Demographic, Clinical Characteristics, and Treatment Outcomes Associated With Dedifferentiated Liposarcoma Patients in China
Conditions: Dedifferentiated Liposarcoma
Sponsor: Boehringer Ingelheim

ABCD
 
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TITLE PAGE 
Non-Interventional Study (NIS) Protocol  
TITLE PAGE 
 
Document Number: 
C42272174 
BI Study Number: 
1403-0024 
BI Investigational 
Product(s): 
Not applicable 
Title: 
Demographic, clinical characteristics, and treatment outcomes 
associated with dedifferentiated liposarcoma patients in China  
Brief lay title: 
Real-world study of dedifferentiated liposarcoma patients in China  
Protocol version 
identifier: 
1.0 
Date of last version of 
protocol: 
Not applicable  
PASS: 
No 
EU PAS register 
number: 
Not applicable 
Active substance: 
Not applicable 
Medicinal product: 
Not applicable 
Product reference: 
Not applicable 
Procedure number: 
Not applicable 
Marketing 
authorization holder(s): 
Not applicable 
Joint PASS: 
No 
Research question and 
objectives: 
This study will characterize patients with dedifferentiated liposarcoma 
(DDLPS) in China, including an understanding of demographic, and 
clinical characteristics as well as treatment patterns and clinical outcomes 
associated with the current real-world treatment. 
Country(-ies) of study: 
China 
Author: 
  

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Marketing authorisation 
holder(s): 
Not applicable 
In case of PASS, add: 
MAH contact person: 
Not applicable 
In case of PASS, add:  
Not applicable 
In case of PASS, add:  
Not applicable 
Date: 
31 May 2023 
 
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Proprietary confidential information 
© 2023 Boehringer Ingelheim Group of 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 ....................................................................................... 3 
2. 
LIST OF ABBREVIATIONS ................................................................................ 5 
3. 
RESPONSIBLE PARTIES .................................................................................... 6 
4. 
ABSTRACT ........................................................................................................... 6 
5. 
AMENDMENTS AND UPDATES ....................................................................... 9 
6. 
MILESTONES ..................................................................................................... 11 
7. 
RATIONALE AND BACKGROUND ................................................................ 11 
8. 
RESEARCH QUESTION AND OBJECTIVES ................................................. 12 
9. 
RESEARCH METHODS .................................................................................... 12 
9.1. 
STUDY DESIGN ............................................................................................ 12 
9.2. 
SETTING ........................................................................................................ 12 
9.2.1. 
Study sites ............................................................................................... 12 
9.2.2. 
Study population ..................................................................................... 12 
9.2.3. 
Study visits .............................................................................................. 13 
9.2.4. 
Study discontinuation .............................................................................. 14 
9.3. 
VARIABLES .................................................................................................. 14 
9.3.1. 
Outcomes ................................................................................................. 14 
9.3.1.1. 
Primary outcomes ............................................................................. 14 
9.3.1.2. 
Secondary outcomes ......................................................................... 14 
9.4. 
DATA SOURCES ........................................................................................... 21 
9.5. 
STUDY SIZE .................................................................................................. 21 
9.6. 
DATA MANAGEMENT ................................................................................ 22 
9.7. 
DATA ANALYSIS ......................................................................................... 23 
9.7.1. 
Analysis of primary objectives ................................................................ 23 
9.7.2. 
Analysis of secondary objectives ............................................................ 23 
9.7.3. 
Analysis of exploratory objectives .......................................................... 24 
9.7.4. 
Subgroup analysis ................................................................................... 24 
9.7.5. 
Sensitivity analyses ................................................................................. 24 
9.7.6. 
Safety Analysis ........................................................................................ 24 
9.8. 
QUALITY CONTROL ................................................................................... 24 

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9.9. 
LIMITATIONS OF THE RESEARCH METHODS ...................................... 25 
9.10. OTHER ASPECTS ......................................................................................... 25 
9.10.1. 
Data quality assurance ............................................................................. 25 
9.10.2. 
Study records ........................................................................................... 26 
10. 
PROTECTION OF HUMAN SUBJECTS .......................................................... 26 
10.1. STUDY APPROVAL, PATIENT INFORMATION, AND INFORMED 
CONSENT ...................................................................................................... 26 
10.2. STATEMENT OF CONFIDENTIALITY ...................................................... 26 
11. 
MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ....................................................................................................... 26 
12. 
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
 ............................................................................................................................. 27 
13. 
REFERENCES .................................................................................................... 27 
13.1. PUBLISHED REFERENCES ......................................................................... 27 
13.2. UNPUBLISHED REFERENCES ................................................................... 28 
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS .............................................. 29 
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS .............................. 29 
ANNEX 3. ADDITIONAL INFORMATION .............................................................. 34 
ANNEX 4. REVIEWERS AND APPROVAL SIGNATURES ................................... 36 

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2. LIST OF ABBREVIATIONS 
1L 
First line 
2L 
Second line 
3L 
Third line 
AE 
Adverse Event 
BI 
Boehringer Ingelheim 
CDC 
Center for Disease Control and Prevention Center 
CI 
Confidence Interval 
CSCO 
Chinese Society of Clinical Oncology 
CTN 
Clinical Trial Notification 
DDLPS 
Dedifferentiated liposarcoma 
ECOG 
Eastern Cooperative Oncology Group 
ENCePP  
European Network of Centres for Pharmacoepidemiology and 
Pharmacovigilance  
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GPP 
Good Pharmacoepidemiology Practice 
GVP 
Good Pharmacovigilance Practices 
HCRU 
Healthcare resource utilization 
IEC 
Independent Ethics Committee 
IQR 
Interquartile range 
IRB 
Institutional Review Board 
KM 
Kaplan-Meier 
LOT 
Line of therapy 
MAH 
Marketing Authorization Holder 
MDM2 
Mouse double minute 2 homolog 
NATDSS 
National Anti-Tumor Drug Surveillance System 
NCC 
National Cancer Center 
NCCN 
National Comprehensive Cancer Network 
NIS 
Non-Interventional Study 
NIS-DMRP  
Non-interventional Study-Data Management and Review Plan 
OS 
Overall survival 
PASS 
Post-Authorization Safety Study 
QC 
Quality control 
SD 
Standard deviation 
SEAP 
Statistical and Epidemiological Analysis Plan 
SEER 
Surveillance, Epidemiology, and End Results 
SOP 
Standard operating procedure 
TP53 
Tumor protein 53 
 

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3. RESPONSIBLE PARTIES 
BI NIS 
 
 investigator: 
 
 
4. ABSTRACT 

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Name of company: 
 
 
Boehringer Ingelheim 
Name of finished medicinal 
product:  
Not applicable 
 
Name of active ingredient: 
Not applicable 
 
Protocol date: 
Study 
number: 
Version/Revision: 
Version/Revision date: 
31 May 2023 
1403.0024 
1.0 
 
Title of study: 
Demographic, clinical characteristics, and treatment outcomes associated 
with dedifferentiated liposarcoma patients in China 
Rationale and 
background: 
Liposarcoma is a malignancy of fat tissue and is one of the most commonly 
occurring types of soft tissue sarcoma, a heterogeneous group of rare 
malignancies with over 150 different histological subtypes. In 2020, the 
World Health Organization, reclassified liposarcomas into the following 
distinct categories: atypical lipomatous tumor/well-differentiated 
liposarcoma; myxoid liposarcoma; pleomorphic liposarcoma; myxoid 
pleomorphic liposarcoma; and dedifferentiated liposarcoma (DDLPS), which 
represents 15-20% of all liposarcoma cases [R23-1182].  
DDLPS is characterized by amplification of the mouse double minute 2 
homolog (MDM2) gene. MDM2 is a negative regulator of tumor protein 53 
(TP53) [P20-03237]. There are few published epidemiological studies of DDLPS 
with quite limited incidence and prevalence data. The mainstay of first line 
(1L) therapy for advanced DDLPS remains an anthracycline-based regimen 
despite its moderate efficacy in this setting (objective response rate <15%; 
median progression-free survival: 2 to 4 months; median overall survival 
(OS, from initiation of 1L treatment to death or end of study): 8 to 12 
months) [R21-0720]. Notably, the natural history, patient journey and treatment 
outcomes of this rare disease is poorly understood in Chinese patients. 
 
Boehringer Ingelheim (BI) is currently developing BI 907828, an orally 
available MDM2-p53 antagonist, for treatment of DDLPS. On 22 August 
2022, BI China received Clinical Trial Notification (CTN) for MDM2 
DDLPS indication from China authority. In the CTN, China authority 
recommended BI to collect Chinese DDLPS patients’ survival and other 
related clinical data in the real-world, to provide support for future analysis 
during New Drug Application. Therefore, we conduct this study to 
investigate the patient characteristics, current treatment patterns and 
outcomes in Chinese DDLPS patients. 

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Research question 
and objectives: 
Primary objective: 
• To describe the overall survival (OS) of Chinese unresectable locally 
advanced or metastatic DDLPS patients 
Secondary objectives: 
• To describe the treatment patterns of Chinese DDLPS patients 
Exploratory objective: 
• To describe demographic, clinical characteristics and treatment 
outcomes of Chinese DDLPS patients 
• To describe the direct medical cost and healthcare resource utilization 
of Chinese DDLPS patients 
Study design: 
This will be a non-interventional/observational study of Chinese DDLPS 
patients using existing data curated by 
. No Boehringer 
Ingelheim (BI) product will be studied, and no new interventions or 
procedures will be collected.   
The proposed study period will be January 1, 2013 through December 31, 
2022. Eligible patients will be identified from January 1, 2013 to December 
31, 2021 (one year before end of study period). Patients will be followed 
from index date until death, end of study period, or loss to follow-up, 
whichever occurs first.  
Population: 
Inclusion criteria: 
• Patient has two or more documented clinical visits in the National 
Anti-Tumor Drug Surveillance System (NATDSS) network on or after 
January 1, 2013. 
• Patient has a confirmed diagnosis of DDLPS during his/her lifetime. 
• At least 18 years old at the date of initial diagnosis 
 No exclusion criteria are applied.  
 
Eligible population will be divided into two groups:  
• Cohort 1 will include unresectable locally advanced or metastatic 
DDLPS patients who received at least one line of systemic antineoplastic 
treatment by the end of cohort identification period (index date = start 
date of 1L treatment). 
• Cohort 2 will include patients with DDLPS who have not initiated 1L 
systemic antineoplastic treatment by the end of cohort identification 
period (index date = date of initial DDLPS diagnosis during cohort 
identification period). Patients initiated 1L treatment afterwards or 
patients received adjuvant and/or neoadjuvant therapy only through 
follow-up will be included in Cohort 2. 
Variables: 
This analysis is descriptive, in that there is no a priori hypothesis being 
assessed. Thus, there are no pre-specified exposures or covariates that will 
be used as the basis for comparison a priori.  
The primary outcome is OS. Secondary outcomes include survival after 
initial diagnosis, and treatment patterns. Exploratory outcomes may include 
patient demographics, clinical characteristics, duration of treatment, time to 
next treatment by lines, healthcare resource utilization and direct medical 
cost, etc.  

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Data sources: 
 will develop a custom, curated dataset for this study based 
on longitudinal electronic medical records data from the National Anti-
Tumor Drug Surveillance System (NATDSS), the largest cancer registry 
database in China. This database, established in 2018 by China National 
Cancer Center (NCC), covers over 1400 hospitals across 31 provinces and 
over 10 million cancer patients in China. This multicenter hospital-based 
database consists of data of 1509 variables from 7 aspects including drug, 
patient basic information, inpatient, outpatient, medical technology, 
treatment and follow up. NATDSS is linked with National Mortality 
Database from Chinese Center for Disease Control and Prevention Center 
(China CDC) to obtain patients’ death information. 
Study size: 
The patient sample will be a convenience population of all eligible patients 
in the database who met inclusion and exclusion criteria during the study 
period; no priori power analyses were conducted. 
Data analysis: 
This study will be descriptive in nature. Continuous variables will be 
summarized using mean, standard deviation (SD), median and range. 
Categorical measures will be summarized using frequencies and 
percentages.  
OS will be estimated by the Kaplan-Meier (KM) method to obtain median 
estimates with two-sided 95% confidence intervals (CIs). OS may be 
assessed by line of therapy (LOT) and type of treatment received in each 
LOT, pending feasibility. 
Subgroup analyses will be conducted in both Cohort 1 and 2: 
• Unresectable locally advanced DDLPS patients 
• Metastatic DDLPS patients 
• Brightline-1-like cohort including patients who received doxorubicin 
monotherapy or doxorubicin-based regimens as 1L treatment. 
• Real-world Brightline-1 cohort including patients matching the 
inclusion and exclusion criteria in Brightline-1 trial       
• Additional subgroups pending feasibility, which may include age, 
sex, and year of diagnosis.  
 
Sensitivity analyses will be conducted: 
• to only include patients in areas covered by the National Mortality 
Database and with higher completeness on survival data 
• to only include patients before COVID-19 emergence (cohort 
identification period: January 1, 2013 – December 31, 2019) to assess the 
possible impact of COVID-19 pandemic on treatment patterns and 
outcomes 
Milestones: 
1) Protocol approval: May 2023 
2) Start of analysis: Dec 2023 
3) End of analysis: Feb 2024 
4) Final report of study results: Apr 2024 
 
5. AMENDMENTS AND UPDATES 

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None.  

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6. MILESTONES 
 
Milestone 
Planned Date 
IRB/IEC approval 
October 2023 
Start of data collection 
December 2023 
End of data analysis 
February 2024 
Final report of study results: 
April 2024 
 
7. RATIONALE AND BACKGROUND 
Liposarcoma is a malignancy of fat tissue and is one of the most commonly occurring types 
of soft tissue sarcoma, a heterogeneous group of rare malignancies with over 150 different 
histological subtypes. Liposarcomas have several forms based on clinical presentation, 
severity, genetic abnormality, and preferred treatment regimens [R23-1186] [R22-3794]. In 2020, the 
World Health Organization, reclassified liposarcomas into the following distinct categories: 
atypical lipomatous tumor/well-differentiated liposarcoma; myxoid liposarcoma; 
pleomorphic liposarcoma; myxoid pleomorphic liposarcoma; and dedifferentiated 
liposarcoma (DDLPS), which represents 15-20% of all liposarcoma cases [R23-1182].  
 
DDLPS is characterized by amplification of the mouse double minute 2 homolog (MDM2) 
gene. MDM2 is a negative regulator of tumor protein 53 (TP53) [P20-03237]. There are few 
published epidemiological studies of DDLPS with quite limited incidence and prevalence 
data. According to an internal BI analysis of Surveillance, Epidemiology, and End Results 
(SEER) registry-21, the age-adjusted incidence rate of DDLPS is 0.18 per 10,000 person-
years. Incidence is higher in men than women (0.26 per 10,000 py vs 0.11 per 10,000 py) 
(data on file).  
 
DDLPS is typically a high-grade tumor that metastasizes in more than 20% of cases (lungs, 
liver, bone, skin, or brain). The mainstay of first line (1L) therapy for advanced DDLPS 
remains an anthracycline-based regimen despite its moderate efficacy in this setting 
(objective response rate <15%; median progression-free survival: 2 to 4 months; median 
overall survival (OS, from initiation of 1L treatment to death or end of study): 8 to 12 
months) [R21-0720]. Notably, the natural history, patient journey and treatment outcomes of this 
rare disease is poorly understood in Chinese patients. 
 
Boehringer Ingelheim (BI) is currently developing BI 907828, an orally available MDM2-
p53 antagonist, for treatment of DDLPS. On 22 August 2022, BI China received Clinical 
Trial Notification (CTN) for MDM2 DDLPS indication from China authority. In the CTN, 
China authority recommended BI to collect Chinese DDLPS patients’ survival and other 
related clinical data in the real-world, to provide support for future analysis during New Drug 
Application. Therefore, we conduct this study to investigate the patient characteristics, 
current treatment patterns and outcomes in Chinese DDLPS patients. 

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8. RESEARCH QUESTION AND OBJECTIVES 
Primary objective: 
To describe the overall survival of Chinese unresectable locally advanced or metastatic 
DDLPS patients 
 
Secondary objectives: 
To describe the treatment patterns of Chinese DDLPS patients 
 
Exploratory objective: 
To describe demographic, clinical characteristics and treatment outcomes of Chinese DDLPS 
patientsTo describe the direct medical cost and healthcare resource utilization of Chinese 
DDLPS patients 
 
9. RESEARCH METHODS 
9.1. STUDY DESIGN 
This will be a non-interventional/observational study of Chinese DDLPS patients using 
existing data curated by 
. No Boehringer Ingelheim (BI) product will be 
studied, and no new interventions or procedures will be performed.   
The primary outcome is overall survival (OS). Secondary outcomes include survival after 
initial diagnosis, and treatment patterns. Exploratory outcomes may include 
patient 
demographics, clinical characteristics, duration of treatment, time to next treatment by lines, 
healthcare resource utilization and direct medical cost, etc. None of the outcomes reflect 
safety issues. 
 
9.2. SETTING 
9.2.1. Study sites 
This is a non-interventional study based on existing data. Details of data source are described 
in Section 9.9.4. 
9.2.2. Study population 
Inclusion criteria: 
• 
Patient has two or more documented clinical visits in the National Anti-Tumor Drug 
Surveillance System (NATDSS) network on or after January 1, 2013. 
• 
Patient has a confirmed diagnosis of DDLPS during his/her lifetime. 
• 
At least 18 years old at the date of initial diagnosis 
 
No exclusion criteria are applied.  
 
Eligible population will be divided into two groups:  

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• 
Cohort 1 will include unresectable locally advanced or metastatic DDLPS patients who 
received at least one line of systemic antineoplastic treatment by the end of cohort 
identification period (index date = start date of 1L treatment). 
• 
Cohort 2 will include patients with DDLPS who have not initiated 1L systemic 
antineoplastic treatment by the end of cohort identification period (index date = date of 
initial DDLPS diagnosis during cohort identification period). Patients initiated 1L 
treatment afterwards or patients received adjuvant and/or neoadjuvant therapy only 
through follow-up will be included in Cohort 2.  
 
In both cohorts, 1L therapy will be defined as the initial set of drugs used after unresectable 
locally advanced or metastatic diagnosis. Metastatic patients will be defined as those with 
metastatic diagnosis or presence of metastatic sites; unresectable locally advanced patients 
will be defined as those with advanced diagnosis and without subsequent surgical resection.   
 
9.2.3. Study visits 
Definitions of relevant time periods are detailed below. 
 
Study period: January 1, 2013 – December 31, 2022 
 
 
Baseline period: All available data prior to index date 
 
Cohort identification period: January 1, 2013 – December 31, 2021 (one year before end of 
study period) 
 
Index date: The index date for Cohort 1 will set to the date of initiation of 1L treatment; the 
index date for Cohort 2 will be the date of initial DDLPS diagnosis during cohort 
identification period.  
 
Follow-up period: From index date until date of death, if available, or the date of censoring 
if there is no record of death, whichever occurs first. For survival and treatment patterns, the 
date of censoring will be the last activity date, defined as the date of the last visit of any type 
prior to the end of the study period.  
 
Figure 1 illustrates the time periods for the study timelines. 
 
(a). Cohort 1 
 
 

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(b). Cohort 2 
 
Figure 1. Overall study period  
9.2.4. Study discontinuation 
Not applicable. 
 
9.3. VARIABLES 
The analysis will be descriptive only, and there are no a priori hypotheses. There will be no 
prespecified exposures or covariates to be used as the basis for formal statistical testing and 
for a priori comparison of groups.  
9.3.1. Outcomes 
9.3.1.1. 
Primary outcomes 
OS 
▪ Outcome type: Primary 
▪ Outcome name: OS 
▪ Time frame: Time from index date until the earliest record of death or end of the study 
period 
▪ Population: Cohort 1 
 
OS as an event for each patient in Cohort 1 will be defined as the date of death minus the 
index date or the start day of each LOT. For patients with no record of death, OS will be 
censored at the last activity date before the end of the study period.  
 
9.3.1.2. 
Secondary outcomes 
Survival after initial diagnosis 
▪ Outcome type: Secondary 
▪ Outcome name: Survival after initial diagnosis  
▪ Time frame: Time from initial diagnosis until the earliest record of death or end of the 
study period  
▪ Population: Cohort 1, Cohort 2  

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Survival after initial diagnosis for each patient will be defined as the date of death minus the 
date of initial diagnosis. For patients with no record of death, survival after initial diagnosis 
will be censored at the last activity date before the end of the study period. 
 
Description of treatment patterns  
▪ Outcome type: Secondary 
▪ Outcome name: Treatment patterns  
▪ Time frame: Treatment patterns are assessed at the index date and during follow-up  
▪ Population: Cohort 1, Cohort 2  
 
The following variables of interest will be assessed to describe treatment patterns defined by 
LOT and regimens.  
 
Treatment patterns by LOT and regimens  
Variable 
Definition 
Timing 
1L Treatment Type 
 
Regimen name from LOT data for treatments 
with line number = 1, 2 and 3. Treatment 
types will be classified as follows, specific 
treatments and categories may change upon 
examination of the data:  
 
NCCN/CSCO preferred 
• Doxorubicin 
• Epirubicin 
• Liposomal doxorubicin 
• AD (doxorubicin, dacarbazine) 
• AIM (doxorubicin, ifosfamide, 
mesna) 
• Ifosfamide, epirubicin, mesna 
• Larotrectinib (NTRK fusion pos 
sarcomas only) 
• Entrectinib (NTRK fusion pos 
sarcomas only) 
• Pazopanib 
• Eribulin 
• Trabectedin 
 
Other 
• 
AD LMS only (doxorubicin, 
dacarbazine) 
• 
Gemcitabine and docetaxel 
Any time after 
index date 
 
 
2L Treatment Type 
3L Treatment Type 
 

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Variable 
Definition 
Timing 
• 
Gemcitabine 
• 
Gemcitabine and vinorelbine 
• 
Gemcitabine and dacarbazine 
• 
Dacarbazine 
• 
Ifosfamide 
• 
Temozolomide 
• 
Vinorelbine 
• 
Regorafenib 
• 
MAID (mesna, doxorubicin, 
ifosfamide, dacarbazine) 
• 
Pembrolizumab 
• 
durvalumab 
• 
Other 
Total number of 
treatment lines 
From LOT data, for all lines after index date, 
categorical variable defined as total of 
treatment lines reported.  
Any time after 
index date 
Concurrent steroid 
therapy 
Any record of a drug classified as a 
corticosteroid.  
Anytime from the 
start to end of 1L, 
2L, or 3L 
Concurrent 
immunosuppressant 
therapy 
Any record of a drug classified as an 
immunosuppressant therapy.  
Anytime from the 
start to end of 1L, 
2L, or 3L 
Concurrent 
hormone 
replacement 
therapy 
Any record of a drug classified as a hormone 
replacement therapy.  
Anytime from the 
start to end of 1L, 
2L, or 3L 
Abbreviations: 1L = first line; 2L = second line; 3L = third line; CSCO = Chinese Society of Clinical Oncology; 
LOT = line of therapy; NCCN = National Comprehensive Cancer Network 
 

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9.4. DATA SOURCES 
 will develop a custom, curated dataset for this study based on longitudinal 
electronic medical records data from the National Anti-Tumor Drug Surveillance System 
(NATDSS), the largest cancer registry database in China. This database, established in 2018 
by China National Cancer Center (NCC), covers over 1400 hospitals across 31 provinces and 
over 10 million cancer patients in China. This multicenter hospital-based database consists of 
data of 1509 variables from 7 aspects including drug, patient basic information, inpatient, 
outpatient, medical technology, treatment and follow up. NATDSS is linked with National 
Mortality Database from Chinese Center for Disease Control and Prevention Center (China 
CDC) to obtain patients’ death information [R23-1183].  
 
9.5. STUDY SIZE 
The patient sample was a convenience population of all eligible patients in the 
 
database who met inclusion and exclusion criteria during the study period; no priori power 
analyses were conducted. 

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A preliminary feasibility check will be conducted to assess potential eligible sample size as 
below.  
Criteria 
Patients with at least one diagnosis of DDLPS  
Patients aged 18 years old or above at initial diagnosis  
Patients have two or more documented clinical visits between January 1, 2013 
and December 31, 2022 
 
We estimated the precision we can expect from the estimates of a median OS for different 
potential sample sizes. It is assumed that the enrollment rates follow uniform distribution in 
the study period and that the survival time follows exponential distribution with median 
OS=8, 10, and 12 months. The censor rate is approximately 20% with type I of right 
censoring. The 95% CI of median OS is shown in the below table under different scenarios. 
 
N (Sample Size) 
Median Overall 
Survival from start of 
1L, Months 
95% CI of Median 
Overall Survival  
1500 
8 
(7.419, 8.625) 
1000 
8 
(7.287, 8.764) 
500 
8 
(7.011, 9.095) 
300 
8 
(6.732, 9.435) 
1500 
10 
(9.262, 10.784) 
1000 
10 
(9.100, 10.972) 
500 
10 
(8.754, 11.378) 
300 
10 
(8.408, 11.814) 
1500 
12 
(11.110, 12.948) 
1000 
12 
(10.916, 13.175) 
500 
12 
(10.491, 13.677) 
300 
12 
(10.073, 14.198) 
 
9.6. 
DATA MANAGEMENT 
The data management plan is summarized below. Full details of the data management plan 
are documented in a separate Non-interventional Study-Data Management and Review Plan 
(NIS-DMRP). 
 

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For this study, BI will not have access to the original data. Data will be managed by 
. 
Source code of data management and data analyses data will be stored for at least 15 years at 
.  
 
9.7. 
DATA ANALYSIS 
The statistical analysis plan for the study is summarized below. Full details of the statistical 
analysis will be documented in the Statistical and Epidemiological Analysis Plan (SEAP), 
which will be finalized before the end of data collection. 
 
This study will be descriptive in nature. 
 
It is anticipated that sample sizes for variables may vary due to unknown or missing data in 
the database. The number of patients with missing data for each variable will be summarized 
and reported. With the exception of the imputation of partial missing date values, no other 
imputation of missing values will be undertaken; however, the impact of missing data on 
interpretation of findings will be acknowledged and discussed in the final study report. 
 
For all analyses, data for patients will be censored when lost to follow-up (i.e., still alive as of 
their last visit prior to end of study period). 
 
9.7.1. Analysis of primary objectives 
OS will be estimated by the Kaplan-Meier (KM) method to obtain median estimates with 
95% CIs and interquartile ranges (IQRs) for Cohort 1, calculated using the log-log 
transformation. OS will be examined from each appropriate index date. Estimates at 
appropriate timepoints (dependent on the data) of the probability of remaining event free will 
be presented, together with a survival plot for OS. OS may be assessed by LOT and type of 
treatment received in each LOT, pending feasibility.  
 
9.7.2. Analysis of secondary objectives 
Survival after initial diagnosis will be estimated by the KM method to obtain median 
estimates with 95% CIs and interquartile ranges (IQRs) for Cohort 1 and Cohort 2.  
 
Treatment patterns for Cohort 1 and Cohort 2 will be tabulated (See Section 9.3.1.2 for 
variable definitions). Continuous variables will be summarized using mean, standard 
deviation (SD), median, and interquartile range (IQR). Categorical variables will be 
summarized using counts (n) and proportions (%). The number of missing values will be 
reported for each variable, and percentages for categorical variables will be based on non-
missing values. 
 

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9.7.3. Analysis of exploratory objectives 
Patient demographic, clinical characteristics and treatment outcomes  will be reported for 
Cohort 1 and Cohort 2 (See Section 9.3.1.3 for variable definitions). If multiple records for a 
variable exist during the baseline period, the record closest to index will be chosen. The 
number of missing values will be reported for each variable, and percentages for categorical 
variables will be based on non-missing values. Time from diagnosis to 1L treatment, time to 
next treatment and duration of treatment by LOT will be estimated using KM methods to 
obtain median estimates with 95% CIs and IQRs.  
 
HCRU including number of visits and days of hospitalization will be summarized as counts 
(n) and proportions (%). Direct medical cost will be summarized using mean, median and 
IQR.   
 
9.7.4. Subgroup analysis 
The above analyses may be performed in additional subgroups for Cohort 1 and Cohort 2, 
pending sample size and feasibility. These include: 
• 
Unresectable locally advanced DDLPS patients 
• 
Metastatic DDLPS patients 
• 
Brightline-1-like cohort including patients who received doxorubicin monotherapy or 
doxorubicin-based regimens as 1L treatment  
• 
Real-world Brightline-1 cohort including patients matching the inclusion and exclusion 
criteria in Brightline-1 trial   
• 
Additional subgroups, which may include age, sex, and year of initial diagnosis.  
 
9.7.5. Sensitivity analyses  
Sensitivity analyses will be conducted: 
• 
to only include patients in areas covered by the mortality surveillance system and with 
higher completeness on survival data. 
• 
to only include patients before COVID-19 emergence (cohort identification period: 
January 1, 2013 – December 31, 2019) to assess the possible impact of COVID-19 
pandemic on treatment patterns and outcomes. 
9.7.6. Safety Analysis 
Not applicable. 
 
9.8. 
QUALITY CONTROL 
The quality control, review, and monitoring plan are summarized below. Greater details are 
documented in the NIS-DMRP. 
 

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The study will strictly follow key elements of the Guideline for Good Pharmacoepidemiology 
Practices (GPP) and other relevant standard operating procedures (SOPs). The study report 
will be reviewed, approved and archived per BI SOP. 
 
One Data Analyst from 
 will build measures (variables) for cohort inclusion 
and outcomes. Whenever possible, validated algorithms will be used for variables, to 
minimize misclassification and information bias. All measures created, cohorts developed, 
statistical analyses implemented, and tables output will undergo quality control review 
performed by at least one additional Analyst from 
. Quality controls include 
checks for the validity and logical content of codes and checks for missing values and 
variables. In order to control for potential inconsistencies and errors, all variables will be 
tabulated. The distribution of each variable will be examined. 
 
The NIS Lead will verify that the Data Analyst has followed methodology specified in the 
protocol, as well as any relevant programming SOPs and good programming practices. 
Documentation of key programming decisions should be evident within the program. The 
investigator or NIS Lead will verify that any assumptions made by the data analyst are 
consistent with expectations.  
 
9.9. 
LIMITATIONS OF THE RESEARCH METHODS 
There are several limitations of this study. Firstly, CDC mortality surveillance data may only 
capture 80% of the total deaths, which may result in over-estimate of the survival outcomes. 
We attempt to conduct sensitivity analyses in area with higher completeness on survival data. 
Still, results should be interpreted with caution. 
 
Secondly, the study could be subjected to missing clinical information that is not routinely 
recorded by clinicians, variations in the reporting, and selection biases arise from the use of 
diagnostic and therapeutic codes. Under-reporting of comorbidities and of treatment received 
outside the oncology clinic setting may result in misclassification of treatments and 
outcomes.  
 
Additionally, as this study population includes patients from tertiary or oncology hospitals in 
China, study results might not be generalizable to entire Chinese DDLPS patients. As 
oncology care remain only possible or most optimally delivered though face-to-face, patients’ 
access to oncological services is possibly limited during COVID-19 pandemic impacts, 
consequently resulting in less patient diagnosis and hospital visits.  
 
9.10. OTHER ASPECTS 
9.10.1. Data quality assurance 
A quality assurance audit/inspection of this study may be conducted by the sponsor or 
sponsor’s designees or by Institutional Review Board (IRBs) / Independent Ethics Committee 
(IECs) or by regulatory authorities. The quality assurance auditor will have access to all 
medical records, the investigator’s study-related files and correspondence of this study. 

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9.10.2. Study records 
Not applicable.  
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, Guidelines for GPP, and the relevant BI SOPs.  
 
10.1. 
STUDY APPROVAL, PATIENT INFORMATION, AND INFORMED 
CONSENT 
This NIS will be initiated only after all required legal documentation has been reviewed and 
approved by the respective IRB/ IEC according to national and international regulations. The 
same applies for the implementation of changes introduced by amendments. 
 
Ethical approval will be obtained prior to start of data collection. The finalized protocol will 
be submitted to an IRB in China for review and approval. 
 
 
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. 
 
Only anonymized data will be used in the study. 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. 
 
11. 
MANAGEMENT AND REPORTING OF ADVERSE 
EVENTS/ADVERSE REACTIONS 
Not applicable based on secondary use of data without any potential that any employee of BI 
or agent working on behalf of BI will access individually identifiable patient data.  
 
Based on current guidelines from the International Society for Pharmacoepidemiology and 
the EMA, non-interventional studies such as the one described in this study protocol, 
conducted using electronic claims and/or health care records, do not require expedited 
reporting of suspected adverse events/reactions. Specifically, as stated in section VI.C.1.2.1 
of Guideline on Good Pharmacovigilance Practices (GVP), Module VI – Management and 
Reporting of Adverse Reactions to Medicinal Products, for non-interventional study designs, 
which are based on use of secondary data, reporting of adverse reactions is not required. In 
addition, this study does not involve BI product and no safety outcomes are included in the 
study. No BI employees will have access to the original data. As such, with no individual 
medical record review, the safety reporting is not applicable.   
 

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12. 
PLANS FOR DISSEMINATING AND COMMUNICATING 
STUDY RESULTS 
The rights of the investigator and of the sponsor with regard to publication of the results of 
this study are described in the investigator contract. As a general rule, no study results should 
be published prior to finalization of the Study Report. 
 
At this time, this study is planned to help inform the asset program and may be used to 
supplement regulatory submissions. However, it is not conducted solely for regulatory 
approval.  
 
13. 
REFERENCES 
13.1. 
PUBLISHED REFERENCES 
P20-03237 
Cornillie J, Wozniak A, Li H, Gebreyohannes YK, Wellens J, Hompes 
D, Debiec-Rychter M, Sciot R, Schöffski P. Anti-tumor activity of the 
MDM2-TP53 inhibitor BI-907828 in dedifferentiated liposarcoma 
patient-derived xenograft models harboring MDM2 amplification. Clin 
Transl Oncol. 2020 Apr;22(4):546-554. doi: 10.1007/s12094-019-02158-
z. Epub 2019 Jun 14. PMID: 31201607. 
R22-3794 
Dei Tos AP (August 2000). "Liposarcoma: new entities and evolving 
concepts". Ann Diagn Pathol. 4 (4): 252–66. 
R23-1186 
Nie L, Chen X, Gong J, Zhang M, Xu M, Chen N, Zhou Q (December 
2020). "Synchronous Renal Dedifferentiated Liposarcoma and 
Retroperitoneal Well-Differentiated Liposarcoma: A Case Report With 
Literature Review". International Journal of Surgical Pathology. 29 (6): 
667–671. 
R23-1182 
Porrino J, Al-Dasuqi K, Irshaid L, Wang A, Kani K, Haims A, Maloney 
E (June 2021). "Update of pediatric soft tissue tumors with review of 
conventional MRI appearance-part 1: tumor-like lesions, adipocytic 
tumors, fibroblastic and myofibroblastic tumors, and perivascular 
tumors". Skeletal Radiology. 51 (3): 477–504 
R21-0720 
Savina M, Cesne A le, Blay JY, et al. Patterns of care and outcomes of 
patients with METAstatic soft tissue SARComa in a real-life setting: the 
METASARC observational study. BMC Med 2017; 15; 78 
R23-1183 
Hongmei Zeng, Yunning Liu, Lijun Wang, Peng Yin, Baohua Wang, 
Ruiying Fu, Xianhui Ran, Rongshou Zheng, Siwei Zhang, Jiangmei Liu, 
Jinling You, Kexin Sun, Shaoming Wang, Li Li, Ru Chen, Wenqiang 
Wei, Maigeng Zhou, Jing Wu, Jie He. National Cancer Data Linkage 
Platform of China: Design, Methods, and Application[J]. China CDC 
Weekly, 2022, 4(13): 271-275. doi: 10.46234/ccdcw2022.068 

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R14-4775 
Quan H, Sundararajan V, Halfon P, et al. Coding algorithms for defining 
comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 
2005;43(11):1130-1139. 
 
13.2. 
UNPUBLISHED REFERENCES 
 
 

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ANNEX 1. LIST OF STAND-ALONE DOCUMENTS 
None.  
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS 
Study title: Demographic, clinical characteristics, and treatment outcomes associated 
with dedifferentiated liposarcoma patients in China 
 
EU PAS Register® number: 
Study reference number (if applicable): 
 
Section 1: Milestones 
Yes 
No 
N/A 
Section 
Number 
1.1 
Does the protocol specify timelines for  
 
 
 
 
1.1.1 Start of data collection1 
 
 
 
 
1.1.2 End of data collection2 
 
 
 
6 
1.1.3 Progress report(s) 
 
 
 
 
1.1.4 Interim report(s) 
 
 
 
 
1.1.5 Registration in the EU PAS Register® 
 
 
 
 
1.1.6 Final report of study results. 
 
 
 
 
Comments: 
 
 
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) 
 
 
 
7 
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 
generalised) 
 
 
 
9.2.2,9.7.4 
2.1.4 Which hypothesis(-es) is (are) to be 
tested? 
 
 
 
 
2.1.5 If applicable, that there is no a priori 
hypothesis? 
 
 
 
9.1, 9.3 
Comments: 
 
 
 
1 Date from which information on the first study is first recorded in the study dataset or, in the case of 
secondary use of data, the date from which data extraction starts. 
2 Date from which the analytical dataset is completely available. 

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Section 3: Study design 
Yes 
No 
N/A 
Section 
Number 
3.1 
Is the study design described? (e.g. cohort, 
case-control, cross-sectional, other design)  
 
 
 
9.1 
3.2 
Does the protocol specify whether the study 
is based on primary, secondary or combined 
data collection? 
 
 
 
9.1, 9.2 
3.3 
Does the protocol specify measures of 
occurrence? (e.g., rate, risk, prevalence) 
 
 
 
9.3.1 
3.4 
Does the protocol specify measure(s) of 
association? (e.g. risk, odds ratio, excess risk, rate 
ratio, hazard ratio, risk/rate difference, number needed 
to harm (NNH)) 
 
 
 
 
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) 
 
 
 
9.3.1 
Comments: 
 
 
Section 4: Source and study populations 
Yes 
No 
N/A 
Section 
Number 
4.1 
Is the source population described? 
 
 
 
9.4 
4.2 
Is the planned study population defined in 
terms of: 
 
 
 
9.2 
4.2.1 Study time period 
 
 
 
 
4.2.2 Age and sex 
 
 
 
 
4.2.3 Country of origin 
 
 
 
 
4.2.4 Disease/indication 
 
 
 
 
4.2.5 Duration of follow-up 
 
 
 
 
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 
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) 
 
 
 
 
5.2 
Does the protocol address the validity of the 
exposure measurement? (e.g. precision, accuracy, 
use of validation sub-study) 
 
 
 
 

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Section 5: Exposure definition and 
measurement 
Yes 
No 
N/A 
Section 
Number 
5.3 
Is exposure categorised according to time 
windows?  
 
 
 
 
5.4 
Is intensity of exposure addressed?  
(e.g. dose, duration) 
 
 
 
 
5.5 
Is exposure categorised based on biological 
mechanism of action and taking into account 
the pharmacokinetics and pharmacodynamics 
of the drug? 
 
 
 
 
5.6 
Is (are) (an) appropriate comparator(s) 
identified? 
 
 
 
 
Comments: 
 
 
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? 
 
 
 
9.3.1 
6.2 
Does the protocol describe how the outcomes 
are defined and measured?  
 
 
 
9.3.1 
6.3 
Does the protocol address the validity of 
outcome measurement? (e.g. precision, accuracy, 
sensitivity, specificity, positive predictive value, use of 
validation sub-study) 
 
 
 
 
6.4 
Does the protocol describe specific outcomes 
relevant for Health Technology Assessment? 
(e.g. HRQoL, QALYs, DALYS, health care services 
utilisation, burden of disease or treatment, compliance, 
disease management) 
 
 
 
9.3.1 
Comments: 
 
 
Section 7: Bias 
Yes 
No 
N/A 
Section 
Number 
7.1 
Does the protocol address ways to measure 
confounding? (e.g. confounding by indication) 
 
 
 
 
7.2 
Does the protocol address selection bias? (e.g. 
healthy user/adherer bias) 
 
 
 
9.9 
7.3 
Does the protocol address information bias? 
(e.g. misclassification of exposure and outcomes, time-
related bias) 
 
 
 
9.9 
Comments: 
 
 

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Section 8: Effect measure 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)  
 
 
 
9.7.4 
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: 
 
 
 
9.3 
9.1.1 Exposure? (e.g. pharmacy dispensing, general 
practice prescribing, claims data, self-report, face-to-
face interview) 
 
 
 
 
9.1.2 Outcomes? (e.g. clinical records, laboratory 
markers or values, claims data, self-report, patient 
interview including scales and questionnaires, vital 
statistics) 
 
 
 
 
9.1.3 Covariates and other characteristics? 
 
 
 
 
9.2 
Does the protocol describe the information 
available from the data source(s) on: 
 
 
 
9.4 
9.2.1 Exposure? (e.g. date of dispensing, drug 
quantity, dose, number of days of supply prescription, 
daily dosage,  prescriber) 
 
 
 
 
9.2.2 Outcomes? (e.g. date of occurrence, multiple 
event, severity measures related to event) 
 
 
 
 
9.2.3 Covariates and other characteristics? 
(e.g. age, sex, clinical and drug use history, co-
morbidity, co-medications, lifestyle) 
 
 
 
 
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), Medical Dictionary for Regulatory 
Activities (MedDRA)) 
 
 
 
 
9.3.3 Covariates and other characteristics? 
 
 
 
 
9.4 
Is a linkage method between data sources 
described? (e.g. based on a unique identifier or other)  
 
 
 
 
Comments: 
 
 
Section 10: Analysis plan 
Yes 
No 
N/A 
Section 
Number 
10.1 Are the statistical methods and the reason for 
their choice described?  
 
 
 
9.7 
10.2 Is study size and/or statistical precision 
estimated? 
 
 
 
9.7 

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Section 10: Analysis plan 
Yes 
No 
N/A 
Section 
Number 
10.3 Are descriptive analyses included? 
 
 
 
9.7 
10.4 Are stratified analyses included? 
 
 
 
 
10.5 Does the plan describe methods for analytic 
control of confounding? 
 
 
 
 
10.6 Does the plan describe methods for analytic 
control of outcome misclassification? 
 
 
 
9.7 
10.7 Does the plan describe methods for handling 
missing data? 
 
 
 
9.7 
10.8 Are relevant sensitivity analyses described? 
 
 
 
9.7 
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) 
 
 
 
 
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: 
 
 
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? 
 
 
 
9.9 
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 uptake, duration of 
follow-up in a cohort study, patient recruitment, precision 
of the estimates) 
 
 
 
9.2, 9.5 
Comments: 
 
 
Section 13: Ethical/data protection issues 
Yes 
No 
N/A 
Section  
Number 
13.1 Have requirements of Ethics Committee/ 
Institutional Review Board been described? 
 
 
 
10 

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Section 13: Ethical/data protection issues 
Yes 
No 
N/A 
Section  
Number 
13.2 Has any outcome of an ethical review 
procedure been addressed? 
 
 
 
 
13.3 Have data protection requirements been 
described? 
 
 
 
10 
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?  
 
 
 
Annex 1 
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: 
 
 
Name of the main author of the 
protocol: 
 
Date:  
 
Signature:   
 
 
 
 
ANNEX 3. ADDITIONAL INFORMATION 
Charlson Comorbidity Index 
Condition 
ICD-9 
ICD-10 
Myocardial infarction 
410.x, 412.x 
I21.x, I22.x, I25.2 
Congestive heart failure 
398.91, 402.01, 402.11, 402.91, 
404.01, 404.03, 404.11, 404.13, 
404.91, 404.93, 425.4–425.9, 
428.x 
I09.9, I11.0, I13.0, I13.2, I25.5, 
I42.0, I42.5–I42.9, I43.x, I50.x, 
P29.0 
Peripheral vascular disease 
093.0, 437.3, 440.x, 441.x, 443.1–
443.9, 47.1, 557.1, 557.9, V43.4 
I70.x, I71.x, I73.1, I73.8, I73.9, 
I77.1, I79.0, I79.2, K55.1, K55.8, 
K55.9, Z95.8, Z95.9 

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Cerebrovascular disease 
362.34, 430.x–438.x 
G45.x, G46.x, H34.0, I60.x–I69.x 
Dementia 
290.x, 294.1, 331.2 
F01.x–F03.x, F05.1, G30.x, 
G31.1 
Chronic pulmonary disease 
416.8, 416.9, 490.x–505.x, 506.4, 
508.1, 508.8 
I27.8, I27.9, J40.x–J47.x, J60.x–
J67.x, J68.4, J70.1, J70.3 
Rheumatic disease 
446.5, 710.0–710.4, 714.0–714.2, 
714.8, 725.x 
M05.x, M06.x, M31.5, M32.x–
M34.x, M35.1, M35.3, M36.0 
Peptic ulcer disease 
531.x–534.x 
K25.x–K28.x 
Mild liver disease 
070.22, 070.23, 070.32, 070.33, 
070.44, 070.54, 070.6, 070.9, 
570.x, 571.x, 573.3, 573.4, 573.8, 
573.9, V42.7 
B18.x, K70.0–K70.3, K70.9, 
K71.3–K71.5, K71.7, K73.x, 
K74.x, K76.0, K76.2–K76.4, 
K76.8, K76.9, Z94.4 
Diabetes without chronic 
complication 
250.0–250.3, 250.8, 250.9 
E10.0, E10.1, E10.6, E10.8, 
E10.9, E11.0, E11.1, E11.6, 
E11.8, E11.9, E12.0, E12.1, 
E12.6, E12.8, E12.9, E13.0, 
E13.1, E13.6, E13.8, E13.9 
Diabetes with chronic 
complication 
250.4–250.7 
E10.2–E10.5, E10.7, E11.2–
E11.5, E11.7, E12.2–E12.5, 
E12.7, E13.2–E13.5, E13.7 
Hemiplegia or paraplegia 
334.1, 342.x, 343.x, 344.0–344.6, 
344.9 
G04.1, G11.4, G80.1, G80.2, 
G81.x, G82.x, G83.0–G83.4, 
G83.9 
Renal disease 
403.01, 403.11, 403.91, 404.02, 
404.03, 404.12, 404.13, 404.92, 
404.93, 582.x, 583.0–583.7, 
585.x, 586.x, 588.0, V42.0, 
V45.1, V56.x 
I12.0, I13.1, N03.2–N03.7, 
N05.2–N05.7, N18.x, N19.x, 
N25.0, Z49.0–Z49.2, Z94.0, 
Z99.2 
Any malignancy  
140.x–172.x, 174.x–195.8, 200.x–
208.x, 238.6 
C00.x–C26.x, C30.x–C34.x, 
C37.x–C41.x, C43.x, C45.x–
C58.xx, C60.x–C76.x, C81.x–
C85.x, C88.x, C90.x–C97.x 
Moderate or severe liver disease 
456.0–456.2, 572.2–572.8 
I85.0, I85.9, I86.4, I98.2, K70.4, 
K71.1, K72.1, K72.9, K76.5, 
K76.6, K76.7 
Metastatic solid tumor 
197.x–198.x 
C78.xx, C79.xx, C7B.xx 
AIDS/HIV 
042.x–044.x 
B20.x 
Abbreviations: AIDS = acquired immune deficiency syndrome; HIV = human immunodeficiency 
virus; ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification; 
ICD-10-CM = International Classification of Diseases, 10th Revision, Clinical Modification 
 

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ANNEX 4. REVIEWERS AND APPROVAL SIGNATURES 
 
The NIS Protocol must be sent for review to the following individuals prior to approval. 
 
Reviewer 
NIS involving BI 
product(s) 
NIS not involving BI product(s) 
 
 
Global NIS 
Local NIS 
NIS Lead 
X 
X 
X 
Global TM Epi 
X 
X 
X  
Global TMM / TMMA / TM Market 
Access 
X 
X 
 
Global Project Statistician 
X 
X 
 
Global TM RA 
X 
 
 
Global PVWG Chair 
X 
 
 
GPV SC 
X 
X 
X 
Global CTIS representative 
X 
 
 
Local Medical Director  
X (if local study) 
 
X 
Local Head MAcc / HEOR Director 
X (if local study) 
 
X 
Global TA Head Epi* 
X 
X  
 
Global TA Head Clinical 
Development / Medical Affairs / 
Market Access* 
X 
X 
 
Global TA Head PV RM* 
X 
 
 
RWE CoE 
X 
X 
 
PSTAT / PSTAT-MA                   
(for NISnd only) 
X 
X 
X 
NIS DM 
X 
X 
X  
Local Head MA/Clinical 
Development 
 
 
X (does not apply to 
NISed without chart 
abstraction) 
* After review by Global TM for function 
 
 
 
 
 
 
 
 
 

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Study Title: Demographic, clinical characteristics, and treatment outcomes associated 
with dedifferentiated liposarcoma patients in China 
 
Study Number:  1403.0024 
 
Protocol Version: 1.0 
 
 
I herewith certify that I agree to the content of the study protocol and to all documents 
referenced in the study protocol. 
Note: Please insert respective signatories with regard to the SOP. 
 
Position: ________ 
Name/Date:  <  /dd mmm yyyy> 
Signature: _______________ 
Position: ________ 
Name/Date:  < / dd mmm yyyy>  
Signature: _______________ 
Position: ________ 
Name/Date: _______________________ 
Signature: _______________ 
Position: ________ 
Name/Date: _______________________ 
Signature: _______________ 
Position: ________ 
Name/Date: _______________________ 
Signature: _______________ 
Position: ________ 
Name/Date: _______________________ 
Signature: _______________ 
Position: ________ 
Name/Date: _______________________ 
Signature: _______________