Investigating Trends in Quality of Life in Patients With Idiopathic Pulmonary Fibrosis (IPF) Under Treatment With Nintedanib
Conditions: Idiopathic Pulmonary Fibrosis
Sponsor: Boehringer Ingelheim

ABCD
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Non-interventional Study Protocol
 
Document Number:
c25576073-03
BI Study Number:
1199-0355
BI Investigational
Product(s):
Ofev®, nintedanib
Title:
Investigating Trends in Quality of Life in Patients with 
Idiopathic Pulmonary Fibrosis (IPF) Under Treatment 
with Nintedanib
Brief lay title
QUALIFY Idiopathic Pulmonary Fibrosis
Protocol version 
identifier:
3.0 
Date of last version of 
protocol:
11 February 2021
PASS:
No
EU PAS register 
number:
Not yet registered
Active substance:
Pharmacotherapeutic group: Antineoplastic agents, 
protein kinase inhibitors, ATC code: L01XE31
Medicinal product:
OFEV,100 mg and 150 mg soft capsules
Product reference:
EU/1/14/979
Procedure number:
EMEA/H/C/3821/WS/1307
Marketing authorization
holder(s):
Boehringer Ingelheim International GmbH

Boehringer Ingelheim
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Joint PASS:
No
Research question and 
objectives:
The aim of this non-interventional-study is to collect data 
on various important Patient Reported Outcomes (PROs) 
in patients with IPF that could provide useful insights 
about Health-Related Quality of Life (HRQoL) over 52 
weeks in patients treated with nintedanib in the real world 
setting in Greece.
Primary objective:
- To evaluate HRQoL changes from baseline for IPF 
patients treated in current clinical practice in Greece 
with nintedanib at time-points of 3, 6, 9 and 12 months 
over a 52-week period, via SGRQ.
Secondary objectives are:
- To assess changes, from baseline, in dyspnoea and 
cough in IPF patients treated with nintedanib in current 
clinical practice in Greece at time-points of 3, 6, 9 and 
12 months over a 52 weeks period, via specific 
questionnaires, such as mMRC score and Cough -
Visual Analogue Scale (Cough - VAS) respectively.
- To evaluate the adherence to nintedanib treatment in 
current clinical practice at time-points of 3, 6, 9 and 12 
months over a 52 weeks period via SMAQ 
Questionnaire (adapted for the treatment of idiopathic 
pulmonary fibrosis (IPF).
- To measure anxiety in IPF patients treated with 
nintedanib in current clinical practice in Greece at time-
points of baseline, 3, 6, 9 and 12 months over a 52 
weeks period via GAD-7 Questionnaire.

Boehringer Ingelheim
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- To estimate the use of Long-Term Oxygen Treatment 
(LTOT) among IPF patients under treatment with 
nintedanib in current clinical practice in Greece at time-
points of baseline, 3, 6, 9 and 12 months over a 52 
weeks period.
Country(-ies) of study:
Greece
Author:
Marketing authorisation 
holder(s):
Boehringer Ingelheim
In case of PASS, add:
MAH contact person:
Not applicable
In case of PASS, add:
<EU-QPPV:>
Not applicable
In case of PASS, add:
<Signature of EU-
QPPV:>
Not applicable
Date:
11 February 2021
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Proprietary confidential information
© 2021 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
TITLE PAGE.......................................................................................................................................................1
1.
TABLE OF CONTENTS ..............................................................................................................................4
2.
LIST OF ABBREVIATIONS .........................................................................................................................6
3.
RESPONSIBLE PARTIES ............................................................................................................................8
4.
ABSTRACT...............................................................................................................................................9
!
Nintedanib treatment (start date, dose).......................................................................................................19
!
Assessment of lung function and exercise capacity (FVC, DLCO, 6-minutes walking test)............................19
!
Physical and vital signs examination (blood pressure, heart rate) ................................................................20
!
Nintedanib treatment (stop date, restart date in case of temporary discontinuation, dose).......................20
5.
AMENDMENTS AND UPDATES..............................................................................................................31
6.
MILESTONES.........................................................................................................................................39
7.
RATIONALE AND BACKGROUND ...........................................................................................................40
7.1
DEFINITION.............................................................................................................................................40
7.2
INCIDENCE AND PREVALENCE ................................................................................................................40
7.3
DIAGNOSIS..............................................................................................................................................41
7.4
NATURAL COURSE ..................................................................................................................................41
7.5
THERAPY.................................................................................................................................................42
7.6
RATIONALE FOR THE PRESENT STUDY ....................................................................................................42
7.6.1
Rationale for questionnaires used ................................................................................................43
8.
RESEARCH QUESTION AND OBJECTIVES................................................................................................46
9.
RESEARCH METHODS............................................................................................................................47
9.1
STUDY DESIGN........................................................................................................................................47
9.2
SETTING..................................................................................................................................................47
9.2.1
Study sites.....................................................................................................................................47
9.2.2
Study population...........................................................................................................................48
9.2.3
Study visits ....................................................................................................................................49
9.2.4
Patient discontinuation.................................................................................................................49
9.2.5
Study discontinuation ...................................................................................................................51
9.3
VARIABLES ..............................................................................................................................................51
9.3.1
Exposures......................................................................................................................................51
9.3.2
Endpoints ......................................................................................................................................52
9.3.2.1
Primary endpoint ................................................................................................................................52
9.3.2.2
Secondary endpoints ..........................................................................................................................52
9.3.3
Covariates .....................................................................................................................................53
9.4
DATA SOURCES.......................................................................................................................................57
9.5
STUDY SIZE..............................................................................................................................................59
9.6
DATA MANAGEMENT .............................................................................................................................61
9.7
DATA ANALYSIS.......................................................................................................................................62
9.7.1
Main analysis................................................................................................................................62
9.8
QUALITY CONTROL .................................................................................................................................63
9.9
LIMITATIONS OF THE RESEARCH METHODS ...........................................................................................64

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9.10 OTHER ASPECTS......................................................................................................................................65
9.10.1
Data quality assurance .................................................................................................................65
9.10.2
Study records ................................................................................................................................66
9.10.2.1
Source documents ..............................................................................................................................66
9.10.2.2
Direct access to source data and documents......................................................................................67
9.10.2.3
Storage of records...............................................................................................................................67
9.10.3
Completion of study......................................................................................................................68
10.
PROTECTION OF HUMAN SUBJECTS......................................................................................................69
10.1 STUDY APPROVAL, PATIENT INFORMATION, AND INFORMED CONSENT...............................................69
10.2 STATEMENT OF CONFIDENTIALITY .........................................................................................................70
11.
MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE REACTIONS .....................................72
11.1 DEFINITIONS OF ADVERSE EVENTS.........................................................................................................72
11.2 ADVERSE EVENT AND SERIOUS ADVERSE EVENT COLLECTION AND REPORTING ...................................73
11.3 REPORTING TO HEALTH AUTHORITIES....................................................................................................77
12.
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS .................................................78
13.
REFERENCES .........................................................................................................................................80
13.1 PUBLISHED REFERENCES ........................................................................................................................80
13.2 UNPUBLISHED REFERENCES ...................................................................................................................82
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS..............................................................................................83
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS ..................................................................................84
ANNEX 3. ADDITIONAL INFORMATION ..........................................................................................................94

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2.
LIST OF ABBREVIATIONS
ADR
Adverse Drug Reaction
AE
Adverse Event
AESI
Adverse Event of Special interest
ALAT
Latin American Thoracic Association
ATS
American Thoracic Society
CA
Competent Authority
CCDS
Company Core Data Sheet
CI
Confidence Interval
CRA
Clinical Research Associate
CRF
Case Report Form
CRO
Clinical Research Organization
CTCAE
Common Terminology Criteria for Adverse Events
CTM
Clinical Trial Manager
CTP
Clinical Trial Protocol
DMP
Data Management Plan
eCRF
Electronic Case Report Form
ENCePP 
PV
European Network of Centres for Pharmacoepidemiology and 
Pharmacovigilance
ERS
European Respiratory Society
FDA
Food and Drug Administration
FGF
Fibroblast Growth Factor
FVC
Forced Vital Capacity
GAD-7
  Generalized Anxiety Disorder Screener Questionnaire
GCP
Good Clinical Practice
GEP
Good Epidemiological Practice
GPP
Good Pharmacoepidemiology Practice
GVP
Good Pharmacovigilance Practices
HRCT
High Resolution Computer Tomography
HRQoL
Health Related Quality of Life
IB
Investigator’s Brochure

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IEC
Independent Ethics Committee
IIP
Idiopathic Interstitial Pneumonia
ILD
Interstitial Lung Disease
IPF
Idiopathic Pulmonary Fibrosis
IRB
Institutional Review Board
JRS
Japanese Respiratory Society
LTOT
Long Term Oxygen Therapy
MAH
Marketing Authorization Holder
mMRC
modified Medical Research Council scale
NIS
Non-Interventional Study
PASS
Post-Authorization Safety Study
PDGF
Platelet Derived Growth Factor
PROs
Patient Reported Outcomes
RCT
Randomized Clinical Trial
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SD
Standard Deviation
SGRQ
St. George’s Respiratory Questionnaire
SMAQ
Simplified Medication Adherence Questionnaire
SmPC
Summary of Product Characteristics
UIP
Usual Interstitial Pneumonia
VAS
Visual Analogue Scale
VEGF
Vascular Endothelial Growth Factor

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3.
RESPONSIBLE PARTIES
Trial Sponsor
Participating Investigators
A contact list of the participating investigators will be stored as a standalone (independent) 
document and will be available upon request.

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4.
ABSTRACT
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Rationale and 
background:
IPF is a rare, chronic and progressive pulmonary disease affecting 2.8-9.3 
persons per 100,000 in the western world (1). IPF is associated with 
chronic dyspnoea and cough and the progressive loss of lung function, 
leading to respiratory failure (2). However, the clinical course of disease 
is variable with some patients progressing slowly, others rapidly and 
some patients experiencing acute exacerbations that are associated with 
increased morbidity and mortality (3). Until recently no effective 
pharmacological treatment besides lung transplantation was available for 
IPF patients. Nintedanib, an oral multi-tyrosine kinase inhibitor, was 
approved in EU on January 2015 for the treatment of IPF patients 
independent of the stage of their disease (4). Nintedanib is available and 
reimbursed in Greece since February 2016. Due to the rarity of IPF, there 
are very limited data regarding the patients’ population, the natural course 
of the disease and the medical treatment these patients receive, as 
highlighted by the call for action towards a worldwide IPF registry (5).

Boehringer Ingelheim
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001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Rationale and 
background
(cont’d):
Especially for the Greek population, very few data are available 
regarding the use  of nintedanib in cohorts of patients with IPF either pre-
treated or treatment-naïve, also in terms of Patients Reported Outcomes 
(PRO) (6). The recently launched observational study INDULGE-IPF 
(NCT03074149) will provide essential data regarding the natural course 
of IPF and the treatment of the disease – including the use of nintedanib 
– in the Greek population. In a chronic disease like IPF, the goal of 
pharmacological treatments should not be only survival prolongation, 
but also delay in the progression of the disease and on the clinical 
deterioration of patients, i.e. delay worsening of symptoms and quality 
of life. In IPF, there is a paucity of well validated PRO measures.  In the 
pooled analysis of nintedanib randomized trials in IPF, the use of SGRQ 
questionnaire as a measurement of health related quality of life provided 
evidence  for a modest effect of nintedanib on the  delay of  clinical 
deterioration of patients (4, 7). 

Boehringer Ingelheim
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Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Rationale and 
background
(cont’d):
In addition a German IPF registry (INSIGHTS-IPF) has recently 
published results for patient reported outcomes (PROs) in enrolled 
patients, showing IPF patients under real-life conditions have lower 
HRQoL compared to those in clinical studies (8). In the Greek population,
analogous results regarding the effect of nintedanib on SGRQ as well as 
other PRO measures are lacking. Therefore, the aim of this non-
interventional-study based on newly collected data is to collect data on 
various important PROs in patients with IPF that could provide useful 
insights about HRQoL over 52 weeks in patients treated with nintedanib 
in the real world setting in Greece.

Boehringer Ingelheim
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001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Research 
question and 
objectives:
Primary objective:
-
To evaluate the HRQoL changes of IPF patients treated in current 
clinical practice in Greece with nintedanib at time-points of 3, 6, 9 
and 12 months over a 52-weeks period, via SGRQ.
Secondary objectives are:
-
To assess changes, from baseline, in dyspnoea and cough in IPF 
patients treated with nintedanib in current clinical practice in Greece
at time-points of 3, 6, 9 and 12 months over a 52 weeks period, via 
specific questionnaires, such as mMRC score and Cough – Visual

Boehringer Ingelheim
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Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Research 
question and 
objectives 
(cont’d):
Analogue Scale (Cough - VAS) respectively.
-
To evaluate the adherence to nintedanib treatment in current clinical 
practice at time-points of 3, 6, 9 and 12 months over a 52 weeks period 
via SMAQ Questionnaire (adapted for the treatment of idiopathic 
pulmonary fibrosis (IPF).
-
To measure anxiety in IPF patients treated with nintedanib in current 
clinical practice in Greece at time-points of baseline, 3, 6, 9 and 12 
months over a 52 weeks period via GAD-7 Questionnaire.
-
To estimate the use of Long-Term Oxygen Treatment (LTOT) among 
IPF patients under treatment with nintedanib in current clinical practice 
in Greece at time-points of baseline, 3, 6, 9 and 12 months over a 52 
weeks period.

Boehringer Ingelheim
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Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Study design:
This is a National, multi-center, non-interventional, prospective cohort 
study aiming to enroll 240 IPF patients receiving treatment with 
nintedanib in a consecutive manner from 10-12 reference centers across 
Greece, representative of the entire Greek population. Recruitment will 
last for 36 months and patients will be followed over a period of 52 
weeks. A baseline visit and 4 follow up visits will be performed during 
the follow-up period according to clinical practice.

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001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Study design 
(cont’d):
In the context of this study, participating physicians shall follow each 
enrolled patient for a planned observation period of 12 months, starting 
from the date of baseline visit and ending at the earliest of treatment 
discontinuation, withdrawal of consent, physician’s decision to withdraw 
the patient, 12-month observation period completion, death or any other 
discontinuation criterion is met. 
Patients that withdraw from the study (consent withdrawal, lost to Follow 
up) or permanently discontinue nintedanib treatment, prior to the follow 
up period completion, for any reason (e.g. due to AE, physician’s 
decision), will no longer be followed-up for the study and the visit that 
discontinuation is recorded will be considered as their end of study visit.
Patients that temporarily interrupt treatment with nintedanib, up to 28 
days, will continue follow up activities according to the study plan and 
will not be discontinued from the study.

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001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Population:
In this study, there will be enrolled approximately 240 consecutive IPF 
patients from 10-12 sites – Academic Hospitals and reference centres. 
Participating centres and therefore participating physicians have large 
experience in the management of patients with IPF and may also be part 
of a larger referral network. 

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Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Population
(cont’d):
Patients will be eligible to enrol in the study if they fulfil all the inclusion 
criteria and none of the exclusion criteria:
Inclusion criteria
!
Patients ≥40 years of age.
!
Patients that have signed Informed Consent Form.
!
Treatment naïve patients with an initial IPF diagnosis no more than 
3 months prior to enrolment according to 2011 ATS/ERS/JRS/ALAT 
guidelines and have initiated treatment with Nintedanib (as 
monotherapy for IPF) within the past 7 days prior to study enrolment. 
!
Patients for whom the decision to prescribe therapy with nintedanib
according to the locally approved product’s Summary of Product 
Characteristics (SmPC) has already been taken prior to their 
enrolment in the study and is clearly separated from the physician’s 
decision to include the patient in the current study.
! Patients that are able to read, understand and complete the study 
specific questionnaires. 

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Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Population 
(cont’d):
Exclusion criteria
!
Treatment with nintedanib for more than 7 days prior to study 
enrolment.
!
Patients receiving a combination therapy of nintedanib & pirfenidone 
for IPF.
!
Patients that meet any of the contraindications to the administration 
of the study drug nintedanib according to the approved SmPC.
!
Prior treatment with pirfenidone or other treatment for IPF.
!
Patients participate in an interventional trial, currently receiving 
treatment with any investigational drug/device/intervention or 
having received any investigational product within 1 month or 5 half-
lives of the investigational agent (whichever is longer) before the 
initiation of therapy with nintedanib.

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Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Variables:
At baseline, a relevant patient history will be recorded. Further, the current 
status of IPF patients will be recorded regarding
!
Basic (Socio-) demographic data
!
Anthropometric characteristics (body weight, height)
!
Physical and vital signs examination (arterial/blood pressure, heart 
rate)
!
IPF risk factors
!
Co-morbidities 
and 
concomitant 
treatments 
(medication 
category/class)
!
Recording of the methods and procedures used in the diagnosis of 
IPF and date of diagnosis (including HRCT and SLB)
!
IPF symptoms
!
Nintedanib treatment (start date, dose)
!
Assessment of lung function and exercise capacity (FVC, DLCO, 
6-minutes walking test)

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BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Variables
(cont’d):
!
Questionnaires (SGRQ, mMRC Score, Cough - VAS, GAD-7 )
!
Long Term Oxygen Therapy
The following variables will be also recorded at follow up visits:
!
Physical and vital signs examination (blood pressure, heart rate)
!
Anthropometric characteristics (body weight)
!
Nintedanib treatment (stop date, restart date in case of temporary 
discontinuation, dose)
!
Questionnaires (SGRQ, mMRC Score, Cough - VAS, SMAQ, 
GAD-7)
!
Long Term Oxygen Therapy 
!
Changes in concomitant treatments (medication category/class).
!
Survival status

Boehringer Ingelheim
Page 21 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Data sources:
New data collection. Data will be recorded via e-CRF, where the 
participating physician will record both clinical data, such as baseline 
characteristics and other medical data, and also the data from the relevant 
questionnaires that the patient will have to fill out either alone or in 
collaboration with the participating physician or the study nurse, if 
available. The following questionnaires will be used for this study:

Boehringer Ingelheim
Page 22 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Data sources
(cont’d):
-SGRQ is a self-administered, 50-item questionnaire assessing three 
domains: symptoms, activity and impact. This questionnaire has been 
validated for use in patients with COPD but also has been tested for 
patients with IPF and could detect alterations in the clinical status of 
the patients. The total score and the score for each domain range from 
0 to 100, with higher scores indicating worse health-related quality of 
life. A minimally important difference in the score has not been 
established for patients with idiopathic pulmonary fibrosis; in patients 
with chronic obstructive pulmonary disease, this difference is 4 
points.
-mMRC is a modified medical research council dyspnoea scale that uses 
same descriptors as the original MRC scale. The descriptors of the 
mMRC scale are numbered 1-5 and are used to estimate the patient’s 
perception of breathlessness. The specific scale has been validated as 
a measurement of disease severity in IPF patients.

Boehringer Ingelheim
Page 23 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Data sources 
(cont’d):
-Cough - VAS is recommended as an instrument for the assessment of 
IPF related cough.
-SMAQ is a validated six-item questionnaire that estimates in a 
qualitative and semi-quantitative manner the adherence of patients to 
treatment.
-GAD-7 is a 7-item instrument validated for anxiety evaluation that could 
be used in outpatient setting.
All questionnaires should be administered to the patients for 
completion at the beginning of their visit by the treating physician and 
prior to any clinical evaluation. All these completed questionnaires 
will be stored safely in the centres for future purposes of Data Review 
& Quality Checks if needed.

Boehringer Ingelheim
Page 24 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Primary and 
Secondary 
Endpoints
The primary endpoint of the study is:
!
The mean change from baseline in HRQoL (with reference to 
SGRQ score, both total score and score of each of the SGRQ 
domain) in patients under treatment with nintedanib, as assessed 
at time-point3, 6, 9 and 12 months over the 52 weeks follow-up 
period.
The secondary endpoints of the study are:
!
Change from baseline to 3, 6, 9 and 12 months follow up period 
of dyspnoea burden as measured by mMRC score at time-point
!
The mean change from baseline to 3, 6, 9 and 12 months follow 
up period of cough burden, as measured via changes in the Cough 
- Visual Analogue Scale (cough - VAS) for coughtime-point
!
Percentage of adhered patients to nintedanib treatment at time-
points of 3, 6, 9 and 12 months over the 52 weeks follow up period, 
as measured via SMAQ questionnaire (adapted for the treatment 
of idiopathic pulmonary fibrosis (IPF).

Boehringer Ingelheim
Page 25 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Primary and 
Secondary 
Endpoints 
(cont’d):
!
The mean change from baseline to 3, 6, 9 and 12 months follow 
up period of anxiety in patients treated with nintedanib at time-
point as measured via GAD-7 questionnaire.
!
Percentage of patients that use LTOT at time-points of 3, 6, 9 and 
12 months over the 52 weeks follow up period.
Study size:
This observational study will be analyzed using descriptively statistics 
following 
standard 
statistical 
and 
epidemiological 
methods. 
Approximately 240 patients are expected to be enrolled in the study in a 
consecutive manner between February 2019 and February 2022 from the 
participating sites according to the feasibility procedure of the sites. The 
number of recruited patients as well as the duration of the study is not 
defined by a formal sample size and power calculation, but is based 
mainly on the availability of eligible IPF patients as well as patient 
population in the selected sites.

Boehringer Ingelheim
Page 26 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Study size
(cont’d):
Next table describes expected 95% confidence limits and precision of the 
estimate of mean change from baseline of SGRQ Total Score at week 52, 
according to different assumption of mean change from baseline and 
standard deviation (SD).
Because SD is unknown at the planning stage, it needs to be assumed 
based on the previous trials. In INPULSIS trials, the sample standard 
deviation of the change from baseline in SGRQ total score at Week 52 
was about 16. In the real-world setting, the more diverse patients are 
expected compared to patients in INPULSIS trials. These calculations are 
based on a total number of 200 evaluable study participants. Taking into 
consideration a withdrawal rate of 17-20%, the number of patients that 
will be enrolled is 240.
Therefore, we assume that SD ranging from 16 to 22, as per the table 
below (95% confidence limits and precision of the estimate of mean 
change from baseline of SGRQ Total Score at week 52, according to 
different assumption of mean change from baseline and standard 
deviation):

Boehringer Ingelheim
Page 27 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Study size 
(cont’d):
Ν
Mean dif
Sd
95% CI
ω
200
2
16
-0.2
4.2
4.4
200
2
18
-0.5
4.5
5.0
200
2
20
-0.8
4.8
5.5
200
2
22
-1.0
5.0
6.1
200
3
16
0.8
5.2
4.4
200
3
18
0.5
5.5
5.0
200
3
20
0.2
5.8
5.5
200
3
22
0.0
6.0
6.1
200
4
16
1.8
6.2
4.4
200
4
18
1.5
6.5
5.0
200
4
20
1.2
6.8
5.5
200
4
22
1.0
7.0
6.1
200
5
16
2.8
7.2
4.4
200
5
18
2.5
7.5
5.0
200
5
20
2.2
7.8
5.5
200
5
22
2.0
8.0
6.1

Boehringer Ingelheim
Page 28 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Data analysis:
Continuous variables will be listed as median with interquartile and/or  
other percentiles and as mean value with standard deviation (SD), along 
with minimum and maximum values and 95% confidence intervals (if 
needed). Categorical values will be summarised as absolute and relative 
frequencies.
Analysis of Primary Outcome
Summary statistics based on observed data will be used to describe the 
mean SGRQ scores at each visit and the mean change of SGRQ scores 
from baseline to each study visit until 12 months.
Change from baseline of SGRQ scores will be statistically investigated 
by mixed models for repeated measures assuming that missing values are 
missing at random. Baseline is defined as the time of the enrolment of 
patients in the study.

Boehringer Ingelheim
Page 29 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Data analysis 
(cont’d):
Analysis of secondary outcomes
Mean change from baseline during the 52 weeks follow up period 
(3,6,9,12 months) for the following endpoints:
!
burden of cough as measured via Cough - Visual Analogue Scale 
(Cough - VAS) and 
anxiety as measured by GAD-7 score, will follow the same analysis as 
the primary outcome. 
Baseline is defined as the time of the enrollment of patients in the study.
Adherence to nintedanib will be accessed via frequency tables of each 
SMAQ item in each follow up visit.
The number and percentage of patients that use LTOT during the 52 
weeks follow up period will also be displayed. The distribution of 
patients with respect to dyspnoea based on the mMRC score at every 
study time-point, will be presented in frequency tables (N, %).

Boehringer Ingelheim
Page 30 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
Name of company:
Boehringer Ingelheim
Name of finished medicinal 
product:
OFEV
Name of active ingredient:
ATC code: L01XE31
Nintedanib
Protocol date:
11 Sep 2018
Study 
number:
1199-0355
Version/Revision: 3.0
Version/Revision date:
11 Feb 2021
Title of study:
Investigating Trends in Quality of Life in Patients with IPF Under 
Treatment with Nintedanib
Data analysis 
(cont’d):
Safety Analysis 
All adverse events recorded during the trial will be presented in listings. 
AEs will be coded based on the MedDRA terminology.
Milestones:
Study timelines depend upon approval of the final protocol
-
feasibility assessment: Sep 2018
-
IRB/IEC approval: Nov 2018  
-
start of data collection: Feb 2019 
-
end of data collection:  Mar 2023
-
final results: Q3 2023
-
final study report: Dec 2023

Boehringer Ingelheim
Page 31 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
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001-MCS-90-118 RD-01 (7 0) / Saved on: 09 Nov 2015
5.
AMENDMENTS AND UPDATES
Number
Date
Section of 
study protocol
Amendment or update
Reason
1
02 June 2020 4. ABSTRACT 
This is a National, multi-center, non-interventional, 
prospective cohort study aiming to enroll 240 IPF 
patients receiving treatment with nintedanib in a 
consecutive manner from 10-12 reference centers 
across Greece, representative of the entire Greek 
population. Recruitment will last for 24 months and 
patients will be followed over a period of 52 weeks. A 
baseline visit and 4 follow up visits will be performed 
during the follow-up period according to clinical 
practice. 
Recruitment period has been 
extended to 24 months and sample 
size has been increased to 240 
patients, in order for the statistical 
power and validity of the study’s 
results to get strengthened. 

Boehringer Ingelheim
Page 32 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118 RD-01 (7 0) / Saved on: 09 Nov 2015
Number
Date
Section of 
study protocol
Amendment or update
Reason
2
02 June 2020 4. ABSTRACT
mMRC is a modified medical research council 
dyspnoea scale that uses same descriptors as the 
original MRC scale. The descriptors of the mMRC 
scale are numbered 1-5 and are used to estimate the 
patient’s perception of breathlessness. The specific 
scale has been validated as a measurement of disease 
severity in IPF patients.
The mMRC description was 
corrected to reflect its constitution 
of five descriptors instead of 6.
3
02 June 2020 4. ABSTRACT
Inclusion Criterion no 3 was updated to:
Treatment naïve patients with an initial IPF diagnosis 
no more than 3 months prior to enrolment according to 
2011 ATS/ERS/JRS/ALAT guidelines who are 
initiating treatment with Nintedanib (as monotherapy 
for IPF) the latest on the enrollment day or have 
initiated treatment with Nintedanib (as monotherapy 
for IPF) within the past 7 days prior to enrolment.
Clarification to Inclusion criterion no 
3, on treatment initiation, was added.

Boehringer Ingelheim
Page 33 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118 RD-01 (7 0) / Saved on: 09 Nov 2015
Number
Date
Section of 
study protocol
Amendment or update
Reason
4
02 June 2020
3. 
RESPONSIBLE 
PARTIES
Trial Sponsor
BI Greece new address was added.
5
02 June 2020
6.MILESTONES
Milestone
Planned Date
IRB/IEC approval
14 NOV 2018
Start of data collection
28 FEB 2019
End of data collection
27 MAR 2022
Final report of study 
results:
DEC 2022
Update of the main milestones 
dates, so that the actual timelines 
and actual plan to be reflected 
accurately, based on the visit 
schedule of the protocol and taking 
into consideration that the first 
investigational site was activated 
on 28 Feb 2019 and the data 
collection initiated on 28 Feb 2019.

Boehringer Ingelheim
Page 34 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118 RD-01 (7 0) / Saved on: 09 Nov 2015
Number
Date
Section of 
study protocol
Amendment or update
Reason
6
02 June 2020
7.6.1 Rationale 
for questionnaires 
used
mMRC is a modified medical research council 
dyspnoea scale that uses same descriptors as the 
original MRC scale. The descriptors of the mMRC 
scale are numbered 1-5 and are used to estimate the 
patient’s perception of breathlessness. The specific 
scale has been validated as a measurement of disease 
severity in IPF patients.
The mMRC description was 
corrected to reflect its constitution 
of five descriptors instead of 6.
7
02 June 2020
9.1 STUDY 
DESIGN
This is a National, multi-center, non-interventional, 
prospective cohort study aiming to enroll 240 IPF 
patients receiving treatment with nintedanib in a 
consecutive manner from 10-12 reference centers 
across Greece, representative of the entire Greek 
population. Recruitment will last for 24 months and 
patients will be followed over a period of 52 weeks.
Recruitment period has been 
extended to 24 months and sample 
size has been increased to 240 
patients, in order for the statistical 
power and validity of the study’s 
results to get strengthened.

Boehringer Ingelheim
Page 35 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
Proprietary confidential information © 2021BoehringerIngelheim International GmbH or one or more of its affiliated companies
001-MCS-90-118 RD-01 (7 0) / Saved on: 09 Nov 2015
Number
Date
Section of 
study protocol
Amendment or update
Reason
8
02 June 2020
9.2.2 Study 
population
Inclusion Criterion no 3 was updated to:
Treatment naïve patients with an initial IPF diagnosis 
no more than 3 months prior to enrolment according to 
2011 ATS/ERS/JRS/ALAT guidelines who are 
initiating treatment with Nintedanib (as monotherapy 
for IPF) the latest on the enrollment day or have 
initiated treatment with Nintedanib (as monotherapy 
for IPF) within the past 7 days prior to enrolment.
Clarification to Inclusion criterion no 
3, on treatment initiation was added.
9
02 June 2020
9.2.3 STUDY 
VISITS
The study is scheduled to run for 3 years in total, i.e. 
2 years of recruitment and 1 year of follow-up.
Recruitment period extended to 2 
years in total and total study 
duration to 3 years e. g 2 tears 
recruitment and 1 year of follow up
10
02 June 2020
9.3.3 Covariates
Long Term Oxygen Therapy: It will be recorded 
whether the patient is on LTOT or not.
Type and duration of Long-term 
Oxygen supplementation therapy 
were deleted, as not required.

Boehringer Ingelheim
Page 36 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
c25576073-03
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001-MCS-90-118 RD-01 (7 0) / Saved on: 09 Nov 2015
Number
Date
Section of 
study protocol
Amendment or update
Reason
11
02 June 2020
Table 1 List of 
variables to be 
documented at 
scheduled visits 
Final Visit (12 months follow up ± 1 month or after
study discontinuation visit) 
Final Visit definition was updated in 
Table 1 & Table 2 to better describe 
study discontinuation visit.
12
02 June 2020
Table 2 Study 
Flowchart
Final Visit (12 months follow up ± 1 month or after 
study discontinuation visit) 
Final Visit definition was updated in 
Table 1 & Table 2 to better describe 
study discontinuation visit.
13
02 June 2020
9.5   STUDY 
SIZE
Table 1. 95% 
confidence limits 
and precision of 
the estimate of 
mean change from 
baseline of SGRQ 
Total Score at 
week 52, according 
to different 
assumption of 
mean change from 
baseline and 
standard deviation.
Ν
Mean
dif
Sd
95% CI
Ω
200
2
16
-0.2
4.2
4.4
200
2
18
-0.5
4.5
5.0
200
2
20
-0.8
4.8
5.5
200
2
22
-1.0
5.0
6.1
200
3
16
0.8
5.2
4.4
200
3
18
0.5
5.5
5.0
200
3
20
0.2
5.8
5.5
Inclusion of the newly calculated 
confidence intervals, based on the 
new sample size into a revised Table 
3.

Boehringer Ingelheim
Page 37 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
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001-MCS-90-118 RD-01 (7 0) / Saved on: 09 Nov 2015
Number
Date
Section of 
study protocol
Amendment or update
Reason
13 
(cont’d)
02 June 2020
9.6 STUDY SIZE
Table 1.  95% 
confidence limits 
and precision of 
the estimate of 
mean change from 
baseline of SGRQ 
Total Score at 
week 52, according 
to different 
assumption of 
mean change from 
baseline and 
standard deviation.
Ν
Mean
dif
Sd
95% CI
Ω
200
3
22
-0.0
6.0
6.1
200
4
16
1.8
6.2
4.4
200
4
18
1.5
6.5
5.0
200
4
20
1.2
6.8
5.5
200
4
22
1.0
7.0
6.1
200
5
16
2.8
7.2
4.4
200
5
18
2.5
7.5
5.0
200
5
20
2.2
7.8
5.5
200
5
22
2.0
8.0
6.1
Inclusion of the newly calculated 
confidence intervals, based on the 
new sample size into a revised Table 
3.

Boehringer Ingelheim
Page 38 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
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001-MCS-90-118 RD-01 (7 0) / Saved on: 09 Nov 2015
Number
Date
Section of 
study protocol
Amendment or update
Reason
14
02 June 2020
ANNEX 3: 
ADDITIONAL 
INFORMATION
mMRC descriptor was corrected to 
“I stop for breath after walking about 100 yards or 
after a few minutes on the level” instead of
“I stop for breath after walking about 100 meters or 
after a few minutes on the level” which was 
previously.
Corrected mMRC U.S version added 
to include at the descriptor yards 
instead of meters:
“I stop for breath after walking 
about 100 yards or after a few 
minutes on the level”
15
11 Feb 2021
6. MILESTONES
Milestone
Planned Date
IRB/IEC approval
14 NOV 2018
Start of data collection
28 FEB 2019
End of data collection
27 MAR 2023
Final report of study 
results:
DEC 2023
Update of the main milestones 
dates, to reflect the extended 
timelines.

Boehringer Ingelheim
Page 39 of 104
Non-interventional Study Protocol
BI Study Number 1199-0355
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001-MCS-90-118_RD-01 (7 0) / Saved on: 09 Nov 2015
6.
MILESTONES
Milestone
Planned Date
IRB/IEC approval
14 NOV 2018 
Start of data collection
28 FEB 2019 
End of data collection
  27 MAR 2023
Final report of study results:
DEC 2023

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7.
RATIONALE AND BACKGROUND
7.1
DEFINITION
Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive 
fibrosing interstitial pneumonia of unknown cause, occurring primarily in older adults, limited 
to the lungs (2). It is characterized by progressive worsening of dyspnea and lung function and 
is associated with a poor prognosis. As stated in an international consensus statement jointly 
issued by ATS/ERS, JRS and ALAT, IPF is a distinct clinical entity associated with the 
histologic and/or radiologic appearance of usual interstitial pneumonia (UIP) (2). The 
definition of IPF requires the exclusion of other forms of interstitial pneumonia including other 
idiopathic interstitial pneumonias (IIP) and interstitial lung disease (ILD) associated with 
environmental exposure, medication, or systemic disease (2).
IPF predominantly presents in older individuals (cases in persons aged less than 50 years are 
rare), with a preponderance in men and previous or current smokers. Patients present with 
unexplained chronic exertional dyspnea, and commonly with cough, bibasilar inspiratory 
crackles, and finger clubbing.
7.2
INCIDENCE AND PREVALENCE
Overall, epidemiological data on the incidence and prevalence of IPF are limited, as stated in 
the consensus statement issued by ATS/ERS/JRS/ALAT (2). IPF prevalence varies widely 
between 1.25 and 63 cases per 100,000 of population in several epidemiological studies (1, 3, 
9-12). Incidence of IPF is also variable. A systematic review reported an incidence range of 
2.8-9.3 per 100,000 population per year in Europe and North America (1). In this analysis, it 
was noted that there was an increase in IPF incidence over time according to most studies, but 
mortality appears to plateau and even decline in USA and Denmark (13, 14). Regarding Greece, 
Karakatsani et al conducted a multicenter survey in 2009, using an one page questionnaire, in 
order to evaluate the incidence and prevalence of Interstitial Lung Diseases in Greece (10). 
Centers covering about 60% of Greek population were analyzed. A total of 967 cases of ILDs 
were registered. The most frequent disease was sarcoidosis (34.1%), followed in decreasing 
order by IPF (19.5%). The annual incidence of IPF was estimated to be 0.93 cases per 100,000, 
whereas prevalence was estimated to be 3.38 cases per 100,000. Since then though, the 

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diagnostic criteria, the international guidelines, the standard medical care and the composition 
of the population have changed and possibly these data do not reflect the current population of 
IPF patients (2, 5, 15).
7.3
DIAGNOSIS
According to the consensus statement jointly issued by ATS/ERS/JRS/ALAT in 2011, the 
diagnosis of IPF requires the following (2):
•
Exclusion of other known causes of ILD (e.g., domestic and occupational 
environmental exposures, connective tissue disease, and drug toxicity).
•
The presence of a UIP pattern on HRCT in patients not subjected to surgical lung 
biopsy.
•
Specific combinations of HRCT and surgical lung biopsy pattern in patients subjected 
to surgical lung biopsy.
7.4
NATURAL COURSE
Data on the natural course of IPF are from retrospective and a few prospective studies, 
including the placebo arms of clinical trials (limited to short observation periods and by in-
/exclusion criteria). The previously reported median survival time of 2-3 years from the time 
of diagnosis could be an underestimate, at least when accounting for patients with preserved 
lung function. Notably, the natural course is unpredictable for a given patient at the time of 
diagnosis, while the majority of patients experience steady worsening (slow progression), other 
remain stable, or have rapid progression of disease (9, 10). Acute respiratory worsening either 
due to secondary complications (e.g. pneumonia, pulmonary embolism, pneumothorax or 
cardiac failure) or due to unknown reasons (in this case the term acute exacerbation is used) 
are suggested to occur in about 5-10% annually (2, 16, 17). A recent retrospective review of 
461 patients with IPF has found that the 1- and 3-year incidences of acute exacerbations were 
14.2% and 20.7%, respectively (10).

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7.5
THERAPY
Until recently, there was no effective pharmacological treatment for IPF, other than lung 
transplantation that was considered the only survival improving intervention. Since 2011, two 
novel agents, pirfenidone and nintedanib,  have been approved by both EMA and FDA for 
patients with IPF, on the basis of phase III randomized clinical trials (RCTs) showing that these 
agents reduce the decline of lung function in comparison to placebo (18-21). 
Nintedanib is a multi-target tyrosine kinase inhibitor with activity against vascular endothelial 
growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor 
(PDGF) receptors, that are implicated in the pathogenesis of IPF (22, 23). Three RCTs – one 
phase 2 study (TOMORROW) and two replicate phase 3 studies (INPULSIS-1 and INPULSIS-
2) – have been conducted to evaluate efficacy of nintedanib in IPF (20, 21). The two phase 3 
trials met their primary endpoint showing that nintedanib at a dose of 150mg twice daily 
reduced statistically significant the adjusted annual rate of decline in FVC (21). Furthermore, 
pooled analysis of all three RCTs conducted with nintedanib in IPF showed a trend for reduced 
mortality and statistically significant reduction in the number of acute exacerbations among 
IPF patients treated with nintedanib (20, 21).
Both drugs have also received conditional recommendation for use according to the latest 
ATS/ERS/JRS/ALAT clinical practice guidelines for IPF (15). 
7.6
RATIONALE FOR THE PRESENT STUDY
Due to the rarity of IPF, there are very limited data regarding the patients’ population, the 
natural course of the disease and the medical treatment these patients receive, as highlighted 
by the call for action towards a worldwide IPF registry (5). Especially for the Greek population, 
very few data are available regarding the use  of nintedanib in cohorts of patients with IPF 
either pre-treated or treatment-naïve, also in terms of Patients Reported Outcomes (PRO) (6). 
The recently launched observational study INDULGE-IPF (NCT03074149) will provide 

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essential data regarding the natural course of IPF and the treatment of the disease – including 
the use of nintedanib – in the Greek population. 
In a chronic disease like IPF, the goal of pharmacological treatments should not be only 
survival prolongation, but also delay in the progression of the disease and on the clinical 
deterioration of patients, i.e. delay in worsening of symptoms and quality of life. In IPF there 
is a paucity of well validated PRO measures. In the pooled analysis of nintedanib randomized 
trials in IPF, the use of SGRQ questionnaire as a measurement of health related quality of life 
provided evidence  for a modest effect of nintedanib on the delay of  clinical deterioration of 
patients (4, 7). In addition a German IPF registry (INSIGHTS-IPF) has recently published 
results for patient reported outcomes (PROs) in enrolled patients, showing IPF patients under 
real-life conditions have lower HRQoL compared to those in clinical studies (8). In the Greek 
population though, analogous results regarding the effect of nintedanib on SGRQ as well as 
other PRO measures are lacking. 
In pharmacological treatments, efficacy is of outmost importance. In chronic diseases like IPF, 
the approval of a new effective treatment may lead to long-term exposure to the drug. This is 
beneficial in terms of disease outcomes for the patients but may also be accompanied by 
adverse events associated with the prolonged use of the treatment. IPF is a progressive disease
and current treatments have shown to slow disease progression. In addition, randomized 
clinical trials with nintedanib have shown that the drug did not adversely affect the quality of 
life of the patients at least as this was evaluated by the SGRQ questionnaire. However, detailed 
description of the several parameters related with the quality of life of IPF patients under 
treatment with nintedanib may provide further insight for the optimal use of the drug and the 
appropriate management of the patients. Furthermore, such data could provide clinicians with 
valuable information related to the anticipated evolution of the quality of life of IPF patients 
under nintedanib treatment. 
7.6.1
Rationale for questionnaires used
In this study, PROs will be used in a cohort of newly diagnosed IPF patients that have recently 
started treatment with nintedanib in order to provide relevant information regarding IPF-related
symptoms and their impact on several aspects of everyday life activities including 

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psychological consequences. Periodical completion of PROs will allow to record in this cohort 
of patients’ evolution of IPF symptoms and their effects on HRQoL. Finally, adherence to 
treatment will be recorded. Patients will be reporting on very specific symptoms (e.g., cough, 
dyspnoea) and their functional impact, which are concepts proximal to patients’ experience 
with the disease and treatment. Although an assessor bias cannot be disregarded in an open-
label setting, it is unlikely that this bias would be of such magnitude as to invalidate the data 
collected through PROs.
Instruments implemented in the study - namely the St George’s Respiratory Questionnaire 
(SGRQ) (24), the modified Medical Research Council scale (mMRC) (25), the Cough - Visual 
Analogue Scale (Cough - VAS), the Simplified Medication Adherence Questionnaire (SMAQ)
(26) and Generalized Anxiety Disorder 7-item scale (GAD-7) (27) - have been selected on the 
basis of their content validity and performance and to minimize patients’ completion burden. 
More specifically SGRQ is a self-administered, 50-item questionnaire assessing three domains: 
symptoms, activity and impact. The symptoms domain addresses the frequency and severity of 
respiratory symptoms; the activity domain assesses activities that cause or are limited by 
breathlessness and the impact domain taps a range of aspects concerned with social functioning 
and the psychological impact of the disease. SGRQ was initially developed for use in patients 
with COPD or asthma (24), but has also been used for IPF patients (4, 28). The total SGRQ 
score and the score for each domain range from 0 to 100, with higher scores indicating worse 
health-related quality of life. A minimally important difference in the score has not been 
established for patients with idiopathic pulmonary fibrosis; in patients with chronic obstructive 
pulmonary disease, this difference is 4 points.
Analogously, mMRC is a modified medical research council dyspnoea scale that uses same 
descriptors as the original MRC scale. The descriptors of the mMRC scale are numbered 1-5 
and are used to estimate the patient’s perception of breathlessness. The specific scale has been 
validated as a measurement of disease severity in IPF patients(29). 
Cough - VAS has been used as an easy and fast method to assess intensity of IPF related cough 
and is a recommended instrument for IPF patients (30).

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SMAQ is a six-item questionnaire that estimates in a qualitative and semi-quantitative manner 
the adherence of patients to treatment. SMAQ has already been validated for several medical 
and non-medical interventions (26). 
Finally, GAD-7 is a 7-item instrument validated for anxiety evaluation that could be used in 
outpatient setting.

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8.
RESEARCH QUESTION AND OBJECTIVES
The aim of this non-interventional-study based on newly collected data is to collect data on 
various important PROs in patients with IPF that could provide useful insights about HRQoL 
over 52 weeks in patients treated with nintedanib in the real world setting in Greece. 
Primary objective:
!
To evaluate changes from baseline of HRQoL for IPF patients treated in current clinical 
practice in Greece with nintedanib at time-points of 3, 6, 9 and 12 months over a 52-weeks 
period, via SGRQ (For a sample of the English version please refer to ANNEX 3: SGRQ).
Secondary objectives are:
!
To assess changes, from baseline, in dyspnoea and cough in IPF patients treated with 
nintedanib in current clinical practice in Greece at time-points of 3, 6, 9 and 12 months 
over a 52 weeks period, via specific questionnaires, such mMRC score (For sample of the 
English version please refer to ANNEX 3: mMRC) and Cough - Visual Analogue Scale 
(Cough - VAS) respectively (For sample of the English version please refer to ANNEX 3: 
Cough - VAS).
!
To estimate the adherence to nintedanib treatment in current clinical practice at time-points 
of 3, 6, 9 and 12 months over a 52 weeks period via SMAQ Questionnaire (adapted for the 
treatment of idiopathic pulmonary fibrosis (IPF) ) – (For a sample of the English version 
please refer to ANNEX 3: SMAQ).
!
To measure anxiety in IPF patients treated with nintedanib in current clinical practice in 
Greece at time-points of baseline, 3, 6, 9 and 12 months over a 52 weeks period via GAD-
7 Questionnaire (For a sample of the English version please refer to ANNEX 3: GAD-7).
!
To estimate the use of Long Term Oxygen Treatment (LTOT) among IPF patients under 
treatment with nintedanib in current clinical practice in Greece at time-points of baseline, 
3, 6, 9 and 12 months over a 52 weeks period.

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9.
RESEARCH METHODS
9.1
STUDY DESIGN
This is a National, multi-center, non-interventional, prospective cohort study aiming to enroll 
240  IPF patients receiving treatment with nintedanib in a consecutive manner from 10-12 
reference centers across Greece, representative of the entire Greek population. Recruitment 
will last for 36 months and patients will be followed over a period of 52 weeks. Only 
consecutive patients with newly diagnosed IPF patients (initial IPF diagnosis no more than 3 
months prior to enrolment) according to 2011 ATS/ERS/JRS/ALAT guidelines who are 
initiating treatment with nintedanib will be enrolled to restrict selection bias. A baseline visit 
and estimated 4 follow up visits will be performed during the follow-up period according to 
clinical practice. In the context of this study, participating physicians shall follow each enrolled 
patient for a planned observation period of 12 months, starting from the date of baseline visit 
and ending at the earliest of treatment discontinuation, withdrawal of consent, physician’s 
decision to withdraw the patient, 12-month observation period completion, death or any other 
discontinuation criterion is met.
Patients that permanently discontinue nintedanib treatment for any reason (e.g. due to AE, 
consent withdrawal, lost to Follow-up) prior to the follow up period completion, will no longer 
be followed-up for the study and the visit that nintedanib discontinuation is recorded will be 
considered as their end of study visit.
9.2
SETTING
9.2.1
Study sites
This is a National multicenter study that will enroll patients in 10-12 sites, academic hospitals 
and reference centers. All included sites are reference centers for IPF. Furthermore, sites both 
in Athens and rest of Greece are included in the study so as patients enrolled will constitute a 
representative population of IPF patients in Greece. 

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9.2.2
Study population
Newly diagnosed IPF patients initiating treatment with nintedanib according to their 
physician’s clinical decision will be enrolled in this study. In details, patients will be eligible 
to enroll in the study if the fulfil all the inclusion criteria and none of the exclusion criteria:
Inclusion criteria
!
Patients ≥40 years of age.
!
Patients that have signed Informed Consent Form.
!
Treatment naive patients with an initial IPF diagnosis no more than 3 months prior to 
enrolment according to 2011 ATS/ERS/JRS/ALAT guidelines who are initiating 
treatment with nintedanib (as monotherapy for IPF), the latest on the enrollment day or 
have initiated treatment with nintedanib (as monotherapy for IPF) within the past 7 days 
prior to enrolment.
!
Patients for whom the decision to prescribe therapy with nintedanib according to the 
locally approved product’s Summary of Product Characteristics (SmPC) has already been 
taken prior to their enrolment in the study and is clearly separated from the physician’s 
decision to include the patient in the current study.
!
Patients that are able to read, understand and complete the study specific questionnaires. 
Exclusion criteria
!
Treatment with nintedanib for more than 7 days prior to study enrolment.
!
Patients receiving a combination therapy of nintedanib & pirfenidone for IPF.
!
Patients that meet any of the contraindications to the administration of the study drug 
nintedanib according to the approved SmPC.
!
Prior treatment with pirfenidone or other treatment for IPF.
!
Participation in an interventional study. 
!
Patients currently receive treatment with any investigational drug/device/intervention or 
have received any investigational product within 1 month or 5 half-lives of the 
investigational agent (whichever is longer) before the initiation of therapy with 
nintedanib.

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According to study design, enrolled patients will constitute a representative population of 
newly diagnosed IPF patients in Greece. Recruitment will last for 36 months  and patients will 
be followed over a period of 52 weeks post enrollment. A baseline visit and estimated 4 follow 
up visits will be performed during the follow-up period according to clinical practice. Patients
will be included in a consecutive manner at each site between February 2019 and February 
2022 in order to avoid selection bias.
A subject screening log should be kept at the site, recording basic information (e.g. initials, 
gender, date of birth, reason for not enrolling the patient etc.) on all patients who were invited 
to participate in the study, with the information on the eligibility (or reasons for non-eligibility) 
and date of signed informed consent. In the case of refusal, reasons for refusal should be given. 
In addition, a log of all patients included into the study (i.e. having given informed consent) 
will be maintained in the study file at the study site.
9.2.3
Study visits
The study is scheduled to run for 4 years in total, i.e. 3 years of recruitment and 1 year of 
follow-up. During the follow up period, data will be collected on 4 standard clinical visits 
which usually are scheduled around: 3-months (± 1 month), 6-months (± 1 month), 9-months 
(± 1 month), 12-months (± 1 month) until the end of participation in the study. Patients that 
permanently discontinue nintedanib treatment for any reason (e.g. due to AE, consent
withdrawal, lost to Follow-up) prior to the follow up period completion, will no longer be 
followed-up for the study and the visit that nintedanib discontinuation is recorded will be 
considered as their end of study visit. 
9.2.4
Patient discontinuation
Patients will be followed up for a 52-weeks follow-up period according to clinical practice and 
will be considered that completed the study upon completion of the last FU data collection at 
week 52. Patients that withdraw from the study prior to the follow up period completion, for 
any reason (consent withdrawal, lost to follow up) will no longer be followed-up for the study 
and the visit that discontinuation is recorded will be considered as their final, end of study visit.

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In case of patient’s permanently treatment discontinuation for any reason (e.g. due to AE, 
physician’s decision), patients will be considered as prematurely/early discontinued and will 
not be further followed up in the scope of the study. The visit that discontinuation is recorded 
will be considered as their final, end of study visit.
Patients that temporarily interrupt treatment with nintedanib, up to 28 days, will continue 
follow up activities according to the study plan and will not be discontinued from the study. In 
case of dose reduction during the course of the study and re-start, patients will continue their 
participation and information on treatment administration will continue to be captured (dose 
reduction, treatment re-start and dose). 
Patients reserve the right to discontinue their participation in the study at any time during its 
conduct and for any reason, without having to justify their decision and with no impact on their 
future medical care and therapy.
Consent withdrawal means that a patient does not want or is unable to further continue 
participating in the study. 
The reasons for patient’s discontinuation may include the following:
!
patient’s withdrawal of informed consent;
!
discontinuation of study treatment (nintedanib) due to any reason;
!
the patient meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation;
!
enrollment or planned participation in any clinical trial, at any time during the study 
observation period, in which the patient has been or will be exposed to an investigational 
product (pharmaceutical agent or device) or intervention;
!
investigator’s/physician’s decision;
!
significant protocol deviation/violation.

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Patients, who withdraw from the study, should be asked about the reason(s) for discontinuation 
and the occurrence of any adverse events, and, if applicable, they shall be examined and 
evaluated by the investigator as per the procedures defined in the Final / Discontinuation Visit. 
Furthermore, investigators will have the right to withdraw any patient from the study, if 
according to their clinical judgment this decision is considered to be in the patient’s best interest.
If a patient withdraws or is removed from the study for any reason, the reason for and date of 
the discontinuation as well as the date of the last dose of study medication should be recorded 
in the appropriate section of the electronic Case Report Form (eCRF).
9.2.5
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 continuation 
of the study, or any other administrative reasons.
3. Violation of Good Clinical Practice (GCP) (as applicable), Good Pharmacoepidemiology 
Practice (GPP), 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
All patients included in the study will receive nintedanib based on the clinical decision of their 
treating physician. Normally nintedanib standard dose is 150mg twice daily, as per the SmPC. 
It is possible to reduce the dose of nintedanib to 100mg twice daily in case of intolerance. 

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Patients will be followed up until end of study period (in case they receive treatment with 
nintedanib for a 52-weeks follow-up period according to clinical practice) or until 
discontinuation. In case of dose reduction this information will be captured and patients will 
continue to be followed-up in the study. 
9.3.2
Endpoints 
9.3.2.1
Primary endpoint
The primary endpoint of the study is:
!
The mean change from baseline in HRQoL (with reference to SGRQ score, both total 
score and score in each of the SGRQ domains) of patients under treatment with 
nintedanib, as assessed by the changes in SGRQ score at time-points of 3, 6, 9 and 12 
months over the 52 weeks follow-up period.
9.3.2.2
Secondary endpoints 
The secondary endpoints of the study are:
!
The mean change from baseline to 3, 6, 9 and 12 months follow up period of 
dyspnoea burden, as measured via changes in the mMRC score 
!
The mean change from baseline to 3, 6, 9 and 12 months follow up period of cough 
burden, as measured via changes in the Cough - Visual Analogue Scale (Cough -
VAS) .
!
Percentage of adhered patients to nintedanib treatment at time-points of 3, 6, 9 and 12 
months over the 52 weeks follow up period, as measured via SMAQ questionnaire
(adapted for the treatment of idiopathic pulmonary fibrosis (IPF).
!
The mean change from baseline to 3, 6, 9 and 12 months follow up period of anxiety
in patients treated with nintedanib , as measured via GAD-7 questionnaire.
!
Percentage of patients that use LTOT at time-points of 3, 6, 9 and 12 months over the 
52 weeks follow up period.

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9.3.3
Covariates
Due to the non - interventional nature and design of this study, it does not require strict timeline 
visit schedule. Patients will receive treatment with nintedanib according to standard clinical 
practice with regards to approximate visit frequencies described above, type of performed 
assessments and according to local prescription requirements.
Following identification of a potential patient, the investigator will follow the below listed 
procedures:
1.
Review of individual patient’s medical history, to confirm that the inclusion/exclusion 
criteria are met.
2.
Explanation of the study objectives to the patient and receipt of signed and dated 
informed consent, after providing the patient with sufficient time to read carefully and 
understand the information sheet.
3.
Data collection from the medical records of eligible for enrollment patients, as required 
by eCRF, and eCRF completion.
Please refer to Section 11.2 for details regarding Adverse Event and Serious Adverse Event 
Collection and Reporting.
A tabulated schedule of assessments that provide information regarding the recommended 
timeline of data collection and represents the standard clinical care of IPF treated patients is 
listed below in Table 1. The exact definitions of the variables are the following:
!
Basic (Socio-) demographic data. Age (date of birth), gender (sex), race
!
Anthropometric characteristics. Height and weight of the patients will be recorded

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!
Physical and vital signs examination. Blood pressure (sitting systolic and diastolic 
arterial pressure), and heart rate will be recorded
!
IPF risk factors. These include smoking habit (past or current smoker, non-smoker or 
unknown) and number of pack-years, environmental and occupational exposure; 
alcohol and substance abuse, exposure to drugs associated with pulmonary fibrosis, 
exposure to viral infection possibly related to IPF, gastro-esophageal reflux, genetic 
factors (family history), or others.
!
Co-morbidities and concomitant treatments (medication category/class).
!
Date and method of IPF diagnosis. Dates and results of High Resolution Chest CT 
(HRCT), surgical lung biopsy and bronchoalveolar lavage will be recorded if already 
performed
!
IPF symptoms. Presence of dyspnea, cough, fatigue, dizziness, chest pain and anxiety 
as reported by the patient will be recorded. 
!
Nintedanib treatment. Start date and stop date, dates of treatment interruption, dose 
reductions and dose re-escalations will be recorded
!
Assessment of lung function and exercise capacity. Data recording FVC, DLCO and 6-
minutes walking test will be recorded at baseline if already performed. 
!
Questionnaires. The following questionnaires will be completed by the enrolled 
patients prior to any clinical assessment at each visit of the study (baseline, follow-up 
visits and final visit): SGRQ, mMRC Score, Cough - VAS and GAD-7. SMAQ 
questionnaire (adapted for the treatment of idiopathic pulmonary fibrosis (IPF) will be 
completed by the enrolled patients prior to any clinical assessment at each follow-up 
visit of the study.
!
Long Term Oxygen Therapy, . It will be recorded whether the patient is on LTOT or 
not.
!
Survival status. Patient dead or alive.

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Table 1
List of variables to be documented (if available) at scheduled visits
Variable 
Assessment
Follow up
1-3*
Final Visit (12 
months 
follow 
up ± 1 month or 
study 
discontinuation 
visit)
Eligibility criteria
x
Baseline information (assessment)
(Socio-)demographic variables: age
(date of birth), gender, race
x
Anthropometric characteristics: height
x
Anthropometric 
characteristics: 
body
weight
x
x
x
Physical 
examination: 
Blood 
pressure
(sitting systolic and diastolic arterial
pressure), heart rate
x
x
x 
(Possible) IPF risk factors
Cigarette 
smoking 
incl. 
pack 
years
(Categorized 
as 
never/past/current/unknown. 
For 
past/current, specify packs/year and for 
past, number of years smoking one pack 
per day); environmental and occupational 
exposure; alcohol and substance abuse;
exposure 
to 
drugs 
associated 
with 
pulmonary fibrosis;
exposure to viral 
infection possibly related to IPF; gastro-
x

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oesophageal reflux; genetic factors (family 
history); others
Co-morbidities
x
Concomitant medications
(changes in 
concomitant medications in follow ups)
x
x
x
IPF
Baseline information (assessment) on IPF
First symptoms; date of first diagnosis, 
dates and results of HRCT, surgical lung 
biopsy, bronchoalveolar lavage.
x
Symptoms
Dyspnea, cough, fatigue, dizziness, chest 
pain, anxiety
x
x
x 
Functional assessment
Lung function test (FVC, DLCO)
6-minute walk distance 
x
Treatment with Nintedanib (start date, 
stop date, restart date in case of temporary 
discontinuation and daily dose)
x
x
x
Long-Term-Oxygen-Therapy 
(liquid 
and/or concentrate)
x
x
x 
Questionnaires
SGRQ
x 
x 
x 
mMRC
x 
x 
x 

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Cough - VAS
x 
x 
x 
GAD-7
x 
x 
x 
SMAQ 
x 
x 
Survival status 
x 
x 
Reason for treatment discontinuation
x
For abbreviations, please refer to glossary.
*3-months (± 1 month), 6-months (± 1 month), 9-months (± 1 month), 
** Final visit is designated as either the 12 months (± 1 month) follow up visit for all patients that 
remain on study until that time-point or the visit performed at the time of a patient’s discontinuation or 
withdrawal from the study.
9.4
DATA SOURCES
The study will mainly include the recording of new data through a web-based system for data 
collection. Data will be collected by the study doctors as they occur according to standard 
clinical practice in the approximate visiting schedule indicated above. 
Source (primary) patient data related to their medical and IPF history will be collected by the 
investigators from the patient’s medical files/records and will be documented in the relevant 
eCRF section. 
Data regarding treatment modifications, concomitant treatments, study related routine clinical 
assessments, and survival status will also be collected. The procedures that should be 
performed at each study visit are presented as a study flow chart in Table 2.

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Table 2
Study flow chart
Baseline 
visit
FU1
3-month 
follow-
up visit ± 
1 month)
FU2
6-month 
follow-up 
visit (± 1 
month)
FU3
9-month 
follow-up 
visit (± 1 
month)
Final visit (12 
months follow-
up visit ± 1 
month or after 
study 
discontinuation
visit)
Inclusion/exclusion 
criteria
X
ICF signed
X
Sociodemographic 
variables (age/date of 
birth, gender, race)
X
Anthropometric 
characteristics (body 
weight)
X
X
X
X
X
Anthropometric 
characteristics 
(height)
X
Physical examination
X
X
X
X
X
Blood pressure 
(sitting systolic and 
diastolic arterial 
pressure), heart rate
X
X
X
X
X
Completion of 
Questionnaires 
(SGRQ, mMRC, 
X
X
X
X
X

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Cough - VAS, GAD-
7)
Completion of 
SMAQ Questionnaire
X
X
X
X
Comorbidities
X
Concomitant 
medication
(medication 
category/class)
X
X
X
X
X
Treatment with 
nintedanib
X
X
X
X
X
Clinical evaluation
X
X
X
X
X
Survival status
X
X
X
X
X
Adverse events 
collection and 
recording
X
X
X
X
X
9.5
STUDY SIZE
This observational study will be analyzed descriptively following standard statistical and 
epidemiological methods. Approximately 240  patients are expected to be included in the study 
in a consecutive manner between February 2019 and February 2022 from the participating sites 
according to the feasibility procedure of the sites. The number of included patients as well as 
the duration of the study is not defined by a formal sample size and power calculation, but is 
based mainly on the availability of eligible IPF patients as well as patient population in the
selected sites.
Table 3 describes expected 95% confidence limits and precision of the estimate of mean change 
from baseline of SGRQ Total Score at week 52, according to different assumption of mean 

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change from baseline and standard deviation (SD). Sample size is assumed to be 200 because 
it is expected that some patients discontinue nintedanib treatment prior to the follow-up period 
completion.
Because SD is unknown at the planning stage, it needs to be assumed based on the previous 
trials. In INPULSIS trials, the sample standard deviation of the change from baseline in SGRQ 
total score at Week 52 was about 16. In the real-world setting, the more diverse patients are 
expected compared to patients in INPULSIS trials. Therefore, we assume that SD may range
from 16 to 22. These calculations are based on a total number of 200 evaluable study 
participants. Taking into account an approximate dropout rate of 17-20%, a final number of 
240  patients will be enrolled in the study.
Table 3
95% confidence limits and precision of the estimate of mean change 
from baseline of SGRQ Total Score at week 52, according to different 
assumption of mean change from baseline and standard deviation.
Ν
Mean dif
Sd
95% CI
ω
200
2
16
-0.2
4.2
4.4
200
2
18
-0.5
4.5
5.0
200
2
20
-0.8
4.8
5.5
200
2
22
-1.0
5.0
6.1
200
3
16
0.8
5.2
4.4
200
3
18
0.5
5.5
5.0
200
3
20
0.2
5.8
5.5
200
3
22
0.0
6.0
6.1
200
4
16
1.8
6.2
4.4
200
4
18
1.5
6.5
5.0
200
4
20
1.2
6.8
5.5
200
4
22
1.0
7.0
6.1
200
5
16
2.8
7.2
4.4
200
5
18
2.5
7.5
5.0

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200
5
20
2.2
7.8
5.5
200
5
22
2.0
8.0
6.1
9.6
DATA MANAGEMENT
This study will include the collection of new data that will be recorded in an existing web-
based database in a consecutive manner (electronic case report form, eCRF) as well as 
transferring already existing data to the system from medical charts. The patients will be 
identified by subject identification number, site number, and study identification number.
Investigators will enter the data of their patients directly into an internet-based electronic case 
record form. At data entry, plausibility checks (e.g., range checks, conditional checks, etc.) will 
be performed. Data will be entered in the eCRF system by the study personnel at the 
Investigator’s site, according to the Investigator Instructions Manual. Data entered in the eCRF 
system will be automatically saved to a central database and changes tracked to provide an 
audit trail. When data have been entered, reviewed and edited, the Investigator shall sign the 
e-CRF electronically as per the agreed project process and data will be locked to prevent further 
editing.
Query management will be performed through built-in query management functionality that 
will be incorporated into the eCRF.
Prior to the onset of data management activities, a detailed data management plan (DMP) will 
be issued describing the procedure to be followed for processing all collected study data in 
order to ensure they are valid, complete and accurate for statistical analysis. In addition, aiming 
at ensuring the expected quality of data, a thorough data cleaning session will be applied. When 
all data have been properly validated and the quality control procedure has been completed, a 
declaration of database lock will take place so that it can be confirmed that all important actions 
have been properly performed. In addition, prior to database lock and prior to the initiation of 
any statistical analysis activities a comprehensive statistical analysis plan (SAP) will be drafted. 

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The SAP will also include information regarding the statistical software(s) to be used for the 
analysis of the study data. 
9.7
DATA ANALYSIS
9.7.1
Main analysis
The objective of this study is neither to confirm nor to reject any predefined hypothesis; 
therefore, the nature of the statistical analyses will be exploratory and descriptive.
Continuous variables will be listed as median with interquartile and/or other percentiles, and 
as mean value with standard deviation (SD), along with minimum and maximum values and 
95% confidence intervals (if needed). Categorical values will be summarized as in absolute 
and relative frequencies. 
In terms of missing data, any reasonable attempt will be undertaken to ensure completeness of 
data collection in this study. Imputation of missing values will not be performed. Missing 
values will be differentiated from negative answers.
Analysis of Primary Outcome
Summary statistics based on observed data will be used to describe the SGRQ scores at each 
visit and the change of SGRQ scores from baseline to each study visit until week 52.
Evaluation of SGRQ total score and each domain score regarding change from baseline until 
each study visit, will be performed by mixed models for repeated measures, assuming that 
missing values are missing at random. Modelling details will be provided in the SAP.
Baseline is defined at time patient is enrolled in the study.
Analysis of secondary outcomes
Mean change from baseline during the 52 weeks follow up period (3, 6, 9, 12 months) for the 
following endpoints:

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!
burden of cough as measured via Cough - Visual Analogue Scale (Cough - VAS) and
!
anxiety as measured by GAD-7 score,
will follow the same analysis as the primary outcome. 
Baseline is defined at time patient is enrolled in the study.
Adherence to nintedanib will be accessed via frequency tables (n, %) of each SMAQ item in 
every follow up visit.
The number and percentage of patients that use LTOT during the 52 weeks follow up period 
will also be displayed.
The distribution of patients with respect to dyspnoea based on the mMRC score at every study 
time-point, will be presented in frequency tables (N, %). 
Safety Analysis 
All adverse events recorded during the trial will be presented in listings. AEs will be coded 
based on the MedDRA terminology.
9.8
QUALITY CONTROL
In order to ensure the quality and integrity of data throughout the course of the study, proper 
quality control mechanisms and methods will be applied. All procedures will be described in 
detail in the study specific Data Management Plan (DMP) and Statistical Analysis Plan (SAP). 
eCRF files from each participating site will be stored in CD-ROMs after completion of the 
study and will be distributed to the participating sites.

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The investigators will be provided with a folder/file by the authorized representative of the 
study, in which they will be required to keep and store all study related documents. All study 
documents will be stored in this file by the Investigator. The contents of this file/folder may be 
subjected to audit/inspection by an authorized auditor, regulatory authorities or Institutional 
Review Boards (IRBs)
Boehringer Ingelheim’s department of Quality Assurance may conduct quality control visits to 
the participating sites to ensure proper implementation of the study protocol and all related 
regulatory and BI procedures.
The Sponsor or designee (contracted CRO) will assure database quality by reviewing the data 
entered into the CRFs by investigational staff for completeness and accuracy, and in 
accordance with the data validation plan.
9.9
LIMITATIONS OF THE RESEARCH METHODS
The basic limitations of the study relate to the general limitations that concern non -
interventional studies. Since this study is a non - interventional study, it could be possible that 
different parameters which were not assessed and thus remain unknown, might lead to 
overestimating/underestimating/non-detection 
of 
differences 
of 
specific 
patients’ 
characteristics. Survival in IPF cohort studies is affected by the clinical characteristics and the 
related baseline patient conditions, as well as by the time interval between the diagnosis and 
the inclusion of the patient in the protocol. In this study, only patients with newly diagnosed 
IPF committed to treatment with nintedanib according to the decision of their treating 
physicians’ will be included. This does not preclude, but definitely minimizes significant 
differences in the baseline characteristic of the enrolled patients. 
Selection bias on the patient level will be minimized by consecutive enrollment.

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No re-evaluation of patients in this study is initially foreseen, something, that can lead to the 
conclusion that patients with overlapping diagnoses (like fibrosing interstitial pneumonia of 
unknown cause) have been included in the study, thus depicting the difficulties in differential 
diagnosis in clinical practice. However, given the fact that the participating sites are reference 
centers for IPF, and considering the eligibility criteria that apply for this study, the expected 
bias might be low. 
The study is going to provide evidence regarding the quality of life of IPF patients treated with 
nintedanib in reference centers that follow up about 70%-80% of IPF patients in Greece.
Given the small numbers and the heterogeneous population no comparisons and causal 
associations can be assessed as shown in Table 3 in Section 9.5. In addition, due to the small 
sample size this study is rather exploratory and no definite conclusions can be drawn regarding 
the efficacy of nintedanib. 
Regarding to patient information/recall bias that may be introduced by the collection of data 
pertaining to patient-reported outcomes, this will be mitigated through the use of widely used 
PROs that employ a short recall period as all questions refer to the symptoms and state of health 
at the day of completion. In addition, the self-administered PROs shall be completed by the 
patients themselves before the performance of any study-specific procedure(s) or clinical 
assessment(s) in order to avoid introducing any response bias.     
9.10
OTHER ASPECTS
None
9.10.1
Data quality assurance
Appropriate quality control procedures will be followed during this study so as to ensure 
quality and accuracy of the data. The delegated representative of the Sponsor (contracted CRO) 
will provide Investigators with a file for the archiving of all study documents. The contents of 

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this file may be subjected to inspection from the regulatory authorities or the Institution Review 
Boards (IRBs). Boehringer Ingelheim quality control department may perform audits in the 
participating centers in order to ensure that all study procedures are followed. The sponsor or 
its delegate (contracted CRO) will ensure electronic database quality through review of the 
captured data regarding their accuracy and completeness of data according to DMP. The eCRF 
data from each participating center will be saved in CD-ROM after the completion of the study 
and will be distributed to the centers.
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, either on 
paper or via remote data capture. 
Every doctor will have a study folder containing:
•
The study contract between the physician and 
•
The protocol
•
The patient identification list (not allowed to be used off site)
•
An approval letter by the Scientific Committee/Ethics Committee for the specific 
site
•
Informed consent forms
•
eCRF Sample printouts
9.10.2.1
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 eCRFs that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may need 
to request previous medical records or transfer records, depending on the study; also, current 
medical records must be available.
For eCRFs all data must be derived from source documents.
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/eCRFs and all source documents, including progress notes and copies of laboratory and 
medical test results must be available at all times for review by the sponsor’s clinical study 
monitor, auditor and inspection by health authorities (e.g. US Food and Drug Administration
(FDA)). The Clinical Research Associate (CRA) / Clinical Trial Manager (CTM) and auditor 
may review all CRFs/eCRFs and written informed consents. The accuracy of the data will be 
verified by reviewing the documents described in Section 9.10.2.1.
9.10.2.3
Storage of records
Patient’s files and other source documents must be kept for the maximum time period permitted 
by the hospital/institution or as defined below. The investigator must consult with the sponsor 
in case they wish to transfer the files to a third party, move them to a different location or if 
they are not capable of maintaining them for the defined period. 
The investigator should keep the study files (e.g. source documents like medical files, contracts, 
electronic files and signed informed consent forms) for as long as it is defined by the applicable 
laws and regulations. The sponsor is responsible for maintaining the documents for at least 25 
years. The archived data can be kept in electronic form so long as there are available backup 
copies in printed form, if it is required.

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The participating sites are responsible for the archiving of the necessary documents/evidence 
for 25 years at least or for as long as it is required by the local legislation.
9.10.3
Completion of study
The Institutional Review Board (Scientific/Administrative Board) in each participating 
hospital center needs to be notified about the end of the study (last patient out) or early 
termination of the study, unless it is differently required by the national regulations that govern 
the conduct of such studies in case these regulations have been amended until the completion 
of the study.

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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.
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 for the implementation of changes introduced by amendments.
Prior to patient participation in the study, written informed consent must be obtained from each 
patient (or the patient’s legally accepted representative) according to ICH GCP and to the 
regulatory and legal requirements of the participating country. Each signature must be 
personally dated by each signatory and the informed consent and any additional patient-
information form retained by the investigator as part of the 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.

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The patient must be informed that his/her personal study-related data will be used by 
Boehringer Ingelheim in accordance with the local data protection law. The level of disclosure 
must also be explained to the patient.
The patient must be informed that his / her medical records may be examined by authorized
monitors (CTM/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.
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.
Patient’s private data are going to be used by Boehringer Ingelheim and will be kept according 
to the requirements of the EU Data Protection Directive (95/46/EC) guidelines and the 
2016/679 EU regulation on the protection of natural persons with regard to the processing of 
personal data and on the free movement of such data and the national legislation regarding 
protection of private data. Data will be collected with the use of key codes. The identification 
codes will be used instead of patient names in order to protect patient identities when referring 
to study data. The level of disclosure should also be explained to the patient.
Only authorized staff (hospital staff, sponsor representatives including monitors, authority 
representatives) will have access to patients’ private data e.g. original source documents 
(medical records). The patient will agree to this specifically by providing informed consent and 
the appropriate statement will be included in the Informed Consent Form (ICF).

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The physician must comply with the confidentiality policy as it is defined within the Study 
Contractual Agreement. The physician will comply with the Protocol that has been approved 
by the Scientific Board/Ethics Committee. The physician is responsible for the conduct of all 
study aspects in the study site and validates the integrity of all forwarded to the sponsor data 
with their signature.

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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. 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 hospitalization, 
-
results in persistent or significant disability or incapacity, or 
-
is a congenital anomaly/birth defect.

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Life-threatening in this context refers to a reaction in which the patient was at risk of death at 
the time of the reaction; it does not refer to a reaction that hypothetically might have caused 
death if more severe.
Medical and scientific judgement should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life threatening or result in death or hospitalization but might jeopardize the 
patient or might require intervention to prevent one of the other outcomes listed above. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization or 
development of dependency or abuse. Any suspected transmission via a medicinal product of 
an infectious agent is also considered a serious adverse reaction.
Adverse Event of Special Interest (AESI)
The term 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.

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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 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 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).
•
The event is typically drug-related and infrequent in the general population not 
exposed to drugs (e.g. Stevens-Johnson syndrome).

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•
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; 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 nintedanib, 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. 

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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 
Nintedanib
immediately within 24 hours
All AEs with fatal outcome in patients 
exposed to Nintedanib
immediately within 24 hours
All non-serious ADRs associated with 
Nintedanib
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.
The NIS AE form and Pregnancy Monitoring Forms should be submitted to the 
Pharmacovigilance Department at
  For details regarding 

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Pregnancy Monitoring Forms, please refer to Section 11.2 paragraphs entitled, “Pregnancy” 
and “Expedited Reporting of AEs and Drug Exposure During Pregnancy.”
Reporting of related Adverse Events associated with any other BI drug
The investigator is encouraged to report all adverse events related to any BI drug other than the 
nintedanib according to the local regulatory requirements for spontaneous AE reporting at the 
investigator’s discretion by using the locally established routes and AE report forms. The term 
AE includes drug exposure during pregnancy, and, regardless of whether an AE occurred or 
not, any abuse, off-label use, misuse, medication error, occupational exposure, lack of effect, 
and unexpected benefit.
11.3
REPORTING TO HEALTH AUTHORITIES
Adverse event reporting to regulatory agencies will be done by the MAH according to local
and international regulatory requirements.

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12.
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY 
RESULTS
Participating physicians and Boehringer Ingelheim will be informed on the progress and status 
of the study on a regular basis. An Annual Report will be issued that contains a section on 
project management (recruitment status, information on technical and administrative issues) 
and tabular listings of data. Further, meetings of the National Scientific Committee as well as 
investigator meetings are planned (preferably in the context of major Pulmonology Meetings).
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.
Following database lock, a final report that summarizes the tables of the analysis and 
explanatory text will be written by the Data Management. Data management according to our 
contractual agreement will prepare a final Study Report which will be used as a basis for the 
final Report that will be written internally. After approval from the members of the National 
Scientific Committee and the sponsor, a final version will be generated that may be used for 
regulatory purposes, but also as basis for the publications of the study.
Every effort will be made, given the collected data, in order to produce scientific publications 
that will in turn contribute to better care for IPF patients and justify the scientific effort. The 
publication strategy and the authors’ list will be agreed between the Medical Department of 
Boehringer Ingelheim Hellas and the participating investigators. Boehringer Ingelheim Hellas 
will be the official owner of all collected date and results. Every study publication should be 
consistent with BI’s publication policy and guided by the Recommendations for the Conduct, 
Reporting, Editing, and Publication of Scholarly Work in Medical Journals of the International 
Committee of Medical Journals (ICMJE) (24).
This study together with the results will be posted to the web-based platform Clinicaltrials.gov 
(CT.gov), in the
EU electronic register of post-authorization studies -ENCEPP 

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(www.encepp.eu/encepp_studies/indexRegister.shtml) and in the platform of Non-
Interventional Studies (NIS) Register [Dilon
(www.dilon.sfee.gr)] according to local 
requirements. This webpage constitutes an electronic register of the NIS conducted in Greece 
and is hosted as part of the Hellenic Association of Pharmaceutical Companies (SFEE) 
website.

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13.
REFERENCES
13.1
PUBLISHED REFERENCES
1.
Hutchinson J, Fogarty A, Hubbard R, McKeever T. Global incidence and mortality of 
idiopathic pulmonary fibrosis: a systematic review. The European Respiratory Journal. 
2015;46(3):795-806 (R17-4824)
2.
Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An official 
ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines 
for diagnosis and management. American Journal of Respiratory and Critical Care Medicine. 
2011;183(6):788-824 (P11-07084)
3.
Anto JM, Cullinan P. Clusters, classification and epidemiology of interstitial lung 
diseases: concepts, methods and critical reflections. The European Respiratory Journal 
Supplement. 2001;32:101s-6s (R18-2836)
4.
Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy 
and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis. New England Journal of 
Medicine. 2014;370(22):2071-82 (P14-07514)
5.
Wilson JW, du Bois RM, King TE, Jr. Challenges in pulmonary fibrosis: 8--The need 
for an international registry for idiopathic pulmonary fibrosis. Thorax. 2008;63(3):285-7
(R16-3079)
6.
Tzouvelekis A, Karampitsakos T, Kontou M, Granitsas A, Malliou I, 
Anagnostopoulos A, et al. Safety and efficacy of nintedanib in idiopathic pulmonary fibrosis: 
A real-life observational study in Greece. Pulmonary Pharmacology & Therapeutics. 
2018;49:61-6 (P18-01159)
7.
Richeldi L, Cottin V, du Bois RM, Selman M, Kimura T, Bailes Z, et al. Nintedanib 
in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW 
and INPULSIS trials. Respiratory Medicine 2016.113:74-9 (P16-04370)
8.
Kreuter M, Swigris J, Pittrow D, Geier S, Klotsche J, Prasse A, et al. Health related 
quality of life in patients with idiopathic pulmonary fibrosis in clinical practice: insights-IPF 
registry. Respiratory Research. 2017;18:139 (R17-2575)
9.
Musellim B, Okumus G, Uzaslan E, Akgun M, Cetinkaya E, Turan O, et al. 
Epidemiology and distribution of interstitial lung diseases in Turkey. The Clinical 
Respiratory Journal. 2014;8(1):55-62 (R14-4379)
10.
Karakatsani A, Papakosta D, Rapti A, Antoniou KM, Dimadi M, Markopoulou A, et 
al. Epidemiology of interstitial lung diseases in Greece. Respir Med. 2009;103(8):1122-9
(R11-5060)
11.
Coultas DB, Zumwalt RE, Black WC, Sobonya RE. The epidemiology of interstitial 
lung diseases. American Journal of Respiratory and Critical Care Medicine. 1994;150(4):967-
72 (R03-2075)
12.
Gribbin J, Hubbard RB, Le Jeune I, Smith CJ, West J, Tata LJ. Incidence and 
mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax. 
2006;61(11):980-5 (R10-2818)
13.
Fernandez Perez ER, Daniels CE, Schroeder DR, St Sauver J, Hartman TE, 
Bartholmai BJ, et al. Incidence, prevalence, and clinical course of idiopathic pulmonary 
fibrosis: a population-based study. Chest. 2010;137(1):129-37 (R10-2800)

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14.
Kornum JB, Christensen S, Grijota M, Pedersen L, Wogelius P, Beiderbeck A, et al. 
The incidence of interstitial lung disease 1995-2005: a Danish nationwide population-based 
study. BMC Pulmonary Medicine. 2008;8:24 (R112-0229)
15.
Raghu G, Rochwerg B, Zhang Y, Garcia CA, Azuma A, Behr J, et al. An Official 
ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary 
Fibrosis. An Update of the 2011 Clinical Practice Guideline. American Journal of Respiratory 
and Critical Care Medicine. 2015;192(2):e3-19 (P15-07539)
16.
Martinez FJ, Safrin S, Weycker D, et al. THe clinical course of patients with 
idiopathic pulmonary fibrosis. Annals of Internal Medicine. 2005;142(12_Part_1):963-7
(R07-0258)
17.
Collard HR, Moore BB, Flaherty KR, Brown KK, Kaner RJ, Talmadge E. King J, et 
al. Acute Exacerbations of Idiopathic Pulmonary Fibrosis. American Journal of Respiratory 
and Critical Care Medicine. 2007;176(7):636-43 (R11-5151)
18.
King TE, Jr., Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg 
MK, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. The 
New England Journal of Medicine. 2014;370(22):2083-92 (R14-2103)
19.
Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, et al. 
Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised 
trials. Lancet. 2011;377(9779):1760-9 (R11-4827)
20.
Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, et al. 
Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. The New England 
Journal of Medicine. 2011;365(12):1079-87 (P11-11216)
21.
Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy 
and safety of nintedanib in idiopathic pulmonary fibrosis. The New England Journal of 
Medicine. 2014;370(22):2071-82 (P14-07514)
22.
Chaudhary NI, Roth GJ, Hilberg F, Muller-Quernheim J, Prasse A, Zissel G, et al. 
Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis. The European Respiratory 
Journal. 2007;29(5):976-85 (P07-07435)
23.
Coward WR, Saini G, Jenkins G. The pathogenesis of idiopathic pulmonary fibrosis. 
Therapeutic Advances in Respiratory Disease. 2010;4(6):367-88 (R18-2840)
24.
Jones PW, Quirk FH, Baveystock CM. The St George's Respiratory Questionnaire. 
Respir Med. 1991;85 Suppl B:25-31; discussion 3-7 (R98-0966)
25.
Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of 
the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients 
with chronic obstructive pulmonary disease. Thorax. 1999;54(7):581-6 (R04-1043)
26.
Knobel H, Alonso J, Casado JL, Collazos J, Gonzalez J, Ruiz I, et al. Validation of a 
simplified medication adherence questionnaire in a large cohort of HIV-infected patients: the 
GEEMA Study. Aids. 2002;16(4):605-13 (R18-2837)
27.
Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing 
generalized anxiety disorder: the GAD-7. Archives of Internal Medicine. 2006;166(10):1092-
7 (R18-2838)
28.
Swigris JJ, Wilson H, Esser D, Conoscenti CS, Stansen W, Kline Leidy N, et al. 
Psychometric properties of the St George's Respiratory Questionnaire in patients with 
idiopathic pulmonary fibrosis: insights from the INPULSIS trials. BMJ Open Respiratory 
Research. 2018;5(1):e000278 (P18-05386)
29.
Papiris SA, Daniil ZD, Malagari K, Kapotsis GE, Sotiropoulou C, Milic-Emili J, et al. 
The Medical Research Council dyspnea scale in the estimation of disease severity in 
idiopathic pulmonary fibrosis. Respir Med. 2005;99(6):755-61 (R18-2839)

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30. Manen MJG van, Birring SS, Vancheri C, Cottin V, Renzoni EA, Russell A-M, et al. 
Cough in idiopathic pulmonary fibrosis. European Respiratory Review. 2016;25(141):278-86
(P18-00823)
13.2
UNPUBLISHED REFERENCES
Not applicable

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ANNEX 1. LIST OF STAND-ALONE DOCUMENTS
Not applicable

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ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS
Study title: Investigating Trends in Quality of Life in Patients with IPF Under Treatment 
with Nintedanib
Study reference number:
Section 1: Milestones
Yes
No
N/A
Section 
Number
1.1
Does the protocol specify timelines for 
1.1.1 Start of data collection
6
1.1.2 End of data collection
6
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.
6
Comments:
1.1.3  Not required according to national requirements for non -interventional studies 
1.1.4  Not required as no interim analysis of data is scheduled 
1.1.5  The present study has not yet been registered in the European Union electronic 
Register of Post-Authorisation Studies (EU PAS register).

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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)
8
2.1.2 The objective(s) of the study?
8
2.1.3 The target population? (i.e. population or 
subgroup to whom the study results are 
intended to be generalized)
9.2.2
2.1.4 Which hypothesis(-es) is (are) to be tested?
2.1.5 If applicable, that there is no a priori
hypothesis?
Comments:
2.1.4 & 2.1.5 Νo hypothesis testing is going to be performed therefore no specific effects 
or endpoints are defined. 
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) 
9.1
3.2
Does the protocol specify whether the study is 
based on primary, secondary or combined data 
collection?
9.4

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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)
9.4
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)
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)
11
Comments:
Section 4: Source and study populations
Yes
No
N/A
Section 
Number
4.1
Is the source population described?
9.1
4.2
Is the planned study population defined in terms 
of:
9.2.2
4.2.1 Study time period?
4.2.2 Age and sex?
4.2.3 Country of origin?
4.2.4 Disease/indication?
9.2.2
4.2.5 Duration of follow-up?

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Section 4: Source and study populations
Yes
No
N/A
Section 
Number
4.3
Does the protocol define how the study 
population will be sampled from the source 
population? (e.g. event or inclusion/exclusion 
criteria)
9.2.2
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)
9.3.1
5.2
Does the protocol address the validity of the 
exposure measurement? (e.g. precision, accuracy, 
use of validation sub-study)
9.3.1
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?
Comments:
5.2. This is new data collection, thus the accuracy of exposure information is very high

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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?
9.3.2
6.2
Does the protocol describe how the outcomes are 
defined and measured? 
9.3.2
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)
9.5
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)
9.3.2
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)
9.2.2

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Section 7: Bias
Yes
No
N/A
Section 
Number
7.2.2. Information biases (e.g. misclassification of 
exposure and endpoints, time-related bias)
9.2.2
7.3
Does the protocol address the validity of the 
study covariates?
Comments:
No confounders or effect modifiers are discussed since no hypothesis testing or assessment 
of effects is being performed.
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:
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)
9.3.1, 9.4

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Section 9: Data sources
Yes
No
N/A
Section 
Number
9.1.2 Outcomes? (e.g. clinical records, laboratory 
markers or values, claims data, self-report, 
patient interview including scales and 
questionnaires, vital statistics)
9.3.2, 9.4
9.1.3 Covariates?
9.3.3, 9.4
9.2
Does the protocol describe the information 
available from the data source(s) on:
9.2.1 Exposure?(e.g. date of dispensing, drug 
quantity, dose,  number of days of supply 
prescription, daily dosage,  prescriber)
9.4
9.2.2 Outcomes?(e.g. date of occurrence, multiple 
event, severity measures related to event)
9.4
9.2.3 Covariates? (e.g. age, sex, clinical and drug 
use history, co-morbidity, co-medications, 
lifestyle)
9.4
9.3
Is a coding system described for: 
9.3.1 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)
9.4

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Comments:
Section 10: Analysis plan
Yes
No
N/A
Section 
Number
10.1 Is the choice of statistical techniques described? 
9.7.1
10.2 Are descriptive analyses included?
9.5
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?
9.7.1
10.6 Is sample size and/or statistical power estimated?
9.5
Comments:
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)
9.8, 9.10.2
11.2 Are methods of quality assurance described?
9.8
11.3 Is there a system in place for independent review 
of study results? 
Comments:
11.3 The study design does not require an independent review of the results. 

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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?
9.9
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)
12.2 Does the protocol discuss study feasibility? 
(e.g. study size, anticipated exposure, duration of 
follow-up in a cohort study, patient recruitment)
9.9
Comments:
Section 13: Ethical issues
Yes
No
N/A
Section  
Number
13.1 Have requirements of Ethics Committee/ 
Institutional Review Board been described?
10.1
13.2 Has any outcome of an ethical review procedure 
been addressed?
13.3 Have data protection requirements been 
described?
10.2

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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? 
5
Comments:
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
ST. GEORGE’S RESPIRATORY QUESTIONNAIRE (SGRQ)
This questionnaire is designed to help us learn much more about how your
breathing is troubling you and how it affects your life. We are using it to find out
which aspects of your illness cause you most problems, rather than what the
doctors and nurses think your problems are.
Please read the instructions carefully and ask if you do not understand anything. Do
not spend too long deciding about your answers.
Before completing the rest of the 
questionnaire:
Please tick in one box to show how you 
describe
your current health:
Very good

Good

Fair

Poor

Very 
poor

Copyright reserved
Tel. 
Fax 
UK/ English (original) version
f:\institut\cultadap\project\4457\study4457\final_versions\sgrqukoriq.doc-14/01/2008

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St. George’s Respiratory Questionnaire, Continued (Page 2 of 6)
PART 1
Questions about how much chest trouble you have had over the past 4 weeks.
Please tick () one box for each question:
most 
days 
a week
several 
days 
a week
a few 
days 
a month
only with 
chest 
infections
not 
at 
all
1.
Over the past 4 weeks, I have coughed:





2.
Over the past 4 weeks, I have brought up 
phlegm (sputum):





3.
Over the past 4 weeks, I have had shortness 
of breath:





4.
Over the past 4 weeks, I have had attacks 
of wheezing:





5.
During the past 4 weeks, how many severe or very 
unpleasant attacks of chest trouble have you had?
Please tick () one:
more than 3 attacks 
3 attacks 
2 attacks 
1 attack 
no attacks 
6.
How long did the worst attack of chest trouble last?
(Go to question 7 if you had no severe attacks)
Please tick () one:
a week or more 
3 or more days 
1 or 2 days 
less than a day 
7.
Over the past 4 weeks, in an average week, how many good days
(with little chest trouble) have you had?
Please tick () one:
No good days 
1 or 2 good days 
3 or 4 good days 
nearly every day is good 
every day is good 
8.
If you have a wheeze, is it worse in the morning?
Please tick () one:
No 
Yes 

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St. George’s Respiratory Questionnaire, Continued (Page 3 of 6)
PART 2
Section 1
How would you describe your chest condition?
Please tick () one:
The most important problem I have 
Causes me quite a lot of problems 
Causes me a few problems 
Causes no problem 
If you have ever had paid employment.
Please tick () one:
My chest trouble made me stop work altogether 
My chest trouble interferes with my work or made me change my work 
My chest trouble does not affect my work 
Section 2
Questions about what activities usually make you feel breathless these days.
Please tick () in each box that
applies to you these days:
True
False
Sitting or lying still 

Getting washed or dressed 

Walking around the home 

Walking outside on the level 

Walking up a flight of stairs 

Walking up hills 

Playing sports or games 


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St. George’s Respiratory Questionnaire, Continued (Page 4 of 6)
PART 2
Section 3
Some more questions about your cough and breathlessness these days.
Please tick () in each box that
applies to you these days:
True
False
My cough hurts 

My cough makes me tired 

I am breathless when I talk 

I am breathless when I bend over 

My cough or breathing disturbs my sleep 

I get exhausted easily 

Section 4
Questions about other effects that your chest trouble may have on you these days.
Please tick () in each box that
applies to you these days:
True
False
My cough or breathing is embarrassing in public


My chest trouble is a nuisance to my family, friends or neighbours


I get afraid or panic when I cannot get my breath


I feel that I am not in control of my chest problem


I do not expect my chest to get any better


I have become frail or an invalid because of my chest


Exercise is not safe for me


Everything seems too much of an effort


Section 5
Questions about your medication, if you are receiving no medication go straight 
to section 6.
Please tick () in each box that
applies to you these days:
True
False
My medication does not help me very much 

I get embarrassed using my medication in public 

I have unpleasant side effects from my medication 

My medication interferes with my life a lot
        
  

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St. George’s Respiratory Questionnaire, Continued (Page 5 of 6)
PART 2
Section 6
These are questions about how your activities might be affected by your breathing.
Please tick () in each box that applies to
you because of your breathing:
True
False
I take a long time to get washed or dressed


I cannot take a bath or shower, or I take a long time


I walk slower than other people, or I stop for rests


Jobs such as housework take a long time, or I have to stop for rests


If I walk up one flight of stairs, I have to go slowly or stop


If I hurry or walk fast, I have to stop or slow down


My breathing makes it difficult to do things such as walk up hills, carrying things
up stairs, light gardening such as weeding, dance, play bowls or play golf


My breathing makes it difficult to do things such as carry heavy loads, dig the
garden or shovel snow, jog or walk at 5 miles per hour, play tennis or swim


My breathing makes it difficult to do things such as very heavy manual work,
run, cycle, swim fast or play competitive sports


Section 7
We would like to know how your chest usually affects your daily life.
Please tick () in each box that applies to
you because of your chest trouble:
True
False
I cannot play sports or games 

I cannot go out for entertainment or recreation 

I cannot go out of the house to do the shopping 

I cannot do housework 

I cannot move far from my bed or chair 


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St. George’s Respiratory Questionnaire, Continued (Page 6 of 6)
Here is a list of other activities that your chest trouble may prevent you doing. (You do not have to tick 
these, they are just to remind you of ways in which your breathlessness may affect you):
Going for walks or walking the dog
Doing things at home or in the garden
Sexual intercourse
Going out to church, pub, club or place of entertainment
Going out in bad weather or into smoky rooms
Visiting family or friends or playing with children
Please write in any other important activities that your chest trouble may stop you 
doing:
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Now would you tick in the box (one only) which you think best describes how your 
chest affects you:
It does not stop me doing anything I would like to do        
It stops me doing one or two things I would like to do 
It stops me doing most of the things I would like to do 
It stops me doing everything I would like to do 
Thank you for filling in this questionnaire. Before you finish would you please check to see 
that you have answered all the questions.

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Modified Medical Research Council (mMRC)
Dyspnea Scale
Grade
0
“I only get breathless with strenuous exercise”
1
“I get short of breath when hurrying on the level or walking up a slight hill”
2
“I walk slower than people of the same age on the level because of 
breathlessness, or I have to stop for breath when walking on my own pace on the 
level”
3
“I stop for breath after walking about 100 yards or after a few minutes on the 
level”
4
“I am too breathless to leave the house” or “I am breathless when dressing”
NB: This is the modified MRC scale that uses the same descriptors as the original 
MRC scale in which the descriptors are numbered 1-5. The modified MRC scale (0-
4) is used for calculation of BODE index.

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Cough - Visual Analogue Scale (Cough - VAS)
Patient’s Assessment of Cough VAS
How much cough have you had because of your idiopathic pulmonary fibrosis (IPF) in the 
past week? 
Place a vertical (│) mark on the line to indicate the intensity of the cough. 
No cough               
Moderate cough
Intense cough
0
50
100

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Simplified Medication Adherence Questionnaire (SMAQ) 1
Adapted for the treatment of idiopathic pulmonary fibrosis (IPF)
1. Do you ever forget to take your medication for IPF?
YES
NO
2. Do you always take your medication for IPF at the indicated 
time?
YES
NO
3. Sometimes if you feel worse, do you stop taking your 
medication for IPF?
YES
NO
4. Did you miss your medication for IPF last weekend?
YES
NO
5. Think on the last week. 
How often did you miss your medication for IPF?
A: Never       
B: 1 - 2      
C: 3 - 5      
D: 6 - 10     
E:  More than 10 
     6.  Think on the past 3 months.
a)
How many days have you missed your medication 
for IPF?
b)
How many days have you missed one of the two 
daily doses of your medication for IPF?
Days ____
Days ____
Adapted from (1) Validation of a simplified medication adherence questionnaire in a large cohort of HIV-
infected patients: the GEEMA Study. Knobel H, Alonso J, Casado JL, Collazos J, Gonzalez J, Ruiz I, Kindelan 
JM, Carmona A, Juega J, Ocampo A; on behalf of the GEEMA Study Group. AIDS 2002;16(4):605-13.

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SMAK - United States/English / Mapi.
SMAQ_TS1.0_eng-USori.doc
Simplified Medication Adherence Questionnaire (SMAQ) 1 , 
Continued (Page 2 of 2)
The patient is considered non-adherent if: 
1: YES
2:  NO
3: YES 
4: YES
5: C, D or E
6: a) More than two (2) days
    b) More than four (4) days 
The questionnaire is dichotomic, any answer in the sense of non-adherent is 
considered non-adherent. 
You can use the question number 5 as semi-quantitative:
A: 95 - 100% compliance
B: 85-94% 
C: 65-84% 
D: 30-64% 
E: < 30% 
Adapted from (1) Validation of a simplified medication adherence questionnaire in a large cohort of HIV-
infected patients: the GEEMA Study. Knobel H, Alonso J, Casado JL, Collazos J, Gonzalez J, Ruiz I, Kindelan 
JM, Carmona A, Juega J, Ocampo A; on behalf of the GEEMA Study Group. AIDS 2002;16(4):605-13.
SMAK - United States/English / Mapi.
SMAQ_TS1.0_eng-USori.doc

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GAD - 7