A Feasibility, Prospective, Repeated-measures Investigation to Investigate Innovations in Clinical Care 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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Clinical Investigation Plan 
Investigation Title: A feasibility, prospective, repeated-measures 
investigation to investigate innovations in clinical care in adult and 
paediatric recipients implanted with CE approved Nucleus cochlear 
implants: an umbrella investigation. 
Short Title: 
Clinical Care 
CIP Number: 
AI5763 
Date:  
Refer to Header 
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 
 
Principal Investigator 
Cochlear Technology Centre Belgium (CTC) 
(a subsidiary of Cochlear Limited) 
Schaliënhoevedreef 20 Building I 
2800 Mechelen 
Belgium 
Phone: +32 15 79 55 11 
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 ......................................................................................................... 7 
2 
Clinical Investigation Synopsis ........................................................................................................ 8 
3 
Schedule of Events ......................................................................................................................... 9 
4 
Background Information and Rationale ........................................................................................ 10 
4.1 
Introduction ......................................................................................................................... 10 
4.2 
Findings of Previous Nonclinical and Clinical Studies ........................................................ 12 
4.2.1 
Nonclinical Data .................................................................................................... 12 
4.2.2 
Clinical Data .......................................................................................................... 12 
4.3 
Study Rationale .................................................................................................................. 13 
5 
Medical Device Information ........................................................................................................... 13 
5.1 
Identity and Description of the Investigational Medical Device (IMD) ................................ 13 
5.2 
Identity and Description of the Comparator ........................................................................ 15 
5.3 
Accessory Device Requirements ........................................................................................ 15 
6 
Objectives ..................................................................................................................................... 15 
6.1 
Primary Objectives .............................................................................................................. 15 
6.2 
Secondary Objective ........................................................................................................... 15 
6.3 
Exploratory Objective .......................................................................................................... 16 
7 
Design of the Clinical Investigation ............................................................................................... 16 
7.1 
General ............................................................................................................................... 16 
7.1.1 
Design Rationale ................................................................................................... 18 
7.2 
Subjects .............................................................................................................................. 20 
7.2.1 
Inclusion Criteria ................................................................................................... 20 
7.2.2 
Exclusion Criteria .................................................................................................. 20 
7.2.3 
Number of Subjects Required ............................................................................... 20 
7.2.4 
Vulnerable Populations ......................................................................................... 21 
7.2.5 
Recruitment and Study Duration ........................................................................... 21 
7.2.6 
Criteria for Subject Withdrawal ............................................................................. 21 
7.2.7 
Randomisation Procedures .................................................................................. 22 
7.2.8 
Post-investigation Medical Care ........................................................................... 22 
7.3 
Performance Evaluations and Procedures ......................................................................... 22 
Intra-operative stage to collect objective measurements: .................................................. 26 
7.4 
Safety Evaluations and Procedures ................................................................................... 26 
7.4.1 
Concomitant Medication and Therapies ............................................................... 26 
7.5 
Equipment Used for Evaluation of Performance and Safety .............................................. 26 
7.6 
Sponsor Role in Conduct of the Clinical Investigation ........................................................ 27 
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8 
Risks and Benefits of the Investigational medical device and Clinical Investigation .................... 27 
8.1 
Anticipated Clinical Benefits ............................................................................................... 27 
8.2 
Anticipated Adverse Device Effects .................................................................................... 27 
8.3 
Risks Associated with Participation in the Clinical Investigation ........................................ 28 
8.4 
Risk Mitigation .................................................................................................................... 29 
8.5 
Risk-to-Benefit Rationale .................................................................................................... 29 
9 
Statistical Considerations .............................................................................................................. 29 
9.1 
General Considerations ...................................................................................................... 29 
9.2 
Endpoints ............................................................................................................................ 30 
9.2.1 
Primary Endpoint .................................................................................................. 30 
9.2.2 
Secondary Endpoints ............................................................................................ 30 
9.2.3 
Exploratory Endpoints ........................................................................................... 30 
9.3 
Hypotheses ......................................................................................................................... 30 
9.3.1 
Primary Hypothesis ............................................................................................... 30 
9.3.2 
Secondary Hypotheses ......................................................................................... 30 
9.3.3 
Exploratory Hypotheses ........................................................................................ 30 
9.4 
Sample Size Determination ................................................................................................ 30 
9.5 
Analysis Populations ........................................................................................................... 31 
9.6 
Primary Endpoint Analyses................................................................................................. 31 
9.7 
Secondary Endpoint Analyses ............................................................................................ 31 
9.8 
Exploratory Endpoint Analyses ........................................................................................... 31 
9.9 
Safety Analyses .................................................................................................................. 31 
9.10 Interim Analyses ................................................................................................................. 31 
10 Informed Consent Process ........................................................................................................... 31 
11 Adverse Events and Device Deficiencies ..................................................................................... 32 
11.1 Definitions ........................................................................................................................... 32 
11.1.1 
Adverse Event ...................................................................................................... 32 
11.1.2 
Adverse Device Effect .......................................................................................... 32 
11.1.3 
Serious Adverse Event ......................................................................................... 32 
11.1.4 
Serious Adverse Device Effect ............................................................................. 33 
11.1.5 
Unanticipated Serious Adverse Device Effect ...................................................... 33 
11.1.6 
Adverse Events of Special Interest ....................................................................... 33 
11.1.7 
Device Deficiency ................................................................................................. 33 
11.2 Recording and Handling of Adverse Events ....................................................................... 33 
11.2.1 
Assessment of Severity ........................................................................................ 34 
11.2.2 
Assessment of Causality ...................................................................................... 34 
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11.2.3 
Assessment of Seriousness ................................................................................. 35 
11.2.4 
Assessment of Expectedness .............................................................................. 35 
11.3 Recording and Handling of Device Deficiencies................................................................. 36 
11.4 Reporting Responsibilities .................................................................................................. 36 
11.4.1 
Investigator Reporting of Serious Adverse Events ............................................... 36 
11.4.2 
Sponsor Notification of Events ............................................................................. 36 
11.5 Independent Data Monitoring Committee ........................................................................... 37 
12 Device Accountability .................................................................................................................... 37 
13 Deviations from the Clinical Investigation Plan ............................................................................. 38 
14 Data Management ........................................................................................................................ 38 
15 Confidentiality ................................................................................................................................ 39 
16 Ethics Committee and Regulatory Authority Approval .................................................................. 39 
17 Suspension or Premature Termination ......................................................................................... 40 
18 Amendments to the Clinical Investigation Plan ............................................................................. 41 
19 Record Keeping and Retention ..................................................................................................... 41 
20 Publication Policy .......................................................................................................................... 41 
21 Statements of compliance ............................................................................................................. 41 
22 Quality Control and Assurance ..................................................................................................... 42 
22.1 Monitoring ........................................................................................................................... 42 
22.2 Audits .................................................................................................................................. 42 
23 Trademarks and Copyright ........................................................................................................... 42 
24 References .................................................................................................................................... 42 
25 Change History ............................................................................................................................. 43 
 
 
 
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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 stimulation/Hybrid). 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 programming and performance measurements 
are very time-consuming tasks for specialised clinics. Moreover, clinical models around the world are 
very different and are evolving rapidly. Therefore, there is a strong tendency to look for less time 
consuming and specialised methods to reach the same goal, namely optimal hearing for the user.  
Hearing loss is a chronic condition, requiring acute but also long-term care. Due to the technological 
evolution, in the coming years the devices may have an in-built wireless connection to the internet. 
Users, including elderly people, are becoming fluent users of mobile and computer devices. Therefore, 
new hearing care models can be developed. Four different models can be identified:  
(1) expert care where the hearing implant user travels to the CI clinic to meet with expert clinicians, 
specialized in hearing implants. 
(2) local care where the hearing implant user can personally meet with a (less specialized) hearing 
professional offering certain services in the local neighbourhood. 
(3) remote care where the implant user can contact professional care providers from home through 
internet and mobile technologies at a time convenient for both parties; and  
(4) self-care where the implant user has access to certain aspects of care (e.g.  counselling materials, 
self-test tools, self-fitting tools, objective datalogs, rehab materials, web shop, …) through internet 
technologies at any time.  
New technologies need to be investigated to accommodate these 4 models. 
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This investigation evaluates these new technologies for the complete hearing journey from the recipient 
and the clinician’s perspectives on the different aspects of device fitting, diagnostics, performance and 
rehabilitation methods for the four models of care.  
Firstly, new fitting technologies and methodologies focus on the work flow and the tools to optimally 
and efficiently program a cochlear implant, be it purely electrical hearing, or a combination of electrical 
and acoustical hearing.  
Secondly this study evaluates the hearing performance and outcomes a user obtains (through e.g.  
audiological tests and questionnaires) as well as the diagnostics in case of degrading performance. 
This includes classic audiological measures such as tonal audiometry and speech understanding, but 
also covers psychoacoustical and objective assessments, cognitive function evaluation etc. These 
measures are used in building predictive models for an individual. A last aspect of diagnostics is 
monitoring hearing performance and the long-term use of the device. Devices must become more 
intelligent and pro-active in reporting problems (e.g. using data logging) and suggesting solutions.  
A well-fitted hearing implant is a necessary condition for the user to reach his/her full hearing potential. 
This goes hand in hand with optimal training and rehabilitation a user must go through with their new 
hearing modality. Therefore, the effectiveness of new training and counselling schemes for the users 
is also evaluated in this study.  
The effectiveness of these different methods for fitting, diagnostics and (re)habilitation will be evaluated 
as well as the usability of each of them for both the cochlear implant recipient and/or parent/legally 
designated representative and the clinician.  
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 diagnostic, fitting or (re)habilitation 
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 
4.2.2 
Clinical Data 
The existing 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. 
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4.3 
Study Rationale 
To evaluate the benefit of new features as mentioned in section 4.1, it is essential that studies 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 onto 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) An 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 medical device standards for optimal 
wearing comfort.  
(3) The firmware is the software running continuously on the sound processor. It determines the 
stimulation that will be provided. Many features have been added to the sound processing 
algorithms, such as noise reduction functions, directionality, sound environment classification, 
flexible audio sources and wireless connectivity, …. The firmware also contains various safety 
related functions, e.g. it stores the electrical stimulation levels that are comfortably loud for the 
specific patient etc. 
(4) The fitting software is the software with which the clinician is programming the sound processor. 
It downloads the firmware onto the sound processor and determines the patient specific 
parameters, e.g. stimulation levels. The fitting software can run on computer, a tablet, or a 
mobile device allowing self-tuning.  
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either in a new build of the existing CSS and 
 software (if the modification to the standard 
functionality is small) or in Cochlear’s research platforms.  
Also, the new diagnostic and outcome prediction methods, as well as the new training and counselling 
methods that are under investigation, will use new software.  
 
. 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 procedures document 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 fitting methodologies and tools will be investigated by using a new build of the existing CSS, 
 
software and by other Cochlear’s research platforms. This will be compared to the commercially 
available fitting methods and tools where available.  
Also new diagnostic and outcome prediction methods, as well as new training and counselling 
methods, using new software and tools, will be compared to the currently available methods and tools.  
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 AI5763. 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 Objectives  
• 
To evaluate the effectiveness of new streamlined and optimized device fitting methods. 
6.2 
Secondary Objective 
• 
To evaluate the effectiveness of new diagnostic and outcome prediction methods. 
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• 
To evaluate the effectiveness of new training and counseling schemes for hearing implant 
users. 
• 
To evaluate the usability of the new fitting, diagnostic methods and training/counseling methods 
from the recipient and/or the clinician’s point of view. 
6.3 
Exploratory Objective 
There are no exploratory objectives stated in the umbrella investigation, however, they 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 10 months will be included. Subjects will be screened and up to 160 eligible 
subjects will be recruited in the umbrella investigation. 
Two separate groups of subjects will be recruited: 
• 
Group 1 will include subjects who are already implanted with a Nucleus cochlear implant. A 
clinical setting can consist of therapeutic elements (fitting, diagnostic or rehabilitation) and 
evaluations. Subjects will be assessed with the commercially available Nucleus sound 
processor. 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 different fitting, 
diagnostic and (re)habilitation methods in as many listening environments as possible. The 
subject might 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. 
• 
Group 2 will include subjects who are scheduled to be implanted with a commercially available 
Nucleus cochlear implant. The diagnostic testing will be conducted in the operating theatre 
during the cochlear implant surgery. Only CE approved devices will be used for this intra-
operative testing in accordance with the approved indication(s) and terms of the market 
authorization. Post-operatively, these subjects might be recruited following the procedures as 
described for the group 1 subjects.  
Figure 5 illustrates the subject enrolment scenarios for group 1 and group 2 subjects.  
 
 
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Figure 5 subject enrolment scenarios for group 1 and group 2 subjects. 
 
  
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 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 listening program, diagnostic or rehabilitation tool in as many 
listening environments and/or in daily life 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 
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. 
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7.1.1 
Design Rationale 
The goals of this study are  
• 
to measure hearing outcomes to assess performance and/or 
• 
to obtain better diagnostics and/or 
• 
to achieve higher convenience for implant users and hearing care professionals and/or  
• 
to determine whether device and procedure improvements deliver an improvement in time 
efficiency for the CI recipient and the clinician involved in the CI process.  
The outcomes of the study will guide Cochlear to select features for inclusion in future cochlear implant 
systems and/or future models of care.  
This investigation can be divided in two stages, namely the intra-operative stage and the post-operative 
stage, during which evaluation will take place. 
 
Post-operative stage to evaluate new fitting, diagnostic and (re)habilitation methods and tools 
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. Classic methods of 
cochlear implant programming involve 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. This process can be time 
consuming and can produce varied results depending on the skill of the clinician and the 
responsiveness of the recipient. 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. At every stage in the cochlear implant 
process (re)habilitation is given to the CI recipient by dedicated professionals, self-care tools, online 
tools etc.  
It is important to continually improve the efficacy of the methods to create programs and make 
performance assessments. The vast majority of the CI users can be considered as routine cases, 
where there are no specific medical complications (such as e.g. cochlear malformations or neuropathy 
etc.). For this group an overall streamlined process resulting in consistent high hearing outcomes can 
be achieved, even when programmed by clinicians with a range of clinical experience, professionals 
or potentially by recipients themselves. The same applies for a streamlining in the diagnostic and 
(re)habilitation methods.  
Cochlear is developing such streamlined methodologies (Botros et al 2013, International Journal of 
audiology).  
To optimally manage the more complex cases, it is important that the clinician still has access to 
detailed device control features (such as activation of individual electrodes). Specific diagnostic 
methods are also needed to identify the areas where the patient is encountering difficulties, e.g. through 
hearing tests or diagnostic tests. The clinician can then better decide how to change elements of the 
therapy. 
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Future clinical management methods should therefore combine device control functions and diagnostic 
tests. It is conceivable even that smart algorithms will be developed that will assist in changing the map 
parameters quasi-automatically. The aim of the programming and performance evaluation methods is 
to improve on average hearing outcomes while streamlining the process, improving the efficacy, and 
lowering the health care cost.  
Incremental changes will be made to the research software used for programming, performance 
evaluations and rehabilitation so that the right balance of ease of use and efficacy is maintained.  
 
Intra-operative stage to collect objective measurements 
Objective measurements, for example Auto-NRT and impedance telemetry are commonly used test 
procedures to test the implant function intra- and post-operatively. These measurements utilise the 
capability of the internal implant to run telemetry tests when commanded by the sound processor. 
Currently these tests are run either via a computer with Custom Sound 
 software or with a remote 
control or App on a mobile device handled by the professional.   
These objective data can be used in fitting and can eventually help the clinician with predicting 
outcomes, increase performance and optimise the clinicians’ efficiency in diagnostics.  
In this investigation, only CE approved devices will be used for this intra-operative testing in accordance 
with the approved indication(s) and terms of the market authorization. Post-operatively, these subjects 
might be recruited following the procedures as described for the group 1 subjects. 
Comparison of programming, diagnostic and/or (re)habilitation methods 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 functionality and/or to assess the concept of a new 
diagnostic, fitting or (re)habilitation method. Each of the sub-studies will be looking at a particular 
approach to address the objectives of the overall umbrella investigation AI5763.  
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 10 months 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, diagnostic and (re)habilitation methods 
compared to adult CI users. The procedure for recruiting subjects is further described in section 7.2. 
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.  
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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 160 adult and paediatric CI recipients older than 10 months 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 investigations. Paediatric subjects will 
be enrolled in Belgium only 
7.2.1 
Inclusion Criteria 
Subjects must meet all the inclusion criteria described below to be eligible for this clinical investigation. 
• 
Group 1 subjects: Users of a CE approved Nucleus cochlear implant, resulting in open set 
speech understanding or  
Group 2 subjects: Subjects assessed by their CI clinic to be suitable for implantation with a 
commercially available CE approved Nucleus cochlear implant. 
• 
Paediatrics: Older than 10 months 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. 
• 
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 Organizations 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 160 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 
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10 months 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 fitting, diagnostics and 
(re)habilitation methods or tools. 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 benefit of new features. Each 
method/tool will be evaluated in a sub-study. Depending on the specific aspect that will be tested, 
children might be involved from the age of 10 months 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. 
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). 
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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 
sub-study documentation. 
7.2.7 
Randomisation Procedures 
Subjects who meet all eligibility criteria for participation may be randomised to an intervention based 
on a randomisation 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: 
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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. 
• 
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/tool 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. 
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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/tools 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, remote control or mobile device 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 programming methodologies. 
- 
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. 
- 
A screen recording of the computer, tablet or mobile device and / or video recording may be 
done for programming tasks when required and where agreed by the recipient. 
 
c) Take home use (if applicable)  
- 
The new programs may be loaded to a loaner sound processor in a randomised and balanced 
order. 
- 
Subjects will be asked to use the new programs or software in real world environments and 
provide feedback. 
- 
Subjects will be encouraged to record their daily experiences in the daily diary or other 
questionnaires if applicable.  
- 
Subjects might be asked to perform at-home tests etc. during this take home use.  
 
 
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d) Evaluation 
The tests used for evaluation will be specified at sub-study level. Table 1 shows an overview of 
possible tests that can be conducted. Not all tests may be relevant for every sub-study, naturally, 
unnecessary tests will be skipped. If applicable, a new diagnostic method is used (i.e. adaptation 
to one of the methods as shown in Table 1).  
- 
Speech perception in free field can be conducted. 
- 
Speech perception tests may also be conducted by delivering inputs directly to the sound 
processor through investigational software and firmware.  
- 
The evaluation tool will be used by the professionals, by recipients or parents/legally designated 
representatives. 
- 
If applicable and available, the subjects might be asked to perform at-home tests  in between 
visits and/or at the clinical visits.  
- 
The order of the tests will be randomised, blinded and balanced where possible.  
- 
If applicable, the clinician may be asked to provide feedback on the ease of use of the new 
method and its training materials. 
Table 1: Example of a post-operative test battery  
Nr 
Test 
Description 
1 
Tonal Audiometry 
Standard tonal audiogram. 
2 
Phoneme detection and 
discrimination tests 
Evaluation of the peripheral auditory function (cochlea) by the test of 
phoneme detection and discrimination. 
3 
Speech in quiet 
Standard audiological word tests in quiet. 
4 
Speech in noise 
Word and sentence tests in noise, with noise either at a fixed level or 
adaptively adjusted. 
5 
Objective measures  
e.g. Electrical measurement of the compound action potential of the 
auditory nerve, pupillometry, impedance measurements etc. 
6 
Questionnaire 
Questionnaires to ask subjects feedback on certain features of the 
system, sound quality, ease of use, music appreciation etc. 
7 
Video tape 
Subjects may be videotaped when agreed to and when required. 
8 
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. 
9 
Directional hearing test 
Multiple speakers in surround set-up. Subject is asked to indicate where 
the sounds come from. 
10 
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/tool etc.  
11 
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.  
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12 
Language development 
tests 
Monitor the language development of young children may be done by 
taking standardized tests on receptive and expressive language skills, 
such as the Peabody Picture Vocabulary Test, Reynell Test, Schlichting 
Test, Preschool Language Scale (PLS) or Clinical Evaluation of 
Language Fundamentals (CELF). 
 
Intra-operative stage to collect objective measurements:  
Only CE approved devices will be used for this intra-operative testing in accordance with the approved 
indication(s) and terms of the market authorization.  
The investigator may request a nurse, the surgeon or a clinician to run the test under the investigator’s 
supervision. 
Video recording may be done during the testing where required. 
If the intra-operative tests take significantly more time under anaesthesia (as judged by the surgeon) 
the testing will be aborted. 
Post-operatively, these subjects might be recruited following the procedures as described for the group 
1 subjects. 
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 Clinical 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 
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 used equipment, the monitoring, maintenance and calibration will be described in the sub-study 
documentation. 
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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 diagnostics, programming and/or (re)habilitation methods may result in increased hearing 
performance or sound quality comparing 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: 
• 
New methods may result in an increased efficiency of time for clinicians and provide a more 
consistent outcome for their CI recipients. Also, in this case the clinician is free to retain the 
preferred method as soon as the necessary CE approval is obtained and when the CI recipient 
agrees to this new method. 
• 
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 or will be implanted with a CE 
approved Nucleus implant device, independent of this study. No medication will be prescribed for the 
study.  
The nature of the investigation is purely hearing therapy related, namely either fitting, diagnostics or 
(re)habilitation. 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.  
The expected risks with use of CE approved sound processors are described in the Investigator’s 
Brochures (IB) and in the Instruction For Use (IFU). 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 
though they are safe from a biological perspective. This hazard has the largest residual probability, but 
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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 is 
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. 
Intra-operative testing only:  There is a risk that the intra-operative tests take longer and lengthen 
the time the subject is under anaesthesia. In this case the surgeon or anaesthetist can abort the testing.  
In summary, the risks involved with the investigational devices are not substantially different from the 
risks associated with normal CI users and the normal clinical handling of a CI. 
8.3 
Risks Associated with Participation in the Clinical Investigation 
Potential clinical risks associated with participation in the clinical investigation include: 
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• 
Impact performance if new programming, diagnostic and (re)habilitation methods 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 their head to stop 
stimulation. 
• 
Subjects will be provided with the Instruction 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 
possible increased hearing performance, or indirect benefits, as described in section 8.1.  
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 
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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 Endpoint 
Monosyllabic word in quiet scores (for standard-of-care and new/optimized device fitting methods). 
9.2.2 
Secondary Endpoints 
There are no secondary endpoints stated in the umbrella investigation, however, 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 Hypothesis 
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.  
9.4 
Sample Size Determination 
This umbrella study explores the feasibility phase of new or improved fitting, diagnostic and 
(re)habilitation software, research fitting and research diagnostic tools. 
Sample size requirements will be described in the sub-study documentation. A maximum of 160 
subjects will be recruited to participate in sub-studies under this umbrella investigation.  
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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, 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. 
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 
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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 AI5763. 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 
AI5763 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 CTC/Cochlear, Melbourne will 
always receive a copy of the signed Informed Consent Form of AI5763 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,  
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 
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• 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. 
NOTE: An anticipated serious adverse device effect is an effect, which by its nature, incidence, 
severity, or outcome has been identified in the 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 involves acute 
treatment only, AE will be recorded only from the 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). 
Source notes should indicate the evaluation for AEs, even if there was none to report. All required AEs 
will be reported if observed, even if anticipated and/or acknowledged as a risk factor in the consent. 
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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. 
CTC: 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. 
Cochlear Melbourne: 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 
surgical risk, audiological risk comparable to clinical follow-up), an IDMC will not be established for this 
study.   
12 DEVICE ACCOUNTABILITY 
Supply of investigational medical devices will be recorded using tracking forms such as the Sponsor 
Device Tracking Form (1295388) and Software Tracking Form (1302326). Investigational medical 
device(s) will be quarantined at the investigational site and clearly labelled to identify exclusively for 
use in a clinical investigation. Subject level device supply will be tracked using the Individual Subject 
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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, 
objectives measures software, imaging (such as CT), 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, objectives measures software, imaging, 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 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 
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. 
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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 
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. 
CTC: 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. 
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Cochlear Melbourne: 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 
participation from 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 
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 
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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, WindShield and Xidium are either trademarks or registered trademarks of the 
Cochlear group of companies [2022]. 
24 REFERENCES 
1) Botros, A., Banna, R., & Maruthurkkara, S. (2013). The next generation of Nucleus(®) fitting: A 
multiplatform approach towards universal cochlear implant management. International Journal of 
Audiology, 52(7), 485–94. 
2) Clinical investigation of medical devices for human subjects — Good clinical practice. 
International Organization for Standardization, ISO 14155. 
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risk mitigation section 8.4); updated 
section 7.2.1 inclusion criteria, updated 
section 7.2.3 for subject numbers; 
section 7.2.4 for additional details 
regarding children to be tested in 
Belgium only, updated language in 
section 7.2.5; updated section 7.3 for 
additional sites details; updated section 
7.4.1 concomitant medications; 
updated section 8.2 to add details of 
risks reported in earlier relevant clinical 
studies; section 11.4.2 Sponsor 
Notification of Events (added details 
about Melbourne); section 14 data 
management (some of the information 
has been transferred to section 7.2.5); 
section17 Suspension or Premature 
Termination (added Melbourne details); 
section 20 updated Trademarks as of 
2020 
reflect that only adults will be recruited in 
Australia, however in Belgium both adults and 
children can be recruited.  
Additional changes made include changes in 
terminology as per the new cochlear template 
and typos. 
Section on concomitant medications has been 
updated to specify the medications information 
that will be collected as part of this study. 
5.0 
Section 11.4.2 update of reportable 
safety events and timelines. 
Change in safety reporting to the regulatory 
authorities as per EU Medical Device Regulation 
2017/745 (MDR), Article 80 (2) 
6.0 
Deletion of not registering on a public 
clinical trial registry. 
Addition of clarification to the number of 
subjects in this feasibility trial. 
Addition of primary endpoint, 
separation of primary and secondary 
objectives. 
 
 
Change of time in between clinical 
visits from 1-4 weeks to 0 (acute)-4 
weeks. 
Addition of AE recording and handling 
for acute visits. 
Addition of registration to public clinical 
trial registry details. 
Updated trademarks and copyrights 
Local Ethics Committee requirement to register 
on a public clinical trial registry. 
Clarification to the number of subjects in this 
feasibility trial. 
 
Majority of research to involve fitting 
methodology evaluation. 
Consistent outcome measure will be 
monosyllabic words in quiet in all sub-studies 
targeting fitting methodologies. 
To correct the time in between clinical visit as 
stated in the CIP. 
 
Additional clarification on AE recording and 
handling for acute visits. 
Additional clarification of registration to public 
clinical trial registry and what will be reported. 
Update to the current trademarks and copyrights  
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Signature Page for 
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Reason for signing: Approved
Date of signature: 19-Apr-2022 08:44:13
GMT+0000
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