The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults
Phase: NA
Conditions: Hearing Loss, Sensorineural, Hearing Loss, Cochlear, Deafness
Sponsor: Oticon Medical

 
Clinical Investigational Plan 
PIC_07 
Edition : G 
CLINICAL INVESTIGATIONAL PLAN 
INTERVENTIONAL TRIAL 
«The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults» 
 
This document contains confidential information belonging to Oticon Medical. Except as otherwise agreed to in 
writing, by accepting or reviewing this document, you agree to hold this information in confidence and not to disclose 
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or suspected breach of this obligation, Oticon Medical should be promptly notified.  
 
 
 
 
 
CLINICAL PROTOCOL  
MEDICAL DEVICE INVESTIGATIONAL PLAN  
 
PIVOTAL STUDY 
Efficacy clinical trial 
 
 
 
 
Application Title: The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults 
Device Name: Neuro Zti Cochlear Implant System 
Sponsor: Oticon Medical, Dan GNANSIA 2720 Chemin Saint Bernard 06224 Vallauris France 
Internal Ref: PIC_07 
Version and date: Version G, February 2019 
 
 
 
 

The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults  
 
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History  
Version 
Date 
Reason(s) 
Written by 
A 
April 2016 
Creation 
S. SAAÏ 
B 
May 2016 
Precision and Change on statistics methodology. 
Sensitivity analysis. 
Sample size determination. 
S. SAAÏ 
C 
June 2016 
Visit interval modification from -4 to -8 weeks for V1 
with interval windows modification from 14 days ± 2 
days to 28 days ± 14 days from V1. 
 Visit interval modification from -2 to -6 weeks for V2 
with interval window modification from 14 days± 2 
days to 28 days ±14 days from V2. 
Change on §3.3.2 study design. 
 
Precision on the inclusion criteria (3) PTA  70db HL, 
average in db of the thresholds for pure tones at 500, 
1000 and 2000Hz on both ear. 
 
ICF pages (Appendix 2) translate from French to 
English. 
 
Team study list removed, from p6-7 and moved to 
the SMF. 
S SAAÏ 
D 
July 2016 
Appendix 7 “CRF” removed 
SAE form: email dagn@oticonmedical.com added. 
Appendix 2 “ICF” Protocol version removed AND title 
rectification “The Neuro Zti Cochlear Implant System 
Efficacy and Safety in Adults” instead of “The Neuro 
Zti Cochlear Implant System Performance in Adults” 
S SAAÏ 
E 
August 2016 
Inclusion criteria: 
- 
Definition of post-lingual added 
- 
“Open-set sentences” completed by “HINT 
sentences” 
Adaptive HINT-N modified to HINT-N at +10dB SNR 
with fixed signal and fixed noise.  
HINT-N baseline added and secondary objectives 
updated consequently. 
Section 3.5.5.1, section 3.5.5.4 and section 3.5.7 
(Visit 2), section 3.6.1.2 updated. 
Appendix 7 removed from protocol. 
Statistical Analysis reviewed, with site effect added 
and language effect comparison removed to 
language trends comparison and secondary 
objectives updated consequently. 
Study planning delayed by 3 months. 
Cable lengths modified from 3 to 2, page 67. 
Appendix 2, procedure updated with HINT-N in ICF.  
S SAAÏ 
F 
October 2017 
Inclusion period: 13 month 
Revised Danish and French speaker participants 
number 
S SAAÏ 

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Visit interval modification for V2 with interval 
window from 28 days (+/14 days) to 28 days (-25 to 
+14 days) from V1 
Pure Tone Audiometry can be performed within 6 
months before the visit 2 (inclusion visit) 
Tympanometry can be performed within 6 months 
before the visit 2 (inclusion visit) 
Typo : 3.5.7 Visual analog pain scale deleted from 
visit 4 
Typo : 3.6.1.1 HINT 6 months following activation 
corrected 
AE form E2 - 18jan2017 implemented (appendix 3) 
SAE form E2 – 18jan2017 implemented (appendix 4) 
Patient Hint Performance Memo added (appendix 7) 
Post-operative ECAP Measurement added (appendix 
8) 
Calibration considerations added (appendix 9) 
G 
February 2019 
Start date updated 
Inclusion period extended 
Completion date postponed 
S SAAÏ 

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STATEMENT OF COMPLIANCE 
The study will be conducted in accordance with the International Conference on Harmonization 
guidelines for Good Clinical Practice (ICH E6), the Code of Federal Regulations on the Protection of 
Human Subjects (45 CFR Part 46). All personnel involved in the conduct of this study have 
completed human subjects’ protection training. 
 
 

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PROTOCOL AGREEMENT 
The signature below constitutes the approval of this protocol and the attachments, and provides 
the necessary assurances that this trial will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable US federal regulations and ICH guidelines. 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
Date: 
 
Name:  
Title:  
Site # 
 
 
Site Name 
 
Address 
 
 
 
 
 
 
 
Phone Number 
 
 
 
 
 

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CONTENT 
0. 
GLOSSARY AND ACRONYMS ...................................................................................................... 9 
1. 
SUMMARY ................................................................................................................................. 10 
2. 
PURPOSE OF THE INVESTIGATION ......................................................................................... 12 
2.1 
Introduction .......................................................................................................................................... 12 
2.2 
Name of the Investigational Device ....................................................................................................... 13 
2.3 
Intended Use of the Investigational Device ........................................................................................... 13 
2.4 
Objectives of the Clinical Investigation.................................................................................................. 14 
2.4.1 
Primary objectives: Efficacy and Safety ............................................................................................. 14 
2.4.2 
Secondary objectives ......................................................................................................................... 15 
2.4.3 
Technical functionalities .................................................................................................................... 15 
2.5 
Anticipated duration of the clinical investigation .................................................................................. 16 
3. 
CLINICAL PROTOCOL ................................................................................................................ 16 
3.1 
Protocol Number and Title of Clinical Protocol ...................................................................................... 16 
3.2 
Protocol Version and Date .................................................................................................................... 16 
3.3 
Study Design ......................................................................................................................................... 16 
3.3.1 
General Study Design ......................................................................................................................... 16 
3.3.2 
Study Design Schematic ..................................................................................................................... 16 
3.4 
Subject Selection ................................................................................................................................... 16 
3.4.1 
General Characteristics of the Proposed Subject Population(s) ........................................................ 16 
3.4.2 
Anticipated Number of Research Subjects ........................................................................................ 17 
3.4.3 
Inclusion Criteria ................................................................................................................................ 17 
3.4.4 
Exclusion Criteria ................................................................................................................................ 17 
3.5 
Study Procedures .................................................................................................................................. 18 
3.5.1 
Screening Procedures ........................................................................................................................ 18 
3.5.2 
Electrode arrays ................................................................................................................................. 18 
3.5.3 
Study Treatment or Diagnostic Product Procedures ......................................................................... 18 
3.5.4 
Withdrawal of Subjects Due to Non-Compliance .............................................................................. 20 
3.5.5 
Follow-up Procedures ........................................................................................................................ 21 
3.5.6 
Permitted visit window periods ......................................................................................................... 26 
3.5.7 
Scheduled Visit Procedures ................................................................................................................ 27 
3.6 
Study Outcome Evaluations .................................................................................................................. 28 
3.6.1 
Study Endpoints ................................................................................................................................. 28 
3.6.2 
Outcome Data and Data Analysis ....................................................................................................... 30 
3.6.3 
Handling of Missing Data ................................................................................................................... 33 
3.6.4 
Futility/Safety Interim Analysis .......................................................................................................... 34 
3.6.5 
Data and Safety Monitoring Board .................................................................................................... 34 
3.6.6 
Early Stopping Rules ........................................................................................................................... 34 
3.6.7 
Study Interruption or Withdrawal ..................................................................................................... 35 
4. 
RISK ANALYSIS ........................................................................................................................... 36 
4.1 
Expected clinical benefits ...................................................................................................................... 36 
4.2 
Anticipated Adverse Events .................................................................................................................. 36 
4.3 
Trial Anticipated Risks ........................................................................................................................... 40 
4.4 
Benefit-risk Ratio .................................................................................................................................. 40 
4.5 
Adverse Event Recording/Reporting ..................................................................................................... 40 
4.5.1 
Adverse Events ................................................................................................................................... 40 
4.5.2 
Reporting Period ................................................................................................................................ 41 
4.5.3 
Definition of Adverse Event (AE) and Adverse Device Effect (ADE) ................................................... 41 
4.5.4 
Abnormal Test/Exam Findings ........................................................................................................... 42 
4.5.5 
Adverse Device Effect Definition ........................................................................................................ 42 
4.5.6 
Serious Adverse Event definition ....................................................................................................... 42 
4.5.7 
Serious Adverse Device Effect ............................................................................................................ 43 
4.5.8 
Unanticipated Serious Adverse Device Effect .................................................................................... 43 
4.5.9 
Eliciting Adverse Effect Information .................................................................................................. 43 

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4.5.10 
Recording and Assessment of Adverse Effects .................................................................................. 43 
4.5.11 
Causality and severity assessment ..................................................................................................... 44 
4.5.12 
Reporting Requirements .................................................................................................................... 45 
4.5.13 
Serious Adverse Event Reporting Requirements ............................................................................... 45 
4.5.14 
Non-serious Adverse Event Reporting Requirements........................................................................ 45 
4.5.15 
Reporting of Serious Adverse Effects to EC/CA .................................................................................. 45 
4.6 
Withdrawal of a Subject Due to Adverse Effect(s) ................................................................................. 46 
5. 
DESCRIPTION OF THE INVESTIGATIONAL DEVICE ............................................................... 47 
6. 
MONITORING PROCEDURES ................................................................................................... 48 
6.1 
Study Monitoring Plan .......................................................................................................................... 49 
6.2 
Auditing and Inspecting ........................................................................................................................ 49 
7. 
DEVICE LABELING...................................................................................................................... 50 
8. 
CONSENT MATERIALS .............................................................................................................. 51 
9. 
ETHICAL COMMITTEE (EC)/COMPETENT AUTHORITY (CA) ............................................... 52 
10. ADDITIONAL RECORDS AND REPORTS .................................................................................. 53 
10.1 Data Handling and Record-Keeping ....................................................................................................... 53 
10.1.1 
Case Report Form ............................................................................................................................... 53 
10.1.2 
Subject Confidentiality ....................................................................................................................... 53 
10.1.3 
Source Documents ............................................................................................................................. 54 
10.2 Record Maintenance and Retention ...................................................................................................... 54 
10.3 Data Management Procedures .............................................................................................................. 54 
10.4 Data Quality Control and Reporting ...................................................................................................... 55 
10.5 Archival of Data .................................................................................................................................... 55 
10.6 Clinical Trial Registration ....................................................................................................................... 55 
10.7 Publication ............................................................................................................................................ 55 
11. BIBLIOGRAPHY .......................................................................................................................... 56 
12. APPENDIX ................................................................................................................................... 59 
 
 
 

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0. GLOSSARY AND ACRONYMS 
 
AAMI 
Association for the Advancement of Medical Instrumentation 
BTE 
Behind The Ear (sound processor) 
CA 
Competent Authority 
CI 
Cochlear Implant 
CIS 
Cochlear Implant System 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CSP 
Cumulative Survival Percentage 
DSMP 
Data and Safety Monitoring Plan 
EC 
Ethical Committee 
ECAP 
Electrically-evoked Compound Action Potential 
EEC 
European Economic Community  
FAS 
Full Analysis Set 
GCP 
Good Clinical Practice 
HINT 
Hearing In Noise Test 
HIPPA 
Health Insurance Portability and Accountability Act of 1996 
HL 
Hearing Level 
ICH 
International Conference of Harmonization 
IFU 
Instructions For Use 
OUS 
Outside of United States 
PMS 
Post Market Surveillance 
PPS 
Per Protocol Set 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PTA 
Pure Tone audiometry 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAS 
Safety Analysis Set 
SNR 
Signal Noise Ratio 
SPL 
Sound Pressure Level 
SRT 
Speech Reception Threshold 
SSID 
Subject Single Identifier 
USADE 
Unanticipated Serious Adverse Device Effect 
 
 

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1. SUMMARY  
Title  
“The Neuro Zti Cochlear Implant System Efficacy and Safety in 
Adults” 
Sponsor 
Oticon Medical 
Investigator Coordinator 
Dr. David Schramm (Canada) 
Phase and Design 
Multinational, multicenter, prospective, open label, single arm. 
Study description 
The new cochlear implant system (CIS) is indicated in individuals 
with serious hearing disabilities who do not obtain benefit from 
appropriately fitted hearing aid(s). Cochlear implant surgery is safe, 
but as with any surgery, possible issues or device related issues may 
occur. The risk benefit balance is well known in cochlear 
implantation. 
The aim is to assess the efficacy and the safety of this new CIS in 
adults. 
Primary objectives 
To demonstrate the efficacy of the new CIS through improvement 
of speech performance in quiet conditions after CIS implantation.  
To evaluate the safety of the CIS. 
Secondary objectives 
To assess the device effect with speech performance in noise. 
To show sustainability of the device effect in quiet and in noise in 
time and after 12 months of use. 
To assess whether the time of course of the response follow the 
same tendencies (increase, decrease, slope inversion) in the three 
languages in quiet and noise conditions. 
Primary endpoints 
HINT score in quiet (HINT-Q) at 6 months of device use. 
Major complications incidence rate at 12 months of device use.  
Secondary endpoints 
HINT in noise (HINT-N) scores at 3, 6 and 12 months of device use 
HINT-Q scores at 3 months and at 12 months,  
Electrodes impedance at each visits  
ECAP at each visit 
Inclusion & exclusion criteria 
Inclusion: 
- 
≥ 18 y.o., 
- 
Bilateral severe-to-profound sensorineural hearing loss,  
- 
Post-lingual deafness 
- 
Limited benefit from appropriately fitted hearing aid(s), 
- 
Primary implantation, 
- 
No anatomic contraindications, 
- 
Fluent in local language,  
Exclusion: 
- 
Medical conditions that contraindicate undergoing surgery, 
- 
Psychologically unsuitable, 
- 
Unwillingness or inability to comply with all investigational 
requirements. 
Investigational medical device 
Neuro CIS, with Neuro Zti implant and Neuro One processor 
Study planning 
Start date: January 2017 
Inclusion period: 23 months 
Running period: 14 months (1 month eligibility period + 13 months 
postoperative follow-up) 
Completion date: December 2019 
Number of subjects planned 
39 English-speaking subjects to assess the primary endpoint with 
additionally 16 non-English (8 Danish and 8 French) speaking 

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subjects to assess safety. In case of shortage of recruitment in a 
given language recruitment can be increased in another language 
provided that a minimum of 5 French and 5 Danish speaking 
patients should be implanted. 
Number of centers 
5 in Canada, 1 in Denmark 
Statistical analysis 
Primary efficacy analysis based on the English speaking patients the 
primary efficacy endpoint (change from baseline to M6 of the HINT-
Q) and a one sample t test.   
Mixed Model for repeated measures with appropriate contrasts. 
 
 

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2. PURPOSE OF THE INVESTIGATION 
2.1 
Introduction  
The gold standard for treating permanent hearing impairment is the cochlear implant (CI); this 
constitutes the most widely used therapeutic surgical intervention in patients with a sensorineural 
bilateral severe-to-profound hearing loss. As of December 2012, approximately 324,200 cochlear 
implants have been implanted worldwide, in the United States roughly 58,000 devices have been 
implanted in adults and 38,000 in children [1,2]. It is estimated that nearly 30,000 additional 
devices have been implanted in the United States since the 2012 report and it is estimated that 
the number of implantees worldwide now exceed 500,000 CIs.  
Balkany et al. [6] reported a HINT score in quiet increase from 11.3±25.6% to 78±24.9%) on 55 
patients at the 6-month follow-up. Similar results were reported by Bradley et al. [8] with a speech 
intelligibility change from 14±17% to 75±28% at 6 months in the same material. Waltzman et al. 
and Lin et al. express their results in mean increase HINT score in quiet from pre- to post-
implantation which are 47.7±26.6% and 60±24.1% respectively [42,43].  
 
Large investments in research and development as well over 30 years of clinical experience have 
established that cochlear implants are safe and clinically effective. The FDA initially approved CIs 
for adults in 1984, however the benefits provided by CIs have led to the extension of indications 
in 2000 to children 12 months and older. In addition to CIs, the tremendous expansion of the field 
of neuromodulation leveraging electrical stimulation via implantable electrodes (i.e. spinal cord 
stimulation, deep brain stimulation, vagal nerve stimulation) as well as the long term electrical 
stimulation for cardiac rhythm management have further established the safety of long term 
electrical stimulation of biological tissues in millions of patients worldwide.  
 
CISs have been shown to improve sound perception and speech understanding with associated 
risks including those related to the surgery itself and related to the device. The major post-surgical 
complication rate is 6.8% patient-years in children and 1.4 to 1.7% in adults. The minor 
complication rate is 34.7% and 35.3% patient-years in children and adults, respectively [12]. In 
addition, there are risks that other adverse events associated with the implant could occur, such 
as mechanical or electrical failure, rejection, infection and problems that require device explant 
and/or device replacement. Despite the aforementioned risks, CIs have been proven to be reliable; 
according to the reliability reports of the four largest manufacturers of CIS the cumulative survival 
percentage (CSP) of implanted components range from 97.37% after 9 years (Digisonic SP), 98.09% 
after 8 years (HiRes 90K), 98.29% after 8 years (Sonata), 99.1% after 11 years (CI24RE) 
(manufacturers reliability reports, 2015 [13,14,15). The literature review gives an weighted 
average of major complication of 7.09% ± 2% [16,17,18,19,20,21]. 
 
Given the historical data, including prior FDA approvals of CIS produced by three different 
manufacturers, the risk/benefit balance is favorable, indicating that cochlear implantation can be 
a safe and effective treatment for severe-to-profound deafness in adults and children. 
 
Oticon Medical has developed a new CIS named “The Neuro Cochlear Implant System” which 
consists of an implantable part (Neuro Zti) and an external part (Neuro One). The Neuro One 
detects and processes sound and is designed to be worn behind the ear (BTE). The Neuro Zti is 
designed to be surgically implanted and consists of the receiver/stimulator which is implanted 
under the skin on the temporal aspect of the skull and a multichannel electrode designed to be 

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placed within the Scala Tympani of the cochlea enabling direct electrical stimulation of the spiral 
ganglion. All power and data are transmitted from the Neuro One to the Neuro Zti via an 
inductively coupled transcutaneous link.  
 
This pivotal study will assess the Efficacy and the Safety of the CIS in adults with severe to profound 
bilateral hearing impairment, across Europe and Canada. It is hypothesized that sentence 
recognition at normal conversational levels in quiet conditions is better at 6 months of device use 
that at baseline and the risks of complications associated with the implanted components is similar 
to those observed in data from literature.  
2.2 
Name of the Investigational Device 
Generic name: Cochlear Implant System 
Commercial name: Neuro Cochlear Implant System  
 
The “Neuro Cochlear Implant System” is the investigational device to be studied and includes the 
internal and external parts of the system. The internal/implanted part is designated as Neuro Zti, 
and external part as the Neuro One sound processor. 
The Neuro CIS is CE and Health Canada approved. 
2.3 
Intended Use of the Investigational Device 
The Neuro Cochlear Implant System is intended to provide the opportunity to detect and recognize 
auditory information through electrical stimulation of the auditory nerve for patients with severe 
to profound bilateral sensorineural hearing impairment, and who obtain limited benefit from 
appropriately fitted hearing aid(s). 
 
The Neuro CIS is foreseen in the following conditions: 
 
• Adults of 18 years old or older with a bilateral, pre- or post- linguistic, sensorineural severe 
to profound deafness and obtain a limited benefit from appropriately fitted hearing aid(s). 
The hearing impairment is determined by a pure tone threshold ≥ 70 dB HL from and 
including 500 Hz. Limited benefit from hearing aid(s) is determined to be a score of 50% 
correct or less in the best-aided condition on an established calibrated recorded test of 
open sentence recognition. 
 
• Children1 aged 12 months to 17 years old, having a profound bilateral hearing loss 
determined by a pure tone threshold ≥ 90 dB HL from and including 500Hz and; 
o In a young child, limited benefit is defined by a lack of auditory progress with 
appropriate fitting hearing aid(s) despite intensive aural rehabilitation over 3-6 
months period.  
o In an older child, lack of auditory progress is defined as < 20% correct on open-set 
word recognition test Multisyllabic Lexical Neighborhood Test (MLNT) or Lexical 
Neighborhood Test (LNT), depending on cognitive ability and linguistic skills. 
                                                 
1 Device intended use for the US market. Pediatric indication is not supported by this clinical trial. Pediatric indications 
are only indicative here and will be investigated in a next step. For this protocol, this device is to be used in a clinical 
investigation framework. The Neuro System is currently approved for adults and children under CE mark and Health 
Canada license. For specific indications within European countries please refer to the instructions for use (IFU) in the 
device sales packaging. 

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2.4 
Objectives of the Clinical Investigation 
Device efficacy is defined as an improvement in the speech recognition battery presented at 
conversational speech levels (60 dB SPL, see Appendix 9: Calibration considerations) in quiet 
after 6 months of use compared to the preoperative condition (best-aided pre-operative 
condition2). 
 
Speech perception tests will be conducted 
• Preoperatively, on both ear with the best fitted hearing aid(s), and 
• Postoperatively, on ipsilateral ear with activated CIS and an occluded contralateral ear with 
ear-plug. 
2.4.1 Primary objectives: Efficacy and Safety 
The primary objectives are: 
• To demonstrate the improvement in the speech recognition, in quiet condition, after 
implantation of the Neuro CIS with respect to pre-operative conditions. 
• To evaluate the device safety profile and in particular the risk of complication. 
 
Evaluation at 6 months compared to baseline will be used to determine the efficacy of the device. 
 
The incidence rate of major complications at 12 months of device use will be estimated to evaluate 
the safety. Data from literature on currently similar devices FDA-approved will be used as 
yardsticks.  
2.4.1.1 
Main effect of device on speech recognition 
The primary population will be composed of English-speaking subjects. In the efficacy assessment, 
a sub-population will be used as a primary set of patients because different languages is expected 
to influence the magnitude of the effect of the device.  
 
Objective:  
To assess in English speaking subjects the performance at month 6 of the device in quiet conditions 
compared to baseline (best-aided condition) using HINT-Q test-sentences presented at 
conversational level. 
 
Hypothesis:  
The mean HINT-Q score obtained with the Neuro CIS after 6 months of device use in English 
speaker subjects is greater than the score at baseline. 
 
H0: µM6 - µ0  0 points 
H1: µM6 - µ0 > 0 points 
 
An improvement of approximately 50 points with respect to baseline is expected and an 
improvement of 20 points3 is considered clinically pertinent. 
                                                 
2 Best aided condition preoperatively: appropriately fitted hearing aids with respect to best clinical practice. 
3 PMA, Summary of Safety and Effectiveness data, Medel, Combi 40+ : 
http://www.accessdata.fda.gov/cdrh_docs/pdf/P000025b.pdf 

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2.4.1.2 
Safety: Major Complications 
Occurrence of major complications in all participants suffering from severe to profound bilateral 
sensorineural hearing loss and for whom an implantation of the device was initiated will be the co-
primary objective. All surgical and device-related events will be reported and the number and 
proportion of major complications will be estimated. 
 
Safety data will be collected from the preoperative visit (during surgical procedure) to the end of 
patient participation. 
 
Adverse events or complications will be classified as medical/surgical or device related. 
Complications will be classified as major if they require surgical intervention and minor if they 
resolve spontaneously or with non-invasive medical treatment categories [12,22,23].  
Any device failure will be investigated and classified according to AAMI-CDV-4 CI86 guideline for 
Cochlear Implants. 
 
A list of adverse events is defined in section 4.2. Unanticipated adverse events (section 4.5.8) may 
occur (not listed in 4.2) and like anticipated events they will be reported, followed and classified. 
 
Occurrence of major complications will be a co-primary endpoint and the presentation of the 
safety profile (all adverse events reported) will be a secondary objective and mainly descriptive. 
Incidence rate of minor and major complications will be estimated globally and per categories in 
order to describe the device safety profile. Data from literature on currently similar devices FDA 
approved will be used as yardsticks. 
2.4.2 Secondary objectives 
Secondary objectives are: 
• To establish the time course of the change from baseline of HINT-Q score in English 
speaking patients and in all patients to assess the efficacy of the device in a dynamic 
perspective.   
 
• To test the sustainability of the device effect in Quiet conditions (HINT-Q) through the 
comparison of the scores at month 6 and month 12 in English speaking patients and 
possibly in all patients in case of absence of significant language effect in the improvement 
from baseline.    
 
• To assess the performance of device in noise using HINT-N test in English speaking and 
possibly in all patients at 3, 6 and 12 months compared to baseline (best-aided condition). 
The comparison of the score at 6 and 12 months will indicate the sustainability of the effect. 
 
• To evaluate the trend of device efficacy in quiet and noise conditions across English 
speaking, French speaking and Danish speaking patients.  
2.4.3 Technical functionalities 
The time course from baseline of impedance values and ECAP responses amplitudes will be 
assessed to check device technical functionality. Mixed model will be used to assess in a 
dynamic perspective the objective measures evolution. 

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2.5 
Anticipated duration of the clinical investigation 
Start date: January 2017 
Inclusion period: 23 months 
Running period: 14 months 
Completion date: December 2019 
3. CLINICAL PROTOCOL 
3.1 
Protocol Number and Title of Clinical Protocol 
Title: The Neuro Cochlear Implant System Efficacy and Safety in Adults 
Protocol number: PIC_07 
3.2 
Protocol Version and Date 
Edition G, February 2019 
3.3 
Study Design 
3.3.1 General Study Design 
This pivotal study is designed as a prospective multi-center, one arm, non-randomized, open label, 
repeated measures clinical study. The subjects will be their own control. 
3.3.2 Study Design Schematic 
 
 
3.4 
Subject Selection 
3.4.1 General Characteristics of the Proposed Subject Population(s) 
The following eligibility criteria are designed to select subjects for whom protocol treatment is 
considered appropriate. All relevant and non-medical conditions should be taken into 
consideration when deciding whether this protocol is suitable for a particular subject. 
 

The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults  
 
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In the event of any doubt about the eligibility of a subject, the investigator should discuss the issue 
with the clinical study manager/clinician who will confirm whether the subject may be entered 
into the trial. 
 
Adults with a bilateral severe-to-profound deafness that are existing candidates for a cochlear 
implant will be included in the study. Subjects enrolled will only be unilaterally implanted for the 
duration of the study. 
 
Potential subjects shall be classical candidates for a cochlear implant that are referred to one of 
the participating cochlear implant centers. The participating center shall provide the assessment 
to determine whether the potential candidate is suitable for cochlear implantation. Subjects will 
enrolled by cochlear implant centers shall meet the eligibility criteria described in section 3.4.3 
and 3.4.4. 
3.4.2 Anticipated Number of Research Subjects 
For the pivotal study, 55 subjects shall be enrolled (section 3.6.1.4) 
3.4.3 Inclusion Criteria 
(1) Patient must understand the investigational nature of this study and sign an independent 
ethical committee (EC) approved written informed consent form prior to any study related 
activities, 
(2) Must be 18 years or older, 
(3) Bilateral severe-to-profound sensorineural hearing loss, PTA4 ≥ 70 dB HL (average in dB of 
the thresholds for pure tones at 500, 1000 and 2000Hz, on both ear), 
(4) Post-lingual5 deafness, 
(5) Limited benefit from appropriately fitted hearing aid(s), with score ≤ 50% correct in HINT 
sentences recognition in quiet, binaurally in the best listening condition, 
(6) Primary implantation, 
(7) No anatomical contraindications: Radiological evaluation showing no obstacles to full 
electrode insertion and verifying the absence of central auditory lesions 
(8) Fluent in local language, including reading and writing,  
(9) Psychologically suitable, 
(10) Updated pneumococcal vaccine.  
 
Note: Patient must understand the investigational nature of this study and sign an independent 
ethical committee (EC) approved written informed consent form prior to any study related activities 
3.4.4 Exclusion Criteria 
(1) Medical conditions that contraindicate undergoing surgery (middle ear diseases i.e. 
AOM/CSOM, lesions of auditory nerve, pathologies of central auditory pathway, 
otosclerosis any cochlear malformation (i.e. Mondini malformation, cochlear ossification, 
Large Vestibular Aqueduct) 
(2) Unrealistic expectations from the candidate regarding the possible benefits, risks, and 
limitations that are inherent to the surgical procedure(s) and the device 
(3) Unwillingness or inability of the candidate to comply with all investigational requirements 
                                                 
4 Pure Tone Audiometry can be performed within 6 months before the visit 2 (inclusion visit) 
5 Post-lingual deafness: occurs after the development of normal speech. 

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3.5 
Study Procedures 
For the complete timing of trial procedures, please refer to the scheduled activities in section 
3.5.5.4. 
 
Speech tests shall be obtained under reproducible conditions through a calibrated system 
(calibrated dedicated software). Tests shall be carried out by the same trained operators in a given 
participating center. 
3.5.1 Screening Procedures 
Prior to undergoing any trial procedures, subjects shall be required to provide a written informed 
consent form which has been approved by an EC/CA and which complies with regulatory 
requirements. Subjects shall be given the prior opportunity to sign this form, to ask the PI any 
questions about the trial, and to discuss the trial with a relative or other staff member. Subjects 
shall also be informed of alternative treatments and local approval.  
 
To fulfill preoperative considerations, the following examinations must be conducted: 
- 
Tympanometry6 to ensure absence of middle ear diseases 
- 
Imaging with CT or MRI to evaluate the inner ear and to ensure absence of auditory nerve 
lesions and/or cochlear malformation and/or more central lesions of the auditory pathway 
3.5.2 Electrode arrays 
The surgeon may elect to use one of two types of lateral-wall electrode arrays that are available 
for the Neuro Zti. The two electrode arrays are the Neuro ZtiCLA and the Neuro ZtiEVO. Both arrays 
have been extensively used OUS for several years on the prior generation implant and now in OUS 
implantations of the Neuro Zti. Both arrays provide 20 contacts, similar cochlear coverage and are 
amenable to round-window, modified round-window or cochleostomy insertions into the scala-
tympani. To date, there is no evidence that speech perception outcome is impacted by the array 
choice and both of the array’s dimensions are much smaller than the scala-tympani dimensions 
reported in the literature. Both arrays demonstrate stiffness profiles that fall within those 
demonstrated in existing designs by other manufacturers currently approved by the FDA. At 
present, the choice is left to the surgeon’s preference. The principle difference between the arrays 
are that the “Classic” Array is slightly stiffer than the ”EVO” making it slightly easier to achieve a 
full insertion. However, the less stiff EVO, is suspected to allow for a “softer” insertion which under 
certain conditions may result in a lower probability of cochlear trauma. To date, the EVO version 
is the most common electrode array used and the classic version tends to be used in cases of more 
difficult insertion due to anatomical issues or other issues that result in difficult insertion such as 
compromised patency of the scala-tympani due to fibrosis or ossification. Temporal bones studies 
have been conducted for both arrays and this data will also be provided in the PMA application. 
3.5.3 Study Treatment or Diagnostic Product Procedures 
Subjects are to be candidates for a cochlear implantation as assessed by tests and exams 
performed before surgery and are of clinical routine evaluation/use. The conventional surgical 
approach is described below. If an alternative surgical method or approach is used (e.g. 
suprameatal, cranial facial, or endomeatal approach), the subject should be excluded from the 
protocol and the investigator shall record this information in the CRF and document the rationale 
for the deviation in surgical approach. 
                                                 
6 Tympanometry can be performed within 6 months before the visit 2 (inclusion visit). 

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The standard mastoidectomy-posterior tympanotomy introduced by House, 1961, is the gold 
standard for cochlear implantation, however some surgeons modified their approach to develop 
simplified and safer procedures, which is adaptable to possible situations such as anatomical 
anomalies or to have a shorter operative time and minimal morbidity with a possible decrease of 
facial nerve damage and chorda tympani sacrifice. 
 
The Neuro CIS does not require special surgical techniques when compared to the CISs currently 
approved by the FDA and in Europe. The exception being that the Neuro Zti incorporates an 
integrated fixation system to prevent device migration. 
 
The approach uses the facial recess is the well-known technique and used for many decades, other 
surgical technique used in this clinical trial will exclude the subject.  
 
Surgical Procedure 
The surgeon performing CI surgery, in this study, shall be experienced in otologic and neurotologic 
surgery. The surgeon shall also be experienced in cochlear implantation. The CI surgery is to be 
done under general anesthesia with a minimally invasive technique. The classical/conventional 
technique for cochlear implantation is to be performed for this study: 
• A small postauricular incision shall be made and the temporal muscle and periosteum shall 
be elevated,  
• The bone shall be exposed anteriorly to the level of the ear canal and posteriorly sufficient 
to accommodate the Neuro Zti’s electronic housing.  
• Mastoidectomy and posterior tympanotomy are to be performed with an extended facial 
recess approach.  
• The tympanic membrane and the ear canal are not to be disturbed during the surgical 
procedure.  
• For a round window (RW) insertion of the electrode, the posterior tympanotomy recess 
shall be drilled sufficiently to obtain a clear view of the round window (RW) and to obtain 
proper landmark identification to ensure electrode insertion into the scala-tympani. If 
warranted, the round-window niche should be reduced to expose the round window.  
• A cochleostomy approach may also be considered, however, proper landmark 
identification and insertion vector shall be determined as standard for FDA approved CI 
systems to ensure scala tympani insertion.  
• Prior to opening the cochlea, either the RW membrane for RW insertion or the endosteum 
for the cochleostomy, a drop of corticosteroid and/or hyaluronic acid may be placed on the 
RW membrane or endosteum to reduce fibrotic reaction.  
• Once scala-tympani access to the cochlea is verified, the Neuro Zti shall then be placed in 
its position under the periosteum, posterior and superior to the ear and secured with the 
included self-tapping screws. Device positioning may be helped by use of included sterile 
surgical dummies of internal and external components. 
• The RW membrane or endosteum shall then be incised and the tip of the electrode array 
shall be guided toward the cochlear opening. During insertion, no excessive force should 
be used (biocompatible lubricants may help smooth insertion). 

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• Following electrode insertion, the cochlea shall be sealed with a piece of fascia graft and/or 
bone wax, bone paté. The periosteum shall be sutured over the implant region and the 
mastoid cavity. 
• The wound shall then be closed in layers with subcutaneous sutures and a suitable dressing 
shall be applied. 
• For each implantation the surgeon shall be required to document the duration of the 
surgery (starting time i.e. skin incision, and ending time i.e. last skin flap suture). 
 
After surgery, the rehabilitation procedures for study subjects shall be managed similar to FDA 
approved CI recipients (i.e. sound processor activation/fittings/mappings, speech therapy). 
3.5.3.1 
Allocation to Treatment 
Not applicable. 
Open label-trial. 
 
A single identification number (SSID) is assigned at the inclusion visit that uniquely identifies each 
subject, it is composed of the site code and subject number |_|_|-|_|_|). The same CI system 
models shall be assigned for all subjects. The sound processor is available in different colors but 
the hardware and electronic features are identical between processors. 
3.5.3.2 
Breaking the Blind 
Not Applicable 
3.5.3.3 
Treatment Adherence/Study Compliance 
The importance of rehabilitation and study visit attendance shall be discussed with each subject.  
 
The cochlear implant system must be used for at least 8 hours per day; system use will be verified 
via the subject diary. If a subject fails to utilize their cochlear implant system for at least 8 hours 
per day for more than 10 consecutive days and/or less than 85% of the total required wearing time 
for the study, the audiologist will ask the subject about the issue(s) and suggest alternatives.  
 
This survey will provide useful information on subject complaints. 
3.5.4 Withdrawal of Subjects Due to Non-Compliance 
Subjects who are not compliant with study visits shall be withdrawn from the study. Subjects may 
withdraw from the trial at any time at their own request, or they may be withdrawn at any time at 
the discretion of the PI and/or the sponsor for safety, behavioral, psychological or administrative 
reasons. If the subject does not return for a scheduled visit, every effort shall be made to contact 
the subject. Regardless, every effort will be made to document subject outcome for all participants 
in the study.  
 
For each subject that withdraws from the assessments detailed in the schedule of activities for 
visits, an “Early termination” shall be carried out. If the subject withdraws from the trial and also 
withdraws consent for disclosure of future information, no further evaluations will be performed 
and no additional data will be collected. The sponsor may retain and continue to use any data 
collected prior to the withdrawal of consent. Any withdrawn subject will be followed as a CI 
implanted patient and followed per regulatory guidelines. 
 

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Withdrawn subjects will not be replaced unless the total number of remaining subjects drops 
below 50 (10% loss). Should a subject withdraw or be withdrawn due to non-compliance, all 
available data regarding those that withdraw or are withdrawn will be provided and documented 
as a subgroup in a due-diligence effort to determine if a failure of the device to perform to 
specification was the reason or contributed to the reason of withdrawal or non-compliance. 
 
The subject cannot participate in another study during this study. However, as there is no wash-
out period at the end of this study, the subject can participate in another clinical trial at the end of 
this study. 
3.5.5 Follow-up Procedures 
An Oticon Medical Clinical Support could support the medical team in fittings and objective 
measurements. Roles and tasks are described in Appendix 6, the clinical support provides an 
assistance to the clinical team and should not interfere with subject clinical results. 
3.5.5.1 
Procedures to Assess Efficacy  
For the timing assessments please refer to the schedule of activities in section 3.5.5.4. 
 
Audiometric testing shall be performed by or under the direct supervision of an otolaryngologist, 
a qualified hearing aid acoustician/specialist, speech-pathologist, technician and/or by an 
audiologist qualified to perform such tests. The pivotal study should not disrupt the routine follow-
up visits of each referral center (i.e. fittings, programming changes, speech therapy, audiology 
tests, and radiological control).  
 
All subjects will use the same signal processing (e.g. directional microphone) and stimulation 
strategy (e.g. pulse shape, pulse rate). 
 
All subjects, English and non-English speakers, will be assessed with the same procedure and 
setups 
The Danish (20-sentences-list), the French Canadian (20-sentences-list) and the American English 
HINT (20-sentences-list) will be used according the local language. 
The HINT tests will be conducted with dedicated HINT software.  
a. 
Description 
The HINT (Hearing in noise Test) was developed at the House Ear Institute (Los Angeles, California) 
and measures speech recognition thresholds in quiet and noise [3]. When used to determine 
implant candidacy, the HINT sentences are generally presented in quiet. 
 
The HINT is recognized as a primary assessment instrument for measuring a subject’s ability to 
hear in quiet and in noise. HINT was originally designed as an adaptive speech recognition test 
based on a correct response of the entire sentence [3]. An intensity level measurement for the 
sentence speech-reception threshold was determined by presenting random HINT sentences in 
competing speech-shaped noise (SSN). However, current clinical use of HINT sentences routinely 
deviates from this original design; instead, HINT sentences are presented in quiet to obtain an 
accuracy measure, which is important for determining cochlear implant candidacy [4]. Disability 
evaluation under social security, requires that this testing be conducted in quiet at 60dB SPL [10]. 
 
A digital recording is presented to the subject placed inside a sound isolation booth.  

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For this protocol, subjects shall be tested with two sentence lists  
- 
during inclusion (visit 2)  
▪ in quiet and in noise in the best aided condition and  
- 
at 3, 6 and 12 months (visits 6, 7 and 8 respectively)  
▪ in quiet and  
▪ in noise condition in the ipsilateral electrically stimulated ear with an occluded 
contralateral ear.  
The noise and/or the signal shall be presented from the front of the recipient at 0° azimuth 
b. 
Procedure 
Speech perception tests will be conducted: 
• Preoperatively, on both ear with the best fitted hearing aid(s), and 
• Postoperatively, on ipsilateral ear with activated CIS and an occluded contralateral ear with 
ear-plug. 
 
Ear-plugs will be supplied for all centers. 
 
At visit 2 (preoperatively) 
The test is conducted in quiet and in noise background, and in the best-aided conditions 
 
In quiet: 
The subject’s is given practice sentences to become familiar with the task before each test.  Then 
two 20-sentences lists of HINT shall be presented to the subject, in front (0° azimuth), in quiet at 
a conversational speech level of 60 dB SPL (Appendix 9: Calibration considerations). All words 
in the sentence repeated correctly, (Nilsson et al. 1994 [5]) shall be computed to calculate a score 
in percent correct of total words.  
 
In noise: 
As described above, the same procedure is applied for HINT-N, sentences are presented at +10dB 
SNR, with noise set at 55 dB SPL, and signal at 65 dB SPL. 
 
From visits 6 to 8 (postoperatively) 
The tests shall be measured in quiet and in noise. Measurements are performed in the ipsilateral 
ear with an occluded contralateral ear with ear-plug 
 
In quiet and in noise, similar conditions of the test are used as described in visit 2.  
 
Speech perception score are computed to calculate score in percent correct (%) 
c. 
HINT score calculation in quiet and noise conditions 
The ratio of words correctly repeated divided by the total of words for each list is multiplied by 
100 to obtain the score in percent correct for the lists.  
3.5.5.2 
Procedures to Assess Safety  
For the timing assessment please refer to the schedule of activities in section 3.5.5.4. 
The PI shall be responsible for safety data collection.  
 
The PI may plan any unscheduled consultations as needed to follow any adverse event. 

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All complications/adverse events are recorded and classified as major or minor complication by 
the investigator. 
 
Serious Adverse Event or Major Complication (related or not related to the device) are those that 
are life-threatening (e.g. meningitis, death), those requiring hospitalization and/or resulting in 
disability or permanent damage (e.g. permanent facial nerve paresis, permanent chorda tympani 
syndrome, permanent vertigo/dizziness, persistent pain discomfort requiring device explant), 
those requiring revision surgery with or without re-implantation (e.g. device explant, surgery to 
prevent permanent impairment, large scalp necrosis, severe infection, electrode shifting, eardrum 
perforation, receiver positioning and cholesteatoma) and tinnitus, facial stimulation, pain that 
could not be alleviate by electrode deactivation; and other serious medical events.  
 
Adverse Event or Minor Complication (related or not related to device) are those that resolve 
spontaneously without surgical intervention (e.g. wound infection treated by antibiotics; skin flap 
hematoma; transient or rising tinnitus; transient vertigo/dizziness; transient pain; transient chorda 
tympani syndrome; transient facial nerve palsy, and tinnitus, facial stimulation and pain that could 
be relieved by electrode deactivation), or with conservative medical management (medical 
complications, pre-existing conditions such otitis media). 
 
All explanted devices returned to the manufacturer will be classified according the AAMI-CDV-4 
CI86 guideline, and ditto for the non-implantable part (i.e. sound processor, accessories). 
 
Description 
All adverse events and serious adverse events related to surgical/medical procedures and/or 
device shall be collected from the time subject is implanted till the completion of the study and 
shall also include any unscheduled visits dealing with adverse events or serious adverse events. 
 
Procedure for all complications 
Any suspected adverse event should be recorded on the “Adverse Event Report Form”, and the 
serious adverse event on the “Serious Adverse Event Report Form” available directly in the ECRF. 
 
For each adverse event, the outcome must specified at the end of the study. 
 
Procedure for explanted device 
Explanted device must be recorded on the “Explanted Device Report Form”  
Every explanted device shall be tested to determine the reason for device failure, and device 
explantation shall be reported as a serious adverse event and classified according to AAMI-CDV-4 
CI86 guideline. 
 
All explanted devices shall be returned to Oticon Medical for a formal evaluation and a report shall 
be made according to the criteria specified in the AAMI-CDV-4 CI86 guideline. It will be the 
responsibility of the Oticon Medical Vigilance System to determine the final classification of the 
device failure. Concurrent with any reporting to Oticon Medical of an explant, a report shall also 
be sent to the Local Competent Authority having relevant jurisdiction. 
 

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Complications may lead to device explantation, in such cases initial SAE reporting shall specify the 
reason: 
a. Explantation due to unrelated medical reasons, for example: 
Device is removed to enable diagnostic or therapeutic procedures for conditions unrelated 
to the implantation or function of the device (e.g. MRI scanning need outside manufacturer 
specification, radiotherapy, surgical resection, etc.) 
b. Explantation for medical reasons associated with the device. 
Any device explanted with medical symptoms that could be related to the device and/or 
caused by device malfunction, for example: 
- 
Meningitis secondary to the cochlear implantation 
- 
Infection near the receiver/stimulator, lead and/or electrodes 
- 
CSF leakage due to the occurrence of CSF leakage secondary to cochlear 
implantation. 
- 
Skin flap complication secondary to the cochlear implantation  
- 
Allergic reaction to device components 
- 
Dizziness due to occurrence of balance and other vestibular-related issues 
- 
Pain or discomfort that cannot be eliminated with changes in program parameter 
settings (e.g. deactivating an electrode). 
- 
Tinnitus appearing during device use or an increase in pre-existing tinnitus 
- 
Extra-cochlear stimulation, stimulation at sites outside the cochlea (e.g. facial 
nerve, chorda tympani, or return electrode placement, etc.) secondary to cochlear 
implantation and resulting from medical related factors (e.g. anatomical 
malformation, otosclerosis, cochlea ossification, etc.)  
- 
Electrode array misplacement during cochlear implantation 
- 
Electrode migration out of the cochlea 
- 
Implant migration/extrusion 
- 
Performance issue, the patient experienced a performance decline and/or failed to 
achieve a clinically-expected performance level attributable to health-related issues  
- 
Change in patient behavior with the device use, such as refusing to wear the device 
- 
Other; a patient may experience a sign or symptom not listed above or due to an 
unforeseen medical reason.  
c. Explantation because of suspected device failure. 
This category is determined by in-vivo testing which confirm malfunctions. For example: 
- 
Sudden loss of sound and/or gradual loss of function that occur over a short time 
- 
Loss of all connectivity with the implant  
- 
Shocking sensations, intermittent “popping” sounds, intermittent surges in 
loudness that exceed the loudness levels set by the clinician, and  
- 
Intermittent or permanent changes in speech perception or reported sound quality 
- 
Abnormal impedances accompanied by a change in sound quality 
- 
Performance decline because of a loss of functional electrode channels 
- 
Magnet issue/displacement  
- 
Case damage 
- 
Intermittent or unstable communication between internal and external 
components  
 
Calculation 
The proportion of patients experiencing a specified events shall be tallied and calculated.  

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Complications shall be classified as major and minor according to the Cohen & Hoffman criteria 
[23]. 
3.5.5.3 
Procedure to assess technical functionalities 
Impedance and ECAP measures will be performed per-operatively at the end of the surgery; at 
implant activation; at 3, 6 and 12 months post activation; and at unscheduled visit if available: 
- 
Impedance helps to ensure the correct electrode/tissue contact, and the correct 
operation of the internal part. The test will takes 30 sec. or more if some electrodes 
impedance are out of range and need to be checked again. 
- 
ECAP (Evoked Compound Action Potential) is the electrophysiological responses of 
the auditory nerve. The test will takes approximately 2 min (standard parameters: 
4 electrodes stimulated, 6 measures and 50 repetitions per measures).  
 
The impedance changes over time will be accessible from the patient maps in the fitting software. 
If any electrode turns out of range, it will be deactivated. Out of range electrode impedances can 
reflect degraded electrode-neuron interface, and can be related to electrical stimulation failure. 
Calculation: average of each electrode impedance at different time points and description of 
localization and number of electrode failures. 
 
The ECAP is the synchronous whole auditory nerve activity in response to an electrical stimulus. 
This is commonly measured by the difference in amplitude between two peaks (N1 and P2), 
characteristic from the human auditory nerve response [44]. These delays suffer from variations 
among both CI users and devices but is situated among 0.3 and 0.6 msec.  
Calculation: average of N1-P2 amplitude at each time point. 
 
 

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3.5.5.4 
Schedule of activities (Study Table) 
Protocol 
activity 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
Unscheduled 
visit(s) # 
8 weeks 
pre-surgery 
4 weeks 
pre-surgery 
Baseline 
2 weeks 
post-surgery 
1 month 
post-
surgery 
3 months 
post-
activation 
6 months 
post-
activation 
12 months 
post-
activation 
 
Screening 
Inclusion 
Surgery 
Follow-up 
Activation 
Follow up 
Follow up 
End of study 
NA 
Week 
(-8) 
Week 
(-4) 
Week 
(0) 
Week 
(+2) post-
surgery 
Month 
(+1) post-
surgery 
Month 
(+4) post-
surgery 
Month 
(+7) post-
surgery 
Month 
(+13) post-
surgery 
NA 
Eligibility 
 
 
 
 
 
 
 
 
 
Informed 
consent 
X* 
X** 
 
 
 
 
 
 
 
Eligibility 
criteria 
 
X 
 
 
 
 
 
 
 
Demographic 
data 
 
X 
 
 
 
 
 
 
 
Medical 
and 
Hearing History 
 
X 
 
 
 
 
 
 
 
Evaluations  
 
 
 
 
 
 
 
 
 
HINT-Q 
 
X 
 
 
 
X 
X 
X 
 
HINT-N 
 
X 
 
 
 
X 
X 
X 
 
Study device 
 
 
 
 
 
 
 
 
 
Surgery   
 
 
X 
 
 
 
 
 
 
Implant 
activation 
 
 
 
 
X 
 
 
 
 
Patient Diary 
 
 
 
 
 
 
 
 
 
Diary issued 
 
 
 
 
X 
X 
X 
 
 
Diary returned 
 
 
 
 
 
X 
X 
X 
 
Safety  
 
 
 
 
 
 
 
 
 
Adverse 
event 
reporting 
 
 
X 
X 
X 
X 
X 
X 
X 
Electrodes 
Impedance 
 
 
X 
 
X 
X 
X 
X 
(X) 
ECAP 
 
 
X 
 
X 
X 
X 
X 
(X) 
Concomitant 
medications 
 
X 
X 
X 
X 
X 
X 
X 
X 
  *Informed consent given 
**Informed consent obtained 
   #unscheduled visits may occur in addition to the predefined protocol specific visits. Unscheduled 
consultations must be related to CI complications/adverse events and/or additional speech 
processor fittings. The PI may plan any unscheduled consultations as needed. Impedance and ECAP 
measurements are optional and depend on the nature of patient visit. 
3.5.6 Permitted visit window periods 
Visit 
Visit interval 
(defined as number of weeks 
relative to visit 3, baseline) 
Visit window 
(defined as number of days from previous visit 
indicated plus and/or minus day stated) 
Visit window 
(defined as a range in days from 
previous visit indicated) 
1 
-8 
NA 
NA 
2 
-4 
28 days from visit 1 (-25 to +14 days) 
3-42 days from visit 1 
3 
0 
28 days from visit 2 (+/- 14 days) 
14-42 days from visit 2 
4 
+2 
14 days from visit 3 (-7 to +6 days) 
7-20 days from visit 3 
5 
+4 
28 days from visit 3 (-3 to +6 days) 
25-34 days from visit 3 
6 
+16 
112 days from visit 3 (-7 to +6 days) 
105-118 days from visit 3 
7 
+28 
196 days from visit 3 (-7 to +6 days) 
189-202 days from visit 3 
8 
+52 
364 days from visit 3 (-7 to +6 days) 
357-370 days from visit 3 

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3.5.7 Scheduled Visit Procedures 
Visit 1 (screening, Week -8 pre-surgery) 
Potential subjects shall be verified to be candidates for standard cochlear implantation, this 
screening process may be utilized to determine whether an individual may be appropriate for this 
study (e.g. motivation, geographical remoteness, willing to commit to protocol requirements, 
language skills).  
 
Screening may be accomplished during a medical visit, telephone or telemedical consultation, by 
mail and/or through medical records. Prior to enrollment, all potential subjects shall be presented 
with the informed-consent form and shall be given the time to read, understand and/or request 
further information or clarification regarding study requirements and associated risks.  
Consent is required once and may be obtained either at this visit or at visit 2. 
 
Visit 2 (inclusion, Week -4 pre-surgery) 
- 
Written informed consent: consent is required once and may be obtained either at this visit 
or at visit 1. 
- 
Subjects will  be assigned a single subject identifier (SSID) by the sponsor 
- 
The physician and/or qualified clinician shall verify that the potential subject has appropriate 
hearing aid settings to be in the best aided condition in accordance with good clinical practice 
and audiological standards. 
- 
Inclusion/exclusion criteria shall be reviewed to verify the potential subject meets all 
enrollment requirements 
- 
Demography, medical history, concomitant medications and any potential contra-indications 
to study inclusion requirements shall be reviewed  
- 
Audiometric evaluations: HINT-Q, HINT-N shall be obtained in the best-aided conditions 
- 
Audiometric evaluations in routine care shall be recorded, if available 
- 
Cochlear implantation scheduling shall be reviewed and confirmed 
 
Visit 3 (implantation, Week 0 surgery) 
Surgery shall be performed according to conventional cochlear implantation standards and good 
surgical clinical practice. 
- 
Time of surgery and surgical approach shall be recorded on the CRF 
- 
Objective measures: electrode impedances and ECAP if obtained, shall be recorded 
- 
Complications/adverse effects shall be recorded 
- 
Concomitant medication(s) shall be noted on the CRF 
 
Visit 4 (follow-up, Week +2 post surgery) 
- 
Perform clinical examination (general state, scarring, skin-flap assessment,) 
- 
Complications/adverse effects shall be recorded 
- 
Concomitant medication(s) shall be recorded 
 
Visit 5 (activation, Month +1) 
- 
Activation and fitting of Neuro CIS shall be performed 
- 
Objective measures: electrode impedances shall be recorded 
- 
Subject will be instructed in the use of Subject’s diary 
- 
Complications/adverse effects shall be recorded 
- 
Concomitant medication(s) shall be recorded 

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Visit 6 (follow-up, Month +3 post-activation) 
- 
Audiometric evaluations: HINT-Q, HINT-N scores shall be recorded 
- 
Audiometric evaluations in routine care shall be recorded, if available 
- 
Objective measures: electrode impedances and ECAP shall be recorded 
- 
Review of returned Subject’s diary 
- 
Subject shall be reminded about the correct use of Subject’s diary 
- 
New Subject’s diary dispensed 
- 
Complications/adverse effects shall be recorded 
- 
Concomitant medication(s) shall be recorded 
 
Visit 7 (follow-up, Month +6 post-activation) 
- 
Audiometric evaluations: HINT-Q, HINT-N scores shall be recorded 
- 
Audiometric evaluations in routine care shall be recorded, if available 
- 
Objective measures: electrode impedances and ECAP shall be recorded 
- 
Review of returned Subject’s diary 
- 
Subject shall be reminded about the correct use of Subject’s diary 
- 
New Subject’s diary dispensed 
- 
Complications/adverse effects shall be recorded 
- 
Concomitant medication(s) shall be recorded 
 
Visit 8 (end of study, Month +12 post-activation) 
- 
Audiometric evaluations: HINT-Q, HINT–N 
- 
Audiometric evaluations in routine care shall be recorded, if available  
- 
Objective measures: electrode impedances and ECAP shall be recorded 
- 
Review of returned Subject’s diary 
- 
Complications/adverse effects shall be recorded 
- 
Concomitant medication(s) shall be recorded 
 
Unscheduled visit 
- 
Visit purpose shall be recorded 
- 
Objectives measures: electrode impedance and ECAP, if available 
- 
Complications/adverse effects shall be recorded 
- 
Concomitant medication(s) shall be recorded 
3.6 
Study Outcome Evaluations 
3.6.1 Study Endpoints 
3.6.1.1 
Primary Endpoints 
Previous studies analyzed their samples based on fixed time intervals after implantation, usually 
1, 3 and 6 months, then annually thereafter. After 6 months of CI experience outcomes appear to 
be stable with the majority of users reaching a performance plateau. Massa et al. [5] observed a 
performance plateau at a median of 4.7 months post-implantation. Similar results were reported 
by Bradley et al. [8] demonstrated a plateaued performance around 6 months in a sample of 55 
patients. In Dillon et al. study [9] the adults tested with HINT in quiet at 70 dB experienced growth 
in speech perception within the first 6 months and remained stable thereafter. This plateau at 6 

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months is generally consistent with findings from others previous research with other speech 
discrimination tools, as Lenarz et al. study [7] using German language tests in a large cohort. 
a) HINT in Quiet (HINT-Q) 
The primary efficacy endpoint of the Neuro CIS is assessed with the HINT score in quiet in the 
ipsilateral ear. The primary endpoint is the difference between the baseline performance in the 
best-aided condition and the performance in the implanted ear within 6 months following 
activation. The mean score of words correctly repeated in quiet will be used as the primary 
outcome measure for assessing the primary benefit. 
b) Safety 
The occurrence of major complications within the first year of follow-up will be the co-primary 
endpoint for assessing the primary risk of device implantation.  
 
Safety data shall be collected through the duration of the study and reflect the type and duration 
of any adverse event(s) and classified as major or minor complications. Evaluations shall be 
performed from baseline, during the operative time, and at each time points.  
Three estimations of incidence rate will be provided:  
- 
Major complications rate (co-primary estimate of device side-effects) 
- 
Minor complications rate (secondary evaluation of side-effects). 
- 
Incidence rate of any complications. 
 
It is expected that major complication incidence rate will be within the range of variation of 
estimations obtained in previous studies on old generations of devices. A forest plot will present 
the estimate and 95% CI of incidence rate for the investigational device and estimates and 95% CI 
obtained in previous studies and previous generations.  
3.6.1.2 
Secondary assessment criteria  
a) HINT in quiet (HINT-Q) at month 3 and 12months 
The secondary endpoint is the score of words correctly repeated in quiet determined at 3, and 12 
months post-activation in the implanted ear and the performances compared overtime. 
b) HINT in Noise (HINT-N)  
This efficacy secondary criterion is the score of words correctly repeated in noise preoperatively 
and at 3, 6 and 12 months post-activation in the implanted ear and the performances compare 
overtime. 
3.6.1.3 
Other outcome of interest – Technical Functionalities 
The average of electrodes impedance values are collected at the different time points and 
observed over time. 
The average of N1-P2 peaks amplitudes are determined at each time point and observed over 
time. 
3.6.1.4 
Sample Size Determination 
Sample size determination is based on the two co-primary endpoints: change from baseline to 6 
months of the HINT-Q (efficacy assessment), and major complication incidence rate during the 12 
month follow-up (safety assessment).  
 

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The expected efficacy is an improvement of 50 points at 6 months of device use. 
 
Change from baseline to 6 months is not available in literature, but 2 studies describe the HINT-Q 
magnitude after 12 months of device use. Waltzman et al. [42] described an increase of 47.7% 
(SD=26.6%) from pre- to 3 months post-implantation, similar results are reported by Lin et al. [43] 
with a magnitude of 60% (SD=24.1%) at 12 months. Considering an observed performance plateau 
around 6 months [5,8,9,7], we can consider that standard deviation obtained at 3 and 12 months 
can be used for 6 months of device use in this study. In addition in the main studies conducted at 
6 months [5,6,8,9], the standard deviation are ranged from 22% to 28%, which is consistent with 
results change from baseline. Data from literature using the same efficacy assessment criterion 
provided a weighted average ± weighted standard deviation change from baseline of 57.43% ± 
25.05%.  
Such estimation has been rounded conservatively to 50% ± 25%.  
 
Sample size 
The sample size required to have 95% chance to get a significant efficacy result assuming a true 
mean improvement of 50%, a standard deviation of change from baseline of 25% and a type I error 
of 0.025 (one-sided) is 7 patients. It means that the expected improvement is so large with respect 
to the variability that the sample size calculation is not driven by efficacy considerations.  
 
As requested by the FDA, the sample size will be set at a total of at least 50 subjects to support the 
safety. If the incidence rate of major complications is 2% then the chance to observe at least one 
event is 63.5%. The exact upper limit of the 95% C.I. will be 10.6% for an observed rate of 2%. 
Regarding any complication the expected rate is 35%. If the observed rate is 36% then the precision 
is around 13% in points. 
 
In order to ensure that at least 50 subjects will be implanted with the device, starting with the 
anesthesia followed by surgery procedure, 55 subjects will be included. 
 
An arbitrary minimum of 39 English speaking patients and 16 non English speaking patients will be 
recruited to meet the FDA requirement. It is possible that the recruitment in a given language be 
smaller than expected. In this case patients from other languages may replace the shortage 
provided that a minimum of 5 French speaking patients and 5 Danish speaking patients be 
recruited to justify the class of language.    
3.6.2 Outcome Data and Data Analysis 
3.6.2.1 
Analysis Set 
a) Full Analysis Set (FAS) 
This set will include all subjects implanted with the device, regardless whether any post-operative 
data are available. The primary analysis will be performed on a subgroup of this set. This subgroup 
is composed of English speaking patients to avoid the probable effect of language on the response. 
b) Per-Protocol Set (PPS) 
This set of patients is composed of participants who complete the clinical trial according to the 
protocol. 
It consists of subjects who satisfy the following criteria: 

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- 
Complete the pivotal study 
- 
Protocol compliance during the pivotal study (complete post-implantation visits) 
- 
No violation of any eligibility criteria that could influence the primary efficacy endpoint 
- 
No violation of the protocol or deviation from the protocol which could influence the 
outcome of efficacy endpoints. 
 
The type of protocol violation and protocol deviations that are considered to influence the 
outcome of the safety endpoints will be defined in the statistical analysis plan. 
 
The English speaking subgroup in the PPS will be used in a sensitivity analysis of the primary 
analysis. 
c) Safety Analysis Set (SAS)  
It consists of all subjects for whom surgery for implantation started.  
3.6.2.2 
Analysis of Efficacy Endpoint(s) 
The primary analysis of the primary efficacy endpoint will be performed on a subgroup of the FAS 
which consists of all English speaking patients (Exclusion of Danish and French Canadian speaking 
patients). The primary test is a one sample T-test performed on the change from baseline to 6 
months after activation of the device. The value of the mean improvement under the null 
hypothesis is zero. The type I error (α) is set to 0.025 (one-sided). 
 
The one sample Wilcoxon rank test will be applied in a sensitivity analysis. In case the normality 
assumption is strongly violated or in the presence of several outliers the result of this sensitivity 
analysis will have a particular importance. The same analysis performed on the Per Protocol Set of 
patients in English speaking people will be another sensitivity analysis of the primary analysis.  
3.6.2.3 
Co-primary Analysis of Safety Endpoint 
No formal hypothesis testing of safety data will be performed. The safety analysis consists of all 
enrolled subjects for whom implantation surgery was initiated. The incidence rate of major 
complications will be presented as well as its 95% exact confidence interval. A forest plot will 
present this rate with its 95% C.I. and the rates with the 95% C.I. of major complications in studies 
carried out with older generations of cochlear implants.  
3.6.2.4 
Secondary analyses 
Claims for labeling will be based only on confirmatory results demonstrate through the primary 
analysis. 
All secondary or sensitivity analyses are supportive estimates of effects related to the primary or 
secondary objectives.  
a) Time course of the HINT-Q response in the primary population  
The time course of the change from baseline in the HINT-Q will be estimated with a mixed model 
for repeated measures using the change from baseline as the response, the patients (random 
effect) and the visit (fixed effect) as covariates. The analysis will be done on the FAS subset of 
English speaking patients. 
 

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The time (visit) effect will be tested (H1: at least two visits differs on average) and if a significant 
effect of visits is observed then visits responsible for the significant difference will be searched. 
The 95% confidence interval of the mean at each visit will be provided. 
b) Sustainability of the effect at month 12 
HINT in quiet conditions performed at month 6 in English speakers will be compared to the result 
at month 12 to assess the sustainability of the effect over time. A one-sided ( = 0.025) t-test for 
paired samples will be used for that purpose. 
c) Difference in the time course of HINT-Q responses across languages  
The FAS including all patients instead of the subset of English speaking patients will be used in 
these secondary analyses. A mixed model for repeated measures will be fitted using the change 
from baseline to M3, M6 and M12 in the HINT-Q score as the responses and the following 
covariates or terms: the visit (M3, M6 and M12, fixed effect), the patient (random effect), the 
language (fixed effect) and the interaction between visit and language. The variance covariance 
matrix will be unstructured. If the p value of the interaction is below 0.15 then a signal of potential 
interaction is detected and the time course of speech performance is possibly dependent upon the 
language. Regardless the p value of interaction a graph will present the time course of the response 
for each language. 
 
A series of contrasts will be performed to estimate and test: 
 
1) The difference between languages in the change from baseline at each time point.    
 
The estimate and test at M6 will be the most supportive result. 
 
2) The overall mean change from baseline at each time point. The test against no change will be 
performed. Results will be easily interpreted in the absence of potential interaction (No significant 
difference in the time course of response between the 3 languages.      
 
3) The overall difference between M6 and M12 in the change from baseline to assess the 
sustainability of effect in the overall population. This estimate is interpretable in the absence of 
interaction between visit and language. In the presence of interaction the difference is not easily 
interpretable and sustainability will be estimated and tested in the English speaking patients only. 
d) Analysis of HINT-N 
All analyses performed on the HINT-Q will be performed on the HINT-N, the response will be the 
change from baseline. 
e) Measures of impedance 
The time course of electrodes impedance performed at each time points will be analyzed through 
a mixed model for repeated measure and contrasts of interest will be described in the SAP. 
f) ECAP 
ECAP measures amplitude between (N1-P2) peaks. Measures will be performed over time from 
baseline to 12 months. The times course of the response will be fitted to a mixed model for 
repeated measures and contrast of interest will be describes in the SAP. 

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g) Safety analysis 
The incidence rates of 1) minor complications, 2) any complications and 3) any adverse events will 
be estimated with their 95% C.I. in the safety population. The time to the first minor or major 
complications will be investigated through Kaplan Meier survival (event free) analysis and the 
graph of the estimated event free probability by the time will be presented. 
 
A breakdown of all adverse events by categories will be done. The occurrence rates and 95% CI 
within each category will represent the safety profile of the new device.  The observed rate in 
previous generations of device will be provided as a yard stick if they are available.  Results from 
safety assessments will be presented in a tabular and/or graphical format (Forest plot). 
 
Data regarding the average surgical time will also be reported. 
h) Handling of site effects 
The site effect is partly confounded with the language effect. Consequently the site effect will be 
investigated in English speaking patients. An analysis of variance using the change from baseline 
to M6 as the response and the site as covariate will be performed. If the site effect is significant, 
then the mean change from baseline to M6 is dependent upon the site. Regardless the p value of 
ANOVA a Forest plot presenting the mean change from baseline to M6 of each site along with the 
95% confidence interval will be presented to verify whether there is just a quantitative difference 
across sites or a qualitative one. In case of significant site effect and qualitative difference the site 
with the largest mean deviation from the overall mean change from baseline will be removed from 
the sample to estimate the overall mean change from baseline in the remaining sites. 
3.6.3 Handling of Missing Data 
3.6.3.1 
Imputation rules used in the primary analysis 
Rule 1: If the assessment at M6 is missing but a further assessment is available the missing 
assessment will be replaced by the next available data. 
Rule 2: If the assessment at M6 and M12 is missing but the assessment at M3 is available then M3 
score will be carried forward.   
Rule 3: If the assessment at M6 and M12 is not available in quiet conditions but available in noise 
then the score at M6 in noise will be used.  
Rule 4: In case of lost to follow-up or withdrawal of the inform consent for unknown reason a 
stochastic regression imputation will be used. 
Rule 5: In case of withdrawal not due to a failure of the implantation or complications the baseline 
will be imputed at month 6. 
Rule 6: In case of withdrawal due to major complications requiring new implantation the worst 
score (0%) will be imputed. 
3.6.3.2 
Sensitivity analyses  
• The best case scenario will consist in deleting patients without data at M6 and M12 (if M12 
is available then M12 will be imputed at M6).    
• The worst case scenario will consist in imputing a total loss of hearing (score = 0%) 
• Tipping point analysis approach will be applied to assess the rules which overturn the 
conclusion. The steps going from the best scenario to the worst one (all missing scores are 
0) and including rules of the primary analysis as intermediary step will be described in the 
SAP.  

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3.6.4 Futility/Safety Interim Analysis 
Interim analyses will be performed on the safety endpoint. This is based on real-time information 
given by the monitoring and ECRF. 
 
The trial could be stopped prematurely if the cumulated number of major complications is beyond 
the worst case scenario reported in the literature. Indeed, literature data reported a weighted 
average of 7.1±2.0% major complication rate over many years of experience [16,17,18,19,20,21]. 
Consequently if the number of observed major complication as described in section 3.5.5.2 is 
beyond (7.1%+2%)*55= 5 cases the study should be stopped prematurely for safety reason. 
 
Actually at the 5th major complications during the inclusion period, the DSMB will meet expressly 
to decide how to move forward on the benefit-risk balance change (e.g. protocol amendment, 
temporary halt or early termination). 
 
Once the inclusion period is over, the study will go to the end and the complications gather in the 
safety final report. 
3.6.5 Data and Safety Monitoring Board 
Each SAE will be submitted to the DSMB. 
If more than 4 major complications are reached during the inclusion period, an extraordinary 
meeting of the DSMB will take place within the 7 calendar days. 
The DSMB shall be notified each time an SAE occurs. Monitoring of key safety endpoints will be 
conducted as described above, and if rates significantly exceed pre-set thresholds, Competent 
Authorities will be notified and information supplied to the DSMB. 
DSMB’s 
Policies 
are 
described 
in 
the 
Oticon 
Medical 
Manual 
Procedures 
(composition/organization). 
The data safety monitoring plan, describe: 
- 
Type of data or events captured under the monitoring plan 
- 
Names of persons who will be responsible for monitoring the data collected 
- 
The frequency of assessments/analysis of data or events captured by the monitoring plan 
(e.g. periodic time interval, or after a specific number of participants are enrolled) 
- 
Time frame for reporting unanticipated issues, adverse effects, protocol deviations, 
protocol violations 
- 
Definition of specific events or stopping rules dictating when some actions are required  
- 
Procedure and timeframes for communication outcomes of monitoring reviews to 
investigator sites, EC and CAs. 
- 
Plans to monitor adherence to the EC/CA-approved protocol and assure the validity and 
integrity of data. 
 
The DSMB should also assess the performance of overall operation study. 
3.6.6 Early Stopping Rules 
No statistical stopping rule for success is applied for the primary efficacy endpoint. 
 
If no interim analysis shows safety endpoint values greater than the pre-set limit, the study shall 
continue until completion (Please refer to section 3.6.4). 

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3.6.7 Study Interruption or Withdrawal 
Premature termination of this clinical trial may occur because of regulatory authority decision, 
change in opinion of the EC/CA, safety problems, or at the discretion of Oticon Medical. In addition, 
Oticon Medical retains the right to discontinue the trial at any time. 
 
If a trial is prematurely terminated or discontinued, Oticon Medical will promptly notify the PI. 
After notification, the PI must contact all participating subjects within 24 hours. As directed by 
Oticon Medical, all trial materials must be collected and all CRFs completed to the greatest extent 
possible. 
 
 

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4. RISK ANALYSIS 
4.1 
Expected clinical benefits  
The Neuro CIS has many similar features to the previous CIS (Digisonic SP + Saphyr SP Neo) and 
incorporate some of the same technologies. The two principle new features implemented into the 
Neuro Zti implant are the removable magnet and the ECAP recording hardware. These 2 features 
are currently incorporated into FDA approved CISs. The new features implemented in the Neuro 
One processor are related to hearing aid technology integration for signal processing (integration 
of directional microphones, etc.), but coding strategy and stimulation principles are similar 
between the Neuro CIS and the Digisonic CIS. 
 
Expected clinical benefits are comparable to other CIS systems available on the market: for 
example Bergeron et al. [28] compared devices with the most recent technologies using HINT tests 
and showed an improvement of Digisonic SP + Saphyr Neo CIS compared to competitors in quiet 
and some noisy conditions (+10dB SNR), and similar performance in other noisy conditions among 
all devices..  
4.2 
Anticipated Adverse Events 
Risks of general anesthesia 
- 
General anesthesia. Individuals may react differently to anesthesia. Although the risk 
associated with general anesthesia to obtain a cochlear implant is outweighed by the 
potential benefit for most candidates, individuals with certain medical conditions may be 
at higher risk for complications. 
 
Risks of cochlear implant surgery 
- 
Injury to the facial nerve. The facial nerve traverses through an anatomical region near the 
cochlea to provide movement to the muscles of the face. The nerve lies close to where the 
surgeon needs to place the implant and may be injured during surgery. An injury to the 
nerve may cause a temporary or permanent weakening or even full paralysis on the same 
side of the individual face as the implant.  
- 
Meningitis. This condition results from an infection that results in inflammation of the 
meninges that line the central nervous system. Meningitis may result in serious 
complications including permanent brain damage or death. Individuals who experience 
inner ear structure anomalies or malformations and/or are implanted with a cochlear 
implant may be at an increased risk of meningitis. 
- 
Cerebrospinal fluid leakage. The brain and central nervous system are surrounded by fluid 
that may leak from a hole created in the inner ear during surgery. An uncontrolled leak of 
CSF may result in serious injury or death.  
- 
Perilymph fluid leakage. The inner ear contains a fluid called perilymph. This fluid, which 
is continuous with CSF, may leak through a hole created for electrode array placement.  
- 
Infection of the wound or the implant. This includes the risk of otitis media which may 
cause infection on the implant either outside the cochlea or within the ear. In the case of 
infection that cannot be resolved with antibiotics, the device may need to be explanted to 
resolve the infection.  
- 
Skin flap issues. Although this will typically resolve with treatment, in the worst case the 
device may need to be explanted, with re-implantation once the infection has resolved. 
- 
Cholesteatoma formation. 

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- 
Blood or fluid collection/edema at the site of the surgery 
- 
Vertigo or dizziness 
- 
Tinnitus 
- 
Taste disturbance. The sensory nerve that conveys taste sensations from the tongue also 
passes through the middle ear and may be injured during the surgical procedure. 
- 
Stiffness or Numbness in the area around the surgical site   
- 
Reparative granuloma. Is the result of localized inflammation and may occur if the body 
rejects the implant. 
- 
Pain. 
- 
Unforeseen complications due to the surgical procedure 
- 
Unforeseen complications that could occur with long term implantation that cannot  be 
predicted beforehand  
 
Risk associated with the device 
A study participant: 
- 
May have skin irritation or redness behind the ear. Removal of the sound processor is 
recommended until the issue is resolved.  
- 
May have skin irritation or redness in and around the implanted area. A magnet holds the 
antenna in place against the skin on the implanted device. Reduction in the magnet 
strength is recommended. 
- 
May have to undergo device explanation if an infection occurs after the implant surgery 
that cannot be resolved with antibiotics. This is a rare complication. 
- 
May have the sensation of heat or burning due to an increase in the processor 
temperature. The individual may remove his/her processor immediately. 
- 
May experience an uncomfortably loud sensation. The T and C level thresholds are based 
on each individual’s responses during the fitting session.  
- 
May remove the processor before medical examinations and treatments; radiotherapy, 
MRI, ultrasound, scan, treatment using electric currents. 
- 
May be able to undergo  some medical examinations and treatments with caution and 
under specified conditions: 
▪ MRI imaging at 3 Tesla may be obtained with implant magnet removal. A minor 
surgery is required to remove the magnet beforehand. The implant is 1.5T 
compatible, however, if the medical region of interest falls within the projected 
artifact produced by the implant, the magnet may be removed to minimize 
artifacts. 
▪ Neurostimulation, when not directly over the implant. 
▪ Electrical surgery. Monopolar electrosurgical instruments may not be used on the 
head or neck area during and following implant placement.  
▪ Ionic radiation therapy.  
▪ Electrotherapy may be not used on the head and neck area. 
▪ Diathermy may be not used on the head and neck area. 
▪ Defibrillation may cause device damage but may be used in life-threatening 
situations. 
- 
May be not able to have electroconvulsive therapy. 
- 
May lose residual hearing. The implant may damage any remaining hearing in the 
implanted ear. 

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- 
May be at risk for dislocation and/or migration and/or demagnetization of the implanted 
magnet through a strong magnet field, or other conditions such as exposure to an MRI 
scan. Such conditions may require revision surgery to replace the magnet. 
- 
May be at risk for electrode array misplacement. This is a rare and correctable complication 
that may require revision surgery to re-insert and secure the electrode. To further mitigate 
this risk, final electrode position is confirmed by visual inspection prior to closing and 
inferred by impedance and ECAP measures at the end of surgery. 
- 
May exhibit device rejection which may result in the extrusion of the implanted 
components and/or necessitating the need for device removal. 
- 
May be at risk for the electrode array being damaged during surgery. 
- 
May be at risk for electrode post-surgical electrode migration requiring revision surgery to 
re-insert and secure the electrode. 
- 
May experience an internal device failure. The individual would need to undergo additional 
surgery to resolve this issue and be exposed to additional surgical risk. 
- 
May develop the need to have the CIS removed for medical reasons. 
- 
May be at risk for impact or trauma near the implanted components resulting in partial or 
complete failure of the implanted components. Accidents, slips, trips, falls, contact sports, 
and any external impact may increase the risk of damage to the implant. Device failure 
would require revision surgery for correction.  
 
Other risks associated with the use of the cochlear implant 
A study participant: 
- 
May hear sounds differently.  Those who could hear before they became deaf report that 
cochlear implants may not sound like “natural” hearing. At first, it is not uncommon for 
users to describe the sound as “mechanical”, “technical” or “synthetic”. This perception 
changes over time and most users do not notice this artificial sound quality after a few 
weeks of CI use.  
- 
May not hear as well as others who have had successful outcomes with their CI. 
- 
May not be able to understand spoken language well. There is no test an individual can 
take before the surgery that predict how he/she will understand language after surgery.  
- 
May have an altered perception of sound. They may require numerous changes to program 
settings to achieve the best sound quality.  
- 
May have to use another processor than their own.  
- 
May fail to use the device properly. User action may be limited by the audiologist with only 
one standard mode program. 
- 
Will depend on batteries for hearing. Autonomy of batteries may be less than a working 
day.   
- 
May receive intermittent, reduced and/or absence of sound. The individual should check 
his/her processor status; correct connection of the antenna cable, quality of the 
microphone using the earphones and battery life. 
- 
Will have to take precautions to avoid electrostatic discharge. Static electricity may 
temporarily or permanently damage the CI. To prevent this issue, it may be good practice 
to remove the processor before contact with static generating materials such as TV screens, 
plastic equipment, or synthetic fabric, or to remove any residual static electricity by 
touching the individual wearing the CI prior to touching the processor.  
- 
May have to undergo lifestyle changes if their CI interacts with the electronic environment 
( e.g. the device may set-off theft detection systems, set-off metal detectors or other 

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security systems, it may be requested that the device be turned off during take-off and 
landing in an aircraft, and the device may interact in unpredictable ways with other 
electronic systems).  
- 
May hear strange sounds or experience interference resulting from device interaction with 
other electro-magnetic fields. 
- 
May have unknown and/or other certain effects. The CI stimulates the nerve directly with 
electrical currents. Although this stimulation appears to be safe, the long term effect of 
these electrical currents on the nerve is unknown. 
 
Performance decline may be related to different causes including but not limited to the following: 
- 
Abnormal sound perception: 
▪ Unusual sounds when thresholds are low 
▪ Loud bursts of sound percepts 
▪ Sound popping 
▪ Other unusual sound perception 
- 
Pain  
▪ Pain over the implant 
▪ Pain under the processor hook (the hook can be replaced or its shape adapted). 
- 
Documented performance decrement 
▪ Sudden loss of auditory ability 
▪ Decrement of hearing ability over time or lack of expected progress according to 
speech perception measures 
▪ Intermittent auditory function 
▪ Failure to meet predicted performance level 
▪ Reduction in or lack of meaningful speech understanding 
▪ Lack of sound clarity 
▪ Loss of electrodes over time 
▪ Implant magnet issues 
▪ Regression in language understanding and speech production 
▪ Deterioration in school or work performance 
▪ Other performance decline 
- 
Medical issues 
▪ Infection 
▪ Meningitis 
▪ Wound issues 
▪ Vertigo, dizziness 
▪ Headaches 
▪ Cholesteatoma  
▪ Facial nerve stimulation while the implant is on  
▪ Other medical issues 
- 
Behavioral issues 
▪ Unwilling to wear the device 
▪ Being frequently “off line”- failure to use the device as prescribed 
▪ Other behavioral issues 
- 
Other observations. 

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4.3 
Trial Anticipated Risks 
Subjects participating in this pivotal study shall be candidates for cochlear implantation, the risks 
are related to the surgery, no additional risks are provided by the trial compared to FDA approved 
cochlear implant designs. Audiometric tests (HINT) used in the trial are standardized and routine 
clinical tests. The 60 dB SPL signal presentation level is the average of conversational speech used 
for HINT-Q. HINT-N follows a routine standardized procedure. The study visits are closely matched 
to a cochlear implant recipients’ routine visits to limit additional subject travel. 
Subjects who agree to participate will have the same expectation of benefit as a routine cochlear 
implant recipient.  
4.4 
Benefit-risk Ratio 
According to the risk analysis of the Neuro One and Neuro Zti, the majority of risks have limited 
severity; any risk to external components may be managed by removing and/or replacing the 
externals. Major risks are related to the implantable part, related to surgical/medical 
complications and device-related failure and they have a limited probability of occurrence as well 
as limited severity. Moreover, cochlear implantation is a therapy now used for more than 25 years, 
ENT knowledge and training is well developed today ensuring limited medical side-effects and 
effective patient care and follow-up. 
 
The Neuro CIS is indicated for patients suffering from severe to profound hearing loss with limited 
benefit from appropriately fitted hearing aids. Therefore, these patients have no other alternative 
than cochlear implantation to enable the possibility of improved auditory function. Expected 
auditory benefits enable cochlear implant users to understand speech even in noisy situations. 
Cochlear implantation has been well documented to enable restored communication ability and 
social interactions for adults. 
 
In light of the expected benefit of this product compliant with the essential requirements, and the 
identified risks, the risk-benefit balance is favorable. 
4.5 
Adverse Event Recording/Reporting  
4.5.1 Adverse Events 
All observed or volunteered adverse events regardless of investigational device or suspected 
causal relationship to the investigational device shall be reported as described in the following 
sections. 
 
For all adverse events, the investigator shall pursue and obtain adequate information both to 
determine the outcome of the adverse event and to assess whether it meets the criteria for 
classification as serious adverse events (see section 4.5.6) requiring immediate notification of 
Oticon Medical or its designated representative. For all adverse events, sufficient information shall 
be obtained by the investigator to determine the causality of the adverse event. The investigator 
shall be required to assess causality. For adverse events with a causal relationship to the 
investigational device, follow-up by the investigator shall be required until the event or its 
sequelae resolve or stabilize at a level acceptable to the investigator and Oticon Medical concurs 
with that assessment. 

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4.5.2 Reporting Period 
Serious adverse events require immediate notification of Oticon Medical or its designated 
representative beginning from the time that the subject provides informed consent, which is 
obtained prior to the subject’s participation in the clinical trial, i.e. prior to undergoing any trial 
related procedure and/or receiving investigational device,  up to and including 28 calendar days 
after last visit. Any serious adverse event occurring any time after the reporting period must be 
promptly reported if a causal relationship to the investigational device is suspected. 
 
Adverse events (serious and non-serious) should be recorded on the CRF from the time the subject 
has been implanted through 28 calendar days following the last subject visit. 
4.5.3 Definition of Adverse Event (AE) and Adverse Device Effect (ADE) 
An AE/ADE is any adverse change from the subject’s baseline condition, i.e. any unfavorable and 
unintended sign including abnormal laboratory findings, symptoms or disease which is considered 
to be clinically relevant by the investigator that occurs whether or not it is considered to be related 
to the medical device. 
 
AE/ADE include: 
- 
Exacerbation of a pre-existing disease. 
- 
Increase in frequency or intensity of a pre-existing episodic disease or medical condition. 
- 
Disease or medical condition detected or diagnosed after treatment with the medical 
device even though it may have been present prior to the start of the clinical investigation. 
- 
Continuous persistent disease or symptoms present at baseline that worsen following the 
start of the clinical investigation. 
- 
Lack of efficacy in the acute treatment of a life-threatening disease. 
- 
Events considered by the investigator to be related to clinical investigation-mandated 
procedures. 
- 
Abnormal assessments, e.g., ECG and physical examination findings, must be reported as 
AEs/ADEs if they represent a clinically significant finding that was not present at baseline 
or worsened during the course of the clinical investigation. 
- 
Laboratory test abnormalities must be reported as AEs/ADEs if they represent a clinically 
significant finding, symptomatic or not, which was not present at baseline or worsened 
during the course of the clinical investigation leading to interruption or permanent 
discontinuation of medical device. 
 
AE/ADE do not include: 
- 
Pre-planned interventions or occurrence of endpoints specified in the CIP that are not 
considered AEs/ADEs, if not defined otherwise. 
- 
Medical or surgical procedures, e.g. surgery, endoscopy, tooth extraction, transfusion. 
However, the event leading to the procedure is an AE. If this event is serious, the procedure 
must be described in the SAE/SADE narrative. 
- 
Pre-existing disease or medical condition that does not worsen. 
- 
Situations in which an adverse change did not occur, e.g., hospitalizations for cosmetic 
elective surgery or for social and/or convenience reasons. 
- 
Misuse of either medical device or concomitant medication without any signs or 
symptoms. However, misuse must be mentioned in the Medical Device Inventory/ 
Treatment Log. 

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An Adverse effect is defined as any untoward medical occurrence in a subject following device 
implantation or device use. 
 
An AE does not need to be a causal relationship between the effect and the investigational device 
procedure or device usage. 
 
AEs include, but are not limited to: 
- 
Abnormal test findings 
- 
Clinically significant symptoms and signs 
- 
Changes in physical examination findings 
- 
Progression/worsening of underlying disease 
All AE are reported on the Adverse Event Form (Appendix 3). 
4.5.4 Abnormal Test/Exam Findings 
The criteria for determining whether an abnormal objective test finding should be reported as an 
adverse event are as follows: 
- 
Test result is associated with accompanying symptoms and/or, 
- 
Test result requires additional diagnostic testing or medical/surgical intervention and/or, 
- 
Test result leads to a change in trial procedure or discontinuation from the trial, significant 
additional concomitant treatment, or other therapy, and/or 
- 
Test result is considered an adverse effect by the investigator or the sponsor. 
 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an adverse event. Any abnormal test result that is determined to be an error does not 
require reporting as an adverse event. 
4.5.5 Adverse Device Effect Definition 
Adverse event related to the use of the investigational medical device. 
This includes any adverse event resulting from insufficiencies or inadequacies in the instruction for 
use, the implantation surgery or any malfunction of the investigational medical device. 
This includes any event that is a result of a use error or intentional misuse. 
4.5.6 Serious Adverse Event definition 
A Serious Adverse Event or Serious Adverse effect is defined as any untoward medical 
occurrence that: 
- 
Results in death,  
- 
Is life-threatening illness or injury,  
- 
Results in inpatient hospitalization or prolongation of existing hospitalization 
- 
Results in a persistent or significant disability/incapacity, or  
- 
Is considered an important medical event 
 
Life-threatening adverse effect. Any adverse effect that places the subject, in the view of the PI-
sponsor, at immediate risk of death from the effect as it occurred (i.e., does not include an adverse 
effect that, had it actually occurred in a more severe form, might have caused death). 
 
Hospitalization shall include any initial admission (even if less than 24 hours) to a healthcare facility 
as a result of a precipitating clinical adverse effect; to include transfer within the hospital to an 

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intensive care unit. Hospitalization or prolongation of hospitalization in the absence of a 
precipitating, clinical adverse effect (e.g., for a preexisting condition not associated with a new 
adverse effect or with a worsening of the preexisting condition; admission for a protocol-specified 
procedure) is not, in itself, a serious adverse effect. 
   
Disability. A substantial disruption of a person’s ability to conduct normal life functions. 
 
Important medical events include experiences that may not result in outcomes meeting the 
seriousness criteria, but that are still considered SAEs and should be reported as such. An 
important medical event may not result in death, be life-threatening, or require hospitalization, 
but would still be considered a SAE when, based on appropriate medical judgment, it 
- 
May jeopardize the subject 
 
and/or 
- 
May require medical or surgical intervention to prevent one of the outcomes listed in the 
SAE definition (e.g. death, life-threatening, hospitalization).  
 
Serious Adverse Event includes device deficiencies that might have led to a serious adverse event 
if a suitable action had not been taken or intervention had not been made or if circumstances had 
been less fortunate. These are handled under the SAE reporting system. 
4.5.7 Serious Adverse Device Effect 
Adverse device effect that has resulted in any of the consequences characteristic of a serious 
adverse event. 
4.5.8 Unanticipated Serious Adverse Device Effect 
Serious adverse device effect which by its nature, incidence, severity or outcome has not been 
identified in the current version of the risk analysis report. 
4.5.9 Eliciting Adverse Effect Information  
Subjects shall be routinely questioned about adverse effects at study visits. Subject may also 
change from one interval or may require unscheduled visits due to changes in subject 
circumstances, for example a subject may be admitted to a health care institution for an issue that 
may or may not be study related after which a study visit is required to determine the impact on 
the study participation, the adverse effects nature/cause. 
4.5.10 Recording and Assessment of Adverse Effects  
All observed or volunteered adverse effects (serious or non-serious) and abnormal test/exam 
findings, or suspected causal relationship to the investigational device shall be recorded in the 
subjects’ case histories.  For all adverse effects, sufficient information shall be pursued and/or 
obtained so as to permit: 
- 
An adequate determination of the outcome of the effect (i.e., whether the effect should 
be classified as a serious adverse effect) and;  
- 
An assessment of the casual relationship between the adverse effect and the 
investigational device 
 
Adverse effects or abnormal test findings felt to be associated with the investigational device shall 
be followed until the effect (or its sequelae) or the abnormal test finding resolves or stabilizes at a 
level acceptable to the PI. 

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Unscheduled visits will allow for additional safety data collection. 
4.5.11 Causality and severity assessment 
The PI will promptly review documented adverse effects and abnormal test findings to determine:  
- 
If the abnormal test/exam finding should be classified as an adverse effect;  
- 
If there is a reasonable possibility that the adverse effect was caused by the investigational 
device; and 
- 
If the adverse effect meets the criteria for a serious adverse effect. 
 
Assessment and monitoring of adverse events are required to be classified as to the severity and 
relatedness to the study intervention. 
 
Severity 
“Severe” does not necessarily mean “Serious”. 
On the CRF, 3 categories of severity are defined for an AE: 
- 
Mild: does not interfere with subject’s usual function. 
- 
Moderate: interferes to some extent with the subject’s usual function. 
- 
Severe: interferes significantly with subject’s usual function. 
 
Relatedness 
Causality assessment involves determination of whether there is a reasonable possibility that the 
investigational device (or clinical study procedure) caused or contributes to an AE. 
The causality of each AE must be assessed and reported in the CRF. In the case of SAEs, this same 
assessment shall also be recorded on the SAE Reports Form (Appendix 4). This report form shall 
include a description of the SAE in sufficient detail to allow for: 
- 
Complete medical assessment 
and 
- 
Independent determination of possible causality 
 
The potential event relationship to the study intervention and/or participation is assessed by the 
site investigator. A comprehensive scale in common use to categorize an event is: 
- 
Definitely Related:  The adverse event is clearly related to the investigational 
device/procedure – i.e. an event that follows a reasonable temporal sequence from 
administration of the study intervention, follows a known or expected response pattern to 
the suspected intervention, that is confirmed by improvement on stopping and 
reappearance of the event on repeated exposure and that could not be reasonably 
explained by the known characteristics of the subject’s clinical state. 
- 
Possibly Related:  An adverse event that follows a reasonable temporal sequence from 
administration of the study intervention, follows a known or expected response pattern to 
the suspected intervention, but that could readily have been produced by a number of 
other factors. 
- 
Not Related: The adverse event is clearly not related to the investigational 
device/procedure. - i.e. another cause of the event is most plausible; and/or a clinically 
plausible temporal sequence is inconsistent with the onset of the event and the study 
intervention and/or a causal relationship is considered biologically implausible.  

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4.5.12 Reporting Requirements 
Each adverse event is to be assessed to determine if it meets the criteria for serious adverse event. 
If a serious adverse event occurs, expedited reporting will follow local and international 
regulations, as appropriate. 
 
All adverse events shall be reported on the adverse event form of the CRF. It should be noted that 
the form for collection of serious adverse event information is not the same as the adverse event 
CRF. Where the same data are collected, the forms shall be completed in a consistent manner. For 
example, the same adverse event term should be used on both forms. Adverse events should be 
reported using concise medical terminology on the CRFs as well as on the form for collection of 
serious adverse event information. 
 
Explantation and revision surgery shall be reported completely and separately on specific forms. 
4.5.13 Serious Adverse Event Reporting Requirements 
If serious adverse event occurs, Oticon Medical shall be notified within 24 hours of awareness of 
the event by the investigator. In particular, if the serious adverse event is fatal or life-threatening, 
notification to Oticon Medical shall be made immediately, irrespective of the extent of available 
adverse event information. This timeframe also applies to additional new information (follow-up) 
on previously forwarded serious adverse event reports. 
 
In the rare event that the investigator does not become aware of the occurrence of a serious 
adverse event immediately, the investigator shall report the event within 24 hours after learning 
of it and document the time of his/her first awareness of the adverse event. 
 
For all serious adverse events, the investigator is obligated to pursue and provide information to 
Oticon Medical in accordance with the timeframes for reporting specified above. In addition, an 
investigator may be requested by Oticon Medical to obtain specific additional follow-up 
information in an expedited fashion. This information may be more detailed than that captured 
for the adverse event in sufficient detail to allow for a complete medical assessment of the case 
and independent determination of causality. Information regarding other possible causes of the 
event, such as concomitant medication and illness must be provided. In case of a subject death, a 
summary of available autopsy findings shall be submitted as soon as possible to Oticon Medical or 
its designated representative. 
 
Contact: 
Oticon Medical Neurelec 
M. Dan GNANSIA 
Mobile: +33 4 93 95 18 18 
Fax: +33 4 93 95 38 01 
Mail: DAGN@oticonmedical.com 
4.5.14 Non-serious Adverse Event Reporting Requirements 
Non-serious adverse events are to be reported on the adverse event CRFs, which are to be 
submitted to Oticon Medical. 
4.5.15 Reporting of Serious Adverse Effects to EC/CA 
Serious adverse effects are reported by the Sponsor to the EC and/or CA. 

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Fatal or life-threatening adverse events shall be reported to the Competent Authority of the 
Concern member state and reported to the Ethical Committee within 7-days. A follow-up report 
shall be submitted within an additional 8-days. Other Unanticipated serious adverse events shall 
be reported to the CA of the concerned Member state as well as to the EC within 15-days. 
4.6 
Withdrawal of a Subject Due to Adverse Effect(s) 
Withdrawal due to adverse effect(s) shall be distinguished from withdrawal due to insufficient 
efficacy, according to the definition of adverse effect noted earlier and recorded on the 
appropriate adverse event CRF. 
 
If a subject withdraws due to a serious adverse effect, the serious adverse event shall be reported 
in accordance with the reporting requirements defined in section 4.5. 
 
 

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5. DESCRIPTION OF THE INVESTIGATIONAL DEVICE 
The Neuro CIS is described in detail in Appendix 1. The principle mechanism of action involves 
detecting acoustic information with an external microphone, processing this information with the 
external sound processor and using the implanted components to directly stimulate the auditory 
nerve with electrical pulses. 
 
The Neuro CIS is composed of an implanted part (named “Neuro Zti”) and an external part (named 
“Neuro One”). The Neuro One detects and processes sound and is designed to be worn behind the 
ear (BTE). The Neuro Zti is designed to be surgically implanted and consists of the 
receiver/stimulator which is implanted under the skin on the temporal aspect of the skull and a 
multichannel electrode designed to be placed within the Scala Tympani of the cochlea enabling 
electrical stimulation of the auditory nerve. All power and data are transmitted from the Neuro 
One to the Neuro Zti via an inductively coupled transcutaneous link. A complete system description 
is provided in Appendix 1. 
 
 

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6. MONITORING PROCEDURES  
Monitoring is accomplished by the quality control activity. 
Responsibilities include overseeing the progress of a clinical study and ensuring that it is 
conducted, recorded, and reported in accordance with the protocol, SOPs, Good Clinical Practice 
(GCP), and the applicable regulatory requirement(s). 
 
The Sponsor or its representative shall be responsible for conducting study monitoring. The 
Sponsor or its representative shall appoint an appropriately qualified person(s) to monitor the trial. 
The monitor(s) shall be trained regarding the study protocol and shall be familiar with all study 
procedures. 
 
Monitoring will focus on the following key processes of the study to ensure the protection of rights 
and well-being of all study participants and the integrity of data: 
• 
Informed consent process 
• 
Study eligibility criteria met for all participants 
• 
Timely completion of Study CRFs 
• 
Review of data management procedure i.e. data entry, handling of data discrepancies and 
data backup 
• 
Reporting of adverse events and protocol violations according to Sponsor or its 
 
representative SOP(s) 
• 
Follow up assessments and procedures  
 
For each visit on site, the monitor shall work according to an agreed schedule of tasks, including 
the following that shall be given as specifics in the monitoring form and guidelines:  
• 
Schedule a date with the study investigator/coordinator for the monitoring procedure and 
provide them with a list or outline of the study sections that will be monitored in this 
particular visit. 
• 
Review last monitoring procedure report. 
• 
Review the Site Study File: ensuring that it is updated appropriately. 
• 
Verify that written informed consent was given by every subject entered into the study and 
obtained according to the consent sponsor or its representative SOP. 
• 
Review current status of the study’s participant enrolment vs. anticipated enrolment, 
losses to follow up, outstanding data issues and reported serious adverse events. 
• 
Review the study forms and database ensuring that the participants were eligible and note 
any safety issues and protocol violations or deviations. 
• 
Source data verification - abstraction of data from clinical and laboratory forms. 
 
During the initial visits, the monitors shall review 100% of the fields of all the study forms.  
Subsequently the monitors shall review 100% of the data contributing to the primary endpoint and 
100% of fields for a randomly selected sample of study forms. All forms monitored during a visit 
shall be detailed in the monitoring visit report. A database check for accuracy of data entry shall 
be performed at regular intervals. The data points to be checked will be safety data endpoints. 
 
The investigator shall permit direct access of medical records and source data to the sponsor or its 
representative and appropriate regulatory authorities to verify the accuracy of this data. 
 

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After each monitoring visit the monitor shall debrief the study team i.e. reinforce aspects where 
they are meeting expectations and highlight areas which need improvement. The monitor shall 
then create a monitoring report citing all findings and status of such findings (resolved or not) and 
forward a signed copy to the sponsor and/or sponsor appointed project manager. The monitoring 
report may be shared with the PI. 
 
At close out visit(s) the monitor will ensure all queries are resolved; the study product is accounted 
for and returned or destroyed according to sponsor or its representative SOP; and study 
documents are properly archived. 
6.1 
Study Monitoring Plan 
This study shall be monitored according to a monitoring plan. The PI shall allocate adequate time 
for such monitoring activities. The PI shall also ensure that the monitor or other compliance or 
quality assurance reviewer is given access to all the above noted study-related documents and 
study related facilities (e.g. pharmacy, diagnostic laboratory, etc.), and has adequate space to 
conduct the monitoring visit. The address is listed below. The monitoring procedures are a part of 
the sponsor’s or its representative SOPs. 
 
The monitoring shall be provided by a Canadian and Danish Clinical Research Organizations. 
Clinical Research Associates (CRA) will travel regularly to each site to perform the quality control 
of the data reported in the CRF. 
6.2 
Auditing and Inspecting 
The trial may be subject to review by the EC/CA and/or to quality assurance audits performed by 
the sponsor or its representative and/or to inspection by appropriate regulatory authorities. 
 
It is important that the PI(s) and their medical staff are available during the monitoring visits and 
possible audits or inspections and that sufficient time is devoted to the process. 
 
 

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7. DEVICE LABELING  
See Appendix 10. 
 
The Neuro Zti system is CE marked, Health Canada registered and distributed/sold into the market 
of participating countries.  
 
The device shall be ordered by the hospital and billed to the social security organization and/or 
insurance company and/or relevant purchasing authority.  
 
 

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8. CONSENT MATERIALS 
See Appendix 2. 
 
All parties shall ensure protection of all subjects’ personal data and shall not include subject names 
on any sponsors forms, reports, publications or any other disclosures. In case of data transfer, 
Oticon Medical shall maintain a high standard of confidentiality and personal data protection. 
 
The informed consent form must be agreed to by Oticon Medical and the EC and must be in 
compliance with ICH-GCP, ISO 14155 standard, local regulatory requirements and legal 
requirements. 
 
The investigator must ensure that each subject is fully informed about the nature and objectives 
of the trial and possible risks associated with participation. The investigator shall obtain written 
informed consent from each subject before any trial specific activity is performed. The informed 
consent form used in this trial, and any change made during the course of the trial, must be 
prospectively approved by both EC and Oticon Medical before use. The investigator shall retain 
the original of each subject’s signed consent form. 
 
 

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9. Ethical Committee (EC)/Competent Authority (CA) 
It is the responsibility of the investigator to have prospective approval of the trial protocol, 
protocol amendments, informed consent forms and other relevant documents from the EC/CA. All 
correspondence with the EC/CA shall be retained in the investigator file. Copies of the EC/CA 
approvals shall be forwarded by Oticon Medical or its representative. 
 
The only circumstance in which an amendment may be initiated prior to EC/CA approval is where 
the change is necessary to eliminate an apparent immediate hazard(s) to the subjects. In such 
cases, the investigator shall notify the EC/CA and Oticon Medical or its representative within 5 
working days after the implementation. 
 
The trial shall be performed in accordance with the protocol, International Conference on 
Harmonization of Good Clinical Practice guidelines, the declaration of Helsinki (Appendix 11), ISO 
14155:2011 standard and all applicable local regulatory requirements and laws. 
 
 

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10. ADDITIONAL RECORDS AND REPORTS   
10.1 Data Handling and Record-Keeping 
10.1.1 Case Report Form 
 
As used in this protocol, the electronic Case Report Form (eCRF) should be understood to refer to 
an electronic data record depending on the data collection method used in this trial. 
 
A CRF is required and should be completed for each subject. The completed original CRFs are the 
sole property of the sponsor. The CRFs shall not be made available in any form to third parties 
without written permission from the sponsor. Written permission is not required if the data is 
requested by the authorized representative(s) of the sponsor or an appropriate regulatory/legal 
authority. 
 
It is the investigator’s responsibility to ensure completion and to review and approve all CRFs. CRFs 
must be signed by the investigator or by an authorized staff member. These signatures serve to 
attest that information contained on the CRFs is true and correct. At all times, the investigator has 
final personal responsibility for the accuracy and authenticity of all clinical and test/exams data 
entered on the CRFs. Subject source documents are the physician’s subject records maintained at 
the trial site. In most cases, the source documents are the hospital or the physician’s chart. Where 
the source documents are the hospital or the physician’s chart, the information collected on the 
CRFs must match those charts. 
 
The eCRF cannot be considered as source document for this trial. Accurate and reliable data 
collection is ensured by the study monitor (source document verification). 
 
The Electronic Data Capture system is compliant with the 21CFR part 11 FDA. 
10.1.2 Subject Confidentiality 
Information about the patients shall be kept confidential and managed according to the 
requirements of the Personal Data Protection law. Those regulations require a signed subject’s 
authorization informing the subject of the following: 
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to the information and why 
• Who will use or disclosure that information 
• The rights of the subject to revoke their authorization for use of their personal health 
information 
 
Note: This information and the subject’s authorization shall be provided to the subject in the 
informed consent form. 
 
In the event that the subject revokes authorization to collect or use their information/data, the PI, 
by regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization. For subjects that have revoked authorization to collect or use PHI, attempts should 
be made to obtain permission to collect at least safety status at the end of their scheduled study 
period. 

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To maintain subject confidentiality, the site number, the subject inclusion number and subject 
initials (SSID) will identify all study subjects on CRFs and all other documentation submitted to the 
Sponsor. 
10.1.3 Source Documents 
Source Data are the clinical findings and observations, laboratory and test data, and other 
information contained in the Source Documents.  
  
Source Documents are the original records (and certified copies of original records); including, but 
not limited to, hospital medical records, physician or office charts, physician or nursing notes, 
subject diaries or evaluation checklists, pharmacy dispensing records, recorded data from 
automated instruments, x-rays, CT Scans, MRI, etc.  When applicable, information recorded on the 
CRF shall match the Source Data recorded in the Source Documents.   
 
Study data shall be recorded directly on the CRF, whereupon the CRF data is to be considered the 
Source Data. Descriptions of these specific data shall be attributable, legible, original and accurate 
and must meet the regulatory requirements for recordkeeping. Source documents include all 
documents, images, files, and folders containing subject’s medical data. 
10.2 Record Maintenance and Retention 
To enable evaluations/audits from regulatory authorities or Oticon Medical, the PI agrees to keep 
records, including the identity of all participants (e.g. Hospital records, CRFs, sufficient information 
to link records), all original signed informed consent forms, copies of all CRFs, serious adverse 
event forms, source documents and detailed records of device fitting/disposition. The records shall 
be retained by the PI according to ICH, local regulation, or as specified in the Clinical Study 
Agreement, whichever is longer. 
 
If the investigator relocates, retires or for any reason withdraws from the study, the sponsor shall 
be prospectively notified. The study records must be transferred to an acceptable designee such 
as another investigator, another institution, or to the sponsor. The investigator must obtain the 
sponsor’s written permission before disposing of any records, even if retention requirements have 
been met. 
 
A unique subject identification code is assigned to each subject to protect subject identity. This 
unique code is used to identify the CRF, adverse events reports or other study-related data.  These 
unique subject identification codes shall be recorded on the subject identification code list and 
kept in a confidential manner in the investigator site file. To protect subject identity, the subject 
names or other directly identifiable information shall not appear on any reports, publications, or 
other disclosures of clinical study outcomes. 
10.3 Data Management Procedures 
The data will be entered into a validated database.  The sponsor or its representative shall be 
responsible for data processing, in accordance with procedural documentation.  Database lock 
shall occur once quality assurance procedures have been completed. 
All procedures for the handling and analysis of data shall be conducted using good computing 
practices meeting FDA guidelines for the handling and analysis of data for clinical trials. 

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10.4 Data Quality Control and Reporting 
After data have been entered into the study database, a system of computerized data validation 
checks shall be implemented and applied to the database on a regular basis. Query reports (Data 
Clarification Requests) pertaining to data omissions and discrepancies shall be forwarded to the 
PIs and study monitors for resolution.  The study database shall be updated in accordance with the 
resolved queries.  All changes to the study database shall be documented. 
10.5 Archival of Data 
Appropriate backup copies of the database and related software files shall be maintained.  
Databases are backed up by the database administrator in conjunction with any updates or 
changes to the database.  At critical junctures of the protocol (e.g., production of interim reports 
and final reports), data for analysis is locked and cleaned per established procedures. 
10.6 Clinical Trial Registration 
This trial shall be registered in www.clinicaltrials.gov, and results reported as required. 
10.7 Publication 
Neither the complete nor any part of the results of the study carried out under this protocol, nor 
any of the information provided by the sponsor for the purposes of performing the study, shall be 
published or passed on to any third party without the written consent of the study sponsor. Any 
PI involved with this study is obligated to provide the sponsor with complete test results and all 
data derived from the study. 
 
 
 

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11. BIBLIOGRAPHY  
1. Estimates based on manufacturers’ voluntary reports of registered devices to the U.S. Food and 
Drug Administration, December 2012.  
2. NIH Publication No. 11-4798 (2013-11-01). "Cochlear Implants". National Institute on Deafness and 
Other Communication Disorders. 
3. Nilsson M, Soli SD, Sullivan JA. Development of the Hearing in Noise Test for the measurement of 
speech reception thresholds in quiet and in noise. J Acoust Soc Am. 1994 Feb; 95(2):1085-99. 
4. Fabry D. Cochlear implants and hearing aids: Converging/colliding technologies. The Hearing 
Journal. 2008; 61(7):10–16. 
5. Massa ST, Ruckenstein MJ. Comparing the performance plateau in adult cochlear implant patients 
using HINT and AzBio. Otol Neurotol. 2014 Apr; 35(4):598-604. 
6. Balkany T, Hodges A, Menapace C, Hazard L, Driscoll C, Gantz B, Kelsall D, Luxford W, McMenomy 
S, Neely JG, Peters B, Pillsbury H, Roberson J, Schramm D, Telian S, Waltzman S, Westerberg B, 
Payne S. Nucleus Freedom North American clinical trial. Otolaryngol Head Neck Surg. 2007 May; 
136(5):757-62. 
7. Lenarz M, Sönmez H, Joseph G, Büchner A, Lenarz T. Long-term performance of cochlear implants 
in postlingually deafened adults. Otolaryngol Head Neck Surg. 2012 Jul; 147(1):112-8. 
8. Bradley J, Bird P, Monteath P, Wells JE. Improved speech discrimination after cochlear implantation 
in the Southern Cochlear Implant Adult Programme. N Z Med J. 2010 Aug 27; 123(1321):34-44. 
9. Dillon MT, Buss E, Adunka MC, King ER, Pillsbury HC 3rd, Adunka OF, Buchman CA. Long-term 
speech perception in elderly cochlear implant users. JAMA Otolaryngol Head Neck Surg. 2013 Mar; 
139(3):279-83. 
10. Disability 
Programs. 
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Adult.htm#2_10 
11. Brand T. & Kollmeier B. 2002. Efficient adaptive procedures for threshold and concurrent slope 
estimates for psychophysics and speech intelligibility tests. J Acoust Soc Am, 111(6), 2801–10. 
12. Bond M, Mealing S, Anderson R, Elston J, Weiner G, Taylor RS, Hoyle M, Liu Z, Price A, Stein K. The 
effectiveness and cost-effectiveness of cochlear implants for severe to profound deafness in 
children and adults: a systematic review and economic model. Peninsula Technology assessment 
group Report, 20 Sept. 2007. 
13. Advanced Bionics, 2014 Total System Reliability Update "028-M476-03" accessed from website 16 
April 2015 
14. MED-EL Data published on their website, http://www.medel.com/reliability-reporting , 16 April 
2015. 
15. Cochlear, Reliability Report, accessed from website Volume 13-February 2015. 
16. Venail F, Sicard M, Piron JP, Levi A, Artieres F, Uziel A, Mondain M. Reliability and complications of 
500 consecutive cochlear implantations. Arch Otolaryngol Head Neck Surg. 2008 Dec;134(12):1276-
81. 
17. Farinetti A, Ben Gharbia D, Mancini J, Roman S, Nicollas R, Triglia JM. Cochlear implant 
complications in 403 patients: comparative study of adults and children and review of the literature. 
Eur Ann Otorhinolaryngol Head Neck Dis. 2014 Jun; 131(3):177-82. 
18. Chen DS, Clarrett DM, Li L, Bowditch SP, Niparko JK, Lin FR. Cochlear implantation in older adults: 
long-term analysis of complications and device survival in a consecutive series. Otol Neurotol. 2013 
Sep;34(7):1272-7. 
19. Arnoldner C, Baumgartner WD, Gstoettner W, Hamzavi J. Surgical considerations in cochlear 
implantation in children and adults: a review of 342 cases in Vienna. Acta Otolaryngol. 2005 
Mar;125(3):228-34. 
20. Postelmans JT, Cleffken B, Stokroos RJ. Post-operative complications of cochlear implantation in 
adults and children: five years' experience in Maastricht. J Laryngol Otol. 2007 Apr;121(4):318-23. 

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21. Ray J, Proops D, Donaldson I, Fielden C, Cooper H. Explantation and reimplantation of cochlear 
implants. Cochlear Implants Int. 2004 Dec;5(4):160-7. 
22. Bhatia K, Gibbin KP, Nikolopoulos TP, O'Donoghue GM. Surgical complications and their 
management in a series of 300 consecutive pediatric cochlear implantations. Otol Neurotol. 2004; 
25:730-9. 
23. Cohen NL, Hoffman RA. Complications of cochlear implant surgery in adults and children. Ann Otol 
Rhinol Laryngol. 1991 Sep; 100(9 Pt 1):708-11. 
24. Jeppesen J, Faber CE. Surgical complications following cochlear implantation in adults based on a 
proposed reporting consensus. Acta Otolaryngol. 2013 Oct; 133(10):1012-21. 
25. Wang JT, Wang AY, Psarros C, Da Cruz M. Rates of revision and device failure in cochlear implant 
surgery: A 30-year experience. Laryngoscope. 2014 Feb 18. 
26. Cohen NL, Hoffman RA. Complications of cochlear implant surgery in adults and children. Ann Otol 
Rhinol Laryngol. 1991 Sep; 100(9 Pt 1):708-11. 
27. Dutt SN, Ray J, Hadjihannas E, Cooper H, Donaldson I, Proops DW. Medical and surgical 
complications of the second 100 adult cochlear implant patients in Birmingham. J Laryngol Otol. 
2005;119:759-64 
28. Bergeron, F., Hotton. M., Millette, I., Lamothe, J., Bussières, R., Côté, M, Philippon, D. 2014. Speech 
recognition with the most recent technologies from the four major cochlear implant 
manufacturers; an update. 13th International conference on cochlear implants and other 
implantable auditory technologies, June 18th-21st 2014, Munich, Germany 
29. Kim CS, Oh SH, Chang SO, Kim HM, Hur DG. Management of complications in cochlear implantation. 
Acta Oto Laryngol. 2008; 128:408-14. 
30. Brito R, Monteiro TA, Leal AF, Tsuji RK, Pinna MH, Bento RF. Surgical complications in 550 
consecutive cochlear implantation. Braz J Otorhinolaryngol. 2012 Jun; 78(3):80-5. 
31. Cohen NL, Roland JT Jr, Marrinan M. Meningitis in cochlear implant recipients: the North American 
experience. Otol Neurotol. 2004 May; 25(3):275-81. 
32. Hansen S, Anthonsen K, Stangerup SE, Jensen JH, Thomsen J, Cayé-Thomasen P. Unexpected 
findings and surgical complications in 505 consecutive cochlear implantations: a proposal for 
reporting consensus. Acta Otolaryngol. 2010 May; 130(5):540-9. 
33. Kandogan T, Levent O, Gurol G. Complications of paediatric cochlear implantation: experience in 
Izmir. J Laryngol Otol. 2005 Aug; 119(8):606-10. 
34. Stratigouleas ED, Perry BP, King SM, Syms CA. Complication rate of minimally invasive cochlear 
implantation. Otolaryngol Head Neck Surg. 2006 Sep; 135(3):383-6. 
35. Telian SA, El-Kashlan HK, Arts HA. Minimizing wound complications in cochlear implant surgery. Am 
J Otol. 1999 May; 20(3):331-4. 
36. Kronenberg J, Migirov L, Dagan T. Suprameatal approach: new surgical approach for cochlear 
implantation. J Laryngol Otol. 2001 Apr; 115(4):283-5. 
37. Postelmans JT, Tange RA, Stokroos RJ, Grolman W. The suprameatal approach: a safe alternative 
surgical technique for cochlear implantation. Otol Neurotol. 2010 Feb; 31(2):196-203. 
38. Colletti V, Fiorino FG, Carner M, Pacini L. Basal turn cochleostomy via the middle fossa route for 
cochlear implant insertion. Am J Otol. 1998 Nov; 19(6):778-84. 
39. Slavutsky V, Nicenboim L. Preliminary results in cochlear implant surgery without 
antromastoidectomy and with atraumatic electrode insertion: the endomeatal approach. Eur Arch 
Otorhinolaryngol. 2009 Apr; 266(4):481-8. 
40. Zernotti ME, Suárez A, Slavutsky V, Nicenboim L, Di Gregorio MF, Soto JA. Comparison of 
complications by technique used in cochlear implants. Acta Otorrinolaringol Esp. 2012 Sep-Oct; 
63(5):327-31.  
41. Balkany TJ, Hodges AV, Buchman CA, Luxford WM, Pillsbury CH, Roland PS, Shallop JK, Backous DD, 
Franz D, Graham JM, Hirsch B, Luntz M, Niparko JK, Patrick J, Payne SL, Staller S, Telischi FF, Tobey 
EA, Truy E. Cochlear implant soft failures consensus development conference statement. Cochlear 
Implants Int. 2005 Sep;6(3):105-22. doi: 10.1002/cii.7. No abstract available. 

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42. Waltzman SB, Cohen NL, Roland JT Jr. A comparison of the growth of open-set speech perception 
between the nucleus 22 and nucleus 24 cochlear implant systems. Am J Otol. 1999 Jul;20(4):435-
41. 
43. Lin FR, Chien WW, Li L, Clarrett DM, Niparko JK, Francis HW. Cochlear implantation in older adults. 
Medicine (Baltimore). 2012 Sep;91(5):229-41. 
44. Brown CJ, Abbas PJ, Etlert CP, O'Brient S, Oleson JJ. Effects of long-term use of a cochlear implant 
on the electrically evoked compound action potential. J Am Acad Audiol. 2010 Jan;21(1):5-15. 
 
 

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12. APPENDIX 
Appendix 1: Neuro Cochlear Implant System description 
Appendix 2: PATIENT INFORMED CONSENT FORM 
Appendix 3: ADVERSE EVENT REPORT FORM 
Appendix 4: SERIOUS ADVERSE EVENT REPORT FORM 
Appendix 5: EXPLANTATION REPORT FORM 
Appendix 6: CLINICAL SUPPORT ROLE 
Appendix 7: PATIENT HINT PERFORMANCE 
Appendix 8: POST-OPERATIVE ECAP MEASUREMENT 
Appendix 9: Calibration considerations 
Appendix 10: DEVICE LABELING 
Appendix 11: DECLARATION OF HELSINKI 
 
 
 
 

 
 
DEVICE DESCRIPTION 
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Appendix 1: Neuro Cochlear Implant System description  
 
1.1 General description of device, intended uses, and model designations ........................................ 60 
1.2 Specific inventory of system components and their essential functions ........................................ 61 
1.2.1 
Implantable components ................................................................................................................... 61 
1.2.2 
Non-implantable components ........................................................................................................... 62 
1.3 System software and processing strategies ................................................................................... 67 
1.4 Essential features of sound processing hardware .......................................................................... 67 
1.5 Electrode specification and characteristics .................................................................................... 68 
1.6 Stimulation methodology and provisions for safe stimulation ...................................................... 69 
1.6.1 
Stimulation Circuitry .......................................................................................................................... 69 
 
 
1.1 
General description of device, intended uses, and model designations 
The Neuro Zti cochlear implant system is a cochlear implant system consisting of the Neuro 
Zti implant, Neuro One sound processor and all components and accessories for the final user, 
and DigiMap software interface, and surgical tools for clinic. 
 
The present technical file describes the “Neuro Cochlear Implant System”. The Neuro 
Cochlear Implant System is the fourth generation developed by Neurelec and the first cochlear 
implant to be developed and marketed by Oticon Medical. The intended use of the 
investigational device is to provide access to sound via direct electrical stimulation of the 
auditory nerve for adults and children suffering from severe to profound hearing loss. The 
Neuro Cochlear Implant system’s components (external and surgically implantable), electrical 
stimulation parameters and mechanism of action are essentially the same as approved 
predicate cochlear implant devices. The implanted component is the Neuro Zti 
receiver/stimulator with associated electrode arrays and the external component is the Neuro 
One sound processor. The implantable receiver/stimulator (Neuro Zti) may be configured with 
one of two different electrode arrays. The array model designations are the “Classic” array 
and the “EVO” array; the product configurations are labeled as Neuro ZtiCLA and Neuro ZtiEVO, 
respectively. 
 
The device description herein has been modeled after guidance provided in the AAMI-CDV-4 
CI86 guideline  
 
The system including fitting interface, processor and implantable component are shown in 
figure 1 below: 
 
 
 

 
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                 Fitting interface: DIGIMAP                    Processor: NEURO ONE    Implantable part: NEURO Zti 
 
 
Computer       Cable       DGUSB       Cable       DGUA      Cable       BTE Processor       Implant/Electrode array 
+DIGIMAP software                                                                              /Antenna/Cable         
 
Figure 1: Schematic of the Neuro cochlear implant system including fitting components. 
 
1.2 
Specific inventory of system components and their essential functions 
1.2.1 Implantable components 
1.2.1.1 Receiver–stimulators 
The system has a single receiver/stimulator model, The Neuro Zti. The Neuro Zti is designed 
to be surgically placed under the periosteum on the temporal aspect of the skull. Unlike 
predicate cochlear implant receiver/stimulators approved by the FDA, the Neuro Zti features 
an integrated fixation system which allows fixation to the skull using two self-tapping titanium 
screws. A schematic of the dimensions of the Neuro Zti can be seen in Figure 2. The Neuro Zti 
Cochlear Implant consists of electrical components hermetically encased within a mechanical 
housing made from zirconia and titanium. This housing is connected to a 20 contact multi-
channel electrode-array with an integrated reference electrode located on the lead close to 
the receiver/stimulator. The feedthroughs in the housing enable the connection between the 
internal electronics and the electrode array. A unique design feature of the 
receiver/stimulator is that it has an opening in the center designed to securely hold a 
removable/replaceable magnet. The purpose of this feature is to allow magnet removal for 
increased MRI compatibility. In addition to being able to provide electrical stimulation to the 
cochlea, the Neuro Zti is equipped with circuitry to enable use of the electrode contacts for 
the recording of electrically evoked compound action potentials (eCAPs). 
 
 
Figure 2: Schematic of the Neuro Zti configured with the “Classic” array (Neuro ZtiCLA). 
Dimensions are in millimeters unless otherwise noted. 

 
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1.2.1.2 Electrodes 
The Neuro Zti may be configured with either the “Classic” or “EVO” array; these two product 
configurations are designated as Neuro ZtiCLA and Neuro ZtiEVO, respectively. A schematic of 
the two electrode options can be seen in Figure 3, while detailed information regarding the 
arrays is further outlined in Section 1.5. The arrays are both constructed from the same raw 
materials with the contacts being machined from platinum/Iridium (10%). The wires between 
contacts and the receiver/stimulator are coated with PTFE for electrical isolation. The PTFE 
coated wires are completely embedded inside an over-molding comprised of medical grade 
silicone; therefore, the wires are not in contact with the tissues. 
The principal differences between the two electrode array options are that the Neuro ZtiEVO 
has a slightly smaller form factor allowing for reduced stiffness and may be more suitable for 
“softer” surgery. Both arrays are currently approved for use in Canada and the European 
Union and have been used with the prior generation device, Digisonic SP. The company makes 
no specific warrantee or prescription as to which array is most appropriate for a given patient; 
thus leaving the array choice to the preference of the surgeon. Furthermore, there are no 
specific restrictions as to the surgical approach to the cochlea (ie. traditional mastoidectomy 
vs transtympanic approach) or to the introduction of the array into the cochlea (round window 
vs cochleostomy approach). Both arrays may be inserted (and re-inserted if necessary) into 
the scala-tympani using the same techniques. 
 
 
Figure 3: Schematic showing the EVO and CLASSIC electrode array options for the Neuro Zti 
 
1.2.1.3 Connector systems 
The system does not include a percutaneous connector. Communication between the 
external and implanted components is accomplished via an inductive link. The mechanical 
stability of the connection is made possible by magnetic coupling between the implanted 
magnet and the magnet inside the external coil. 
1.2.2 Non-implantable components 
1.2.2.1 Sound processors and body-worn accessories 

 
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The sound processor for the investigational device is called the Neuro One (see Figure 4). The 
Neuro One enables the functionality of the Neuro Zti by delivering the power and data 
required for electrical stimulation of the cochlea.  Without the external processor, the 
implanted components will not function. The Neuro One is powered by two Zinc-air batteries 
with electrical components housed within a mechanical design to enable the patient to wear 
the processor behind the ear (BTE). The inductive link to the implanted Neuro Zti is established 
using an external coil connected to the Neuro One via a replaceable cable. The external coil 
also contains a magnet, which couples with the magnet of the implanted Neuro Zti to keep 
the external coil in place. Magnet strength may be adjusted to improve retention and/or 
reduce the risk of skin-flap complications.   
 
FIGURE 4 
 
Figure 4 shows a schematic illustrating the mechanical design of the Neuro One sound 
processor. The principal components and their associated functions are labeled and 
indicated in the processor description on the left. 
 
1.2.2.2 Non-body-worn accessories and replaceable body-worn components 
It is planned that the commercial version of the Neuro One processor will be packaged with 
essential accessories, components and associated documentation. Figure 5 shows and 
describes the non-body-worn accessories and replaceable body-worn components included 
with the Neuro system.  
 

 
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Figure 5 shows and describes the components and accessories included in the Neuro One 
patient kit. 
 
1.2.2.3 Body-worn and non-body-worn cables 
The Neuro One sound processor requires a cable between the processor and the external coil. 
The cable is replaceable, comes in a single length and is illustrated in Figure 5 #3. In addition 
to the antenna/coil cable, the Silouette (Figure 5 #12) includes an integrated cable used to 
communicate to the Neuro One via telecoil input. 
 
1.2.2.4 Components for system clinical support (e.g., clinical programming pods, 
clinical mapping software, test materials) 
External communication with the Neuro One is necessary for programming the processor and 
performing certain diagnostic testing (Impedance measures, ECAP measures, EABR and ESRT 
trigger outputs). This communication requires a Windows PC with a USB port, USB cable, a 
programming interface box with electrical isolation and a mini-din 6-pin cable to complete the 
connection from the interface box to the Neuro One. The general specifications of the 
Programming interface box are outlined in Table 1. In addition to the aforementioned 
hardware, PC compatible software, called DigiMap, is necessary to program and configure the 
Neuro One processor. 
 
 
 
 
 

 
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TABLE 1: Specification of the Programming Interface Hardware 
Power 
5 Volts/300 mA (via USB ) 
Protective Fuse 
500 mA 
PC Interface 
USB (compatible with USB 1.1, 2.0 and 
3.0) 
External Trigger 
Connector : BNC 
Output  Range : 0V to 5V 
Pulse Duration: 50 μs 
Safety : Electrical Isolation via 
Capacitive coupling 
Control: Via DigiStim PC Software 
Weight 
208 g 
Dimensions 
10.2 cm X 18.8 cm 
Temperature 
Functioning: 0-40C 
Stock/Storage: -10-55C 
 
1.2.2.5 Components for surgical support (e.g., insertion tools, templates) 
The components of the system intended to support surgical placement and fixation of the 
implantable components are shown in figures 6-8 below.  
 
FIGURE 6 
 
 
 
 
 
 
 
 
 

 
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FIGURE 7 
 
 
 
FIGURE 8 
 
 
 
 
 
 

 
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1.3 
System software and processing strategies 
The processing strategies of the Neuro Cochlear Implant system utilize square-wave charge-
balanced pulsatile non-simultaneous stimulation protocols. For the sound coding strategy, the 
incoming sound is converted into the spectral domain using an FTT. Essentially, the stimulation 
strategy is what is known in the field as an “N of M” strategy, meaning N electrodes are 
activated from M electrodes per frame. Unique to the Neuro system, the wide input dynamic 
range per sample is not compressed until the final stage of processing. Furthermore, the 
compression mapping is divided into four frequency (electrode) groups. This final stage multi-
band compression is designed to avoid transient artifacts and cross-modulation frequency 
distortion inherent in broad-band automatic gain control strategies that operate in the time 
domain. 
 
1.4 
Essential features of sound processing hardware 
TABLE 2: Technical Specifications of the Neuro One Processor 
Mechanical Properties 
Dimensions 
50.5 x 50 x 10.6 mm 
Weight 
11.4 g (with batteries) 
Characteristics 
Colors 
7 
Number of Magnet Strength   Options 
8 
Cable Lengths 
2  
Condition Of Use 
Operating Temperature Range 
5° C to 40° C 
Moisture Resistance 
0 to 90 % 
Atmospheric pressure 
700 hPa to 1060 hPa 
Packaging And Storage 
Storage Temperature Range 
-20° C to 50° C 
Moisture Resistance 
0 to 90 % 
Atmospheric pressure 
700 hPa to 1060 hPa 
Microphones 
Number 
2 
Automatic Adaptive Directionality 
Yes - Free Focus offers : 
• 
3 directionality modes (Full, Split, Omni) 
• 
2 adaptive modes (Auto-Tri, Auto-Dual) 
Input Dynamic Range (IDR) 
25 dB SPL – 115 dB SPL (programmable range: 23 dB SPL to 95 
dB SPL) 
Sound Processing 
Automatic Environment Detection 
Yes 
Audio Sound Capture 
18 bits resolution  
Sound Input Frequency Range 
Up to 8333Hz  
Effective Audio Sampling Rate 
16667 Hz – 3 input sources with up to 2 parallel input sources 
Gain Management 
Yes - Voice Guard back-end multiband compression 
Maximum Stimulation Rate 
47500 pps, Software limited to 37500 pps 
Supported Strategies 
“NEW STRATEGY NAME”/CRYSTALISXDP / MPISXDP  
Noise Reduction Features 
Voice Track, Wind Noise Reduction 
Speech Enhancement Features 
Voice Guard, Free Focus 

 
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Audio Inputs 
Telecoil 
Yes – In built 
Direct Connection  
Yes – Universal (FM, auxiliary inputs) 
Bluetooth 
Yes – Using Telecoil with 3rd party system 
User Interfaces 
Program push button 
Up to 4 programs 
Wheel Selector 
On/Off – Sensitivity control ± 6 dB 
Diagnostic Tools 
Indicator Light 
Orange indicator for program selection, start-up test, 
stimulation status, battery status, and error conditions – Can be 
disabled by audiologist. 
Private Beeps 
Sound indicator for self-check test, program selection, battery 
status, and error conditions - Can be disabled by audiologist 
Self-Check Diagnostics 
Integrated full system diagnostics (processor, cable, antenna) – 
Easy operating using push button 
Neuro ECAP 1.0 Telemetry 
Patented Masker Probe ECAP detection with efficient artefact 
cancellation 
Integrated DSP high sampling rate system up to 200 samples 
Programmable stimulation rate 21Hz to 83Hz 
Programmable number of recording electrodes 
Other implant measurements 
EABR, ESRT, impedances 
 
1.5 
Electrode specification and characteristics 
As previously mentioned, the Neuro Zti may be configured with one of two different 
electrodes. Tables 3-4 describe the details for the Classic and EVO arrays, respectively. 
 
TABLE 3: Specifications and characteristics of the Neuro ZtiCLA 
Identification number 
M80184 
Material components 
Connecting wire: Platinum iridium 10% 
Stimulation electrode: Platinum iridium 10% 
Number of independent active electrodes 
20 
Insertion length 
26 mm 
Active length 
25 mm 
Dimensions 
Active area: 0.39 mm² to 0.77 mm² 
Diameter at apex: 0.5 mm 
Diameter at base: 1.07 mm 
Reduced cochleostomy size 
Diameter of 1 mm (may be inserted via 
round window) 
General shape 
Straight  
Straight: distance between electrodes and 
silicone, inferior to 0.1 mm 
Shape at apex 
Rounded shape 
Shape at the base 
Diameter push rings: 2x1.5 mm 
Insulation 
PE (polyester): wire 
Si (silicone): external tubing 
 
TABLE 4: Specifications and characteristics of the Neuro ZtiEVO 
Identification number 
M80185 
Material components 
Connecting wire: Platinum iridium 10% 
Stimulation electrode: Platinum iridium 10% 

 
Page 69 of 115 
DEVICE DESCRIPTION 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
Number of independent active electrodes 
20 
Insertion length 
25 mm 
Active length 
24 mm 
Dimensions 
Active area: 0.46 mm² to 0.60 mm² 
Diameter at apex: 0.4 mm 
Diameter at base: 0.5 mm 
Reduced cochleostomy size 
Diameter of 0.8 mm (may be inserted via the 
round window 
General shape 
Straight  
Straight: distance between electrodes and 
silicone, inferior to 0.1 mm 
Shape at apex 
Rounded shape 
Shape at the base 
Diameter push rings: 1x1.5 mm & 1x1.2 mm 
Insulation 
PE (polyester): wire 
Si (silicone): external tubing 
 
 
1.6 
Stimulation methodology and provisions for safe stimulation 
1.6.1 Stimulation Circuitry 
A general description of the specifications of the internal components can be found in table 
5. 
 
TABLE 5: Technical Specification of the Neuro Zti Cochlear Implant  
Stimulation capacity 
Primary function 
Cochlear implant  
Stimulation mode (depending on 
configuration) 
Anodic with Common Cathodic Ground, biphasic monopolar, biphasic 
multipolar in sequential or simultaneous modes 
Maximum stimulation rate 
47500 pps, Software limited to 37500 pps, default 20800 pps 
Objective measurements 
Impedance measurement 
Measurement of the implant’s power 
Electrically evoked compound action potential (eCAP) 
Psychoacoustic tests (gap, test, etc.) 
Identification 
Electrode Array options 
Classic or Evo (see Tables 3-4 for array specifications) 
Independent output circuits 
24 (20 used in current configuration) 
Radio Frequency Telemetry  
6.78 MHz (bi-directional) 
Surgical approach 
In accordance with standard/routine clinical practice with no specific 
restriction  
Mechanical properties 
Weight  
10.5 g 
Dimensions 
Diameter: 30.5 mm. Thickness: ranging from 4.0 mm (center) to 4.5 mm 
(edge) 
Volume  
4.15 cm3 
Integrated Fixation System 
2 self-tapping titanium screws with typical penetration depth of 1.73 mm 
below the surface of the implant 
Material in direct contact with human tissue 
LSR 40 shore A silicone 
HCR 35 shore A & HCR 50 shore A silicone 
Adhesive silicone 
Platinum iridium 10% 
Titanium grade 2 
Titanium grade 5 
Receiver  
Titanium base – encapsulation in Zirconia 

 
Page 70 of 115 
DEVICE DESCRIPTION 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
Insulation 
PE (polyester): wire 
Si (Silicone) : external tubing 
Implanted Components 
Hermetically sealed receiver/stimulator connected to an electrode array 
Performance characteristics 
Characteristics of the output signal (on 
resistance of 1 kΩ) 
Max 2V – 255 µs  
Charge: 5nC – 200nC 
Independence measurement  
Normal values: 500 Ω – 7 kΩ 
Safety 
Communication security 
Unique implant identification (ID) is paired to a specific external 
processor 
Maximum Charge Density 
<50µC/cm² (Neuro ZTIEVO) 
<59µC/cm² (Neuro ZTICLA) 
DC Current Prevention 
Blocking Capacitors for each output circuit, software programmable 
shorting between stimulation frames and/or between individual pulses 
MRI safety level 
Compatible 1,5 Tesla with the magnet in place. 
Compatible with 3 Tesla (after removing the magnet).  
Ionizing Radiation 
Dose max 112 Grays 
Methods recommended for determining the 
proper functioning of the system 
Impedance measurement and integrity test (with collection equipment) 
Operating pressure 
Absolute pressure of 3 bars (corresponding to a diving depth of 20 
meters) 
Reference electrode  
1 cylindrical ground electrode – 17 mm². Diameter: 2.1 mm. Length: 2.5 
mm 
Impact Resistance 
≥ 2.5 Joules 
Packaging And Storage 
Storage Temperature Range 
-30°C to +60°C 
Moisture resistance 
0% to 90% 
 
 
 

Consent Form 
LI_07 
Edition : C 
Subject information and Consent form 
«The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults» 
 
 
Edition: C, August 2016 
Author: S. SAAÏ 
Page 71 of 115 
CONFIDENTIAL 
Do not reproduce without Neurelec Oticon Medical authorization 
Appendix 2: PATIENT INFORMED CONSENT FORM 
 
SUBJECT INFORMATION AND CONSENT FORM 
Title of research: « The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults » 
Protocol n°: PIC_07 
Sponsor: Oticon Medical, 2720 Chemin Saint Bernard 06224 Vallauris, France. 
Investigator: [name and contact information]  
 
1. SUMMARY 
You are being asked to participate in research study. The purpose of this consent form is to help you 
decide if you want to participate in the research study. 
You should not join this research study until all of your questions are answered.  
Things to know before deciding to take part in this research study: 
- 
The main goal of a research study is to confirm/endorse efficacy and safety of the Neuro Zti 
cochlear implant system to help patients in the future. 
- 
The decision to join or not join the research study will not cause you to lose any medical 
benefits. If you decide not to take part in this study, your doctor will continue to treat you. 
- 
Parts of this study involve standard medical care. Standard care is the treatment normally 
given for a certain condition or illness. 
- 
Other parts of this study involve an investigational device that is being tested according its 
intended use. In this study, the investigational device is a cochlear implant CE marked and 
approved in the different participant’s countries. CE marking means that the product conforms 
to all EU directives and EU regulations that apply, it is also Health Canada approved.  
- 
After reading the consent form and having a discussion with the research staff, you should 
know which parts of the study are experimental and which are standard medical care. 
- 
Your medical records may become a part of the research record. If that happens, your medical 
records may be looked at and/or copied by the sponsor of this study and/or health agencies 
associated with the study. 
- 
Your usual care cost such as cochlear implant device, surgery, hospital stays, audiometric tests, 
imaging exam(s) that you receive whether or not you were participating in this study  will be 
covered by your health care system and/or medical insurance The sponsor will pay extra care 
costs or a lump sum, associated with this study, directly your hospital. Taking part in a research 
study would not affect your current or future health care and/or medical insurance coverage. 
- 
If you take part in this research study, you will be given a copy of this signed and dated consent 
form. 

Consent Form 
LI_07 
Edition : C 
Subject information and Consent form 
«The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults» 
 
 
Edition: C, August 2016 
Author: S. SAAÏ 
Page 72 of 115 
CONFIDENTIAL 
Do not reproduce without Neurelec Oticon Medical authorization 
2. PURPOSE OF THE STUDY 
The Neuro Zti Cochlear implant System is indicated for severe to profound deafened individuals. It 
includes both external and implantable components. Surgery is required to place the implanted part 
(the Neuro Zti Implant) while the external components (Neuro One sound Processor) are worn behind 
the ear. A small antenna coil connected to the Neuro One Sound Processor is used to deliver both 
power and information to the implanted Neuro Zti. Using an electrode array, the Neuro Zti provides 
direct electrical stimulation to the hearing nerve to restore the perception of sound. 
This cochlear implant is already approved in the different countries and placed on the market in Europe 
and Canada. The system is CE marked and Health Canada approved, and has been sold in Europe and 
in major parts of world since September 2015. This cochlear implant meets the essentials requirements 
of medical device regulation focus on its safety and its efficacy. 
The purpose of this study is to systematically collect efficacy and safety data that can be leveraged to 
expand access of Neuro CI Technologies to other countries under different regulatory jurisdictions.  
To test the efficacy of the device several audiometric exams will be done to assess your auditory 
performance over time. In addition, the safety of the device will be monitored throughout the study 
and thereafter within the required manufacturer vigilance framework. 
3. WHO CAN TAKE PART IN THIS STUDY? 
To take place in this study you must: 
• 
be determined to be a candidate for cochlear implantation  
• 
choose to be implanted with the Neuro Zti 
• 
understand the study requirements and associated constraints and 
• 
provide informed consent  
You should not take part in this study if you do not meet all requirements. 
You cannot participate if  
- 
You have an inflammatory disease of the middle ear disease or other medical conditions such 
as auditory nerve lesions, pathologies of central auditory pathway, cochlea malformation or 
ossification. 
- 
You are unable or unwilling to use the cochlear implant system appropriately or to comply 
with all study requirements. 
- 
You have unrealistic expectations regarding the possible benefits, risks and limitations 
inherent to the surgical procedure. 
- 
You have not had an appropriate meningococcal meningitis vaccination or not updated. 
4. WHAT DOES THE STUDY INVOLVE? 
4.1. Study plan 
 The study plan seeks to enroll a total of 55 subjects. 

Consent Form 
LI_07 
Edition : C 
Subject information and Consent form 
«The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults» 
 
 
Edition: C, August 2016 
Author: S. SAAÏ 
Page 73 of 115 
CONFIDENTIAL 
Do not reproduce without Neurelec Oticon Medical authorization 
Your participation in this study is expected to last until the completion of the study or until you and/or 
your doctor decides that there is no clear benefit for you to continue the study. However, your doctor 
will request regular follow-up visits and will also monitor to your health status. The expected minimal 
trial duration is approximatively 14 months. 
If you decide to take part of this study, the procedures and visits you can expect are described in section 
5.3. This will give you information about what taking part in the study will require from you, for 
example how often you have to come to see the doctor as well as what tests and procedures will be 
performed. 
4.2. Treatment assignment 
All participants will be implanted with the Neuro Zti implant and use the Neuro One sound Processor. 
After the study ends, you will be followed as a standard cochlear implant patient in a routine care 
framework. 
5. PROCEDURES OF THE STUDY 
All subjects consenting to participate in this study are to be implanted with the Neuro Zti cochlear 
implant.  
5.1. Standard care procedures 
- 
Surgery methodology and anesthetic care 
- 
Postoperative care 
- 
Visit appointments are set on the standard care visits 
- 
Postoperative programming and auditory rehabilitation. 
- 
Objectives measurements such as electrode impedance measures are routinely performed 
during cochlear implantations and thereafter during fitting sessions. These measurements are 
used to check electrode-array integrity and are useful in the monitoring of implant functioning. 
 
5.2. Exploratory procedures  
The assessments used are those commonly used in standard practice of cochlear implant rehabilitation 
program. 
- 
Audiometry assessment with HINT (Hearing In Noise Test) sentences. The HINT measures the 
person’s ability to hear speech in quiet and in noise, it is used in routine audiological practice. 
Even though the assessment of your hearing can be done with different test, the HINT provides 
an efficient and reliable method for assessing person hearing across different languages. 
Pre-operatively, the HINT test will be performed with your hearing aid(s) in the best fitted 
conditions, and post-operatively, only your implanted ear will be tested. 
 
- 
Objectives measurements eCAP (electrically evoked Compound Action Potential). The eCAP 
measures are readily available in the clinical software of all cochlear implants on the market 

Consent Form 
LI_07 
Edition : C 
Subject information and Consent form 
«The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults» 
 
 
Edition: C, August 2016 
Author: S. SAAÏ 
Page 74 of 115 
CONFIDENTIAL 
Do not reproduce without Neurelec Oticon Medical authorization 
for measuring auditory nerve responses to electrical stimulation. The Neuro Zti ECAP features 
and functionality may be evaluated at the end of your surgery and at follow-up visits.   
 
You will be asked at each visit about your health status and if any adverse events occurred since your 
last visit.  
 
You will be asked to complete a patient diary to collect information on the period of device use, any 
issues related to non-device use and miscellaneous comments. 
 
5.3. Schedule visit procedures 
Visit 1 (screening visit, 8 weeks before surgery) 
- 
Candidates for cochlear implantation may be candidates to participate in this research study.  
- 
Screening may be done during a medical visit, by telephone, by mail or through medical 
records. 
- 
This screening process may determine if you are an appropriate candidate for this study (e.g. 
motivation, geographical remoteness, willing to commit protocol requirements). 
- 
You should be informed with the inform consent form and you should be given sufficient time 
to consider your decision and to clarify any questions you may have. 
 
Visit 2 (inclusion visit, 4 weeks before surgery) 
No study procedure can be performed without your signed consent form. 
- 
Your Informed consent is obtained 
- 
You will be assigned a single subject identifier (SSID) by the sponsor 
- 
Your physician will make sure that you have appropriate hearing aid settings to be in the best 
aided condition according to the clinical practice 
- 
Inclusion/exclusion criteria will be reviewed 
- 
Demography, medical history and concomitant medications will be reviewed 
- 
Audiometric evaluations with HINT test in Quiet and in Noise will be performed 
- 
Cochlear implantation scheduling will be confirmed 
 
Visit 3 (cochlear implant surgery) 
Surgery shall be performed according the conventional cochlear implantation procedures and standard 
surgical practice. 
- 
Time of surgery will be recorded 
- 
Objective measures: electrode impedances and ECAP 
- 
Complications/adverse effects collected 
- 
Concomitant medications collected 
 
Visit 4 (follow-up visit, 2 weeks after surgery) 

Consent Form 
LI_07 
Edition : C 
Subject information and Consent form 
«The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults» 
 
 
Edition: C, August 2016 
Author: S. SAAÏ 
Page 75 of 115 
CONFIDENTIAL 
Do not reproduce without Neurelec Oticon Medical authorization 
- 
Clinical examination (general state, scarring) performed 
- 
Complications/adverse effects collected 
- 
Concomitant medications collected 
 
Visit 5 (cochlear implant activation, 1 month after surgery) 
- 
Activation and fitting of your cochlear implant 
- 
Objective measures: electrode impedance 
- 
Complications/adverse effects collected 
- 
Concomitant medications collected 
- 
Patient diary issued 
 
Visit 6 (follow-up visit, 3 months after implant activation) 
- 
Audiometric evaluations with HINT test in Quiet and in Noise 
- 
Objective measures: electrode impedance and ECAP 
- 
Fitting of your cochlear implant 
- 
Complications/adverse effects collected 
- 
Concomitant medications collected 
- 
Previous patient diary collected and new patient diary delivery 
 
Visit 7 (follow-up visit, 6 months after implant activation) 
- 
Audiometric evaluations with HINT test in Quiet and in Noise 
- 
Objective measures: electrodes impedance and ECAP 
- 
Complications/adverse effects collected 
- 
Concomitant medications collected 
- 
Previous patient diary collected and new patient diary delivery 
 
Visit 8 (end of study, 12 months after implant activation) 
- 
Audiometric evaluations with HINT test in Quiet and in Noise 
- 
Objective measures: electrodes impedance and ECAP 
- 
Complications/adverse effects collected 
- 
Concomitant medications collected 
Previous patient diary collected 
 
Unscheduled visit(s), may be done at any time during the study 
- 
Complications/adverse effects collected 
- 
Concomitant medications collected 
- 
Objective measures: impedance and ECAP, where appropriate 
 
6. POTENTIAL RISKS 
Risks 

Consent Form 
LI_07 
Edition : C 
Subject information and Consent form 
«The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults» 
 
 
Edition: C, August 2016 
Author: S. SAAÏ 
Page 76 of 115 
CONFIDENTIAL 
Do not reproduce without Neurelec Oticon Medical authorization 
Electrical stimulation of the hearing nerve with cochlear implants has been in use for over 30 years 
without any report of damage to tissue resulting from electrical stimulation. If problems should 
develop in the future, the implant can either be not used or surgically removed. 
The rate of complications associated with cochlear implant surgery is small and post-complications are 
rare but it is critical that you review and understand the potential risks prior to singing the informed 
consent.  
Potential risks include but are not limited to: 
- 
Risks associated with general anesthesia: include but are not limited to lightheadedness, 
nausea, skin rash, constipation, death. 
- 
Risks associated with surgery: include but are not limited to dizziness, vertigo, dryness of the 
mouth, ringing (tinnitus) in the ear, partial or complete facial nerve paralysis, pain near the 
implant, numbness near the implant, changes in taste perceptions, death. 
- 
Meningitis is a rare but potentially serious complication. To minimize the increased lifetime 
risk with a cochlear implant you must be properly vaccinated and know the symptoms of 
meningitis to minimize the time between symptoms and treatment should they ever occur.  
- 
There is a risk that you may have some bleeding after the operation.  Complications associated 
with bleeding or healing may require local treatment and/or more invasive surgical 
intervention. 
- 
You may experience numbness and/or stiffness occur around the ear. In most cases, such 
symptoms improve gradually over time but may not completely disappear. 
- 
You may have some loss of taste on the side of the operation, which may be temporary or 
permanent 
- 
Rarely, you may have some temporary weakness of your facial muscles that may result from 
swelling near the facial nerve. Such symptoms typically resolve within several weeks, but 
permanent paralysis may occur. 
- 
Your wound may become infected and may require local and/or systemic antibiotic therapy. 
It is possible that the skin wound may fail to heal and the device may need to be removed. 
- 
You may have some pain in the area of the coil, which generally improves over time. 
- 
It is possible that your body may reject the implant, which may result in extrusion of the 
implant and/or necessitate surgical intervention to remove the device. 
- 
The external equipment may be fail and/or require re-mapping 
- 
The internal device may be fail requiring the need for a second surgery to replace the damaged 
device. You will need to avoid sports and activities where there is a potential to damage the 
device.  
- 
Prior to undergoing any other medical or therapeutic intervention you must inform the 
medical staff that you have a cochlear implant, as some procedures or investigations may 
damage the device and/or expose you to serious risk of injury or death. 
- 
There may be circumstances where it may not be possible to insert the implant electrodes 
completely and this may have a negative impact on potential outcome. 
- 
There is a risk that modern imaging will be unable to determine the integrity of your auditory 
pathways and their ability to processes electric stimulation. The ability of the implant to 

Consent Form 
LI_07 
Edition : C 
Subject information and Consent form 
«The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults» 
 
 
Edition: C, August 2016 
Author: S. SAAÏ 
Page 77 of 115 
CONFIDENTIAL 
Do not reproduce without Neurelec Oticon Medical authorization 
improve speech perception will depend on the existence and ability of auditory nerve to 
conduct impulses. The functional integrity of the pathways is known to impact outcome and is 
difficult to predict in advance.  
- 
It is impossible to predict in advance how well you will perform with a cochlear implant. It is 
important for you to understand that a cochlear implant will not cure your deafness nor will it 
completely restore or provide normal hearing.  
- 
You should take care to avoid static electricity. Static electricity may damage the electronic 
components of the device or the programs.  
Even though the Neuro Zti has approval for certain MRI conditions, there are risks associated with an 
MRI exam, as for all other cochlear implants. Therefore, prior to undergoing any MRI exam for any part 
of your body, you must inform the physician that you have a cochlear implant and present your implant 
identification card. Even optimal conditions, during an MRI exam it is possible that you may experience 
discomfort and/or auditory sensations such as cracking, beeping and/or humming sounds. Should you 
experience discomfort during an MRI exam it is important to notify the clinician immediately. 
Should other medical therapies be considered, please consult your identification card and/or a 
qualified clinician prior to therapy. In addition, please take notice of the Neuro One processor 
instructions for use. 
7. NEW INFORMATION 
You will be told about any important new information that is found during the study that might affect 
your health, well-being or willingness to stay in the study. You may be asked to sign a new consent 
form if this occurs. 
8. BENEFITS 
Your speech perception and hearing skills may be improve following cochlear implantation. The 
improvement depends upon many factors which have been explained to you by the investigator and 
your medical team. 
The results of this study may be help people with severe-to-profound hearing loss in the future and 
may be used to improve the cochlear implant system. 
You do not to have to take part of this study to be treated for your deafness. You may also benefit 
from the Neuro cochlear implant system in routine care without enrolling in the study. 
9. COMPENSATION FOR INJURY 
Health care is provided through a system of national or provincial insurance depending on your 
country.  
This insurance may or may not provide coverage for certain types of injuries that might result from 
taking part in the study. To this extent:  
Oticon Medical will provide the study over-costs free of charge during the study (experimental tests 
and procedures). Standard tests and procedures that are done for the study that would also be done 

Consent Form 
LI_07 
Edition : C 
Subject information and Consent form 
«The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults» 
 
 
Edition: C, August 2016 
Author: S. SAAÏ 
Page 78 of 115 
CONFIDENTIAL 
Do not reproduce without Neurelec Oticon Medical authorization 
for a standard non-study patient will not be billed to you but billed to the health care system and/or 
your insurance company. 
The health care system and/or your insurance company may be billed for: 
- 
Any standard medical given during this research study 
- 
Other specific local reasons. 
You may want to talk with your insurance company about payment policy for standard medical care 
given during surgery. If your insurance company does not pay, you may be billed for those charges. 
You might have unexpected expenses from being in this study. Ask your study investigator to discuss 
the costs that will or will not be covered by the sponsor. This discussion should include who will pay 
the costs of treating possible side effects. 
Signing this form does not mean you that you have given up any of your legal rights. The investigator, 
sponsor or hospital would still have legal and professional responsibilities to you.  
10. COSTS 
Your cochlear implant will be provided by the hospital as any conventional cochlear implant and billed 
to health care system and/or your insurance company. 
For unscheduled visits, you might have to pay for some expenses related to your taking part in this 
study, such as transportation, parking, others. You will be reimbursed of up to 100€/study visit for 
expenses related to your taking part in this study only if the unscheduled visit is related to side effects 
related to the cochlear implant. This does not include side effects related to surgery or medical reasons 
other than related to the device. 
11. WHO DO I CONTACT IF I WANT TO REPORT HEALTH PROBLEM OR HAVE QUESTIONS? 
If you have any injury, side effects or any unusual health experience during this study, make sure that 
you tell the investigator or study staff immediately. You may call at any time to report an adverse 
event. 
If you have any questions or concerns about this study, your rights, please contact your investigator: 
[Name+Contact phone investigator]: _________________________________________________ 
Do not sign this informed consent document until all of your questions and concerns have been 
addressed. 
12. VOLUNTARY PARTICIPATION AND WITHDRAWAL 
Your taking part in this study is entirely voluntary. Whether or not you take part is completely up to 
you. You will continue to receive the best possible care no matter what you decide. 
If you choose to take part and later change your mind, you may do so. You may stop participating at 
any time. A decision to stop being in the study will not affect how your health care is provided to you. 
If you decide to stop the study, please inform the investigator and/or one of the staff involved in the 

Consent Form 
LI_07 
Edition : C 
Subject information and Consent form 
«The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults» 
 
 
Edition: C, August 2016 
Author: S. SAAÏ 
Page 79 of 115 
CONFIDENTIAL 
Do not reproduce without Neurelec Oticon Medical authorization 
study. Should you decide to withdraw, you can arrange follow-up care with your physician and/or clinic 
staff. 
The investigator and the sponsor reserve the right to, at any time and for any reason, either withdraw 
you and/or stop the study independent of your desire to continue. This could happen if you experience 
serious side effects, have a serious adverse event and/or if there is new information about the safety 
and effectiveness of the Neuro Zti cochlear implant system. The investigator or its study staff will 
explain the reason(s) for any early termination and arrange for your continued healthcare.  
13. ALTERNATIVE TREATMENT 
The Cochlear implant is designed to treat severe-to-profound hearing loss.  There are other cochlear 
implants commercially available. The investigator can discuss these possibilities with you. 
14. AUTHORIZATION TO USE AND DISCLOSE INFORMATION FOR RESEARCH PURPOSES 
The investigator and study staff will handle your personal health information in a confidential manner 
and in compliance with applicable law. Your health information will be used and disclosed as defined 
in the following data privacy statements. 
In this section “personal health information” means information about a person that relates to things 
like the person’s physical and/or family health history, health care, health care provider and 
information that directly identifies the person (name, date of birth, address etc.).  The term “study 
data” means study-related health information that does not directly identify a person (that is, does 
not contain the person’s name, address, health number or other identifying information) but that does 
contain an assigned code number for the person and the person’s initials.  
By signing the consent document for this study, you will be giving permission for the use and disclosure 
of your personal health information that are described in this data privacy statement. If you do not 
wish to allow the disclosure and use of your personal information as described herein, you should not 
participate in this study. 
If you agree to participate in this study, your personal health information and study data will be 
maintained, used and shared in the following way: 
- 
The study monitor, study auditor, the sponsor’s clinical research staff and regulatory 
authorities might have access to your personal health information. This may include 
information from your health records such as medical history, auditory test results, special 
reports and medications that you have had in the past and/or are currently undergoing. Your 
records will be kept and disposed of in accordance with applicable laws and regulation. 
- 
The investigator and their study staff will send your study data to the sponsor, and/or its 
associated representatives. Because the sponsor conducts business related to clinical research 
in many countries, this may involve sending your study data outside of your country. If your 
study data is sent to other country, your privacy will remain protected as described in this 
section. 

Consent Form 
LI_07 
Edition : C 
Subject information and Consent form 
«The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults» 
 
 
Edition: C, August 2016 
Author: S. SAAÏ 
Page 80 of 115 
CONFIDENTIAL 
Do not reproduce without Neurelec Oticon Medical authorization 
- 
Your study data will be used by the sponsor for research purposes to support the scientific 
objectives of the study. The primary objectives being to further confirm the efficacy and safety 
of the Neuro Cochlear Implant system. In addition, data from the study may be used to 
improve the system and/or improve the design of future studies with the aim of maximizing 
performance outcomes.  
- 
Your study data, either alone or combined with data from other studies, might be shared with 
your local regulatory authorities and similar government agencies from another country, as 
well as with the ethics review board overseeing this study. 
- 
Study data (which does not identify you) might be published in medical journals or shared with 
other others as part of scientific discussion. 
- 
To extent permitted by applicable laws, the sponsor, the ethic review board, the regulatory 
authority and/or other regulatory agencies in other countries, might review the original health 
records, which contain information that directly identifies you to verify the accuracy and 
completeness of the data collected during the study. 
Subject to applicable laws, you will have the right to see and copy personal health information related 
to the study for as long as the investigator holds this information. However, you will not be able to see 
or copy this information until after the study has been completed. 
You may withdraw your permission at any time by providing notice to the investigator. The investigator 
and their staff would then no longer use or share your personal information in connection with the 
study unless it is essential to ensure that the study is scientifically reliable. However, the sponsor would 
still use your study data that was collected before you withdrew your permission. In addition, a 
withdrawal from the study means that you would no longer able to participate in the study. 
15. SOURCE OF FUNDING FOR THE STUDY 
The sponsor will pay for this research study. 
Depending on countries, the sponsor is paying the investigator for their work in this study. 
 
 
 

Consent Form 
LI_07 
Edition : C 
Subject information and Consent form 
«The Neuro Zti Cochlear Implant System Efficacy and Safety in Adults» 
 
 
Edition: C, August 2016 
Author: S. SAAÏ 
Page 81 of 115 
CONFIDENTIAL 
Do not reproduce without Neurelec Oticon Medical authorization 
CONSENT FORM 
To take part to this study and to allow the use and disclosure of my personal health information for 
the purpose of the study, I must sign and date this page. 
 
By signing this page, I confirm the following: 
I give permission for my personal health information and study data to be maintained, used and shared 
as described in this document. 
I have read the subject information and consent form and I have had time to think about whether or 
not I want to take part in this study. 
I understand the risks, as described herein, of cochlear implant surgery. 
All of my questions about the study or this form were answered to my satisfaction. If I don’t understand 
any of the words in this form, the investigator or their staff explained them to me.  
I understand that I may have other therapeutic options and/or cochlear implant device choices and 
have voluntarily agreed to be implanted with the Neuro Zti cochlear implant. 
I voluntarily agree to take part in this study, to follow the study procedures and to provide necessary 
information to the investigator or its staff members as requested. 
I understand that I may freely to stop being a part of this study at any time. 
I have received a copy of the subject information and consent for. 
 
By signing this consent form, I have not given up any of my legal rights. 
 
____________________________________
_ 
Subject’s name (printed) 
 
____________________________________
_ 
Investigator’s name (printed) 
 
____________________________________
_ 
Subject Signature  
 
____________________________________
_ 
Investigator signature 
Date: |__|__|/|__|__|/|__|__|__|__| 
Date: |__|__|/|__|__|/|__|__|__|__| 
 

 
Page 82 of 115 
ADVERSE EVENT REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
Appendix 3: ADVERSE EVENT REPORT FORM 
 
 

 
Page 83 of 115 
ADVERSE EVENT REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
 
 
Study ID 
 
Site number 
 
Investigator  
 
 
Adverse 
event 
Start 
date 
Stop 
date 
Severity  
Relationship to the 
study device 
Relationship to trial 
procedure? 
Action taken 
Treatment/therapy? 
(If 
yes, 
complete 
concomitant form) 
Outcome of AE 
Anticipated AE? 
Serious Adverse 
Event? 
(If yes, complete 
SAE form) 
1. 
 
 
☐Mild 
☐Moderate 
☐Severe 
☐ Definitely related 
☐ Possible related 
☐ Not related 
☐ Unknown 
☐ Improbable  
☐ Possible 
☐ Probable 
☐ Certainly  
☐ Unknown 
☐ None 
☐ 
Discontinued 
permanently 
☐ 
Discontinued 
temporarily 
☐ Unknown 
☐ Yes 
☐ No 
☐ Death 
☐ Not Recovered 
☐ Recovered 
☐ 
Recovered 
with 
sequelae 
☐ Recovering 
☐ Unknown 
☐ Yes 
☐ No 
 
☐ Yes  
☐ No  
2. 
 
 
☐Mild 
☐Moderate 
☐Severe 
☐ Definitely related 
☐ Possible related 
☐ Not related 
☐ Unknown 
☐ Improbable  
☐ Possible 
☐ Probable 
☐ Certainly  
☐ Unknown 
☐ None 
☐ 
Discontinued 
permanently 
☐ 
Discontinued 
temporarily 
☐ Unknown 
☐ Yes 
☐ No 
☐ Death 
☐ Not Recovered 
☐ Recovered 
☐ 
Recovered 
with 
sequelae 
☐ Recovering 
☐ Unknown 
☐ Yes 
☐ No 
 
☐ Yes  
☐ No 
3. 
 
 
☐Mild 
☐Moderate 
☐Severe 
☐ Definitely related 
☐ Possible related 
☐ Not related 
☐ Unknown 
☐ Improbable  
☐ Possible 
☐ Probable 
☐ Certainly  
☐ Unknown 
☐ None 
☐ 
Discontinued 
permanently 
☐ 
Discontinued 
temporarily 
☐ Unknown 
☐ Yes 
☐ No 
☐ Death 
☐ Not Recovered 
☐ Recovered 
☐ 
Recovered 
with 
sequelae 
☐ Recovering 
☐ Unknown 
☐ Yes 
☐ No 
 
☐ Yes  
☐ No 
4. 
 
 
☐Mild 
☐Moderate 
☐Severe 
☐ Definitely related 
☐ Possible related 
☐ Not related 
☐ Unknown 
☐ Improbable  
☐ Possible 
☐ Probable 
☐ Certainly  
☐ Unknown 
☐ None 
☐ 
Discontinued 
permanently 
☐ 
Discontinued 
temporarily 
☐ Yes 
☐ No 
☐ Death 
☐ Not Recovered 
☐ Recovered 
☐ 
Recovered 
with 
sequelae 
☐ Yes 
☐ No 
 
☐ Yes  
☐ No 

 
Page 84 of 115 
ADVERSE EVENT REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
Adverse 
event 
Start 
date 
Stop 
date 
Severity  
Relationship to the 
study device 
Relationship to trial 
procedure? 
Action taken 
Treatment/therapy? 
(If 
yes, 
complete 
concomitant form) 
Outcome of AE 
Anticipated AE? 
Serious Adverse 
Event? 
(If yes, complete 
SAE form) 
☐ Unknown 
☐ Recovering 
☐ Unknown 
5. 
 
 
☐Mild 
☐Moderate 
☐Severe 
☐ Definitely related 
☐ Possible related 
☐ Not related 
☐ Unknown 
☐ Improbable  
☐ Possible 
☐ Probable 
☐ Certainly  
☐ Unknown 
☐ None 
☐ 
Discontinued 
permanently 
☐ 
Discontinued 
temporarily 
☐ Unknown 
☐ Yes 
☐ No 
☐ Death 
☐ Not Recovered 
☐ Recovered 
☐ 
Recovered 
with 
sequelae 
☐ Recovering 
☐ Unknown 
☐ Yes 
☐ No 
 
☐ Yes  
☐ No 
6. 
 
 
☐Mild 
☐Moderate 
☐Severe 
☐ Definitely related 
☐ Possible related 
☐ Not related 
☐ Unknown 
☐ Improbable  
☐ Possible 
☐ Probable 
☐ Certainly  
☐ Unknown 
☐ None 
☐ 
Discontinued 
permanently 
☐ 
Discontinued 
temporarily 
☐ Unknown 
☐ Yes 
☐ No 
☐ Death 
☐ Not Recovered 
☐ Recovered 
☐ 
Recovered 
with 
sequelae 
☐ Recovering 
☐ Unknown 
☐ Yes 
☐ No 
 
☐ Yes  
☐ No 
7. 
 
 
☐Mild 
☐Moderate 
☐Severe 
☐ Definitely related 
☐ Possible related 
☐ Not related 
☐ Unknown 
☐ Improbable  
☐ Possible 
☐ Probable 
☐ Certainly  
☐ Unknown 
☐ None 
☐ 
Discontinued 
permanently 
☐ 
Discontinued 
temporarily 
☐ Unknown 
☐ Yes 
☐ No 
☐ Death 
☐ Not Recovered 
☐ Recovered 
☐ 
Recovered 
with 
sequelae 
☐ Recovering 
☐ Unknown 
☐ Yes 
☐ No 
 
☐ Yes  
☐ No 
8. 
 
 
☐Mild 
☐Moderate 
☐Severe 
☐ Definitely related 
☐ Possible related 
☐ Not related 
☐ Unknown 
☐ Improbable  
☐ Possible 
☐ Probable 
☐ Certainly  
☐ Unknown 
☐ None 
☐ 
Discontinued 
permanently 
☐ 
Discontinued 
temporarily 
☐ Unknown 
☐ Yes 
☐ No 
☐ Death 
☐ Not Recovered 
☐ Recovered 
☐ 
Recovered 
with 
sequelae 
☐ Recovering 
☐ Unknown 
☐ Yes 
☐ No 
 
☐ Yes  
☐ No 

 
Page 85 of 115 
SERIOUS ADVERSE EVENT REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
Appendix 4: SERIOUS ADVERSE EVENT REPORT FORM 

 
Page 86 of 115 
SERIOUS ADVERSE EVENT REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
1. REPORT SEQUENCE                          ☐ Initial           ☐ Follow-up           ☐ Final 
 
FAX to Dan GNANSIA, PhD: +00 33 4 93 95 38 01 or dagn@oticonmedical.com  
 
2. Country where the AER occurred:_______________________________ 
Center ID: ____ 
Investigator name: ___________________________________________ 
 
3. Source for clinical trial only 
Protocol/study 
ID: 
________________ 
☐PMS/PMA 
RBM n° : ________________ 
 
 
4. PATIENT DATA 
Initials______ ____ 
patient ID____         
Gender: ☐Male ☐ Female 
Date of Birth ____  ______  ________ (mm/ddd/yyyy)   weight: ______kg   height: ______ cm 
Date of enrolment: ____  ______  ______ __ (mm/ddd/yyyy)    
Date of implantation: ____  ______  ________ (mm/ddd/yyyy)    
Date of death: ____  ______  ________ (mm/ddd/yyyy)    
5. NARRATIVE : provide clear narrative description of the sequence of events, diagnosis and any relevant details. If additional 
space is needed, use a Narative supplement page. 
☐ Check if Narrative Supplemental page 
_____________________________________________________________________________________________________________
_____________________________________________________________________________________________________________
_____________________________________________________________________________________________________________
_____________________________________________________________________________________________________________ 
6. REACTION DATA 
Complete below reaction level characteristics for this specific adverse event 
Reporter awarness date: ____  ______  ________                                          
Onset date/date of incidence: ____  ______  ________ 
Stop date/date of incidence resolved: ____  ______  ________ 
Is there a reasonable possibility the serious adverse event is related to the clinical trial procedure? 
☐Yes                                                               ☐No  
Adverse event description: _____________________________________ 
Serious criteria 
(check all that apply) 
*death is an outcome 
☐ Death*  
date: __________________ 
Cause: 
_________________________________ 
Autopsy: ☐ Yes ☐ No   
Conclusion: 
_________________________________ 
Chek this box: 
if the subject died 

 
Page 87 of 115 
SERIOUS ADVERSE EVENT REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
☐ Serious injury 
Check this box: 
 if the device SAE led to a serious 
deterioration in state of health. 
Deterioration of state of health can 
include: life- threatening illness or injury, 
permanent damage to a body structure, 
or a medical or surgical intervention to 
prevent permanent impairment of a 
body function or permanent damage to a 
body structure.  
☐ Life-threatening 
Check this box: 
If the subject was immediate risk of 
death from the device SAE 
☐ Permanent impairement/damage of 
the body structure/function (disability) 
Check this box: 
If the subject sustained permanet 
impairement, 
damage 
of 
a 
body 
srtructure or function (disability) as a 
result of the device SAE. 
☐ Required medical surgical 
intervention to prevent permanent 
impairement/Damage to a body 
function/structure, specify 
treatement/intervention 
_________________________________
_________________________________
_________________________________ 
Check this box: 
If the device SAE required medical or 
surgical 
intervention 
to 
prevent 
permanet impairement/damage to a 
body structure/function. 
Specify the treatment/intervention in the 
space provide. 
☐ Other, specify: 
_________________________________
_________________________________
_________________________________ 
Check this box: 
If the the criteria listed above are not 
relevant. 
Specify in the space provided the 
seriousness criteria 
Clinical outcome 
(check one box only) 
☐ Death (if the outcome is death due to the listed SAE (ie, where “Death” is checked 
off in the Serious Criteria field above), leave this field blank.)) 
☐ Not recovered (check Not recovered if the SAE is not only still present at the time 
of the report, but also the same or worse than at outset) 
☐ Recovered 
☐ Recovered with sequelae 
☐ Recovering (chek Recovering if the SAE was still present but improved or better 
than at outset) 
☐ Unknown  

 
Page 88 of 115 
SERIOUS ADVERSE EVENT REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
Investigator Causality: 
Relatedness of AE/Device Deficiency 
*specify in Remarks Section 
Is there a reasonable possibility that the event is related to the device? 
☐ Yes                                                                    ☐ No  
If No, what is the most likely cause? 
☐ Procedure-related 
☐ Disease under study 
☐ Other illness* 
☐ Concomitant treatment/Therapy* 
☐ Other* 
☐ Unknown 
Remarks: ____________________________________________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
7. Subject suspect device data 
Device trade/brand name: _______________________________ 
Licence n°: ____________________________________________ 
☐ Implant                  ☐ Processor                ☐ Accessories 
Labelled Sterile: ☐ Yes       ☐ No 
Model n°: ____________________________________________ 
Software version: ______________________________________ 
Serial n°: ______________________________________________ 
Batch/lot n°: ___________________________________________ 
Date of implantation: ____  ______  ________ 
(dd/mmm/yyyy) 
Date of end use: ____  ______  ________ 
(dd/mmm/yyyy) 
Date of first use: ____  ______  ________ 
(dd/mmm/yyyy) 
Date of explantation: ____  ______  ________ 
(dd/mmm/yyyy) 
Device sent for the manufacturer for expertise: ☐ Yes, date: ____  ______  ________ ☐ No 

 
Page 89 of 115 
SERIOUS ADVERSE EVENT REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
 
 
8. Event qualification  
Expectedness:                                      ☐ Anticipated advese event                                       ☐ Unanticipated adverse event 
9. Action taken 
(multiple choice is possible) 
The event stopped after the 
taken action? 
Reliationship to medical device? Relationship 
to 
trial 
procedure? 
☐ None 
☐ Discontinued permanently 
☐ Discontinued temporarily 
☐ Unknown  
☐ 
Device 
change 
(external 
part/accessories) 
☐ Treatment/Therapy given, please 
complete concomittant traitement 
supplemental page. 
☐ Revision surgery, please complete 
section 10. 
☐ Yes 
☐ No 
☐ In progress 
☐ N/A 
☐ Definitely related 
☐ Possible related 
☐ Not related 
☐ Unknown 
☐ Improbable  
☐ Possible 
☐ Probable 
☐ Certainly  
☐ Unknown 
 
 
10. Revision surgery*, please fill in the Explantation Report Form if applicable 
☐ Skin flap infection/wound complication 
 
 
☐ Implant body rejection 
 
 
☐ Implant receiver extrusion 
 
 
☐ Electrode array damaged/not put in the right 
place/migrate out of place 
 
 
☐ Implant failure, please attached the clinical 
report 
 
 
 
11. Suspected treatment(s), if applicable, 
Name/DCI/dose(s)/route 
Date Start/Date End 
Action taken with this suspected 
treatment 
Accountability of suspected 
treatment  
 
 
☐ No action taken 
☐ Dose decresae 
☐ Discontinuation treatment 
☐ Stopping treatment 
☐ Requiring therapy 
☐ Improbable  
☐ Possible 
☐ Probable 
☐ Certainly  
☐ Unknown 
 
 
☐ No action taken 
☐ Dose decresae 
☐ Discontinuation treatment 
☐ Stopping treatment 
☐ Requiring therapy 
☐ Improbable  
☐ Possible 
☐ Probable 
☐ Certainly  
☐ Unknown 
 

 
Page 90 of 115 
SERIOUS ADVERSE EVENT REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
 
12. Additional information  
Medical history,  surgical history, patient therapeutic treatment (must be reported if they may have an impact on advesre events, 
e.g. allergy, renal insufficiency, etc.) 
☐ Check if patient history supplemental page 
 
Results of additional test/exam, precise type of test and result(s) 
☐ Check if Lab data supplemental page 
 
 
 
13. Investigator 
 
Print 
Name: 
_________________________________________________________________________________ 
Contact information (address, phone, fax and e-mail): _____________________________________ 
_________________________________________________________________________________ 
Authorized 
signature: 
________________________________________________________________________________ 
Date: ____  ______   ________ 
 
 
 
 
 

 
Page 91 of 115 
SERIOUS ADVERSE EVENT REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
NARRATIVE SUPPLEMENTAL PAGE 
1. Narrative 
Provide a clear narrative description of the sequence of events, diagnosis and any other relevant details. 
________________________________________________________________________________________
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________________________________________________________________________________________
________________________________________________________________________________________
________________________________________________________________________________________ 
 
 

 
Page 92 of 115 
SERIOUS ADVERSE EVENT REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
CONCOMITANT TREATMENT SUPPLEMENTAL PAGE 
2. Concomitant drugs 
Drug name (trade or 
generic)  
Include all drugs taken 
within 2 weeks before onset 
of the event. Exclude drug 
used to treat the event. 
Therapy 
continuing 
Date (or duration if dates unknown) 
Route 
(e.g. oral, 
etc.) 
Start 
(dd/mmm/yyyy) 
End 
(dd/mmm/yyyy) 
 
☐ Yes  
☐ No 
☐ Unknown  
 
 
 
 
☐ Yes  
☐ No 
☐ Unknown 
 
 
 
 
☐ Yes  
☐ No 
☐ Unknown 
 
 
 
 
☐ Yes  
☐ No 
☐ Unknown 
 
 
 
 
☐ Yes  
☐ No 
☐ Unknown 
 
 
 
 
☐ Yes  
☐ No 
☐ Unknown 
 
 
 
 
☐ Yes  
☐ No 
☐ Unknown 
 
 
 
 
☐ Yes  
☐ No 
☐ Unknown 
 
 
 
 
☐ Yes  
☐ No 
☐ Unknown 
 
 
 
 
☐ Yes  
☐ No 
☐ Unknown 
 
 
 
 
 
 

 
Page 93 of 115 
SERIOUS ADVERSE EVENT REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
PATIENT HISTORY SUPPLEMENTAL PAGE 
3. Patient history 
Include any other illness present at the time of onset of the event, relevant medical history and pre-existing medical 
conditions (e.g. allergies, previous drug reaction, alcohol/drug abuse, etc.). Specify disease entity for each drug 
listed in the concomitant drug supplemental page) 
Disease/Syndrome (specify) 
Date of Onset 
(dd/mmm/yyyy) 
Continuing  
Pertinent details 
Include surgical procedures and 
dates 
 
 
☐ Yes  
☐ No 
☐ 
Unknown 
 
 
 
☐ Yes  
☐ No 
☐ 
Unknown 
 
 
 
☐ Yes  
☐ No 
☐ 
Unknown 
 
 
 
☐ Yes  
☐ No 
☐ 
Unknown 
 
 
 
☐ Yes  
☐ No 
☐ 
Unknown 
 
 
 
☐ Yes  
☐ No 
☐ 
Unknown 
 
 
 
☐ Yes  
☐ No 
☐ 
Unknown 
 
 
 
☐ Yes  
☐ No 
☐ 
Unknown 
 
 
 
 

 
Page 94 of 115 
SERIOUS ADVERSE EVENT REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
LAB DATA SUPPLEMENTAL PAGE 
LAB DATA TEST/EXAM FINDINGS 
List only relevant confirmatory test results for event (including autopsy results, medical 
imaging results, etc.) if available, source documents are considered relevant/necessary, 
please attach after transcribing results. 
Test  
Test date 
(dd/mmm/yyyy) 
Test result 
Test unit 
Normal low 
Normal high 
 
 
 
 
 
 
Comments: 
Test  
Test date 
(dd/mmm/yyyy) 
Test result 
Test unit 
Normal low 
Normal high 
 
 
 
 
 
 
Test  
Test date 
(dd/mmm/yyyy) 
Test result 
Test unit 
Normal low 
Normal high 
 
 
 
 
 
 
Test  
Test date 
(dd/mmm/yyyy) 
Test result 
Test unit 
Normal low 
Normal high 
 
 
 
 
 
 
Test  
Test date 
(dd/mmm/yyyy) 
Test result 
Test unit 
Normal low 
Normal high 
 
 
 
 
 
 
Test  
Test date 
(dd/mmm/yyyy) 
Test result 
Test unit 
Normal low 
Normal high 
 
 
 
 
 
 
Test  
Test date 
(dd/mmm/yyyy) 
Test result 
Test unit 
Normal low 
Normal high 
 
 
 
 
 
 
Test  
Test date 
(dd/mmm/yyyy) 
Test result 
Test unit 
Normal low 
Normal high 
 
 
 
 
 
 
Test  
Test date 
(dd/mmm/yyyy) 
Test result 
Test unit 
Normal low 
Normal high 
 
 
 
 
 
 

 
Page 95 of 115 
 
EXPLANTATION REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
Appendix 5: EXPLANTATION REPORT FORM 
 
 

 
Page 96 of 115 
EXPLANTATION REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adult 
The implantable device could be explanted for technical or medical issues. 
This explantation report form should be completed with a clinical support from Oticon Medical 
Neurelec and sent to Oticon Medical Neurelec whether the internal part is removed or remains in situ. 
 
Date of filing: |__|__|/|__|__|__|/|__|__|__|__| 
SOURCE OF THE INCIDENT 
 
Please describe 
☐ Device failure 
 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 
 
☐ Medical reason 
 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 
 
☐ Other  
 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 
 
 
Oticon 
Medical 
representative 
contacted 
prior 
explantation:  
 
☐ Yes
 
 
☐ 
No, 
comment:____________________________________ 
 
PATIENT INFORMATION & IMPLANT INFORMATION 
Center ID 
 
Subject ID 
 
Implantation date 
 
Explantation date 
 
Explanted device model 
☐Neuro ZtiCLA                          ☐NeuroZTIEVO 
Explanted device serial number  
Sound processor serial number  

 
Page 97 of 115 
EXPLANTATION REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adult 
 
CLINICAL REPORT 
Incident onset date: |__|__|/|__|__|__|/|__|__|__|__| 
Incident report: 
 
 
 
 
Medical reason which could be linked to the incident: 
 
 
 
 
EABR testing performed 
 
☐ Yes  
☐ No 
If yes, did Oticon Medical 
determine that device failed 
prior explantation 
☐ Yes 
☐ No 
☐ Inconclusive  
 
Integrity testing performed 
 
☐ Yes  
☐ No 
If yes, did Oticon Medical 
determine that device failed 
prior explantation 
☐ Yes 
☐ No 
☐ Inconclusive  
 
Please document that the following has taken place: 
☐ 
SAE reporting form completed and sent to Oticon Medical 
☐ 
Vigilance report completed and sent to Oticon Medical 
☐ 
Vigilance report completed and sent to local competent 
authority 
☐ 
Other, 
please 
specify: 
________________________________  
 
Please document the medical reason for device explant (multiple choice is possible) 
☐ 
Performance issue 
☐ 
Electrode migration 
☐ 
Electrode array misplacement 

 
Page 98 of 115 
EXPLANTATION REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adult 
☐ 
Implant migration/extrusion 
☐ 
Facial nerve stimulation 
☐ 
Shocking with device ON/OFF (please delete as appropriate) 
☐ 
Pain and/or discomfort with device ON 
Precise location (e.g. over implant stimulator, ear canal, neck, 
etc.): _______________________________________________ 
____________________________________________________ 
☐ 
Pain and/or discomfort with device OFF 
Precise location (e.g. scalp, flap, incision line, ear canal, neck, 
etc.): ________________________________________________ 
_____________________________________________________ 
 
SURGICAL OBSERVATIONS during device explant 
Any physical signs of device failure prior explant? 
☐ Yes, please describe: _______________________________________________________________ 
__________________________________________________________________________________ 
☐ No  
Electrode status, did the electrode array appear to have moved since initial placement? 
☐ Yes, please describe: _______________________________________________________________ 
__________________________________________________________________________________ 
☐ No  
Any evidence of infection or tissue reaction? 
☐ Yes, please describe: _______________________________________________________________ 
__________________________________________________________________________________ 
☐ No 
 
Was a device re-implanted? 
☐ Yes, please precise, model and serial number: __________________________________________ 
__________________________________________________________________________________ 
☐ No 
If yes, please describe the surgical placement of the second device 
☐ Similar to placement of the first device 
☐ Insertion with some resistance 
☐ Partial / full insertion 

 
Page 99 of 115 
EXPLANTATION REPORT FORM 
Neuro Zti cochlear implant-system Efficacy and Safety in Adult 
☐ 
Other: 
_____________________________________________________________________ 
______________________________________________________________________
_____ 
 
Explanted device returned to Oticon Medical? 
☐ Yes 
☐ No, please explain: ________________________________________________________________ 
__________________________________________________________________________________ 
 
Investigator 
Authorized signature: ________________________________________________________________ 
Print name: ________________________________________________________________________ 
Date: ____  ______  ________ 
 
 
 

 
Page 100 of 115 
 
CLINICAL SUPPORT ROLE 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
Appendix 6: CLINICAL SUPPORT ROLE 
0. Purpose  
This document describes the function and duties of the clinical support in this clinical trial. The 
main task of the clinical trial support is to make sure that medial team are properly used the 
Neuro cochlear implant system. The clinical trial support is an Oticon Medical employee, he/she 
have a background in audiology, speech therapy, PhD or engineer in audiology. 
1. Scope  
This document applies to the clinical trial which will be conducted in Canada and Denmark to 
support the PMA-FDA submission. 
2. References 
- 
Neurelec Clinical Support procedure (PG0005) 
3. Abbreviation 
eCAP: electrical Evoked Compound Action Potential 
OR: Operating Room 
4. Basic role of the clinical support 
The clinical support provide clinical, expertise and support to Oticon Medical’s participants’ 
centers. 
Provide clinical support, information and advice to clinical teams on topics such as surgery, and 
post-implantation management. Also, assist with clinical trial and research studies on Oticon 
Medical products. 
The role focus on providing clinical expertise on product,  support initial stimulation, assist with 
clinical problems, as well as performing training to build clinical capability through clinical 
investigation sites. 
Cochlear implant centers must have the highest quality clinical and technical support available 
from the manufacturer. 
5. Function and duties of technical support in this clinical trial 
- 
Represents Oticon Medical during surgeries and cochlear implants by providing all 
necessary advice and support. 
- 
Support the audiologist or its representative in conducting the objective measures 
(impedance and ECAPs) in the OR. 
- 
Undertake eCAP and impedance measures in OR if there is nobody from the medical 
team dedicated for this task. 
- 
Supervise eCAP and impedance measure in clinic. 

 
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CLINICAL SUPPORT ROLE 
Neuro Zti cochlear implant-system Efficacy and Safety in Adult 
- 
Evaluate the external, internal part or accessories for a better subject management. 
- 
Provide expertise in all aspects of implant and troubleshooting techniques. 
- 
Provides on-call support as needed for surgeries, reprogramming, troubleshooting, and 
follow-up on all visits. 
- 
Support the audiologist or its representative in device fittings especially for the first one. 
The following fittings could be supervise by the clinical support at the request of the 
investigator site. 
- 
Troubleshoot by testing and reprogramming device integrity testing and communicate 
the results to the managing audiologist. 
6. Education support in this clinical trial 
- 
Educates and train surgeon and hospital team (hearing aid specialist, speech-
pathologist, technician or audiologist) on technical matters relating to the cochlear 
implant system by conducting or coordinating: 
o One on one training session 
o In-service education programs 
- 
Help audiologist in patient fittings 
- 
Provide advice in and guidance to audiologist 
7. What the clinical support Does Not Do in this clinical trial 
- 
Will never been alone with the patient, the patient is supported by the medical team 
involved in this clinical trial. 
- 
Does not provides audiological assessment of patient 
- 
Does not provides “switch-on” device programming of the recipient following surgery. 
The audiologist switch-on the device and the clinical support advice and guide the 
audiologist in the fittings. 
- 
Does not provides routine ongoing device programming 
- 
Does not carry out evaluation of candidate outcomes 
- 
Does not undertake eCAP or impedance measures in clinic 
- 
Does not interfere in management of recipient device repairs 
- 
Does not interfere in management of recipient device accessories 
- 
Does not interfere in equipment and products required for the device implant 
- 
Does not provide recommendation about cochlear implant candidacy following 
assessment 
 
 

 
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PATIENT HINT PERFORMANCE 
Neuro Zti cochlear implant-system Efficacy and Safety in Adult 
Appendix 7: PATIENT HINT PERFORMANCE 
 
Preoperative evaluation 
a) If the patient has a poor speech understanding in HINT-Q during the training (i.e. score 
of 0), it is recommended to performed the entire training list.  
If the patient have a poor speech understanding in HINT-Q during the evaluation with 
a score of 0 words correctly repeated on the first six sentences: 
- 
Stop the evaluation in Quiet  
- 
Don’t conduct the evaluation in Noise 
- 
Record in the eCRF:  
o HINT-Q raw score =0 , % correct = 0 and percent correct=0 for the 2 lists 
o HINT-N raw score =0 , % correct = 0 and percent correct=0 for the 2 lists 
 
 
b) If the patient has a proper speech understanding in HINT-Q during the training, AND, 
the patient has a poor speech understanding during the evaluation with a score of 0 
words correctly repeated on six consecutive sentences: 
- 
Give a short break to the patient, and when it’s time, carry on with the evaluation  
- 
If the score still remains at 0 in the next 3 consecutive sentences, stop the 
evaluation. 
- 
Record in the eCRF the score of 0 in the respective input fields 
 
Postoperative evaluation 
 
Please, see above

 
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POST-OPERATIVE ECAP MEASUREMENT 
Neuro Zti cochlear implant-system Efficacy and Safety in Adult 
Appendix 8: POST-OPERATIVE ECAP MEASUREMENT 
 
When performing post-operative ECAP measurements, follow the 
guidelines/recommendations below: 
 
As a minimum, perform ECAP on one electrode (electrode 18) 
If possible, perform ECAP on four electrodes (electrode 3, 8, 13, 18) 
 
 
 
Neuro ECAP 
 
The Neuro ECAP 1.0® function allows to measure the electrophysiological responses of the 
auditory nerve by scanning with a range of Amplitude, for a fixed stimulation duration 
several electrodes. 
 
Two modes are available: 
Basic: where you can select the number of electrode to stimulate, the repetition frequency 
and the ECAP parameters (Minimum: Minimum Amplitude of the range tested, Maximum: 
Maximum Amplitude and Duration: Pulse Duration) 
Advanced: where you can also choose the increment in the range of Amplitude tested, the 
stimulation and collection electrodes and the Number of repetitions for the measures.  
 
Attention: Before setting the ECAP parameters during a post op. measurement, be sure to 
be lower than the C level of the patient.  
 
If C levels are below 30 µs 
You should respect the following rule: C levels (perceived by the patient) are defined by an 
amplitude A and a duration T. 
Then post op ECAP should have the following parameters: 
Min 10  
Max= A+5 
Increment=2 
Duration= T-10 µs 
 
For example, if patient is describing a sound as comfortable in a fitting window with an 
amplitude A of 20 and C of 25µs, then ECAP research on the corresponding electrode should 
be the following graph: 
 
 
 

 
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POST-OPERATIVE ECAP MEASUREMENT 
Neuro Zti cochlear implant-system Efficacy and Safety in Adult 
Depending on the patient perception, it is possible to go higher than those values or to stop 
the stimulation prior to that if auditory perception is too loud. 
 
 
 
If C levels are above 30 µs 
You should respect the following rule: C levels (perceived by the patient) are defined by an 
amplitude A and a duration T. 
Then post op ECAP should have the following parameters: 
Min 10  
Max= T - 5 
Increment=3 
Duration= A 
 
Note : Max should not exceed 70 CU. 
 
For example, , if patient is describing a sound as comfortable on electrode 18 in a fitting 
window with an amplitude A of 23 and C of 45µs, then ECAP research parameters on the 
corresponding electrode should be the following graph: 
 
 
 
 
 
On a general point of view, this post op ECAP protocol is meant to provide 
recommendations, the audiologist has a crucial role in the post op ECAP recording procedure 
as if the patient is describing a loud auditory sensation and the measurement is still running, 
then it is important to stop the recording to prevent the patient from receiving a too loud 
auditory sensation.  
On the other side, if the patient is perceiving an auditory sensation that is considered as soft 
even at the MAX value, then the audiologist could decide to increase the MAX value.

 
Page 105 of 115 
 
CALIBRATION CONSIDERATIONS 
Neuro Zti cochlear implant-system Efficacy and Safety in Adult 
Appendix 9: Calibration considerations  
0. Purpose  
This document discusses the calibration procedure for audiological assessments, taking into 
consideration audiological guidelines, as well as speech tests assessment tools calibration 
possibilities. 
1. Scope  
This document applies to the clinical trial which will be conducted in Canada and Denmark to 
support the PMA-FDA submission. 
2. References 
American National Standard Specification for Sound Level Meters. ANSI S1.4-1983 
(R2006)/ANSI S1.4a-1985 (R2006), American National Standards Institute. 
Firszt, J. B., & Holden, L. K., Skinner, W., Tobey, E., Peterson, A., & Gaggl, W., et al. (2004). 
Recognition of speech presented at soft to loud levels by adult cochlear implant recipients of 
three cochlear implant systems. Ear Hear, 25(4), 375-87. 
HINT Pro 7.2 Audiometric system Operating instructions, Bio-logics Systems Corp. 
IEC 61672-1:2013 Electroacoustics - Sound level meters - Part 1: Specifications. IEC. 2013 
Raman G, Lee J, Chung Met al., authors; Sen S, editor. Effectiveness of Cochlear Implants in 
Adults with Sensorineural Hearing Loss. Rockville (MD): Agency for Healthcare Research and 
Quality (US); 2011 Jun 17. Available from: https://www.ncbi.nlm.nih.gov/books/NBK285762/   
Westhorp Sue, “Decibel scales in audiology.” BATOD Magazine November 2009: pages 11- 12. 
Web. 
URL: 
http://www.batod.org.uk/content/resources/audiology/refreshers/general/G3-
decibels.pdf  
Zwolan, T., Thomas, E. Contemporary Protocols for Evaluating Cochlear Implant Candidacy of 
Children. Perspectives on Hearing and Hearing Disorders in Childhood 19(1):4-13 · March 2009 
DOI: 10.1044/hhdc19.1.4 
3. Abbreviations 
dB SPL: Decibel Sound Pressure Level 
dBA: Decibel with A-weighted correction 
HINT: Hearing In Noise Test 
4. Recommendations and guidelines 
In the clinical protocol “Neuro Zti cochlear implant-system Efficacy and Safety in Adult”, efficacy 
is assessed using HINT sentences tests presented at 60dB SPL. This presentation level has been 

 
Page 106 of 115 
CALIBRATION CONSIDERATIONS 
Neuro Zti cochlear implant-system Efficacy and Safety in Adult 
chosen in accordance with previous literature reporting HINT results in adult and children with 
cochlear implant, where presentation levels were expressed in dB SPL (e.g. Firszt et al., 2004; 
Zwolan & Thomas, 2009), and it is also consistent with American technology assessment report 
on the effectiveness of cochlear implants in adults (Raman et. al., 2011). Moreover, 60dB SPL 
is also a presentation level chosen for cochlear implant candidacy preoperative testing (Firszt 
et al., 2004). 
HINT sentences in quiet at 60 dB SPL is therefore a relevant speech test to assess cochlear 
implant effectiveness, with comparison of preoperative and postoperative scores. 
5. Calibration of speech test software tool in dBA 
HINT speech tests are conducted with the help of a dedicated software that facilitates 
sentences presentation at controlled level and recording of patient’s responses. Depending on 
language, either HINT Pro software of an in-house replica is used. 
These tools are calibrated in dBA, and do not use the dB SPL scale for presentation levels (see 
HINT Pro Operating Instructions). The dBA scale reflects the sensitivity of the human ear at 
different frequencies and it is used for measures of sound field assessments (Westhorp, 2009). 
The dBA scale is the most commonly used one among those defined in the International 
standard IEC 61672:2003 and in other standards on sound level measurement like ANSI 
standard ANSI S1.4-1981 (R2006). This scale is applied in order to account for the relative 
loudness perceived by the human ear, known to be less sensitive to lower frequencies.  
6. The dB SPL sound scale and differences with dBA 
The dB SPL scale refers to physical sound pressure level of the physical acoustic vibration. This 
scale is used to measure sound levels evoked by vibrations of physical objects (vibrating plates, 
membranes…), it is therefore widely used to describe microphones and loudspeakers acoustic 
characteristics. In auditory science, dB SPL may refer to hearing aid (Westhorp, 2009) or 
cochlear implant microphone characteristics as a measure of acoustic sensitivity of the device. 
The dB SPL and dBA scale therefore differ, especially at low frequencies. Below is a table 
(adapted from Westhorp, 2009) with conversion values at different frequencies. 
Converting dBA to dB SPL 
250 Hz 
500 Hz 
1000 Hz 
2000 Hz 
40000 Hz 
+5 dB 
-6 dB 
-3 dB 
-1 dB 
-1 dB 
 
According to this table, for a spectrally flat white noise, mean difference between dBA and dB 
SPL is -6dB on average across frequencies. For a speech signal, known to carry richer 
information at low frequencies, this difference will be less than 5dB on average across 
frequencies. 

 
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CALIBRATION CONSIDERATIONS 
Neuro Zti cochlear implant-system Efficacy and Safety in Adult 
7. Conclusions 
Audiological recommendations suggest 60 dB SPL presentation level for cochlear implant 
assessment of performance. Speech test tools do not offer the possibility to calibrate 
presentation levels in dB SPL but rather in dBA, consistently with sound perception of speech. 
The comparison of the 2 scales shows differences lower than 5dB for speech, and is considered 
limited.  
Therefore, for the study “Neuro Zti cochlear implant-system Efficacy and Safety in Adult”, all 
HINT tests are conducted at 60 dBA, in all participating centers in all countries, and for all 
evaluations. 
 
This document discusses the calibration procedure for audiological assessments, taking into 
consideration audiological guidelines, as well as speech tests assessment tools calibration 
possibilities. 

 
Page 108 of 115 
 
DEVICE LABELING 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
 
Appendix 10: DEVICE LABELING 
 
The packaging of device will be stamped with the self-adhesive label with the statement “ONLY FOR 
CLINICAL TRIAL”. 
 
Self-adhesive label  
 
 
Neuro Zti cochlear implant  
Outer pack & outer pack label 
 
 
 
 

 
Page 109 of 115 
DEVICE LABELING 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
 
 
 
Neuro One sound processor  
Outer pack & outer pack label 

 
Page 110 of 115 
DEVICE LABELING 
Neuro Zti cochlear implant-system Efficacy and Safety in Adults 
 
 
 

 
Page 111 of 115 
 
Appendix 11: DECLARATION OF HELSINKI 
 
 
 
 

 
Page 112 of 115 
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the: 29th WMA General 
Assembly, Tokyo, Japan, October 1975  
35th WMA General Assembly, Venice, Italy, October 1983  
41st WMA General Assembly, Hong Kong, September 1989  
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996  
52nd WMA General Assembly, Edinburgh, Scotland, October 2000  
53rd WMA General Assembly, Washington, DC, USA, October 2002 (Note of Clarification added) 55th WMA General 
Assembly, Tokyo, Japan, October 2004 (Note of Clarification added)  
59th WMA General Assembly, Seoul, Republic of Korea, October 2008  
64th WMA General Assembly, Fortaleza, Brazil, October 2013 
 
Preamble 
 
1. The World Medical Association (WMA) has developed the 
Declaration of Helsinki as a statement of ethical principles for 
medical research involving human subjects, including research 
on identifiable human material and data. 
 
The Declaration is intended to be read as a whole and each of its 
constituent paragraphs should be applied with consideration of 
all other relevant paragraphs.  
 
2. Consistent with the mandate of the WMA, the Declaration is 
addressed primarily to physicians. The WMA encourages others 
who are involved in medical research involving human subjects 
to adopt these principles 
 
General Principles  
 
3. The Declaration of Geneva of the WMA binds the physician 
with the words, “The health of my patient will be my first 
consideration,” and the International Code of Medical Ethics 
declares that, “A physician shall act in the patient's best interest 
when providing medical care.”  
 
4. It is the duty of the physician to promote and safeguard the 
health, well-being and rights of patients, including those who 
are involved in medical research. The physician's knowledge and 
conscience are dedicated to the fulfilment of this duty.  
 
5. Medical progress is based on research that ultimately must 
include studies involving human subjects.  
 
6. The primary purpose of medical research involving human 
subjects is to understand the causes, development and effects 
of diseases and improve preventive, diagnostic and therapeutic 
interventions (methods, procedures and treatments). Even the 
best proven interventions must be evaluated continually 
through research for their safety, effectiveness, efficiency, 
accessibility and quality 
 
7. Medical research is subject to ethical standards that promote 
and ensure respect for all human subjects and protect their 
health and rights. 
 
8. While the primary purpose of medical research is to generate 
new knowledge, this goal can never take precedence over the 
rights and interests of individual research subjects.  
 
9. It is the duty of physicians who are involved in medical 
research to protect the life, health, dignity, integrity, right to 
self-determination, privacy, and confidentiality of personal 
information of research subjects. The responsibility for the 
protection of research subjects must always rest with the 
physician or other health care professionals and never with the 
research subjects, even though they have given consent.  
 
10. Physicians must consider the ethical, legal and regulatory 
norms and standards for research involving human subjects in 
their own countries as well as applicable international norms 
and standards. No national or international ethical, legal or 
regulatory requirement should reduce or eliminate any of the 
protections for research subjects set forth in this Declaration. 
 
11. Medical research should be conducted in a manner that 
minimises possible harm to the environment.  
 
12. Medical research involving human subjects must be 
conducted only by individuals with the appropriate ethics and 
scientific education, training and qualifications. Research on 
patients or healthy volunteers requires the supervision of a 
competent and appropriately qualified physician or other health 
care professional. 
 
13. Groups that are underrepresented in medical research 
should be provided appropriate access to participation in 
research.  
 
14. Physicians who combine medical research with medical care 
should involve their patients in research only to the extent that 
this is justified by its potential preventive, diagnostic or 
therapeutic value and if the physician has good reason to believe 
that participation in the research study will not adversely affect 
the health of the patients who serve as research subjects.  
 
15. Appropriate compensation and treatment for subjects who 
are harmed as a result of participating in research must be 
ensured. 

 
Page 113 of 115 
Risks, Burdens and Benefits  
 
16. In medical practice and in medical research, most 
interventions involve risks and burdens.  
 
Medical research involving human subjects may only be 
conducted if the importance of the objective outweighs the risks 
and burdens to the research subjects.  
 
17. All medical research involving human subjects must be 
preceded by careful assessment of predictable risks and burdens 
to the individuals and groups involved in the research in 
comparison with foreseeable benefits to them and to other 
individuals or groups affected by the condition under 
investigation.  
 
Measures to minimise the risks must be implemented. The risks 
must be continuously monitored, assessed and documented by 
the researcher.  
 
18. Physicians may not be involved in a research study involving 
human subjects unless they are confident that the risks have 
been adequately assessed and can be satisfactorily managed.  
 
When the risks are found to outweigh the potential benefits or 
when there is conclusive proof of definitive outcomes, 
physicians must assess whether to continue, modify or 
immediately stop the study. Vulnerable Groups and Individuals  
 
19. Some groups and individuals are particularly vulnerable and 
may have an increased likelihood of being wronged or of 
incurring additional harm.  
 
All vulnerable groups and individuals should receive specifically 
considered protection.  
 
20. Medical research with a vulnerable group is only justified if 
the research is responsive to the health needs or priorities of 
this group and the research cannot be carried out in a 
nonvulnerable group. In addition, this group should stand to 
benefit from the knowledge, practices or interventions that 
result from the research. 
 
Scientific Requirements and Research Protocols  
 
21. Medical research involving human subjects must conform to 
generally accepted scientific principles, be based on a thorough 
knowledge of the scientific literature, other relevant sources of 
information, and adequate laboratory and, as appropriate, 
animal experimentation. The welfare of animals used for 
research must be respected. 
 22. The design and performance of each research study 
involving human subjects must be clearly described and justified 
in a research protocol. The protocol should contain a statement 
of the ethical considerations involved and should indicate how 
the principles in this Declaration have been addressed.  
 
The protocol should include information regarding funding, 
sponsors, institutional affiliations, potential conflicts of interest, 
incentives for subjects and information regarding provisions for 
treating and/or compensating subjects who are harmed as a 
consequence of participation in the research study.  
 
In clinical trials, the protocol must also describe appropriate 
arrangements for post-trial provisions. Research Ethics 
Committees  
 
23. The research protocol must be submitted for consideration, 
comment, guidance and approval to the concerned research 
ethics committee before the study begins. This committee must 
be transparent in its functioning, must be independent of the 
researcher, the sponsor and any other undue influence and 
must be duly qualified. It must take into consideration the laws 
and regulations of the country or countries in which the research 
is to be performed as well as applicable international norms and 
standards but these must not be allowed to reduce or eliminate 
any of the protections for research subjects set forth in this 
Declaration.  
 
The committee must have the right to monitor ongoing studies. 
The researcher must provide monitoring information to the 
committee, especially information about any serious adverse 
events. No amendment to the protocol may be made without 
consideration and approval by the committee. After the end of 
the study, the researchers must submit a final report to the 
committee containing a summary of the study’s findings and 
conclusions.  
 
Privacy and Confidentiality  
 
24. Every precaution must be taken to protect the privacy of 
research subjects and the confidentiality of their personal 
information.  
 
Informed Consent 25. Participation by individuals capable of 
giving informed consent as subjects in medical research must be 
voluntary. Although it may be appropriate to consult family 
members or community leaders, no individual capable of giving 
informed consent may be enrolled in a research study unless he 
or she freely agrees. 
 
 
 

 
Page 114 of 115 
26. In medical research involving human subjects capable of 
giving informed consent, each potential subject must be 
adequately informed of the aims, methods, sources of funding, 
any possible conflicts of interest, institutional affiliations of the 
researcher, the anticipated benefits and potential risks of the 
study and the discomfort it may entail, post-study provisions 
and any other relevant aspects of the study. The potential 
subject must be informed of the right to refuse to participate in 
the study or to withdraw consent to participate at any time 
without reprisal. Special attention should be given to the specific 
information needs of individual potential subjects as well as to 
the methods used to deliver the information.  
 
After ensuring that the potential subject has understood the 
information, the physician or another appropriately qualified 
individual must then seek the potential subject’s freely-given 
informed consent, preferably in writing. If the consent cannot 
be expressed in writing, the non-written consent must be 
formally documented and witnessed.  
 
All medical research subjects should be given the option of being 
informed about the general outcome and results of the study.  
 
27. When seeking informed consent for participation in a 
research study the physician must be particularly cautious if the 
potential subject is in a dependent relationship with the 
physician or may consent under duress. In such situations the 
informed consent must be sought by an appropriately qualified 
individual who is completely independent of this relationship.  
 
28. For a potential research subject who is incapable of giving 
informed consent, the physician must seek informed consent 
from the legally authorised representative. These individuals 
must not be included in a research study that has no likelihood 
of benefit for them unless it is intended to promote the health 
of the group represented by the potential subject, the research 
cannot instead be performed with persons capable of providing 
informed consent, and the research entails only minimal risk and 
minimal burden. 
  
29. When a potential research subject who is deemed incapable 
of giving informed consent is able to give assent to decisions 
about participation in research, the physician must seek that 
assent in addition to the consent of the legally authorised 
representative. The potential subject’s dissent should be 
respected. 
 
30. Research involving subjects who are physically or mentally 
incapable of giving consent, for example, unconscious patients, 
may be done only if the physical or mental condition that 
prevents giving informed consent is a necessary characteristic of 
the research group. In such circumstances the physician must 
seek 
informed 
consent 
from 
the 
legally 
authorised 
representative.  
If no such representative is available and if the research cannot 
be delayed, the study may proceed without informed consent 
provided that the specific reasons for involving subjects with a 
condition that renders them unable to give informed consent 
have been stated in the research protocol and the study has 
been approved by a research ethics committee. Consent to 
remain in the research must be obtained as soon as possible 
from the subject or a legally authorised representative. 
 
31. The physician must fully inform the patient which aspects of 
their care are related to the research. The refusal of a patient to 
participate in a study or the patient’s decision to withdraw from 
the study must never adversely affect the patient-physician 
relationship.  
 
32. For medical research using identifiable human material or 
data, such as research on material or data contained in biobanks 
or similar repositories, physicians must seek informed consent 
for its collection, storage and/or reuse. There may be 
exceptional situations where consent would be impossible or 
impracticable to obtain for such research. In such situations the 
research may be done only after consideration and approval of 
a research ethics committee.  
 
Use of Placebo  
 
33. The benefits, risks, burdens and effectiveness of a new 
intervention must be tested against those of the best proven 
intervention(s), except in the following circumstances:  
 
Where no proven intervention exists, the use of placebo, or no 
intervention, is acceptable; or  
 
Where for compelling and scientifically sound methodological 
reasons the use of any intervention less effective than the best 
proven one, the use of placebo, or no intervention is necessary 
to determine the efficacy or safety of an intervention  
 
and the patients who receive any intervention less effective than 
the best proven one, placebo, or no intervention will not be 
subject to additional risks of serious or irreversible harm as a 
result of not receiving the best proven intervention.  
 
Extreme care must be taken to avoid abuse of this option.  
 
Post-Trial Provisions  
 
34. In advance of a clinical trial, sponsors, researchers and host 
country governments should make provisions for post-trial 
access for all participants who still need an intervention 
identified as beneficial in the trial. This information must also be 
disclosed to participants during the informed consent process.  
 
 

 
Page 115 of 115 
Research Registration and Publication and Dissemination of 
Results  
 
35. Every research study involving human subjects must be 
registered in a publicly accessible database before recruitment 
of the first subject. 
 
36. Researchers, authors, sponsors, editors and publishers all 
have ethical obligations with regard to the publication and 
dissemination of the results of research. Researchers have a 
duty to make publicly available the results of their research on 
human subjects and are accountable for the completeness and 
accuracy of their reports. All parties should adhere to accepted 
guidelines for ethical reporting. Negative and inconclusive as 
well as positive results must be published or otherwise made 
publicly available. Sources of funding, institutional affiliations 
and conflicts of interest must be declared in the publication. 
Reports of research not in accordance with the principles of this 
Declaration should not be accepted for publication. 
Unproven Interventions in Clinical Practice  
 
37. In the treatment of an individual patient, where proven 
interventions do not exist or other known interventions have 
been ineffective, the physician, after seeking expert advice, with 
informed consent from the patient or a legally authorised 
representative, may use an unproven intervention if in the 
physician's judgement it offers hope of saving life, re-
establishing health or alleviating suffering. This intervention 
should subsequently be made the object of research, designed 
to evaluate its safety and efficacy. In all cases, new information 
must be recorded and, where appropriate, made publicly 
available