documents, including progress notes and copies of laboratory and 
medical test results must be available at all times for review.
The Clinical Research Associate (CRA)/ on site monitor and auditor may review all e-CRF
and written informed consents.
10.9.2.2.1 Storage of records
Site(s)
The trial site(s) must retain the source and essential documents (including ISF) according to
the national or local requirements (whatever is longer) valid at the time of the end of the trial.
Sponsor
The sponsor must retain the essential documents according to the sponsor’s SOPs. 

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11.
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.
11.1
STUDY APPROVAL, PATIENT INFORMATION, AND INFORMED 
CONSENT
In addition to review and approval by Drug controller general of India (DCGI), the approval 
of Institutional Review Board (IRB) or Ethics Committee will be sought as per the 
institutional procedures before the start of this active surveillance.
Prior to patient participation in this active surveillance study, written informed consent must 
be obtained from each patient (or the patient’s legally accepted representative) according to 
the regulatory and legal requirements of India. 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 Investigator must give a full explanation to the participants of this active surveillance 
regarding the collection of the safety data at specific time points. The Investigator obtains 
written consent of the patient’s own free will with the informed consent form after 
confirming that the patient understands the contents. The Investigator must sign and date the 
informed consent form.
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.

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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.
11.2
STATEMENT OF CONFIDENTIALITY
Upon PraxbindTM administration, anonymized patient data will be collected. Every site 
participating in the surveillance program should collect the patient data anonymously. No 
data will be key-coded to the patient’s identity. 
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.

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12.
MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS
12.1
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 reaction
An adverse reaction 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 reactions may arise 
from use of the product within or outside the terms of the marketing authorization or from 
occupational exposure. Conditions of use outside the marketing authorization include off-
label use, overdose, misuse, abuse and medication errors.
Serious adverse event
A serious adverse event is defined as any AE which
-
results in death, 
-
is life-threatening, 
-
requires in-patient hospitalization, or
-
prolongation of existing hospitalisation, 
-
results in persistent or significant disability or incapacity, or 
-
is a congenital anomaly/birth defect 
Life-threatening in this context refers to a reaction in which the patient was at risk of death at 
the time of the reaction; it does not refer to a reaction that hypothetically might have caused 
death if more severe.
Medical and scientific judgement should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life threatening or result in death or 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. 
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 

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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.
12.2
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 (e) CRF from signing the informed 
consent onwards until the end of the study: 
-
all adverse drug reactions (ADRs, serious and non-serious) associated with PraxbindTM,
-
all AEs with fatal outcome in patients exposed to PraxbindTM.  
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 
•
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).

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•
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
The intensity of adverse events should be classified and recorded according to the Common 
Terminology Criteria for Adverse Events (CTCAE) criteria in the (e) CRF.
Pregnancy:
In rare cases, pregnancy might occur in a study. Once a subject has been enrolled into the 
study, after having taken PraxbindTM, 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 NIS AE form is to be completed and forwarded as well within the respective 
timelines. 

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Expedited Reporting of AEs and Drug Exposure During Pregnancy
BI
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 
PraxbindTM
immediately within 24 hours
All AEs with fatal outcome in patients 
exposed to PraxbindTM
immediately within 24 hours
All non-serious ADRs associated with 
PraxbindTM
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 (e)CRF pages and the NIS AE form.
Reporting of the indication for which PraxbindTM is used 
For patients not participating in 1160.189 or 1160.248, the investigator must report the 
indication for which PraxbindTM is used (emergency surgery/urgent procedures or life-
threatening or uncontrolled bleeding) as spontaneous Pradaxa (dabigatran etexilate) case to 
the 
above 
mentioned 
BI 
contact 
for 
AE/Pregnancy 
Reporting.
For emergency surgery/urgent procedures the underlying condition requiring the 
surgery/procedure 
must 
be 
indicated 
in 
the 
report.
This reporting obligation is independent of causality assessment, but a causality assessment 
must always be provided.

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For patients participating in 1160.189 or 1160.248, the reporting of the indication for which 
PraxbindTM is used must occur within those trials following the requirements for 1160.189 or 
1160.248 respectively.
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 
PraxbindTM 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.
(If the event associated to the indication for PraxbindTM is considered related to Pradaxa 
(dabigatran etexilate), see section “Reporting of the indication for which PraxbindTM is 
used”).
12.3
REPORTING TO HEALTH AUTHORITIES
Adverse event reporting to regulatory agencies will be done by the MAH according to local
and international regulatory requirements.
13.
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY 
RESULTS
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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14.
REFERENCES
14.1
PUBLISHED REFERENCES
None
14.2
UNPUBLISHED REFERENCES
None 

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ANNEX 1. LIST OF STAND-ALONE DOCUMENTS
None

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ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS
Doc.Ref. EMA/540136/2009 
ENCePP Checklist for Study Protocols (Revision 3)
Adopted by the ENCePP Steering Group on 01/07/2016
The European Network of Centers for Pharmacoepidemiology and Pharmacovigilance (ENCePP)
welcomes innovative designs and new methods of research. This Checklist has been developed by 
ENCePP to stimulate consideration of important principles when designing and writing a 
pharmacoepidemiological or pharmacovigilance study protocol. The Checklist is intended to 
promote the quality of such studies, not their uniformity. The user is also referred to the ENCePP 
Guide on Methodological Standards in Pharmacoepidemiology, which reviews and gives direct 
electronic access to guidance for research in pharmacoepidemiology and pharmacovigilance.
For each question of the Checklist, the investigator should indicate whether or not it has been 
addressed in the study protocol. If the answer is “Yes”, the section number of the protocol where 
this issue has been discussed should be specified. It is possible that some questions do not apply 
to a particular study (for example, in the case of an innovative study design). In this case, the 
answer ‘N/A’ (Not Applicable) can be checked and the “Comments” field included for each section 
should be used to explain why. The “Comments” field can also be used to elaborate on a “No” 
answer. 
This Checklist should be included as an Annex by marketing authorisation holders when 
submitting the protocol of a non-interventional post-authorisation safety study (PASS) to a 
regulatory authority (see the Guidance on the format and content of the protocol of non-
interventional post-authorisation safety studies). The Checklist is a supporting document and does 
not replace the format of the protocol for PASS as recommended in the Guidance and Module VIII 
of the Good pharmacovigilance practices (GVP).
European Network of Centers for 
Pharmacoepidemiology and 
Pharmacovigilance

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Study title:
Post marketing surveillance program of PraxbindTM use in India.
Study reference number:
1321-0023
Section 1: Milestones
Yes
No
N/A
Section
Number
1.1 Does the protocol specify timelines for 
1.1.1 Start of data collection1
1.1.2 End of data collection2
1.1.3 Study progress report(s) 
1.1.4 Interim progress report(s)
1.1.5 Registration in the EU PAS register
1.1.6 Final report of study results.
7
7
Pg. no. 1
7
Comments:
1.1.5
EU PAS registration completed and number added in the title page.
Section 2: Research question
Yes
No
N/A
Section
Number
2.1 Does the formulation of the research question and 
objectives clearly explain: 
2.1.1 Why the study is conducted? (e.g. to address an 
important public health concern, a risk identified in the risk 
management plan, an emerging safety issue)
2.1.2 The objective(s) of the study?
8
9
2.1.3 The target population? (i.e. population or 
subgroup to whom the study results are intended to be 
generalised)
2.1.4 Which hypothesis(-es) is (are) to be tested?
2.1.5 If applicable, that there is no a priori
hypothesis?
10.1.2
Comments:
2.1.4.- No formal hypothesis is being tested in the PMS study
2.1.5.- No formal hypothesis is being tested in the PMS study
Section 3: Study design
Yes
No
N/A
Section 
Number
3.1 Is the study design described? (e.g. cohort, case-
control, cross-sectional, new or alternative design) 
10.1
3.2 Does the protocol specify whether the study is 
based on primary, secondary or combined data 
collection?
10.2.2
                                                
1 Date from which information on the first study is first recorded in the study dataset or, in the case of 
secondary use of data, the date from which data extraction starts.
2 Date from which the analytical dataset is completely available.

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Section 3: Study design
Yes
No
N/A
Section 
Number
3.3 Does the protocol specify measures of occurrence? 
(e.g. incidence rate, absolute risk)
3.4 Does the protocol specify measure(s) of 
association? (e.g. relative risk, odds ratio, excess risk, 
incidence rate ratio, hazard ratio, number needed to harm 
(NNH) per year)
10.6.1
3.5 Does the protocol describe the approach for the 
collection and reporting of adverse events/adverse 
reactions? (e.g. adverse events that will not be collected in 
case of primary data collection)
12
Comments:
3.3.- This is not applicable in case of a NIS study on PraxbindTM with no defined 
incidence rate for this study.
Section 4: Source and study populations
Yes
No
N/A
Section 
Number
4.1 Is the source population described?
10.1.2
4.2 Is the planned study population defined in terms 
of:
4.2.1 Study time period?
4.2.2 Age and sex?
4.2.3 Country of origin?
4.2.4 Disease/indication?
4.2.5 Duration of follow-up?
10.2
10.2
4.3 Does the protocol define how the study population 
will be sampled from the source population? (e.g. 
event or inclusion/exclusion criteria)  
10.1.2
Comments:
Section 5: Exposure definition and measurement
Yes
No
N/A
Section
Number
5.1 Does the protocol describe how the study 
exposure is defined and measured? (e.g. operational 
details for defining and categorising exposure, measurement of 
dose and duration of drug exposure)
10.2
5.2 Does the protocol address the validity of the 
exposure measurement? (e.g. precision, accuracy, use 
of validation sub-study)
5.3 Is exposure classified according to time windows?
(e.g. current user, former user, non-use)
5.4 Is exposure classified based on biological 
mechanism of action and taking into account the 
pharmacokinetics and pharmacodynamics of the 
drug?

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Comments:
PraxbindTM is administered as a total dose (5g) across two separate vials of 2.5g each 
one after the other immediately.
Section 6: Outcome definition and measurement
Yes
No
N/A
Section 
Number
6.1 Does the protocol specify the primary and 
secondary (if applicable) outcome(s) to be 
investigated?
10.2.2
6.2 Does the protocol describe how the outcomes are 
defined and measured? 
10.2.2
6.3 Does the protocol address the validity of outcome
measurement? (e.g. precision, accuracy, sensitivity, 
specificity, positive predictive value, prospective or 
retrospective ascertainment, use of validation sub-study)
6.4 Does the protocol describe specific endpoints 
relevant for Health Technology Assessment? (e.g.
HRQoL, QALYs, DALYS, health care services utilisation, burden 
of disease, disease management)
Comments:
Section 7: Bias
Yes
No
N/A
Section
Number
7.1 Does the protocol describe how confounding will 
be addressed in the study?
7.1.1. Does the protocol address confounding by 
indication if applicable? 
7.2 Does the protocol address:
7.2.1. Selection biases (e.g. healthy user bias)
7.2.2. Information biases (e.g. misclassification of 
exposure and endpoints, time-related bias)
7.3 Does the protocol address the validity of the study 
covariates?
Comments:
Since there is no comparator arm in the study and only one standard dose of study drug 
is studied, there are no confounding variables. Hence, the entire section is not 
applicable.
Section 8: Effect modification
Yes
No
N/A
Section 
Number
8.1 Does the protocol address effect modifiers? (e.g. 
collection of data on known effect modifiers, sub-group analyses,
anticipated direction of effect)
Comments:
This is an India only study and hence there will be no sub-group analysis done for this 
study. 

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Section 9: Data sources
Yes
No
N/A
Section
Number
9.1 Does the protocol describe the data source(s) 
used in the study for the ascertainment of:
9.1.1 Exposure? (e.g. pharmacy dispensing, general 
practice prescribing, claims data, self-report, face-to-face 
interview, etc.)
9.1.2 Outcomes? (e.g. clinical records, laboratory markers 
or values, claims data, self-report, patient interview including 
scales and questionnaires, vital statistics, etc.)
9.1.3 Covariates?
10.3
10.3
9.2 Does the protocol describe the information 
available from the data source(s) on:
8.2.1 Exposure? (e.g. date of dispensing, drug quantity, 
dose,  number of days of supply prescription, daily dosage,  
prescriber)
8.2.2 Outcomes? (e.g. date of occurrence, multiple event, 
severity measures related to event)
8.2.3 Covariates? (e.g. age, sex, clinical and drug use 
history, co-morbidity, co-medications, life style, etc.)
10.2.1
10.2.2
10.2.3
9.3 Is a coding system described for:
9.3.3 Exposure? (e.g. WHO Drug Dictionary, Anatomical 
Therapeutic Chemical (ATC)Classification System)
9.3.2 Outcomes? (e.g. International Classification of 
Diseases (ICD)-10, Medical Dictionary for Regulatory Activities
(MedDRA))
9.3.3 Covariates?
9.4 Is a linkage method between data sources 
described? (e.g. based on a unique identifier or other)
Comments:
9.3.- The coding system will be a part of the Data Analysis plan.
Section 10: Analysis plan
Yes
No
N/A
Section 
Number
10.1 Is the choice of statistical techniques described? 
10.6.1
10.2 Are descriptive analyses included?
10.6.1
10.3 Are stratified analyses included?
10.4 Does the plan describe methods for adjusting for 
confounding?
10.5 Does the plan describe methods for handling 
missing data?
10.6 Is sample size and/or statistical power 
estimated?
10.4
Comments:

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Section 11: Data management and quality 
control
Yes
No
N/A
Section
Number
11.1 Does the protocol provide information on data 
storage? (e.g. software and IT environment, database 
maintenance and anti-fraud protection, archiving)
10.9.2.2.1
11.2 Are methods of quality assurance described?
10.9.1
11.3 Is there a system in place for independent 
review of study results? 
Comments:
Section 12: Limitations
Yes
No
N/A
Section
Number
12.1
Does the protocol discuss the impact on the 
study results of:
12.1.1 Selection bias?
12.1.2 Information bias?
12.1.3 Residual/unmeasured confounding?
(e.g. anticipated direction and magnitude of such biases, 
validation sub-study, use of validation and external data, 
analytical methods)
10.9
10.9
12.2 Does the protocol discuss study feasibility? (e.g. 
study size, anticipated exposure, duration of follow-up in a 
cohort study, patient recruitment)
10.4
Comments:
Section 13: Ethical issues
Yes
No
N/A
Section
Number
13.1 Have requirements of Ethics Committee/ 
Institutional Review Board been described?
11.1
13.2 Has any outcome of an ethical review procedure 
been addressed?
11.1
13.3 Have data protection requirements been 
described?
11.1
Comments:
Section 14: Amendments and deviations
Yes
No
N/A
Section
Number
14.1 Does the protocol include a section to document 
amendments and deviations? 
6
Comments:

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Section 15: Plans for communication of study 
results
Yes
No
N/A
Section
Number
15.1 Are plans described for communicating study 
results (e.g. to regulatory authorities)?
12
15.2 Are plans described for disseminating study 
results externally, including publication?
12
Comments:

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ANNEX 3. ADDITIONAL INFORMATION
Not Applicable

 
 
 
 
APPROVAL / SIGNATURE PAGE 
 
Document Number: 
 
Technical Version Number:
 
Document Name: 
 
 
 
                                                                                                                 
 
Title: 
 
 
 
 
                                                                                                                   
 
Signatures (obtained electronically) 
 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
c17261390
4.0
non-interventional-study-protocol-version-03
Post marketing surveillance program of PraxbindTM use in India.
Approval-Team Member Drug
Safety
26 Mar 2018 15:32 CEST
Author-Trial Clinical Monitor
26 Mar 2018 16:50 CEST
Approval-
 Safety Evaluation
Therapeutic Area
26 Mar 2018 17:02 CEST
Approval-Team Member Medical
Affairs
26 Mar 2018 19:27 CEST
Approval-Biostatistics
27 Mar 2018 07:35 CEST
Approval-EU Qualified Person
Pharmacovigilance
27 Mar 2018 12:10 CEST
Approval-Therapeutic Area 
29 Mar 2018 12:57 CEST
Verification-Paper Signature
Completion
29 Mar 2018 13:02 CEST

Boehringer Ingelheim 
Page 2 of 2
Document Number: 
 Technical Version Number:
 
 
 
(Continued) Signatures (obtained electronically) 
 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
c17261390
4.0

Boehringer Ingelheim 
BI Trial No.: 1321.0023 
cl 7261390-04 
Clinical Trial Protocol 
23 Mar 2018 
Page 1of1 
Proprietary confidential infonnation © 2018 Boehringer lngelheim International GmbH or one or more of its affiliated companies 
LOCAL SIGNATURE(S) 
(Medical
 
Trial Title: 
Post marketing surveillance program of Praxbind TM use in India. 
Trial Number: 
1321.0023 
Clinical Trial Protocol Version: 
3.0 
I herewith certify that I agree to adhere to the Clinical Trial Protocol and to all 
documents referenced in the Clinical Trial Protocol. 
Medical
 (Print full name) 
Boehringer Ingelheim India Pvt. Ltd. 
Date (dd Mmm yyyy) 
Signature 
~01-MCS-40-106 RD-09 (5.0) I Saved on: 15 Mar 201 ~