Cochlear Implant and Healthy Aging: A Multinational, Multicentre Observational Study
Conditions: Hearing Loss
Sponsor: Cochlear

Official Title: Cochlear Implant and Healthy Aging: A Multinational, Multicentre 
Observational Study 
 
NCT Number: NCT03072862        
 
Document Date: 10 December 2019 

Document Number: D1280780 
CEL5671- Clinical Investigation Plan 
Version 4.0 
 
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OBSERVATIONAL STUDY PROTOCOL  
 
 
Cochlear Implant and Healthy Aging:  
A Multinational, Multicentre Observational* 
Study 
 
Short Study Tittle: “CI & Healthy Aging” 
 
 
 
Study Number: CEL5671 
 
 
 
 
ENGLISH MASTER VERSION 
Date: 10 December 2019 
Version number: 4.0 
 
 
Authors: 
 
* Investigator does not intervene on the treatment.  
 
 

 
 
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Table of contents 
 
1 
Clinical Investigation Synopsis .................................................................................. 6 
2 
Terms and Abbreviations ............................................................................................ 8 
3 
Introduction .................................................................................................................. 9 
4 
Identification and description of the device ............................................................ 11 
5 
Justification for the design of the observational study .......................................... 11 
5.1 
Study Design .......................................................................................................... 11 
5.2 
Evaluation Tools ..................................................................................................... 11 
5.2.1 
Generic Health Status.................................................................................................... 11 
5.2.2 
Hearing .......................................................................................................................... 12 
5.2.2.1 
Speech Spatial Qualities (SSQ). .............................................................................................. 12 
5.2.2.2 
Hearing Handicap Inventory in the Elderly Screening test (HHIE-S). ....................................... 12 
5.2.2.3 
Categories of Auditory Perception II (CAP-II) ........................................................................... 12 
5.2.2.4 
Routine speech discrimination assessment in quiet ................................................................. 12 
5.2.2.5 
Routine speech discrimination assessment in noise ................................................................ 13 
5.2.2.6 
Routine assessment of unaided pure tone audiometry (PTA) for air conduction ..................... 13 
5.2.2.7 
Routine assessment of aided sound field thresholds (SFT) for warble tones........................... 13 
5.2.3 
Falls ............................................................................................................................... 13 
5.2.4 
Depression ..................................................................................................................... 14 
5.2.5 
Cognition ........................................................................................................................ 14 
5.2.5.1 
Mini Mental State Examination (MMSE)................................................................................... 14 
5.2.5.2 
Digit Symbol Substitution Test (DSST) .................................................................................... 14 
5.2.5.3 
Trail B Test ............................................................................................................................... 14 
5.2.6 
Dependency ................................................................................................................... 15 
5.2.7 
De Jong Loneliness ....................................................................................................... 15 
5.2.8 
Data Logging ................................................................................................................. 15 
5.2.9 
Patient profile data ......................................................................................................... 16 
5.2.10 
Healthcare Resource Utilization (HRU) data ................................................................. 16 
6 
Risks associated with participation in the observational study ............................. 17 
7 
Objectives and hypothesis........................................................................................ 17 
7.1 
Study Objectives .................................................................................................... 17 
8 
Design of the observational study ............................................................................ 18 
8.1 
General .................................................................................................................. 18 
8.2 
Overview to Assessment Schedule and Visits ........................................................ 18 
8.2.1 
Preimplant visit 1 = Pre1 ................................................................................................ 19 
8.2.2 
Postimplant Visit 2 = Post1 ............................................................................................ 19 
8.2.3 
Postimplant Visit 3 = Post2 ............................................................................................ 19 
8.3 
Global Overview of Data Collection ........................................................................ 19 

 
 
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8.4 
End-points .............................................................................................................. 21 
8.5 
Investigational device and comparator ................................................................... 22 
8.6 
Subjects ................................................................................................................. 22 
8.6.1 
Inclusion Criteria ............................................................................................................ 22 
8.6.2 
Exclusion Criteria ........................................................................................................... 22 
8.6.3 
Criteria and procedures for subject’s withdrawal or discontinuation ............................. 22 
8.6.4 
Point of enrolment .......................................................................................................... 23 
8.6.5 
Expected duration of the clinical investigation ............................................................... 23 
8.6.6 
Expected duration of each subject's participation ......................................................... 23 
8.6.7 
Number of subjects required to be included in the clinical investigation ....................... 23 
8.6.8 
Estimated time needed to select this number (i.e. enrolment period) ........................... 23 
8.7 
Procedures ............................................................................................................. 23 
8.8 
Monitoring Plan ...................................................................................................... 23 
9 
Statistical Considerations ......................................................................................... 24 
10 
Data Management ...................................................................................................... 24 
11 
Amendments to the Observational Study Protocol (CIP)........................................ 24 
12 
Deviations from the Observational Study Protocol ................................................. 25 
13 
Device accountability ................................................................................................ 25 
14 
Statements of compliance ........................................................................................ 25 
14.1 Declaration of Helsinki and compliance with standards .......................................... 25 
14.2 Ethics Committee and Competent Authority Approval ............................................ 25 
14.3 Audits and Supervision ........................................................................................... 26 
14.4 Study Records ........................................................................................................ 26 
15 
Patient Informed Consent (PIC) process .................................................................. 26 
15.1 Obtaining informed consent .................................................................................... 26 
15.2 Data Privacy ........................................................................................................... 26 
16 
Incident reporting ...................................................................................................... 27 
16.1 Incident Reporting .................................................................................................. 27 
16.2 Reporting process .................................................................................................. 27 
17 
Vulnerable population ............................................................................................... 27 
18 
Suspension or premature termination ..................................................................... 28 
19 
Publication Policy ...................................................................................................... 28 
20 
Revision History ........................................................................................................ 28 
20.1 Changes from version 1.0 to version 2.0 ................... Error! Bookmark not defined. 
21 
Bibliography ............................................................................................................... 29 
22 
Appendix I: List of Investigators............................................................................... 31 
 

 
 
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1  Clinical Investigation Synopsis 
Name of device: 
Commercially available Nucleus Cochlear Implant Systems, 
including Data Logging functionality 
Short study title and 
study number: 
CI & Healthy Aging CEL 5671 
Principal 
Investigators and 
sites: 
 - Ospedale Guglielmo da Saliceto - Piacenza - Italy 
 - Hôpital Purpan - 
Toulouse - France 
 - 
Universidad de Las Palmas de Gran Canaria - Spain 
 - Bnai Zion Medical Center - Haifa - Israel 
 – Rabin Medical Center (Beilinson) - Petah Tikva - Israel 
 - Clinica Universitaria de Navarra - Pamplona - 
Spain 
 - Azienda Ospedaliera di Padova - Padova -Italy 
 - Complejo Hospitalario Universitario Insular 
Materno Infantil - Las Palmas de Gran Canaria - Spain 
 - Hôpital La Pitié 
Salpétrière - Paris - France 
Study start: 
06 November 2017 
Total expected 
duration of the 
clinical investigation: 
4 years 
Enrolment period: 
31 months 
Expected duration 
per subject: 
20 Months (+/- 1 month) 
Study design: 
Observational prospective comparative cohort repeated measures 
Number of subjects: 
100 
Inclusion criteria: 
• 
Unilateral CI candidates with bilateral postlingual deafness 
with intention to treat 
• 
  > 60 years at first unilateral cochlear implant  
• 
Implant ear: meets all local criteria for CI treatment  
• 
Contralateral ear: average pure tone thresholds indicate a 
moderately-severe to profound hearing loss (4 freq. average: 
0.5, 1, 2 and 3 or 4 kHz > 56 dBHL). 
• 
Willingness to participate in and to comply with all study 
procedures 
• 
Fluency in languages used to assess clinical performance 
• 
Appropriate expectations from routine CI treatment 
• 
Able to decide on study participation personally and 
independently sign their consent 

 
 
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Exclusion criteria: 
• 
Significantly/severely dependent or fragile 
• 
Unable to provide consent personally 
• 
Unable to complete questionnaires for self-assessment 
independently 
• 
Unilateral hearing loss 
• 
Sequential and simultaneous bilateral cochlear implant 
recipients 
• 
Ossification or other cochlear anomalies preventing full 
electrode insertion 
• 
Retro cochlear or central origins of hearing impairment. 
• 
Significant comorbidities preventing study participation (e.g. 
blindness, immobility or in a wheel chair, severe aphasia,.) 
• 
Medical contraindications to surgery  
• 
Clinic Standard fail criteria for CI candidacy in regards to 
chronic depression, dementia, and cognitive disorders. 
• 
Unrealistic expectations on the part of the subject, regarding 
the possible benefits, risks and limitations that are inherent 
to the procedure and prosthetic device. 
 
Primary objective: 
To evaluate the change in health related quality of life following 
CI treatment in the elderly individuals by using the generic Health 
Utilities Index Mark III (HUI 3) tool prospectively.  
Secondary 
objectives: 
To evaluate the impact of CI treatment in the elderly on the 
domains that have an impact on healthy aging and overall well-
being such as hearing ability, dependency, cognition, falls, 
depression. 
Tertiary objective: 
To identify healthcare resource utilisation that is impacted by CI 
treatment versus no treatment.  
Treatment and 
follow up schedule:  
Q - questionnaire 
A - standard audiological 
measure 
G- standard geriatric 
measure 
NA –not Applicable 
 
 
Q/A. 
Pre1 
Visit 1 
Post 1  
Visit 2 
Post 2 
Visit 3 
Patient Profile 
Q 
x 
x 
x 
Healthcare  
resources  
Q 
x 
x 
x 
CAP-II 
Q 
x 
x 
x 
L-IADL 
Q 
x 
x 
x 
Data Logging 
A 
NA 
x 
x 
HUI3 
Q  
x 
x 
x 
GDS-15 
Q  
x 
x 
x 
HHIE-S 
Q  
x 
x 
x 
SSQ 
Q  
x 
x 
x 
PTA 
A 
x 
x 
x 
SFT 
A 
x 
x 
x 
Speech in Quiet 
A 
x 
x 
x 
Speech in Noise 
A 
x 
x 
x 
MMSE 
G 
x 
x 
x 
DSST 
G 
x 
x 
x 
TRAIL B 
G 
x 
x 
x 
De Jong Loneliness 
scale 
Q 
x 
x 
x 
TUG 
G 
x 
x 
x 

 
 
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Primary endpoints: 
Change in HUI3 multi-attribute index scores preimplant to 
postimplant at 12 and 18 months post surgery. 
Secondary 
endpoints: 
Change in scores on evaluation tools for specified health related 
domains on  each of the following from preimplant to post implant at 
12 and 18 months surgery: MMSE, DSST & Trail B  (Cognition); TUG 
(falls); GDS-15 (depression); L-iADL (independency); HHIE-S 
(hearing handicap); SSQ (hearing & communication ability); CAP-II 
(capabilities of audition); De Jong Loneliness Scale; Speech 
recognition tests in Quiet ( daily hearing function); Speech 
recognition tests in Noise (daily hearing function); Consistent daily 
use of CI via automatic data logging (hrs/day and listening 
environments) 
Tertiary endpoint 
Change in healthcare resource utilisation with CI treatment 
postimplant versus preimplant (assessed over a 6 month time frame 
at each test interval). 
 
2 Terms and Abbreviations 
Abbreviation Definition 
Category of assessment 
CAP-II 
Capabilities of Auditory Performance 
Hearing ability 
L-IADL 
Lawton –Instrumental Activities of Daily Living 
Independence 
HUI3 
Health Utilities Index Mark III 
Quality of Life 
GDS-15 
Geriatic Depression Scale -15 
Depression 
HHIE-S 
Hearing Handicap Inventory for the Elderly 
Scale 
Hearing Handicap 
SSQ 
Speech Spatial and Qualities 
Hearing ability 
MMSE 
Mini Mental State Examination  
Cognition 
DSST 
Digit Symbol Substitution test  
Cognition 
TRAIL B 
Trail Making Test version B 
Cognition 
PTA 
Pure tone Audiometry 
Hearing levels 
SFT 
Sound Field Thresholds 
Hearing levels 
TUG 
Time Up and Go test 
Risk of fall 

 
 
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3 Introduction 
Burden of disease in the aging population 
has a high economic impact for society.  
In 2014, Prince et al. published a report in 
Lancet on the leading contributors to the 
burden of disease in people aged > 60 
years.  
Cochlear Implant, (CI) restores hearing 
function and communication abilities 
which in turn help to reduce social 
isolation (Olze et al 2012, Lachowska et 
al 2014). An increasing number of 
publications demonstrate CI treatment 
also has a positive impact on depression 
and may delay cognitive decline (Mosnier 
et al 2015, Lin et al 2011 Olze et al 2012). 
Routine clinical follow shows a trend for 
added benefits of CI treatment upon 
dependency, mobility and the risk of falls 
(Lin et al 2011, Lachowska et al 2014). 
Therefore, we may assume that through 
CI treatment for permanent deafness, 
there is a potential to decrease the 
burden of disease in aging adults by 
improving important social, health and cognitive functions in addition to restoring hearing 
function. 
With reference to Prince et al., CI treatment is expected to impact the following contributors to 
the global burden of disease: Sensory, MND (Mental and neurological disorders) and 
Unintentional injury. 
Today, with aging population and its impact on the health care systems, policy makers for 
provision of health and social services are aiming to keep older adults in good health for longer, 
in other words  towards “Healthy aging”.  
Increasing number of health technology assessment (HTA) bodies recommend the use of 
generic health related quality of life tools (i.e. EQ-5D, HUI, SF 36) which in the end yield generic 
outcome -Quality Adjusted Life Years- which enable comparison of different health 
technologies for the HTA bodies (Massetti et al 2015). 
Our study objective is to show that CI treatment improves the overall health related 
quality of life and general well-being which translate into healthy aging.  The study data 
collected will provide transparent and comparable medical evidence that can support health 
care policy makers to take informed decisions on the provision of health services for the 
treatment of hearing loss  

 
 
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The World Health Organisation, (WHO), defines active aging as ‘the process of optimizing 
opportunities for health, participation and security in order to enhance quality of life as people 
age’, allowing people to ‘realize their potential for physical, social and mental well-being 
throughout the life course’. The list of contributors to healthy aging is long and varied with the 
majority of items independent of hearing loss. Nevertheless, by treating deafness, positive 
effects upon various health related quality of life domains can occur which in turn impacts the 
overall health status. 
Therefore, while it is anticipated to show improvement in the overall health status, the study 
aim is also to evaluate the impact of consistent daily use of CI on specific health-related 
quality of life domains (i.e. hearing, communication, dependency, physical mobility, risk of 
falls, depression, social isolation & cognition) and to further explore and qualify the main 
contributors to the better health. 
The utilization of cochlear implants is low in elderly adults. It is estimated to be under 5% 
globally of the elderly population with a significant hearing loss. Various reasons that may 
contribute to the low rate of CI treatment in aging adults listed below: 
• 
Lack of awareness by geriatricians, general practitioners on when and where to refer 
elderly for auditory rehabilitation. 
• 
Lack of self-awareness within the elderly population on the benefits they can expect 
from cochlear implantation. 
• 
Assumption that elderly have reduced listening demands and therefore do not need to 
aim for the optimal auditory function (aided condition). 
• 
Limited funding leading to lower prioritization of treatment for elderly hearing impaired 
versus children, adolescents, young and working age adults. 
In 2030, 20% of the population will be aged > 65 yrs; one in three will suffer from significant 
hearing loss.  Therefore, there is a sense of urgency for: 
• 
Health care policy makers to build evidenced based informed decisions for the 
provision of interventions in the elderly, which in turn can create cost savings 
from a societal perspective in the long term.  
• 
Increased awareness and development of guidance principles to support 
professionals as well as aging individuals, on the suitability for timely referral for 
further assessment for cochlear implant candidacy.  
The study aim is to provide medical evidence that CI treatment in aging adults has the potential 
to improve the overall health status including but not exclusive to hearing function, which in 
turn can create cost savings from a payer and societal perspective. This information may be 
used to support referring professionals and potential CI candidates in their decision for CI 
treatment as soon as significant hearing loss is diagnosed which can impact overall healthy 
aging. 
Figure 2 Elements of Wellness (source 
http://www.invivowellness.com/blog/wp-
content/uploads/2013/07/seven-wellness 

 
 
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4 Identification and description of the device  
The observational study includes treatment with commercially available cochlear implant 
devices available for routine clinical treatment of deafness in all ages in each collaborating 
investigator clinic.  
Devices are provided with standard product labelling and documentation and ordered through 
routine purchase channels regionally. 
5 Justification for the design of the observational study 
5.1 Study Design  
The study design is an observational prospective repeated measures study performed to 
evaluate the benefits for overall health following CI treatment in the elderly population treated 
in clinical routine practice.  
The benefits of CI treatment postimplant are compared to the preimplant health status via intra-
subject controls using standard assessment scales for various health domains.  
CI treatment effect is examined via repeated measures for intra-subject controls as follows:  
• 
Preimplant assessment before implant surgery date @ < 2 months   
• 
Postimplant assessment post surgery @ 12 months + 1 month  
• 
Postimplant assessment post surgery @ 18 months +1 month  
5.2 Evaluation Tools 
A selection of observational clinical assessment tools have been selected for repeated 
assessment and to reflect changes in the overall health status of the elderly individual at pre 
and post CI treatment intervals. These are commonly used in audiology and/or geriatric 
practices.  
5.2.1 
Generic Health Status  
Health Utility Mark III (HUI3): The HUI3 is a generic tool to assess health-related quality of 
life completed by the patient (Feeny et al 1995; Feeny et al 2000). The “four-week recall” 
version of the self-assessed HUI3 with 15 questions is included as the main outcome for 
repeated assessment at each time interval. Licensed versions per language for use in the 
observational study are obtained from the developers, Health Utilities Inc. The HUI3 is a 
sensitive measure that assesses the impact of medical treatments including CI, over time, 
across eight health domains: vision, hearing, speech, ambulation, dexterity, emotion, cognition 
and pain. The 15 questions provide a descriptive response system enabling classification of 
the respondents into predefined HUI3 health states. The focus of the questionnaire is on health 
state of the individual, assessing the degree of their perceived impairment for each domain. 
Responses for each domain are converted to between five to six levels, and then a health state 
is identified among possible 972,000 health states. The scoring function was derived from 
Standard Gamble and Visual Analog Scale methods employed for assessment of a random 
sample of Canadians (n = 504), resulting in utility scores from – 0.36 to 1.00, where a negative 
score is a state worse than death (Feeny et al 2000) A clinically significant change is set at 
0.03 or more between time points.This form can be completed in approximately 10 to 15 
minutes by the candidate/recipient.  
 

 
 
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5.2.2 
Hearing 
5.2.2.1 Speech Spatial Qualities (SSQ).  
The SSQ is a self-assessment scale of hearing ability and communication in daily 
environments, completed by the patient (Noble, 2006). Forty nine questions are divided into 
three subcategories: speech (comprehension), spatial (hearing in space) and quality (speech 
and sounds) and are appropriate for use in adults of all ages and children from nine years 
(Gatehouse and Noble 2004). Each question is scored on a 10-point rating scale, with higher 
numeric values reflecting greater ability for the responder. The resulting scores are generally 
reported as mean ratings for each category but may also be regrouped or assessed individually 
and the ratings over two time points compared. Clinically significant differences were set at a 
rating change of 1.0 for each subcategory score between test intervals, as a typically observed 
difference rating reported in the literature for assessment of unaided and aided hearing aid or 
implant users). This form can be completed in approximately 30 minutes by the 
candidate/recipient. 
 
5.2.2.2 Hearing Handicap Inventory in the Elderly Screening test (HHIE-S). 
The HHIE-S is a short form self-assessment scale designed to assess the effects of hearing 
impairment on the emotional and social adjustment in everyday life of the elderly individual 
before and after hearing treatment. The HHIE-S comprises ten questions (5 emotional & 5 
social/situational). Possible scores range from 0 (no handicap) to 40 (maximum handicap) 
with a significant change at the 95% confidence interval of > 9.3 change points (Newman, 
1991). The higher the HHIE-S score, the greater the handicapping effect of a hearing 
impairment. This form can be completed in approximately 5 minutes by the 
candidate/recipient. 
 
5.2.2.3 Categories of Auditory Perception II (CAP-II) 
CAP-II is an auditory skill rating index consisting of nine hierarchical categories. The CAP-II is 
completed by the clinician as an observation of the individuals hearing abilities. Ranging from 
1 to 9, the auditory skills increase in perplexity ranging from perception of environmental 
sounds to telephone conversation with an unfamiliar speaker. A score of 1 to 9 is provided for 
assessment at each preimplant and postimplant evaluation interval. (Archbold 1995, Gilmore 
2010). This form can be completed in approximately 2 minutes by the clinician using patient 
hospital file. 
 
5.2.2.4 Routine speech discrimination assessment in quiet  
As is performed routinely, assessment of speech recognition in quiet, is performed and the 
results recorded at preimplant and post implant visits in the subject’s daily listening 
condition, i.e.:  
• 
aided binaurally or  
• 
aided monaurally, one ear unaided, or  
• 
bilaterally unaided (i.e. no hearing aid available at preimplant assessment, only in 
cases with clinical record of a recent unsuccessful hearing aid trial).  
As per local routine practices, standardly used speech materials are presented in the sound 
field at varied presentation levels, to determine the speech intensity function curve per 
individual, which includes 65 dB SPL. Recorded speech stimuli are presented from a loud 
speaker at 00 Azimuth, 1 meter away at head level.  Speech test materials may include 
monosyllabic or disyllabic word lists in the native language.  
Recorded outcomes will include the percent of items correctly identified compared to the total 
number of speech items presented at 65dB SPL and the speech reception threshold level, 

 
 
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dBSPL, at which 50% of speech items are correctly recognized, i.e. SRT50%. This routine test 
is completed in approximately 10 to 15 minutes by the clinician together with the 
candidate/recipient. 
 
5.2.2.5 Routine speech discrimination assessment in noise 
As is performed routinely, assessment of speech recognition in noise, is performed and the 
results recorded at preimplant and post implant visits in the subject’s daily listening 
condition, i.e.:  
• 
aided binaurally or  
• 
aided monaurally, one ear unaided.  
Tests in noise are typically done for patients who can correctly understand a minimum of 50% 
of speech items in quiet. Speech tests are performed in the free field sound booth with 
competing background NOISE. According to local routine practices, standardly used speech 
materials are presented in the sound field at adaptively to obtain the SRT50% in noise, OR 
speech stimuli may presented fixed at 65 dBSPL and the competing background noise (i.e. 
pink noise) varied for each presentation list to obtain the SRT50%. Recorded speech stimuli 
and the competing background noise are presented from a loud speaker at 00 Azimuth, 1 meter 
away at head level. Test materials may include sentences or words as is typically used in the 
native language.. This routine test is completed in approximately 10 to 15 minutes by the 
clinician together with the candidate/recipient. 
 
5.2.2.6 Routine assessment of unaided pure tone audiometry (PTA) for air 
conduction 
Unaided Hearing thresholds, dBHL, for pure-tone stimuli via air conduction, presented under 
headphones, following routine clinical practices at the preimplant clinic visit for each individual. 
Frequencies for measurement include 250, 500, 1000, 2000 and 4000 Hz. Threshold data, will 
be combined for all subjects for descriptive analysis. This routine test is completed in 
approximately 5 minutes by the clinician together with the candidate/recipient. 
 
5.2.2.7 Routine assessment of aided sound field thresholds (SFT) for warble 
tones 
Aided thresholds, dB SPL, for warble tone stimuli presented in the sound field following routine 
clinical practices at preimplant and post implant visits for each individual in their daily listening 
condition with hearing device(s). 
• 
aided binaurally or  
• 
aided monaurally, one ear unaided 
Frequencies for measurement include 250, 500, 1000, 2000 and 4000 Hz. Warble tones are 
presented from a loud speaker at 00 Azimuth, 1 meter away at head level. This routine test is 
completed in approximately 5 minutes by the clinician together with the candidate/recipient. 
Threshold data, will be combined for all subjects for descriptive analysis at each assessment 
interval. 
5.2.3 
Falls 
The Time Up and Go test (TUG). The TUG test measures the time a person takes to stand 
up from a standard armchair, walk three meters (i.e. 10 feet), turn around, walk back to the 
chair, and then sit down again. The test is performed by the patient wearing regular footwear, 
using customary assistive devices, if any, and walks at a comfortable and safe pace. The 

 
 
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clinician uses a stop watch to measure the required timing accurately for the complete 
physical maneuver and the seconds taken to perform it recorded. The test is performed at 
preimplant and post implant assessment intervals. [Podsiadlo 1991]. This test can be 
completed in approximately 3 minutes by the clinician together with the candidate/recipient. 
5.2.4 
Depression 
Geriatric Depression Scale-15 (GDS-15). The GDS-15 is a self-report measure of depression 
in older adults completed by the patient. The 15-item version was developed as a time efficient 
and easy to complete version with responses in a Yes/No format. The items included have 
demonstrated a high correlation with depressive symptoms in previous validation studies 
(Sheikh & Yesavage, 1986). Of the 15 items, 10 indicate the presence of depression when 
answered positively while the other 5 are indicative of depression when answered negatively. 
This form can be completed in approximately 5 to 7 minutes by the candidate/recipient. 
5.2.5 
Cognition 
5.2.5.1 Mini Mental State Examination (MMSE).  
The MMSE is a 30-point screening test used extensively in clinical and research settings to 
measure likely cognitive impairment. It is often used to estimate the severity and progression 
of cognitive impairment and to follow the course of cognitive changes in an individual over time; 
thus making it an effective way to document an individual's response to treatment.  
Administration of the test requires no special training or equipment and takes between 5–10 
minutes. The MMSE examines functions including registration, attention and calculation, 
recall, language, ability to follow simple commands and orientation. Scores indicate the 
following cognitive functionality:  > 24/30 is normal; 19-23, mildly impaired; 10-18, moderately 
impaired;   ≤ 9 severe impairment.  
For analysis scores will be adjusted according to age, gender and education level as 
established by covariates affecting outcomes on this measure. Normative data available for 
the various language groups will be considered in the interpretation of the results. This form 
can be completed in approximately 7 minutes by the candidate/recipient together with the 
clinician. 
5.2.5.2 Digit Symbol Substitution Test (DSST) 
Digit symbol substitution test is a neurophysiological test sensitive to brain damage, 
dementia age and depression assessing working memory. It consists of (e.g. nine) digit-
symbol pairs (e.g. 1/-, 2/ ┴ ... 7/Λ, 8/X,9/=) followed by a list of digits. Under each digit the 
subject should write down the corresponding symbol as fast as possible. The number of 
correct symbols within the allowed time (i.e. 120 sec) is measured.  Symbol copy shows a 
strong decline with age.  
This form can be completed in approximately 2 minutes by the candidate/recipient together 
with the clinician. 
The DSST contained in the Wechsler Adult Intelligence Scale is called 'Digit Symbol' (WAIS-R), 'Digit-
Symbol-Coding' (WAIS- IV).  
5.2.5.3 Trail B Test 
The Trail B is neuro physiological test assessing executive function requiring skills of visual 
search, scanning, speed processing and mental flexibility. Trail B is a Trail Making Test that 

 
 
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consists of 25 circles distributed over a sheet of paper. The circles include both numbers (1 – 
13) and letters (A – L); the patient draws lines to connect the circles in an ascending pattern, 
with the task of alternating between the numbers and letters (i.e., 1-A-2-B-3-C, etc.). The 
patient should be instructed to connect the circles as quickly as possible, without lifting the 
pen or pencil from the paper. The time the patient takes to connect the "trail." is scored. If the 
patient makes an error, it is pointed out immediately and the patient is allowed to correct it. 
Errors affect the patient's score only in that. 
The correction of errors is included in the completion time for the task. The test is stopped 
after 5 minutes.This form can be completed in maximum 5 minutes by the candidate/recipient 
together with the clinician. 
5.2.6 
Dependency  
Lawton Instrumental Activities of Daily Living Scale, (L-IADL). The L-IADL is a valuable 
tool completed by the clinician to assess patients with early-stage disease, both to assess the 
level of disease and to determine the patient's ability to care for him or herself. Performance 
of IADLs requires mental as well as physical capacity. The IADL scale measures the functional 
impact of emotional, cognitive, and physical impairments and their need for personal care 
services. IADLs are scored based on what an individual can do rather than what he/she is 
doing. IADLs are scored based on how an individual usually performs each of eight tasks. The 
tasks assessed include: telephone use; food preparation; shopping; housekeeping; laundry, 
transportation mode; responsibility for own medication and ability to handle finances.  The 
patient receives a score of 1 for each category item if his or her competence is rated at some 
minimal level or higher, or a score of zero if below minimum capacity. The total sum of scores 
may range from 0 – 8. A lower score indicates a higher level of dependence. This form can be 
completed in approximately 5 minutes by the clinician using patient hospital file & Interview 
5.2.7 
De Jong Loneliness  
The development and testing of an explanatory loneliness model were described in De Jong 
Gierveld (1987 & 1998). A 6 item validated version of the loneliness scale was developed by 
De Jong Gierveld & Van Tilburg (2006), three questions assessing social isolation and 3 on 
emotional loneliness. The scale may be used in face-to-face interviews, telephone interviews, 
self-administered (mail) questionnaires, as well as in electronic data collection. It is 
recommended by developers that the scale be presented somewhere in the middle of the 
interview or questionnaire style; that is, at a moment when a considerable degree of self-
disclosure from the respondents may be expected. Ideally, questions about characteristics of 
the respondents' networks of social relationships should precede the scale items.  
The model is based on the so-called cognitive theoretical approach to loneliness. 
Characteristic of this approach to loneliness is the emphasis on the discrepancy between what 
one wants in terms of interpersonal affection and intimacy, and what one has; the greater the 
discrepancy, the greater the loneliness. Background characteristics (such as marital status, 
sex and living arrangements), descriptive characteristics of the social network, number and 
frequency of contacts with network members, and personality and health are identified as 
important loneliness-provoking factors. Other factors are found to be of crucial importance as 
well, such as social norms and values, expectations of support associated with certain 
relationships, and the positive or negative evaluation of the network of relationships-as-
realized.  
This form can be completed in approximately 1 minute by the clinician using patient Interview. 
5.2.8 
Data Logging 
In general, healthy aging population operate in a wide range of listening environments with 
listening profiles that are unique to them. 

 
 
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A measure of success of CI treatment is the average daily use (hrs/day). Furthermore the 
variety of listening environments experienced will be automatically recorded at each post 
implant assessments interval(s) as an indicator for social integration. 
The sound processor features an in-built data-logging function. Data are extracted 
automatically at each programming session while the sound processor is connected to the 
fitting software, Custom Sound. Information on daily usage is saved into the local Custom 
Sound data base at the clinic. Subsequently the individual daily usage data can be exported 
through a software function (i.e. as CDX files), with the patient’s details kept anonymous. 
Specifics of the data to be collected at each programing session includes the print screen 
below & additional record of: 
• 
Connection to Custom Sound Date 
• 
Number of days since last connection to Custom Sound 
• 
Average Time on air per day 
• 
Average Time in Noise, Speech in Noise, Speech, Quiet, Music, Wind 
 
 
 
There is no form to be completed for data logging as data are contained within the CDX file 
exported. The investigator will send the anonymized exported CDX file after the 18-month visit 
has been completed to the sponsor using the Patient ID code as the file name (e.g. 
PatientID.CDX) 
5.2.9 
Patient profile data 
Coded demographic data will be collected via a customized case report that is completed by 
the clinician. The information is used to profile and describe the patient group characteristics 
in terms of audiological history, telephone use, living environment and educational level at the 
preimplant interval. 
Data gathered will be summarized for the group. Select variables may be examined for 
correlation with one or more outcomes. 
This form can be completed in approximately 5 minutes by the clinician using the patient’s 
hospital file & via interview. 
5.2.10 Healthcare Resource Utilization (HRU) data 
General Healthcare data. A customized case report is completed by the clinician.  
This questionnaire has been designed by department of Health Economics from Gran-Canaria 
University (Author: Beatriz González López-Valcárcel & Patricia Barber). It is based on general 
European health survey and adapted to be relevant to the CEL5671 study . The questionnaire 
is color coded where data in pink should be taken from the medical records and data in black 
are collected through interview with the Subject. 
 

 
 
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Collected data includes 
• 
Type of  health care coverage and employments status 
• 
Use of primary care and emergency services 
• 
Use of specialist practices and/or outpatient surgery services 
• 
Diagnostic tests performed such as radiology, laboratory tests,… 
• 
All hospitalization within the time period observed 
• 
The list and dose of prescribed medication taken 
• 
The list and dose of non-prescription medication taken 
• 
Visits to physiotherapy and rehabilitation 
• 
Sessions with a speech therapist 
• 
Sessions at psychologist 
• 
Use of social welfare care 
• 
Whether subject has lived in a residential care home 
• 
Use of home help or social services 
• 
Support and help from family, friends or others 
 
Data collected will represent the 6-Month time-frame prior to each of the 3 test intervals.  
Data will be used to quantity the use of health resource across the duration of the study. The 
quantification will be done in the corresponding units (i.e. number of visits, exams, doses of 
medication, subject’s health expenses,..). In a second stage and in collaboration with national 
experts, these quantities will be converted in health care costs. 
Data obtained would potentially be used for economic modelling of direct and indirect costs in 
the long term related to the intervals post CI treatment and prior to CI treatment.  
 
This form can be completed in approximately 30 minutes by the clinician using the subject’s 
patient hospital file & via interview. 
6 Risks associated with participation in the observational study 
Participation in the observational study presents no additional risk to the patient over and 
above routine clinical care using commercially available cochlear implant devices. There is no 
additional clinical visit outside the routine management.  
7 Objectives and hypothesis 
7.1 Study Objectives 
1. To evaluate the change in health related quality of life following CI treatment in elderly 
individuals by using the generic Health Utilities Index Mark III (HUI 3) assessment 
scale prospectively. 
2. To evaluate the impact of CI treatment on the domains that have impact on overall well-
being and healthy aging in the elderly such as :  
a) hearing ability and communication 
b) dependency  
c) cognition 
d) falls 
e) depression/mood  
3. To identify the changes in healthcare resource utilisation following CI treatment 
compared to preimplant. 
The hypotheses: 
Primary hypothesis  

 
 
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CI implant treatment significantly improves the overall health related quality of life of elderly 
individuals compared to their preimplant condition as measured on the HUI-3. 
Secondary hypothesis  
CI treatment in the elderly significantly impacts the healthy aging domains and therefore overall 
well-being in addition to hearing function compared to the preimplant condition as measured 
on clinically standard evaluation tools in the geriatric and audiological fields.  
Tertiary hypothesis 
CI treatment has the potential to create cost savings from the perspective of health care 
payer(s), health care provider(s) and society, by reducing health care resource utilisation for 
bilaterally severe to profound hearing impaired adults over 60 years of age, post implant 
compared to their preimplant status.  
8 Design of the observational study 
8.1 General 
A repeated measure, single-subject observational design will be used for assessment of the 
changes in health related quality of life and overall well-being as the primary end-point of the 
study, in which each subject acts as his/her own control. Subjects are evaluated subjectively 
at pre- and post-operative intervals that coincide with their routine visits to the clinic.  
This study is observational as no additional intervention is applied to the CI recipient. 
Outcomes from routine practice and application of CI intervention are recorded through 
observational measures using clinically standard scales used widely in geriatrics and 
audiology.  
The study design is multi-centre, and multi-language; Italian, French, Spanish, Arabic and 
Hebrew. Translations of questionnaires have been controlled for via a validated translation 
process, and thus enabling collation of the data gathered cross culturally. The implant clinics 
have been chosen due to their long standing history in providing cochlear implant intervention 
for the treatment of hearing impaired individuals and for their existing capacity to recruit and 
treat elderly CI candidates for the study within a reasonable time frame. 
Each participating clinic is anticipated to recruit a minimum of 8 and a maximum of 20 subjects 
in total if not agreed differently 
8.2 Overview to Assessment Schedule and Visits 
Figure 3 below represents an overview of the evaluation visits for each enrolled subject, 
designed to coincide with routine clinical visits involved in provision of CI intervention. Each 
subject will be assessed during three visits while participating in the study, creating three data 
sets and evaluation points per subject. The full battery of tests will be repeated at each of the 
three visits.  

 
 
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 Figure 3 Overview to evaluation schedule flow and visits for each enrolled subject.  
8.2.1 
Preimplant visit 1 = Pre1  
Preimplant visit 1 corresponds to the first evaluation with the full assessment battery for each 
subject before surgery and corresponds to his/her absolute baseline.  
• 
Preimplant assessment before implant surgery date  < 2 months   
8.2.2 
Postimplant Visit 2 = Post1  
Postimplant Visit 2, (Post 1) corresponds to the first assessment after implantation @ 12 
months (+/- 1 month) post surgery.  
• 
Postimplant assessment post surgery @ 12 months + 1 month.  
8.2.3 
Postimplant Visit 3 = Post2  
Postimplant Visit 3, (Post 2) corresponds to the second assessment after implantation @ 18 
months (+/- 1 month) post surgery.  
• 
Postimplant assessment post surgery @ 18 months +1 month. 
8.3 Global Overview of Data Collection 
Table 1 provides an overview of the standardly available assessment tools making up the test 
battery to be used at each evaluation Visit (1 to 3). The corresponding health domain(s) 
assessed by each evaluation tool, as referred to and described under the primary and 
secondary hypotheses are indicated. In addition to the evaluation tools listed below, 
customized case report forms to summarize the Patient Profile and Healthcare resource 
utilisation over time will be completed by the clinician for each enrolled subject. Table 2 
illustrates for whom completion of each assessment is targeted and the schedule.  

 
 
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Table 1. Overview to Evaluation Tools and health domains assessed. 
 
 
 
 
Table 2 Evaluations by Visit by Clinician and by Candidate/Recipient 

 
 
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8.4 End-points 
 
Primary end-point 
Change in overall health related quality of life via comparison of HUI3 multi-attribute utility 
scores at:  
o Post1 implant Visit compared to Pre1 implant Visit  
o Post2 implant Visit compared to Post1 implant Visit  
o Post2 implant Visit compared to Pre1 implant Visit 
Secondary end-points: 
Change in scores on battery of evaluation tools for health related domains and overall well-
being on each of the following:  
MMSE, DSST & Trail B  (Cognition); TUG (falls); GDS-15 ( depression); iADL 
(independency); HHIE-S (hearing handicap); SSQ (hearing & communication ability); CAP-II 
(capabilities of audition); De Jong Loneliness Scale, Speech recognition tests in Quiet ( daily 
hearing function); Speech recognition tests in Noise (daily hearing function); Consistent daily 
use of CI via automatic data logging (hrs/day and listening environments). 
o Post1 implant Visit compared to Pre1 implant Visit  
o Post2 implant Visit compared to Post1 implant Visit  
o Post2 implant Visit compared to Pre1 implant Visit  
 
Pre1
Post1
Post 2
Visits
Visit1
Visit2
Visit3
Patient Profile
x
x
x
Societal Cost
x
x
x
CAP2
x
x
x
i-ADL
x
x
x
De Jong Loneliness
x
x
x
HUI-3
x
x
x
GDS-15
x
x
x
HHIE-S
x
x
x
SSQ
x
x
x
PTA
x
x
x
SFT
x
x
x
Speech in Quiet
x
x
x
Speech in noise
x
x
x
DSST
x
x
x
Trail B
x
x
x
MMSE
x
x
x
TUG
x
x
x
 Questionnaires filled by clinicians using patient hospital files 
and/or interview 
Self assesment Questionnaires
Routine audiological assesments
Routine Geriatric assesments

 
 
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Tertiary end point: 
Changes in healthcare resource utilisation with CI treatment compared to preimplant, 
collected at each test interval, i.e., Pre 1, Post1 and Post 2 will be compared. Each 
assessment will reflect a 6 month period immediately before assessment. Data reviewed for 
this measure will be obtained from the customized HRU questionnaire completed by the 
clinician on behalf of the subject (data sources available for use will be in accordance with 
regional guidelines). 
8.5 Investigational device and comparator 
No investigational device is used in the study design. Only approved products for market 
release are used for routine CI treatment during the course of the observational study.  
Each subject will act as their own control. As such the comparator for all subjects will be their 
daily preimplant listening situation. 
8.6 
Subjects  
8.6.1 
Inclusion Criteria 
• 
Unilateral CI candidates with bilateral postlingual deafness with intention to treat 
• 
  > 60 years at first unilateral cochlear implant  
• 
Implant ear: meets all local criteria for CI treatment  
• 
Contralateral ear: average pure tone thresholds indicate a moderately-severe to 
profound hearing loss (4 freq. average: 0.5, 1, 2 and 3 or 4 kHz >56dBHL). 
• 
Willingness to participate in and to comply with all study procedures 
• 
Fluency in languages used to asses clinical performance 
• 
Appropriate expectations from routine CI treatment 
• 
Able to decide on study participation personally and independently sign their consent 
8.6.2 
Exclusion Criteria 
• 
Significantly/severely dependent or fragile 
• 
Unable to provide consent personally 
• 
Unable to complete questionnaires for self-assessment independently 
• 
Unilateral hearing loss 
• 
Sequential and simultaneous bilateral cochlear implant recipients 
• 
Ossification or other cochlear anomalies preventing full electrode insertion 
• 
Retro cochlear or central origins of hearing impairment. 
• 
Significant comorbidities preventing study participation (e.g. blindness, immobility or in 
a wheel chair, severe aphasia,..) 
• 
Medical contraindications to surgery  
• 
Clinically standard fail criteria for CI candidacy in regards to chronic depression, 
dementia, and cognitive disorders. 
• 
Unrealistic expectations on the part of the subject, regarding the possible benefits, 
risks and limitations that are inherent to the procedure and prosthetic device. 
8.6.3 
Criteria and procedures for subject’s withdrawal or discontinuation 
Subjects can decide to withdraw from the investigation without indicating any reasons at any 
time. The patient will then continue to be managed by the clinic as per the routine clinical 
practice with the intention to treat the hearing impairment accordingly.  
The investigator may decide to discontinue a patient due to major non-compliance with the 
Observational Study Protocol requirements (e.g. three-visit schedule not met) or in the event 

 
 
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the patient demonstrates rapid decline in overall health and is unable to participate in the study 
procedures.   
8.6.4 
Point of enrolment 
Subjects are enrolled into the clinical investigation when they have signed the Patient Informed 
Consent Form prior to Pre-implant assessment Visit 1 (Pre1). 
8.6.5 
Expected duration of the clinical investigation 
From first enrollment of the first subject to final assessment at Visit 3 of the last enrolled subject 
the total expected duration is 4 years. 
8.6.6 
Expected duration of each subject's participation 
The expected duration for each subject from enrolment is 20 months (+/- 1 month).  
8.6.7 
Number of subjects required to be included in the clinical investigation 
The number of subjects to be enrolled will be N=100 subjects across the seven investigator 
implant sites.    
In view of possible attrition rate of 5 to 10 % of enrolled subjects, randomly lost to follow up 
during the course of the study any time after enrolment, all subjects enrolled will be included 
in the final analysis as the “intention to treat” cohort with the majority being assessed “as per 
protocol”.  
The number of subjects recruited per site will reflect the local normal practices for treatment in 
the elderly population during the study enrolment time frame of 24 months. The study will aim 
to accrue subjects distributed across all study sites and languages to avoid site and cultural 
bias. 
8.6.8 
Estimated time needed to select this number (i.e. enrolment period) 
Thirty-one months from first to last (100th) patient enrolled at Visit 1 in 8 implant clinics.  
8.7 Procedures 
As an observational study, there will be no change in the treatment of the hearing impaired 
patient’s hearing loss compared to local routine practices. When the patient agrees to 
participate as a subject in the study, a set of data related to their outcomes from the routine 
hearing treatment will be gathered for the purposes of the study. 
The dataset gathered is composed of outcomes from routine audiological and geriatric 
assessments that are completed by experienced professionals at the clinic, as well as self- 
assessments via questionnaires completed by the patient directly and with assistance as 
needed.  
A detailed list of the evaluations performed, the data gathered and guidelines for administration 
of questionnaires are described in a separate document “Procedure document”. 
8.8 Monitoring Plan 
The monitoring schedule and documents viewed are detailed in a separate document 
“Monitoring Plan”. 

 
 
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9 Statistical Considerations 
For primary, secondary and tertiary study objectives an Intra subject endpoint comparison is 
used: All pairwise comparisons are of interest i.e. preimplant to 12 months postimplant, 
preimplant to 18 months postimplant, and the change from 12 to 18 months. 
The power analysis applied for the study design was based on an available data set (n= 67, 
Cochlear-IROS data)  of repeated measures on the HUI3, collected for elderly CI-patients, at 
preimplant and 12 months post implant intervals. The HUI 3 will serve as the primary outcome 
measure for this study to measure the added health utility gain for the multi- attribute health 
status from preimplant (@ < 2 months first activation) to the postimplant (@ 12 months post 
activation) interval in a population of implanted 60+ year olds. 
The minimum clinically important change over two intervals for the HUI3 is 0.03 units on a 
scale of 0 representing poor health and 1.0 representing full health. 
The power calculations were performed using the free package G*Power 3.1 by a consultant 
statistician at the Macquarie Sydney University. 
The differences observed for the implanted elderly population in the existing Cochlear IROS 
dataset demonstrated a mean change = 0.165 at 95% confidence interval, with a range of 
0.109 to 0.221 and a non-normal distribution for the cohort of 67 implanted elderly recipients 
over the age of 60 years examined.  
Using this information to estimate the sample size required for significant changes on the HUI3 
multi attribute score, for intra subject comparisons of endpoints, aiming for a change of > 0.10 
units between the two test intervals, and a power of 90% and using a two-side paired t-test to 
calculate the 5% significance level, a sample of N=68 is required for the multi-attribute health 
utility. For comparison of changes in self ratings individual health domains of the HUI3, aiming 
for a power of 80% a sample of N=100 is required.    
Study statistical analysis plan is available as separate document. 
10 Data Management  
Data collection will be performed using eCRFs within a validated and verified electronic data 
capture system (EDC) with role based security and unique login credentials for each individual 
user. Site personnel will be trained on the completion of the eCRFs. The investigator will 
confirm data accuracy by providing an electronic signature. 
Data will be collected, stored and analysed in a secure manner in compliance with 21 CFR 
Part 11 and privacy regulations. 
The EDC has built-in edit checks and will generate automated data clarification forms (DCFs). 
The clinical project manager (CPM), monitor and data manager may review the data for 
medical, scientific and data integrity, and will create manual DCFs where appropriate. 
Responses to DCFs will be entered into the EDC, with updates to the study data where 
required. 
Following completion of the study, investigators will be provided with the data for their site (e.g. 
on a CD-ROM) for national and site specific archiving requirements. 
After the final clinical investigation report (CIR) has been approved the data will be stored on 
CD-ROM and archived with the trial master file at the sponsor’s site. The data are stored for a 
period of 15 years. 
11 Amendments to the Observational Study Protocol (CIP) 
No changes in the study procedures shall be effected without mutual agreement of the 
investigator(s) and the Sponsor. All changes must be documented by a signed (CIP) 

 
 
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amendment. Substantial changes that impact the patient experience during the trial will require 
notification to the responsible Ethics Committee(s). 
12 Deviations from the Observational Study Protocol 
As an observational study, it is recommended that the investigator comply with the protocol as 
far as possible for all enrolled subjects. Protection of the subjects’ rights, safety, privacy and 
well-being is always paramount throughout the study and at any time. Deviations to the study 
protocol shall be documented and reported to the Sponsor as soon as possible. The EC should 
be informed by the investigator as applicable.   
13 Device accountability 
Routine procedures for commercially implanted device registration and accompanying 
warranty are to be followed. 
14 Statements of compliance 
14.1 Declaration of Helsinki and compliance with standards 
The observational study shall be conducted in accordance with the ethical principles that have 
their origin in in the most recent version of the Declaration of Helsinki (2013 or later), the EN 
ISO 14155:2011 and any regional or national regulations, as appropriate. The study will be 
registered on ClinicalTrials.gov. 
14.2 Ethics Committee and Competent Authority Approval 
Each clinic wishing to collaborate and publish their data must obtain Ethics Committee (EC) 
Approval/Opinion (or Competent Authority (CA) Approval if applicable) for their participation in 
the study and obtain formal approval prior to enrolling the first subject locally. 
The observational study shall not commence prior to the written favourable opinion or approval 
from the EC and or CA (if appropriate) is obtained. 
The investigator shall submit the final version of the observational study protocol, the patient 
informed consent (PIC) and all subsequently required documents to the Ethics Committee.  A 
copy of the Ethics Committee opinion/approval shall be provided to the sponsor. A copy of the 
EC approval shall be retained in the clinic for the locally dictated time requirements.  
Sponsor and investigator shall continue the communication with the EC as required by national 
regulations, the observational study protocol, or the responsible EC.  
Any additional requirements imposed by the EC or CA shall be followed. 
The investigator shall submit the appropriate documentation if any extension or renewal of the 
EC approval is required. In particular substantial amendments to the observational study 
protocol, the informed consent, or other written information provided to subjects must be 
approved in writing by the EC. 
The investigator will report to the EC any new information that may affect the safety of the 
subjects or the conduct of the observational study. The investigator shall send written status 
summaries of the observational study to the EC regularly as per local EC requirements. 
Upon completion of the observational study, the investigator shall provide the EC with a brief 
report of the outcome of the observational study as per local EC requirement. 

 
 
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The observational study is covered by a clinical trial insurance meeting the requirements of the 
participating countries. National requirements are specified in the national patient informed 
consent (PIC).  
14.3 Audits and Supervision 
Study sites and study documentation may be subject to Quality Assurance audits during the 
course of the observational study. In addition, regulatory bodies at their discretion may conduct 
inspections, during and after study completion. 
14.4 Study Records 
The investigational site will receive and has to maintain an Investigator’s File which does 
include without limitation at a minimum the signed Observational Study protocol, the EC 
approval letter, the CA approval letter (if applicable), completed Patient Informed Consent 
Forms, Investigator copies of all CRFs, correspondence with the Sponsor and third parties (if 
applicable) related to the Study, a subject identification list, and a site delegation and signature 
sheet. All study records and defined source documents shall be archived at the investigational 
centre for at least 15 years after the end of the study. 
15 Patient Informed Consent (PIC) process 
15.1 Obtaining informed consent 
The investigator must obtain written informed consent from the subject prior to any study 
related examination or activity, and after explaining the rationale for and the details, aims and 
objectives of the study, the risks and benefits and alternative treatments, and the extent of the 
subject’s involvement. Ample time must be provided for the subject to inquire about details of 
the observational study and to decide whether to participate. All questions about the 
observational study should be answered to the satisfaction of the subject or the subject’s 
legally acceptable representative. Subjects must not be coerced or unduly influenced to 
participate or to continue to participate in the study. 
Each subject and the person who conducted the informed consent discussion must sign and 
date the patient informed consent form. Where required, a witness must sign and personally 
date the consent form. 
A copy of the information leaflet and consent form must be given to the subject. All signed 
Informed Consent Forms must be archived in the Investigator’s File at the investigational site, 
according to the requirements of the country’s health regulations, after completion of the 
observational study.  
The subject or the subject’s legally acceptable representative must be informed in a timely 
manner if new information becomes available that may be relevant to the subject’s willingness 
to continue participation in the observational study. The communication of this information 
must be documented. 
The investigator shall forward any amendment made to the approved subject informed consent 
for review to the Sponsor or Study Monitor and any other written information to be provided to 
the subject, prior to submission to his EC.  
15.2 Data Privacy 
Subjects will be identified on CRFs or similar documents (e.g. questionnaires) by a unique 
anonymized subject identification code. Completed CRFs or similar documents are confidential 
documents and will only be available to the Sponsor and their representatives, the investigator, 
the study statistician, and if requested to the Ethics Committee and national regulatory 
authorities.  

 
 
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Section 1: Principal Investigators and sites are updated accordingly. Enrolment period is 
extended from 24 to 31 months. 
Section 8.1: “if not agreed differently” is added as a condition to the anticipated subject 
recruitment number. 
Section 8.6.8: Enrolment period and number of clinics are updated accordingly.  
Section 11: The reference to a template is removed as no longer used to document CIP 
changes. 
Section 22 Appendix I: List of investigators is updated accordingly. 
20.2 Changes from version 1.0 to version 2.0 
Cover page: A note is added for “Observational” as this terminology tends to disappear from 
national classification. In France and in Spain, the study is classified as “low risk intervention” 
in regards to the additional assessments performed. 
Introductory table: The details of the Clinical Research Organisation (CRO) is updated 
CIP Signature page:  Sponsor signature, the name and function are updated 
Section 1: Starting date is updated in the Clinical Investigation Synopsis to the real starting 
date: 06 November 2017 
Section 5.2.10: HRCU paragraph has been updated to answer Ethical committee request to 
provide additional details. The time to complete the assessment has been updated. 
Section 9: For clarity additional text was added in regards to Intra endpoint comparison. As 
well, it was added that statistical analysis plan is available as separate document. 
Section 16: Definition of incidents has been updated to reflect changes in the MDR regulation 
Section 19: A potential preliminary publication for completion of 1 year evaluation by a 
subgroup of the study cohort has been added. 
21 Bibliography 
Archbold S, Lutman ME, Marshall DH. Categories of Auditory Performance. Ann Otol Rhinol Laryngol Suppl 1995, 
166:312. 
de Jong Gierveld, J., & van Tilburg, T.G. (2006). A 6-item scale for overall, emotional, and social loneliness: 
Confirmatory tests on survey data. Research on Aging, 28, 582-598  
http://home.fsw.vu.nl/tg.van.tilburg/manual_loneliness_scale_1999.html 
De Raeve L, and van hardeveld R, Prevalence of cochlear implants in Europe: what do we know and what can we 
expect? Journal of Hearing Science, 2013, Vol 3, 9-16 
Derouesne C, Poitreneau J, Hugonot L, et al. Mini-Mental State Examination (MMSE): a practical tool for 
evaluating cognitive status. The consensual French version. Press Med.1999; 28(21): 1141-1148. 
Feeny, D., Furlong, W., Boyle, M., & Torrance, G. W. (1995).Multi-attribute health status classification systems. 
Health Utilities Index. Pharmacoeconomics, 7(6), 490–502. 
Feeny, D., Furlong, W., Torrance, G. W., Goldsmith, C. H., Zhu, Z., DePauw, S., Denton, M., & Boyle, M. (2002). 
Multi-attribute and single-attribute utility functions for the health utilities index mark 3 system. Medical Care, 40(2), 
113–128. 
Folstein MF, Folstein SE, McHugh PR. “MiniMental State”: A practical method for grading the cognitive state of 
patients for the clinician. J Psychiatr Res. 1975; 12(3):189-198. 
Gatehouse,S and Noble, W. The speech, spatial and qualities of hearing scale (SSQ). International journal of 
audiology 2004; 43(2): 85-99. 
Gilmore, L.(2010) “The Inter-Rates Rehability of Categories of Auditory Performance-II (CAP)-II”, University of 
Southampton, Faculty of Engineering, Science, Mathematics, Institute of sound and vibration research, p.20. 

 
 
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Newman C, Jacobson G, Hug G, Weinstein B, and Malinoff R. Practical Method for Quantifying Hearing 
Aid Benefit in Older Adults, J Am Acad Audiol (1991) ; 2 : 70-75.  
Lachowska M, Pastuszka A, Glinka P, Niemczyk K. Benefits of cochlear implantation in deafened adults. Audiol 
Neurootol. 2014;19 Suppl 1:40-4. 
Lawton MP. The functional assessment of elderly people. J Am Geriatr Soc. 1971;19(6):465-481. 
Lichtenberger, E.O.; Kaufman, A.S. (2009). Essentials of WAIS-IV assessment. Essentials of Psychological 
Assessment. Hoboken, N.J.: Wiley. p. 27.  
Lechevallier-Michel N, Fabrigoule C, Lafont S, et al. Normative data for the MMSE, the Benton visual retention 
test, the Isaac’s set test, the digit symbol substitution test and the Zazzo’s cancellation task in subjects over the 
age 70: results from the PAQUID study. RevNeurol (Paris). 2004; 160(11): 1059-1070. 
Lin F. Implications of Hearing Loss for Older Adults. Audiology & Neurotology 2011:17. 
Noble W and Gatehouse S. Interaural asymmetry of hearing loss, Speech, Spatial and Qualities of Hearing Scale 
(SSQ) disabilities, and handicap. Int J Audiol. 2004 Feb;43(2):100-14. 
Massetti M, Aballe S, Videau Y, Remuzat C, Roız J, and Toumi M. A comparison of HAS & NICE guidelines for 
the economic evaluation of health technologies in the context of their respective national health care systems and 
cultural environmentsJournal of Market Access & Health Policy 2015, 3: 24966 - 
http://dx.doi.org/10.3402/jmahp.v3.24966 
Mosnier, I., Bebear, J. P., Marx, M, Fraysse, B., Granade, G. L., Mondain, M., Sterkers-Artieres, F., and Bordure, 
P.: Improvement of cognitive function after cochlear implantation in elderly patients. JAMA Otolaryngol Head Neck 
Surg. 2015 May 1;141(5):442-50 
Olze H, Gräbel S, Förster U, Zirke N, Huhnd LE, Haupt H, Mazurek B. Elderly patients benefit from cochlear 
implantation regarding auditory rehabilitation, quality of life, tinnitus and stress. Laryngoscope. 2012 
Jan;122(1):196-203. 
Pangman, VC; Sloan, J; Guse, L. (2000). "An Examination of Psychometric Properties of the Mini-Mental State 
Examination and the Standardized Mini-Mental State Examination: Implications for Clinical Practice". Applied 
Nursing Research 13 (4): 209–213.  
Podsiadlo D, Richardson S. The timed "Up & Go": a test of basic functional mobility for frail elderly persons. J Am 
Geriatr Soc. 1991 Feb;39(2):142-8. 
Prince MJ, Wu F, Guo Y, Gutierrez Robledo LM, O’Donnell M, Sullivan R, Yusuf S.  The burden of disease in 
older people and implications for health policy and practice. Lancet. 2015 Feb 7;385(9967):549-62. doi: 
10.1016/S0140-6736(14)61347-7. Epub 2014 Nov 6 
Sheikh, J. I., & Yesavage, J. A. (1986). Geriatric Depression Scale (GDS): Recent evidence and development of a 
shorter version. Clinical Gerontologist, 5, 165-173. 
Tombaugh T, Trail Making Test A & B:Normative data stratified by age and education. Archives of Clinical 
Neuropsychology 19 (2004) 203-214.  
 
World Health Organisation (2011). Hearing Loss Estimates. Mortality and Burden of Disease unit, WHO.