Cochlear Implantation in Adults With Asymmetric Hearing Loss Clinical Trial
Phase: NA
Conditions: Hearing Loss
Sponsor: Washington University School of Medicine

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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Cochlear Implantation in Adults with 
Asymmetric Hearing Loss  
Clinical Trial 
 
Protocol 
Version 1.4 
NCT03052920 
December 5, 2014 
Revised January 4, 2015 
Revised January 12, 2017 
Revised June 1, 2017 
Revised April 27, 2018 
Study Sponsor: 
Washington University School of Medicine in St. Louis 
Department of Otolaryngology – Head and Neck Surgery 
660 South Euclid Avenue 
Campus Box 8115 
St. Louis, MO 63110 
 
 
Principal Investigator:  Jill B. Firszt, PhD 
Principal Medical Investigator:  Richard A. Chole, MD, PhD 
 
 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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Cochlear Implantation in Adults with Asymmetric Hearing Loss  
Clinical Trial 
Protocol Table of Contents 
Study Sponsor: ............................................................................................................. 1 
Principal Investigator: .................................................................................................. 1 
Principal Medical Investigator: .................................................................................... 1 
Cochlear Implantation in Adults with Asymmetric Hearing Loss  Clinical Trial ...... 2 
Protocol Table of Contents ...................................................................................... 2 
Introduction .................................................................................................................. 6 
Study Objectives .......................................................................................................... 9 
Study Design ................................................................................................................ 9 
Device Descriptions ....................................................................................................10 
Advanced Bionics LLC ...........................................................................................10 
Cochlear Americas .................................................................................................10 
Med-EL Corporation ...............................................................................................10 
Participant Population ................................................................................................10 
Inclusion Criteria ....................................................................................................10 
Exclusion Criteria ...................................................................................................11 
Spouse/Significant Other ............................................................................................11 
Investigation Procedures ............................................................................................11 
Test Measures .............................................................................................................11 
Unaided Audiometric Threshold Levels ..................................................................11 
Aided FM, Tone Sound Field Threshold Levels ......................................................11 
Consonant-Vowel Nucleus-Consonant (CNC) Word Test .......................................12 
AzBio Sentence Test ..............................................................................................12 
Bamford-Kowal-Bench Speech-in-Noise (BKB-SIN) Test .......................................12 
Localization Test ....................................................................................................12 
Questionnaires .......................................................................................................13 
Hearing Handicap Inventory for the Elderly (HHIE) .................................................13 
Health Utilities Index Mark 3 (HUI3) ........................................................................13 
Speech, Spatial and Sound Qualities (SSQ) Questionnaire ....................................13 
Glasgow Benefit Inventory (GBI) ............................................................................13 
Satisfaction with Amplification in Daily Life (SADL) .................................................13 
Participant Interview Form ......................................................................................13 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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The Communication Profile for the Hearing Impaired (CPHI) – Communication 
Performance ...........................................................................................................14 
The Hearing Impaired Impact – Significant Other Profile (HII-SOP) ........................14 
Study Schedule ...........................................................................................................14 
Pre-Implant Candidacy Evaluation .............................................................................14 
Informed Consent ...................................................................................................14 
Hearing History ......................................................................................................16 
Unaided Audiometric Threshold Levels ..................................................................16 
Verification of Hearing Aids ....................................................................................16 
Aided, FM Tone Sound Field Threshold levels .......................................................16 
CNC Word Recognition Testing .............................................................................16 
Alternative Therapy Assessment ............................................................................16 
Sentence testing .....................................................................................................17 
Localization ............................................................................................................17 
Candidacy Determination .......................................................................................17 
Pre-Implant Study Testing ..........................................................................................17 
Hearing Aid in the Better Ear ..................................................................................17 
Aided, FM Tone Sound Field Threshold Levels ......................................................17 
Sentence testing .....................................................................................................17 
Localization ............................................................................................................18 
Hearing Aid in the Poor Ear ....................................................................................18 
Aided, FM Tone Sound Field Threshold Levels ......................................................18 
Sentence Testing ...................................................................................................18 
Hearing Aid in Both Ears ........................................................................................18 
CNC Word Testing .................................................................................................18 
Sentence Testing ...................................................................................................18 
Localization ............................................................................................................18 
Questionnaires .......................................................................................................18 
HHIE ......................................................................................................................18 
HUI3 .......................................................................................................................18 
SSQ .......................................................................................................................18 
SADL ......................................................................................................................19 
Participant Interview Form ......................................................................................19 
Counseling .............................................................................................................19 
Surgery .........................................................................................................................19 
Initial Stimulation of the Cochlear Implant ................................................................19 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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Unaided Audiometric Threshold Levels* .................................................................19 
Participant Interview Form ......................................................................................20 
Participants’ take-home speech processor programs .............................................20 
Aural Rehabilitation .....................................................................................................20 
Post-Implant Study Testing (3, 6, 9 and 12 months after Initial Stimulation) ..........20 
Unaided Audiometric Threshold Levels* .................................................................20 
Hearing Aid in the Better Ear ..................................................................................20 
Verification of Hearing Aid ......................................................................................20 
Aided, FM Tone Sound Field Threshold Levels ......................................................21 
CNC Word Test ......................................................................................................21 
Sentence Testing ...................................................................................................21 
Cochlear Implant Ear ..............................................................................................21 
CI, FM Tone Sound Field Threshold Levels ............................................................21 
CNC Word Test ......................................................................................................21 
Sentence Testing ...................................................................................................21 
Bimodal (HA and CI together) ................................................................................21 
CNC Word Test ......................................................................................................21 
Sentence Testing ...................................................................................................21 
Localization ............................................................................................................22 
Questionnaires .......................................................................................................22 
Participant Interview Form ......................................................................................22 
Participants’ speech processor programs used for testing ......................................22 
Safety ...........................................................................................................................23 
Efficacy ........................................................................................................................23 
Sample Size Justification .......................................................................................23 
Data Analysis .........................................................................................................24 
Risk Benefit Statement................................................................................................25 
Good Clinical Practices Statement ............................................................................26 
Access to Study Documents and Monitoring ............................................................26 
Quality Control Assurance .........................................................................................26 
Data and Safety Monitoring Board (DSMB) ...............................................................26 
Institutional Review Board ..........................................................................................26 
Informed Consent Process .........................................................................................27 
Confidentiality .............................................................................................................27 
Protocol Amendments ................................................................................................27 
Data Management ........................................................................................................28 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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Record Keeping and Retention ..................................................................................28 
Study Report and Publication.....................................................................................29 
Adverse Events ...........................................................................................................29 
Adverse Event (AE) ................................................................................................29 
Serious Adverse Event (SAE) ................................................................................29 
Unanticipated Adverse Device Effect (UADE) ........................................................29 
Investigator Responsibilities ...................................................................................29 
Adverse Event Follow-up – Investigator Responsibilities ........................................30 
Adverse Event Follow-up – Sponsor Responsibilities .............................................30 
Protocol Deviations ................................................................................................30 
Study Completion ........................................................................................................31 
Completed Participants ..........................................................................................31 
Discontinued Participants .......................................................................................31 
Premature Study Termination .................................................................................31 
Product Accountability ...............................................................................................31 
References ...................................................................................................................31 
 
 

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Cochlear Implantation in Adults with Asymmetric Hearing Loss  
Clinical Trial 
Protocol 
Introduction 
The advantages of binaural hearing (listening with two ears) over monaural hearing 
(listening with one ear) have been well documented and include sound localization, 
speech understanding in noise, judgments of distance and movement, and detection of 
soft or distant speech (Cochran et al., 1968; Durlach and Colburn, 1978; Grantham, 
1986; Bronkhorst and Plomp, 1988, 1989; Akeroyd, 2006; Colburn et al., 2006).  These 
advantages are achieved by the ability to receive and compare acoustic signals from two 
ears.  Because ears are spatially separated, the sound received at each ear differs in 
both time and amplitude information.  For example, whether localizing a sound or 
listening in noise, one ear is typically closer to the signal than the other, with the head 
acting as a barrier between the ears.  Consequently, the signal arrives at the near ear 
before the far ear, creating discrepancies in arrival time referred to as interaural time 
differences (ITDs).  Furthermore, because the head impedes the sound, the signal has 
greater amplitude at the near ear compared to the far ear, which results in loudness 
differences between the ears referred to as interaural level differences (ILDs).  All 
audible sounds generate both ITDs and ILDs that are crucial for central processing of 
auditory information.  The ability to reconcile these differences with great precision 
enables binaural listeners to localize sound and understand speech in background noise 
with little effort.  Having input to both ears also provides a redundant signal to the 
auditory system, which is important for understanding soft speech and hearing distant 
sounds (Levitt and Rabiner, 1967a, b; Morera et al., 2005; Morera et al., 2012).  Studies 
utilizing self-assessment questionnaires have confirmed that monaural listeners perceive 
deficits in everyday communication for understanding soft speech and speech in noise 
as well as for spatial hearing.  Moreover, studies have identified secondary effects of 
hearing loss such as fatigue, increased effort, anxiety and social isolation (Hétu et al., 
1988; Ringdahl and Grimby, 2000; Hicks and Tharpe, 2002; McCoy et al., 2005; 
Nachtegaal et al., 2009).  The degradation or complete loss of binaural abilities can have 
a significant impact on daily communication and overall quality of life.   
Individuals with asymmetric hearing, that is, one ear with moderate hearing loss and one 
ear with severe to profound hearing loss (SPHL), lack binaural input and are thus unable 
to attain binaural hearing advantages.  Clinically, attempts to fit amplification in the poor 
ear with SPHL are problematic due to the severity of the hearing loss and the limitations 
of hearing aid (HA) technology, which result in insufficient gain and reduced sound 
quality.  Patients often discontinue amplification in this ear due to lack of perceived 
benefit and are consequently rendered monaural listeners (Kochkin, 2010; Kaplan-
Neeman et al., 2012).  Interestingly, Noble and Gatehouse (2004) reported that patients 
with asymmetric hearing were significantly more disabled than those with symmetric 
hearing loss for speech recognition, spatial hearing and quality of sound.  
A treatment option for individuals with asymmetric hearing loss is a bilateral contralateral 
routing of the signal HA (BiCROS) (Oeding and Valente, 2013).  This system consists of 
a transmitter worn on the poor ear that picks up sound through a microphone and a HA 
with an integrated receiver that is worn on the better ear.  The HA provides amplification 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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to that ear and also receives the sound from the microphone worn on the poor ear.  In 
other words, sound from the poor side is routed via wireless transmission to the better 
hearing ear.  Although a BiCROS HA allows sound to be detected from both sides of the 
head, all sound is heard by the better ear.  New technology, such as improved digital 
signal processing and noise reduction circuitry, has been implemented in current 
BiCROS HAs in hopes of improving performance; these features were preferred by 
individuals who used older BiCROS technology (Williams et al., 2012; Oeding and 
Valente, 2013).  However, test measures, specifically testing in noise, did not show a 
significant difference in performance between newer and older BiCROS technology.  In 
fact, Oeding and Valente (2013) found no difference between the unaided test condition 
and three BiCROS test conditions (no noise reduction circuitry, mild noise reduction, and 
maximum noise reduction).  Williams et al. (2012) also reported no statistically significant 
improvement when testing in noise with newer versus older BiCROS technology.  
Furthermore, group mean scores in noise were no different when participants were 
tested with just a HA on the better ear (nothing on poor ear) versus the full BiCROS 
system.  These results were consistent regardless of the technology used (i.e., new or 
older).  A significant limitation of the BiCROS HA is that it does not provide binaural 
input.  As a result, individuals fit with a BiCROS are unable to take advantage of ITDs 
and ILDs, which are necessary for binaural processing to improve speech understanding 
in noise.  As noted above, ITDs and ILDs are also necessary for sound localization.  The 
research in this area (BiCROS and sound localization) is sparse; however, Arndt et al. 
(2011) evaluated localization abilities of 11 individuals who had worn a contralateral 
routing of the signal (CROS) device for three weeks.  These individuals had one ear with 
SPHL and one ear with normal hearing.  Like the BiCROS system, the CROS device 
routes the signal from the poor hearing side to the good hearing side but does not 
provide amplification to the better (normal hearing) ear.  Results of the Arndt study 
revealed no difference in sound localization ability between the CROS device and no 
device conditions.  Therefore, it is unlikely that a BiCROS HA would be beneficial in 
localizing sound.  Again, because the BiCROS and CROS systems do not restore 
hearing to the poor ear, individuals using this technology do not receive binaural cues, 
such as ILDs or ITDs and consequently, cannot achieve advantages derived from 
binaural hearing.     
The treatment option most typically used for individuals with asymmetric hearing loss is 
a HA fitted to the better ear only and no HA in the poorer ear.  As stated above, fitting a 
HA to an ear with a SPHL and poor word recognition is generally unsuccessful and 
therefore not routinely done for individuals with a better hearing ear.  Insufficient gain, 
poor sound quality, and lack of perceived benefit when the poor ear is aided are 
common concerns.  Additionally, it is often assumed that these individuals can function 
sufficiently well with conventional amplification in the better ear alone.  A weakness of 
this assumption is that fitting of amplification in one ear does not allow ITD or ILD 
comparisons and all binaural processes are lost.  Therefore, optimized auditory function 
for real-life listening in conditions of noise, reverberation, speaker variation and distance 
is virtually eliminated. 
Adult cochlear implant (CI) candidates typically have moderate to profound or severe to 
profound hearing loss in both ears.  In these cases, one ear or both ears may be 
implanted.  In cases of bilateral implantation, many studies have shown the feasibility of 
integrating signals from both ears, providing bilateral CI recipients the highly beneficial 
effects of bilateral input including better speech understanding in quiet and in noise, 
better understanding of soft speech and improved localization compared to a unilateral 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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CI (Litovsky et al., 2006; Buss et al., 2008; Dunn et al., 2012; Reeder et al., 2014).  A 
number of studies have also examined effects of bimodal input, listening with a CI in one 
ear and a HA in the other, in comparison to a unilateral CI alone (Tyler et al., 2002; 
Morera et al., 2005; Ching et al., 2007; Potts et al., 2009; Morera et al., 2012).  
Participants in these studies had very little residual hearing in the non-implanted ear; the 
majority had moderately-severe-to-profound or severe-to-profound hearing loss in the 
non-implanted ear.  Even so, the results revealed improved speech understanding in 
noise, improved speech understanding in quiet at both conversational and soft listening 
levels, and improved localization abilities in the bimodal listening condition (CI + HA) 
compared to the CI alone listening condition.  In addition, participants preferred the 
combined input from a CI in one ear and a HA in the other, and showed higher ratings 
compared to either the CI or HA alone conditions on self-assessment questionnaires that 
probe communication functioning in everyday situations (Potts et al., 2009; Dwyer et al., 
2014). 
Recent studies at Washington University School of Medicine in St. Louis have 
investigated the effects of asymmetric hearing loss and the possibility of restoring 
binaural abilities through cochlear implantation.  Study participants had at least a 
moderate-to-profound hearing loss in one ear (that received a CI) but less hearing loss 
in the opposite ear (that continued HA use).  Initial results from 10 participants indicated 
the CI successfully restored hearing to the poor ear by improving hearing detection in 
the sound field.  In general, CI sound field threshold levels from 250-6000 Hz were 30 
dB HL or better (Firszt et al., 2012).  Adults with postlingual hearing loss demonstrated 
significant open-set speech recognition in the implanted ear at the six month test interval 
for measures in quiet and noise (Firszt et al., 2011; Firszt et al., 2012).  In addition to 
improved audibility and speech recognition with the implant in the poor hearing ear, 
study participants demonstrated significantly improved speech recognition and 
localization when comparing the six-month bimodal condition (CI + HA) to the pre-
implant, everyday listening condition (HA in the better ear alone) (Firszt et al., 2012).  
For sentences presented at a soft level in quiet and for localization, scores at the six-
month test interval were significantly better in the bimodal condition than the HA in the 
better ear alone condition.  Furthermore, the improvements seen between pre- and post-
implant test conditions were supported by participant reports on the Speech, Spatial and 
Qualities of Hearing Scale (SSQ), (Firszt et al., 2012; Dwyer et al., 2014).   
In summary, many hearing-impaired patients function with noticeable hearing 
asymmetry.  When hearing is asymmetric and the loss in the poor ear is moderate-to-
profound, lack of treatment for that ear is very common, which results in monaural 
hearing.  Listening with just one ear, particularly a hearing-impaired ear, is detrimental to 
signal segregation and communication.  Individuals with asymmetric hearing loss 
frequently seek medical care due to pervasive communication difficulties.  The only 
available treatment that can provide hearing to the deaf ear is a CI.  At this time, 
individuals with asymmetric hearing loss are not routinely implanted in the poor hearing 
ear simply because the contralateral, better hearing ear has hearing loss in the 
moderate range rather than the severe to profound range.  A prospective, single-arm, 
multi-center clinical trial is critically needed to address the deficits of patients with 
asymmetric hearing loss and explore potential treatment with a CI.  Outcomes from this 
study will also inform a future pivotal clinical trial.   
 
 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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Study Objectives 
Primary Objective:  Obtain preliminary efficacy data in adults with asymmetric hearing 
loss who receive a cochlear implant (CI) in the poor hearing ear and maintain a hearing 
aid (HA) in the better hearing ear.  Efficacy is defined as post-implant improvement in 
the poor ear with a CI compared to pre-implant with a HA.  Measures are sound field 
threshold levels and CNC monosyllabic words in quiet.  
Secondary Objectives:   
1. Obtain efficacy data related to bimodal hearing.  Efficacy is defined as post-implant 
improvement (CI in poor ear + HA in better ear) compared to the pre-implant best-
aided condition (either HAs in both ears, or a HA in the better ear alone for adults 
with no aidable hearing in the poor ear).  Measures are sound localization, speech 
recognition in noise, speech recognition at soft presentation levels, perceived 
hearing handicap, and reported quality of life.   
2. Evaluate safety associated with cochlear implantation in individuals with asymmetric 
hearing loss.  The safety evaluation will be based on the number, type and degree of 
all adverse events. 
3. Collect essential preliminary information related to test measures and methodology 
that can be used clinically in a future Phase III clinical trial (e.g., localization, listening 
in noise, listening at soft levels).   
Study Design 
The study will be conducted as a multicenter, prospective, single-arm clinical trial, 
evaluating the efficacy and safety of cochlear implantation in patients with asymmetric 
hearing loss.  A repeated-measures analysis will be employed whereby patients will act 
as their own controls.  Thirty-seven individuals with asymmetric hearing loss will 
participate at three to four investigational sites.  Participants will be recruited from 
surgeons and audiologists in Otolaryngology departments at the participating sites.  Prior 
to receiving a CI in the poor hearing ear, participants will be evaluated as follows:  
• 
HA in the better ear alone 
• 
HA in the poor ear alone 
• 
Bilateral HAs 
Post-implant evaluations will occur at 3, 6, 9, and 12 months after initial stimulation of 
the CI.  Participants will be evaluated as follows: 
• 
HA in the better ear alone 
• 
CI in the poor ear alone 
• 
HA and CI together 
The study length for individual participants will be approximately 18 months.  The overall 
study is expected to last approximately 5 years. 
These study results are essential for the development of a Phase III multi-center clinical 
trial, helping to refine inclusion/exclusion criteria, test protocols, pre-implant baseline 
condition(s), and final sample size estimates.   

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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Device Descriptions 
Participants will be counseled and provided information regarding the CI devices 
commercially available in the United States.  Currently, there are three devices, each 
manufactured by a different company:  Advanced Bionics, LLC, Cochlear Americas, and 
Med-EL Corporation.  In consultation with the participant’s audiologist and surgeon, the 
participant will chose the device that best fits the participant’s lifestyle and preferences 
(e.g. ease of controls, size, water resistance, warranty length, available accessories, or 
other speech processor features). The CI surgeon will have the final recommendation if 
there is a surgical preference.  We plan to recruit at least 10 participants with each of the 
three devices.   
Advanced Bionics LLC 
The HiResolutionTM Bionic Ear Cochlear Implant System consists of 1) the implanted 
device, the HiRes90KTM Advantage Cochlear Implant with HiFocusTM Mid-Scala 
electrode; 2) the externally worn Naida behind-the-ear speech processor and/or Neptune 
body-worn speech processor; and 3) the SoundWave 2 custom fitting software used to 
program the speech processors.  Subject to change as commercial availability changes. 
Cochlear Americas 
The CochlearTM NucleusTM Cochlear Implant System consists of 1) the implanted device, 
CI24 RE (Contour Advance), and the CI422 (Slim Straight); 2) the externally worn 
Nucleus 6 speech processor; and 3) the Custom Sound fitting software used to program 
speech processors.  Subject to change as commercial availability changes. 
Med-EL Corporation 
The Med-EL MaestroTM Cochlear Implant System consists of 1) the implanted device, 
the ConcertTM Medium or Standard; 2) the externally worn Opus 2 speech processor 
and/or Rondo speech processor; and 3) the Maestro System fitting software used to 
program speech processors.  Subject to change as commercial availability changes. 
Participant Population 
Thirty-seven to forty individuals with asymmetric hearing loss will participate at three to 
four U.S. CI centers.  Participants will be sequentially recruited into the study to ensure a 
participant pool representative of the general adult population with asymmetric hearing 
loss.  Participants will not be pre-selected based on age (other than being at least 18), 
gender or ethnicity.  Each participant will meet the following inclusion and exclusion 
criteria: 
Inclusion Criteria  
• 
18 years of age or older 
• 
Proficient in English   
• 
Have a desire for functional binaural hearing 
• 
Have failed a previous HA treatment for asymmetric hearing loss (BiCROS or 
poor ear HA) or willing to complete a trial if necessary 
• 
Willingness to comply with all study requirements 
• 
Ability to provide informed consent 
• 
Poor ear (ear to be implanted): 
o Pure-tone average (PTA) at .5, 1 and 2 kHz > 70 dB HL (hereafter 
referred to as severe to profound hearing loss – SPHL) 
o Aided word recognition score (CNC Word Test) at 60 dB SPL ≤ 30% 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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o Duration of SPHL ≥ 6 months 
o Onset of hearing loss ≥ 6 years of age 
• 
Better ear: 
o PTA at .5, 1, 2, 4 kHz of 40 to 70 dB HL 
o Currently using a HA  
o Aided word recognition score (CNC Word Test) at 60 dB SPL > 40% 
o Stable hearing for the previous 1-year period.  “Stable” is defined as 
thresholds that have not changed by more than 10 dB at 2 or more 
octave interval audiometric frequencies 
Exclusion Criteria  
• 
Medical condition that contraindicates surgery 
• 
Actively using an implantable device in the ear to be implanted 
• 
Known cochlear malformation or obstruction that would preclude full insertion 
of the electrode array in the ear to be implanted 
• 
Hearing loss of neural or central origin 
• 
Unrealistic expectations related to the benefits and limitations of cochlear 
implantation 
• 
Unwillingness or inability to comply with all investigational requirements 
Spouse/Significant Other 
The spouse/significant other of the cochlear implant study participants will also be asked 
to participate in the study. They will be asked to complete questionnaires that examine 
the impact of asymmetric hearing loss and cochlear implantation on communication 
function, personal adjustment, and social-emotional aspects of daily life.  The 
information collected will relate to both the cochlear implant study participant as well as 
the spouse/significant other.   
Investigation Procedures 
Test Measures 
All testing will take place in a sound booth using calibrated equipment and test stimuli.   
Unaided Audiometric Threshold Levels 
Air and bone conduction audiometric threshold levels in dB HL will be obtained for both 
ears using standard audiometric test procedures (Carhart and Jerger, 1959).   
Air conduction threshold levels, using insert earphones, will be obtained at 250, 500, 
1000, 2000, 3000, 4000, 6000 and 8000 Hz.  When necessary, narrow band noise will 
be used to mask the better hearing ear.   
Bone conduction threshold levels will be obtained at 250, 500, 1000, 2000, 3000 and 
4000 Hz.  When necessary, narrow band noise will be used to mask the better hearing 
ear.   
Aided FM, Tone Sound Field Threshold Levels 
Sound field threshold levels will be obtained in the sound booth using frequency 
modulated (FM) tones presented through a loudspeaker situated at ear level at 0° 
azimuth.  The loudspeaker will be located 1.5 meters from the center of the participant’s 
head.  Sound field levels will be obtained in dB HL at 250, 500, 1000, 2000, 3000, 4000 
and 6000 Hz.  Levels will be obtained at each frequency in 2 dB steps using the 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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Hughson-Westlake procedure (Carhart and Jerger, 1959).  Participants will be instructed 
to press the response button every time the tone is heard, even if the tone is very soft.   
Consonant-Vowel Nucleus-Consonant (CNC) Word Test 
The CNC monosyllabic word test (Peterson and Lehiste, 1962) is part of the Minimum 
Speech Test Battery (Luxford and Ad Hoc Subcommittee, 2001) for CI candidates and 
recipients.  The test consists of 10 lists of monosyllabic words with 50 words per list.  
The words are spoken by a male talker; each word is preceded by the carrier “ready.”   
CNC word testing will be administered in the sound field through a loudspeaker at ear 
level at 0° azimuth and 1.5 meters from the center of the participant’s head.  The test will 
be presented at 60 dB SPL.  Participants will be instructed to repeat the word that is 
heard and will be encouraged to guess when possible.  The tester will write down the 
participant’s response and words will be scored as a percent correct.   
AzBio Sentence Test 
The AzBio Sentence Test (Spahr et al., 2012) consists of 33 lists of 20 sentences per list 
and is part of the 2011 New Minimum Speech Test Battery for Adult Cochlear Implant 
Users.  AzBio sentences are spoken by four talkers, two males and two females; each 
talker presents five of the 20 sentences.  The sentences are spoken in a conversational 
style, are 4-10 words in length, and approximate a fourth grade reading level (King et al., 
2012).   
The sentences will be presented in the sound field through a loudspeaker (0° azimuth, 
1.5 meters from center of participant’s head) at 60 dB SPL, at 50 dB SPL and at 60 dB 
SPL in 4-talker babble noise using a +8 dB signal-to-noise ratio (SNR).  When sentences 
are presented in 4-talker babble noise, sentences and noise will be presented through 
the same loudspeaker (0° azimuth).  The participant will repeat as much of the sentence 
as possible.  The test will be scored as percent correct.  
Bamford-Kowal-Bench Speech-in-Noise (BKB-SIN) Test 
The BKB-SIN Test (Etymotic Research, 2005) will be administered in the sound field at 
65 dB SPL with sentences presented from the front loudspeaker (0° azimuth) and 4-
talker babble noise presented from a loudspeaker 90° to the participant’s right and 90° to 
the participant’s left.  The BKB-SIN Test includes 18 lists of sentences.  The sentences 
are spoken by a single male talker, are 5-6 words in length and are at a 1st grade 
reading level.  The 4-talker babble begins at a +21 dB SNR for the first sentence and 
decreases by 3 dB after each sentence in order to obtain an SNR-50 score; that is, an 
SNR for which 50% of the key words are repeated by the participant.  The BKB-SIN Test 
is part of the New Minimum Speech Test Battery for Adult Cochlear Implant Users, 2011.   
Localization Test 
A localization test will be administered in the sound field with stimuli presented from a 
140°, eight loudspeaker array.  Loudspeakers will be spaced 20° apart.  The participant 
will sit facing the center of the array (0° azimuth).  The loudspeakers are approximately 
at head level and numbered 1 through 8.  The stimuli consist of CNC words presented at 
65 dB SPL with the level roved by ± 6 dB.  Each CNC word is preceded by the carrier 
“ready,” and both are presented from the same loudspeaker.  Prior to the onset of each 
trial, participants are instructed to keep their gaze fixed at 0° azimuth until the word 
“ready” is heard, at which point they are free to turn their head if desired.  After stating 
the loudspeaker number from which they heard the word, participants will reposition their 
gaze to 0° azimuth.  Eight words are presented from each of the eight loudspeakers 
(total of 64 presentations); loudspeaker order is pseudo randomized.  A root mean 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
Page 13 
 
square (RMS) error score is calculated as the mean source-response difference, 
irrespective of error direction (the square root of the quotient resulting from the sum of 
each source-response difference squared and divided by the number of trials).  A lower 
RMS error score indicates less localization error, or greater accuracy.  Localization in 
Noise will be evaluated using the same system and stimuli with the addition of 60 dB 
SPL restaurant noise originating from all loudspeakers. 
Questionnaires 
Hearing Handicap Inventory for the Elderly (HHIE) 
The HHIE (Ventry and Weinstein, 1982) is a 25-item, self-assessment scale that 
quantifies the perceived emotional and social/situational consequences of hearing loss.  
It is composed of 13 emotional subscale items and 12 social/situational subscale items.  
Each item is a question that the participant answers as “Yes”, “Sometimes” or “No”.  The 
HHIE can be used to identify changes in handicap scores following a specific treatment 
or over time. 
Health Utilities Index Mark 3 (HUI3) 
The HUI3 (Furlong et al., 2001) provides descriptive evidence on multiple dimensions of 
health status and results in a score for each dimension of health, and a health related 
quality of life overall score.  Health dimensions include vision, hearing, speech, 
ambulation/mobility, pain, dexterity, self-care, emotion and cognition.  Each dimension 
has 3- 6 levels of function from which the participant selects the one that best describes 
their perceived ability.  The overall scores are on the conventional scale of dead = 0.00 
to perfect health = 1.00.  The HUI3 has been used in numerous clinical studies 
worldwide.  The HUI3 can be used to identify current health status as well as a change 
in health status over time or as the result of a specific event or treatment. 
Speech, Spatial and Sound Qualities (SSQ) Questionnaire 
The SSQ (Gatehouse and Noble, 2004) is a self-assessment questionnaire.  The 
participant will rate their perceived hearing ability for a number of listening situations.   
The questionnaire includes a broad range of domains and reflects the individual’s 
perception of functioning in real-world situations.  Section I, Speech hearing, probes 
speech recognition in a variety of sound environments with varying degrees of talker 
variability.  Section II, Spatial hearing, examines three components of spatial hearing, 
sound direction, distance, and movement.  Section III, Qualities of hearing, considers 
segregation of sound, naturalness, and listening effort.   
Glasgow Benefit Inventory (GBI) 
The Glasgow Benefit  Inventory (Robinson and Summerfield, 1996) was specifically 
developed for otorhinolaryngological conditions and interventions.  The GBI is a post-
intervention questionnaire that measures change in health status following surgical 
intervention, e.g., CI surgery.  The GBI was designed to be patient-oriented, maximally 
sensitive to otorhinolaryngological interventions, and provide a common metric to 
compare benefit across different interventions.  The questionnaire has 18 items and 
employs a five-point Likert scale that ranges from much better to much worse. 
Satisfaction with Amplification in Daily Life (SADL)  
The SADL (Uriate et al, 2005) probes patient satisfaction with hearing aids; wording is 
modified for bimodal listeners. The participant will rate satisfaction for 13 questions that 
address overall benefit, cost, use, and communication.  The participants rate their 
satisfaction along a 7-point scale from “Not at all” to “Tremendously”. 
Participant Interview Form 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
Page 14 
 
This form guides investigators as they query participants about tinnitus, dizziness, 
medications, and the incision/implant site (post-implant only).  The form will be used pre- 
and post-implant and will assist investigators in the identification of adverse events.  
The Communication Profile for the Hearing Impaired (CPHI) – Communication 
Performance 
The CPHI (Demorest and Erdman, 1987) Communication Performance section is 18 
questions focused on situations the participant experiences at home, work and in social 
situations.  The spouse/significant other will complete regarding the participant’s 
communication abilities.  Each question is answered along a 5-point scale from “Rarely, 
Almost Never” to “Usually, Almost Always”.    
The Hearing Impaired Impact – Significant Other Profile (HII-SOP)  
The HII-SOP (Preminger and Meeks, 2010) is designed for the spouse/significant other; 
and addresses the impact of hearing loss on the spouse/significant other (rather than on 
the participant).  It is comprised of 20 questions that include specific situations related to 
Communication Strategy, Relationship and Emotions, and Social Impact.  The 
spouse/significant other answers Yes, Sometimes, or No to each question. 
Study Schedule 
A summary of the pre-implant and post-implant study test visits is provided in the Table 
on the following page.   
Pre-Implant Candidacy Evaluation 
The duration of this testing will be approximately 4 hours and will be completed in 1-2 
visits. 
Informed Consent 
A research study team member, either the surgeon or audiologist working with the 
patient, will identify potential participants.  If a patient indicates interest in participation, 
the surgeon or audiologist will have a detailed conversation about the study procedures, 
purpose, schedule, and time commitments and provide a copy of the consent document.  
Potential participants will have the opportunity to take the consent document home to 
read and discuss with family and friends and will be encouraged to contact the surgeon 
and/or the audiologist if there are questions.  Study team members will ensure that the 
potential participant is aware of all aspects of cochlear implantation as well as study 
expectations, the surgical procedure, and the post-implant study schedule.  When 
informed consent is obtained, each section of the consent form will be reviewed and the 
potential participant will be given an opportunity to ask questions.  Individuals who are 
still interested in participating will sign and date the consent form.  Several aspects of the 
individual’s participation will be highlighted during the consent process: (1) participation 
is voluntary; (2) the participant can withdraw from the study at any point for any reason; 
and (3) the participant will receive appropriate clinical care whether or not they 
participate in the study.  The participant will be given a copy of the signed consent 
document.   
 
 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
Page 15 
 
Summary of Study Schedule 
w 
 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
Page 16 
 
Hearing History 
A complete hearing history will be obtained from the participant.  The information 
obtained from the participant will include etiology of hearing loss, onset of hearing loss, 
HA use, and duration of SPHL.  Previous audiograms to confirm hearing history will be 
obtained if possible.  An area of interest will be previous treatments and results for 
asymmetric hearing loss, specifically a poor ear HA or BiCROS HA trial.  Participants 
who have never had a failed poor ear HA or BiCROS HA trial will be fit during the 
Candidacy Evaluation and complete a 1-2 week trial followed by an assessment with the 
poor ear HA or BiCROS HA (Alternative Therapy Assessment). 
Unaided Audiometric Threshold Levels 
Unaided audiometric threshold levels will be obtained to determine if the participant 
meets inclusion criteria.   
Air conduction threshold levels using insert earphones will be obtained at 250, 500, 
1000, 2000, 3000, 4000, 6000, and 8000 Hz.  Masking will be used as necessary.   
Bone conduction threshold levels will be obtained at 250, 500, 1000 2000, 3000, and 
4000Hz in each ear.  Masking will be used as necessary.   
Verification of Hearing Aids  
Participants will have their HAs assessed to ensure proper functioning and adequate 
amplification prior to testing.  The American National Standard Institute S3.22-2009 for 
electroacoustic assessment will be used to ensure proper HA functioning.  Amplification 
will be evaluated using real-ear measures with the AudioScan VerifitTM (or equivalent) 
system with speech stimuli for input levels of 50, 60 and 70 dB SPL.  The evaluation will 
be based on the National Acoustic Laboratories’ nonlinear fitting procedure, version 2 
(NAL-NL2).  If the participant’s HAs do not meet NAL-NL2 targets within +10 dB from 
500-4000 Hz, the HAs will be re-programmed until targets are met.  If the HAs cannot be 
adjusted to meet targets, the participant will be fit with clinic loaner HAs.  If the severity 
of the hearing loss or tolerance issues prohibit amplification at the prescribed levels, the 
HA will be programmed as close as possible to NAL-NL2 targets.  
Aided, FM Tone Sound Field Threshold levels 
Aided, FM tone threshold levels will be obtained in the sound field for each ear at 250, 
500, 1000, 2000, 3000, 4000, and 6000 Hz.  When testing the poor ear, the better ear 
will be plugged and muffed (Howard Leight Pre-Shaped Foam Earplug and Howard 
Leight Hearing Protection Thunder T1 earmuff) (Howard Leight, 2014a, b).  Based on 
pilot data from Washington University School of Medicine, the plug and muff provided an 
attenuation average of 48 dB for frequencies 250 – 8000 Hz.   
CNC Word Recognition Testing  
Two list of the CNC word test will be given to participants at 60 dB SPL in two listening 
conditions, 1) HA in the better ear only and 2) HA in the poor ear only.  When testing the 
poor ear, the better ear will be plugged and muffed.  Testing will determine if the 
participant meets inclusion criteria. 
Alternative Therapy Assessment 
Participants who have not previously failed a poor ear HA or BiCROS HA trial will be fit 
with one of those two HA options.  The audiologist will determine which HA to fit based 
on the participant’s hearing loss and preferences.  After at least 1 to 2 weeks of use, the 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
Page 17 
 
participant will return to the center and complete an evaluation.  Performance will be 
compared (using measures listed below) between the better ear HA-alone condition and 
the bilateral or BiCROS HA condition.  If performance is better in the bilateral or BiCROS 
HA condition versus the better ear HA-alone condition, and the participant prefers the 
alternative therapy, the participant will not continue in the study.  For participants who do 
continue in the study, these measures will not need to be repeated at the Pre-Implant 
Testing visit. 
Sentence testing 
Two lists of AzBio sentences will be administered at 60 dB SPL in 4-talker babble at +8 
dB SNR. 
Localization 
CNC words will be presented through the eight loudspeaker array at a roved level of 65 
dB SPL (±6 dB). 
Candidacy Determination 
The Investigator is required to submit the pre-operative candidacy evaluation CRFs for 
review by the Sponsor once the candidacy evaluation (when necessary, including the 
alternative therapy assessment) is complete.  The information collected will be reviewed 
by the Sponsor, and a written approval or disapproval will then be provided to the 
Investigator.  The Pre-Implant Candidacy Evaluation should take place within 4 months 
of surgery.  Portions of the Candidacy Evaluation will be reassessed if more than 4 
months have elapsed prior to the surgery date.   
Pre-Implant Study Testing 
The duration of this testing will be approximately 4 hours and will be completed in 1-2 
visits.  Pre-Implant study testing will be completed in the following three conditions:  a 
HA in the better ear only, a HA in the poor ear only, and bilateral HAs.    
Hearing Aid in the Better Ear 
The participant will wear the HA and HA settings verified during the candidacy 
evaluation.  If a loaner clinic HA was needed during the pre-implant candidacy 
evaluation, the participant will have worn this HA for at least 2 weeks prior to the pre-
implant study testing.  Participants will continue to use this HA for the remainder of the 
study. 
Aided, FM Tone Sound Field Threshold Levels 
Aided FM tone sound field levels will be obtained at 250, 500, 1000, 2000, 3000, 4000 
and 6000 Hz  
Sentence testing 
Two lists of AzBio sentences will be administered in quiet at a soft level of 50 dB SPL.  
Two lists of AzBio sentences will be administered at 60 dB SPL in 4-talker babble at +8 
dB SNR. 
Two lists of the BKB-SIN test will be administered in two listening conditions, sentences 
from the front loudspeaker and noise 90° to the participant’s right and sentences from 
the front loudspeaker and noise 90° to the participant’s left. 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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Localization 
CNC words will be presented through the eight loudspeaker array at a roved level of 65 
dB SPL (±6 dB).  Localization will be completed in quiet and in the presence of 
restaurant noise. 
Hearing Aid in the Poor Ear 
When testing the poor ear alone, the better ear will be plugged and muffed. 
The participant will wear the HA and HA settings verified during the candidacy 
evaluation.     
Aided, FM Tone Sound Field Threshold Levels 
Aided FM tone sound field levels will be obtained at 250, 500, 1000, 2000, 3000, 4000 
and 6000 Hz.  
Sentence Testing 
Two lists of AzBio sentences will be administered in quiet at a conversational level of 60 
dB SPL.   
Hearing Aid in Both Ears 
CNC Word Testing 
Two lists of CNC words will be administered in quiet at 60 dB SPL.   
Sentence Testing 
Two lists of AzBio sentences will be administered in quiet at a soft level of 50 dB SPL.  
Two lists of AzBio sentences will be administered at 60 dB SPL in 4-talker babble noise 
at +8 SNR. 
Two lists of the BKB-SIN test will be administered in two listening conditions, sentences 
from the front loudspeaker and noise 90° to the participant’s right and sentences from 
the front loudspeaker and noise 90° to the participant’s left. 
Localization 
CNC words will be presented through the eight-loudspeaker array at a roved level of 65 
dB SPL (±6 dB).  Localization will be completed in quiet and in the presence of 
restaurant noise. 
Questionnaires 
HHIE 
The HHIE will be completed by the participant.  The HHIE will provide a baseline 
measure of the participant’s perceived emotional and social/situational consequences of 
hearing loss. 
HUI3 
The HUI3 will be completed by the participant.  The HUI3 will provide a baseline 
measure of the participant’s overall health related quality of life. 
SSQ 
The SSQ will be completed by the participant.  The SSQ will provide a baseline measure 
of the participant’s perceived hearing ability in daily life.   

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
Page 19 
 
SADL 
The SADL will be completed by the participant.  The SADL will provide a baseline 
measure of the participant’s perceived satisfaction with amplification.   
Participant Interview Form 
The Participant Interview Form will be completed by the investigator after questioning 
the participant.  This will provide a baseline for tinnitus, dizziness, medications and other 
relevant information.  
Counseling 
Along with the pre-implant candidacy evaluation and pre-implant study testing, 
participants will be seen by the surgeon and audiologist at their CI center for routine, 
clinical visits that occur prior to CI surgery.  These visits will include discussions 
regarding the risks of CI surgery as well as performance outcomes with a CI to assure 
appropriate expectations.   
Spouse/Significant Other – Pre-Implant Questionnaires 
CPHI 
The CPHI will be completed by the participant’s spouse/significant other and will provide 
a baseline measure of the participant’s communication in everyday life from the 
perspective of the spouse/significant other. 
HII-SOP 
The HII-SOP will be completed by the participant’s spouse/significant other.  The HII-
SOP will provide a baseline of the perceived impact of the participant’s hearing loss on 
the participant’s spouse/significant other. 
Surgery 
Participants will be implanted with their selected CI device.  The surgical procedure for 
implantation of each device will be according to each device’s current approved labeling.  
Each surgeon will determine the length of participants’ hospital stay based on their 
recovery.  The following data will be obtained: date of surgery, device specifics and 
adverse event information. 
Initial Stimulation of the Cochlear Implant  
The initial stimulation of the CI will take place 2-4 weeks after surgery based on the 
surgeon’s recommendation.  Programming of each participant’s CI speech processor will 
be performed according to each center’s typical CI programming schedule.  Selection of 
programming parameters will be determined by each center’s routine, clinical 
procedures for optimizing CI recipient performance.  At this visit the following will be 
obtained: 
Unaided Audiometric Threshold Levels* 
Air conduction thresholds using insert earphones will be obtained for each ear at 250, 
500, 1000, 2000, 3000, 4000, 6000 and 8000 Hz.  Masking will be used when 
appropriate. 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
Page 20 
 
*If pre-implant, unaided audiometric testing reveals no response at each frequency in the 
poor ear, unaided audiometric testing in that ear does not need to be completed at this 
or any of the post-implant test sessions.   
Participant Interview Form 
The Participant Interview Form will be completed by the investigator after questioning 
the participant.  This will provide information regarding tinnitus, dizziness, medications, 
the incision/implant site, and other relevant information.   
Participants’ take-home speech processor programs  
The audiologist at each center will provide a de-identified copy of the speech processor 
programs.  This will document relevant information regarding the parameters used by 
the participant with their speech processor. 
Aural Rehabilitation 
All participants will be encouraged by their audiologist to practice daily for 15-30 minutes 
listening with their CI only for at least the first 6 weeks of implant use and then 3 times a 
week for an additional 6 weeks.  During practice, participants can listen with their CI 
through direct audio input to their CI or can listen through the CI alone by plugging the 
better hearing ear with an earplug.  Each participant will be given a list of practice 
materials available for use on a computer, tablet, smart phone or through a CD player.   
Post-Implant Study Testing (3, 6, 9 and 12 months after Initial 
Stimulation) 
The duration of each session will be approximately 4-5 hours and will be completed in 
1-2 visits.  Audiometric, speech recognition, localization, self-assessment, speech 
processor program, and adverse event data will be obtained at each of the four post-
implant test intervals.  Post-implant test intervals should occur within a ± 30 day window 
around the target test date.  Speech recognition and localization data will be obtained in 
multiple listening conditions as listed below.   
Unaided Audiometric Threshold Levels* 
Air conduction thresholds using insert earphones will be obtained for each ear at 250, 
500, 1000, 2000, 3000, 4000, 6000 and 8000 Hz.  Masking will be used when 
appropriate 
*If unaided audiometric testing at the initial stimulation reveals no response at each 
frequency in the CI ear, unaided audiometric testing in the CI ear does not need to be 
done at each post-implant test session.   
Hearing Aid in the Better Ear  
Verification of Hearing Aid 
Each hearing aid will be checked for proper function and sound quality (e.g., listening 
check, electroacoustic analysis, patient report).  
 
 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
Page 21 
 
Aided, FM Tone Sound Field Threshold Levels 
Aided FM tone sound field levels will be obtained at 250, 500, 1000, 2000, 3000, 4000 
and 6000 Hz.  
CNC Word Test 
Two lists of the CNC word test will be administered in quiet at a conversational level of 
60 dB SPL. 
Sentence Testing 
Two lists of AzBio sentences will be administered in quiet at a soft level of 50 dB SPL.  
Two lists of AzBio sentences will be administered at 60 dB SPL in 4-talker babble noise 
at +8 SNR. 
Two lists of the BKB-SIN test will be administered in two listening conditions, sentences 
from the front loudspeaker and noise 90° to the participant’s right and sentences from 
the front loudspeaker and noise 90° to the participant’s left. 
Localization 
CNC words will be presented through the eight-loudspeaker array at a roved level of 65 
dB SPL (±6 dB).  Localization will be completed in quiet and in the presence of 
restaurant noise. 
Cochlear Implant Ear  
Standard clinical procedures will be used to verify that the CI speech processor is 
functioning properly and the speech processor program is optimal prior to testing.   
When testing the CI ear alone, the better ear will be plugged and muffed. 
CI, FM Tone Sound Field Threshold Levels 
CI, FM tone sound field levels will be obtained at 250, 500, 1000, 2000, 3000, 4000 and 
6000 Hz.     
CNC Word Test 
Two lists of the CNC word test will be administered in quiet at a conversational level of 
60 dB SPL. 
Sentence Testing 
Two lists of AzBio sentences will be administered in quiet at a conversational level of 60 
dB SPL.   
Bimodal (HA and CI together) 
CNC Word Test 
Two lists of the CNC word test will be administered in quiet at a conversational level of 
60 dB SPL. 
Sentence Testing 
Two lists of AzBio sentences will be administered in quiet at a soft level of 50 dB SPL.  
Two lists of AzBio sentences will be administered at 60 dB SPL in 4-talker babble noise 
at +8 SNR. 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
Page 22 
 
Two lists of the BKB-SIN test will be administered in two listening conditions, sentences 
from the front loudspeaker and noise 90° to the participant’s right and sentences from 
the front loudspeaker and noise 90° to the participant’s left. 
Localization 
CNC words will be presented through the eight-loudspeaker array at a roved level of 65 
dB SPL (±6 dB).  Localization will be completed in quiet and in the presence of 
restaurant noise. 
Questionnaires 
HHIE:  The HHIE will be completed by the participant at the 6-month post-implant study 
visit.  The HHIE will record the participant’s post-implant perceived emotional and 
social/situational consequences of hearing loss. 
HUI3:  The HUI3 will be completed by the participant at the 6-month post-implant study 
visit.  The HUI3 will provide a post-implant measure of the participant’s overall health 
related quality of life. 
SSQ:  The SSQ will be completed by the participant at the 6-month and 12-month post-
implant study visits.  The SSQ will provide a measure of the participant’s perceived 
hearing ability in daily life with the CI and HA.  The SSQ will be anchored for each of the 
post-implant test intervals; that is, participants will see how each question was answered 
at their previous test interval.   
GBI:  The GBI will be completed by the participant at the 6-month post-implant study 
visit.  The GBI will document how the CI has affected the participant’s health status and 
overall quality of life. 
SADL 
The SADL will be completed by the participant at the 6-month post-implant study visits.  
The SADL will provide a post-implant measure of the participant’s satisfaction of the 
cochlear implant. 
Participant Interview Form 
The Participant Interview Form will be completed by the investigator after questioning 
the participant.  This will provide information regarding tinnitus, dizziness, medications, 
the incision/implant site, and other relevant information.   
Participants’ speech processor programs used for testing 
The audiologist at each center will provide a de-identified copy of the speech processor 
programs.  This will document relevant information regarding the parameters used by 
the participant with their speech processor. 
Spouse/Significant Other – Post-Implant Questionnaires 
CPHI 
The CPHI will be completed by the participant’s spouse/significant other at the 6-month 
post-implant study visit.  The CPHI will provide a post-implant measure of the 
participant’s communication in everyday life from the perspective of the 
spouse/significant other. 
 
 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
Page 23 
 
HII-SOP 
The HII-SOP will be completed by the participant’s spouse/significant other at the 6-
month post-implant study visit.  The HII-SOP will provide a post-implant measure of the 
perceived impact of the participant’s hearing loss on the participant’s spouse/significant 
other. 
Safety 
A secondary objective of this study is to obtain data regarding the safety of cochlear 
implantation in adults with asymmetric hearing loss who receive a CI in the poor hearing 
ear and maintain a HA in the better hearing ear.  The safety evaluation will be based on 
the number, type and degree of all adverse events.   
A record of all adverse events will be kept.  No formal statistical hypothesis will be 
tested.  The primary safety endpoint will be 6 months post-implant.  Adverse event 
information through 6 months post-implant will be summarized by event type, 
severity/seriousness, and whether related to the device and/or implant procedure.   
Efficacy 
The primary study objective is to obtain preliminary efficacy data in adults with 
asymmetric hearing loss who receive a CI in the poor hearing ear and maintain a HA in 
the better hearing ear.  Efficacy is defined as post-implant improvement in the poor ear 
with a CI compared to pre-implant with a HA.  Measures are sound field threshold levels 
and CNC monosyllabic words in quiet. 
A secondary objective is to obtain efficacy data related to bimodal hearing.  Efficacy is 
defined as post-implant improvement (CI in poor ear + HA in better ear) compared to the 
pre-implant best-aided condition (either HAs in both ears, or a HA in the better ear alone 
for adults with no aidable hearing in the poor ear).  Measures are sound localization, 
speech recognition in noise, speech recognition at soft presentation levels, perceived 
hearing handicap, and reported quality of life.   
Sample Size Justification 
The primary efficacy endpoint is change in CNC performance from pre-implant to post-
implant, with most of the gain expected to be achieved by 6 months.  A clinically 
meaningful change on the CNC test is .10.  In our past research we have found CNC 
standard deviations that range from .06 to .24.  Assuming a correlation between 
repeated measures of .5 (typical in our work) these values translate into standardized 
mean differences (Cohen’s d) ranging from .42 to 1.67.  At the minimum effect size, a 
sample size of 37 is necessary for power of .80, the common standard (Cohen and 
Cohen, 1983; Keppel, 1991; Cohen, 1992).  As indicated, the planned sample size will 
provide adequate to excellent power to detect clinically meaningful differences.  Up to 40 
participants will be enrolled to allow for attrition. 
Note that the analyses described later will often be more complex than the simple 
approach used here for power calculations (a dependent means t-test), often involving 
change over longer periods of time, examining nonlinearity in the change profiles, and 
including additional predictors (e.g., patient characteristics).  The impact of these 
modifications will generally be to increase power by including additional measures that 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
Page 24 
 
will make detection of change more sensitive or to include additional predictors that will 
reduce the error terms against which change is compared.  We chose this simpler power 
analysis approach because it represents well the clinical meaning of improvement and is 
not complicated by extra statistical assumptions. 
Data Analysis 
Prior to the major analyses, the data will be examined for distributional abnormalities and 
outliers that might indicate the need for transformation to conform to the assumptions 
(e.g., multivariate normality) underlying the planned statistical procedures.  When 
indicated, standard power transformations will be used to produce approximately normal 
distributions (e.g., (Tukey, 1977; Hamilton, 1992).  If acceptable transformations are not 
available, resampling procedures will be used to confirm the conclusions drawn from the 
analyses. Resampling (e.g., Hamilton, 1992; Mooney and Duval, 1993; Chernick, 1999) 
represents a general statistical approach that bypasses possibly intractable assumptions 
necessary for the use of theoretical sampling distributions in favor of computer-intensive 
re-sampling of the obtained data to produce empirical sampling distributions for 
construction of confidence intervals.  The approach is especially helpful when standard 
statistical approaches cannot be used with confidence and standard remedies (e.g., 
transformations) are not available.  
Because of the longitudinal nature of the data, the major analytic approach we will use is 
hierarchical linear modeling (HLM; Raudenbush and Bryk, 2002; Heck and Thomas, 
2009; Hox, 2010; Snijders and Bosker, 2012).  We chose this approach because the 
data have a hierarchical structure, with the measures over time nested within individual 
patients. Thus for the majority of the analyses, we will use a two-level growth curve 
model, with both linear growth and quadratic growth (i.e., change in linear growth over 
time or departure from an overall linear or straight line pattern) included.  HLM analysis 
is particularly well suited for longitudinal data with unequal spacing of measures and 
occasional missing data, both likely to be true in this study.  Standard approaches, such 
as repeated measures analysis of variance, cannot be used because the measurement 
spacing will vary at the individual level.  Missing data, which is not expected to be 
substantial, is handled in the HLM approach via maximum likelihood estimation (e.g., 
Enders, 2010).  When HLM is used with smaller samples, standard errors may be 
reduced, although parameter estimates should not be biased (Raudenbush and Bryk, 
2002).  Accordingly, it may be necessary to use more conservative significance levels.   
Estimation in the HLM approach is best thought of as occurring at different levels.  At 
Level 1 of the statistical model, performance for a particular participant will be estimated 
as a quadratic polynomial growth curve.  This can be described by the following model, 
using CNC performance as the example outcome: 
e
Time
Time
CNC
ti
2
ti
i
2
ti
i1
i
0
ti
+
+
+
=



 
where the CNC performance at time t (e.g., six months) for participant i is estimated to 
be a function of an intercept (0i), a linear component for time (1i), and a quadratic 
component for time (2i).  The coefficients are expected to vary systematically across 
patients. At Level 2 of the model, the coefficients from Level 1 are viewed as outcomes 
that depend on patient characteristics: 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
Page 25 
 
r
D
D
D
r
D
D
D
r
D
D
D
i2
i
3
23
i2
22
i2
21
20
i2
i1
i
3
13
i2
12
i1
11
10
i1
i
0
i
3
03
i2
02
i1
01
00
i
0
+
+
+
+
=
+
+
+
+
=
+
+
+
+
=















 
The three equations represent the intercept, linear component, and quadratic component 
of growth, respectively.  The variables D1i, D2i, and D3i, represent generic predictors such 
as dummy codes that could represent the particular center from which a patient’s data 
were collected or patient characteristics (e.g., age) that might moderate the efficacy of 
the implant.  These Level 2 predictors allow for systematic differences in patient 
performance to be detected. 
The HLM approach includes omnibus tests that can be used prior to more focused 
comparisons so that the Type I error rate is not inflated.  Judicious choice of centering 
the time variable allows targeted inferences about particular follow-up time-points. An 
important part of the HLM analysis are the diagnostic procedures to check assumptions 
(e.g., homogeneity of Level 1 variances) or to determine if models can be simplified 
(e.g., Level 2 residual variances of 0).  When necessary, standard model modifications 
will be applied (e.g., modeling sources of Level 1 heterogeneity). 
Some analyses will call for simpler approaches. For example, performance at particular 
measurement points will be of interest (e.g., at Pre-Implant, at 6 months Post-Implant, or 
at the conclusion of the study).  In these simpler analyses, standard univariate and 
multivariate procedures (e.g., univariate or multivariate multiple regression [if continuous 
predictors are included] or analysis of variance [if only discrete predictors are tested]) will 
be used (Maxwell and Delaney, 1990; Keppel, 1991). 
Risk Benefit Statement 
The risks associated with CI surgery in this population are no greater than those 
associated with cochlear implantation in general.  Cochlear implantation is an accepted 
treatment option for those with bilateral moderate to profound sensorineural hearing 
loss.  However, the study population will have more residual hearing in the non-
implanted ear and there may be an additional risk of sound interference when adding a 
CI with a contralateral HA.  This will be monitored and recorded based on participant 
reports and comparison of performance between the HA-alone and bimodal conditions.  
Cochlear implantation is the only treatment option that can restore partial hearing to an 
ear with severe to profound hearing loss.  It is well established that a CI can significantly 
improve audibility and speech understanding for individuals with postlingual onset of 
deafness.  Individuals with SPHL in one ear and better hearing in the other ear may 
benefit from cochlear implantation by providing auditory stimulation in the poor hearing 
ear.  Additionally, individuals with asymmetric hearing have the opportunity to benefit 
from HA use in the contralateral ear that has better hearing.  Research has shown that 
bimodal hearing, a CI in one ear and a HA in the other ear, is well accepted by patients 
with residual hearing in the non-implant ear and is beneficial when listening to soft 
speech, listening to speech in noise and in localizing sound (Ching et al., 2007; Potts et 
al., 2009; Firszt et al., 2012; Morera et al., 2012; Dwyer et al., 2014).  The potential to 
significantly improve speech recognition in the poor hearing ear, to improve 
understanding of soft speech and speech in noise, and to improve sound localization 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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suggests cochlear implantation of the poor ear may provide an acceptable risk-benefit 
ratio for individuals with asymmetric hearing loss as described in this protocol. 
Good Clinical Practices Statement 
The study will be conducted in compliance with federal standards of Good Clinical 
Practice, applicable government regulations and each investigational site’s Institutional 
Review Board.  Verification of IRB approval will be provided by each site to the Sponsor 
prior to study commencement.  Any deviations from the protocol will be reported to the 
site’s Primary Investigator and the institution’s IRBs following each IRB’s institutional 
guidelines. 
Access to Study Documents and Monitoring 
Research staff at the sponsor site will communicate with investigational sites at least 
quarterly to review study progress and assure the integrity of the accumulated data.  On- 
site visits to the investigational sites will occur prior to study initiation and at least 
annually thereafter.  Data generated by the study and the source documents will be 
open to inspection by the Sponsor, the FDA and other regulatory agencies. 
Upon completion of the study, a representative from the Sponsor will conduct a final site 
visit to verify that all participants and their data are accounted for and that the regulatory 
records are complete. 
Quality Control Assurance 
Data will be provided to the Sponsor on case report forms.  When CRFs are received, 
the forms will be reviewed to verify completeness and to identify inconsistencies or 
erroneous information.  Corrections to the case report forms shall be made by approved 
methods only (i.e., single line through the incorrect entry, correct entry noted, initials of 
individual making correction, and date correction was made).  The investigational site 
will be contacted to resolve any discrepancies in the case report forms. 
Data received on CRFs will be entered into a database using typical data entry 
techniques.  All data entry will be compared to the CRFs by someone other than the 
data entry research member.  Samples of the CRFs received by the Sponsor and 
database entries will be compared with source documents during site visits to 
investigational sites.  More comprehensive verification will be completed if deemed 
necessary. 
Data and Safety Monitoring Board (DSMB) 
The DSMB consists of three members, none of whom are directly involved in the 
research project:  an otologist, a biostatistician and an audiologist with cochlear implant 
experience.  The DSMB will review interim/cumulative data for evidence of study-related 
adverse events, efficacy, and data quality, compliance with recruitment goals, adherence 
to the protocol, and factors that might affect the study outcome or impact participant 
safety.   
Institutional Review Board 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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Prior to study initiation at each investigational site, the IRB must have approved the 
Investigational Plan and the consent materials to be used.  A copy of the approved 
investigational plan, consent materials and documentation of IRB approval for the study 
will be submitted to the Sponsor prior to participant recruitment and study initiation. 
Informed Consent Process 
An IRB approved investigator will be responsible for obtaining informed consent for each 
participant prior to initiating any study procedures.  The consent process will include 
informing each participant of the study purpose, possible risks and potential benefits.  
These include the normal risks associated with general anesthesia, as well as other risks 
such as facial paralysis, dizziness, meningitis, postoperative discomfort, and flap 
complications.  Potential participants will be given ample time to read the informed 
consent.  Potential participants will be able to take the informed consent home to read 
and discuss study participation with friends and family.  Individuals will be encouraged to 
ask questions.  Once all questions are answered, both the participant and the 
investigator obtaining informed consent will sign and date the consent form.  The original 
signed and dated form will be kept with the participant study records and a copy given to 
the participant.   
Confidentiality 
In accordance with Good Clinical Practices and with the Health Insurance Portability and 
Accountability Act of 1996 (HIPAA), all information concerning study participants will be 
treated as confidential by all persons involved in the study.  Each investigational site will 
follow the requirements of the site’s IRB regarding confidentiality. 
Data generated for the study will be stored in a limited-access file area and accessible 
only to study site research team members, the Sponsor, and FDA/relevant health 
authorities/regulatory agencies.  All reports and communications with the Sponsor 
relating to study participants will identify participants only by a unique participant 
identification code.  Full participant identification will be kept by the investigators at each 
investigational site. 
Protocol Amendments 
Protocol modifications that impact participant safety or study validity will be approved by 
the FDA prior to implementation.  In addition, modifications will be documented in written 
form and approved by each investigational site’s IRB prior to implementation.  In the 
case of a medical emergency, to remove immediate apparent hazard to participants, a 
change may be made, preferably after discussion with the Sponsor.  In these instances, 
the IRB and FDA will be notified as soon as possible. 
 
 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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Data Management 
The study case report form (CRF) is the primary data collection instrument for the study.  
All data requested on the CRF will be recorded by the study investigator.  All missing 
data must be explained.  If a space on the CRF is left blank because the procedure was 
not done (N/D) or the question was not asked, “N/D” will be written to indicate such.  If 
the item is not applicable (N/A) to the individual case, “N/A” will be written next to the 
entry.  All entries should be printed legibly. 
If any entry error has been made, to correct such an error, a single straight line should 
be drawn through the incorrect entry and enter the correct data above it.  All such 
changes must be initialed and dated.  For clarification of illegible or uncertain entries, 
investigators will print the clarification above the item, then initial and date it. 
Record Keeping and Retention 
As described under Confidentiality, data generated for the study will be stored in a 
limited-access file area and be accessible only to each study site’s research team 
members, the Sponsor, and FDA/relevant health authorities/regulatory agencies.  All 
reports and communications relating to study participants will identify participants only by 
a unique participant identification code.   
The Investigator must provide the Sponsor or designee with the following documents at 
the time of site qualification and prior to study initiation and retain a copy in the site study 
file:  
• 
A copy of the original approval for conducting the study by the IRB.  Renewals, 
with continuance of the study, must be submitted at yearly intervals or as 
required by IRB policy and a copy of the approved and dated renewal provided to 
the Sponsor.  
• 
A copy of the IRB approved informed consent form along with any modifications 
initiated by the Sponsor over the course of the study.  
• 
The Investigator Agreement of this protocol signed and dated by the Primary 
Investigator from each site.  In addition to the documents listed above, the study 
site will also retain the following items and make them available for Sponsor 
review upon request.   
• 
Certifications and/or calibration records for applicable study equipment 
(audiometers, etc.).  The Sponsor will verify all equipment requirements at the 
study qualification and/or initiation.   
• 
All original informed consent forms with required signatures.  
• 
Copy of the Study Monitoring Log.  
• 
Copies of all correspondence pertaining to the study between Sponsor and the 
site.   
• 
Copies of all case report forms submitted to the Sponsor. 
• 
Site Delegation Signature Log.   
All study-related records must be maintained for at least two years after study closure.  
The Sponsor will notify investigators at each site when records are no longer needed.  
The investigator will not discard any records without notifying the Sponsor. 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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Study Report and Publication 
Neither the complete nor any part of the results of the study carried out under this 
protocol, or any of the information provided by the sponsor site for the purposes of 
performing the study, will be published or passed on to any third party without the 
consent of the Sponsor (via the study Principal Investigator, Jill B. Firszt).  Any 
investigator involved with this study is obligated to provide the Sponsor with complete 
test results and all data derived from the study. 
At completion of the study, the compiled data will be analyzed and results shared with 
investigators from the investigational sites.  Likewise prior to publication of results, the 
investigators from the investigational sites will be provided a copy of the accepted 
publication manuscript.   
Adverse Events 
Adverse Event (AE)  
An AE is any unexpected medical occurrence or worsening of a pre-existing medical 
condition following implantation and exposure to the device, regardless of whether the 
AE is related to the surgery or device.   
Adverse events (AEs) that occur during this study may be associated with the CI 
surgery, including AEs from general anesthesia, or specifically associated with the 
device use.  An AE will be deemed device-related when, in the judgment of the study 
site’s Primary Investigator, there is a logical connection between the device use and the 
event, above and beyond the study procedure itself. 
Serious Adverse Event (SAE) 
A SAE is any unexpected medical occurrence which: 
• 
Results in death 
• 
Is life-threatening 
• 
Requires in-patient hospitalization for more than 24 hours or prolongation of 
hospitalization which is not specifically required by the protocol 
• 
Results in permanent impairment of a body function or permanent damage to 
a body structure 
• 
Requires medical or surgical intervention to preclude permanent impairment 
of a body function or permanent damage to a body structure 
Unanticipated Adverse Device Effect (UADE)  
A UADE is “any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, problem, or 
death was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), or any 
other unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects.” [FDA 21 CFR 812.3(s)] 
Investigator Responsibilities  
Throughout the course of the study, all efforts will be made to remain alert to possible 
AEs.  Of primary concern will be the participant’s safety and providing appropriate 
medical care.  Detailed information regarding AEs will be recorded by the study site at 

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
Page 30 
 
the time an AE occurs using the “Adverse Event CRF”.  All AEs will be recorded from the 
day of enrollment to the time when the participant exits the study or to study termination, 
whichever is the last, even if the event was acknowledged as a risk factor in the 
Informed Consent. 
AEs will be recorded on the “Adverse Event CRF” and will include the following 
information: 
• 
Date of onset 
• 
Date reported to the clinic 
• 
Description of the AE 
• 
Seriousness (yes or no) 
• 
Investigator’s assessment of the relationship of the AE to the device 
• 
Investigator’s assessment of the relationship of the AE to the procedure 
• 
Treatment 
• 
Outcome 
• 
Relationship to device, implantation procedure and/or underlying disease 
A UADE will be reported directly to the study site’s IRB and the Sponsor within 10 
working days of learning of the event or as dictated by the study site’s IRB, whichever is 
sooner.  Information regarding the UADE will be recorded on the “Unanticipated Adverse 
Device Effect CRF”.   
Adverse Event Follow-up – Investigator Responsibilities 
All AEs must be followed until resolution.  The study site will follow-up as necessary with 
the participant to explain as well as possible the reason for and nature of the AE.  This 
may include additional tests or consultation with other health care professionals.  The 
Sponsor may request that the study site perform additional specific evaluations.  AE 
follow-up information, as needed, will be recorded using a “Previously Reported AE or 
UADE Follow-Up CRF”. 
Adverse Event Follow-up – Sponsor Responsibilities 
All AEs will be reported annually to FDA in accordance with the IDE regulation [FDA 21 
CFR Part 812.150(b)(5)].  All UADEs will be reported to FDA within 10 calendar days of 
the event in accordance with FDA 21 CFR Part 812.46(b) and 812.150(b)(1).  The 
Sponsor will notify all study sites of new safety information that alters the current risk-
benefit assessment or that would be sufficient to consider changes in the overall conduct 
of the clinical trial. 
Protocol Deviations 
Any study-related activity not in compliance with the approved protocol is considered to 
be a protocol deviation.  Deviations required to protect the life or welfare of a participant 
do not require approval and should be performed immediately.  The IRB must be notified 
within 5 days of the event.   
If a study participant is unable to return for a study visit within the allotted ± 30 day 
window around the target visit, or if a study visit is incomplete or otherwise completed 
incorrectly, these events will be tracked and logged.  The Primary Investigator at each 
site will monitor this log and continually assess the nature and degree of these 
deviations to determine the impact of these events on safety or performance of the 
participant or data integrity.   

Cochlear Implantation of Adults with Asymmetric Hearing Loss Clinical Trial 
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Study Completion 
Completed Participants 
Participants are considered completed when all assessments through 12 months post-
implant have been completed as mandated by the study protocol.  Only participant data 
obtained with the originally implanted device will count toward the primary endpoint. 
Discontinued Participants 
Any participant can discontinue the study at any time without prejudice.  The site’s 
Primary Investigator may also discontinue a participant at any time if health is a risk or if 
the participant is uncooperative and otherwise impacting the integrity of the data.  All 
withdrawals will be documented including the reason for withdrawal.  Efforts will be put 
forth to ensure near complete follow-up, particularly on assessment of primary outcomes 
and occurrence of adverse events.  Regular reminders, flexibility in scheduling of study 
visits to coincide with clinical visits, and close monitoring of due dates will facilitate 
obtaining as complete data as possible.  Participants lost to follow-up will be contacted 
at least three times by phone, email or mail.    
Premature Study Termination 
Each study site reserves the right to discontinue the study for any safety, ethical or 
administrative reasons at any time.  Participants who have already been implanted with 
the device will receive support, independent of study continuation.    
Product Accountability 
The three CI devices commercially available in the United States will be used during the 
study.  The devices are manufactured by Advanced Bionics, LLC (PMA 
P960058/S089/S098/S102), Cochlear Americas (PMA P970051/S028/S064/S096), and 
Med-EL Corporation (PMA P000025/S023/S029/S050/S061/S077).  All devices are 
commercially available and ship with their current commercial labeling. 
Because these devices are commercially available, no investigational labeling is 
included. 
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