A Feasibility, Prospective, Repeated-measures Investigation to Investigate Innovations in Sound Processing in Adult and Paediatric Recipients Implanted With CE Approved Nucleus Cochlear Implants: an Umbrella Investigation.
Phase: NA
Conditions: Hearing Loss
Sponsor: Cochlear

 
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Official Title: A feasibility, prospective, repeated-measures investigation 
to investigate innovations in sound processing in adult and paediatric 
recipients implanted with CE approved Nucleus cochlear implants: an 
umbrella investigation 
 
NCT Number: NCT05476328 
 
Document Date: 03 June 2022 
 

 
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Clinical Investigation Plan 
 
Investigation Title: A feasibility, prospective, repeated-measures 
investigation to investigate innovations in sound processing in adult and 
paediatric recipients implanted with CE approved Nucleus cochlear 
implants: an umbrella investigation. 
 
Short Title: 
Sound Processing 
CIP Number: 
AI5762 
Date:  
Refer to system version control 
Sponsor 
Cochlear Limited 
1 University Avenue  
Macquarie University NSW 2109 
Australia 
Phone: +61 294 28 65 55 
 
This clinical investigation shall be conducted in accordance with ethical principles that have their 
origin in the Declaration of Helsinki, International Standard ISO 14155 Clinical investigation of 
medical devices for human subjects - Good Clinical Practice, and any regional or national 
regulations, as applicable. 
 
Confidential Information 
The information contained in this document is confidential and should not be copied or distributed to persons not involved 
in the conduct or oversight of the clinical investigation 
 

 
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Manufacturer 
Cochlear Limited 
1 University Avenue 
Macquarie University NSW 2109 
Australia 
Phone: +61 294 28 65 55  
Sponsor Organisations 
 
Cochlear Limited 
1 University Avenue  
Macquarie University NSW 2109 
Australia 
Phone: +61 294 28 65 55 
Coordinating Investigator 
 
 
 
 
 
 
 
Clinical Research Organisation 
Belgium: 
TRIUM Clinical Consulting 
Baron Opsomerlaan 32 
2500 Lier, Belgium 
 
Australia: 
Avania Pty Limited 
13/76 Reserve Road,  
Artarmon NSW 2064  
Safety Contact 
 
CLTD-SafetyMonitor@cochlear.com 
A complete list of participating Principal Investigators’ names, titles and addresses, and the names 
and addresses of participating institutions (sites) will be maintained by the Sponsor and will be 
provided as a separate Principal Investigator List. The definitive Principal Investigator list will be 
provided in the Clinical Investigation Report. 
 
 

 
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INVESTIGATOR AGREEMENT 
 
Coordinating Investigator Approval and Declaration 
By my signature below, I confirm my review and approval of this Clinical Investigational Plan (CIP). 
I also confirm that I will strictly adhere to the requirements therein and undertake to ensure that all 
staff with delegated responsibilities in the conduct of this CIP have read, understood and will strictly 
adhere to the requirements therein. This CIP will not be implemented without prior written approval 
from the Ethics Committee, any applicable National Competent Authorities, and the Sponsor. If 
amendments to this plan become necessary, written approval by the Ethics Committee and any 
applicable National Competent Authorities will be obtained before the changes are clinically 
implemented per the amendment, except under emergency circumstances to protect the rights, 
safety, and well-being of subjects. 
Name 
Title 
 
Coordinating Investigator 
Signature 
Date 
 
 
 
Principal Investigator Declaration 
By my signature below, I confirm that I have read, understood and will strictly adhere to the 
requirements therein. I undertake to ensure that all staff with delegated responsibilities in the conduct 
of this CIP have also read, understood and will strictly adhere to the requirements therein. This CIP 
will not be implemented without prior written approval from the Ethics Committee, any applicable 
National Competent Authorities, and the Sponsor. If amendments to this plan become necessary, 
written approval by the Ethics Committee and any applicable National Competent Authorities will be 
obtained before the changes are clinically implemented per the amendment, except under 
emergency circumstances to protect the rights, safety, and well-being of subjects. 
Name 
Title 
 
Principal Investigator 
Site Name 
Site Address 
 
 
Signature 
Date 
 
 
 
 

 
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TABLE OF CONTENTS 
1 
Definitions and Abbreviations ......................................................................................................... 8 
2 
Clinical Investigation Synopsis ........................................................................................................ 9 
3 
Schedule of events ....................................................................................................................... 10 
4 
Background Information and Rationale ........................................................................................ 11 
4.1 
Introduction ......................................................................................................................... 11 
4.2 
Findings of Previous Nonclinical and Clinical Studies ........................................................ 13 
4.2.1 
Nonclinical Data .................................................................................................... 13 
4.2.2 
Clinical Data .......................................................................................................... 14 
4.3 
Study Rationale .................................................................................................................. 14 
5 
Medical Device Information ........................................................................................................... 14 
5.1 
Identity and Description of the Investigational Medical Device (IMD) ................................ 14 
5.2 
Identity and Description of the Comparator ........................................................................ 18 
5.3 
Accessory Device Requirements ........................................................................................ 18 
6 
Objectives ..................................................................................................................................... 18 
6.1 
Primary Objective ............................................................................................................... 18 
6.2 
Secondary Objectives ......................................................................................................... 18 
6.3 
Exploratory Objective .......................................................................................................... 19 
7 
Design of the Clinical Investigation ............................................................................................... 19 
7.1 
General ............................................................................................................................... 19 
7.1.1 
Design Rationale ................................................................................................... 20 
7.2 
Subjects .............................................................................................................................. 21 
7.2.1 
Inclusion Criteria ................................................................................................... 21 
7.2.2 
Exclusion Criteria .................................................................................................. 21 
7.2.3 
Number of Subjects Required ............................................................................... 22 
7.2.4 
Vulnerable Populations ......................................................................................... 22 
7.2.5 
Recruitment and Study Duration ........................................................................... 22 
7.2.6 
Criteria for Subject Withdrawal ............................................................................. 23 
7.2.7 
Randomisation Procedures .................................................................................. 24 
7.2.8 
Post-investigation Medical Care ........................................................................... 24 
7.3 
Performance Evaluations and Procedures ......................................................................... 24 
7.4 
Safety Evaluations and Procedures ................................................................................... 27 
7.4.1 
Concomitant Medication and Therapies ............................................................... 27 
7.5 
Equipment Used for Evaluation of Performance and Safety .............................................. 28 
7.6 
Sponsor Role in Conduct of the Clinical Investigation ........................................................ 28 
8 
Risks and Benefits of the Investigational medical device and Clinical Investigation .................... 28 

 
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8.1 
Anticipated Clinical Benefits ............................................................................................... 28 
8.2 
Anticipated Adverse Device Effects .................................................................................... 28 
8.3 
Risks Associated with Participation in the Clinical Investigation ........................................ 30 
8.4 
Risk Mitigation .................................................................................................................... 30 
8.5 
Risk-to-Benefit Rationale .................................................................................................... 30 
9 
Statistical Considerations .............................................................................................................. 31 
9.1 
General Considerations ...................................................................................................... 31 
9.2 
Endpoints ............................................................................................................................ 31 
9.2.1 
Primary Endpoints ................................................................................................. 31 
9.2.2 
Secondary Endpoints ............................................................................................ 31 
9.2.3 
Exploratory Endpoints ........................................................................................... 31 
9.3 
Hypotheses ......................................................................................................................... 31 
9.3.1 
Primary Hypotheses .............................................................................................. 31 
9.3.2 
Secondary Hypotheses ......................................................................................... 31 
9.3.3 
Exploratory Hypotheses ........................................................................................ 31 
9.4 
Sample Size Determination ................................................................................................ 32 
9.5 
Analysis Populations ........................................................................................................... 32 
9.6 
Primary Endpoint Analyses................................................................................................. 32 
9.7 
Secondary Endpoint Analyses ............................................................................................ 32 
9.8 
Exploratory Endpoint Analyses ........................................................................................... 32 
9.9 
Safety Analyses .................................................................................................................. 32 
9.10 Interim Analyses ................................................................................................................. 32 
10 Informed Consent Process ........................................................................................................... 32 
11 Adverse Events and Device Deficiencies ..................................................................................... 33 
11.1 Definitions ........................................................................................................................... 33 
11.1.1 
Adverse Event ...................................................................................................... 33 
11.1.2 
Adverse Device Effect .......................................................................................... 33 
11.1.3 
Serious Adverse Event ......................................................................................... 33 
11.1.4 
Serious Adverse Device Effect ............................................................................. 34 
11.1.5 
Unanticipated Serious Adverse Device Effect ...................................................... 34 
11.1.6 
Adverse Events of Special Interest ....................................................................... 34 
11.1.7 
Device Deficiency ................................................................................................. 34 
11.2 Recording and Handling of Adverse Events ....................................................................... 34 
11.2.1 
Assessment of Severity ........................................................................................ 35 
11.2.2 
Assessment of Causality ...................................................................................... 35 
11.2.3 
Assessment of Seriousness ................................................................................. 36 

 
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11.2.4 
Assessment of Expectedness .............................................................................. 37 
11.3 Recording and Handling of Device Deficiencies................................................................. 37 
11.4 Reporting Responsibilities .................................................................................................. 37 
11.4.1 
Investigator Reporting of Serious Adverse Events ............................................... 37 
11.4.2 
Sponsor Notification of Events ............................................................................. 38 
11.5 Independent Data Monitoring Committee ........................................................................... 38 
12 Device Accountability .................................................................................................................... 39 
13 Deviations from the Clinical Investigation Plan ............................................................................. 39 
14 Data Management ........................................................................................................................ 39 
15 Confidentiality ................................................................................................................................ 40 
16 Ethics Committee and Regulatory Authority Approval .................................................................. 41 
17 Suspension or Premature Termination ......................................................................................... 41 
18 Amendments to the Clinical Investigation Plan ............................................................................. 42 
19 Record Keeping and Retention ..................................................................................................... 42 
20 Publication Policy .......................................................................................................................... 42 
21 Statements of compliance ............................................................................................................. 43 
22 Quality Control and Assurance ..................................................................................................... 43 
22.1 Monitoring ........................................................................................................................... 43 
22.2 Audits .................................................................................................................................. 43 
23 Trademarks and Copyright ........................................................................................................... 43 
24 References .................................................................................................................................... 44 
25 Change History ............................................................................................................................. 44 
 
 
 

 
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4 BACKGROUND INFORMATION AND RATIONALE 
4.1 
Introduction 
Cochlear implants (CI) are electronic devices for adults and children who do not receive adequate 
benefit from conventional hearing aids. The cochlear implant system consists of an internal implant 
and an externally worn sound processor (SP). The microphone of the sound processor picks up the 
sound and turns it into a digital encoded signal. The sound processor transmits this digitally coded 
signal through the coil to the implant. The implant converts this signal into electrical pulses and sends 
them along the electrode array placed in the cochlea. The electrodes of the implant then stimulate the 
cochlea’s hearing nerve (Figure 1).  
 
Figure 1 Nucleus cochlear system: electrical hearing 
 
For those recipients who have severe to profound high frequency hearing loss but who maintain useful 
low frequency hearing in the implanted ear, acoustic hearing can be added to the electrical hearing 
path (electro-acoustic/Hybrid stimulation). An acoustic component is attached to the sound processor, 
thereby delivering acoustic amplification in a similar way to a conventional hearing aid (Figure 2).  
In case the recipient has residual hearing in the contralateral ear, a standard hearing aid can be used 
in the non-implanted ear. 
 
 
 
 

 
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Figure 2 Nucleus cochlear system with acoustic component: electro-acoustic hearing 
 
Programming of the sound processor is in general done by an expert clinician using clinical 
programming software. Clinicians also perform performance measurements to assist in the 
programming and management of the CI recipient.  
The way how the sound is encoded can have an influence on the hearing performance and the quality 
perception of the CI recipient. Therefore, adaptations to the sound coding and signal processing are 
made and new principles are developed. Different innovations can be identified: 
1) Hearing impaired listeners suffer from adverse conditions such as background noise, 
reverberation, and wind noise. Improving the hearing performance (objective and subjective) in 
those difficult situations can be achieved by for example developing and improving the single 
channel or multiple microphone noise reduction algorithms, minimizing the effect of 
reverberation, minimizing the effect of wind on the signal quality etc. This is generally called 
‘pre-processing’. 
 
2) The way we translate incoming acoustical sound to a series of electrical signals delivered to 
the cochlea is key to delivering the best possible outcomes. Improving the electrical coding can 
have an impact on the efficiency, the hearing performance and/or sound quality percept to the 
CI user.  These improvements can be achieved by changes to the temporal coding, the 
selectivity and/or spatial resolution, channel selection etc. This is generally called ‘electrical or 
sound coding’. 
 
3) Traditionally, CI coding algorithms were developed to improve the understanding of speech 
only. There is a growing interest in music performance. Although it is clear that music enjoyment 
is highly related to experience, practice and mind-set, specific sound coding strategies might 
also help to improve specific aspects of the signal in order to give recipients better enjoyment 
of music. 
 

 
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4) Traditionally, CI coding algorithms were developed to improve the understanding of speech 
only. There is a growing interest in listening effort. Specific sound coding strategies might also 
help to improve certain aspects of the signal in order to reduce listening effort. 
 
5) Gain models describe how we deal with intensity/loudness of auditory signals and how we ‘map’ 
the large dynamic range of available sounds on the smaller dynamic range of electrical hearing 
or impaired acoustical hearing. Using the right gain for each frequency ensures audibility, 
comfort and modulation sensitivity (these can be degraded by sounds being too soft or by 
clipping/distortion). In addition, using the wrong kind of gain/compression can cause co-
modulation which degrades speech understanding. Innovations in acoustical compression 
models, in the coding of loudness in the electrical domain etc. can increase the performance of 
the CI user. 
 
6) CI recipients can wear multiple systems and therefore synergy needs to be built between the 
contralateral system, i.e. bimodal or bilateral, and between the acoustic and electrical 
stimulation. Strategies developed specifically for bilateral and bimodal users, Hybrid users 
might improve localization, focussing on a specific talker in a multi-talker environment, 
improving the performance and the sound quality, etc. 
 
7) Sound processors become more and more complex. In order not to overload the recipients with 
options and buttons, the control of sound coding in the device needs to be made as simple as 
possible. This can be done by using e.g. environmental classifiers that analyse the incoming 
sound and decide which set of parameters or algorithms are best selected to have the best 
performance and sound quality percept for the CI user.  
 
8) Tinnitus is a condition that is significantly more prevalent in the hearing-impaired population. 
Many users of hearing implants notice significant improvement in their tinnitus after implantation 
but part of them still experience residual tinnitus that has a negative influence on their quality 
of life. A very small group actually experiences an increase in tinnitus after the implantation. It 
is possible to minimize the effect of tinnitus by using specific background sounds or stimulation 
patterns, but at this moment not much is known about which sounds are more effective and 
which sounds lead to better acceptance. 
 
The umbrella investigation will be conducted in different sub-studies to assess the incremental change 
of the software functionality and/or to assess the concept of a new sound coding or signal processing 
method. Each sub-study will be submitted separately with a sub-study specific Clinical Investigation 
Plan (CIP) and a sub-study specific Informed Consent Form (ICF). A status update will be reported 
yearly and a close-out report will be provided at the end of the study. For each sub-study a Clinical 
Investigation Report (CIR) will be delivered.  Since different methods will be tested, subjects may be 
recruited for multiple sub-studies or stages of the project. Each subject can only participate in one sub-
study at a time. This is further described in section 7. 
4.2 
Findings of Previous Nonclinical and Clinical Studies 
4.2.1 
Nonclinical Data 
Not applicable. 

 
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4.2.2 
Clinical Data 
The existing sound coding algorithms and signal processing methods are studied extensively, and 
many publications are available. Current literature on the sound processors is contained within the 
Investigator Brochures (IB) of the current commercially available sound processors.  
A detailed description of clinical data for the sub-study will be described in the sub-study specific 
documentation. 
4.3 
Study Rationale 
As adaptations to the sound coding and signal processing are made and new principles are developed 
as mentioned in section 4.1, it is essential to evaluate the benefit of new features in studies that are 
performed with a relevant group of human users (adults or paediatrics) that is, cochlear implant users 
(including electro-acoustic), either unilateral, bilateral and/or bimodal. The evaluation can be performed 
in the laboratory in an acute session or in real world environments with take-home device use to further 
validate their benefits. A sub-study specific rationale can be found in the sub-study specific 
documentation. 
5 MEDICAL DEVICE INFORMATION 
5.1 
Identity and Description of the Investigational Medical Device (IMD) 
As mentioned in section 4.1, a cochlear implant system consists of the internal implant and the 
externally worn sound processor. This system also contains a remote control unit or an application on 
a mobile device (e.g. Nucleus Smart App). The external hardware is programmed using fitting software 
which downloads the firmware on the sound processor. Different diagnostic and (re)habilitation 
applications are used to diagnose and optimize the performance and use of the cochlear implant 
system. 
The hardware and software of the current generation Nucleus cochlear implant system are shown in 
Figure 3 and Figure 4. It is expected that these components will evolve over the next 5 years. However, 
the basic architecture will remain unchanged.  
Essentially the following technological components are needed: 
1) The implantable receiver/stimulator is implanted in the mastoid with the electrode placed in the 
inner ear. In the hermetic titanium housing is a specialized electronics board that produces the 
electrical stimulation pattern that is delivered to the auditory nerve. The unit is specifically 
designed for stimulation of the auditory nerve (pulse strength, pulse waveform) and contains 
many in-built safety functions (capacitors blocking DC currents, current source strength 
limitations and continuous error checking. 
 
2) The sound processor is typically worn on the ear (i.e. behind-the-ear processor or BTE) or on 
the head (i.e. off-the-ear processor or OTE) and consists of an electronics board and a battery 
in a plastic housing. Its role is to capture the sound - typically from the in-built microphones but 
other inputs are supported as well – and to analyze the sound and calculate the corresponding 
electrical stimulation pulses and acoustic output (in case of electro-acoustic stimulation). These 
are sent as commands to the implantable receiver/stimulator through the wireless link. The 
hardware is designed in compliance with all applicable standards for optimal wearing comfort.  

 
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Figure 4 Software: Programming Software (Custom Sound), Nucleus Fitting Software (NFS) and 
electrophysiology software (CSEP)  
 
 
  
 
 
  
The Cochlear Device Interface is a layer between the fitting application and the Cochlear hardware 
systems (i.e. remote control, sound processor, implant, programming interface such as NFS or CS). 
The CDI driver acts as a server to the client applications and offers a (software) framework for 
programming the Nucleus cochlear implant system in a uniform way while providing run-time services. 
A screenshot of the CDI software is shown in Figure 5. 
Figure 5 Screenshot of Cochlear Device Interface (CDI) 
 
 
The Nucleus Implant Communicator or NIC is a set of libraries to be used by researchers for specifying 
or generating a sequence of stimuli that NIC will subsequently send to a recipient's implant, and/or 
making use of the implant's  telemetry capabilities, whether this is for ensuring compliance, measuring 
impedances, or performing Neural Response Telemetry (NRT) measurements (eCAPs). The set-up of 
the NIC system is shown in Figure 6. 
 
 
Figure 6 Set up of Nucleus Implant Communicator system (NIC), consisting of the NIC4 software on PC, 
Programming interface (Pod) and CP910 sound processor   

 
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The Speedgoat xPC is equipment employed to implement cochlear implant and hearing aid algorithms 
in real-time.  The equipment is comprised of both software and hardware. The xPC Speedgoat Target 
is an element within a larger system dubbed the ‘real-time system’.  Cochlear employs this system   to 
implement its signal path and novel algorithms in real-time for testing on the bench and with humans 
for research purposes.  The real-time or xPC system has been chosen as an engineering and clinical 
development tool primarily because of its strength as a rapid prototyping tool.  The system permits an 
engineer, or for that matter a clinician, to develop algorithms using a high-level visual language 
(Simulink).  These algorithms can then be rapidly compiled by the system into real-time code that is 
then run on the Target PC. The set-up of the hardware as well as a screenshot of the software is shown 
in Figure 7. 
Figure 7 Speedgoat xPC 
 
 
Statements of conformity for the investigational software and firmware will be provided in the sub-study 
documentation.  

 
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To evaluate the benefit of new features, it is essential that studies are performed with a relevant group 
of human users (adults or paediatrics) i.e. cochlear implant users (including electro-acoustic), either 
unilateral, bilateral and bimodal. The evaluation can be performed in the laboratory in an acute session 
or in real world environments with take-home device use to further validate their benefits. Subjects will 
use the IMD for the duration of the sub-study only, and that device will be removed when each sub-
study is concluded. 
The specific manufacturer, build or version of each investigational component (software, firmware or 
application), will be logged and described in the study documentation of each sub-study. Statements 
of conformity for the investigational software and firmware will be provided in the sub-study 
documentation. For each investigational component there will be a test plan, test report and release 
report. The IMD and/or the packaging for the device will be clearly labelled to identify it as exclusively 
for use in a clinical investigation, as mentioned in section 12. Traceability of the build number will be 
documented in the tracking forms such as the Sponsor Device Tracking Form (1295388) and Software 
Tracking Form (1302326), as mentioned in section 12. The investigator will be trained on using the 
IMD. This training will be logged in a training log.   
The investigational devices will not be in contact with body fluid or tissue. 
5.2 
Identity and Description of the Comparator 
New and improved algorithms will be investigated by using a new build of the existing CSS and NFS 
software and by other investigational tools such as the CDI, NIC and xPC. These new/improved 
algorithms will be compared to the commercially available algorithms where available.  
A detailed description of the comparator will be described in the sub-study specific documentation. 
5.3 
Accessory Device Requirements 
Not applicable. 
6 OBJECTIVES 
The following objectives apply for umbrella study AI5762. A sub-study addresses aspects of one or 
more of these objectives and will be specified in the study documentation of that specific sub-study.  
6.1 
Primary Objective  
• 
To evaluate clinical outcomes using novel pre-processing and sound coding strategies.  
6.2 
Secondary Objectives 
• 
To evaluate effectiveness of novel sound coding paradigms aiming at optimizing the 
conversion from acoustical to electrical auditory stimuli in terms of speech intelligibility, sound 
quality, temporal pitch perception, music appreciation, listening effort, spectral resolution and 
dynamic range. 
• 
To evaluate effectiveness of gain management algorithms aimed at improving signal quality 
and speech intelligibility through modifying coding of loudness. 

 
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• 
To evaluate sound processing innovations aimed at improving the synergetic use of two 
devices (bilateral use) in terms of sound quality, speech intelligibility and localization abilities. 
• 
To evaluate sound processing innovations aimed at improving the synergetic use of combined 
auditory and electrical stimulation (bimodal and hybrid use) in terms of sound quality, speech 
intelligibility, localization abilities and gain management. 
• 
To evaluate automation technologies in signal processing that aim to minimize the need for 
the user to manually adjust device settings when listening in different environments. 
• 
To evaluate the effect of new coding algorithms and signal processing on the subjective 
experience of tinnitus for the user. 
6.3 
Exploratory Objective 
There are no exploratory objectives stated in the umbrella investigation, however, will be specified in 
the sub-study documentation if appropriate. 
 
7 DESIGN OF THE CLINICAL INVESTIGATION 
7.1 
General 
This is a feasibility, prospective with sequential enrolment, multicenter, clinical investigation in adults 
and paediatrics with a CE approved Nucleus cochlear implant.  
Subjects older than 5 years will be included. Subjects will be screened and up to 120 eligible subjects 
will be recruited in the clinical investigation.  
Subjects will attend scheduled study visits over a period up to 5 years in different sub-studies as 
described in the sub-study documentation.  
A clinical setting can consist of therapeutic elements and evaluations. Subjects will be assessed with 
the commercially available Nucleus sound processor or via the xPC, NIC, etc. if required. Acute testing 
will be done where possible. Take home use will be applied when learning effects may play a significant 
role and to evaluate the acceptance of the new or improved sound coding algorithm or signal 
processing, in as many listening environments as possible. The subject might also be asked to 
complete questionnaires, to perform at-home tests etc. during this take home use and/or at the clinical 
visits.  The time for a clinical visit will be limited to a maximum of 4 hours. The time in between clinical 
visits will vary with typical spacing of between 0 (acute) to 4 weeks. 
The description of the measures taken to minimize bias, such as randomization and blinding, will be 
described in each sub-study specific documentation. Also, the sub-study specific method and timing 
for assessing, recording and analyzing variables, the equipment used, the monitoring maintenance 
and calibration will be described in the sub-study specific documentation. 
Section 7.3 describes the procedure used in the umbrella investigation. 
Safety will be assessed by recording and summarizing all Adverse events (AEs)/Adverse Device 
Effects (ADEs) and Device Deficiencies (DDs). Sub-study specific endpoints and details such as 
specific measurements and time points for assessment of each measure, will be described in each 

 
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sub-study specific study documentation. No Independent Data Monitoring Committee (IDMC) will be 
used for this clinical investigation. Analyses, including interim analyses where required, will be specified 
in the sub-study CIP. All subjects will have an End-of-Study visit at the time they complete each sub-
study and the umbrella study. 
The specific study design of each sub-study will be described in the study documentation of the sub-
study. 
7.1.1 
Design Rationale 
The goals of this umbrella investigation are  
• 
to measure hearing outcomes to assess performance and/or 
• 
to achieve higher convenience for implant users and hearing care professionals.  
The outcomes of the study will guide Cochlear to select features for inclusion in future Nucleus cochlear 
implant systems and/or future models of care.   
Multi-channel cochlear implants have been highly successful in restoring speech understanding to 
individuals with severe-to-profound hearing loss. Optimal programs are those programs or parameter 
settings that result in an optimal hearing outcome with the cochlear implant. Individualized device fitting 
is provided by experienced clinicians. They choose between a wide variety of program parameters and 
options, followed by measuring the lowest stimulation level at which the recipient is able to detect sound 
through the cochlear implant (threshold, or T-level) and also the highest stimulation level that provides 
a comfortable percept (comfort, or C-level) to the recipient. Such measurements are obtained on 
electrodes across the electrode array. Upon these programs, features such as noise reduction 
algorithm, front end algorithms (such as ASC, Whisper, Beam, Zoom) and concepts such as 
environmental classifier and wind noise reduction can be added. Performance measurements (e.g. 
audiological tests, questionnaires quality ratings etc.) and/or objective measurements (e.g. 
datalogging, impedances, neural response telemetry etc.) are also collected to assist in programming 
and to monitor the impact of the different algorithms.  
Comparison of algorithms is typically conducted using repeated-measures design, in which each 
subject is acting as his/her own control, which accommodates the heterogeneity across the population.  
The baseline condition will be compared to one or more of the investigational conditions.   
As mentioned in section 4.1, this umbrella investigation will be conducted in different sub-studies to 
assess the incremental change of the software/firmware functionality and/or to access the concept of 
a new sound coding algorithm or signal processing. Each of the sub-studies will be looking at a 
particular approach to address the objectives of the overall umbrella investigation AI5762. 
Since different methods will be tested, subjects may be recruited for multiple sub-studies, during the 
full duration of the umbrella investigation. Each subject can only participate in one sub-study at a time.  
CI recipients from the age of 5 years upwards can participate in the study, as long as they meet the 
inclusion- and exclusion criteria as described in section 7.2. Children are included in the study as they 
are a specific group of CI users, requiring adapted fitting, having a different life style and therefore 

 
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having different needs compared to adult CI users. The procedure for recruiting subjects is further 
described in section 7.2.5. 
Where possible, each sub-study will be blinded (i.e. information is concealed from the recipient) or 
double-blinded (i.e. information is concealed from the recipient and the investigator) and randomized 
(i.e. the order of testing).  
Given that the sub-studies are feasibility studies, there is no need to statistically power the study. 
However, where possible sample size calculation will be made to enable assessment of non-inferiority 
or superiority. This is described in section 9.    
7.2 
Subjects 
Written, informed consent must be obtained from the subject or subject’s legally authorized 
representative before any study procedures are initiated. 
Eligibility of subjects shall be supported by medical, demographics and audiological information that 
confirm the subject inclusion as stated in section 7.2.1. 
Up to 120 adult and paediatric CI recipients older than 5 years can participate into the umbrella study. 
Each sub-study will specify their own subject population and indications for which the IMD is intended, 
within the population and indications of the umbrella investigation. Paediatric subjects will be recruited 
in Belgium only. 
7.2.1 
Inclusion Criteria 
Subjects must meet all the inclusion criteria described below to be eligible for this clinical investigation. 
• 
Users of a CE approved Nucleus cochlear implant, resulting in open set speech 
understanding. 
• 
Paediatrics: Older than 5 years and <18 years when entering the study (Belgium only) 
or 
• 
Adults: ≥18 years when entering the study (Belgium and Australia) 
• 
Subject/legally designated representative is fluent speaker in the language used for 
assessments. 
• 
Willing and able to provide written informed consent (for paediatric populations this criterion 
applies to the parent/legally designated representative). 
7.2.2 
Exclusion Criteria 
Subjects who meet any of the exclusion criteria described below will not be eligible for this clinical 
investigation. 
• 
Unable or unwilling to comply with the requirements of the clinical investigation as determined 
by the investigator. 
• 
Additional health factors, known to the investigator, that would prevent or restrict participation 
in the audiological evaluations. 

 
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• 
Investigator site personnel directly affiliated with this study and/or their immediate families; 
immediate family is defined as a spouse, parent, child, or sibling. 
• 
Cochlear employees or employees of Contract Research Organisations or contractors 
engaged by Cochlear for the purposes of this investigation. 
• 
Currently participating, or participated within the last 30 days, in another interventional clinical 
investigation/trial involving an investigational drug or device. 
 
7.2.3 
Number of Subjects Required 
Up to 120 subjects will be included in this umbrella study. Most subjects will be unilateral adult users 
and additionally bilateral and bimodal users will be recruited. Also, paediatric subjects from the age of 
5 years upwards (see section 7.2.4) could be recruited, but only when strictly required by a specific 
sub-study. 
This umbrella study explores the feasibility phase of new or improved sound coding algorithms and 
signal processing. No formal power calculations are performed on the level of the umbrella 
investigation. In case a sample size calculation is done for a specific sub-study, the total number of 
subjects to be recruited in the sub-study as well as the expected dropout rate will be described in the 
study documentation of the sub-study. 
7.2.4 
Vulnerable Populations 
As described in previous sections, this umbrella study will evaluate the effectiveness of new or 
improved sound coding algorithm and signal processing. Each method/concept will be evaluated in a 
sub-study. Depending on the specific aspect that will be tested, children might be involved from the 
age of 5 years upwards. The sub-study specific information will be given to the parents/ legally 
designated representative of the subject and will be adapted as well towards the cognitive level of the 
subject. The Informed Consent Form (ICF) will be signed by the parents and/or legally designated 
representative of the subject. 
Paediatric subjects will be enrolled in Belgium only.  
No extra medical care will need to be provided after the clinical investigation. 
7.2.5 
Recruitment and Study Duration 
The following subject status definitions apply: 
Enrolled: A subject that has a signed Informed Consent form for the study. 
Screen Fail: An enrolled subject that has been determined to not meet one or more eligibility criteria. 
Participated: Subjects who have met all eligibility criteria and started on protocol defined procedures.  
Withdrawn: An enrolled subject who withdrew or was withdrawn by the investigator or Sponsor before 
the expected End of Study visit. Withdrawn subjects may still continue in safety follow up until their 
scheduled End of Study visit for reasons described in section 7.2.6. 

 
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The recruitment period for the clinical investigation is estimated to be 4 years and 10 months from the 
time of first subject consent to recruitment of the last subject. No new subjects will be recruited in the 
last 2 months of the study. 
Each participant can participate in several sub-studies (one at a time).  
Clinical Investigation completion is last subject last visit. In the event of ongoing Serious Adverse 
Events (SAEs)/Serious Adverse Device Effects (SADEs) at the time of this last visit, the clinical 
investigation completion will be extended for a further 30 days, or until resolution or stabilization of the 
event, whichever comes first. Any variations to these requirements will be documented in each sub-
study documentation (for example, variations to account for in-booth only or take-home use). 
7.2.6 
Criteria for Subject Withdrawal 
Subjects can decide to withdraw from the investigation at any time. The reason for withdrawal should 
be documented in the subject’s source files and the case report form (CRF). If a subject does not wish 
to provide a reason, the reason will be recorded as ‘subject withdrew consent’ in the CRF. 
The Investigator or Sponsor may also decide to withdraw a subject from the clinical investigation if it is 
considered to be in the subject’s best interests. 
Subject withdrawal may be for any of the following reasons: 
• 
Adverse Event (AE) 
• 
Device Deficiency (DD) 
• 
CIP or GCP deviation 
• 
Subject withdrew consent 
• 
Subject lost to follow-up 
• 
Subject death 
• 
Sponsor decision 
• 
Investigator decision 
• 
Other  
If subject withdrawal is due to problems related to the IMD and/or comparator safety or performance, 
the Investigator shall ask for the subject's permission to continue in safety follow up (i.e., adverse 
events) until their scheduled End-of-Study visit. Withdrawal from the umbrella investigation will also 
result in withdrawal from any active sub-study under this umbrella investigation. 
If a subject is lost to follow-up, every possible effort must be made by the study site personnel to contact 
the subject. At least 3 separate attempts taken to contact the subject must be documented. 
Participating subjects who are withdrawn/discontinued might be replaced. This will be specified in the 
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7.2.7 
Randomisation Procedures 
Subjects who meet all eligibility criteria for participation may be randomized to an intervention based 
on a randomization schedule prepared by the Sponsor. Any randomisation requirements (such as the 
storage and access of randomization codes), will be defined on a sub-study basis and defined in the 
sub-study documentation.  
7.2.7.1 
Blinding Procedures 
Where possible, each sub-study will be blinded (i.e. information is concealed from the recipient) or 
double-blinded (i.e. information is concealed from the recipient and the investigator). 
When blinding will be used in a sub-study, the procedures of blinding and unblinding, the emergency 
situations for unblinding etc. will be described in the sub-study documentation.  
7.2.8 
Post-investigation Medical Care 
No extra medical care needs to be provided after the clinical investigation. 
7.3 
Performance Evaluations and Procedures 
The study is a multi-center study conducted at following sites: 
Belgium:  
External sites: GZA Sint-Augustinus Antwerp and AZ Sint-Jan Brugge-Oostende AV  
Internal (Cochlear) site: Cochlear Technology Centre Belgium (CTC).  
Australia:  
External site: HEARnet (in collaboration with Royal Victorian Eye and Ear Hospital, East Melbourne) 
Internal (Cochlear) site: Cochlear Ltd. Melbourne.    
The principal investigators of the external sites are responsible for subject recruitment, obtaining 
Informed Consent, assessment of inclusion- and exclusion criteria and assessment of hearing and 
medical history related to this umbrella Clinical Investigation Plan. Subjects may then be referred to 
the sponsor principal investigator of internal (Cochlear) sites, who will conduct the remaining study 
procedures as described in the umbrella and sub-study Clinical Investigation Plan. Section 10 
describes the Informed Consent process. 
The following scenarios for sub-studies are distinguished: 
• 
The sponsor principal investigator or study staff of internal (Cochlear) sites will conduct study 
procedures at the facilities of internal (Cochlear) sites. The conduct of the study procedures is 
the responsibility of the sponsor principal investigator. 
• 
The sponsor principal investigator or study staff of internal (Cochlear) sites will conduct study 
procedures at the facilities of the site of the external principal investigator. The conduct of 
these study procedures remains the responsibility of the sponsor principal investigator of 
internal (Cochlear) sites. 

 
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• 
The external principal investigator or study staff of external site(s) will conduct study 
procedures at the facilities of the site of the external principal investigator. The conduct of the 
study procedures is the responsibility of the external principal investigator. 
• 
The external principal investigator or study staff of the external principal investigator will 
conduct study procedures at the facilities of internal (Cochlear) sites. The conduct of these 
study procedures remains the responsibility of the external principal investigator. 
For all scenarios, the coordinating investigator of the sub-study is the coordinating investigator of the 
umbrella investigation. Study staff (e.g., technical expert) of the external site(s) of the umbrella study 
may conduct study procedures for which the sponsor principal investigator of a sub-study is 
responsible, only in case the study staff have the qualification and competence to conduct these study 
procedures. The conduct of these study procedures is the responsibility of the sponsor principal 
investigator. 
In each sub-study, the new method/concept will be evaluated by using a set of tests. A detailed 
description of the tests that will be used shall be provided in the sub-study specific documentation. The 
scope of this study will include tests such as those given in Table 1. As a part of these tests, and as 
mentioned in section 7.1, the subject might be asked to complete questionnaires, to perform at-home 
tests etc. during the take home use.    
Evaluation of each method will be done by a repeated-measures design, in which each subject is acting 
as his/her own control. Some methods/concepts will be tested in acute laboratory sessions, while 
others will require take-home experience to be able to fully evaluate the benefit and provide feedback 
by the user. In case a take-home trial will be performed, the IMD will be provided to the subject for real 
life listening experience. Tests may be repeated. When applicable, a cross-over study design will be 
used during another evaluation session after completion of the second set-up/test condition. Subjects 
may revert to their own sound processor programs, if in a situation where it is felt that performance is 
not sufficient with the new programs. 
At the end of each sub-study, the investigational software and/or firmware will be taken off the sound 
processor or remote control and the subject will go back to his/her own program. 
The time for a clinical visit will be limited to a maximum of 4 hours. The time in between clinical visits 
will vary with typical spacing of between 0 (acute) to 4 weeks. The following activities might be applied: 
a) Review of MAP/Clinical History 
The subject’s latest available cdx file (a file containing the ‘map’ or fitting for that specific subject) 
will be imported into the Custom Sound database as sent from the recipient’s local clinic. 
b) Programming (if applicable)  
− 
Different programs will be created using different algorithms. 
− 
The software will be used by the clinician or professionals or by recipients themselves. 
− 
The order of creating the programs will be randomised and balanced across subjects where 
possible according to the subject’s study number. 

 
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Objective measures  
e.g. Electrical measurement of the compound action 
potential of the auditory nerve, pupillometry, impedance 
measurements etc.  
Questionnaire 
Questionnaires to ask subjects feedback on certain features 
of the system, sound quality, ease of use, listening effort, 
music appreciation, tinnitus etc. 
Video tape 
Subjects may be videotaped when agreed to and when 
required. 
Psychophysics 
Psychophysical experiments may be performed to test how 
sensitive implant users are to small differences between 
stimuli and to rate the quality of the different stimuli. For 
example, we may present 2 different sounds (varying in 
loudness or pitch) and ask subjects to rank their loudness 
or pitch. 
Directional hearing 
test 
Multiple speakers in surround set-up. Subject is asked to 
indicate where the sounds come from. 
Diary 
Subjects may be asked to keep track of e.g. battery usage, 
report on the different listening environments they were in, 
how they experienced the effect of the new program etc.  
Device metrics  
State of the art cochlear implant systems have in-built data 
logging containing device diagnostics and statistics on the 
use of the device, on the sound environment etc. 
 
Where possible the comparing measurements will be provided blinded to subject and/or tester. 
Subjects can participate in several sub-studies (one at a time). 
The results of the tests will be carefully monitored during the study and compared with the baseline 
results and with the benchmark results (where applicable) typical for each category of subjects. 
A detailed description of the procedure shall be provided in the sub-study specific documentation. 
7.4 
Safety Evaluations and Procedures 
The risks and anticipated ADEs for the investigational device, as identified in Sections 8.2 and 8.3 of 
the CIP, will be assessed in the clinical investigation via reporting of all AEs/ADEs from the time of first 
subject first visit until last subject last visit for every sub-study. 
Safety data adjudication may be conducted by the Sponsor’s Medical Officer in accordance with the 
Sponsor’s standard operating procedures. 
7.4.1 
Concomitant Medication and Therapies 
In case of concomitant medication, this is administered as part of the safety Case Report Forms. 
Possible interactions with concomitant medications are not anticipated in this clinical investigation. 
Information on baseline concomitant medication (all medications related to hearing health, balance or 

 
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known ototoxic) will be collected during enrollment for each sub-study. In the event of AE’s and ADE’s, 
any medications taken in relation to these events will also be collected. 
7.5 
Equipment Used for Evaluation of Performance and Safety 
The equipment used, the monitoring, maintenance and calibration will be described in the sub-study 
documentation. 
7.6 
Sponsor Role in Conduct of the Clinical Investigation 
As mentioned in section 7.3, the sponsor principal investigator of the internal (Cochlear) sites may 
conduct study procedures upon referral of subjects from the external principal investigator. Section 10 
describes the Informed Consent process. The procedures performed by the sponsor principal 
investigator will be clearly described in the sub-study documentation.  
There is no mitigation for potential bias to the data integrity. Where possible, a sub-study will be blinded. 
8 RISKS AND BENEFITS OF THE INVESTIGATIONAL MEDICAL DEVICE AND 
CLINICAL INVESTIGATION 
8.1 
Anticipated Clinical Benefits  
Potential direct benefits for subjects associated with participation in the clinical investigation include: 
• 
New or improved algorithms may result in increased hearing performance or sound quality 
compared to the baseline condition and/or may be preferred by the recipient. In this case, 
the subject may have access to the program at the end of the study if the CE approval is 
obtained and after proper consultation with the recipient’s hearing professional. 
Potential indirect benefits include: 
• 
Through this clinical investigation Cochlear may bring product improvements to the market 
that will benefit all cochlear implant users. 
8.2 
 Anticipated Adverse Device Effects 
The subjects of this umbrella investigation are already implanted with a CE approved Nucleus implant 
device.  No medication will be prescribed for the study. Therefore, there are no additional medical or 
surgical risks associated with participation in this study.  
The nature of the investigation is purely hearing therapy related, namely adaptations are made to the 
way sound is encoded and transferred to the cochlear implant through the external sound processor. 
The electrical stimulation can be somewhat different from an approved sound processor device due to 
changes in the software or firmware. The risks associated with this change are listed below.  
Anticipated adverse device effects specific to this study (i.e. not cochlear implants in general) include 
the following audiological risks: 
Uncomfortably loud stimulation: Since every subject has a different sensitivity to the electrical 
stimulation, some levels of stimulation may be provided at a level perceived as being too loud even 

 
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though they are safe from a biological perspective. This hazard has the largest residual probability, but 
the severity is limited to discomfort. This hazard is essentially controlled during fitting of the implant. 
Fitting is a key step of the investigational studies and the associated risk is not exceeding the risk 
during normal clinical handling of a CI. To mitigate this risk, the same level of control measures are 
implemented in the software as in the standard clinical fitting software. Furthermore, the fitting is 
conducted or overseen by an experienced clinician. 
Note that during previous umbrella studies (CTC5585 ‘Innovation in Clinical Care for Users of a 
Nucleus Cochlear Implant’ and CTC5595 ‘Innovation in Sound Coding for Users of a Nucleus Cochlear 
Implant’) where programming was involved, one subject reported a louder stimulation than comfortable 
(pain) during programming. The uncomfortable stimulus was immediately stopped and the issue was 
resolved. A second subject reported a headache during the measurements, which resolved after some 
time. 
Non-auditory stimulation: In rare cases, stimulation of the CI can lead to stimulation of non-auditory 
structures such as the facial nerve. It is a standard hazard in clinical management of hearing implant 
users. It is essentially controlled during fitting of the implant. Also, this will always be known already 
from the clinical experience with the subject and can be prevented by e.g. stimulating just below the 
level when the non-auditory stimulation occurs or by deactivating that specific electrode. Also, the fitting 
is conducted or overseen by an experienced clinician. The associated risk is not exceeding the normal 
clinical handling of a CI. 
Wrong stimulation delivered (within safety limits): It is conceivable that due to an implementation 
error in research firmware or software a wrong stimulus would be delivered. Through thorough formal 
verification the probability that unintended electrical pulses would be delivered is low. 
Sub-optimal fitting of the device resulting in sub-optimal performance: It is possible that 
investigational alternatives result in a decline of hearing outcomes. It is well known that some types of 
changes to a map may lead to an acute minor decline in hearing outcomes. As the CI user adapts to 
the new sound quality, this decline is often temporary. But in the worst case a user may not adapt, and 
he/she may decide not to wear the sound processor anymore, resulting in an absence of hearing. In 
this study a CI clinician will be available to provide hearing care, and address reports of degraded 
performance. Subjects will also have access to their standard baseline map that they can return to at 
all times. Again, this risk is similar to the risk in normal clinical management.  
In the case of prolonged observed systematic decrease in performance the particular test set-
up/condition can be halted. Subjects can always revert to their baseline map as this is kept available 
to them. After the study has been finished, the patients will return to their original/preferred 
strategy/condition. 
Increase in subjective tinnitus: It is possible that new coding algorithms (temporarily) increase the 
level of tinnitus that subjects experience. The risk of this happening is very low since the actual 
stimulation pulses (shape, mode) are not changed in this study, and if it happens the solution is simply 
to withdraw the subject from the study and go back to their original stimulation. There is no known 
permanent or long-term increase in tinnitus caused by listening to different sounds. 
In summary, the risks involved with the investigational devices are not substantially different from the 
risks associated with the normal clinical handling of a CI. 

 
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8.3 
Risks Associated with Participation in the Clinical Investigation 
Potential clinical risks associated with participation in the clinical investigation include: 
• 
Impact performance if new/improved algorithms may involve inconveniences and 
discomfort with increased listening practice/effort. 
• 
Inconveniences related to attending study sessions and completing study procedures. 
It is expected that there may be increased inconvenience and potential discomforts to study subjects, 
but no potential risk of physical or psychological harms have been identified. In summary, the risks 
involved with the clinical investigation procedures are not substantially different from the risks 
associated with a normal clinical session with CI users. 
8.4 
Risk Mitigation 
The investigational software and firmware to be assessed in individual sub-studies will undergo safety 
and performance testing according to Cochlear product risk management procedures, in accordance 
with EN ISO 14971 (Medical devices – Application of risk management to medical devices) standards. 
The following will be performed during the clinical investigation to mitigate the risks identified above: 
• 
Detailed study procedures are provided for each sub-study to the investigator to mitigate the 
risks of inappropriate use of the investigational device. 
• 
Investigators are trained to avoid over-stimulation and/or non-auditory stimulation and the 
recipient has the possibility to remove the coil of the sound processor from the head to stop 
stimulation. 
• 
Subjects will be provided with the Instructions For Use of the applicable commercial sound 
processor used during the clinical investigation. 
• 
Subjects may revert to using their own Nucleus sound processor programs, if in a situation 
where it is felt that performance is not sufficient with the new program(s). 
• 
Adverse events will be collected as described in section 11. 
8.5 
Risk-to-Benefit Rationale 
In summary, the risks involved with the investigational devices to be evaluated under this umbrella 
investigation are not substantially different from the risks associated with normal CI users, and the risks 
involved with the clinical investigation procedures are not substantially different from the risks 
associated with a normal clinical session for CI users. 
The potential temporary inconveniences and discomforts associated with participation in one or more 
sub-studies under this umbrella investigation is proportional to the potential direct short-term benefits 
of possible increased hearing performance or sound quality, or indirect benefits as described in section 
8.1. 

 
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9 STATISTICAL CONSIDERATIONS 
9.1 
General Considerations 
Data will be analysed separately per sub-study. Analysis of the data will take place at Cochlear. Sub-
study specific endpoints and other statistical considerations such as hypothesis and sample size 
determination will be described in the sub-study documentation and a sub-study CIR will be written 
when these endpoints are reached.  
9.2 
Endpoints 
Each sub-study addresses aspects of one or more of the innovations described in section 4.1. Sub-
study specific endpoints and details such as specific measurements and time points for assessment of 
each measure, will be described in the sub-study documentation. 
9.2.1 
Primary Endpoints 
Monosyllabic word in quiet scores (for conventional ACE and new sound coding strategy). 
9.2.2 
Secondary Endpoints 
There are no secondary endpoints stated in the umbrella investigation, however, they will be specified 
in the sub-study documentation if appropriate. 
9.2.3 
Exploratory Endpoints 
There are no exploratory endpoints stated in the umbrella investigation, however, they will be specified 
in the sub-study documentation if appropriate. 
9.3 
Hypotheses 
Sub-study specific hypotheses and details such as margins for the hypothesis’s tests, will be described 
in the sub-study documentation. 
9.3.1 
Primary Hypotheses 
There are no primary hypotheses stated in the umbrella investigation, however, they will be specified 
in the sub-study documentation. 
9.3.2 
Secondary Hypotheses 
There are no secondary hypotheses stated in the umbrella investigation, however, they will be 
specified in the sub-study documentation if appropriate. 
9.3.3 
Exploratory Hypotheses 
There are no exploratory hypotheses stated in the umbrella investigation, however, they will be 
specified in the sub-study documentation if appropriate. 

 
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9.4 
Sample Size Determination 
This umbrella study explores the feasibility phase of new or improved sound coding algorithms and 
signal processing. Sample size requirements will be described in the sub-study specific documentation. 
A maximum of 120 subjects will be recruited to participate in sub-studies under this umbrella 
investigation.  
9.5 
Analysis Populations 
A detailed description of the statistical analysis that will be used for each sub-study will be described 
in the sub-study documentation.  
9.6 
Primary Endpoint Analyses 
Primary endpoint analysis will be done on the level of the sub-study. A detailed description of the 
statistical analysis will be specified in the sub-study documentation.  
9.7 
Secondary Endpoint Analyses 
There are no secondary endpoints stated in the umbrella investigation, however, they will be specified 
together with a detailed description of the statistical analysis in the sub-study documentation if 
appropriate. 
9.8 
Exploratory Endpoint Analyses 
There are no exploratory endpoints stated in the umbrella investigation, however, they will be specified 
together with a detailed description of the statistical analysis in the sub-study documentation if 
appropriate.  
9.9 
Safety Analyses 
Per sub-study adverse events will be listed by verbatim term, according to severity, seriousness and 
relationship to the investigational device and investigation procedures. Also, device deficiencies will be 
listed by verbatim term. 
9.10 Interim Analyses 
Not applicable, unless specified differently in sub-study documentation. 
10 INFORMED CONSENT PROCESS 
The Investigator shall obtain written informed consent from the subject using an approved ICF prior to 
any clinical investigation-related examination or activity. The rationale of the clinical investigation, as 
well as the risks and benefits, what participation will involve, and alternatives to participation will be 
explained to the subject. Ample time will be provided for the subject to enquire about details of the 
clinical investigation and to decide whether to participate. 
All questions about the clinical investigation shall be answered to the satisfaction of the subject or the 
subject’s legally acceptable representative. Subjects shall not be coerced or unduly influenced to 
participate or to continue to participate in a clinical investigation. 

 
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Each subject/ or their legally authorised representative and the person who conducted the informed 
consent discussion, shall sign and date the ICF. Where required, a witness shall sign and personally 
date the ICF. A copy of the signed ICF shall be given to the subject. The original signed ICF shall be 
archived in the Investigator’s Site File or subject file at the investigational site. 
The subject or the subject’s legally authorised representative shall be informed in a timely manner if 
new information becomes available that may be relevant to the subject’s willingness to continue 
participation in the clinical investigation. The communication of this information must be documented 
as an update to the ICF and re-consent of the subject. 
The external principal investigator or study staff of external principal investigator shall be responsible 
for subject recruitment and obtaining Informed Consent for the umbrella investigation AI5762. Each 
sub-study will have its own sub-study specific ICF in which the detailed procedure of the sub-study is 
described. All other aspects such as insurance and privacy verbatim of the ICF of umbrella study 
AI5762 still apply. 
The principal investigator or study staff responsible for the conduct of the sub-study will obtain Informed 
Consent for each sub-study. The sponsor principal investigator of Cochlear will always receive a copy 
of the signed Informed Consent Form of AI5762 and the sub-study. 
11 ADVERSE EVENTS AND DEVICE DEFICIENCIES 
11.1 Definitions 
11.1.1 Adverse Event  
An adverse event (AE) is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other persons whether or 
not related to the medical device or the procedures required for implant or use. 
NOTE 1: This definition includes events related to the medical device or the comparator device. 
NOTE 2: This definition includes events related to the procedures involved. 
NOTE 3: For users and other persons, this definition is restricted to events related to medical devices. 
11.1.2 Adverse Device Effect 
An adverse device effect (ADE) is an AE related to the use of a medical device. 
NOTE 1: This includes any AE resulting from insufficiencies or inadequacies in the instructions for use, 
the deployment, the implantation, the installation, the operation, or any malfunction of the medical 
device. 
NOTE 2: This definition includes any event resulting from use error or from intentional misuse of the 
medical device. 
11.1.3 Serious Adverse Event 
A serious adverse event (SAE) is any AE that: 
1) led to a death,  

 
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2) led to a serious deterioration in the health of the subject that either resulted in: 
• a life-threatening illness or injury, or 
• a permanent impairment of, or damage to, a body structure or a body function, or 
• in-patient hospitalisation or prolonged hospitalisation, or 
• medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment or damage to a body structure or a body function, or 
• Chronic disease. 
3) led to foetal distress, foetal death or a congenital physical or mental abnormality, or birth defect 
NOTE: Planned hospitalisation for a pre-existing condition, or a procedure required by the CIP, without 
serious deterioration in health, is not considered a SAE. 
11.1.4 Serious Adverse Device Effect 
A serious adverse device effect (SADE) is an ADE that has resulted in any of the consequences 
characteristic of a SAE. 
11.1.5 Unanticipated Serious Adverse Device Effect 
An unanticipated serious adverse device effect (USADE) is a SADE, which by its nature, incidence, 
severity, or outcome has not been identified in the current version of the Investigator’s Brochure or 
CIP. 
11.1.6 Adverse Events of Special Interest 
There are no Adverse Events of Special Interest. 
11.1.7 Device Deficiency 
A Device Deficiency (DD) is an inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety, or performance. 
NOTE: Device Deficiencies include malfunctions, use errors, and inadequate labelling or information 
supplied by the manufacturer. 
11.2 Recording and Handling of Adverse Events 
Subjects shall be carefully monitored during the clinical investigation of the sub-study and the 
investigator should enquire about AEs at investigation visits.  
All AEs will generally be recorded on sub-study basis from the time of treatment assignment and 
continue for each subject until completion of their End of Study visit. Where the study involves acute 
treatment only, AEs will be recorded only from time of treatment assignment and continue for each 
subject until 4 hours after their study visit. Ongoing SAEs and SADEs will be followed for 30 days, or 
until resolution or stabilisation of the event, whichever comes first. Any variations to these requirements 
will be documented in each sub-study documentation (for example, variations to account for in-booth 
only or take-home use). 

 
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The Investigator is responsible for reporting of safety events to their local Ethics Committee (EC) using 
the applicable report form, in accordance with local regulations. 
11.4.2 Sponsor Notification of Events 
The Sponsor is responsible for reviewing all safety data to evaluate potential causality and anticipation 
of all ADEs. 
The Sponsor is also responsible for reporting all reportable events according to the requirements and 
timelines of the regulatory authorities relevant to this clinical investigation, and shall conduct an 
expedited assessment of all SAEs, unanticipated ADEs, DDs that could have led to a SADE. 
Belgium: The sponsor is responsible for reporting to the FAMHP (Federal Agency for Medicines and 
Health Products): ct.rd@famhp.be, by using the MDCG 2020-10/2 form: (a) any serious adverse event 
that has a causal relationship with the investigational device, the comparator or the investigation 
procedure or where such causal relationship is reasonably possible; (b) any device deficiency that 
might have led to a serious adverse event if appropriate action had not been taken, intervention had 
not occurred, or circumstances had been less fortunate; and (c) any new findings in relation to any 
event referred to in points (a) and (b). 
Reporting must be: a) for all reportable events which indicate an imminent risk of death, serious injury, 
or serious illness and that requires prompt remedial action for other patients/subjects, users or other 
persons or a new finding to it: immediately, but not later than 2 calendar days after awareness by 
sponsor of a new reportable event or of new information in relation with an already reported event; or 
b) any other reportable events or a new finding/update to it: immediately, but not later than 7 calendar 
days following the date of awareness by the sponsor of the new reportable event or of new information 
in relation with an already reported event. In case an initial notification of an SAE/SADE would be 
incomplete, on receipt of additional information the Sponsor must submit a clearly referenced and 
numbered follow-up report of the event.  
Australia: The sponsor is responsible for reporting serious adverse events (SAE) that occur in Royal 
Victorian Eye and Ear Hospital participants to the Human Research Ethics Committee as soon as 
possible and within 72 hours of occurrence. All internal SAEs (occurring in Eye and Ear participants) 
must be reported to the Eye and Ear HREC as soon as possible and within 72 hours of occurrence.  
External SAEs (occurring in participants at other sites) must be reported in a prompt manner if the 
information would reasonably be expected to adversely affect the continued ethical acceptability of the 
trial. This includes cases where the information would lead the HREC to require a change in the trial 
protocol or information statement, including changed monitoring (using the Single SAE form). The 
Sponsor is required to report to the Therapeutic Goods Administration any fatal or life-threatening 
Australian USADEs, and all other Australian USADEs within 7 and 15 days respectively. 
The Safety Monitor for AE/DD assessment and any AE/DD related queries can be contacted via CLTD-
SafetyMonitor@cochlear.com. 
11.5 Independent Data Monitoring Committee 
Given the low residual risk associated with this study (such as no changes to the implant, no significant 
changes to the stimulation pattern, only minor changes to the sound processor firmware, absence of 

 
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datapoints necessary to determine the subject status according to the criteria described in section 
7.2.6. 
Source data will be captured in clinic notes, paper-based source data worksheets, questionnaires or 
printed directly from testing software. Data such as clinical performance data, questionnaires etc. can 
be entered directly into the eCRF which shall be considered source data for these items. If electronic 
medical records do not permit read only access for monitoring purposes, a certified printout must be 
provided. 
The system used for data collection will be specified at the sub-study level, including the use of 
electronic data capture (EDC) on eCRFs.  
In addition, de-identified electronically generated data will be collected from clinical fitting software, 
objective measures software, videography, diagnostic tools etc. The unamended data file shall be 
regarded as the source. 
In case the full eCRF option is not utilized, data collection for demographics, device exposure, medical 
history, adverse events, device deficiencies, concomitant medications, protocol deviations and 
completion will be performed using electronic data capture (EDC) on electronic Case Report Forms 
(Safety eCRF), to support safety analysis and reporting. All other data will be collected from clinical 
fitting software, objective measures software, videography, clinical performance data etc. or captured 
into paper Case Report Forms and entered in a suitable database or directly into the study report after 
review by the study monitor. In case specific procedures are used for data management such as data 
collection and review, this will be specified in the sub-study documentation. Site personnel will be 
trained on the completion of the CRFs. Unamended data files shall be regarded as the source. 
Site personnel will be trained on the completion of the Safety eCRF prior to obtaining access to the 
system and will have their own Login/Password. Access to clinical study information will be based on 
an individual’s role and responsibilities. 
The eCRF will have role-based user permissions for data entry, viewing, and reporting options. All 
communications between users and the EDC server are encrypted. Web servers are protected by a 
managed firewall. This application is designed to be in compliance with applicable regulations including 
21 CFR Part 11. 
The application will include programmed data consistency checks and supports manual generation of 
data clarifications/queries, including documentation of site responses. The application maintains a 
comprehensive audit trail for all data entered, including updates and queries, and documents the time 
that each entry occurred and who made the entry. 
Principal Investigators will affirm that the data for each subject at their site is accurate and complete 
by way of an electronic signature. 
15 CONFIDENTIALITY 
The investigator and site staff will collect and process personal data of the subjects in accordance with 
governing data privacy regulations [such as the EU GDPR regulations]. 
Data will be reported to the Sponsor on CRFs or related documents (e.g. questionnaires). Subjects will 
be identified on CRFs and other related documents only by a unique subject identification code and 
shall not include the subject’s name or other personal identifiable information. Completed CRFs or 

 
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related documents are confidential and will only be available to the Investigator and site staff, the 
Sponsor and their representatives, and if requested to the Ethics Committee and national regulatory 
authorities. Publications or submission to a regulatory authority shall not disclose the identity of any 
subject. 
16 ETHICS COMMITTEE AND REGULATORY AUTHORITY APPROVAL 
The clinical investigation will not commence prior to the written favourable opinion or approval from the 
EC and or regulatory authority (if appropriate) is obtained. 
The final Sponsor-approved version of the CIP, Informed Consent Form, and other necessary 
documents shall be submitted to the EC. A copy of the EC opinion/approval shall be provided to the 
Sponsor. 
The Investigator shall forward to the Sponsor, for review and approval, any amendment made to the 
approved ICF and any other written information to be provided to the subject prior to submission to the 
EC. 
The Sponsor and Principal Investigator will continue communications with the EC, as required by 
national regulations, the clinical investigational plan, or the responsible regulatory authority. 
Any additional requirements imposed by the EC or regulatory authority will be implemented by the 
Sponsor. 
The Investigator shall submit the appropriate documentation if any extension or renewal of the EC 
approval is required.  In particular, substantial amendments to the CIP, the ICF, or other written 
information provided to subjects will be approved in writing by the EC. 
The Investigator shall report to the EC any new information that may affect the safety of the subjects 
or the conduct of the clinical investigation. The Investigator will send written status summaries of the 
investigation to the EC regularly, as per local EC requirements. Upon completion of the clinical 
investigation, the Investigator shall provide the EC with a brief report of the outcome of the clinical 
investigation, as per local EC requirements.  
The clinical investigation is covered by clinical trial insurance, meeting the requirements of the 
participating countries. 
17 SUSPENSION OR PREMATURE TERMINATION 
The Sponsor will discontinue the clinical investigation site if: 
1) major non-adherence to the CIP or GCP principles is occurring 
2) it is anticipated that the subject recruitment will not be adequate to meet the objectives of the 
clinical investigation 
An ongoing clinical investigation may be discontinued in case of: 
1) device failure 
2) serious or intolerable ADE, leading to the explant or discontinued use of the device 
3) subject’s death 

 
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In case of a blind sub-study, the criteria for access to and breaking the blinding/masking code in the 
case of suspension or premature termination of the clinical investigation will be described in the sub-
study documentation. 
Belgium: Upon end of a clinical investigation, the sponsor shall notify the regulatory authority within 
15 days. In the case the clinical investigation is temporarily halted or terminated early, notification of 
this shall be made to the regulatory authority within 15 days. Justification for the halt or termination 
shall be included. If either situation is on safety grounds, then the reporting timeframe is 24 hours. 
Australia: If a trial is prematurely terminated or suspended, the sponsor should promptly inform the 
investigator(s), institution(s), the ethics committee, and the TGA. The sponsor should provide the 
reason(s) for the termination or suspension. 
18 AMENDMENTS TO THE CLINICAL INVESTIGATION PLAN 
No changes in the CIP or investigation procedures shall be made without mutual agreement of the 
Principal Investigators and the Sponsor.  This agreement will be documented as a CIP amendment.  
Amendments will require notification to the Ethics Committees (ECs) by the Principal Investigators (and 
to the relevant regulatory authority(s) by the Sponsor, if applicable). 
19 RECORD KEEPING AND RETENTION 
Data generated from the clinical investigation will be stored in a limited-access file area and be 
accessible only to representatives of the study site, the Sponsor and its representatives, and relevant 
health authorities/regulatory agencies.  All reports and communications relating to study subjects will 
identify subjects only by subject unique identification code.  Complete subject identification will be 
maintained by the Investigator. This information will be treated with strict adherence to professional 
standards of confidentiality. 
The investigator must retain study-related records for a period of at least 15 years after completion of 
the investigation or after the last device was placed on the market, if the IMD has market authorisation. 
The Sponsor will notify the Principal Investigator when records are no longer needed. The Investigator 
will not discard any records without notifying the Sponsor. If the Principal Investigator moves from the 
current investigational site, the Sponsor should be notified of the name of the person who will assume 
responsibility for maintenance of the records at the investigational site or the new address at which the 
records will be stored. The Investigator will notify the Sponsor as soon as possible in the event of 
accidental loss or destruction of any study documentation. 
20 PUBLICATION POLICY 
This clinical investigation will be retrospectively registered at a public clinical trial registry 
ClinicalTrials.gov. Due to the local Ethics Committee requirement, the results from sub-studies with 
participating Melbourne sites will be reported in the public clinical trial registry. 
A joint peer-reviewed publication authored by the clinical investigator(s) and Sponsor may be prepared. 
In addition, the results of the clinical investigation may also be disseminated as conference 
presentations (for example abstract and poster session). Manuscript authorship and responsibilities 
will be discussed and agreed upon prior to investigation start and in accordance with guidelines and 
recommendations provided by the International Committee of Medical Journal Editors (ICMJE) to 

 
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enable communication in a timely manner. All contributors who do not meet the criteria for authorship 
will be listed in an acknowledgments section of the publication. 
Further details are described in the Clinical Investigation Research Agreement (CIRA) of the study. 
21 STATEMENTS OF COMPLIANCE 
This clinical investigation shall be conducted in accordance with ethical principles that have their origin 
in the Declaration of Helsinki, International Standard ISO 14155 Clinical investigation of medical 
devices for human subjects - Good Clinical Practice, and any regional or national regulations, as 
applicable. 
22 QUALITY CONTROL AND ASSURANCE 
In accordance with Cochlear’s Quality Management System, all clinical investigations shall be 
conducted according to internationally recognised ethical principles for the purposes of obtaining 
clinical safety and performance data about medical devices. 
The Sponsor employees (or designee) shall use standard operating procedures (SOP) to ensure that 
clinical study procedures and documentation are consistently conducted and compliant with the ISO 
14155 Standard, Good Clinical Practice (GCP), and applicable local regulations. 
22.1 Monitoring 
The Sponsor will perform on-site and remote monitoring visits as frequently as necessary to oversee 
conduct, data collection and record keeping by sites. The clinical investigation monitoring plan is a 
separate document describing all the activities performed during initiation, monitoring and close out. 
The monitoring plan is described at umbrella level. In case monitoring differs from this monitoring plan 
for a specific sub-study (e.g. more monitoring is required), an additional sub-study monitoring plan will 
be created. 
22.2 Audits 
An Investigator must, in reasonable time, upon request from a relevant health authority or regulatory 
agency, permit access to requested records and reports, and copy and verify any records or reports 
made by the Investigator. Upon notification of a visit by a regulatory authority, the Investigator will 
contact the Sponsor or its designee immediately.   
The Investigator will grant the Sponsor representatives the same access privileges offered to relevant 
health authority or regulatory agents, officers, and employees. 
23 TRADEMARKS AND COPYRIGHT 
ACE, Advance Off-Stylet, AOS, Ardium, AutoNRT, Autosensitivity, Baha, Baha SoftWear, BCDrive, 
Beam, Bring Back the Beat, Button, Carina, Cochlear, 科利耳, コクレア, 코클리어, Cochlear 
SoftWear, Contour, コントゥア, Contour Advance, Custom Sound, DermaLock, Freedom, Hear now. 
And always, Hugfit, Human Design, Hybrid, Invisible Hearing, Kanso, LowPro, MET, MP3000, 
myCochlear, mySmartSound, NRT, Nucleus,Osia, Outcome Focused Fitting, Off-Stylet, Piezo Power, 
Profile, Slimline, SmartSound, Softip, SoundArc, True Wireless, the elliptical logo, Vistafix, Whisper,