A Multi-center, Retrospective Registry Study on the Safety of Hakim Programmable Shunt System
Conditions: Hydrocephalus
Sponsor: Integra LifeSciences Corporation

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001  
Date of proposal: V1.1/2019-11-18 
Page 1  
 
 
Clinical Registry Study on Codman 
HAKIM Programmable Valve System 
 
 
A Multi-center, Retrospective Registry Study on the Safety of Codman 
HAKIM Programmable Valve System 
 
Product Name: Codman HAKIM Programmable Valve System 
Model and Specifications: See Appendix 1  
Proposal No.: C-HAKIM-001 
Version No.: V1.1 
Date of Version: November 18, 2019  
Category of Test: Registry study 
Lead Institution: Xuanwu Hospital, Capital Medical University  
Sponsor: Integra LifeSciences (Shanghai) Co., Ltd. 
NCT number: NCT04285489 
Confidentiality 
The contents of this document are confidential and may not be disclosed to others, excluding 
subjects who signed the Informed Consent Form (ICF) or their legal representatives, or staff 
involved in this study, without the written authorization of Integra LifeSciences, except for the 
sake of discussion with regulatory agencies or institutional review boards (IRBs)/independent 
ethics committees (IECs). 
 
 
 
 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001  
Date of proposal: V1.1/2019-11-18 
Page 2  
 
Signature Page for the Review of the Study Protocol 
Research Topic: A Multi-center, Retrospective Registry Study on the Safety of Codman HAKIM 
Programmable Valve System 
Study No.: C-HAKIM-001 
Date of Version: V1.1/November 18, 2019 
The signatures of the following team members indicate that, prior to submission to the Ethics 
Committee (EC), this clinical study, including understanding of techniques involved, statistical 
methods, research procedures, regulatory compliance, and quality control, has obtained the internal 
approval of Integra LifeSciences (Shanghai) Co., Ltd. 
 
 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
Page 3  
 
Signature Page for Investigator: 
Research Topic: A Multi-center, Retrospective Registry Study on the Safety of Codman HAKIM 
Programmable Valve System 
Proposal No.: C-HAKIM-001 
Date of Revision: V1.1/November 18, 2019 
 
I, the signer, have reviewed the study proposal and its attachments. I will conduct this clinical study in 
accordance with the requirements of this proposal, Good Clinical Practice (GCP), the ethical principles 
of the Declaration of Helsinki, and all applicable laws and regulations. I will provide a copy of this 
proposal and all relevant and permanent information to the participating research staff and supervise 
them. 
 
 
<Name> Investigator  
<Date> 
 
 
<Institution> Hospital 
 
 
  
 
 
 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
Page 4  
 
Contents 
1 Introduction ...................................................................................................................................................... 5 
2. Benefits/Risks .................................................................................................................................................. 6 
2.1 Benefits ...................................................................................................................................................... 6 
2.2 Risks .......................................................................................................................................................... 6 
3 Research purpose .............................................................................................................................................. 6 
3.1 Indications ................................................................................................................................................. 6 
3.2 Purpose ...................................................................................................................................................... 6 
4. Research Design .............................................................................................................................................. 6 
5. Endpoint .......................................................................................................................................................... 7 
5.1 Endpoint .................................................................................................................................................... 7 
5.2 Safety indicators ........................................................................................................................................ 7 
6 Study Population .............................................................................................................................................. 8 
6.1 Selection of subjects .................................................................................................................................. 8 
6.2 Inclusion criteria ........................................................................................................................................ 8 
6.3 Exclusion criteria ....................................................................................................................................... 8 
7 Research Process .............................................................................................................................................. 8 
7.1 Screening and enrollment .......................................................................................................................... 8 
7.1.1 Screening of subjects .............................................................................................................................. 8 
7.1.2 Informed consent ..................................................................................................... 错误!未定义书签。 
7.1.3 Enrollment of subjects ............................................................................................................................ 9 
7.2 Days -30 to -1 before the operation ........................................................................................................... 9 
7.3 Operation period (Day 0, the day of operation):........................................................................................ 9 
7.4 Postoperative follow-up period: Days 1-365 ............................................................................................. 9 
8 Adverse Event Reporting ............................................................................................................................... 10 
8.1 Adverse events......................................................................................................................................... 10 
8.1.1 Adverse events...................................................................................................................................... 10 
8.1.2 Anticipated operation-related adverse events ....................................................................................... 10 
8.2 Unanticipated adverse device effect ........................................................................................................ 11 
8.3 Serious Adverse Events ........................................................................................................................... 11 
8.4 Duration of follow-up after an adverse event .......................................................................................... 11 
8.5 Adverse event reporting .......................................................................................................................... 11 
8.5.1 Severity criteria .................................................................................................................................... 12 
8.5.2 Determination of causal relationship .................................................................................................... 12 
9 Early Termination of the Study .................................................................................................................... 122 
9.1 Reason of early termination ................................................................................................................... 122 
9.2 Early termination of this study by a subject ............................................................................................ 13 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
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9.3 Early termination of this study by the sponsor ........................................................................................ 13 
10 Statistical Methods ....................................................................................................................................... 13 
10.1 Research design ..................................................................................................................................... 13 
10.2 General considerations .......................................................................................................................... 14 
10.3 Sample size ............................................................................................................................................ 14 
10.4 Criteria of qualification/disqualification of the trial results ................................................................ 155 
10.5 Interim analysis ................................................................................................................................... 155 
10.6 Analysis plan ....................................................................................................................................... 155 
10.7 Report .................................................................................................................................................. 156 
11 Research Management and Administration ................................................................................................ 166 
11.1 Responsibilities of investigators and the sponsor ................................................................................ 166 
11.1.1 Responsibilities of investigators ......................................................................................................... 16 
11.1.2 Responsibilities of the sponsor ........................................................................................................... 16 
11.2 Assessment, initiation, monitoring, and close of visits ......................................................................... 16 
11.2.1 Assessment of visits ........................................................................................................................... 16 
11.2.2 Initiation of visits ................................................................................................................................ 16 
11.2.3 Monitoring of visits .......................................................................................................................... 177 
11.2.4 Last visit to research centers ............................................................................................................. 177 
11.3 Documents required ............................................................................................................................... 17 
11.3.1 Source documents ............................................................................................................................. 188 
11.3.2 Source data verification (SDV) .......................................................................................................... 18 
11.3.3 Case Record Form (CRF) ................................................................................................................... 18 
11.3.4 Archive and data retention ................................................................................................................ 199 
1 Introduction .................................................................................................................................................. 5 
2. Benefits/Risks .............................................................................................................................................. 6 
2.1 Benefits ...................................................................................................................................................... 6 
2.2 Risks ........................................................................................................................................................... 6 
3 Research purpose ......................................................................................................................................... 6 
3.1 Indications ................................................................................................................................................. 6 
3.2 Purpose ...................................................................................................................................................... 6 
4. Research Design .......................................................................................................................................... 6 
5. Endpoint ...................................................................................................................................................... 7 
5.1 Endpoint .................................................................................................................................................... 7 
5.2 Safety indicators ........................................................................................................................................ 7 
6 Study Population .......................................................................................................................................... 8 
6.1 Selection of subjects .................................................................................................................................. 8 
6.2 Inclusion criteria ........................................................................................................................................ 8 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
Page 6  
 
6.3 Exclusion criteria ........................................................................................................................................ 8 
7 Research Process .......................................................................................................................................... 8 
7.1 Screening and enrollment ......................................................................................................................... 9 
7.1.1 Screening of subjects .............................................................................................................................. 9 
7.1.2 Informed consent ................................................................................................................................... 9 
7.1.3 Enrollment of subjects ............................................................................................................................ 9 
7.2 Days -30 to -1 before the operation .......................................................................................................... 9 
7.3 Operation period (Day 0, the day of operation): ....................................................................................... 9 
7.4 Postoperative follow-up period: Days 1-365 ........................................................................................... 10 
8 Adverse Event Reporting ............................................................................................................................ 10 
8.1 Adverse events ........................................................................................................................................ 10 
8.1.1 Adverse events ..................................................................................................................................... 10 
8.1.2 Anticipated operation-related adverse events .................................................................................... 10 
8.2 Unanticipated adverse device effect ....................................................................................................... 11 
8.3 Serious Adverse Events ........................................................................................................................... 11 
8.4 Duration of follow-up after an adverse event ......................................................................................... 11 
8.5 Adverse event reporting .......................................................................................................................... 11 
8.5.1 Severity criteria..................................................................................................................................... 12 
8.5.2 Determination of causal relationship ................................................................................................... 12 
9 Early Termination of the Study ................................................................................................................... 12 
9.1 Reason of early termination .................................................................................................................... 12 
9.2 Early termination of this study by a subject ............................................................................................ 13 
9.3 Early termination of this study by the sponsor ....................................................................................... 13 
10 Statistical Methods ................................................................................................................................... 13 
10.1 Research design ..................................................................................................................................... 13 
10.2 General considerations .......................................................................................................................... 14 
10.3 Sample size ............................................................................................................................................ 14 
10.4 Criteria of qualification/disqualification of the trial results .................................................................. 15 
10.5 Interim analysis...................................................................................................................................... 15 
10.6 Analysis plan .......................................................................................................................................... 15 
10.7 Report .................................................................................................................................................... 16 
11 Research Management and Administration............................................................................................. 16 
11.1 Responsibilities of investigators and the sponsor ................................................................................. 16 
11.1.1 Responsibilities of investigators ......................................................................................................... 15 
11.1.2 Responsibilities of the sponsor........................................................................................................... 15 
11.2 Assessment, initiation, monitoring, and close of visits ......................................................................... 16 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
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11.2.1 Assessment of visits ............................................................................................................................ 16 
11.2.2 Initiation of visits ................................................................................................................................ 16 
11.2.3 Monitoring of visits............................................................................................................................. 17 
11.2.4 Last visit to research centers .............................................................................................................. 17 
11.3 Documents required .............................................................................................................................. 17 
11.3.1 Source documents .............................................................................................................................. 18 
11.3.2 Source data verification (SDV) ............................................................................................................ 18 
11.3.3 Case Record Form (CRF) ..................................................................................................................... 18 
11.3.4 Archive and data retention................................................................................................................. 19 
11.3.5 Audit and inspection........................................................................................................................... 19 
11.4 Data Collection and Management Responsibilities ............................................................................. 199 
12 Ethical and Regulatory Requirements .......................................................................................................... 20 
12.1 Ethics Committee .................................................................................................................................. 20 
12.2 Informed consent ................................................................................................................................... 20 
12.3 Subject confidentiality ........................................................................................................................... 20 
12.4 Revision of the study proposal .............................................................................................................. 20 
12.5 Proposal deviation ................................................................................................................................. 21 
13 Publication Policies .................................................................................................................................... 211 
14 Devices ....................................................................................................................................................... 222 
14.1 Count of research-related devices........................................................................................................ 222 
14.2 Return of research-related devices ........................................................................................................ 22 
14.3 Complaint about devices ....................................................................................................................... 22 
14.3.1 Complaint about devices .................................................................................................................... 22 
References ....................................................................................................................................................... 233 
Appendix 1: Table of Product Specifications and Models .............................................................................. 244 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
Confidential 
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Summary of the Proposal 
Research Topic: 
A Multi-center, Retrospective Registry Study on the Safety of Hakim 
Programmable Shunt System 
Research Purpose:
This study aimed to collect safety information from subjects implanted with a 
shunt system (trade name: Hakim Shunt Programmable System) produced by 
Codman & Shurtleff, Inc. of the United States. Device safety would be assessed 
based on all the adverse events that occurred within one year after the subjects 
implanted the catheter. 
No. of Subjects: 
130 
No. 
of 
Research 
Centers: 
About six research centers 
Research Design: 
This study was designed to be single arm, multi-center, observational and 
retrospective trial. It is designed to gather information from actual clinical 
practice from the clinical records of patients in relation to the one-year clinical 
safety to the use of implant of Hakim programmable shunt system. 
A total of 130 patients would be retrospectively enrolled. Information would be
collected on adverse events of subjects enrolled within one year after the 
implantation of the Hakim Shunt Programmable System from April 01, 2017 to
August 31, 2019. 
The following information would be collected from subjects' medical records or 
hospitals' databases (if any): 
1. General condition of the subjects 
2. Intraoperative condition and shunt system implantation 
3. Information on the shunt system product 
4. Adverse events of subjects within one year after the operation and 
classification of the adverse events 
5. Relevant examinations in case of postoperative infection 
6. Other adverse event-related information (except anticipated adverse events) 
Research Duration:2019-2020 
Inclusion Criteria: 
Subjects who met all of the following inclusion criteria would be enrolled: 
1. The informed consent was exempted by the Ethics Committee of a research 
center. Either a subject or his/her legal representative signed the informed 
consent form (ICF) prior to enrollment. 
2. A subject had an indication suitable to use Hakim Shunt Programmable 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
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System. 
3. A subject received a Hakim Shunt Programmable System at least one year ago.
Exclusion Criteria:
Subjects who met any of the following exclusion criterion were excluded: 
1. A subject didn't have an indication suitable to use the product. 
2. A subject was known to be allergic to a component or ingredient of the product 
to be implanted, including silicone tubing and other components. 
3. According to the comprehensive judgment of an investigator, a subject had an 
infection of the implant site when the shunt system was implanted, such as 
ventriculitis, meningitis, peritonitis, and local implant skin infection. 
4. A subject was simultaneously implanted with another shunt system different 
from Hakim Shunt Programmable System. 
5. A subject had a contraindication of the shunt operation. 
6. A subject had uncorrected coagulopathy or any bleeding disorder. 
Endpoint 
1. Non-infection rate of a subject within one year 
2. Type and incidence of adverse events of a subject within one year  
 
 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
Confidential 
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Schedule of Data Collection Form 
 
Screening 
Preoperative 
Operation 
Postoperative 
follow-up 
Time of data collection 
NA 
-30 to -1 days
0 
Days 1-365 
Signed the ICF (if applicable)1 
X 
 
 
 
Review of inclusion and exclusion 
criteria 
X 
 
 
 
Medical History 
 
X 
 
 
Laboratory examination 
 
X 
 
X+ 
Operative process 
 
 
X 
 
Device application record 
 
 
X 
 
Adverse events2 
 
 
X* 
X* 
Serious Adverse Events 
 
 
X* 
X* 
End of study/exit 
 
 
X 
X 
Record of concomitant medication3
 
X* 
X* 
X* 
Record of concomitant treatment4 
 
 
X* 
X* 
 
+ 
Suspicious or proven infection 
* 
If any 
Notes: 1. The ICF (if applicable) needed to be completed before screening. 
2. A postoperative anticipated adverse event was not counted as an adverse event. 
3. Only antibiotics and medications related to postoperative adverse events were recorded. Only the 
administration of antibiotics within seven days prior to the operation was recorded. 
4. Only the treatment and operation associated with postoperative adverse events were recorded. 
 
 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
Confidential 
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Abbreviations: 
AE 
Adverse events 
CRF 
Case Record Form 
CV 
Curriculum Vitae 
EC 
Ethics Committee 
ICF 
Informed Consent Form 
IFU 
Instructions for Use 
GCP 
Good Clinical Practice 
NMPA 
National Medical Products Administration 
SAE 
Serious adverse event 
SDV 
Source data verification 
UADE 
Unanticipated adverse device effect 
 
 
 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
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1 Introduction 
1.1 Background and principle 
Abnormal enlargement of part or all of subarachnoid space or ventricles, the abnormal accumulation 
of cerebrospinal fluid (CSF) in subarachnoid space or ventricles is called hydrocephalus. It is a 
circulation disorder of CSF caused by many pathological reasons1. A shunt system mainly drains CSF 
from the accumulation site to the abdominal cavity, the lumbar cistern, and the atria through a catheter 
so as to address dilated ventricles and alleviate the pressure on the brain. 
The earliest permanent CSF shunt operation occurred in 1893. A glass catheter was placed in a lateral 
ventricle of a patient with hydrocephalus, the end of which was placed under the skin. The head 
circumference of the patient was significantly reduced after the operation2. The principle of modern 
shunt operation can be dated back to the 1870s. Ventriculo-peritoneal shunt operation had become a 
common treatment for hydrocephalus3. China released Specialist Consensus on the Standardized 
Treatment of Hydrocephalus in China in 2013, which regarded CSF shunt as an important operation 
for hydrocephalus and proposed suggestions on technical key points.  
However, in terms of the treatment of neurosurgical diseases, the incidence of complications of shunt 
operations is the highest, mainly including shunt infection, obstruction or rupture of a shunt catheter, 
displacement of an intracranial or abdominal shunt catheter, excessive or insufficient drainage of CSF, 
intracranial hemorrhage, and epilepsy1. Infection is a common complication and important cause of 
revision. Its incidence rate is 3-29%. Approximately 90% of the cases occur within one year after the 
operation. If it is combined with ventriculitis, the mortality rate can be as high as 30-40%3. For 
children, even if the infection can be controlled, long-term complications, such as epilepsy, cognitive 
impairment, and physical and delayed psychological development, may occur4. 
According to the analysis of recent literature, among a total of 8,588 shunt operations (3,291 cases 
with an antibiotic-impregnated catheter, 5,297 cases with a non-antibiotic-impregnated catheter), the 
postoperative infection of normal shunt system was 7.2%5.  
In addition to infection, complications of CSF shunt operations include excessive and insufficient 
drainage of CSF associated with pressure regulation; obstruction of the shunt catheter, usually due to 
a poor position of an intracranial shunt catheter, the accumulation of red blood cells or brain tissues in 
the shunt pump, or wrapping of a shunt catheter by abdominal omentum majus; rupture of shunt 
catheter, mostly occurring at the junction of the catheter and the pump and a subcutaneous area; and 
rare complications, such as displacement of a shunt catheter, wound, intracranial hemorrhage, and 
symptoms of Parkinson's Disease1. 
Hakim Programmable Shunt System manufactured by Codman & Shurtleff, Inc. in the United States 
constitute of a systemic silicon catheters and programmable valves. Hakim Programmable Shunt 
System has been safely used around the world for more than a decade. However, there is a lack of data 
on the safety of the product in long-term follow-up and clinical application in the Chinese population. 
1.2 Research-related devices 
Devices verified in this study were programmable shunt system catheters (trade name: Hakim 
programmable shunt system) manufactured by Codman & Shurtleff, Inc., U.S.A. Its registration 
number is G.S.Y.J.X. (J) 2017 3661104. Please refer to the Appendix 1 for the product specifications 
and models in this study. 
 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
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2. Benefits/Risks 
2.1 Benefits 
Hakim programmable shunt system serves as the shunt system of hydrocephalus treatment. 
Hydrocephalus shunt operations can alleviate or eliminate hydrocephalus and improve clinical 
symptoms and signs. Meanwhile, retrospective collection of data and experience of clinical safety can 
be used as a reference for investigators and enterprises and conducive to the diagnosis and treatment 
of future subjects. However, such data and experience had no extra benefits for the participants in this 
study. 
2.2 Risks 
This is a retrospective study. It did not intervene in subjects' normal treatment. It objectively collected 
patients' clinical data. Hence, there were no additional risks associated with participating in this study. 
 
3 Research purpose 
3.1 Indications 
Hakim programmable shunt system: Hakim programmable shunt system serves as the shunt system of 
hydrocephalus treatment. 
3.2 Purpose 
This study aimed to collect safety information from subjects implanted with a programmable shunt 
system (trade name: Hakim programmable shunt system) produced by Codman & Shurtleff, Inc. of 
the United States. Device safety would be assessed based on all the adverse events that occurred within 
one year after the subjects were implanted with the catheter. 
 
4. Research Design 
4.1 Basic design 
This study was designed to be single arm, multi-center, observational and retrospective.  It is designed 
to gather information from actual clinical practice from the clinical records of patients in relation to 
the one-year clinical safety to the use of operation of Hakim programmable shunt system.  The 
treatment date would be defined as the implant date of the Hakim programmable shunt system.  The 
study period includes a general history period that includes up to 30 days prior to the treatment date 
and a follow-up period of up to 365 days post implant operation. A total of 130 patients would be 
enrolled and adverse events would be collected for subjects enrolled within one year after the 
implantation of Hakim programmable shunt system from April  01, 2017 to August  31, 2019, through 
case review or hospital database (if any). 
 
4.2 Data collection 
The following information would be collected from subjects' medical records: 
1. General condition and medical history of the subjects  

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Proposal No.: C-HAKIM-001 
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2. Intraoperative condition and shunt system implantation 
3. Information on the shunt system product 
4. Adverse events of subjects within one year after the operation and classification of the adverse events 
5. Relevant examinations in case of postoperative infection 
6. Other adverse event-related information (except anticipated adverse events)  
Information on adverse events would be collected. And the safety of clinical application of the product 
would be assessed. 
 
5. Objectives and Endpoint 
5.1. Objectives 
The objective of this study is to assess the safety of the Hakim programmable shunt system. 
 
5.2 Primary Endpoint 
1. Non-infection rate of a subject within one year post implant 
2. Incidence of adverse events within one year post implant 
5.2 Safety indicators 
The incidence of adverse events was observed in line with the IFU. Key attention should be paid to: 
 Obstruction of a cerebral ventricular catheter 
 Falling out of a programmable shunt system 
 Poor position of a catheter 
 Intestinal perforation, abdominal and pseudocysts, umbilical fistula, pseudo-acute appendicitis, 
infection, and ascites 
 Subcutaneous twist, rupture, distal obstruction, and distal retraction from the abdominal cavity 
 Failure of a programmable shunt system 
 Mechanical failure 
 Obstruction or infection of the shunt path  
 Leakage of CSF in an implanted programmable shunt system 
 Excessive drainage 
 Damage of intracranial or abdominal tissue 
 Fibrous adhesion 

Integra LifeSciences (Shanghai) Co., Ltd. 
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6 Study Population 
6.1 Selection of subjects 
Subjects who received a hydrocephalus shunting operation between April 01, 2017 and August 31, 
2019 and met the inclusion criteria were enrolled. As this was a retrospective study, it would apply for 
the exemption of informed consent from the Ethics Committee of a center. For the centers which did 
not exempt informed consent, the informed consent process would be completed prior to the start of 
data collection, either by telephone or by anyway approved by the Ethics Committee. 
6.2 Inclusion criteria 
Subjects who met all of the following inclusion criteria would be enrolled: 
1. The informed consent was exempted by the Ethics Committee of a research center. Or a subject or 
his/her legal representative signed the informed consent form (ICF) prior to the enrollment; 
2. A subject had an indication suitable to use Hakim programmable shunt system; 
3. A subject received a Hakim Shunt Programmable System at least one year ago. 
6.3 Exclusion criteria 
Subjects who met any of the following exclusion criterion were excluded: 
1. A subject didn't have an indication suitable to use the product; 
2. A subject was known to be allergic to a component or ingredient of the product to be implanted, 
including silicone tubing and other components;  
3. According to the comprehensive judgment of an investigator, a subject had an infection of the 
implant site, when the shunt was implanted, such as ventriculitis, meningitis, peritonitis, and local 
implant skin infection; 
4. A subject was simultaneously implanted another shunt system different from Hakim programmable 
shunt system; 
5. A subject had a contraindication of the shunt operation; 
6. A subject had uncorrected coagulopathy or any bleeding disorder. 
 
7 Research Process 
The research process included: Screening and enrollment of subjects, Days -30 to -1 before the 
operation, Day 0, the day of operation, and one-year follow-up (Days 1-365) after the operation. 
7.1 Screening and enrollment 
7.1.1 Screening of subjects  
Qualified and authorized investigators or clinical study coordinators reviewed the medical records of 
subjects to screen subjects eligible for this study. 

Integra LifeSciences (Shanghai) Co., Ltd. 
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7.1.3 Enrollment of subjects  
If a subject met all the inclusion criteria and did not meet any exclusion criterion, he/she could be 
included in the retrospective analysis cohort. Subjects could be considered as enrolled in this study 
only if they met the following requirements: 
1) A subject met all the inclusion criteria and did not meet any exclusion criterion; and 
2) The ICF was signed (in terms of a research center that did not waive informed consent). 
7.2 Days -30 to -1 before the operation 
The following information needed to be collected and recorded: 
1. Demographic information and medical history of a subject before the operation: including patient 
age, gender, height, weight, preoperative diagnosis; past medical history, past surgical history, personal 
history; preoperative laboratory examination results: including white blood cells, red blood cell count, 
neutrophilic granulocyte count, hemoglobin content, platelet count, alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), C-reactive protein, albumin, blood glucose, APTT, PT, and INR. If 
there were multiple laboratory tests before the operation, the latest results should be collected. 
2. Concomitant medication: Only the administration of antibiotics within seven days prior to the 
operation was recorded. 
7.3 Operation period (Day 0, the day of operation): 
The following information needed to be collected and recorded: 
1. Operation: date of surgery, surgeon, surgical procedure, start and stop time of the operation, blood 
loss during the operation, medications, intraoperative complications, intraoperative shunt, and 
combined treatment; 
2. Record of devices used during the operation: type, No. and batch No. of the cerebral ventricular 
shunt catheter; type, No. and batch No. of the pressure regulating valve; and type, No. and batch No. 
of shunt catheters at the abdominal cavity/the lumbar cistern/ the atria. 
7.4 Postoperative follow-up period: Days 1-365 
An adverse event (except an anticipated adverse event) discovered during the review of postoperative 
history or hospital database (if any) should be recorded: 
The date, description, concomitant therapy, and outcome of an adverse event, information related to 
the operation and the product, not matter the implanted part was taken out due to an adverse event, and 
concomitant medication and treatment should be recorded. 
Additional records were required for the following special adverse events: 
1. Infection: Infection site which is usually classified into intracranial, skin, and abdominal infections. 
For intracranial infection, date of infection, white blood cell count, red blood cell count, neutrophilic 
granulocyte count, hemoglobin content, alanine aminotransferase (ALT), aspartate aminotransferase 
(AST), C-reactive protein, blood glucose, traits and color of CSF, cell count, Pan's test results, contents 
of protein, sugar, and chloride in CSF, bacterial culture type, and bacterial susceptibility to rifampicin 
and clindamycin should be recorded. For skin infection and abdominal infection: white blood cell 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
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Confidential 
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count, red blood cell count, neutrophilic granulocyte count, bacterial culture type, and bacterial 
susceptibility to rifampicin and clindamycin should be recorded. 
2. Obstruction of catheter: site, reason (judged by an investigator), and nature of obstruction should be 
recorded. 
3. Leakage of CSF: date and position of leakage should be recorded. 
4. Mechanical failure: type of mechanical failure should be recorded, including falling out, 
displacement, twisting, and rupture.  
A patient who died within one year was still considered as a complete case. The form of SAE should 
be completed. And the death should be specified in this study endpoint table. 
 
8 Adverse Event Reporting 
8.1 Adverse events 
8.1.1 Adverse events 
Adverse event (AE) refers to any adverse medical event of a subject, no matter if it is related to this 
study or a research-related device. 
During the assessment of a subject enrolled to this clinical study, an investigator should each time 
determine whether there was an AE and collect information, including date, severity, treatment, 
prognosis, and analysis of the AE, and research-related device, operation, or drug, in as detailed a way 
as possible. 
Information of all AEs, research-related device failures, and other product issues should be as much as 
possible collected from existing medical records, and entered into CRFs. 
8.1.2 Anticipated operation-related adverse events  
Anticipated AE refers to an event that occurred after the operation during hospitalization (relative to 
the baseline change of a subject), which was an anticipated consequence of the operation. If an 
anticipated AE occurred, it would not be reported to the sponsor. 
Currently, postoperative anticipated AEs known include: 
 Wound pain within 48 hours followed by agitation 
 Fever lower than 38.5°C within 48h 
 Abdominal distension and constipation within 48h 
 A small amount of wound exudation within 48h 
 Mild anemia (hemoglobin > 90g/L) 
 Increase in white blood cells within 48h 

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8.2 Unanticipated adverse device effect 
Unanticipated adverse device effect (UADE) refers to a serious adverse effect, a life-threatening issue, 
or death caused by or related to the devices, or a serious and unanticipated issue related to the rights, 
safety, or health of a subject and the devices. In addition, the nature, severity, or frequency of such an 
event was not specified in the study proposal, IFU, and clinical trial instructions. 
8.3 Serious Adverse Events 
Serious adverse event (SAE) refers to any of the following adverse events:  
1) 
Cause Death, 
2) 
Serious deterioration of a subject's health, including: 
a. 
A life-threatening illness or injury, 
b. Permanent damage of the body structure or a body function, 
c. 
Hospitalization or extension of the current hospital stay: 
d. Medical or surgical intervention required to avoid a life-threatening disease or prevent 
permanent damage to the body structure or a body function, 
3) 
Fetal distress, fetal death, congenital malformation, or birth defects.  
In this retrospective study, planned hospitalization or medical intervention due to a disease existing 
before the operation not followed by serious deterioration of health was not regarded as a serious 
adverse event. 
8.4 Duration of follow-up after an adverse event 
As this is a retrospective study, it did not intervene in subjects' normal treatment. Therefore, all adverse 
events were properly evaluated by an investigator based on medical requirements. And no additional 
follow-up would be performed. 
8.5 Adverse event reporting 
Within one year after the shunt operation of a subject, all the adverse events (except anticipated adverse 
events) recorded in the medical records or hospital database (if any) should be reported. An investigator 
reported AEs to the sponsor via CRF. 
An investigator should record the nature, severity, treatment and prognosis of an AE and determine the 
correlation with the devices, medication, or operation involved in this clinical study. 
An investigator must report SAEs and UADEs to the sponsor (or a designated person) within 24h after 
their occurrence, and report them to the Ethics Committee in a timely manner. In the event of any 
request by the sponsor, additional information should be provided. The investigator should judge the 
time associated with the research product. The research center should report them to a local medical 
device adverse event monitoring organization. Death should be reported within 7 days, after it was 
known. A serious injury or an event that might result in death or a serious injury should be reported 
within 20 days after it was known. The sponsor would report to NMPA and/or a local medical device 
adverse event monitoring organization in line with the same requirements as those of the research 

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center. If the adverse event had existed or been reported in the previous reporting system, it would be 
unnecessary to report it repeatedly. 
The sponsor should regularly inform all the clinical investigators of this study of all SAEs and UADEs. 
8.5.1 Severity criteria  
The severity of an adverse event could be classified as mild, moderate, and severe according to the 
following criteria. 
 Mild: It was transient and mild with no influence on daily life, and no special measures or 
treatment was required. 
 Moderate: It had a slight impact on daily life. Measures or treatments were needed, if necessary. 
 Severe: It had a serious impact on daily life. Special measures or treatment must be taken, and 
hospitalization was required, if necessary. 
8.5.2 Determination of causal relationship  
The relevance between any adverse event and a research-related device should be judged, according 
to the following criteria, including unrelated, possibly unrelated, possibly related, probably related, 
and definitely related. If an AE was judged to be possibly related, probably related, or definitely related 
to a research-related device, such an AE was related to the devices. 
 Unrelated: An AE was not related to the devices. 
 Possibly unrelated: An adverse event was more likely to be related to other factors, such as 
concomitant medication or disease. Or the timing of the AE indicated that it was unlikely to be 
caused by a research-related device. 
 Possibly related: An AE might be caused by a research-related device. Other reasons were not 
excluded, such as concomitant medication or disease. When the occurrence of an AE and the use 
of a research-related device had a reasonable time sequence, the causal relationship between the 
event and a research-related device could not be excluded. 
 Probably related: An AE was probably caused by a research-related device. An AE and the use of 
a research-related device had a reasonable time sequence. For example, the causal relationship 
was proved after the device was taken out. There was unlikely to be another explanation, such as 
concomitant medication or disease. 
 Definitely related: The type of an AE was identified as a side effect of a research-related device, 
which could not be explained by other reasons, such as concomitant medication and disease. The 
time of an AE strongly implied a causal relationship (e.g. reaction after the removal and re-
implantation of a device). 
 
9 Early Termination of the Study 
9.1 Reason of early termination 
Possible reasons of early termination include, but are not limited to, the following: 

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 Withdrawal of informed consent: (For a research center which required its subjects to sign the 
ICF) a subject decided to withdraw from this study. The decision must be "determined by the 
subject himself/herself" and recorded in the subject's research file; 
 Early termination of this study: The sponsor might decide to suspend this study in advance for any 
reason. 
9.2 Early termination of this study by a subject 
For a research center which required its subjects to sign the ICF, if a subject terminated this study in 
advance, the reason must be recorded in the source document and the file of the research center and 
submitted via CRF.  
A subject who terminated this study in advance could not be replaced, and his/her data would be 
included in the results analysis, unless the subject submitted a written request to withdraw the data.  
9.3 Early termination of this study by the sponsor 
The sponsor had the right to temporarily suspend or terminate in advance the research of a single 
research center, multiple research centers, or all the research centers at any time. The reasons include, 
but are not limited to: Security or ethical issues, inaccurate or incomplete data records, non-
compliance, or unsatisfactory quantity or quality of enrollment. 
If this study was terminated or suspended, the sponsor or its representative should follow applicable 
regulatory requirements to inform investigators/their organizations and regulatory authorities of the 
reason. The sponsor or investigators/their organizations should comply with applicable regulatory 
requirements to notify the Ethics Committees and submit the reason. 
 
10 Statistical Methods 
 
10.1 Primary endpoint 
The primary endpoint of the study is: 
Non-CSF infection within one year post implant. 
Incidence of adverse events within one year post implant, which includes: 
 Obstruction of a cerebral ventricular catheter 
 programmable shunt system slipping  
 Poor position of a catheter 
 Intestinal perforation, abdominal and pseudocysts, umbilical fistula, pseudo-acute appendicitis, 
infection, and ascites caused by catheter 
 Subcutaneous twist, rupture, distal obstruction, and distal retraction from the abdominal cavity 
 Failure of a programmable shunt system 

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 Mechanical failure 
 Obstruction or infection of the shunt path  
 Leakage of CSF in an implanted programmable shunt system 
 Excessive drainage 
 Damage of intracranial or abdominal tissue 
 Fibrous adhesion related to distal catheter 
 
10.2 General considerations 
The primary analysis will be descriptive in nature and will be based on information in the data 
collection form.  
The extraction of the data from the medical records will be done by the investigators who care for the 
patients; in this way, the possible limitation of the study that is normally observed in other studies of 
review of clinical histories in which the information can be interpreted incorrectly is minimized.  
 
10.3 Sample size 
This study will provide infection free survival at 1 year for Hakim programmable shunt system and 
ensure 95% confidence bounds acceptable (half width < 5%). If N0 is the number of enrolled 
subjects, the number of infection free subjects after t years will be approximately: 
 
N(t) = N0 e -(r1+r2) t 
where r1 and r2 are the infection rate and the dropout rate respectively. 
Following the Peto method, parameter estimation (e.g., infection free survival) in survival analysis will 
be performed. Defined S(t) as the survival rate at t years post operation, the Kaplan-Meier half 95% 
confidence width for the survival rate is given by: 
 
 
margin = 1.96 ඥ[𝑆(𝑡)]ଶ[1 −𝑆(𝑡)]/𝑁(𝑡). 
 
Based on published data, the annual infection rate of a normal shunt system is assumed to be 7.2%5, 
then the 1-year infection free rate is 92.8%. With an enrollment of 130 patients and a dropout rate of 
10%, by using the aforementioned formula, the sample size for infection free survival at one year post 
operation is given by: 
 
N(1) = N0 e –(r1+r2) = 130 * e –(0.072+0.1) = 109.  
 

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The half 95% confidence width of the survival given by: 
margin = 1.96 ඥ[92.8%]ଶ[1 −92.8%]/109 = 4.7%.  
 
The precision of 4.7% is less than 5% and is considered acceptable.    
10.4 Criteria of qualification/disqualification of the trial results 
This study is to collect post-marketing safety data on the Chinese population implanted Hakim 
programmable shunt system, according to product registration requirements. The occurrence, type, 
severity, frequency, of all AEs occurring during the study period, as well as the correlation between 
AEs and the product will be collected and presented. Hence, criteria of qualification/disqualification 
were not applicable. 
10.5 Interim analysis 
No interim analysis is planned for this study. 
10.6 Analysis plan 
All study data collected in this study will be presented in subject data listings.  Statistical analyses will 
be performed using SAS 9.3 or later version. Other valid software might also be used as appropriate.   
Data analysis will be carried out primarily using descriptive statistics.  In general, mean, standard 
deviation, median, minimum and maximum will be calculated for continuous variables, and   
frequencies and percentages will be presented for categorical variables.  If necessary, additional 
descriptive statistics may be calculated.    
Analysis population 
The primary analysis population for this study is the Per Protocol (PP) populations.  The PP population 
will include all subjects who meet the inclusion/exclusion criteria  
Subgroup analyses 
The main subgroups that will be analyzed, in addition to the total population per protocol, will be 
adults and children. 
Endpoint analysis 
The primary endpoint of1-year infection free survival rate will be estimated by the Kaplan-Meier 
method, the 95% confidence width for the survival rate will be estimated by the Peto method.  The 
Kaplan-Meier survival curve will be presented. 
 
10.7 Report  
After the data of all subjects were completely collected (within one year after the operation), a clinical 
study report would be compiled and submitted to NMPA for review as material supporting the 
extension of product registration. 
 

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11 Research Management and Administration 
11.1 Responsibilities of investigators and the sponsor 
11.1.1 Responsibilities of investigators  
An investigator should ensure that all the work and services herein or incidental matters of all the work 
and services herein were implemented in accordance with the highest standards of medical and clinical 
study practice. An investigator should perform his/her duties according to all applicable laws and 
regulations. An investigator should provide a copy of the current study proposal to all assistant 
investigators or research staff of other research centers in charge of research implementation, and 
ensure all research staff are qualified, trained, and competent. 
An investigator should submit the progress report, the safety report required by local regulations or 
national regulatory requirements, and study completion notice to the EC within the specified time limit. 
11.1.2 Responsibilities of the sponsor  
The sponsor should be solely responsible for the implementation of this study. The sponsors should 
ensure compliance with all applicable regulations and guidelines during this study.  
The sponsor should properly monitor clinical study centers, obtain subjects' informed consent, 
provided quality data in compliance with regulations, notify investigators, ECs, and regulatory 
authorities of AEs, revocation of ethical approval, a list of current investigators (if necessary), and 
relevant safety issues, in accordance with international and local guidelines, and describe proposal 
deviation, as appropriate. The sponsor should write the safety report, the progress report, and the final 
clinical study report. 
 
11.2 Assessment, initiation, monitoring, and close of visits 
11.2.1 Assessment visits  
The main requirements for which a research center and an investigator are selected and continue to 
participate in this study include: They have sufficient experience in relevant research areas and all 
research operations, and adhere to safety commitments and the study proposal. The number of subjects 
should also be consistent with what is specified in the study proposal. The sponsor and its designated 
personnel should select qualified investigators, obtain a copy of signed research agreement from the 
latter, and provide the latter with the information necessary to implement this study, including any 
amendment or update to the research information specific to this study. 
11.2.2 Initiation visits  
At the beginning of this study, the monitor designated by the sponsor would visit research centers to 
confirm that all investigators personnel and research-related items were in place. The monitor would 
offer research-related training to investigators, including study proposals, informed consent procedures 
(if applicable), complaint of adverse events and research-related devices, completion of CRF, 
maintenance of research documents, responsibility of immediate notification to the sponsor of 
investigator changes, monitoring process, and GCP. During the initiation of visits, all preparations for 
subjects enrolled should be carried out. 

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11.2.3 Monitoring visits 
At all research centers, the monitoring of this study should be carried out by the sponsor or personnel 
designated by the sponsor. Monitoring should ensure: 
 Rights and health of subjects were protected; 
 This study was conducted in accordance with all applicable regulations and guidelines; 
 The study proposal and corresponding amendments were complied with; 
 The accuracy of data recorded should be confirmed by verifying source documents.  
Throughout the clinical study period, all effective research centers should be regularly monitored and 
visited to ensure that investigators fulfilled their obligations. These visits were to ensure that the 
research centers met requirements for facilities, follow the study proposal and all amendments, 
informed their ECs of changes to the proposal as required, maintain complete records, report to the 
sponsor and their ECs appropriately and in a timely manner, and that investigators were implementing 
all agreed matters. 
11.2.4 Closing visiting of research centers  
At the completion of the clinical study (Data were completely collected from all subjects enrolled. All 
CRFs were completed. And all data queries were resolved), the sponsor or designated personnel should 
inform research centers to end this study and close their visit to the centers. 
At the last visit to research centers, all unused research materials should be collected and returned to 
the sponsor or destroyed at research centers. The monitor and investigator should ensure that the 
investigator folder and other research-related materials were up-to-date and complete, and that all 
outstanding issues of previous visits were resolved. During this visit, others issues to be reviewed 
included: storage of research materials, possibility of audit of research centers, open policies, and 
notice to ECs about the end of this study. 
If a research center failed to enroll any subject for any reason, and the sponsor decided that the research 
center should stop further participation in this study, before the end of this clinical study, the last visit 
to the research center could be planned. In this case, the sponsor should instruct investigators to 
complete the notification to the EC of the participation of the research center in this study and prepare 
the final documents required by the sponsor. 
11.3 Documents required 
Before enrolling subjects, at least the following documents should be submitted to the sponsor or 
designated personnel: 
 The confidentiality agreement; 
 Signed signature page of the study proposal; 
 CVs of primary investigators and assistant investigators recently signed and dated; The CVs 
should clearly describe the qualifications and experience of research personnel; 
 A copy of the written approval of the study proposal by ECs (including version number and date) 
and informed consent (including version and date) (if applicable); 

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 A list of current EC members, including name, title, occupation, and name of any organization of 
each member; 
 Signed research contract. 
11.3.1 Source documents  
Regulations state that investigator should maintain the information in subjects' medical records (i.e., 
source documents). Such information could verify the data collected in CRFs. In order to comply with 
these regulatory requirements, the following information should be stored and available upon request 
by the monitor and/or inspectors of regulators: 
 Information on medical history/physical condition of a subject that could prove the subject met 
the inclusion criteria of this study before participating in this study; 
 Records on the informed consent process (if applicable); 
 Description of implantation; 
 All exam results and follow-up information; 
 Dated and signed exam reports (e.g., X-ray); 
 Description of an adverse event (description, severity, date, and duration of the adverse event, 
correlation with a research-related device, prognosis and treatment of the adverse event, and 
concomitant medication); 
 Condition of a subject at the completion of or withdrawal from this study.  
Source documents of a subject should include at least but not be limited to the above information. 
11.3.2 Source data verification (SDV) 
During visits, the monitor should check all the following key items in accordance with CRF entries of 
100% of the subjects: all inclusion/exclusion criteria, the ICF (if applicable), demographic information 
of a subject, all events that met the criteria of reporting of adverse events (the inducing factor that 
indicated the occurrence of an event), safety and efficacy endpoints, use of devices, re-operation, and 
all device failure/complaint reports. The monitor should check the other data of 50% of the subjects. 
For complete and details of verification of source data, please refer to the monitoring plan.  
During a visit by the monitor, a research coordinator and/or an investigator   should be present. The 
research coordinator or the investigator should ensure that the monitor could review source documents 
and provide the latter with an appropriate environment to review relevant documents. All 
inconsistencies should be identified and discussed with the investigator or designated personnel for 
resolution. 
11.3.3 Case Record Form (CRF)  
The CRF of each subject should be completed by an authorized investigator or another authorized 
personnel of research center. All the data on subjects required must be collected in CRFs. CRFs could 
not be used as a source document. The monitor should check completed CRFs at a research center to 
confirm the accuracy of the data collected in CRFs. All corrections to CRFs should be carried out by 
an authorized investigator or another authorized personnel of research center.to CRFs should be carried 

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out by an authorized investigator or other authorized personnel of the research center. The investigator 
/assistant investigator must sign and date at a specific part of CRF to prove that he/she had reviewed 
the data and ensured the data were complete and accurate. 
A investigator should complete CRFs as soon as possible after a subject was screened or relevant 
information was collected. This would facilitate timely monitoring visits. 
11.3.4 Archive and data retention  
After being informed of the end of all research, an investigator should keep all research records, 
reports, and source documents supporting the completion of CRFs for at least ten years and could 
continue to keep the data in line with the local and international guidelines specified in the clinical 
study agreement. 
Investigators should be able to provide the document records at the request of regulators and the 
sponsor (designated personnel). Before the transfer of the documents, the sponsor or designated 
personnel must approve in writing the filing or transfer of the documents so as to relocate the 
documents. Investigators must notify the sponsor in writing of the location of the transfer and duration 
and procedures of reviewing the documents. Before destroying any records and reports related to this 
study, an investigator must contact the sponsor or designated personnel to confirm that the records and 
reports were no longer to be retained. 
If an investigator no longer shouldered the main responsibility of storage of research records due to 
retirement, relocation, or other reasons, the investigator must transfer in writing the right of storage to 
the sponsor or designate personnel and indicate the name and address of the person with the primary 
responsibility. 
11.3.5 Audit and inspection 
In the case of an audit initiated by the sponsor (or its designated personnel), or a regulator, an 
investigator should ensure that auditors and inspectors had access to the original medical records 
during their audit or inspection and provide all necessary information. In the case of an audit initiated 
by a regulator, an investigator should notify the sponsor immediately. 
11.4 Data Collection and Management Responsibilities 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
Investigator. The Investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
The recruitment of the study centers and the extraction of data from patients' medical records will be 
closely monitored to reach the proposed sample sizes. The study investigators will be asked to extract 
the data from the medical records of all patients implanted with Hakim programmable shunt system 
for the study in their respective centers. Integra Clinical Operations will follow up with the centers 
during the data collection process when appropriate to ensure a rapid completion of the data collection 
process. 
Hardcopies of the study visit CRFs will be provided for use to collect data for each subject enrolled in 
the study.  Data recorded in the CRFs derived from any source documents should be consistent with 
the data recorded on those source documents.  
Clinical data (including AEs), concomitant medications, and expected adverse reactions data) and 
clinical laboratory data will be entered into Microsoft Access database by Sponsor by double data 

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entry.   The data will be reviewed and validated.  Queries for any missing, inconsistent or illogical data 
points will be forwarded to the research center for resolution. After all data queries are resolved, the 
data will be transferred to a biostatistician for analysis. 
 
12 Ethical and Regulatory Requirements 
12.1 Ethics Committee 
Before enrolling subjects, a research center should submit the study proposal, the ICF (if applicable), 
and other applicable documents related to this study to its EC, obtain a written approval from the latter, 
and submit the approval to the sponsor or designated personnel. 
An investigator should immediately report any change to the appointment of primary investigator s 
and all unanticipated issues related to risk of subjects. Without the consent of the EC, an investigator 
was not allowed to alter the study proposal, excluding necessary changes to eliminate immediate 
hazards to subjects. Amendments involving significant risks or changes requiring EC approval and the 
written approval by an EC must be submitted to the sponsor or designated personnel. 
12.2 Informed consent 
If informed consent was not exempted by a research center, before any research-related action outside 
of routine treatment or nursing was implemented, each subject (or their legally authorized 
representative) must complete the informed consent process in line with the requirements of the EC of 
a research center, after having the nature of this study fully explained to them. At a research center 
which did not exempt informed consent, for a subject younger than 18 years old, an investigator should 
obtain a signed ICF from either of the parents or the statutory guardian. A subject aged between 6 and 
18 should also sign a relevant version of an ICF in person. 
The voluntary process of informed consent demonstrated that a subject (or his or her statutory 
guardian) was willing to participate in this study. Before an ICF was signed, an investigator must 
explain all aspects of this study to and answer all questions raised by a subject (or his/her statutory 
guardian). An investigator and/or a designated personnel must clearly document the process of 
obtaining informed consent in a subject's clinical record. An investigator should ensure that the 
informed consent process was implemented in accordance with all applicable regulations and 
requirements of the EC. 
12.3 Subject confidentiality 
Throughout the clinical study period, all data should be traceable to the original records; and subject 
data should be kept confidential. To this end, unique subject identification numbers (research center 
number and subject number) were used, via which all data reported on each subject could be identified. 
If data were encrypted and subjects' privacy was protected, information related to this study could be 
used by third parties (e.g. regulatory authorities during inspection). 
12.4 Revision of the study proposal 
Changes to the study proposal could be submitted by the sponsor or designate personnel to an 
investigator or by an assist investigator to his/her EC. Before any change to the study process was 
implemented, all major amendments must be approved by the EC of a research center. 
If it was likely to significantly impact the following items, an amendment would be a major 

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amendment: 
 The safety or physical or mental health of a subject; 
 Scientific value of the trial; 
 Implementation or management of the trial; 
 Quality or safety of equipment used in the trial. 
12.5 Protocol deviation 
Protocol deviation stands for the deviation of actual implementation of the study protocol from a 
particular part of the study protocol (e.g. non-compliance with inclusion/exclusion criteria). This study 
only retrospectively collected data. An exam item required in the protocol yet missing was not regarded 
as a protocol violation. 
No matter if it was medically sound, or if a violation was made to protect a subject in an emergency, 
the violation should be reported to the sponsor. An investigator should follow procedures as well as 
reporting policies and requirements of the EC of the research center to report a violation to the EC. 
Relevant regulations required an investigator 's records should be accurate, complete, and up-to-date, 
including documentation recording the date and cause of each protocol violation. 
Protocol violation could be classified into primary protocol violation and secondary protocol violation. 
A violation related to inclusion/exclusion criteria or informed consent (if applicable) or affecting the 
endpoint would be regarded as a primary protocol violation. Other violations other than primary 
protocol violations were secondary protocol violations. 
The final confirmation of a protocol violation should be agreed by an investigator, a data analyst, and 
the sponsor. 
 
13 Publication Policies 
At the end of this study, an article reflecting the results of the multi-center study would be published 
in prestigious scientific journals. Prior to the compilation and publication of the multi-center study 
results, any main results of any single research center in this study were not allowed to be published. 
Exceptions to this rule were subject to prior approval by the sponsor and the primary investigator. 
Other pre-defined and non-pre-defined endpoint analysis would be implemented by the data 
management department. Secondary analysis and other proposed research studies were subject to the 
approval by the primary investigator and the sponsor. In order to promptly extract and publish 
statements, secondary publication would be delegated to a relevant main author. The final analysis and 
review of all multi-center data should be approved by the primary investigator and the sponsor. 
The results of the study may be published in scientific literature and may also be used in submissions 
to regulatory authorities. It is the intent of the Sponsor to publish or present the study results together 
with study results from the other sites, unless specific written permission is obtained in advance from 
the Sponsor to publish separate results. The Investigator will ensure that any site and/or Sponsor 
personnel making a significant contribution to the study or development of a manuscript are recognized 
as co-authors in any publication according to guidelines set forth by the International Committee of 

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Medical Journal Editors (ICJME). 
All information received by the Investigator concerning the Sponsor’s business operations (such as 
patent applications, product design, formulae, manufacturing processes, basic scientific data, or 
characterization or formulation information supplied to the Investigator and not previously published) 
is considered confidential by the Sponsor and shall remain the sole property of the Sponsor. The 
Investigator agrees not to use it for any purpose other than conduct of the study without the prior 
written consent of Sponsor. 
It is understood by the Investigator that the Sponsor will use the information developed in this clinical 
trial (“Study Data”) in connection with the development of the Hakim programmable shunt system. 
Therefore, Study Data may be disclosed to other Investigators or appropriate regulatory authorities. 
By agreeing to participate in this clinical trial, the Investigator understands that he/she has an obligation 
to provide the Sponsor with complete and accurate Study Data.  
Publication and Disclosure: Because this is a multi-center trial, Investigators and/or their academic 
Institutions shall not independently publish, publicly disclose, present or discuss any Study Data or 
other information pertaining to their respective activities conducted under this study protocol until a 
multi-center publication is released under Sponsor’s direction, unless otherwise agreed upon in the 
study agreement. 
 
14 Devices 
14.1 Count of research-related devices 
This is a retrospective study. Devices were implanted. Hence, this entry does not apply. 
14.2 Return of research-related devices 
This is a retrospective study. Devices were implanted. Hence, this entry does not apply. 
14.3 Complaint about devices 
An investigator should immediately notify the sponsor or designated personnel of an issue regarding 
authenticity, identification, quality, and performance of the research product. 
14.3.1 Complaint about devices 
Relevant personnel of the sponsor must report the complaint to the email of the Custom Service China  
of Integra LifeSciences (Shanghai) Co., Ltd.within 24 hours after receiving a complaint about the 
research product: 
custsvcchina@integralife.com 
 
 

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References 
1. Chinese Medical Doctor Association, Specialist Consensus on the Standardized Treatment of 
Hydrocephalus in China (2013 edition). 
2. Aschoff A., Kremer P., Hashemi B. et al. The Scientific History of Hydrocephalus and its Treatment. 
Neurosurg Rev, 1999, 22: 67-93. 
3. Song Ming, Zhan Xiangxin et al., Common Complications and Countermeasures of Ventriculo-
peritoneal Shunt, Chinese Journal of Neurosurgery, 2011, 27(4): 428-430.  
4. Vinchon M. & Dhellemmes P. The Transition from Child to Adult in Neurosurgery. Adv Tech Stand 
Neurosurg 32:3-24, 2007. 
5. Natalie C. Edwards, Luella Engelhart et al. Cost-consequence Analysis of Antibiotic-impregnated 
Shunts and External Ventricular Drains in Hydrocephalus. J Neurosurg 122:139-147, 2015. 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
Confidential 
Page 24 of 29 
Appendix 1: Table of Product Specifications and Models 
Model  
EN Description 
161015 
ELSBERG VENTRICULAR CANNULA 5F 
161016 
ELSBERG VENTRICULAR CANNULA 7F 
161017 
ELSBERG VENTRICULAR CANNULA 9F 
161055 
DISPOSABLE SCOTT CANNULA 8CM 
161056 
DISPOSABLE SCOTT CANNULA 10CM 
161057 
ICP LUER CONNECTOR ASSY 
451020 
TOUHY NEEDLE 
821201 
ACCU-FLO*VENT CATH BA 
821203 
ACCU-FLO* VENT CATH 30CM 
821221 
ACCU-FLO VENT CATH DOTTED 
821231 
ACCU-FLO* VENT CATH RA 5 
821232 
ACCU-FLO* VENT CATH RA 7 
821233 
ACCU-FLO* VENT CATH RA 9 
821234 
ACCU-FLO* VENT CATH RA 11 
821301 
ACCU-FLO DIST CATH BA36L 
821302 
ACCU-FLO*DIST CATH BA36M 
821303 
ACCU-FLO*DIST CATH BA36H 
821380 
ACCU-FLO*DIST CATH OPEN 
821401 
ACCU-FLO*RESV 14MM 
821411 
ACCU-FLO*RESV SING FLAT 
821501 
ACCU-FLO* CONNECT STRGHT METAL 
821504 
ACCU-FLO* PL STR CONN 
821507 
ACCU-FLO* PL RT ANG CONN 
821511 
ACCU-FLO* CONNECT RT ANG 
821515 
DISPOSABLE CATH PASSER 36CM 
821516 
DISPOSABLE CATH PASSER 55CM 
821517 
DISPOSABLE CATH PASSER 65CM 
821520 
ACCU-FLO* PL 3-WAY CONN 
821521 
ACCU-FLO* 3 WAY CONN 
821615 
HOLTER* RICKHAM RESV PLAS 
821616 
HOLTER*RICKHAM RES,LGPLAS 
821617 
HOLTER*SALMON RICKHAM LP 
821618 
HOLTER*SELKER RES,SM,PLAS 
821619 
HOLTER*SELKER RESV LGPLAS 
821621 
VENT RES TR RICKHAM ST BA 
821623 
VENT RES TR RICKHAM LG BA 
821625 
VENT RES TR SAL-RIC ST BA 
821630 
CEREBRAL CATHETER BAI 3CM 
821632 
CEREBRAL CATHETER BAI 4CM 
821634 
CEREBRAL CATH RES BAI 5CM 
821636 
CEREBRAL CATH RES BAI 6CM 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
Confidential 
Page 25 of 29 
821638 
CEREBRAL CATH RES BAI 7CM 
821640 
CEREBRAL CATH RES BAI 8CM 
821642 
CEREBRAL CATH RES BAI 9CM 
821650 
VENTRIC CATH BAR STR 15CM 
821652 
VENTRIC CATH BAR RA 3CM 
821654 
VENTRIC CATH BAR RA 4CM 
821656 
HOLTER* VENTRICULAR CATHETER R 
821658 
VENTRIC CATH BAR RA 6CM 
821660 
VENTRICULAR, CATHETER, RA 
821662 
VENTRIC CATH BAR RA 8CM 
821664 
HOLTER* VENTRICULAR CATHETER R 
821666 
HOLTER* VENTRICULAR CATHETER R 
821670 
ATRIAL CATH BAR TYPE A 
821676 
ATRIAL CATH BAR TYPE E 
821682 
PERIT CATH BA TYPE A 90CM 
821684 
PERIT CATH BA SALMON 90CM 
821692 
SALMON TUBE PASSER MDFD 
821693 
PERIT CATH PLACEMENT TOOL 
821694 
TYPE A CONNECTORS 
821695 
TYPE B CONNECTORS 
821696 
#N/A 
821697 
SHUNT FILTER 
821715 
HOFFMAN SHUNT PASS SHORT 
821716 
HOFFMAN SHUNT PASS LONG 
823001 
HAKIM PRECISION VALVE SYSTEM 
823002 
HAKIM PRECISION VALVE SYSTEM 
823003 
HAKIM PRECISION VALVE SYSTEM 
823004 
HAKIM PRECISION VALVE SYSTEM 
823005 
HAKIM PRECISION VALVE SYSTEM 
823006 
STD PV PRECHAMBER UNITIZED VL 
823007 
STD PV PRECHAMBER UNITIZED L 
823008 
STD PV  PRECHAMBER UNITIZED ML 
823009 
STD PV  PRECHAMBER UNITIZED MH 
823010 
STD PV  PRECHAMBER UNITIZED H 
823011 
HAKIM PREC VALV W/PC - VL 
823012 
HAKIM PREC VALV W/PC - LO 
823013 
HAKIM PREC VALV W/PC - ML 
823014 
HAKIM PREC VALV W/PC - MH 
823015 
HAKIM PREC VALV W/PC - HI. 
823016 
INFANT HAKIM PRECISION VALVE 
823017 
INFANT HAKIM PRECISION VALVE 
823018 
INFANT HAKIM PRECISION VALVE 
823019 
INFANT HAKIM PRECISION VALVE 
823020 
INFANT HAKIM PRECISION VALVE 
823021 
MICRO PV W RICKHAM UNITIZED VL 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
Confidential 
Page 26 of 29 
823022 
MICRO PV W RICKHAM UNITIZED L 
823023 
MICRO PV W RICKHAM UNITIZED M 
823024 
MICRO PV W RICKHAM UNITIZED MH 
823025 
MICRO PV W RICKHAM UNITIZED H 
823026 
MIRCO VLV, PREC, NO CATH, V LO 
823027 
MIRCO VLV, PREC, NO CATH, LOW 
823028 
MIRCO VLV, PREC, NO CATH, MED 
823029 
MIRCO VLV, PREC, NO CATH, M HI 
823030 
MIRCO VLV, PREC, NO CATH, HIGH 
823035 
MICRO PV UNITIZED VL 
823036 
MICRO PV UNITIZED L. 
823037 
MICRO PV UNITIZED M 
823038 
MICRO PV UNITZED MH 
823039 
MICRO PV UNITIZED H 
823041 
HAKIM VENTRICULAR CATH 
823044 
HAKIM ATRIAL CATH, 46CM 
823045 
HAKIM PERITON CATH,120CM 
823048 
HAKIM STR CONN S/S 
823049 
CODMAN*-MEDOS* RTANG CONNECTOR 
823052 
ACCESSORIES MEDOS 
823053 
Shunt Connector Titanium Strl  
823055 
HAKIM VALVE INTROD/PLAST 
823082 
HAKIM PREC, VL INTRD, PL CNNCT 
823083 
HAKIM PREC, L INTRD, PL CNNCT 
823084 
HAKIM PREC,ML INTRD, PL CNNCT 
823085 
HAKIM PREC,MH INTRD, PL CNNCT 
823086 
HAKIM PREC, H INTRD, PL CNNCT 
823090 
SIPHONGUARD, CSF FLD CONTRL DV 
823095 
MICRO PV W RICKHAM VL 
823096 
MICRO PV W RICKHAM L 
823097 
MICRO PV W RICKHAM ML 
823098 
MICRO PV W RICKHAM MH 
823099 
MICRO PV W RICKHAM H 
823100 
HAKIM PROGRAMMABLE VALVE 
823101 
MEDOS* PROG INFANT VALVESYSTEM 
823110 
PROG VALVE CLYNDRICAL W PRECHA 
823111 
STD CHPV W PRECHAMBER UNITIZED 
823112 
PROG VALVE MICRO 
823113 
MICRO CHPV W RICKHAM UNITIZED 
823114 
MICRO CHPV UNITIZED 
823115 
PROG VALVE CLYNDRICAL 
823116 
PROG VAVLE MICRO W RICKHAM 
823136 
PROG VALVE RIGHT ANGLE W SG 
823146 
CHPV RT ANG RES W SG UNITIZED 
823148 
CHPV RT ANG RESERVOIR UNITIZED 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
Confidential 
Page 27 of 29 
823162 
PROG VALVE INLINE W SG 
823164 
PROG VALVE INLINE 
823182 
PROG VALVE RIGHT ANGLE W SG 
823184 
PROG VALVE RIGHT ANGLE 
823261 
PREC RT ANG RES UNTZ SG VL 
823262 
PREC RT ANG RES UNTZ SG L 
823263 
PREC RT ANG RES UNTZ SG M 
823264 
PREC RT ANG RES UNTZ SG MH 
823265 
PREC RT ANG RES UNTZ SG H 
823281 
PREC RT ANG RES UNTZ VL 
823282 
PREC RT ANG RES UNTZ L 
823283 
PREC RT ANG RES UNTZ M 
823284 
PREC RT ANG RES UNTZ MH 
823285 
PREC RT ANG RES UNTZ H 
823361 
PRECISION VALVE SYSTEM RIGHT 
823362 
PRECISION VALVE SYSTEM RIGHT 
823363 
PRECISION VALVE SYSTEM RIGHT 
823364 
PRECISION VALVE SYSTEM RIGHT 
823365 
PRECISION VALVE SYSTEM RIGHT 
823801 
SYST VALVE NP VL ANGL INT 
823802 
SYST VALVE NP L ANGL INT 
823803 
SYST VALVE NP M ANGL INT 
823804 
SYST VALVE NP MH ANGLE INT 
823805 
SYST VALVE NP H ANGL INT 
823806 
PV INLIN UNIT INTGRL CON  VL 
823807 
PV INLIN UNIT INTEGRAL CON  L 
823808 
PV INLIN UNIT INTEGRL CON  ML 
823809 
PV INLIN UNIT INTEGRL CON  MH 
823810 
PV INLIN UNIT INTEGRL CON  H 
823811 
SYST VALVE NP VL LINE ASD 
823812 
SYST VALVE NP L LINE ASD 
823813 
SYST VALVE NP M LINE ASD 
823814 
SYST VALVE NP MU LINE ASD 
823815 
SYST VALVE NP H LINE ASD 
823816 
SYST VALVE NP VL LINE INT 
823817 
SYST VALVE NP L LINE INT 
823818 
SYST VALVE NP M LINE INT 
823819 
SYST VALVE NP MH LINE INT 
823820 
SYST VALVE NP H LINE INT 
823821 
PV INLIN W SG INTGRAL CON  VL 
823822 
PV INLIN W SG INTGRAL CON  L 
823823 
PV INLIN W SG INTGRAL CON  ML 
823824 
PV INLIN W SG INTGRAL CON  MH 
823825 
PV INLIN W/SG INTGRAL CON  H 
823832 
PROG VALVE INLINE W SG 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
Confidential 
Page 28 of 29 
823834 
PROG VAVLE INLINE 
823838 
PROG VALVE RIGHT ANGLE 
823842 
CHPV INLIN/SG INTEGRAL CON 
823844 
PROGRAMMABLE VALVE INLINE UNTZ 
824095 
DISPOSABLE SPLIT TROCAR 
825461 
IN LINE PRECISION VAVLE SG VL 
825462 
IN LINE PRECISION VAVLE SG L 
825463 
IN LINE PRECISION VAVLE SG M 
825464 
IN LINE PRECISION VAVLE SG MH 
825465 
IN LINE PRECISION VAVLE SG H 
825471 
IN LINE PRECISION VAVLE VL 
825472 
IN LINE PRECISION VAVLE  L 
825473 
IN LINE PRECISION VAVLE M 
825474 
IN LINE PRECISION VAVLE MH 
825475 
IN LINE PRECISION VAVLE H 
825481 
RT ANGLE PRECISION VALVE SG VL 
825482 
RT ANGLE PRECISION  VALVE SG L 
825483 
RT ANGLE PRECISION  VALVE SG M 
825484 
RT ANGLE PRECISION VALVE SG MH 
825485 
RT ANGLE PRECISION VALVE SG H 
825491 
RT ANGLE PRECISION VALVE VL 
825492 
RT ANGLE PRECISION  VALVE L 
825493 
RT ANGLE PRECISION  VALVE  M 
825494 
RT ANGLE PRECISION  VALVE MH 
825495 
RT ANGLE PRECISION VALVE H 
826001 
#N/A 
826010 
ACCU-FLO*BURRHOLE BUTTONS 
826025 
ACCU-FLO* SIL COVER 3/8 
826100 
ACCU-FLO* CSF RESV 14 MM 
826101 
ACCU-FLO* CSF RESV 24 MM 
826200 
JAMES L-P SHUNT 25CM 
826201 
JAMES L-P SHUNT 50CM 
826202 
JAMES L-P SHUNT 80CM 
828501 
UNI-SHUNT*W/RES 53CM 2-5 
828502 
UNI-SHUNT*W/RES 53CM 5-9 
828511 
UNI-SHUNT*W/RES 62CM 2-5 
828512 
UNI-SHUNT*W/RES 62CM 5-9 
828521 
UNI-SHUNT*W/RES 78CM 2-5 
828522 
UNI-SHUNT*W/RES 78CM 5-9 
828531 
UNI-SHUNT*W/RES 90CM 2-5 
828532 
UNI-SHUNT*W/RES 90CM 5-9 
828533 
UNI-SHUNT*W/RES 90CM 9-14 
828541 
UNI-SHUNT*W/RES 102CM 2-5 
828542 
UNI-SHUNT*W/RES 102CM 5-9 
828543 
UNI-SHUNT*/RES 102CM9-14 

Integra LifeSciences (Shanghai) Co., Ltd. 
Proposal No.: C-HAKIM-001 
Date of proposal: V1.1/2019-11-18 
Confidential 
Page 29 of 29 
828591 
UNI-SHUNT*W/RESV ANCH.CL. 
831371 
#N/A