Assessment of Novel Sound Changing Principles in Hearing Instruments to Determine Their Application - 2020_09
Phase: NA
Conditions: Hearing Loss
Sponsor: Sonova AG

Study Protocol & Statistical Analysis Plan 
 
Assessment of Novel Sound Changing Principles in Hearing Instruments to 
Determine Their Application – Sonova2020_09 
 
NCT04578457 
 
 

s wi s s e t h i c s  
Schweizerische Ethikkommissionen für die Forschung am Menschen 
Commissions d’éthique suisses relative à la recherche sur l'être humain 
Commissioni etiche svizzere per la ricerca sull'essere umano 
Swiss Ethics Committees on research involving humans 
 
Clinical Study Protocol  
ST-P4AC, Version 1.4 of 28.06.2018 
Page 1 of 54 
 
 
Clinical Study Protocol: Assessment of novel sound changing principles 
in hearing instruments to determine their application 
 
 
 
  
 
 
Study Identifier: S&T-P4AC 
 
 

 
Clinical Study Protocol  
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Assessment of novel sound changing principles in 
hearing instruments to determine their application 
 
Clinical Study Protocol 
 
ASSESSMENT OF NOVEL SOUND CHANGING PRINCIPLES IN HEARING INSTRUMENTS TO DETERMINE 
THEIR APPLICATION. 
[A methodical evaluation of novel sound changing principles in CE-labelled Sonova brand hearing 
instruments (e.g. Phonak hearing instruments) is intended to be conducted on hearing impaired and 
normal hearing participants. These sound changing principles are enabled by respective hearing 
instrument technologies and hearing instrument algorithms. The aim of the study is to investigate and 
asses strength and weaknesses of these novel sound changing principles in terms of hearing 
performance to determine their application in hearing instruments (Phase of development). Both, 
objective laboratory measurements as well as subjective evaluations in real life environment will be 
carried out. This will be a controlled, single blinded and randomised active comparator clinical 
evaluation which will be conducted mono centric at Sonova AG Headquarter based in Stäfa] 
 
Study Type: 
Clinical trial with Medical Device (MD)  
Study Categorisation: 
Risk category according to LHR is A 
Study Registration: 
This study will be registered at clinicaltrials.gov as a primary 
register and additionally it will be registered in the Swiss Federal 
Complementary Database as soon as the ethics application is 
approved by CEC 
Study Identifier: 
S&T-P4AC 
Sponsor: 
Sonova AG 
Contact Person: Juliane Raether 
Laubisrütistrasse 28 
CH-8712 Stäfa   
Email: Juliane.Raether@sonova.com 
 
Phone: 058 928 86 37 
Investigational Product: 
MD: Sonova brand hearing systems (primarily Phonak hearing 
systems). The hearing systems comprise hearing instruments 
containing respective hearing instrument software and acoustic 
couplings, fitting software and wireless accessories.  
Protocol Version and Date: 
Version 1.4, 28.06.2018   
 
 
CONFIDENTIAL 
The information contained in this document is confidential and the property of the sponsor. The 
information may not - in full or in part - be transmitted, reproduced, published, or disclosed to others 
than the applicable Competent Ethics Committee(s) and Regulatory Authority(ies) without prior written 
authorisation from the sponsor except to the extent necessary to obtain informed consent from those 
who will participate in the study. 
 

Signature Page(s)
Study number
Study Title
Study-ID: 2016-00624
Assessment of novel
sound
changing
principles
in
hearing
instruments to determine their application
The Sponsor-Investigator and
trial
statistician
have approved the
protocol version
1.3 (dated
07.06.2018, and confirm hereby to conduct the study accotding to the protocol, current version ofthe
World Medical Association Deciaration
of Helsinki,
ICH-GCP guidelines or ISO
14155 norm
if
applicable and the local legally applicable requirements.
Sponsor:
Stäfa /28.06.2018
Place/Date
Principle Investigator:
Stäfa / 28.06.2018
Place/Date
Sonova AG (contact person: Juliane Raether)
SiXature - -
Juliane Raether
).j
Signre
Clinical Study Protocol
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Page 3 of 54

Local Principal Investigator at study site*:
1 have read and understood this trial protocol and agree to conduct the trial as Set out in this study
protocol, the current version of the World Medical Association Declaration of Helsinki, ICH-GCP
guidelines or ISO 14155 norm and the local Iegally applicable requirements.
Site
Sonova AG
Laubisrütistrasse 28
CH-8712 Stäfa
Principal investigator
Juliane Raether
StäfaI28.06.2018
Place/Date
Si ature
*Note. In multicentre studies, this page must be individually signed by all participating Local Principal
1 nvestigators.
Clinical Study Protocol
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Clinical Study Protocol  
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Table of Contents 
STUDY SYNOPSIS ................................................................................................................................. 8 
STUDY SUMMARY IN LOCAL LANGUAGE ....................................................................................... 11 
ABBREVIATIONS ................................................................................................................................. 11 
STUDY SCHEDULE .............................................................................................................................. 14 
1. 
STUDY ADMINISTRATIVE STRUCTURE .................................................................................... 17 
1.1 
Sponsor, Sponsor-Investigator .....................................................................................................17 
1.2 
Principal Investigator(s) ................................................................................................................17 
1.3 
Statistician ("Biostatistician") ........................................................................................................17 
1.4 
Laboratory ....................................................................................................................................17 
1.5 
Monitoring institution ....................................................................................................................18 
1.6 
Data Safety Monitoring Committee ..............................................................................................18 
1.7 
Any other relevant Committee, Person, Organisation, Institution ................................................18 
2. 
ETHICAL AND REGULATORY ASPECTS .................................................................................. 19 
2.1 
Study registration .........................................................................................................................19 
2.2 
Categorisation of study.................................................................................................................19 
2.3 
Competent Ethics Committee (CEC) ...........................................................................................19 
2.4 
Competent Authorities (CA) .........................................................................................................19 
2.5 
Ethical Conduct of the Study ........................................................................................................19 
2.6 
Declaration of interest ..................................................................................................................20 
2.7 
Patient Information and Informed Consent ..................................................................................20 
2.8 
Participant privacy and confidentiality ..........................................................................................20 
2.9 
Early termination of the study .......................................................................................................20 
2.10 Protocol amendments ..................................................................................................................21 
3. 
BACKGROUND AND RATIONALE .............................................................................................. 22 
3.1 
Background and Rationale ...........................................................................................................22 
3.2 
Investigational Product (treatment, device) and Indication ..........................................................25 
3.3 
Preclinical Evidence .....................................................................................................................25 
3.4 
Clinical Evidence to Date .............................................................................................................25 
3.5 
Dose Rationale / Medical Device: Rationale for the intended purpose in study (pre-market MD)26 
3.6 
Explanation for choice of comparator (or placebo) ......................................................................26 
3.7 
Risks / Benefits .............................................................................................................................26 
3.8 
Justification of choice of study population ....................................................................................27 
4. 
STUDY OBJECTIVES ................................................................................................................... 27 
4.1 
Overall Objective ..........................................................................................................................27 
4.2 
Primary Objective .........................................................................................................................27 
4.3 
Secondary Objectives ..................................................................................................................28 
4.4 
Safety Objectives .........................................................................................................................28 
5. 
STUDY OUTCOMES ..................................................................................................................... 29 
5.1 
Primary Outcome .........................................................................................................................29 
5.2 
Secondary Outcomes ...................................................................................................................30 
5.3 
Other Outcomes of Interest ..........................................................................................................31 
5.4 
Safety Outcomes ..........................................................................................................................31 
6. 
STUDY DESIGN ............................................................................................................................ 32 
6.1 
General study design and justification of design ..........................................................................32 
6.2 
Methods of minimising bias ..........................................................................................................33 

 
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6.2.1 Randomisation .....................................................................................................................33 
6.2.2 Blinding procedures .............................................................................................................33 
6.2.3 Other methods of minimising bias ........................................................................................33 
6.3 
Unblinding Procedures (Code break) ...........................................................................................33 
7. 
STUDY POPULATION .................................................................................................................. 34 
7.1 
Eligibility criteria ............................................................................................................................34 
7.2 
Recruitment and screening ..........................................................................................................34 
7.3 
Assignment to study groups .........................................................................................................35 
7.4 
Criteria for withdrawal / discontinuation of participants ................................................................35 
8. 
STUDY INTERVENTION ............................................................................................................... 36 
8.1 
Identity of Investigational Products (treatment / medical device) .................................................36 
8.1.1 Experimental Intervention (treatment / medical device) .......................................................36 
8.1.2 Control Intervention (standard/routine/comparator treatment / medical device) .................36 
8.1.3 Packaging, Labelling and Supply (re-supply) ......................................................................36 
8.1.4 Storage Conditions...............................................................................................................36 
8.2 
Administration of experimental and control interventions ............................................................36 
8.2.1 Experimental Intervention ....................................................................................................36 
8.2.2 Control Intervention ..............................................................................................................37 
8.3 
Dose / Device modifications .........................................................................................................37 
8.4 
Compliance with study intervention ..............................................................................................37 
8.5 
Data Collection and Follow-up for withdrawn participants ...........................................................37 
8.6 
Trial specific preventive measures ...............................................................................................37 
8.7 
Concomitant Interventions (treatments) .......................................................................................37 
8.8 
Study Drug / Medical Device Accountability ................................................................................38 
8.9 
Return or Destruction of Study Drug / Medical Device ................................................................38 
9. 
STUDY ASSESSMENTS ............................................................................................................... 39 
9.1 
Study flow chart(s) / table of study procedures and assessments ...............................................39 
9.2 
Assessments of outcomes ...........................................................................................................40 
9.2.1 Assessment of primary outcome ..........................................................................................40 
9.2.2 Assessment of secondary outcomes ...................................................................................41 
9.2.3 Assessment of other outcomes of interest ...........................................................................41 
9.2.4 Assessment of safety outcomes ..........................................................................................41 
9.2.5 Assessments in participants who prematurely stop the study .............................................41 
9.3 
Procedures at each visit ...............................................................................................................41 
9.3.1 Screening Appointment ........................................................................................................42 
9.3.2 Pre-study appointment .........................................................................................................42 
9.3.3 Main study appointments .....................................................................................................42 
9.3.4 Final appointment .................................................................................................................42 
10. SAFETY ......................................................................................................................................... 43 
10.1 Drug studies .................................................................................................................................43 
10.2 Medical Device Category C studies .............................................................................................43 
10.3 Medical Device Category A studies .............................................................................................43 
10.3.1 Definition and Assessment of safety related events ............................................................43 
10.3.2 Reporting of Safety related events.......................................................................................43 
11. STATISTICAL METHODS ............................................................................................................. 44 
11.1 Hypothesis ....................................................................................................................................44 

 
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11.2 Determination of Sample Size ......................................................................................................44 
11.3 Statistical criteria of termination of trial ........................................................................................44 
11.4 Planned Analyses .........................................................................................................................44 
11.4.1 Datasets to be analysed, analysis populations ....................................................................45 
11.4.2 Primary Analysis ..................................................................................................................45 
11.4.3 Secondary Analyses ............................................................................................................45 
11.4.4 Interim analyses ...................................................................................................................45 
11.4.5 Safety analysis .....................................................................................................................45 
11.4.6 Deviation(s) from the original statistical plan .......................................................................45 
11.5 Handling of missing data and drop-outs.......................................................................................45 
12. QUALITY ASSURANCE AND CONTROL .................................................................................... 46 
12.1 Data handling and record keeping / archiving ..............................................................................46 
12.1.1 Case Report Forms ..............................................................................................................46 
12.1.2 Specification of source documents ......................................................................................46 
12.1.3 Record keeping / archiving ..................................................................................................47 
12.2 Data management ........................................................................................................................47 
12.2.1 Data Management System ..................................................................................................47 
12.2.2 Data security, access and back-up ......................................................................................47 
12.2.3 Analysis and archiving .........................................................................................................47 
12.2.4 Electronic and central data validation ..................................................................................47 
12.3 Monitoring .....................................................................................................................................47 
12.4 Audits and Inspections .................................................................................................................47 
12.5 Confidentiality, Data Protection ....................................................................................................48 
12.6 Storage of biological material and related health data .................................................................48 
13. PUBLICATION AND DISSEMINATION POLICY.......................................................................... 49 
14. FUNDING AND SUPPORT ............................................................................................................ 50 
14.1 Funding ........................................................................................................................................50 
14.2 Other Support ...............................................................................................................................50 
15. INSURANCE .................................................................................................................................. 50 
16. REFERENCES ............................................................................................................................... 51 
17. APPENDICES ................................................................................................................................ 54 
 
 
 

 
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STUDY SYNOPSIS  
(Clin O, Appendix 3, 1.1, 2.1, 3.1, 4.1; Appendix 5, 2b; AGEK Sum mary)  
 
Sponsor /  Sponsor -
Investigat or 
Sonova AG 
Study Title: 
Assessment of novel sound changing principles in hearing instruments to 
determine their application 
Short Title / Study ID: 
S&T-P4AC / 2016-00624 
Protocol Version  and 
Date: 
Version 1.3, 07.06.2018   
Trial regist ratio n: 
After approval by CEC in:                                                             
• 
clinicaltrials.gov     
• 
Swiss Federal Complementary Database                                            
Study category and 
Ration ale 
Risk category A. 
The study is a trial with medical devices (comprising hearing instruments, 
hearing instrument software, acoustic couplings, fitting software and 
wireless accessories). All investigational devices are CE-labelled and their 
application is done according to the specialised information. 
Clinical  Phase: 
Phase of development  
Back ground and 
Ration ale: 
This study is the description of a series of several studies concerning the 
evaluation of novel sound changing principles in hearing instruments  
which are continuously developed and improved. For each sound changing 
principle a separate (sub-) study will be conducted. These sound changing 
principles are enabled by respective hearing instrument technology and 
hearing instrument algorithms. The mentioned technology and algorithms 
are applied in hearing instruments as features and functions and intend to 
improve the hearing performance for an hearing impaired end-user. 
The purpose of this evaluation is to investigate these novel applications 
regarding their supposed benefit and possible secondary effects with 
respect to hearing performance. The results should promote the hearing 
instrument development to create meaningful applications, improve the 
hearing instrument products and hence provide a maximum benefit in 
terms of hearing performance for an end user.  
Objective(s): 
 
 
 
 
 
 
 
All studies pursue the same goal: to investigate the audiological 
performance for each of these novel sound changing principles on hearing 
impaired subjects using respective hearing performance outcome 
measures. The results are assessed in referenced to those from sound 
changing principles used in recent hearing instruments and/or with the 
sound changing principle disabled. 
Primary Objective:  
Assess the performance of the respective novel applications for their 
intended use and examine different parameter settings of the sound 
changing principles for the associated hearing dimensions. These hearing 
dimensions are either: 
- 
speech intelligibility, 
- 
signal clarity or 
- 
sound quality / hearing comfort  
Secondary Objective:  
Investigate the effect of the respective applications to hearing impaired 
subjects in real world environment.    

 
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Outcom e(s): 
 
The primary outcomes are the laboratory test results. These tests intend to 
evaluate the hearing performance for a corresponding hearing dimension 
(speech intelligibility, signal clarity, sound quality / hearing comfort). For 
each sound changing principle the suited test method is chosen.    
The secondary outcomes are the subjective test results and comments 
gathered in real world environment (e.g. during guided walks) and with 
questionnaires during the home trials.  
Study design : 
Active comparator study, controlled, single blinded, randomised, cross-over 
design. 
Inclu sion  / Exclusion  
criteria: 
Participants fulfilling all of the following inclusion criteria are eligible for the 
study:  
• 
Adult hearing impaired persons (minimum age: 18 years) with and 
without (experience with) hearing aids 
• 
Adult normal hearing persons (minimum age: 18 years) 
• 
Healthy outer ear (without previous surgical procedures)  
• 
Ability to fill in a questionnaire conscientiously 
• 
Informed Consent as documented by signature  
 
The presence of any one of the following exclusion criteria will lead to 
exclusion of the participant: 
• 
Contraindications to the MD in this study, e.g. known 
hypersensitivity or allergy to the investigational product 
• 
Limited mobility and not in the position to attend weekly 
appointments  
• 
Limited ability to describe listening impressions/experiences and 
the use of the hearing aid 
• 
Inability to produce a reliable hearing test result  
• 
Massively limited dexterity  
• 
Known psychological problems  
• 
Known central hearing disorders 
Measure ments and 
procedures: 
The study intervention comprises hearing performance assessment 
measures concerning speech intelligibility, signal clarity and sound quality / 
hearing comfort. Each study concerns the evaluation of a specific sound 
changing principle. With respect to the particular sound changing principle 
and the focused aim regarding hearing performance the corresponding 
outcome measures will be chosen. 
Study Product / 
Intervention :  
MD: Sonova brand hearing systems (comprising hearing instruments with 
respective hearing instrument software and acoustic couplings, fitting 
software and wireless accessories). Primarily Phonak hearing systems will 
be chosen. The product will be applied for the duration of the study only.   
Control Int ervention  
(if applic able): 
MD: Sonova brand hearing systems (comprising hearing instruments with 
respective hearing instrument software and acoustic couplings, fitting 
software and wireless accessories). Primarily Phonak hearing systems will 
be chosen. The product will be applied for the duration of the study only.   
Number of 
Participant s with 
Ration ale: 
For a single study one or more pre-studies are conducted with only a few 
participants to proof the study concept and/or find valuable settings. If the 
results of the pre-studies are promising, the respective main study will start. 
For each pre-study a maximum of 5 participants is considered. For the 
main study normally 20 - 25 participants are considered. If possible a 
power analysis is carried out for each study to determine the necessary 
number of subjects. A maximum of 60 subjects will participate per year. 
This is a maximum of 600 subjects in total over 10 years. 
Study Duratio n: 
10 years (01.07.2016 – 30.06.2026) 
Study Sched ule: 
Month Year of First-Participant-In (planned): March 2018 
Month Year of Last-Participant-Out (planned): June 2026  

 
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Investigat or(s): 
Juliane Raether (Principle Investigator, further investigators are specified in 
a staff list) 
Sonova AG, Laubisrütistrasse 28, 8712 Stäfa, Phone: 058 928 01 01 
Study Centre(s): 
Single-centre (Sonova AG, Stäfa).  
Statist ical 
Consider atio ns: 
Sample size according to experience and to established specialized 
literature.  
Descriptive statistics: Frequency distribution, mean and standard deviation, 
median and quartile, boxplot, histogram, scatterplot, correlation coefficient 
(Pearson, Spearman). 
Inferential statistics: t-Test, Mann-Whitney-U-Test, Wilcoxon-Test, ANOVA, 
MANOVA. 
GCP Statement : 
This study will be conducted in compliance with the protocol, the current 
version of the Declaration of Helsinki, the ICH-GCP or ISO EN 14155 (as 
far as applicable) as well as all national legal and regulatory requirements.  
 
 
 

 
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STUDY SUMMARY IN LOCAL LANGUAGE  
In dieser Studienreihe findet eine methodische Evaluation neuartige Schalländerungsprinzipien in 
Hörgeräten an Studienteilnehmern mit Hörminderung statt. Die Schalländerungsprinzipien werden 
durch 
entsprechende 
Hörgerätetechnologien 
und 
Hörgerätealgorithmen 
ermöglicht. 
Diese 
Technologien und Algorithmen sind als sogenannte „Features und Funktionen“ in Hörgeräten 
implementiert. Sie haben das Ziel die Hörleistung für den Nutzer in Bezug auf Sprachverständlichkeit, 
Signalklarheit und Klangqualität / Hörkomfort zu verbessern.  
 
Das Ziel der Evaluierungsstudien ist es, diese neuartigen Schalländerungsprinzipien bezüglich ihres 
Nutzens sowie möglicher Sekundäreffekte für schwerhörige Personen zu untersuchen. Dazu werden 
den Probanden Hörgeräte angepasst und entsprechende audiologische Testverfahren im Labor und 
Befragungen mit Hilfe von Fragebögen nach Tests in realen Umgebung durchgeführt. So sollen 
Stärken und Schwächen der jeweiligen Applikation bestimmt und in Referenz zu Ergebnissen mit 
bisherigen 
Hörgeräten 
bewertet 
werden. 
Des 
Weiteren 
sollen 
unterschiedliche 
Parametereinstellungen der neuen Schalländerungsprinzipien untersucht werden um die für den 
Hörgerätenutzer sinnvollste Einstellung zu ermitteln. Die Studien erfolgen unter kontrollierten, 
randomisierten Bedingungen am Hauptsitz der Sonova AG in Stäfa.   
 
Die Resultate dieser Untersuchungen unterstützen die Weiterentwicklung von Hörgeräten. Es sollen 
sinnvolle Anwendungen der neuen Technologien und Algorithmen bestimmt und die Hörgeräte 
hinsichtlich ihres Nutzens verbessert werden. Das Ziel dieser Entwicklung ist es, den grösstmöglichen 
Vorteil für den Hörgerätenutzer zu erzeugen.      
ABBREVIATIONS 
AE 
Adverse Event  
ANL 
Acceptable Noise Level  
ASR 
Annual Safety Report 
BMLD 
Binaural Masking Level Difference 
BTE 
Behind-The-Ear device 
CA 
Competent Authority (e.g. Swissmedic) 
CEC 
Competent Ethics Committee 
CRF 
Case Report Form  
CU 
Categorial Unit 
ClinO 
 
Ordinance on Clinical Trials in Human Research (in German: KlinV, in French: 
OClin) 
CTCAE 
Common terminology criteria for adverse events 
dB 
Decibel 
DD 
Device Deficiencies 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDA 
Electro Dermal Activity (Galvanic Skin Response) 
EDC 
Electronic Data Capture 
EEG 
Electroencephalography 
EMG 
Electromyography 
FM 
Frequency Modulation 

 
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GCP 
Good Clinical Practice  
GöSa 
Göttinger Satztest 
HEG 
Hemoencephalography 
IB 
Investigator’s Brochure 
IIC 
Invisible-In-Canal device 
ILD 
Interaural Level Difference 
IPD 
Interaural Phase Difference 
ISF 
Investigator Site File 
ITD 
Interaural Time Difference 
ITE 
In-The-Ear device 
Ho 
Null hypothesis 
H1 
Alternative hypothesis 
HI 
Hearing instrument 
HFG 
Humanforschungsgesetz (Law on human research) 
HMG 
Heilmittelgesetz  
HRA 
Federal Act on Research involving Human Beings 
IMP 
Investigational Medicinal Product 
ISO 
International Organisation for Standardisation 
ITT 
Intention to treat 
JND 
Just Noticeable Difference 
KlinV 
Verordnung über klinische Versuche in der Humanforschung (in English: ClinO, in 
French OClin) 
LPTh 
Loi sur les produits thérapeutiques 
LRH 
Loi fédérale relative à la recherche sur l’être humain 
MD 
Medical Device 
MUSHRA 
Multi-Stimulus Test with Hidden Reference and Anchor 
N/A 
Not Applicable 
OClin 
 
Ordonnance sur les essais cliniques dans le cadre de la recherche sur l'être humain 
(in German : KlinV, in English : ClinO) 
OLSA 
Oldenburger Satztest 
pCRF 
Paper Case Report Form  
PI 
Principal Investigator  
PPT 
Phoneme Perception Test 
REM 
Real-Ear Measurement 
RIC 
Receiver-In-The-Canal device 
SNR 
Signal-to-Noise Ratio 
SOP 
Standard Operating Procedure 
SPL 
Sound Pressure Level 
SRT 
Speech Reception Threshold 
SSQ 
The Speech, Spatial and Qualities of Hearing Scale 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 

 
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TEN test 
Threshold-Equalizing-Noise test 
TMF 
Trial Master File  
UAT 
User Acceptance Test 
UCL 
UnComfortable Level 
WaKo 
Einsilber-Reimtest nach von Wallenberg und Kollmeier 
 
 
 
 
 
 
 

 
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STUDY SCHEDULE  
(AGEK 4.2; SPIRIT #13; ICH E6 6.4.2) 
For each study there are two parts (pre-study and main study). Each study part consists of a 
screening, several study appointments and one follow-up appointment.  
 
The pre-study serves to determine and test sensitive outcome measures. Furthermore several 
parameter adjustments of the sound changing principle will be investigated with the aim to find the 
most promising setting for the main study for different kinds and degrees of hearing loss. Thereby the 
number of unnecessary appointments in the main study shall be reduced to cause less burden for the 
test subjects. Several pre-studies may be necessary and conducted. The Schedule for a pre-study is 
visualized in Table 1. The number of the pre-study appointments may vary, a maximum of 6 
appointments is considered (Number of participants N = max 5).  
 
Table 1: Pre-Stud y schedule 
Study Period 
 
Screening 
Pre-study appointments 
Follow-up 
(final 
appointment) 
Visit Number 
1 
2    
(3) 
(4) 
(5) 
3…6 
Time [hrs] 
1.5 
2 
(2) 
(2) 
(2) 
2 
Subject Information and Informed Consent 
x 
 
 
 
 
 
Audiological History 
x 
 
 
 
 
 
Physical Examination of Ear and Ear Canal  
x 
x 
(x) 
(x) 
(x) 
x 
Audiogram  
x 
 
 
 
 
x 
Check In- /Exclusion Criteria 
 
x 
 
 
 
 
 
Decision Subject Participation 
x 
 
 
 
 
 
Encoded Subject ID 
x 
 
 
 
 
 
Fitting HI 
 
x 
(x) 
(x) 
(x) 
(x) 
Objective Measurements 
 
x 
(x) 
(x) 
(x) 
(x) 
Subjective Measurements 
 
x 
(x) 
(x) 
(x) 
(x) 
Introduction to Handling (depending on 
randomisation list for home trials) 
 
x 
(x) 
(x) 
(x) 
 
Scheduling Next Visit  
x 
x 
(x) 
(x) 
(x) 
 
Capture of Adverse Events and Device 
Deficiencies 
 
x 
(x) 
(x) 
(x) 
x 
 
 
 
 
 
 
 
 
 

 
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To determine the most useful settings for the main study, a looped workflow is foreseen (Figure 1). A 
maximum of 3 loops is considered resulting in a maximum of 4 pre-study appointments, whereas 
fewer appointments are possible.   
 
Figure 1: Looped pre-study work flo w 
 
 
 
 
 
Initial 
Setting 
Pre Study 
Appointments 
Promising 
Setting? 
Modified 
Setting 
Yes 
No 
Start of Pre-
study 
End of Pre-Study 
Pre Study 
Results 

 
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The main study represents the actual study for the investigation of one sound changing principle. The 
results from the pre-studies are used to specify the main study. The Schedule for a main study is 
visualized in Table 2. The number of the study appointments may vary depending on the number of 
tests and test methods being executed for a respective sound changing principle. For a main study a 
maximum of 8 study appointments is considered.  
 
Table 2: Main study schedule 
Study Period 
 
Screening 
Main study appointments 
Follow-up 
(final 
appointment) 
Visit Number 
1 
2 
3 
(4) 
(5) 
(6) 
(7) 
4…8 
Time [hrs] 
1.5 
2 
2 
(2) 
(2) 
(2) 
(2) 
2 
Subject 
Information 
and 
Informed Consent 
x 
 
 
 
 
 
 
 
Audiological History 
x 
 
 
 
 
 
 
 
Physical Examination of Ear 
and Ear Canal  
x 
x 
x 
(x) 
(x) 
(x) 
(x) 
x 
Audiogram  
x 
 
 
 
 
 
 
x 
Check In- /Exclusion Criteria 
x 
 
 
 
 
 
 
 
Decision 
Subject 
Participation 
x 
 
 
 
 
 
 
 
Encoded Subject ID 
x 
 
 
 
 
 
 
 
Fitting HI 
 
x 
x 
(x) 
(x) 
(x) 
(x) 
(x) 
Objective Measurements 
 
x 
x 
(x) 
(x) 
(x) 
(x) 
(x) 
Subjective Measurements 
 
x 
x 
(x) 
(x) 
(x) 
(x) 
(x) 
Introduction 
to 
Handling 
(depending 
on 
randomisation list for home 
trials) 
 
x 
x 
(x) 
(x) 
(x) 
(x) 
 
Scheduling Next Visit  
x 
x 
x 
(x) 
(x) 
(x) 
(x) 
 
Capture of Adverse Events 
and Device Deficiencies 
 
x 
x 
(x) 
(x) 
(x) 
(x) 
x 
 
 
 
 
 
 
 
 
 
 

 
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1. STUDY ADMINISTRATIVE STRUCTURE  
(ICH/E6 6.1.2-6.1.7; AGEK 1.1; SPIRIT 5a-d) 
This section contains complete contact details. 
1.1 Sponsor,  Sponsor -Investigator  
(ICH/E6 6.1.2; AGEK 1.1; SPIRIT 5b) 
ICH: Name and address of the sponsor ….. 
The Sponsor is the company Sonova AG. Sonova AG will provide the study budget, the staff, the 
spatial resources, the measurement equipment and the investigational products (hearing systems 
including the hearing instruments). 
 
Company:  Sonova AG, Stäfa 
Contact:     Juliane Raether, Dipl.-Ing. (FH)  
Address:    Laubisrütistrasse 28, CH-8712 Stäfa 
Phone:       058 928 86 37  
 
Email:        Juliane.Raether@sonova.com 
Role:          Financier 
 
1.2 Princ ipal Investigator( s)  
(ICH/E6 6.1.5, 6.1.6; AGEK 1.1; SPIRIT 5a-d) 
ICH: Name and tit le of the investig ator( s) who is (are) responsible for conducting the tria l, and the 
address and telephone number(s) of the tria l site(s). 
In Sonova AG, the Performance Profiling Team within the P4AC (Program Algorithmic-, Audiological-, 
Acoustical- and Assessment-Concepts) group undertakes clinical trials to investigate the audiological 
performance of novel sound changing principles in hearing instruments.  
Each Performance Profiling Team member is qualified to take on the role as an Investigator. The 
function as the Principle Investigator is taken on by: 
 
Site:           Sonova AG, Stäfa 
Contact:     Juliane Raether, Dipl.-Ing. (phone: 058 928 01 01)                     
Address:    Laubisrütistrasse 28, CH-8712 Stäfa 
Email:        juliane.raether@sonova.com 
Role:     
• 
Study design 
• 
Data collection 
• 
Data analysis 
• 
Report 
 
1.3 Statis tic ian ("Bios tatis tic ian" )  
(ICH/E6 6.1.7; SPIRIT 5a-d) 
ICH: Name(s) and address(es) of the clinical laborator y(ies) and oth er medical and/or technical 
departme nt(s) and/or in stitu tions involved in the tria l. 
The role as the Statistician is adopted by the Principle Investigator.  
 
1.4 Labora tory 
(ICH/E6 6.1.7; SPIRIT 5a-d) 
ICH: Name(s) and address(es) of th e clinical laborato ry(ies) …………. involved in the tria l. 
The study will take place in the research labs of the Headquarter of Sonova AG, Laubisrütistrasse 28, 
8712 Stäfa (see 08_QualifikationPruefort_d_S&T-P4AC.docx). 

 
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1.5 Monito ring ins tit ution  
(ICH/E6 6.1.2; SPIRIT 5a-d) 
ICH: Name and address of the …. monitor (i f oth er tha n the sponsor). 
Monitoring is not conducted by an external institution but by the sponsor. 
 
1.6 Data Safety Monitori ng Co mmi ttee  
(ICH/E6 6.1.7; SPIRIT 5a-d) 
ICH: Name(s) and address(es) of the clinical laborator y(ies) and oth er medical and/or technical 
departme nt(s) and/or in stitu tions involved in the tria l. 
N/A 
 
1.7 Any other relevant Commi ttee, Person, Organis ation, Instit ution  
(ICH/E6 6.1.7; SPIRIT 5a-d) 
ICH: Name(s) and address(es) of the clinical laborator y(ies) and oth er medical and/or technical 
departme nt(s) and/or in stitu tions involved in the tria l. 
N/A 
 
 

 
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2. ETHICAL AND REGULATORY ASPECTS  
(ICH/E6 6.12; AGEK 11; SPIRIT #24, 5) 
ICH: Descripti on of ethical considerations relatin g to the tria l. 
The decision of the CEC and Swissmedic/foreign competent authority concerning the conduct of the 
study will be made in writing to the Sponsor-Investigator before commencement of this study. The 
clinical study can only begin once approval from all required authorities has been received. Any 
additional requirements imposed by the authorities shall be implemented. 
 
2.1 Study regis tration  
(Clin O, Art. 1d, 64; SPIRIT #2a-b) 
This study will be registered at clincaltrials.gov as a primary register and, additionally, it will be 
registered in the Swiss Federal Complementary Database as soon as the ethics application is 
approved by the CEC. 
 
2.2 Categoris ation of  study  
(Clin O, Art. 19, 20, App 3, 1.1) 
Risk category A. 
The study is a trial with medical devices (comprising hearing instruments, hearing instrument software, 
acoustic couplings, fitting software and wireless accessories). All investigational devices in this trial  
are CE-labelled and their application is done according to the specialized information. 
 
2.3 Competent Ethic s Commi ttee (CEC)  
(Clin O, Art 24-29; SPIRIT #24) 
The responsible investigator ensures that approval from an appropriately constituted CEC is sought 
for the clinical study.                                                                                                    
Reporting duties and allowed time frame have to be abided concerning all changes in the research 
activity and all unanticipated problems involving risks to humans, including in case of planned or 
premature study end and the final report. No essential changes are made to the protocol without prior 
Sponsor and CEC approval, except where necessary to eliminate apparent immediate hazards to 
study participants.  
Premature study end or interruption of the study is reported within 15 days. The regular end of the 
study is reported to the CEC within 90 days, the final study report will be submitted within one year 
after study end. Amendments are reported according to chapter 2.10. 
 
2.4 Competent Authoritie s (CA)  
(Clin O, Art. 23, 27, 30-39, 42, 43, 46-48, 57; SPIRIT #24) 
There is no need for a CA approval or other local requirements because this study is of risk category A 
according to LHR. 
 
2.5 Ethical Conduct of  the Study  
(Clin O, Art. 5; AGEK 11; ICH E6 6.12, 6.2.5) 
ICH: A statement that the tri al will be conducted in compliance with  the prot ocol, GCP and the applicable 
regulator y requirement(s). 
The study will be carried out in accordance to the protocol and with principles enunciated in the 
current version of the Declaration of Helsinki, the guidelines of Good Clinical Practice (GCP) issued by 
ICH, in case of medical device: the European Directive on medical devices 93/42/EEC and the ISO 
Norm 14155 and ISO 14971, the Swiss Law and Swiss regulatory authority’s requirements. The CEC 
and regulatory authorities will receive annual safety and interim reports and be informed about study 
stop/end in agreement with local requirements.  

 
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2.6 Declaration of  interest  
(Clin O, Art. 3b; SPIRIT #28) 
In accordance to ISO 14155 and KlinV, Art. 3b scientific integrity will be preserved. Therefore, any 
potential conflicts of interest, including financial, that interfere with the conduct of this clinical 
investigation or interpretation of the according results could be disclosed. 
 
2.7 Patient Informa tion a nd Info rmed Con sent 
(Clin O, Art. 7-9, Art. 15-17, Appendix 3, 1.4, 2.4, 3.4, 4.3, Appendix 4, 3.6; AGEK submission checklist item 
5; SPIRIT #26, 32) 
The investigators will explain to each subject the nature of the study, its purpose, the procedures. 
involved, the expected duration, the potential risks and benefits and any discomfort it may entail. Each 
subject will be informed that the participation in the study is voluntary and that he may withdraw from 
the study at any time and that withdrawal of consent will not lead to consequences for the subject. The 
subject must be informed that his medical records may be examined by authorized individuals.  
All subjects for the study will be provided a participant information sheet and a consent form 
describing the study and providing sufficient information for subjects to make an informed decision 
about their participation in the study. This participant information sheet contains also a list of 
independent fiduciary doctors which can be contacted by the participant, especially in cases of 
undesirable events, whereas these doctors have no relation to the described study (see 
03_Studieninformation_ST_P4AC_Version_1.2) The subjects will be given enough time (minimum 
time frame for this study: 1 week) for their participation decision. The patient information sheet and the 
consent form will be submitted to the CEC to be reviewed and approved.  
The formal consent of a subject, using the approved consent form, must be obtained before the 
subject is submitted to any study procedure. The subject should read and consider the statement 
before signing and dating the informed consent form, and should be given a copy of the signed 
document. The consent form must also be signed and dated by the investigator (or his designee) and 
it will be retained as part of the study records.  
 
2.8 Partic ipant pri vacy and c onf identiality  
(Clin O, Art. 18; ICH/E6 6.10; AGEK 12.2, SPIRIT #27) 
ICH: The sponsor should ensure that it is specifi ed in the proto col or oth er writte n agreement that the 
investig ator(s )/institu tion(s) will permit tria l-related monito ring , audits , IRB/IEC review, and regulator y 
inspection(s), prov iding direct access to source data/documents. 
The investigator affirms and upholds the principle of the subject‘s right to privacy and that they shall 
comply with applicable privacy laws. Especially, anonymity of the subjects shall be guaranteed when 
presenting the data at scientific meetings or publishing them in scientific journals.  
Individual subject audiological information obtained as a result of this study is considered confidential 
and disclosure to third parties is prohibited. Subject confidentiality will be further ensured by utilising 
subject identification code numbers to correspond to measurement data in the computer files. 
For data verification purposes, authorised representatives of the Sponsor, a competent authority (e.g. 
Swissmedic), or an ethics committee may require direct access to parts of the measurement records 
relevant to the study, including participants’ audiological history. 
 
2.9 Early termi nation of  the study  
(Clin O Art. 47; ICH/E6 6.4.6; SPIRIT #21b) 
ICH: A descripti on of the "stopping rule s" or "discontin uatio n crite ria"  for individual partic ipants , parts of 
tria l and enti re tri al. 
The Sponsor or the Principle Investigator may terminate the study prematurely according to certain 
circumstances, for example: 
• 
ethical concerns, 
• 
insufficient participant recruitment, 
• 
when the safety of the participants is doubtful or at risk, respectively, 

 
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• 
alterations in accepted clinical practice that make the continuation of a clinical trial unwise,  
• 
early evidence of benefit or harm of the experimental intervention  
 
2.10 Proto col amendm ents 
 (ClinO, Art. 29, 34, 55; SPIRIT #25) 
Every person who is involved in the study performance is able to draft an amendment. All 
amendments have to be reviewed and signed by the Principle Investigator of the main study site 
before they get forwarded to the responsible approval institution.  
 
Substantial amendments are only implemented after approval of the CEC.  
 
Under emergency circumstances, deviations from the protocol to protect the rights, safety and well-
being of human subjects may proceed without prior approval of the sponsor and the CEC. Such 
deviations shall be documented and reported to the sponsor and the CEC as soon as possible.  
All non-substantial amendments are communicated if applicable to the CEC within the Annual Safety 
Report (ASR). 
 
 
 

 
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3. BACKGROUND AND RATIONALE 
(ICH 6.2; AGEK 3; SPIRIT #6) 
This section includes any statements that rely on existing knowledge or published information 
concerning the study. 
 
3.1 Backgroun d and Rati onal e  
(ICH/E6 6.2; AGEK 3.1; SPIRIT #6) 
Research with hearing instruments on hearing impaired participants has been done frequently with the 
aim to investigate and assess the effect of the respective devices. Extensive surveys have shown, that 
recent development in hearing instrument technology provides benefit for the end users. Additionally it 
has been shown that further improvement is requested by the end users [10, 11]. Therefore novel 
sound changing principles, which aim to improve the hearing performance for the end user, are 
continuously developed and improved. This study is the description of a series of studies concerning 
the evaluation of novel sound changing principles in Sonova brand hearing instruments. For each 
sound changing principle a separate (sub-) study will be conducted. These sound changing principles 
are enabled by respective hearing instrument technology and hearing instrument algorithms. The 
mentioned technology and algorithms are applied in hearing instruments as features and functions 
and intend to improve the hearing performance provided by the device.  
 
The purpose of this evaluation is to investigate these novel sound changing principles regarding their 
supposed benefit and possible secondary effects for hearing impaired users. The results should 
promote the hearing instrument development to create meaningful applications, improve the hearing 
instrument products and hence provide a maximum benefit in terms of hearing performance for an end 
user. The primary purpose is to investigate and assess the performance of the novel sound changing 
principles and compare them to those recently used in hearing instruments. Furthermore different 
parameter adjustments of the respective novel applications will be examined with the aim to determine 
the optimal setting. The secondary purpose is to investigate the effect of the applications in real world 
environment.  
 
Study Overview: 
A table of relevant and clinical significant studies with hearing instruments concerning audiological 
benefit can be found below (Table 3). The mentioned literature investigates for the most parts the 
following hearing instrument features and functionalities: Automatic Functionality, Binaural 
Directionality, Feedback Management, Frequency Lowering, Monaural Directionality and Noise 
Suppression.  
 
Table 3: Overview of relevant stud ies 
Reference # 
Relevant and Signifi cant Literatu re 
Level of Evidence 
Publication Class 
1. 
Appleton J, König G. Improvement in speech intelligibility and subjective benefit with binaural beamformer 
technology. Hearing Review. 2014;21(11)[Nov]:40-42. 
IIb 
b 
2. 
Aspell E, Picou E, Ricketts T. Directional benefit is present with audiovisual stimuli: limiting ceiling effects. J 
Am Acad Audiol. 2014 Jul-Aug;25(7):666-75. 
Ib 
a 
3. 
Bentler R., Palmer C.V., Mueller H.G.: Evaluation of a Second-Order Directional Microphone Hearing Aid: I. 
Speech Perception Outcomes, Journal of the American Academy of Audiology, Vol. 17, No. 3, 2006 
Ib 
 
a 
4. 
Bentler RA, Tubbs JL, Egge JL, Flamme GA, Dittberner AB. Evaluation of an adaptive directional system in a 
DSP hearing aid. 2004 Am J Audiol. 2004 Jun;13(1):73-9. 
IIb 
a 

 
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5. 
Boymans M, Dreschler WA.Field trials using a digital hearing aid with active noise reduction and dual-
microphone directionality.Audiology. 2000 Sep-Oct;39(5):260-8. 
IIb 
a 
6. 
Büchler MC, Algorithms for Sound Classification in Hearing Instruments, Diss. ETH no 14498 (2002), pp 33-
37 / Internal library 
IIb 
d 
7. 
Büchler, M. (2001). Nützlichkeit und Akzeptanz einer automatischen Programmwahl in Hörgeräten., 
Hörakustik 10/2001, 64–71 / Internal library 
IIb 
b 
8. 
Chung K., Killion MC., Christensen LA.: Ranking hearing aid input-output functions for understanding low-, 
conversational-, and high-level speech in multitalker babble. J Speech Lang Hear Res., Vol. 50, 2007. 
Ib 
a 
9. 
Dillon H. et al.: Sound quality comparisons of advanced Hearing Aids, The Hearing Journal, Vol. 56, No. 4, 
2003 
IIa 
b 
10. 
Dyrlund O, Henningsen LB, Bisgaard N, Jensen JH, “Digital feedback suppression (DFS). Characterization of 
feedback-margin improvements in a DFS hearing instrument,” Scand Audiol 1994; 23(2):135-8. 
IIb 
b 
11. 
Ellis, R. Benefit and predictors of outcome from frequency compression hearing aid use. University of 
Manchester 2012, doctoral thesis. 
Ib 
d 
12. 
Fortune T.W.: Real Ear Compression Ratios: The Effects of Venting and Adaptive Release Time, American 
Journal of Audiology, Vol. 6, No.2, 1997 
IIa 
a 
13. 
Glista D. Nonlinear Frequency Compression Hearing Aid Signal Processing for Listeners with High-
Frequency Hearing Loss: Aided Speech Perception and Acclimatization Effects. University of Western 
Ontario 2010, Doctoral Thesis 
Ib 
a 
14. 
Hearing_Review_user_control_of_directional_focus_jan09.pdf Hearingreview.com, 2009_01 
IIa 
b 
15. 
Hoetink A, Körössy L, Dreschler W (2009) Classification of steady state gain reduction produced by amplitude 
modulation based noise reduction in digital hearing aids. Int J Audiol; 48:444 455 
IIa 
a 
16. 
Johnson EE, Ricketts TA, Hornsby BW. The effect of digital phase cancellation feedback reduction systems 
on amplified sound quality. J Am Acad Audiol. 2007 May;18(5):404-16. 
IIb 
b 
17. 
Keidser G, O'Brien A, Hain JU, McLelland M, Yeend I. The effect of frequency-dependent microphone 
directionality on horizontal localization performance in hearing-aid users. Int J Audiol. 2009 Nov;48(11):789-
803. 
IIb 
a 
18. 
Kühnel V, Margolf-Hackl S, Kiessling J. Multi-microphone technology for severe-to-profound hearing loss 
2001 scandinavian Audiology 2001, Vol. 30, No. 1 , Pages 65-68 
IIb 
a 
19. 
Lebart, K. Boucher, J.M. (2001) A New Method Based on Spectral Subtraction for Speech Dereverberation. 
Acta Acustica, Vol 87, pp 359-366 
IIb 
a 
20. 
Levitt H, (2001) Noise reduction in hearing aids: An overview. J Rehabil Res Dev  38 
III 
a 
21. 
Mackenzie E, Lutman ME. Speech recognition and comfort using hearing instruments with adaptive 
directional characteristics in asymmetric listening conditions. 2005 Ear Hear. 2005 Dec;26(6):669-79. 
IIa 
a 
22. 
McCreery RW, Venediktov RA, Coleman JJ, Leech HM. An evidence-based systematic review of frequency 
lowering in hearing aids for school-age children with hearing loss. Am J Audiol. 2012 Dec;21(2):313-28. 
Ia 
a 
23. 
Mueller H.G., Weber J., Bellanova M.: Clinical evaluation of a new hearing aid anti-cardioid directivity pattern. 
International Journal of Audiology, 2011, 50(4). 
IIa 
a 
24. 
Mueller, G.H., Weber, J., & Hornsby, B.W.Y. (2006). The effects of digital noise reduction on the acceptance 
of background noise. Trends in Amplification, 10(83), 83-93. 
Ib 
a 
25. 
Nordrum S, Erler S, Garstecki D, Dhar S. Comparison of performance on the hearing in noise test using 
directional microphones and digital noise reduction algorithms. 2006 Am J Audiol. 2006 Jun;15(1):81-91. 
IIb 
a 
26. 
Peeters H,  Kuk F,  Lau C, Keenan D. (2009) Subjective and Objective Evaluation of Noise Management 
Algorithms.  J Am Acad Aud, 20 (2): 89-98 
Ia 
a 
27. 
Picou EM, Aspell E, Ricketts TA. Potential benefits and limitations of three types of directional processing in 
hearing aids. Ear Hear. 2014 May-Jun;35(3):339-52. 
Ib 
a 
28. 
Preves DA, Sammeth CA, Wynne MK. Field trial evaluations of a switch directional/omnidirectional in-the-ear 
hearing instrument.1999 J Am Acad Audiol. 1999 May;10(5):273-84. 
IIb 
a 
29. 
Ricketts T; Johnson  E; Federman J: Individual Differences within and across Feedback Suppression Hearing 
Aids. Journal of the American Academy of Audiology, Volume 19, Number 10, November/December 2008 , 
pp. 748-757(10) 
IIb 
b 
30. 
Ricketts TA and Henry P. Evaluation of an adaptive, directional-microphone hearing aid. 2002 International 
Journal of Audiology 2002, Vol. 41, No. 2 , Pages 100-112 
IIb 
a 
31. 
Ricketts TA, Picou EM. Speech Recognition for Bilaterally Asymmetric and Symmetric Hearing Aid 
Microphone Modes in Simulated Classroom Environments. A2. Ear Hear. 2013 Mar 21. [Epub ahead of print] 
PubMed PMID: 23524508. 
IIa 
a 

 
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32. 
Savage I, Dillon H, Byrne D, Bächler H.: Experimental evaluation of different methods of limiting the 
maximum output of hearing aids. Ear & Hearing, Vol. 27, No. 5, 2006. 
Ia 
a 
33. 
Simpson A, Hersbach AA, McDermott HJ. Improvements in speech perception with  an experimental 
nonlinear frequency compression hearing device. Int J Audiol. 2005 May;44(5):281-292. 
Ib 
a 
34. 
Smith P., Davis A., Day J., Unwin S., Day G., Chalupper J.: Real-world preferences for linked bilateral 
processing. Hearing Journal, Vol. 61, No.7, 2008 
Ia 
b 
35. 
Sockalingam R., Holmberg M., Eneroth K., Schulte M.: Binaural Hearing Aid communication shown to 
improve sound quality and localization, Hearing Journal., Vol. 62, Issue. 10, 2009 
IIa 
b 
36. 
Souza PE, Arehart KH, Kates JM, Croghan NB, Gehani N. Exploring the limits of frequency lowering. J 
Speech Lang Hear Res. 2013 Jun 19. 
Ib 
a 
37. 
Surr RK, Walden BE, Cord MT, Olson L. Influence of environmental factors on hearing aid microphone 
preference. 2002 J Am Acad Audiol. 2002 Jun;13(6):308-22. 
IIb 
a 
38. 
Uys M, Pottas L, Vinck B, van Dijk C. The influence of non-linear frequency compression on the perception of 
music by adults with a moderate to severe hearing loss: subjective impressions. S Afr J Commun Disord. 
2012 Dec;59:53-67. 
Ib 
a 
39. 
Wolfe J, John A, Schafer E, Nyffeler M, Boretzki M, Caraway T, Hudson M. Long-term effects of non-linear 
frequency compression for children with moderate  hearing loss. Int J Audiol. 2011 Jun;50(6):396-404. 
Ib 
a 
40. 
Wolfe J, John A, Schafer E, Nyffeler M, Boretzki M, Caraway T. Evaluation of nonlinear frequency 
compression for school-age children with moderate to moderately severe hearing loss. J Am Acad Audiol. 
2010 Nov-Dec;21(10):618-28. 
Ib 
a 
41. 
Wu YH, Stangl E, Bentler RA, Stanziola RW. The effect of hearing aid technologies on listening in an 
automobile, A1. J Am Acad Audiol. 2013 Jun;24(6):474-85. doi: 10.3766/jaaa.24.6.4. PubMed PMID: 
23886425. 
IIa 
a 
42. 
Wu YH, Stangl EA, Bentler RA, Stanziola RW (2012): “The effect of hearing aid technologies on listening in 
cars.” JAAA (accepted) 
IIb 
a 
Levels of Evidence 
 
Ia -     Well-designed meta-analysis of >1 randomized controlled trial 
Ib -     Well-designed randomized controlled study 
IIa -    Well-designed controlled study without randomization 
IIb -    Well-designed quasi-experimental study 
III -     Well-designed no experimental studies, i.e., correlational and case studies 
IV -     Expert committee report, consensus conference, clinical experience of respected authorities 
Publication Class  
 
a. 
Public peer reviewed 
b. 
Published  
c. 
Conference contribution 
d. 
Phd thesis 
e. 
Master / Bachelor  thesis 
f. 
Expert opinion / white paper / letter 
g. 
Internal reports / Unpublished 
 
 
 
 
 
 
 
 
 
 

 
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3.2 Investigationa l Product (t reatment, de vice) and Indic ation  
(ICH/E6 6.2.1; AGEK 2; SPIRIT #6) 
ICH: Name and descripti on of the investigatio nal prod uct(s). 
All investigational products are CE-labelled MDs. All MDs (hearing instruments with respective hearing 
instrument software and acoustic couplings, fitting software and wireless accessories) are bearing 
product names and unique serial numbers for an unambiguous assignment and retracing of the 
product to the subject. State of the art methods may be used to verify the fitting of the hearing systems 
(e.g. Real Ear Measurements [12]).  
 
Hearing Instruments: 
In general, the hearing instruments themselves can be separated in different form factors: In-The-Ear 
(ITE), Invisible-In-Canal (IIC), Receiver-In-Canal (RIC) and Behind-The-Ear (BTE) including different 
acoustic couplings depending on the hearing loss and on the anatomical conditions of the hearing 
instrument user. 
 
Hearing Instrument Software: 
The hearing instrument software comprises the operating system and the signal processing of a 
hearing instrument. It contains the algorithmic approaches and can be operated in a respective 
hearing instrument. 
                                            
Acoustic coupling:  
Together with a BTE or RIC, the acoustic coupling (e.g. earpiece) is a system which is also a medical 
device. Without the merge of the acoustic coupling and hearing instrument the earpiece has no 
medical harness.  
 
Fitting Software:  
The hearing instruments will be set and fine-tuned to the individual hearing loss and needs of the 
subject by using the corresponding fitting software in accordance to the specialised information 
whereof the latest version can always be printed out (e.g. of the Phonak Fitting Software). 
 
Wireless Accessories: 
The Sonova brand Wireless Accessories comprise various solutions to simplify the volume adjustment 
as well as the program switching in a hearing instrument but also to enhance speech intelligibility in 
noisy environments, in making phone calls or in bridging distances between a talker and the hearing 
instrument user like in class/conferences/lectures. The subsequent current Sonova brand Wireless 
Accessory solutions are also MDs. They also have a unique serial number for an unambiguous 
assignment and retracing of the product to the subject. The intended purpose is also according to the 
instruction manual.  
 
3.3 Preclinic al Evidence  
(ICH/E6 6.2.2; SPIRIT #6a)  
ICH: A summary of fi ndings from  nonclinical studies that potenti ally have clinical signific ance ….. 
For MD this entry is only applicable if needed for pre-marketed/marketed devices needing Swissmedic 
notification (Guidance on the biological evaluation of medical devices is given in ISO 10993). 
Therefore, this entry is not applicable for this study. 
 
3.4 Clini cal Evidence to Date  
(ICH/E6 6.2.2; SPIRIT #6a) 
ICH: A summary of fi ndings from  … and fro m clinical tria ls that are relevant to the tri al. 
There is no available clinical research data to date on the investigational product. 
 

 
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3.5 Dose Rationa le / Medic al Device: Ration ale for the intende d purpo se in 
study (pre-market MD)  
(ICH/E6 6.2.4; SPIRIT #6a) 
ICH: Descripti on of and justifi cation for the route of administrati on, dosage, dosage regimen, and 
treatment period (s). 
The hearing instruments will be set and fine-tuned to the individual hearing threshold and needs of the 
subject in accordance to established audiological test methods and according to the best knowledge 
and conscience of trained staff to promote new developments.  
 
3.6 Explanation f or choic e of c ompa rator (or pl acebo)  
(AGEK 11.3; SPIRIT #6b) 
To investigate the effect of the sound changing principles in hearing instruments, different parameter 
settings of the respective application will be compared. This may include a setting in which the sound 
changing principle is disabled (switched off). If applicable the novel sound changing principle will be 
compared with those used in previous hearing instruments. Depending on which application will be 
compared the number of comparators may differ. 
 
3.7 Risks / Benefit s  
(Clin O, Appendix 4, 3.5; Art 25d2; ICH/E6 6.2.3; AGEK 11.1; SPIRIT #6a; MD: ISO 14155 Annex A & ISO 
14971) 
ICH: Summary of th e known and potenti al risks and benefits , if any, to human subjects. 
 
Risks regarding the Investigational device (MD). 
 
1. Infections can be caused by injuries of the ear canal which can occur by the placement of the 
acoustic coupling (e. g. receiver, earpiece) to the outer ear canal or by the placement of an 
ITE or IIC device. Therefore, the ear canal will be thoroughly checked and assessed during 
the study.  
 
2. Pressure points can be caused by the hearing instrument or the acoustic coupling. In case of 
pressure points, the hearing instrument should not be worn until it healed up. The cause of the 
pressure point would then be investigated.    
 
3. Tinnitus can be caused by wearing of the hearing instrument. An existing tinnitus can be 
temporarily amplified. If the tinnitus doesn’t improve after several days of not wearing the 
hearing instrument, an assessment with an independent doctor (ENT) is necessary.  
 
4. A headache can occur, especially for new hearing instrument users. If a headache appears, 
the subject is instructed to interrupt the hearing instrument use until the audiologist applies a 
new fitting (e.g. reduced gain level) to acclimatize the subject to the devices.   
 
5. The hearing instrument can reach a high maximum power output (MPO). The MPO will be set 
accordingly to clinical expertise at a level that no injuries can occur.  
 
Risks regarding the involved procedures. 
 
1. Used Loudspeakers or Headphones can reach high maximum power outputs. Only standard  
Loudspeakers and Headphones having a limited maximum power output will be used. 
 
2. Study appointments might be tiring for the subjects, therefore regular pauses will be done 
during the appointments.  
 
Benefits of the study. 
 

 
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1. Participating subjects learn something new about their own hearing. 
 
2. Participating subjects are fitted with the latest hearing system products and have the 
opportunity to try it out during the study period. 
 
3. Participating subjects acquire knowledge about how she/he can be served audiologically. 
 
4. Gained knowledge about novel and innovative sound changing principles will drive further 
development to provide audiologically meaningful and useful solutions for hearing impaired 
end-users. 
 
3.8 Justif ication of  choi ce of s tudy popula tion   
(Clin O, Art 25d4, Art. 15-17; ICH/E6 6.2.6; AGEK 11.2) 
ICH: Descripti on of th e populatio n to be studied. 
In this study, adult persons with different degrees of hearing abilities will participate. The sound 
processing in the inner ear significantly differs between normal hearing and hearing impaired persons 
and, furthermore, is dependent on the degree of the hearing loss. For this reason, the benefit and the 
performance of new sound changing principles in hearing instruments, which can be individually fitted 
to a hearing loss, can only be reliably evaluated by appropriate hearing impaired persons. To know the 
performance for normal hearing abilities also normally hearing subjects may be included. For the 
assessment of psychoacoustic, behavioural and psychophysiological performance data (Table 6) it is 
essential to have a comparison against the performance of normal hearing participants who serve as a 
control group and as an anchor for these kinds of tests. Normal hearing subjects are considered as 
vulnerable population. 
Sonova Employees may be selected for the experiments as they have special education and 
experience in evaluation trials for sound changing principles and/or work in innovation projects. 
Additionally they are easily accessible and are highly interested into meaningful evaluation studies.  
They are considered as vulnerable population since they are in a dependence-relation to Sonova. 
 
4. STUDY OBJECTIVES  
(ICH/E6 6.3; AGEK 3; SPIRIT #7) 
ICH: A detailed descripti on of the objectiv es and the purpose of the tria l. 
This section includes a description of the overall, primary and secondary objective(s) of the study. 
4.1 Overall Objective 
This study is the overall summation of a series of several sub-studies concerning the evaluation of 
novel sound changing principles in hearing instruments over the next 10 years. These novel sound 
changing principles are continuously developed and improved in the mentioned time frame. For each 
sound changing principle a separate study (sub-study) will be conducted. All of these sub-studies 
pursue the goal to investigate strength and weaknesses of the respective novel sound changing 
principle.  
 
The overall objective is to investigate the audiological performance for each of these sound changing 
principles on hearing impaired subjects using respective hearing performance outcome measures. 
The results are assessed in referenced to those from sound changing principles used in recent 
hearing instruments and/or with the sound changing principle disabled.  
 
4.2 Prim ary Objective 
The primary objective of each study is to determine and assess the benefit of these novel sound 
changing principles for their intended use in terms of the associated hearing dimension (speech 
intelligibility, signal clarity and sound quality / hearing comfort) respectively. Depending on the aim of 
the respective sound changing principle the associated hearing performance outcome measure will be 

 
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chosen. Furthermore different parameter adjustments of the novel sound changing principle will be 
examined to determine the most useful setting. The results are assessed in referenced to those from 
sound changing principles used in recent hearing instruments and/or with the sound changing 
principle disabled.  
 
4.3 Secondary  Objectives 
The secondary objective is to investigate and assess the effect of the respective sound changing 
principle in real world environment. The results are assessed in referenced to those from sound 
changing principles used in recent hearing instruments and/or with the sound changing principle 
disabled.  
    
4.4 Safety Objectives 
N/A 
 
 
 

 
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5. STUDY OUTCOMES  
(ICH/E6 6.4.1; AGEK 4.1; SPIRIT #12) 
ICH: A specifi c statement of the prim ary endpoints and the secondary endpoints, if any, to be measured 
during  the tria l. 
This section includes a description of the outcomes of the study including the specific measurement 
variable and analysis metric.  
 
5.1 Prim ary Outcome 
The primary outcomes are the laboratory test results. These tests intend to evaluate the hearing 
performance in terms of speech intelligibility, signal clarity and sound quality / hearing comfort. With 
help of the received data from these outcome measurements it can be concluded whether the 
experimental condition is superior to the comparator with regard to hearing performance. 
Each sub-study focuses specifically on one of these hearing dimensions. The corresponding other 
hearing dimensions may be additionally examined to investigate a trade-off (e.g. trade-off for speech 
intelligibility versus sound quality / hearing comfort). Depending on the investigational sound changing 
principle and the corresponding focused feature or function (aim) the appropriate audiological testing 
method will be chosen (Table 4). 
 
Table 4: Audiological testing metho ds for ou tcome measures in the laborator y 
Performa nce 
Aim 
Metho d 
Result [u nit] 
Speech 
intelligibility 
Assessment of speech 
intelligibility in quiet 
Freiburger Sprachtest [13] 
Discrimination [%] 
Assessment of speech 
intelligibility in noise 
Oldenburger Satztest (OLSA) [14, 15] 
Speech intelligibility 
threshold in noise 
[dB SNR] 
Assessment of speech 
intelligibility in quiet or in noise 
Einsilber-Reimtest nach von Wallenberg 
und Kollmeier (WaKo) (quiet/noise) [16] 
Discrimination [%] 
Assessment of speech 
intelligibility in quiet or in noise 
Göttinger Satztest (GöSa) (quiet/noise) 
[17] 
SRT in quiet [dB], in noise 
[dB SNR] 
Assessment of speech 
intelligibility with variable target 
location and talker identity 
Coordinate Response Measure [18, 19, 
20] 
SRT [dB] or performance 
level (%-correct responses) 
Assessment of cognitive 
influences on speech 
perception 
Cognitive Measures, e.g. for Working-
Memory Capacity (e.g., Reading Span 
[21]), Executive Functioning and Attention 
(e.g., Stroop Task), Overall Cognitive 
Ability (e.g., MoCA [22]) 
Performance Level [%-
correct responses or time-
to-complete outcomes] 
Objective Assessment of 
Listening Effort and Spare 
Capacity 
Response Delays during above listed 
Speech Intelligibility Tests; Dual-Task 
Paradigms with Speech Intelligibility as 
primary task and a Cognitive Outcome 
Measure as the Secondary Add-On Task 
(e.g., Assessment of Cognitive Capacity 
for tasks of Selective Attention or Working 
Memory during the Primary Task [23, 24, 
25]) 
SRT [%] and Errors [%] or 
Response Times [ms] 
 
 
 
 
Signal 
Clarit y 
Determination of hearing 
threshold of pure tones  
Pure Tone Audiometry [26] 
Yes/No replies 
Determination of threshold of 
fricatives 
Phoneme Perception Test (PPT) [Error! R
eference source  not foun d. - 29] 
Detection, Distinction and 
Recognition Threshold [dB 
SPL] 
Determination of localization 
capabilities with and/or without 
hearing systems 
Localization Test in Quiet, Noise, 
Reverberation. [31] 
Average RMS localization 
error [°], back-front 
confusions [%] 
Assessment of music 
perception 
Adaptive Music Perception Test [32] 
Detection Threshold 
 
 
 
 
Sound 
Quality / 
Hearing  
Comfort  
Qualitative description 
Interviews: Qualitative and Quantitative 
(ad hoc list of questions, semi-
standardized, standardized or normed), 
Focus Groups [43] 
Narrative, open/closed 
replies, ranking, 
single/multiple choice, or 
point on a rating scale 
Assessment of sound quality 
Subjective Rating Scale [33, 34] 
Point on a scale 

 
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Judgment which of the entities 
in pairs is preferred or has a 
greater amount of some 
quantitative property 
Paired Comparison [35] 
Preference or point on a 
scale 
Subjective evaluation of the 
audio quality of a defined 
sound 
Multi-Stimulus Test with Hidden 
Reference and Anchor (MUSHRA) [36] 
Point on a scale 
Quantitative assessment of a 
person’s perception of facts or 
circumstances regarding 
hearing system  
Semantic Differential Analysis/ Polarity 
Profile [37] 
Point on a scale 
Assessment of a person’s 
perception of a specific 
listening situation through 
selected hearing systems or 
hearing aid programs 
Simulations of Various Listening 
Situations (in 
Car/Cafeteria/Reverberation) via 
Loudspeakers including Preference 
Rating or Subjective Rating Scale 
Preference or point on a 
scale 
Determination of acceptable 
noise intensities while listening 
to speech 
Acceptable Noise Level (ANL) Test  
[38, 39] 
Tolerated SNR [dB] 
Assessment of the subjectively 
perceived loudness of a test 
signal 
Categorial Loudness Scaling [40] 
Loudness [CU] 
Assessment of a hearing aid 
user’s affection by objective 
occlusion (closed ear canals) 
Occlusion Measurement and Leakage 
Measurement using REM method [41] 
Frequency Responses 
[magnitude and phase of 
the output as a function of 
frequency] => Level 
differences [dB] and  
Level Loss [dB] 
 
5.2 Secondary  Outcome s 
The secondary outcomes are the subjective test results and comments gathered in real world 
environment (e.g. during guided walks) and with questionnaires during the home trials. Depending on 
the investigational sound changing principle and the corresponding focused feature or function (aim) 
the appropriate audiological testing method will be chosen. A collection of possible methods is listed 
below (Table 5). 
 
Table 5: Audiological testing metho ds for ou tcome measures in real world  environ ment 
Performa nce 
Aim 
Metho d 
Result [u nit] 
Subjectiv e 
test in real 
world  
environ ment 
Subjective Assessment of 
Listening Effort and Hearing 
Fatigue 
Questionnaires about Listening Effort in 
Everyday Life (e.g., CTO [42]), Rating 
Scales of Effort perceived during above 
listed Audiological Tests 
Score on a Continuous 
Rating Scale or on a Likert 
Rating Scale 
Assessment of system stability 
Quantitative Questionnaires [43] 
Yes/No replies and open-
ended 
Assessment of real-time 
individual information regarding 
hearing system and/or listening 
situation via Phonak App on 
Smartphone in daily life 
MobEval [44, 45, 46] 
Logging of predefined HI 
parameters, time [h/min/s], 
open/closed replies or 
single/multiple choice 
Survey of audibility of 
distortions, artefacts, 
interruptions, feedback, system 
noise or other malfunctions 
Quantitative Questionnaires [43] 
Yes/No replies and open-
ended 
Determination of individual 
information or circumstances 
regarding hearing system 
and/or listening situation 
Interviews: Qualitative and Quantitative 
(ad hoc list of questions, semi-
standardized, standardized or normed), 
Focus Groups [43] 
Narrative, open/closed 
replies, ranking, 
single/multiple choice, or 
point on a rating scale 
Measurement of self-reported 
auditory disability across a 
wide variety of domains, 
reflecting the reality of hearing 
in the everyday world 
The Speech, Spatial and Qualities of 
Hearing Scale (SSQ) [47] 
Score on a Continuous 
Rating Scale 
 
 
 
 

 
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5.3 Other  Outcomes of In terest 
Other outcomes of interest are potential side effects and informal feedback from the subjects 
regarding subjective rating of the performance. Additionally further measures (e.g. regarding 
psychoacoustic function) may be used to determine the individual hearing abilities and/or compare 
and correlate these results with the ones from the primary outcomes (Table 6Table 6:).  
 
Table 6: Additi onal furth er measures 
Performance 
Aim 
Method 
Result [unit] 
Audito ry functio n 
Assess Psychoacoustic 
measures 
Basic psychoacoustic measurements 
(e.g. ITD/IPD/ILD, JNDs, BMLDs, 
frequency discrimination thresholds, 
measures of frequency selectivity, 
frequency modulation detection), 
Tinnitus pitch and loudness 
matching, TEN (Threshold-
Equalizing-Noise) Test   [48 - 51] 
 
Detection threshold 
Behavioural 
observatio ns 
Observation of behaviour 
during the test session  
Video analysis, recordings, motion- 
and position sensor, reaction time 
measurement 
Analysis of respective  
observation method 
Periph eral 
psychophysiological 
observatio ns 
Assess Peripheral 
psychophysiological 
measures 
HEG (hemoencephalography), EEG 
(electroencephalography), ECG 
(electrocardiogram), EMG 
(electromyography), EDA (Electro 
Dermal Activity or Galvanic Skin 
Response), Respiratory rate, Pulse 
rate, Pupillometry [52 – 54] 
Respective result of 
peripheral 
psychophysiological 
measure 
 
5.4 Safety Outcomes 
N/A 
 
 

 
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6. STUDY DESIGN  
(ICH/E6 6.4; AGEK 4; SPIRIT #8) 
This section describes the design of the study and its rationale, the type, allocation ratio and 
framework. 
6.1 General study design a nd j ustif ication of  design  
(ICH/E6 6.4.2, 6.4.5; AGEK 4.2; SPIRIT #8) 
ICH: The scienti fic integrit y of the tria l and the credibility of th e data from  the tria l depend substanti ally on 
the tria l design.  
ICH: A descripti on of the type/design of tria l to be conducted (e.g., double-blind, placebo-control led, 
parallel design) and a schematic  diagram of tria l design, proc edures and stages. 
ICH: The expected duratio n of subject partic ipatio n, and a descripti on of the sequence and durati on of all 
tria l period s, including follow-up, if any. 
A methodical evaluation of novel sound changing principles in CE-Labelled Sonova brand hearing 
instruments (primarily Phonak hearing instruments) is intended to be conducted on hearing impaired 
and normal hearing subjects. This will be a controlled, single blinded (participants), randomised 
(sequence of test procedure and sequence of tested setting/device), cross-over (investigational 
product/setting) active comparator study which will be conducted mono centric at Sonova AG 
Headquarters based in Stäfa. 
 
Treatments/Intervention s: 
Hearing systems (hearing instruments with hearing instrument software and respective acoustic 
coupling, fitting software and wireless accessories). All CE labelled MDs. 
 
Populatio n: 
Adult participants with different degrees of hearing abilities. In the pre-studies it is planned to include 
up to 5 participants. The main studies will normally include 20 - 25 participants each. If possible a 
power analysis is carried out for each study to determine the necessary number of subjects. 
 
Level and method of blin ding /mask ing : 
The tests will be at least single blinded.   
When testing different parameter settings of the novel application and/or comparing novel with 
previous applications whereas these approaches are available as optional settings in one hearing 
instrument, the subjects will not know which setting is activated during the respective testing.  
In cases where these settings are not accessible in one hearing instrument (e.g. previous sound 
changing principle is not supported by the latest hearing instrument technology any more), the test 
needs to be undertaken with several (two) separate hearing instruments, whereas the housing of 
these hearing instruments may differ. The subjects will not be informed about the setting or the sound 
changing principle in the specific hearing instrument. 
If possible double blinding will be accomplished with help of computer controlled testing procedures 
(e.g. software tool for MUSHRA test). 
 
Kin d of com parators: 
The comparators are different parameter setting of novel sound changing principles in recent hearing 
instrument (this may include a setting in which the sound changing principle is switched off) as well as 
sound changing principles in previous hearing instruments. 
 
Method of assign ment to treatment/int ervention : 
This study will be a controlled cross-overs study. Each subjects will receive the intervention to be 
tested (hearing systems with novel sound changing principles) as well as the respective comparator 
and serves therefore as his or her own control.  The order of the investigational settings and/or 
products will be randomized. For home trials a respective wash-out period of one week is considered 
and applied if possible and meaningful. 

 
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Sequence of duratio n of all s tudy period s: 
The studies shall take place within the timeframe from 01.07.2016 to 30.06.2026 after approval by 
CEC. Each study part will take about 6 months and may overlap with other sub studies. The detailed 
duration of the appointments are listed in the study schedule. 
6.2 Methods of minimi sing bia s  
(ICH/E6 6.4.3; AGEK 4.3; SPIRIT #16, 17) 
ICH: A descripti on of th e measures taken to minimize/avoid bias, including: Randomizatio n, Blin ding. 
In order to minimize bias, the following measures will be taken: 
 
6.2.1 
Randomisatio n  
As this is a controlled cross-over study each subject serves as his or her own control. For the 
reduction of order effects the sequence of the tested settings (and/or tested devices) will be 
randomized. To do so block randomization will be used. The randomization is applied to all 
investigational settings for both the laboratory trials and the trials in real world environment. For sub-
studies with several test methods the order of the test methods will be also randomized with help of 
block randomization. Randomization and concealment of randomization list is generated by the 
Principle Investigator.  For laboratory tests where several individual ratings are executed with help of 
computer controlled testing procedures (e.g. software tool for MUSHRA test) simple randomization is 
applied to the sequence of the respective settings. This simple randomization is done automatically by 
the tool, the individual simple randomization can be examined afterwards.  
 
6.2.2 
Blind ing  procedu res  
Trial participants will be blinded after assignment to interventions. The subjects will not know which 
hearing instrument technology they are wearing or which hearing instrument setting is activated during 
the respective testing (Please refer to section 6.1 General study design and justification of design). If 
possible double blinding will be executed with help of computer controlled testing procedures (e.g. 
software tool for MUSHRA Test). 
 
6.2.3 
Other methods of  min imi sing  bias  
In addition the following methods will be carried out: 
• 
Sensitizing the investigators to bias (e.g. Halo-Effects).  
• 
Application of standardized test methods according to their instructions to avoid training 
effects 
• 
Usage of validated questionnaires to the greatest possible extent. However, specifically 
adapted questionnaires are inevitable to validly capture the appropriate information needed 
• 
Orthogonal design of the questionnaires  to fulfil the criteria for test quality (objectivity, validity, 
reliability)  
• 
Limited information will be given to the subjects regarding the products and the sound 
changing principles being tested  
• 
In order to ensure a high satisfaction of the subject, the physical position in and on the ear 
must be comfortable and it must be ensured that the subject can operate the device well (e. g. 
putting the hearing instruments on, changing batteries, switching on/off ). These aspects will 
be observed and checked throughout the study sections so that they are not the form factor to 
cause any bias in results, especially subjective results 
 
6.3 Unblinding P roc edur es (Code break)  
(ICH/E6 6.4.8; AGEK 4.2; SPIRIT #17b) 
ICH: Maintenance of tria l treatment randomization codes and proc edures for bre aking codes. 
N/A 
 

 
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7. STUDY POPULATION  
(ICH/E6 6.2.6, 6.4.6; AGEK 3.2, 5; SPIRIT #9, 10, 15, 16, 21) 
ICH: Descripti on of th e populatio n to be studied. 
This section describes the population to be studied. 
 
7.1 Eligibil ity crite ria  
(Clin O, Art 25d5; ICH/E6 6.5.1&6.5.2; AGEK 5.2&5.3; SPIRIT #10) 
ICH: Subject inclusion and exclusion crite ria. 
Only adult subjects will participate. Hearing impaired subjects as well as normal hearing subjects will 
participate, the latter as a control group. 
 
Participants fulfilling all of the following inclusion criteria are eligible for the study:  
• 
Adult (minimum age: 18 years) hearing impaired subjects both with and without (experience 
with) hearing aids 
• 
Adult normal hearing subjects (minimum age: 18 years) 
• 
Healthy outer ear (without previous surgical procedures)  
• 
Ability to fill in a questionnaire conscientiously 
• 
Informed Consent as documented by signature  
 
The presence of any one of the following exclusion criteria will lead to exclusion of the participant: 
• 
Contraindications to the MD in this study, e.g. known hypersensitivity or allergy to the 
investigational product 
• 
Limited mobility and not in the position to attend weekly appointments  
• 
Limited ability to describe listening impressions/experiences and the use of the hearing aid 
• 
Inability to produce a reliable hearing test result  
• 
Massively limited dexterity  
• 
Known psychological problems  
• 
Known central hearing disorders  
 
7.2 Recruitme nt and screening  
(Clin O, Art 25, Appendix 3, 1.4 & 1.6; AGEK 5.1; SPIRIT #15) 
The recruitment will take place outside the study site for external subjects and will also take place 
internal (at Sonova) for internal subjects. 
At Sonova AG Headquarters, a participant database is existing which is currently containing approx. 
700 hearing impaired subjects (various degrees of hearing loss) from circumjacent cantons. 
Furthermore, this database is containing hearing impaired employees from Sonova AG (internal 
subjects). The database is permanently extended (study independently) with new subjects recruited 
via different paths and screened by qualified Audiologists employed at Sonova AG. One examples for 
this recruiting is a flyer for Phonak Field studies (see attachment: Flyer_Phonak_Feldstudie.pdf). 
 
Recruitment and screening outside:  
The pre-selection of suitable participants will be done by the principal investigator after receiving the 
study approval of the responsible CEC by using the participant database belonging to the study site. 
The preselected participants will be listed in a password locked file. Only the study personal will have 
access to this file. The preselected potential participant will be contacted via telephone. At this initial 
contact, the time expenditure and the availability period will be discussed. If a participant is interested 
in participating in the study, the screening appointment for a preliminary clarification will be arranged 
and the participant information and informed consent will be sent to the potential participant by post or 
email at least one week before the screening appointment takes place. The assessment of the 
screening serves to judge the inclusion criteria (e. g. pure tone audiometry), giving answers to any 
questions which the subjects may have, giving information about the study and sign of the informed 
consent. 
For all study related appointments at Sonova AG, the participants will receive a compensation of 25 
CHF/hour and a SBB train ticket (2nd class) from their home address to Sonova AG, Laubisrütistrasse 

 
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28, 8712 Stäfa, by the end of the study. 
 
Recruitment and screening inside:  
The participants are recruited by the study team in the according study site (Sonova AG). The 
participants are employees at the study site. The pre-selection of suitable hearing impaired 
participants will be done by the principal investigator after receiving the study approval of the 
responsible CEC by using the participant database belonging to the study site. 
The time expenditure and the availability period will be directly discussed with the participant. If a 
participant is interested in participating in the study, the screening appointment for a preliminary 
clarification will be arranged and the participant information and informed consent will be sent to the 
potential participant by email at least one week before the screening appointment takes place. The 
assessment of the screening serves to judge the inclusion criteria (e. g. pure tone audiometry), giving 
answers to any questions which the subjects may have, giving information about the study and sign of 
the informed consent.  
The participants participate on a voluntary basis and contribute to an investigational benefit for the 
company. 
 
7.3 Assignme nt to study group s  
(AGEK 5; SPIRIT #16) 
This study will be a controlled cross-overs study with active comparator whereas each subjects will 
receive the intervention to be tested (hearing systems with novel sound changing principles) as well as 
the respective comparator and serves therefore as his or her own control. For the reduction of order 
effects the sequence of the test procedures as well as the sequence of the tested settings (and/or 
tested devices) will be randomized. The randomization is applied to all investigational settings for both 
the laboratory trials and the trials in real world environment .  (refer to 6.2.1 Randomisation). 
 
7.4 Crit eria for withdra wal / discont inua tion o f par tic ipants  
(Clin O, Art 9; ICH/E6 6.5.3; SPIRIT #21b) 
Subject with drawal crite ria (i.e., termi natin g investigatio nal pro duct treatment/trial treatment) and 
proc edures specifying: a) When and how to with draw subjects from  the tria l/ investig atio nal prod uct 
treatment. c) Whether and how subjects are to be replaced. 
If a subject will be withdrawn (e. g. withdrawal of informed consent, non-compliance, disease 
progression, safety etc. or study or routine procedure must be stopped, e. g. due to safety concerns), 
a final assessment of the ear and ear canal will be carried out and all products as well as all study 
material that had been used have to be returned by the participant to the study site. The participants 
participate on a voluntary basis and can abort the participation on the study at any point of the study. 
The withdrawn participant will be replaced by another voluntary participant, if needed. The 
measurement results of the withdrawn participants will be excluded of the evaluation if the results are 
not complete to be included in the analysis. A new participant has to pass each study trial from the 
beginning. 
 
 
 

 
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8. STUDY INTERVENTION  
(SPIRIT #11) 
8.1 Identity of Investigationa l Products (treatment / medical device)  
(ICH/E6 6.2.1, 6.4.2, 6.4.4; AGEK Checklist 2, item 3) 
ICH: A descripti on of the tria l treatment(s) and the dosage and dosage regimen of the investig ational 
produ ct(s).  
This section describes all trial treatments for each arm of the study. 
 
8.1.1 
Experimen tal Intervention  (treatment / medical  device) 
ICH: Name and descripti on of the investigatio nal prod uct(s).  
All investigational devices are CE marked and based on the Sonova brand hearing system portfolio. 
This includes hearing systems comprising hearing instruments with hearing instrument software and 
respective acoustic coupling, fitting software and wireless accessories. The application is done 
according to the specialised information. 
 
8.1.2 
Control Int ervention  (stan dard/routine/com parator treatment / medical device)  
ICH: Name and descripti on of the investigatio nal prod uct(s).  
Same as in 8.1.1, whereas the respective sound changing principle is disabled (switched off or 
switched to a parameter setting with weakest effect) as well as previous hearing instrument 
technology (containing comparable previous sound changing principles). 
 
8.1.3 
Packaging , Labelling  and Supply (re-sup ply)  
ICH: Also include a descripti on of the dosage form , packaging, and labelling of the investig atio nal 
prod uct(s). 
N/A 
 
8.1.4 
Storage Condition s  
All MD and MD supplies have to be stored according to standard procedures as mentioned in the 
manufacturer directions. The hearing instruments will be stored in their hearing instrument cases (dry 
and dust-free). There are no special environmental conditions necessary for storage. 
 
8.2 Admini stration of  experim ental and c ont rol i nterventions   
(ICH/E6 6.4.4) 
8.2.1 
Experimen tal Intervention   
ICH: Descripti on of and justifi catio n of the treatment(s) to be administered, including the name(s) of all 
the prod uct(s), the dose(s), the dosing schedule(s), the route /mode(s) of administrati on, and the 
treatment period (s), including the follow-up period (s) for subjects for each investig ational prod uct 
treatment/tri al treatment gro up/arm of the tria l. 
The study is an clinical trial with medical devices. 
All medical devices in this trial are CE marked and the application is done according to the specialized 
information. 
 
Description of route, dose and the rationale for timing of the investigational medical devices, see the 
following chapters: 
• 
3.5 Dose Rationale / Medical Device: Rationale for the intended purpose in study (pre-market 
MD) 
• 
6.1 General study design and justification of design 
 

 
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Description of study procedures, use and estimated exposure to humans, see the following chapters: 
• 
STUDY SCHEDULE 
• 
5  STUDY OUTCOMES 
• 
6.1 General study design and justification of design 
 
8.2.2 
Control Int ervention  
ICH: Descripti on of and justifi catio n of the treatment(s) to be administered, including the name(s) of all 
the prod uct(s), the dose(s), the dosing schedule(s), the route /mode(s) of administrati on, and the 
treatment period (s), including the follow-up period (s) for subjects for each investig ational prod uct 
treatment/tri al treatment gro up/arm of the tria l. 
Same as in 8.2.1 
 
8.3 Dose / Device modifi cations  
(SPIRIT #11b) 
N/A 
 
8.4 Compli ance with s tudy intervention  
(ICH/E6 6.6.3; AGEK Checklist 2, item 2; SPIRIT #11c) 
ICH: Proc edures for monitorin g subject compliance.  
N/A 
 
8.5 Data Coll ection and Follo w-up fo r withdr awn partic ipants  
(ICH/E6 6.5.3; AGEK 9.2; SPIRIT #18b) 
ICH: ………..b) The type and timing of the data to be collected for w ith drawn subjects. d) The fol low-up for 
subjects with drawn from  investig ational prod uct tr eatment/tria l treatment. 
The subjects participate on a voluntary basis and can abort the participation on the study at any point 
of the study. The withdrawn subject will be replaced by another voluntary subject. The measurement 
results of the withdrawn subject will be included to the evaluation if data are complete for the 
appropriate trial. The new subject has to pass each study trial from the beginning. 
 
8.6 Trial specifi c preventive measures 
(ICH/E6 6.6.2; AGEK 9; SPIRIT #11d) 
ICH: Medicatio n(s)/treatment(s) permi tted (including rescue medicatio n) and not permi tted before  and/or 
during  the tria l. 
To avoid discomfort through too loud output levels of the hearing instruments which could harm the 
subjects ear, the uncomfortable level (UCL) will be measured within the pure tone audiogram during 
the screening appointment. The UCL will be used for the fitting of the hearing instruments to ensure a 
comfortable maximum power output.  
After fitting the hearing instruments to the individual hearing loss of the subject, the subjective 
acceptance of loud input signals will be tested (tolerance test) to ensure that the individual maximum 
power output (based on the UCL measurement) of the hearing instruments is guaranteed and 
accepted by the subject. 
 
8.7 Concomitant Inter ventions  (treatments)  
(ICH/E6 6.6.2; AGEK 9; SPIRIT #11d) 
ICH: Medicatio n(s)/treatment(s) permi tted (including rescue medicatio n) and not permi tted before  and/or 
during  the tria l. 
N/A 
 

 
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8.8 Study Drug /  Medic al Device Account abili ty  
(ICH/E6 6.4.7; AGEK Checklist 2, item 1; SPIRIT 11c) 
ICH: Accountability proc edures for the investigatio nal pro duct(s), including the placebo(s) and 
comparator(s ), if any. 
N/A 
 
8.9 Return or De structio n of Study Drug /  Medic al Device  
(AGEK Checklist 2, item 1; SPIRIT 11c) 
At the end of the study during the final appointment, all study devices will be returned to the according 
PI. 
 
 
 

 
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9. STUDY ASSESSMENTS  
(ICH/E6 6.7, 6.8; AGEK 6, 7; SPIRIT #18a) 
This section includes a description of the procedures, measurements, collections and storage of 
samples taken. 
 
9.1 Study flow  chart(s) / table of s tudy proc edure s and assessments 
Each study is a combination of a pre-study and a main study. Each study part consists of a screening,  
study appointments and one follow-up appointment.  
 
Several pre-studies may be necessary and conducted. The Schedule for a pre-study is visualized in 
Table 7Table 1. The number of the pre-study appointments may vary whereas a minimum of 3 
appointments and a maximum of 6 appointments is considered. The main study represents the actual 
study for the investigation of one sound changing principle. The results from the pre studies are used 
to specify the main study. The Schedule is visualized in Table 8. The number of the study 
appointments may vary depending on the number of tests and test methods being executed for a 
respective sound changing principle. For a main study a minimum of 4 and a maximum of 8 study 
appointments is considered. Please note the following tables repeat those of the section STUDY 
SCHEDULE. 
 
Table 7: Pre-Stud y schedule 
Study Period 
 
Screening 
Pre-study appointments 
Follow-up 
(final 
appointment) 
Visit Number 
1 
2    
(3) 
(4) 
(5) 
3…6 
Time [hrs] 
1.5 
2 
(2) 
(2) 
(2) 
2 
Subject Information and Informed Consent 
x 
 
 
 
 
 
Audiological History 
x 
 
 
 
 
 
Physical Examination of Ear and Ear Canal  
x 
x 
(x) 
(x) 
(x) 
x 
Audiogram  
x 
 
 
 
 
x 
Check In- /Exclusion Criteria 
x 
 
 
 
 
 
Decision Subject Participation 
x 
 
 
 
 
 
Encoded Subject ID 
x 
 
 
 
 
 
Fitting HI 
 
x 
(x) 
(x) 
(x) 
(x) 
Objective Measurements 
 
x 
(x) 
(x) 
(x) 
(x) 
Subjective Measurements 
 
x 
(x) 
(x) 
(x) 
(x) 
Introduction to Handling (depending on 
randomisation list for home trials) 
 
x 
(x) 
(x) 
(x) 
 
Scheduling Next Visit  
x 
x 
(x) 
(x) 
(x) 
 
Capture of Adverse Events and Device 
Deficiencies 
 
x 
(x) 
(x) 
(x) 
x 
 

 
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Table 8: Main study schedule 
Study Period 
 
Screening 
Main study appointments 
Follow-up 
(final 
appointment) 
Visit Number 
1 
2 
3 
(4) 
(5) 
(6) 
(7) 
4…8 
Time [hrs] 
1.5 
2 
2 
(2) 
(2) 
(2) 
(2) 
2 
Subject 
Information 
and 
Informed Consent 
x 
 
 
 
 
 
 
 
Audiological History 
x 
 
 
 
 
 
 
 
Physical Examination of Ear 
and Ear Canal  
x 
x 
x 
(x) 
(x) 
(x) 
(x) 
x 
Audiogram  
x 
 
 
 
 
 
 
x 
Check In- /Exclusion Criteria 
x 
 
 
 
 
 
 
 
Decision 
Subject 
Participation 
x 
 
 
 
 
 
 
 
Encoded Subject ID 
x 
 
 
 
 
 
 
 
Fitting HI 
 
x 
x 
(x) 
(x) 
(x) 
(x) 
(x) 
Objective Measurements 
 
x 
x 
(x) 
(x) 
(x) 
(x) 
(x) 
Subjective Measurements 
 
x 
x 
(x) 
(x) 
(x) 
(x) 
(x) 
Introduction 
to 
Handling 
(depending 
on 
randomisation list for home 
trials) 
 
x 
x 
(x) 
(x) 
(x) 
(x) 
 
Scheduling Next Visit  
x 
x 
x 
(x) 
(x) 
(x) 
(x) 
 
Capture of Adverse Events 
and Device Deficiencies 
x 
x 
x 
(x) 
(x) 
(x) 
(x) 
x 
 
9.2 Assessments of out comes  
ICH: Specifi catio n of the effi cacy parameters. Specifi cation of safety parameters. 
This section includes a description of each endpoint, what variables will be assessed/observed and 
how it will be done, including any related processes to promote data quality. 
 
9.2.1 
Assessment of primar y outcom e  
ICH: Metho ds and timing for  assessing, recordi ng, and analysing of effic acy & safety parameters. 
The primary outcomes are the laboratory test results (Reference to section 5.1 Primary Outcome). 
These tests intend to determine the hearing performance provided by the device. They are conducted 
with help of corresponding measurement tools, whereas the results are stored automatically in an 
appropriate format (e.g. xls file). Depending on the investigated sound changing principle the suited 
outcome measurement is chosen. The respective measurements are carried out at each study 
appointment. In general the content of these assessments in one sub-study includes measurements to 
investigate one of the three hearing performance dimensions (speech intelligibility, signal clarity, 
sound quality / hearing comfort). The respective other hearing dimensions may be investigated 
additionally to examine trade-off aspects. As well the investigational application and the comparator 
have to pass the same measurements to get comparable data. With help of the received data it can be 
concluded whether the experimental condition is superior to the comparator with regard to hearing 
performance. 
  

 
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9.2.2 
Assessment of secondary ou tcom es 
ICH: Metho ds and timing for  assessing, recordi ng, and analysing of effic acy & safety parameters. 
The secondary outcomes are the subjective test results of questionnaires during tests in real world 
environment (Reference to section 5.2 Secondary Outcomes). This includes home trials and may 
include guided walks. This assessment will be done between the appointments (home trials) and/or at 
specifically defined study appointments (guided walks). Depending on the investigated sound 
changing principle the suited outcome measurement is chosen. With the questionnaire as well the 
investigational application and the comparator are subjectively evaluated by the participants. 
Depending on the study part, the questionnaire will be filled out directly in the laboratory or in an home 
trial. 
 
9.2.3 
Assessment of other outcom es of int erest 
ICH: Metho ds and timing for  assessing, recordi ng, and analysing of effic acy & safety parameters. 
Other outcomes of interest like side-effects will be carefully investigated, evaluated and documented. 
This outcome will also be documented in the form of questionnaires. Additional further measurements 
(investigating basic psychoacoustic function for instance) will be done at specifically defined study 
appointments if necessary (Reference to section 5.3 Other Outcomes of Interest). 
 
9.2.4 
Assessment of safety outcom es 
ICH E6 6.8: Specificatio n of safety parameters. The metho ds and tim ing for assessing, recordi ng, and 
analysing safety parameters 
9.2.4.1 
Adverse events  
Basically, all participants will be instructed to immediately report any problems, oddness or difficulties 
which occurred with or through the testing devices by contacting the appropriate investigator. 
Additionally, the investigator will request the same after each home trial at the beginning of the subject 
appointment. Any feedback will be recorded in the appropriate eCRF. 
 
9.2.4.2 
Laboratory parameters 
N/A 
 
9.2.4.3 
Vital signs 
N/A 
 
9.2.5 
Assessments in p articipa nts who prematu rely sto p the study 
Withdraw without Adverse Event: If a subject is withdrawn from the study without having an Adverse 
Event (AE), an audiogram will be recorded in a final appointment and the outer ear will be controlled to 
ensure that there are no damages through the study.  
 
Withdraw with Adverse Event: If a subject is withdrawn in case of an AE, a referral to an independent 
doctor will be carried out. In accordance with the subject and the doctor, an additional appointment will 
be arranged to record a status update.  
 
9.3 Proc edure s at each visit 
Each study part follows the same pattern:  
• 
Pre-Study  
o 
Screening  
o 
Pre-study appointments 
o 
Follow Up 
• 
Main study 

 
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o 
Screening 
o 
Main study appointments 
o 
Follow Up 
 
This pattern ensures the best method to not unnecessarily extend the study and to not perform tests 
with subjects, which are not needed. For that reason first a pre-study is conducted with only a few 
participants to test and determine sensitive outcome measures and promising parameter adjustments 
of the sound changing principle. The aim of the pre-study is to proof the study concept and the 
scientific interrogation behind it. Several pre-studies may be carried out. If the results of the pre-study 
are promising, the main study will start.   
 
9.3.1 
Screening  Appoint ment 
• 
Mapping to an encoded and randomized subject ID 
• 
Discussion of the subject information and signing of the informed consent which were sent in 
advance by post or email  
• 
Recording of the subject’s audiological history  
• 
Ear and ear canal assessment (otoscopy) 
• 
Hearing test (pure tone and speech audiometry)  
• 
In case of tinnitus: Tinnitus Pitch and Loudness Matching 
• 
Explanation of in-/exclusion criteria  
• 
Decision if patient can participate in the trial regarding to the in-/exclusion criteria  
• 
Scheduling of the next visit 
 
9.3.2 
Pre-stu dy appoint ment 
• 
Ear canal assessment  
• 
Fitting of hearing instrument (randomized) 
• 
Measurements objective and subjective (randomized), see section 9.2.1 and 9.2.2 
• 
Fine tuning hearing instrument, if necessary  
• 
Introduction to handling of hearing system (randomized)  
• 
Signing of the device delivery form  
• 
Schedule next visit  
 
9.3.3 
Main stu dy appoint ments 
A main study appointment will only be executed if the pre-study results were promising. The procedure 
for the main study appointments is the same as for the pre-study appointments (see section 9.3.2).  
 
9.3.4 
Final app oint ment 
• 
Ear canal assessment 
• 
Measurements objective and subjective (randomized), see section 9.2.1 and 9.2.2 
• 
Hearing test (pure tone)  
• 
Calculation and signing of the compensation form  
• 
Signing of the device return form  
• 
Collecting all study material 
• 
Hand out of study feedback form  
 
 
 
 

 
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10. SAFETY  
(Clin O Art. 37-43; ICH/E6 6.8; ISO14155 8.2.5, A.14; AGEK 4.1; SPIRIT # 22, 30) 
Description of plans for collecting, documenting, assessing, reporting, and managing solicited and 
spontaneously reported adverse events and other unintended effects of trial interventions or trial 
conduct. 
 
10.1 Drug  studies 
N/A 
 
10.2 Medic al Device Categor y C studies 
N/A 
 
10.3 Medic al Device Categor y A studies 
10.3.1 Definit ion  and Assessment of safety related  events 
All hearing systems are CE-labelled, i.e. the safety of the user is granted. However, the hearing 
instrument can reach a high maximum power output (MPO) which can be louder than the user’s 
threshold of  uncomfortable levels is. For this reason, the MPO will always be set accordingly to 
clinical expertise at a level so that no injuries can occur (Refer to 8.6 Trial specific preventive 
measures). Consequently, neither during the measurements nor in the daily routine the safety of the 
participants will be compromised.  
In order to ensure that each MD works correctly, every device will be checked before each application 
by the appropriate investigator. Furthermore, the participant is instructed to take note of any 
unexpected incidences (e.g. redness or swelling of the outer ear) and to document these in the 
questionnaires. Pressure points are also controlled by the investigator at the beginning and at the end 
of an appointment. In the case that wearing the test devices in the time between the appointments 
becomes uncomfortable or even painful, the subjects are instructed not to wear the devices anymore 
and to contact the investigator for information and, if necessary, a doctor.  
Furthermore, the participants are advised not to wear the device if a setting is not acceptable or 
tolerable, but to contact the investigator for an additional appointment. If any unexpected incidences 
occur during the lab trials the participant will be encouraged to immediately report the issue to the 
investigator.  
In all cases of undesirable events the responsible supervising investigator within Sonova must be 
informed immediately. Where appropriate the test subject will be forwarded to an independent 
fiduciary doctor for further clarification. 
10.3.2 Reporting  of Safety related events 
Reporting to Sponsor:  
Health hazards that require measures are reported to the Sponsor within 24 hours upon becoming 
aware of the event. If any unexpected AEs are to occur (e.g. chronic pain in the ear canal after MD 
application), the event has to be documented in the AE eCRF. Depending on the event, a decision 
needs to be made whether the participation in the study has to be interrupted or even cancelled. If 
required, a referral to an independent doctor is to be carried out. An additional appointment will be 
arranged with the test participant (e.g. after one to two weeks) in order to record and document the 
status update.  
 
Reporting to authorities:  
In Category A studies it is the investigator’s responsibility to report health hazards requiring measures 
to the local Ethics Committee within 2 days. 
 
 
 

 
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11. STATISTICAL METHODS  
(ICH/E6 6.9; AGEK 8; SPIRIT # 14, 20) 
Statis tic al consideratio ns 
ICH: A descripti on of the statis tic al methods to be employed, including tim ing of any planned interim  
analysis(ses). 
This section describes the statistical considerations done for the study and the level of significance 
that will be used. The traceability of the study data is warranted for both the pre-study and the main 
study at any time.  
 
11.1 Hypot hesis 
This is a methodical evaluation in which different parameter settings of novel sound changing 
principles in hearing instruments shall be investigated and new hardware and software technologies of 
Sonova brand products shall be compared with previous outstanding Sonova brand hearing systems. 
Hence, this study will not test a specific hypothesis. 
 
11.2 Determi nation of  Sample  Size  
ICH: The number of subjects planned to be enro lled. In multic entre  tria ls, the numbers  of enrol led 
subjects proj ected for each tria l site should be specifi ed. Reason for choice of sample size, including 
refl ectio ns on (or c alculations of) the power of the trial and clinical justif ication. 
Based on numerous publications in the field of audiology research using standardized measurement 
methods testing hearing impaired subjects as well as on Sonova AG’s extensive study experience, a 
number of maximum 20 - 25 subjects per study is sufficient to obtain statistically significant results on 
a significance level of 5%. 
In the case of the pre-study a maximum of 5 subjects is included, since merely the study concept 
needs to be proven, and no inferential but only descriptive statistics is carried out. Later, during the 
main study, both descriptive and inferential statistics are executed. In the past, typically 20 subjects 
participated per study leading to significant results approaching the primary objective (determine and 
assess the performance of novel sound changing principles in hearing instruments). To tackle the 
secondary objective (investigate and assess the effect of the respective sound changing principles in 
real world environment) mainly descriptive statistics is carried out.  
 
11.3 Statis tic al crit eria of t ermi nation of  tria l  
ICH: A descripti on of the "stopping rule s" or "discontin uatio n crite ria" for individual partic ipants , parts of 
tria l and enti re tri al. 
After each pre-study an analysis is performed. The corresponding results are the basis for the further 
progress of either an additional pre-study or the main study which might be adjusted accordingly, if 
necessary. If the study design has to be adjusted severely or changed based on former results this will 
be reported to the ethics commission via an amendment. 
 
11.4 Planned Analyses  
ICH: A descripti on of the statis tic al methods to be employed, including tim ing of any planned interim  
analysis(ses). 
In a first step, the distribution of the collected subjective and objective data is verified. Based on this 
outcome (normally distributed yes/no) and depending on the scale level (nominal, ordinal, interval or 
rational) of the variables, descriptive statistics is executed in the form of determining the mean value 
and standard deviation or the median and quartile, respectively. Furthermore, diagrams for 
visualization are compiled such as boxplots, histograms and scatterplots.  
Then, after a determination of the measurement variables regarding their relationship or their 
difference, inference statistics is executed by applying the appropriate parametric or non-parametric 
test depending on the data’s distribution either using the correlation coefficient (Pearson, Spearman), 
t-Test, ANOVA, MANOVA, Mann-Whitney-U-Test, or the Wilcoxon-Test. Generally, a significance 
level of 5% is pursued. 

 
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11.4.1 Datasets to be analysed, analysis populatio ns 
ICH: The selectio n of subjects to be included in the analyses (e.g., all randomized subjects, all dosed 
subjects, all eligible subjects, evaluable subjects). 
The data of all participants and measurement methods will be analysed. Subgroups typically 
composed are hearing loss dependent groups (mild, moderate, severe, profound) and groups 
depending on their experience level wearing hearing instruments or using accessories (non-
experienced, short-term, experienced, long-term user).  In case of a subject withdrawal, the statistician 
will decide if the data can be used for a part of the statistical analysis or if the data will be dropped out 
completely. 
 
11.4.2 Primary Analysis 
The primary analysis will be done by the statistician with help of appropriate software programs (e.g. 
Matlab, Statistica) by the end of the study (end of the pre-study and end of the main study). 
 
11.4.3 Secondary Analyses 
The secondary analysis is done in the same way as the primary analysis. 
 
11.4.4 Interim an alyses 
ICH 6.9.1: ...... including timing of any planned interim  analysis(ses). 
The procedure for each study is, to first make a pre-study with a small group of participants. After the 
pre-study an analysis is done, which can be also named interim analysis. Several pre-studies may be 
carried out. If the results of the pre-study (the pre-studies) do not look promising, it is decided whether 
to review the study design or to discontinue the study completely. If the results of the pre-study are 
sufficient one will continue with the main study.    
 
11.4.5 Safety analysis 
The safety analysis will be done permanently during the study by the PI. 
 
11.4.6 Deviatio n(s) from the ori ginal stat isti cal pl an  
(ICH/E6 6.9.6) 
ICH: Proc edures for reportin g any deviatio n(s) from  the orig inal statistic al plan (any deviatio n(s) from  the 
orig inal statis tical plan should be describe d and justifi ed in proto col and/or in the fin al report, as 
appropria te). 
Deviation(s) from the original statistical plan will be described and justified in a protocol and in a final 
report, as appropriate. 
 
11.5 Handli ng of  missing data and drop -out s  
(ICH/E6 6.9.5; AGEK 8.5; SPIRIT 20c) 
ICH: Proc edure for a ccounting for missing, unused, and spuriou s data. 
If data records are complete from subjects who dropped out of the study early, these data will also be 
used in the analysis. If the data sets are not complete, they will not be integrated in the analysis.  
 
 
 

 
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12. QUALITY ASSURANCE AND CONTROL  
(ICH/E6 6.11, 6.13; AGEK 12; SPIRIT #19, 23, 27) 
ICH: Quality Control and Quality Assurance Proc edures 
This section describes how quality is assured and controlled. 
 
12.1 Data handling a nd record k eeping /  archiv ing  
(Clin O, Art. 18, 45, 57, 62; ICH/E6 6.13; AGEK 12; SPIRIT #19, 27) 
ICH: Data Handling and Record Keeping 
All data and documents recorded during the study are only accessible to the clinical study team and to 
the monitor. Results from the laboratory measurements are stored automatically by the corresponding 
measurement tool in an appropriate format (e.g. xls file). The personal data, the source data of 
measurements, the documents inclusive all notes get coded and monitored. The code list for the 
codification is safely kept within the clinical study team.  
All listed clinical investigators have access to the code list. This code list is not accessible to other 
people. The whole original data and personal data are accessible to the whole clinical study team. The 
study data are to undergo a comprehensive analysis. A written final report containing all phases of the 
study as well as a summary is to be written after the study is finished and is available to Sonova 
headquarters. The participants names have to be coded when they have to be used in an analysis.  
At the end of the study all of the collected data, either collected in paper form or electronically, will be 
saved in an investigator site file (ISF) on CD or DVD. The ISF will be archived at Sonova AG Stäfa. 
The final data export will be stored electronically and in paper form. 
 
12.1.1 Case Report Forms  
(ICH/E6 6.4.9) 
ICH: The identi fic atio n of any data to be recorde d directly on the CRFs (i.e., no prio r writte n or electroni c 
record of data), and to be considered to be source data. 
Study data is recorded both with paper and with electronic Case Report Forms (p/eCRF). For each 
enrolled study participant a CRF is maintained. All CRFs are kept current to reflect the subject’s status 
at each phase during the course of study. Participants cannot be identified in the CRF by name or 
initials and birth date but an appropriate coded identification is used, e.g. VP10SL15 containing the 
subject number and the study identifier. All study team members are authorized for the CRF entries 
and it is assured that any authorised person can be identified both for pCRFs and eCRFs. If pCRFs 
are used, the investigator’s acronym as well as the subject ID is filled in and data are entered into an 
electronic file for analysis by the respective investigator and data get monitored by the assigned 
monitor. In case of a self-evident corrections, either the subject does it by himself or the investigator 
undertakes the correction by crossing out the word/sentence with a single horizontal line and by 
adding the correction including his personal identifier and the date. 
 
12.1.2 Specification  of sou rce docum ents  
(ICH/E6 6.4.9) 
ICH: The identi fic atio n of any data to be recorde d directly on the CRFs (i.e., no prio r writte n or electroni c 
record of data), and to be considered to be source data. 
Source data are available at the site to document the existence of the study participants and can be 
found as described in section 12.1. The source data include the original documents relating to the 
study as follows: 
• 
Demographic data / audiological history 
• 
Visit dates 
• 
Informed Consent Forms 
• 
Randomisation number 
• 
AEs/SAEs 
• 
Device Deficiencies (DD) 
• 
Results of relevant measurements 
• 
Directly recorded data in p/eCRFs  
 

 
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12.1.3 Record keepin g / archiv ing   
(ICH/E6 6.13) 
ICH: Data Handling and Record Keeping 
All study data will be archived for a minimum of 10 years after study termination or premature 
termination of the clinical trial. The location of storage is on SharePoint as well in the archive at 
Sonova AG, Stäfa, as explained in section 12.1. 
 
12.2 Data management  
(ICH/E2; AGEK 12.2; SPIRIT #19) 
This section describes plans for data entry, coding, security, and storage, including any related 
processes to promote data quality. 
 
12.2.1 Data Management  System  
The data management is carried out as described in section 12.1 with help of a data management 
system. Data management systems that may be applied are the database IBM Clinical Development 
(former eClinicalOS), the SharePoint Web Application (Microsoft) and the SQL server (Microsoft). The 
EDC system gets verified and validated by the study team in the form of User Acceptance Tests (UAT) 
prior to each study start to ensure a proper working of the solution for the user. In addition, the study 
team accesses a permanent SharePoint site which is verified as well as validated and the filing of the 
documents follows a predefined scheme. The SQL server working in the background is controlled by 
the IT at Sonova AG, Stäfa. 
 
12.2.2 Data securit y, access and back -up  
Data security is fully granted, the access is limited to specified persons and both systems IBM Clinical 
Development and SharePoint undergo a daily backup on appropriate servers. 
 
12.2.3 Analysis and archiv ing  
Data are extracted via the Microsoft SQL server and can be converted to an arbitrary format, e.g. xls 
file. For the data analysis, different programs are used such as Microsoft Excel, SPSS, Statistica and 
MatLab. Archiving is done according to section 12.1 for a minimum of 10 years. 
 
12.2.4 Electronic and central data validatio n  
The data is validated by the monitor. 
 
12.3 Monito ring  
(AGEK 12.1; SPIRIT #23) 
During this Study the Monitor will perform the Monitoring on a regular base - including the initiation 
visit, the routine visit and the close-out visit - in order to ensure that the study is conducted in 
accordance to the clinical investigation plan, further written procedures (if applicable), the ISO 
14155:2011 as well as further applicable requirement. The extent and nature of the monitoring 
appropriate for the particular sub-study is assessed separately, including the strategy for source data 
verification. This will be  based on considerations such as the objective, design, complexity, size 
critical data points and endpoints of the particular sub-study. 
 
12.4 Audits and Ins pectio ns  
(Clin O, Art. 58, 59; AGEK 12.1; SPIRIT #23) 
The study documentation and the source data/documents are accessible to auditors/inspectors and 
questions are answered during inspections. All involved parties have to keep the participants data 
strictly confidential. 

 
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12.5 Confidentiality, Data Protec tion  
(Clin O, Art. 18, 58; SPIRIT #27, 29) 
Direct access to source documents will be permitted for purposes of monitoring (12.3), audits and 
inspections (12.4) (ICHE6, 6.10). Confidentiality and data protection is granted since access to the 
original data is only allowed to the study team, the monitor and the auditor. In case of publications by 
Sonova AG, the data is anonymized and no conclusion can be made to the subjects. 
 
12.6 Storage of biologic al materi al and r elated health da ta  
(Clin O, Art. 18; HVF Art. 28-32; SPIRIT #33) 
N/A 
 
 

 
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13. PUBLICATION AND DISSEMINATION POLICY  
(ICH/E6 6.15) 
ICH: Publicatio n policy, if not addressed in a separate agreement. 
The results are documented in a final report and will be communicated to relevant employees of the 
Sonova AG. Occasionally parts of the results could be published in internal papers, specialised press 
(industry magazine), or in respective journals.  
 
 

 
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14. FUNDING AND SUPPORT  
(Clin O, Art. 25i; ICH/E6 6.14; SPIRIT #4) 
This section provides a brief statement of sources and types of financial, material, and other support 
for the trial. 
 
14.1 Fund ing  
(Clin O, Art. 25i) 
ICH: Financing and insurance if not addressed in a separate agreement. 
All sources and types of financial support for the study is provided by the Sponsor, Sonova AG. 
 
14.2 Other  Suppo rt  
(Clin O, Art. 25i) 
ICH: Financing and insurance if not addressed in a separate agreement. 
All material is provided by the Sponsor, Sonova AG. 
15. INSURANCE  
(Clin O Art 12, 13; ICH/E6 6.14, AGEK 10.3; SPIRIT #30) 
ICH: ….and insurance if not addressed in a separate agreement. 
Category A studies are exempt hence no insurance is required. However, insurance will be provided 
by the Sponsor, Sonova AG: Police (Nr. CHCANA00770) „Versicherung für klinische Versuche in der 
Humanforschung“ from the insurance broker KESSLER & CO AG Forchstrasse 95, CH-8032 Zürich. A 
copy of the specific certificate for each study part is filed in the ISF.  
 
 
 

 
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16. REFERENCES  
(ICH/E6 6.2.7) 
ICH: References to literature and data that are relevant to the tria l, and that prov ide backgrou nd for the 
tria l. 
List of the references cited in the protocol: 
1. Declaration of Helsinki, Version October 2013, 
(http://www.wma.net/en/30publications/10policies/b3/index.html )  
2. International Conference on Harmonization (ICH, 1996) E6 Guideline for Good Clinical 
Practice. 
(http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/Step
4/E6_R1__Guideline.pdf ) 
3. International Conference on Harmonization (ICH, 1997) E8 Guideline: General Considerations 
for Clinical Trials 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E8/Step4/E8
_Guideline.pdf) 
4. Humanforschungsgesetz, HFG Bundesgesetz über die Forschung am Menschen 
(Bundesgesetz über die Forschung am Menschen, HFG) vom 30. September 2011/ Loi 
fédérale relative à la recherche sur l’être humain (loi relative à la recherche sur l’être humain, 
LRH) du 30 septembre 2011. 
(http://www.bag.admin.ch/themen/medizin/00701/00702/07558/index.html?lang=de) 
5. Verordnung über klinische Versuche in der Humanforschung (Verordnung über klinische 
Versuche, KlinV) vom 20. September 2013 / Ordonnance sur les essais cliniques dans le 
cadre de la recherche sur l’être humain (Ordonnance sur les essais cliniques, OClin) du 20 
septembre 2013. 
(http://www.bag.admin.ch/themen/medizin/00701/00702/12310/index.html?lang=de) 
6. Heilmittelgesetz, HMG Bundesgesetz über Arzneimittel und Medizinprodukte (Heilmittelgesetz, 
HMG) vom 15. Dezember 2000/Loi fédérale sur les médicaments et les dispositifs médicaux 
(Loi sur les produits thérapeutiques, LPT) du 15 décembre 2000. 
(http://www.admin.ch/ch/d/sr/8/812.21.de.pdf) 
7. ISO 14155:2011 Clinical investigation of medical devices for human subjects -- Good clinical 
practice (www.iso.org) 
8. ISO 10993 Biological evaluation of medical devices (www.iso.org) 
9. WHO, International Clinical Trials Registry Platform (ICTRP) (http://www.who.int/ictrp/en/) 
10. Kochkin, S. (2010). MarkeTrak VIII, Consumer satisfaction with hearing aids is slowly 
increasing, Hearing Journal, Vol. 63, No. 1, 2010 
11. Kochkin, S. (2011). MarkeTrak VIII, Patients report improved life with hearing aid usage, 
Hearing Journal, Vol. 64, No. 6, 2011  
12. Aazh, H. and Moore, B.C.J (2007). The Value of Routine Real Ear Measurement of the Gain 
of Digital Hearing Aids. J. Acoust. Soc. Am., 18: 653-664(12). 
13. Kollmeier, B. (1992), Moderne Verfahren der Sprachaudiometrie, Band 1. Medianverlag von 
Killisch-Horn GmbH 
14. Wagener, K., Kühnel, V. & Kollmeier, B. (1999a). Entwicklung und Evaluation eines 
Satztestes für die deutsche Sprache Teil III: Evaluation des Oldenburger Satztestes. 
Zeitschrift für Audiologie 38, 1999. p: 86-95  
15. Wagener, K., Brand, T. & Kollmeier, B. (1999b). Entwicklung und Evaluation eines Satztestes 
für die deutsche Sprache Teil I: Design des Oldenburger Satztests. Zeitschrift für Audiologie 
38(1), p: 4-14  
16. Wallenberg v., E. & Kollmeier, B. (1989). Sprachverständlichkeitsmessungen für die 
Audiologie mit einem Reimtest in deutscher Sprache: Erstellung und Evaluation von Testlisten. 
Audiologische Akustik, 28(2):50-65. 
17. Sukowski H., Brand T., Wagener K.C., Kollmeier B. (2010). Vergleich des Göttinger Satztests 
und des Einsilber-Reimtests nach Wallenberg und Kollmeier mit dem Freiburger Sprachtest. 
HNO Volume 58 Nr. 6  
18. Bolia R. S., Nelson W. T., Ericson M. A., Simpson B. D. (2000). A speech corpus for 
multitalker communications research. Journal of the Acoustical Society of America, 107, 
1065–1066; 
19. Marrone N. L., Mason C. R., Kidd G., Jr. (2008c) Evaluating the benefit of hearing aids in 
solving the cocktail party problem. Trends in Amplification 12: 300–315. 
20. Helfer and Freyman (2009), “Lexical and indexical cues in masking by competing speech,” 

 
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JASA 
21. Carroll, R., Meis, M., Schulte, M., Vormann, M., Kießling, J., & Meister, H. (2015). 
Development of a German Reading Span Test with dual task design for application in 
cognitive hearing research. International Journal of Audiology, 54(2), 136-141. 
22. Nasreddine, Z.S., Phillips, N.A., Bédirian, V., Charbonneau, S., Whitehead, V., Collin, I.,  
Cummings, J.L., Chertkow, H. (2005). The Montreal Cognitive Assessment, MoCA: a brief 
screening tool for mild cognitive impairment. Journal of the American Geriatric Society, 53(4), 
695-699. 
23. Mishra, S. (2014). Exploring cognitive spare capacity: executive processing of degraded 
speech. Linköping University. 
24. Rudner, M., Ng, H.N.E., Rönnberg, N., Mishra, S., Rönnberg, J., Lunner, T., and Stenfelt, S. 
(2011). Cognitive spare capacity as a measure of listening effort. Journal of Hearing Science 
1, 47-49. 
25. Wickens, C.D. (2008). Multiple resources and mental workload. Hum Factors 50, 449-455.  
26. Lehnhardt, E. and Laszig, R. (2000). Praxis der Audiometrie, 8. überarbeitete und erweiterte 
Auflage. Thieme-Verlag Stuttgart. 
27. Wolfe, J., John, A., Schafer, E., Nyffeler, M., Boretzki, M., & Caraway, T. (2010). Evaluation of 
nonlinear frequency compression for school-age children with moderate to moderately severe 
hearing loss. Journal of the American Academy of Audiology, 21(10), 618-628. doi: 
10.3766/jaaa.21.10.2. 
28. Wolfe, J., John, A., Schafer, E., Nyffeler, M., Boretzki, M., & Caraway, T., et al. (2011). Long-
term effects of non-linear frequency compression for children with moderate hearing loss. 
International Journal of Audiology, 50(6), 396–404. doi: 10.3109/14992027.2010.551788. 
29. Phoneme Perception Test: URL (status: 04.06.2015) 
https://www.phonakpro.com/com/b2b/de/professional_tools/diagnostic/phoneme-perception-
test/overview.html 
30. Schmitt, N.; Winkler, A.; Boretzki, M.; Holube, I. (2015). A Phoneme Perception Test Method 
for High-Frequency Hearing Aid Fitting. Journal of the American Academy of Audiology, 00:1-
13(2015). DOI: 10.3766/jaaa.15037 
31. Mueller, M.F., Meisenbacher, K., Lai, W., Dillier, N. (2014). Sound localization with bilateral 
cochlear implants in noise: how much do head movements contribute to localization? 
Cochlear Implants Int.: 15(1):36-42. doi 10.1179/1754762813Y.0000000040. Epub 2013 Nov 
25. 
32. Kirchberger, M. J. & Russo, F. A. (2015). Development of the adaptive music perception test. 
Ear and Hearing, 36(2), 217-228. 
33. Borg, I. and Staufenbiel, T. (1997). Theorien und Methoden der Skalierung: eine Einführung. 
Bern: Huber, Auflage 4. ISBN-10: 34568444476. 
34. Hellbrück, J. and Ellermeier, W. (2004). Hören – Physiologie, Psychologie und Pathologie. 
Hogrefe, 2. aktualisiert und erweiterte Auflage.  
35. David, H.A. (1988). The Method of Paired Comparisons. New York: Oxford University Press 
36. MUSHRA: ITU-R recommendation BS.1534 
37. Gustav H. Blanke (1973). Einführung in die semantische Analyse. Hueber, München, 135–137. 
38. Freyaldenhoven, M.C., Nabelek, A.K., Burchfield, S.B., & Thelin, J.W. (2005). Acceptable 
noise level (ANL) as a measure of directional benefit. Journal of the American Academy of 
Audiology 16, 228-236. 
39. Nabelek, A.K., Freyaldenhoven, M.C., Tampas, J.W., Burchfield, S.B., & Muenchen, R.A. 
(2006). Acceptable noise level as a predictor of hearing aid use. Journal of the American 
Academy of Audiology,17, 626-639. 
40. Brand, T. and Hohmann, V. (2002). An adaptive procedure for categorical loudness scaling. J. 
Acoust. Soc. Am., 112(4): 1597-604. 
41. Blau, M., Sankowsky, T., Oberdanner, H., Stirnemann, A. (2008). Einfluss des 
Otoplastikprofils auf den objektiven Okklusionseffekt. DAGA, 2008. 
42. Schulte, M., Krüger, M., Meis, M., Wagener, K.C., (2015) Subjective listening effort. The 
Journal of the Acoustical Society of America, 137(4), 2236-2236. 
43. Neumann, W.L. (2005). Social Research Methods: Qualitative and Quantitative Approaches 
(6th Edition), ISBN-13: 978-0205457939. 
44. Larson, R. and Csikszentmihalyi, M. (1983). The Experience-Sampling method. Naturalistic 
Approaches to Studying Social Interaction: New Directions for Methodology of Social and 
Behavioral Science. San Francisco, CA: Jossey-Bass. 
45. Stone, A. and Shiffman, S. (1994). Ecological momentary assessment (EMA) in behavorial 
medicine. Annals of Behavioral Medicine, Vol 16(3), 199-202.  

 
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46. Intille, S.S., Rondoni, J., Kukla, C., Iacono, I., Bao, L. (2003). A Context-Aware Experience 
Sampling Tool. 5-10, Ft. Lauderdale, Florida, USA. ACM 1-58113-630-7/03/0004 
47. Gatehouse, S., and Noble, W. (2004). "The Speech, Spatial and Qualities of Hearing Scale 
(SSQ)," Int. J. Audiol. 43, 85-9. (https://www.ihr.mrc.ac.uk/pages/products/ssq) 
48. Moore, B.C.J. (2012). An Introduction to the Psychology of Hearing. Sixth edition. Emerald 
Group Publishing Limited. 
49. Moore, B.C., Huss, M., Vickers, D.A., Glasberg, B.R., Alcántara, J.L. (2000). A test for the 
diagnosis of dead regions in the cochlea. Br. J. Audiol., Aug, 34(4):205-24.  
50. Hoare, D.J., Edmonson-Jones, M., Gander, P.E., Hall, D.A. (2014). Agreement and Reliability 
of Tinnitus Loudness Matching and Pitch Likeness Rating. PloS ONE 9(12): e114553. 
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51. Strelcyk, O.; Dau, T. (2009). Relations between frequency selectivity, temporal fine-structure 
processing, and speech reception in impaired hearing. The Journal of the Acoustical Society 
of America 125 (5), 3328-3345; 
52. Bartosinski. 2017. Hemoencephalography (HEG) Biofeedback as a method of stress control 
among healthy subjects. International Journal of Humanities and Social Science Invention. 
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54. Serra-Sala et al. 2016. Clinical usefulness of Hemoencephalography beyond the 
neurofeedback. Neuropsychiatric Disease & Treatment. 12, 1173-1180. 
 
 
 
 

 
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17. APPENDICES 
ICH: (NOTE: Since the prot ocol and the clinical tria l/stud y report are closely related, furth er relevant 
inform atio n can be found in the ICH Guid eline for Stru cture and Content of Clinical Stud y Reports. ) 
N/A