SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

I. GENERAL INFORMATION

Device Generic Name: Cochlear Implant System

Device Trade Name: MED-EL Cochlear Implant System

Device Procode: PGQ

Applicant’s Name and Address: MED-EL Corporation

Fürstenweg 77a
6020 Innsbruck, Austria

Date(s) of Panel Recommendation: None

Premarket Approval Application (PMA) Number: P000025/S084

Date of FDA Notice of Approval: September 15, 2016

The original PMA (P000025) for the MED-EL Cochlear Implant System was approved
on August 20, 2001 and is intended to provide the opportunity to detect and recognize
auditory information through electrical stimulation of the auditory nerve for severe to
profoundly hearing-impaired individuals (children aged 18 months and older; adults aged
18 years and older) who obtain little or no benefit from conventional acoustic
amplification in the best-aided condition. The SSED to support the indication is available
on the CDRH website and is incorporated by reference here
(http://www.accessdata.fda.gov/cdrh_docs/pdf/P000025b.pdf). The current supplement
was submitted to expand the indication for the MED-EL Cochlear Implant System to
include the MED-EL EAS System, consisting of:
 MED-EL implant variant (SONATATI100 +FLEX24, Mi1000 MED‐EL
CONCERT (PIN) +FLEX24, Mi1200 SYNCHRONY (PIN) +FLEX24,
SONATATI100 +FLEX20, Mi1000 MED‐EL CONCERT (PIN) +FLEX20,
Mi1200 SYNCHRONY (PIN) +FLEX20)
 SONNET EAS Audio Processor, DUET 2 Audio Processor
 MAESTRO 6.0.1 programming software

II. INDICATIONS FOR USE

The MED-EL EAS System is intended to provide electrical stimulation to the mid- to
high-frequency region of the cochlea and acoustic amplification to the low-frequency
regions, for candidates with residual low frequency hearing sensitivity.

The MED-EL EAS System is indicated for partially deaf individuals aged 18 years and
older who have residual hearing sensitivity in the low frequencies sloping to a

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 severe/profound sensorineural hearing loss in the mid to high frequencies, and who
obtain minimal benefit from conventional acoustic amplification. Typical preoperative
hearing of candidates ranges from normal hearing to moderate sensorineural hearing loss
in the low frequencies (thresholds no poorer than 65 dB HL up to and including 500 Hz)
with severe to profound mid- to high-frequency hearing loss (no better than 70 dB HL at
2000 Hz and above) in the ear to be implanted. For the non-implanted ear, thresholds
may be worse than the criteria for the implanted ear, but may not be better. The CNC
word recognition score in quiet in the best-aided condition will be 60% or less, in the ear
to be implanted and in the contralateral ear. Prospective candidates should go through a
suitable hearing aid trial, unless already appropriately fit with hearing aids.

III. CONTRAINDICATIONS

The device is contraindicated for individuals as follows:

 If the individual is known to be intolerant of the materials used in the implant

(medical grade silicone, platinum, platinum iridium).
 If there is an absence of cochlear development.
 If the cause of deafness is non-functionality of the auditory nerve and/or the auditory
pathways.
 If external or middle ear infections are present or if the tympanic membrane is
perforated in the ear to be implanted.
 If there are medical contraindications present against surgery of the middle and inner
ear and anesthesia as required.
 If anatomic abnormalities are present that would prevent appropriate placement of the
stimulator housing in the bone of the skull, or prevent placement of the chosen
electrode array into the cochlea. In such cases, using the cochlear implant must be
carefully considered prior to surgery.
 If the psychological status of the patient is unstable or,
 If the patient has unrealistic expectations.

Furthermore, the MED-EL EAS System is contra-indicated for partially deaf individuals
with unstable progressive hearing loss, who are unable to use amplification devices, and /
or have cochlear malformations.

IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the MED-EL EAS System labeling.

V. DEVICE DESCRIPTION

A. General Description

The “MED-EL EAS System” is an electric-acoustic stimulation (EAS) cochlear implant

system. The MED-EL EAS System provides an electric stimulation in the high frequency
region of the cochlea and an acoustic stimulation via acoustic amplification in the low
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 frequency region of the cochlea where patients have normal hearing to a moderate
sensorineural hearing loss. The system consists of both internal and external components,
as illustrated in Figure 1.

Figure 1 – EAS Principle of Operation

Coil

Implant

Audio
Processor

Cochlea
Electrode

Ear Mold

1a) Acoustic Stimulation 1b) Electric Stimulation

(To cover the low frequencies) (To cover the higher frequencies)

Note: EAS is the use of a hearing aid and a cochlear implant in the same ear. Complete cochlear
coverage (i.e. stimulation of the entire cochlea) is achieved by combined electric and acoustic
stimulation. (2) The illustration above indicates Mi1200 SYNCHRONY PIN (implant) and SONNET
EAS (audio processor). The operation principles are the same for the other relevant implant and
audio processor variants.

Acoustic amplification (Figure 1a)

(1) Low-frequency sounds are picked up by the microphone of the audio processor
and are digitally processed and separated via a dedicated EAS circuitry.
(2) These sounds are acoustically amplified by the loudspeaker located in the ear
hook and relayed via the earmold to the ear canal.
(3) Sounds reach the undamaged areas of the cochlea responsible for processing low
frequency sound.
(4) The auditory nerve relays the signals to the brain.

Electric stimulation (Figure 1b)

(1) High frequency sounds are picked up by the microphone of the audio processor
and transforms it into coded signals.

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 (2) This coded electrical signal is sent to the coil and transmitted across the intact
skin via the inductive link.
(3) The electronics within the implant interprets the coded signals and sends a
corresponding pattern of stimulation pulses to the individual electrode contacts
of the active electrode array within the cochlea.
(4) These stimulation pulses excite action potentials which travel along the auditory
nerve to the brain, where the brain can categorize the sound and assign meaning.

Complete cochlear coverage (i.e. stimulation of the entire cochlea) is therefore achieved
by the combined electric and acoustic stimulation.

B. Implants and Electrodes

i. SONATATI100 +FLEX24, Mi1000 MED‐EL CONCERT (PIN) +FLEX24 and

Mi1200 SYNCHRONY (PIN) +FLEX24 (to extend the indication for EAS)

All the implant types (i.e., receiver-stimulators) and the +FLEX24 electrode array
have been previously approved for the conventional cochlear implant indication.
Through the current PMA supplement, these implant types and the +FLEX24
electrode array are also approved for the EAS indication.

ii. +FLEX20 electrode array

The +FLEX20 electrode array is a shorter version (approximately 20 mm of the

electrode insertion depth) of the existing FLEX electrode variants. The +FLEX20
electrode array is intended to be used for the EAS indication and is compatible
with the SONATATI100, Mi1000 MED‐EL CONCERT (PIN), and Mi1200
SYNCHRONY (PIN) implants. The design of the +FLEX20 electrode array is
based on the approved +FLEX24 electrode array. The main differences include
the length of the active electrode array (20 mm for the +FLEX20 vs. 24 mm for
the +FLEX24), electrode contact spacing (1.4 mm for the +FLEX20 vs. 1.9 mm
for the +FLEX24) and the electrode lead length (88 mm for the+FLEX20 vs.
102.2 mm for the +FLEX24).

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 Figure 2: An example of one of the ten implant variants approved for EAS, the
Mi1200 SYNCHRONY Implant

C. Audio Processors

i. DUET2 audio processor

As shown in Figure 3, the DUET2 audio processor includes an antenna coil and
its cable, control unit (typically called as the sound processor), acoustic unit (AU)
ear hook and ear mold, and battery pack. The DUET2 audio processor uses the
OPUS2 control unit which is the same control unit for the approved OPUS2 audio
processor. The DUET2 audio processor also uses accessories that are the same
with those used for the approved OPUS2 audio processor including a remote
control (FineTuner), programming cable, audio adapter cables, sound processor
test device, electrical drying kit and desiccants, clean brush, and etc. The DUET2
audio processor is designed to provide electric-acoustic stimulation. For the
acoustic stimulation, the DUET2 audio processor needs to be configured and used
with an ear mold. For the electric cochlear implant stimulation, the DUET2 audio
processor needs to be used in combination with an internal device.

ii. SONNET EAS Audio Processor

As shown in Figure 3, the SONNET EAS audio processor includes SONNET

EAS Control Unit including an audio receiver, SONNET Battery Pack, coil and
coil cable, and EAS earhook. The SONNET EAS audio processor uses the same
design as the approved SONNET for cochlear implant electric stimulation, but the
SONNET EAS audio processor provides additional hearing aid functionality for
amplification of low frequency sound. The SONNET EAS audio processor also
uses accessories that are the same with those used for the approved SONNET
audio processor including a remote control (FineTuner), MAX programming

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 cable, microphone covers, audio adapter cables, sound processor test device,
electrical drying kit and desiccants, clean brush, and etc.

The main differences between the SONNET audio processor and the SONNET
EAS audio processor include the SONNET EAS Control Unit and the EAS
earhook. The DUET2 or SONNET EAS user accessible audio processor functions
are accessed via the existing approved and unchanged FineTuner remote control
which communicates with the audio processor via a radio frequency (RF) link. In
addition, due to the integrated front-end hearing aid audio processor firmware in
the SONNET EAS, the volume of the acoustic amplification is adjustable together
with the electric stimulation via the same volume control on the FineTuner. For
the DUET2 processor, the volume for acoustic amplification is only adjustable
manually via the trimmer on the device.

Figure 3. EAS Processors: DUET 2 (left), FineTuner remote control (center),

SONNET EAS (right)

   
 
 
 

iii. Fitting Software and Accessories

The fitting or programming of SONNET EAS and DUET2 audio processors requires the
MAESTRO System Software 6.0.1 (and higher) with the MAX Programming Interface
for both the cochlear implant signal processing and the acoustic signal processing. There
are no trimmers on the SONNET EAS for manual adjustment of acoustic amplification.

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VI. ALTERNATIVE PRACTICES AND PROCEDURES

The most common alternative treatment of severe to profound bilateral high-frequency

sensorineural hearing loss with residual low-frequency hearing is the use of conventional
air conduction hearing aids or, in some cases, frequency transposition hearing aids.
Patients may also choose to forego obtaining a hearing device and pursue rehabilitation
via speechreading and/or sign language training. Each of these alternatives has its own
advantages and disadvantages. A patient should fully discuss the alternatives with his/her
physician and audiologist in order to select the treatment that best meets his/her
expectations and lifestyle.

VII. MARKETING HISTORY

The MED-EL EAS system has been marketed for use in adults and children in over 110
countries, including Albania, Algeria, Argentina, Armenia, Australia, Austria,
Azerbaijan, Bahamas, Bahrain, Bangladesh, Belarus, Belgium, Benin, Bolivia, Bosnia,
Brazil, Bulgaria, Canada, Chile, China, Colombia, Costa Rica, Croatia, Cyprus, Czech
Republic, Denmark, Ecuador, Egypt, Estonia, Finland, France, Georgia, Germany,
Greece, Guatemala, Hong Kong, Hungary, India, Indonesia, Iran, Iraq, Ireland, Israel,
Italy, Ivory Coast, Japan, Jordan, Kazakhstan, Korea, Kosovo, Kuwait, Latvia, Lebanon,
Libya, Lithuania, Luxembourg, Macedonia, Malawi, Malaysia, Malta, Mexico, Moldavia,
Mongolia, Montenegro, Morocco, Nepal, Netherlands, New Zealand, Nigeria, Norway,
Oman, Pakistan, Panama, Peru, Phillipines, Poland, Portugal, Qatar, Romania, Russian
Federation, Saudi Arabia, Senegal, Serbia, Singapore, Slovakia, Slovenia, South Africa,
Spain, Sri Lanka, Sudan, Sweden, Switzerland, Syria, Tajikistan, Taiwan, Thailand,
Turkey, U. Arab Emirates, UK, Ukraine, Uruguay, Venezuela, Vietnam, Yemen.

Since market introduction, over 4600 implants with +FLEX20 and +FLEX24 electrode
variants have been implanted worldwide and over 5000 DUET, DUET 2 and SONNET
EAS processors have been sold worldwide.

The MED-EL EAS system has not been withdrawn from any market for any reason
related to safety or effectiveness.

VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Below is a list of potential adverse effects/complications associated with the implantation

and use of the MED-EL EAS system:

 Sudden losses of residual low-frequency hearing

 Total loss of residual hearing
 Vertigo, dizziness, or balance problems that did not exist preoperatively or
worsened postoperatively
 Facial nerve problems including injury and unintended stimulation
 Meningitis
 Perilymphatic fistulae
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  Tinnitus that did not exist preoperatively or worsened postoperatively
 Implant Migration/Extrusion
 Skin flap problems
 Device-related problems including programming problems and device failure
requiring explantation/reimplantation.

For the specific adverse events that occurred in the clinical studies, please see Section X
below.

IX. SUMMARY OF NONCLINICAL STUDIES

A. Laboratory Studies

i. SONATATI100 +FLEX24, Mi1000 MED‐EL CONCERT (PIN) +FLEX24 and

Mi1200 SYNCHRONY (PIN) +FLEX24 (to extend the indication for EAS)

The +FLEX24 electrode array was previously approved to be used with the SONATA
and CONCERT (PIN) implants (P000025/S057 and S058) and SYNCHRONY (PIN)
implant (P000025/S079) for the conventional cochlear implant indications. There are no
device changes in the +FLEX24 electrode array associated with the EAS indication.
Through the review and approval of the +FLEX24 electrodes, Verification and
Validation (V&V) activities were reviewed as part of the review and approval of MED-
EL’s PMA supplements listed in Table 1. Therefore, no additional V&V tests were
needed to approve the +FLEX24 electrode arrays for the EAS indication.

Table 1. PMA supplements relevant to the approval of the +FLEX24 electrode

array for the conventional cochlear implant indication

ii. +FLEX20 electrode array

Table 2 summarizes the nonclinical testing conducted for the +FLEX20 electrode array
and lead, including information about the test, purpose, acceptance criteria and results.

Table 2. The +FLEX20 electrode array and lead testing

Test Purpose Acceptance Criteria Results
Physical To verify the The length of the array All test
dimensions physical dimensions must be verified as part requirements

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 and and electrical of the electrode are fulfilled.
performance properties assembly verification;
characteristics all other physical
dimensions of the
implant have been
verified during
previous tests.
Tensile tests To demonstrate that Two tests were No short
the electrode performed according to circuits after the
withstands tensile ISO 14708‐7(23.3), pull test and
forces that might 1) Sustained tensile elongations are
occur during or after force of min 1.05N for all between 4 ‐6
implantation, without at least one minute. mm. Insulation
fracture of any 2) All insulation impedance
conductor or impedances> 100kΩ were measured
deterioration to any direct current as planned. All
functional electrical resistance of each acceptance
insulation active electrode wire ≤ criteria were
100Ω fulfilled.
Multiple To demonstrate The array is to At the
insertion test sufficient robustness withstand 4 times completion of
of the electrode to partial insertions into the insertion
withstand the forces an obstructed scala test, the final
exerted during tympani model and 2 electrical
implantation times full insertions properties were
into an open scala tested and no
tympani model without open or short
any open and/or short circuits were
circuits. found. The test
requirements
were fulfilled.
Flex test To demonstrate that Per ISO 14708‐7 sec All test
(Drop test) the electrode 23.5, Test 1, no open or requirements
withstands the short circuit after five were fulfilled.
flexural stresses that times of stimulator The results are
might occur during drop must be shown, valid for
implantation as while the lead is CONCERT
required clamped close to the (PIN) and
most proximal SYNCHRONY
electrode contact. (PIN).
Sterilization To perform the Adoption evaluation The candidate
evaluation sterilization should be performed product may be
validation via according to adopted into the
product adoption TIR28:2009, sec 3.4 product’s
and assessment of ISO sterilization
11135‐1:2007 Sec validation of
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 C12.3.2 the SONATA.
Temporal To assess the Electrodes were Smooth and
Bone test insertion trauma inserted into scala atraumatic
caused by the tympani with the same insertion can be
electrode procedures via the expected. No
round window (RW). tissue damages
Various evaluations were observed.
were performed to
verify that the insertion
properties of the
electrode are
acceptable for human
implantation.

Preclinical Safety Analysis:

Charge density calculations were performed to specify safe stimulus current levels for
the +FLEX20 electrode array. Taking into account the area and periphery of the smallest
electrode surface, charge density calculations were completed to assure safe current
stimulation by electrodes in the cochlea. All temporal bone tests demonstrated consistent
results, indicating that the +FLEX20 electrode can be smoothly and fully inserted into
the scala tympani without significant intra-cochlear trauma. This is consistent with the
findings of insertion tests performed on the other FLEX electrodes, including +FLEX24.

Biocompatibility:
There has been no change associated with the processed materials, manufacturing
processes, packaging and sterilization methods for the +FLEX20 electrode array
compared to the previously approved electrode variants through P000025-S021, S050,
and S057. Therefore, the biocompatibility of the +FLEX20 electrode array is equivalent
to the approved electrode variants.

iii. DUET2 audio processor

Like the SONNET EAS audio processor, the DUET2 audio processor also provides
electric-acoustic stimulation. The DUET2 audio processor utilizes the approved OPUS2
control unit, FineTuner and COMT+ P coil, of which verification and validation
activities are reviewed and approved through P000025/S029. Table 3 summarizes the
nonclinical testing conducted for the acoustic unit of the DUET2 audio processor.

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 Table 3. Nonclinical laboratory tests for the DUET2 audio processor
Test Purpose Acceptance Criteria Results
Acoustic To verify that the The acoustic attributes All acceptance
Output hearing aid of DUET of the DUET 2 with criteria were
Verification 2 fulfills design OPUS 2 were tested to met. The design
requirements and the hearing aid requirements
hearing aid standards. standards (ANSI S3 are fulfilled.
Tests were further 22-2003 and IEC
repeated to verify the 60118.1994)
extended frequency ANSI S3.22,
range (125 – IEC60118-0,
1700Hz). IEC60118-0-2 +
A1+A2
Audio input To verify the audio The acoustic attributes All acceptance
verification input with mixed of the DUET 2 with criteria were
microphone and FM OPUS 2 were tested to met. The design
system mode for both the hearing aid requirements
acoustic standards (ANSI S3 are fulfilled.
amplification and 22-2003 and IEC
electric stimulation 60118.1994)
Telecoil To verify the telecoil ANSI standard S3.22 All acceptance
verification function 2003 (section 5.8.1); criteria were
IEC standard EN met.
60118-1 (section 5.8.1)
The DUET2 can be
fitted to user needs
either with help of SW-
programming and/or
with help of 4
trimmers.
Current To verify that the Current consumption All acceptance
consumption battery life is not was to IEC60118-0, criteria were
verification unacceptably IEC60118-0-2 + met. The design
shortened by the A1+A2, including requirements
addition of the 1. The DUET2 is are fulfilled.
acoustic powered by 3 zinc-air
amplification. batteries (or
equivalent), size 675,
connected in series.
Each battery has a
nominal voltage of 1.4
V. Supply voltage
ranges from 3.1V to
6.0 VDC.
2. The current
consumption of the
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 DUET2 Battery Pack
and AU Ear Hook
depends on the
acoustic output of the
AU Ear Hook. It
ranges from 0.5 mA to
1.0 mA (typical
values). The maximum
current consumption
should not exceed the
current demand of
OPUS2 by more than
1.5mA.
3. Internally in the
DUET2 Battery Pack
electronic circuit,
voltage is regulated to
1.2 V (± 0.1 V).
Trimmer To verify the Confirm 4 trimmer All acceptance
function functionality of the 4 controls perform as criteria as
verification trimmer controls to defined. defined in the
adjust acoustic attachment of
parameters the TP were
met. The
design
requirements
are fulfilled.
Connector Purpose of test was Measured signal All acceptance
signals to verify the electric should have the same criteria as
verification functionality of the frequency as the input defined in the
AU Earhook signal. attachment of
connector, CPU the TP were
Plug, audio input met. The
socket and the design
programming socket requirements
are fulfilled.
Physical To verify the The weight of the All acceptance
Characteristics dimensions, weight, DUET2 Battery Pack is criteria were
power considerations 5.3 g (± 0.5 g) (without met. The design
batteries). The weight requirements
of the AU Ear Hook is are fulfilled.
1.3 g (± 0.2 g). The
weight of the OPUS2
CPU is defined with
max. 2.4g (SP15400).
The total system
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 (OPUS2 plus AU Ear
Hook and DUET2
Battery Pack including
batteries) adds up to 14
g (± 1 g). Surfaces that
are exposed to view
after assembly shall be
clean and free of
visible scratches and
impairments when
checked with the
unaided eye in normal
lighting. (IEC60118-0,
IEC60118-0-2 +
A1+A2)
Environmental To verify the •Temperature range for All test samples
Requirement mechanical and operation: 0°C to 50°C worked within
electric performance •Temperature range for specifications.
under environmental storage: -20°C to 60°C DUET
stress during daily •Relative humidity 2 is robust
use range: 10% to 93% against
(EN60068-2-1, 2-2, 2- environmental
30, 2-33, 2-47, 2-56, 2- influence.
67)
Interference To validate that the No significant All acceptance
between Interferences influence of the criteria as
DUET 2 and between DUET 2 and acoustic parameters defined in the
OPUS 2 OPUS 2 components (Freq. Response, Gain, attachment of
have no influence on Total Harmonic the TP were
the acoustic output of Distortion (THD) and met.
DUET 2, nor the Equivalent Input
electric output of the Noise) of the DUET 2.
OPUS 2 No influence on
electric output of the
OPUS 2.
Electrical To demonstrate the Criteria as specified in All applicable
safety compliance with the IEC60601‐1:2005 tests were
relevant standard ANSI/AAMI performed and
ES60601‐1:2005 the product
fulfils the
requirements of
IEC
60601‐1:2005
EMC, ESD, To demonstrate As specified in All applicable
EMI compliance with the IEC60601‐1‐ tests were
relevant standards 2:2007; EN301 489‐3 performed and
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 V1.4.1: ISO 14708‐7, the product
Clause 24, 27 fulfils the
relevant EMC
requirements

Biocompatibility
The DUET 2 uses the exact same body contacting materials as the OPUS 2 (approved in
P000025/S029) audio processor. As validated and reviewed in P000025/S029, the
DUET2 audio processor is biocompatible.

Packaging and shipping

The packaging of the DUET 2 audio processor is the same as the OPUS 2 (approved in
P000025/S029) audio processor. All V&V activities as reviewed in P000025/S029 are
valid for the DUET2 audio processor.

iv. SONNET EAS audio processor

The SONNET EAS and SONNET (approved in P000025/S078) audio processors were
developed and validated together. Most of the V&V activities are valid for both audio
processors, such as electric stimulation, EMC, ESD, EMI, biocompatibility and
packaging etc. All V&V activities on the SONNET EAS audio processor have been
reviewed accepted in P000025/S078. Table 4 summarizes the nonclinical testing
conducted for the assemblies, components, and design requirements that are related to
acoustic amplification of the SONNET EAS audio processor.

Table 4. Nonclinical laboratory tests for the SONNET EAS audio processor
Test Purpose Acceptance Criteria Results
Verification To verify that the Frequency response All acceptance
of CPU CPU meets its and distortion criteria were
(internal specifications for (THD+N) of acoustic met. The CPU
power functional behavior output as specified; meets its
supply, of internal supply OSPL 90 according to specifications.
current voltage, current IEC 60118-0 + A1 as The design
consumption, consumption, input specified; No internal requirement is
audio input, selection, acoustic feedback at fulfilled.
telecoil input) microphone maximum gain;
frequency response No internal magnetic
and dynamic ranges, feedback at maximum
telecoil, external gain
audio input
Functional To verify that the Functions of the CPU All acceptance
verification of CPU meets its perform as intended, criteria were
CPU (acoustic specifications for and operate within met. The CPU
output) functional prescribed acoustic meets its
behavior of acoustic output levels specifications.
output The design
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 (device, OSPL90, requirement is
internal fulfilled.
acoustic feedback,
internal
magnetic feedback)
Verification To verify the hearing Hearing aid functions All acceptance
of front‐end aid functionalities of as intended, and criteria were
hearing aid the filterband, operate within met. The design
functionality frequency range, prescribed requirement is
compressor, characteristics fulfilled.
compression including prescribed
threshold and latency, filterbank
ratio, gain, output parameters,
limit, OSPL90, compression
feedback cancellation parameters, expansion
etc. parameters, sound
output levels,
feedback cancellation
parameters, etc.
Verification To verify the Functions of the All acceptance
of front‐end front‐end hearing aid firmware perform as criteria were
hearing aid firmware meets its intended, and operate met. The design
firmware requirement. within prescribed requirement is
values fulfilled.

X. SUMMARY OF PRIMARY CLINICAL STUDY

The applicant conducted a clinical study to establish reasonable assurance of safety and
effectiveness of the MED-EL EAS system in subjects 18 years an older in the US under
IDE G040002. Data from this clinical study were the basis for the PMA approval
decision. In addition, the applicant has conducted three earlier clinical studies outside of
the US on the MED-EL EAS system which are briefly described below.

Outside US studies of MED-EL EAS System

Between 2003 ~ 2006, a study of the MED-EL EAS system (COMBI 40+ M electrode
and TEMPO+ plus Oticon Adapto HA) was initiated by the applicant in Europe at five
sites as a proof-of-concept evidence to support the EAS indication. Eighteen subjects
were implanted and followed up to 12 months post-EAS fitting. Three of the eighteen
subjects (16.8%) completely lost their hearing. Three of the eighteen subjects (16.6%)
had some preserved hearing but not enough for acoustic amplification. The remaining
twelve subjects (66.6%) had sufficient residual low frequency hearing to allow for
acoustic amplification. Group mean word recognition scores reportedly improved. The
devices used in this feasibility study have undergone significant development to result in
the devices included in current supplement submission.
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 Between 2005 ~ 2010, the applicant initiated a multicenter prospective study in the
European Union (Germany and Belgium) with the PULSAR FLEX24 electrode and
DUET EAS audio processor, with a follow-up period of 12 months post-EAS fitting.
There were three study sites and eighteen subjects were enrolled and implanted with a
limited insertion depth of 18 to 22 mm. Residual hearing reportedly was preserved to
some extent in all eighteen subjects with no complete hearing loss. The group mean for
the low-frequency threshold average across 250-1000 Hz worsened by 21.5 dB at 12
months post-implantation. Group mean word/sentence recognition scores both in quiet
and noise and subjective questionnaire scores were reportedly improved from
preoperative baseline to 12 months postoperative Electric-only condition and EAS
condition.

Between 2010 ~ 2013, a multicenter prospective study was conducted in Japan with the
PULSAR FLEX24 electrode and the DUET 2 audio processor, with a follow-up period of
12 months. The Japanese study used the same electrode variant (FLEX24) as the US IDE
pivotal study and the upgraded external audio processor DUET 2, which is one of the
processors included in current supplement submission. Twenty-four adults were enrolled
and implanted with a full insertion depth of 24 mm. Residual hearing reportedly was
preserved to allow the use of acoustic amplification in twenty-three out of twenty-four
subjects at 12 months post-implantation. The group mean for the low-frequency
threshold average across 250-1000 Hz worsened by 19.6 dB at 12 months post-
implantation. The magnitude of the improvement in group mean speech perception scores
from pre-operative baseline to 12 months post-implantation were reportedly similar to
that observed in the European EAS study.

A. Study Design

The pivotal study for the MED-EL EAS system was conducted under IDE G040002 to
evaluate the safety and effectiveness of the MED-EL EAS system in individuals 18 years
of age and older who demonstrated significant residual low-frequency hearing and
profound high-frequency (above 1500 Hz) sensorineural hearing loss.

The study was a prospective, multi-center, non-randomized, non-blinded, repeated-

measures clinical study. Both objective and subjective performance data were collected.
Each subject served as her or his own control so that postoperative performance was
compared to each subject’s baseline (preoperative) performance. Seventy-three subjects
were implanted with a SONATA FLEX24 or a PULSAR FLEX24 across 14
investigational sites.

Investigational Sites

The following list identifies the 14 investigational sites (all US sites); the number of
subjects enrolled at each site is identified in parentheses:

 Boys Town National Research Hospital, Nebraska (2)

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  Duke University Medical Center, North Carolina (3)
 Hospital of University of Pennsylvania, Pennsylvania (6)
 Indiana University School of Medicine, Indiana (1)
 Medical College of Wisconsin, Wisconsin (5)
 New York Eye & Ear Infirmary Otolaryngology, New York (4)
 Oregon Health Sciences University, Oregon (3)
 Stanford University, California (3)
 Swedish Neurosciences Center for Hearing & Skull Based Surgery,
Washington (1)
 University of Kansas Medical Center, Kansas (6)
 University of Miami, Florida (5)
 University of Michigan, Michigan (2)
 University of North Carolina, North Carolina (35)
 University of Texas SW Medical Center, Texas (3)

1. Clinical Inclusion and Exclusion Criteria

Enrollment in G040002 was limited to patients who met the following inclusion
criteria:

 18 years of age or older at the time of implantation

 Severe to profound sensorineural hearing loss for frequencies > 1500 Hz
(i.e., threshold no better than 70dB HL at 2000-8000 Hz). Low-frequency
thresholds up to and including 500 Hz should be no poorer than 65 dB HL
in the ear to be implanted and the contralateral ear
 CNC word recognition score (mean of two lists) less than 60% inclusively
in the ear to be implanted and the contralateral ear
 English spoken as a primary language

Patients were excluded from the study if they met any of the following exclusion
criteria:

 Conductive, retrochchlear or central auditory disorders

 Hearing loss in the ear to be implanted that has demonstrated a recent
fluctuation at two or more frequencies of 15 dB in either direction in the
last 2 years
 Any physical, psychological, or emotional disorder that interferes with
surgery or the ability to perform on test and rehabilitation procedures
 Developmental delays or organic brain dysfunction
 Unrealistic expectations on the part of the subject, regarding the possible
benefits, risks, and limitations that are inherent to the surgical procedure(s)
and prosthetic devices
 Unwillingness or inability of the candidate to comply with all
investigational requirements

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 2. Follow-up Schedule

This study involved up to eight visits before and after implantation, for about a
one-year period. Candidacy testing included medical and audiological evaluations
to determine study eligibility. A 30-day hearing aid trial was required for those
prospective subjects who were not previous users of appropriately fit hearing aids
prior to being accepted as a study candidate, which required one or two additional
visits. After confirming eligibility, the subject underwent baseline testing. The
device was subsequently implanted in one ear in accordance with the subject
candidacy criteria. The device was activated following a healing period of 3 to 4
weeks.

The baseline and postoperative measurements are summarized in Table 5. All

patients were scheduled to return for follow-up examinations at 3, 6, and 12
months postoperatively. Preoperatively, a baseline evaluation was conducted that
included collection of both unaided and hearing-aided threshold measures, and
also hearing-aided baseline measures for the primary/secondary effectiveness
endpoints. Adverse events and complications were recorded at all visits.

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 Table 5. Schedule of study visits1
Baseline Initial CI Initial EAS 3-month 6-month 12-month
Evaluation Stimulation Stimulation Post- Post- Post-
operative operative operative
Informed
X
Consent
Medical and
Hearing History X
Verification of
Hearing Aid X X X X
functioning
Unaided
X X X X X X
Hearing
Thresholds and
Tympanometry
Aided
Audiometric X X X X X
Thresholds
Aided CNC test
X X X X X
in quiet
Aided CUNY
sentences-in- X X X X X
noise test
Adaptive SRT
X
in noise X X X X
Questionnaires
(APHAB, X X X X
HDSS)
Psychophysical
X X X X X
Ts and Cs and
electrical
impedance
Adverse event
X X X X X
reporting X
1
Subjects continued to be monitored on a semi-annual basis after the 12-month
interval until study closure (may conduct the same measurements as 12-month
postoperative evaluation but not required by protocol).

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 3. Clinical Endpoints

Test Conditions

Three test conditions were proposed: preoperative Acoustic-only (acoustic

stimulation to the ear to be implanted), postoperative Electric-only (electric
stimulation to the ear to be implanted), and postoperative EAS (simultaneous
electric and acoustic stimulation in the implanted ear via the MED-EL EAS
system; Note: only one subject who lost residual hearing immediately following
surgery early in the study was tested in a bimodal condition (electric stimulation
only using the MED-EL EAS system minus the Acoustic Component with
contralateral acoustic stimulation )).

Endpoints

Safety Endpoint: The primary safety endpoint was the number and proportion of
individuals experiencing an adverse event, defined as any surgical and/or device-
related event. The adverse events include anticipated and unanticipated adverse
events. The list of anticipated adverse device effects identified by the applicant
follows:

1. Sudden changes in residual low-frequency hearing.

2. Total loss of residual hearing.
3. Vertigo, dizziness, or balance problems that did not exist preoperatively or
worsened postoperatively.
4. Facial nerve problems.
5. Meningitis.
6. Perilymphatic fistulae.
7. Tinnitus that did not exist preoperatively or worsened postoperatively.
8. Implant Migration/Extrusion.
9. Skin flap problems.
10. Device-related/programming problems.

The applicant did not propose formal statistical hypothesis testing for the safety
endpoint but specified following success criteria for the safety endpoint: an
observed rate of device related adverse events less than or equal to 8.5%; The
two-sided 95% exact confidence bound was presented for the overall device-
related adverse event rate, indicating an upper limit of 17.6%.

Primary Effectiveness Endpoint: The primary effectiveness endpoint was

CUNY sentence-in-noise scores. The score was compared across two conditions:
the Acoustic-only condition (baseline) and the 12-month post-activation EAS
condition (ipsilateral Electric + ipsilateral Acoustic). Subjects were tested to
determine the overall benefit received from the MED-EL EAS system compared
to the preoperative Acoustic-only condition.

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 An improvement in CUNY sentence score (CUNY post EAS- pre A) was defined as at
least a 10 point absolute change in score from pre-operative to the 12-month
interval. A t-test was used to evaluate the null hypothesis that the change from
baseline is equal to 10.

H0: µ∆ = 10
H1: µ∆ ≠ 10

A 95% two-sided confidence interval was calculated for the mean change from
baseline.

Secondary Effectiveness Endpoints:

 The comparison of CUNY sentence in noise scores between the

postoperative EAS condition and the postoperative Electric-only condition
(CUNY post EAS – post E) is used to determine the benefit of the MED-EL
EAS system at 12 months. An improvement in CUNY sentence score was
defined as a 10 point absolute change in the score. A t-test was used to
evaluate the null hypothesis:

H0: µ∆ = 10
H1: µ∆ ≠ 10

The 98.75% two-sided confidence intervals were calculated for the mean
change from baseline.

 The comparison of CNC word scores between the postoperative Electric-

only condition and the preoperative Acoustic-only condition (CNC post E-pre
A) is used to determine whether subjects would perform the same or better
with the Electric-only condition compared to preoperative Acoustic-only
condition. Similar performance was defined as the Electric-only condition
being no worse than 10 points lower than the preoperative Acoustic-only
condition. A t-test was used to evaluate the null hypothesis:

H0: µCI-AC ≤ −10

H1: µCI-AC > −10

The 98.75% two-sided confidence intervals were calculated for the mean
change from baseline.

Audiometric Test Methods & Effectiveness Measures

Audiometric Thresholds
Unaided audiometric thresholds were obtained for each ear, with insert earphones,
using the standard audiometric technique for pure-tone testing. Aided audiometric
thresholds were obtained for each ear in the sound-field using narrow band noise
PMA P000025/S084: FDA Summary of Safety and Effectiveness Data Page 21
 and the standard audiometric technique with the speakers positioned at 0° azimuth
relative to the subject’s head. The contralateral ear was masked/plugged during
aided testing.
Unaided testing for both ears included air conduction thresholds at 125, 250, 500,
750, 1000, 1500, 2000, 3000, 4000, 6000, and 8000 Hz, and bone conduction
thresholds at 125, 250, 500, 750, 1000, 1500, 2000, and 4000 Hz. Aided
thresholds were measured at the following frequencies: 250, 500, 750, 1000,
1500, 2000, 3000, 4000, 6000, and 8000 Hz.
The low-frequency hearing threshold was defined as the threshold averaged over
the range 250 through 1000 Hz, inclusively, in the implanted ear.

For the purposes of adverse event reporting, any change in the low-frequency
hearing threshold that resulted in a profound loss (Pure Tone Average (PTA) across
250-1000 Hz > 90 dB HL) and possibly also total loss (defined as no measurable
hearing at the maximum output of the audiometer) in the implanted ear was
considered by the applicant as an anticipated adverse event. All cases of
profound/total loss of residual low-frequency hearing were included in the adverse
event tabulations and analyses.
Effectiveness Measures

Consonant-Nucleus-Consonant (CNC) Word Recognition Test

The CNC Word Recognition Test (Peterson & Lehiste, 1962) is a

psychometrically validated test of open set word recognition to determine speech
intelligibility in listeners with hearing impairments. This test consists of 10
recorded lists of 50 monosyllabic words. At each test interval, two lists were
administered in quiet at 60 dBA in the sound field and scored as percent correct
for words and phonemes. Subjects were tested using a configuration where the
target speech was presented via a loudspeaker at 0º azimuth.

City University of New York (CUNY) Sentence in Noise Test

The CUNY Sentence-in-Noise Test is a psychometrically validated test to assess

CI recipients’ ability to understand sentences in the presence of background noise.
This test consisted of 50 lists of 12 sentences spoken by an Australian female
speaker. At each test interval, four lists of the CUNY sentences were presented at
70 dB SPL with the competing speech weighted noise, to achieve a +10, +5, and 0
dB signal-to-noise, which was determined based on subject’s performance in the
Electric-only condition. Stimuli were presented from a single loudspeaker located
at 0º azimuth.

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 B. Accountability of PMA Cohort

A total of 79 subjects were consented to be evaluated for participation in the study. Of

these 79 subjects,
 6 were potential candidates, but discontinued participation and did not
proceed with implantation. Of these 6:
o 3 could not secure insurance and withdrew
o 2 elected to pursue other options (nonsurgical or traditional cochlear
implantation). Of these 2:
 1 pursued traditional cochlear implantation
 1 pursued hearing aid amplification
o 1 withdrew due to a lengthy insurance issue and subsequent change in
hearing outside of candidacy
 The remaining 73 subjects were implanted with the MED-EL EAS system.

Of the 73 subjects who were enrolled and implanted (all implanted unilaterally), all
subjects had their device activated and completed the EAS activation interval. At the
12-month interval, 67 subjects (92%) completed the audiometric testing for hearing
sensitivity and all effectiveness outcome assessments. One subject was withdrawn at
6-month evaluation due to the electrode array migration out of the cochlea and re-
implanted with a standard array. One subject was withdrawn before completing the 6-
month evaluation due to health concerns unrelated to the device that resulted in an
inability to follow the protocol. One subject withdrew prior to reaching the 12-month
interval. Two subjects were lost-to-follow-up. The remaining one subject is still
undergoing follow‐up. Safety data, however, was collected and monitored throughout
the study duration for all 73 implanted subjects.

C. Study Population Demographics and Baseline Parameters

Of the 73 implanted subjects, 42 were female and 31 were male. At the time of
implantation, subjects ranged in age from 17 to 76 years (including two subjects
implanted under compassionate clearance). The duration of hearing loss ranged from
2 to 60 years. The duration of hearing aid use ranged from 1 – 48 years. Further
information on subject demographics is summarized in Table 6 below.

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 Table 6. Descriptive statistics for subject variables*
Parameter/Category or Statistic Total (n=73)
Gender
Male 42.5% (31/73)
Female 57.5% (42/73)
Age (years) 53.7 (73) (17 – 76)
Duration of noticeable hearing loss (years)
Left 25.7 (73) (2 – 60)
Right 25.7 (73) (2 – 60)
Duration of hearing aid use (years)
Left 17.4 (73) (1 – 48)
Right 17.4 (72) (1 – 47)
*Numbers are % (Count/Sample Size) or Mean (N) (Min – Max)

Figure 4 below shows the preoperative unaided air conduction mean thresholds along
with ±1 standard deviation bars in the ear to-be-implanted for all subjects. The shaded
region represents the range of audiometric thresholds according to the subject
candidacy criteria. Consistent with the study inclusion criteria, hearing thresholds
ranged from within normal limits to moderately severe loss up to 500 Hz, sloping
downward to severe or profound loss at higher frequencies.  
 
Figure 4. Average pre-operative audiogram and audiometric fitting range (gray
region)

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 D. Safety and Effectiveness Results

1. Safety Results

The analysis of safety was based on all 73 implanted patients. The key safety
outcomes for this study are presented below in Table 7 through 9.

Adverse effects that occurred in the PMA clinical study:

Many of the 10 possible anticipated adverse events (defined earlier) were reported
by the applicant to have occurred during the study. Adverse events were classified
as anticipated/unanticipated, serious/non-serious, or device-related/unrelated. In
summary, a total of 35 adverse events were reported (see Table 7 below) to be
related to the device or procedure. No adverse events were reported as
unanticipated.

 Table 7. Number and percentage of adverse events observed for EAS

subjects
Events Reported as No. of No. of % of %
Device- or Procedure- Events Subjects Subjects Resolved
Related
Type B or Type C 8 6 8% 100%
tympanogram
Profound/Total loss of 8 8 11% 0%
residual hearing1
Conductive hearing loss 5 5 7% 0%
Pain at site 3 3 4% 67%
Electrode lead breakage 1 1 1% 100%
after excessive micro-
movements, caused by
patient massaging area2
Electrode migration2 1 1 1% 100%

Occasionally off- balance 1 1 1% 100%

Ulnar nerve palsy after 1 1 1% 100%
operation
Telemetry showed high 1 1 1% 0%
status on electrode channels

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 Events Reported as No. of No. of % of %
Device- or Procedure- Events Subjects Subjects Resolved
Related
Facial stimulation 1 1 1% 100%

Aural fullness 1 1 1% 100%

Sensation of device shifting 1 1 1% 100%
when pushing over the
implant site
Temporary shift in hearing 1 1 1% 100%
threshold

Beeping/ringing in 1 1 1% 0%
implanted ear
Bitter taste on right side of 1 1 1% 100%
tongue
Total 35 29* 40% 57%

Notes: 1Although the profound/total loss of residual hearing was specified in the
applicant’s protocol to be reported as an adverse event by applicant, smaller amounts of
hearing loss are discussed below. 2Electrode lead breakage and electrode migration fall
under device-related problems. *Some subjects experienced more than one device-
related adverse event.

As listed in Table 7, the most frequently observed adverse events were

profound/total loss of residual hearing occurred in 8 of the 73 subjects (11%) and
conductive hearing loss occurred in 5 of the 73 subjects (7%), none of which were
resolved. Type B or C tympanogram (8%) occurred eight times and was resolved
in all cases.

In terms of the unresolved adverse events observed in this study, profound/total

loss of residual low-frequency hearing was by far the most frequently observed
adverse event, occurring in 8 of 73 (11%) of subjects. No subjects who had
profound/total loss of hearing in the implanted ear were explanted or reimplanted
with a standard electrode array due to dissatisfaction or poor performance with the
MED-EL EAS system. Loss of residual hearing and device explants are discussed
further below.

Loss of residual low-frequency hearing

The proportions of subjects stratified by the amount of low-frequency hearing loss
at the 3-, 6- and 12-month intervals are summarized in Table 8. The same data,
PMA P000025/S084: FDA Summary of Safety and Effectiveness Data Page 26
 stratified by postoperative residual low-frequency hearing sensitivity at the 3-, 6-
and 12-month intervals, are summarized in Table 9.

Table 8. Proportion of subjects with various amounts of low-frequency

hearing loss at 3, 6 and 12 months
Time Point < 10 dB 10-20 dB 20-30 dB > 30 dB
3 Month 10/71 (14.08%) 30/71 (42.25%) 18/71 (25.35%) 13/71 (18.31%)
6 Month 11/69 (15.94%) 23/69 (33.33%) 20/69 (28.99%) 15/69 (21.74%)
12 Month 8/67 (11.94%) 25/67 (37.31%) 20/67 (29.85%) 14/67 (20.90%)

Table 9. Proportion of subjects’ low-frequency hearing sensitivity at 3, 6, and

12 months
Time Moderate-
Point Normal Mild Moderate Severe Severe Profound
3 0/71 2/71 7/71 30/71 28/71 4/71
Month (0%) (2.82%) (9.86%) (42.25%) (39.44%) (5.63%)
6 0/69 2/69 9/69 26/69 26/69 6/69
Month (0%) (2.90%) (13.04%) (37.68%) (37.68%) (8.70%)
12 0/67 2/67 5/67 28/67 24/67 8/67
Month (0%) (2.99%) (7.46%) (41.79%) (35.82%) (11.94%)

As shown in the Table 9, there are eight subjects who had profound hearing loss
in the implanted ear at the 12-month follow up visit. Two subjects experienced a
total loss of residual hearing immediately after surgery and were unable to use the
acoustic component of the audio processor. Six additional subjects experienced a
profound loss of hearing within the 12-month follow-up period but were still able
to use the acoustic unit based on at least one low-frequency threshold better than
80 dB HL. All eight of these adverse events at the 12-month follow-up visit are
reported above in Table 7 as “profound/total loss of residual hearing”.

Device Explants

Two subjects have undergone device explantation. One subject was withdrawn
from the study at the 6-month interval, when it was determined that the electrode
array migrated out of the cochlea. This subject was subsequently implanted with a
standard electrode array. The second subject experienced a device failure after
excessive micro-movements caused the lead to break. The micro-movements
occurred due to the subject massaging the area over the implant. This subject was

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 reimplanted with a FLEX24 electrode and maintained residual hearing after the
second surgery.

No subjects have been explanted/reimplanted due to loss of residual hearing in the

implanted ear, sound quality issues, or poor performance.

2. Effectiveness Results

The analysis of effectiveness was based on the previously defined co-primary and
secondary effectiveness endpoints at the 12-month time point.

Primary Effectiveness Endpoint

A statistically significant improvement in mean CUNY sentence in noise score
(CUNY post EAS- pre A) occurred from the baseline (preoperative Acoustic-only
condition) to the 12-month follow-up interval (postoperative EAS condition).
Hence, the primary effectiveness endpoint was met. These data are based on 66 of
67 (99%) subjects who were assessed at the baseline and the 12-month interval.
One subject was not tested in the EAS condition due to loss of residual hearing
immediately following surgery. When worst-case imputed scores for the missing
subject were included in the sample, the primary endpoint was still met: the mean
improvement with 95% confidence intervals was 42.4% (33.6%, 51.2%) for the
CUNY sentences (p = 0.000). These analyses revealed that the result for the
primary endpoint is robust to the missing data. 

Secondary Effectiveness Endpoints

 For the comparison of CUNY sentence in noise scores between the

postoperative EAS condition and the postoperative Electric-only
condition (CUNY post EAS – post E), a mean improvement with 95%
confidence intervals was 18.4% (-19%, 77%) and was statistically
significant (p = 0.003). This secondary effectiveness endpoint was met.
This data is based on the 66 of 67 (99%) subjects who were able to be
tested in both the EAS and Electric-only conditions at the 12-month
interval.

 For the comparison of CNC word scores between the postoperative

Electric-only condition and preoperative Acoustic-only condition
(CNC post E-pre A), a mean improvement with 95% confidence intervals
was 17.9% (12.5%, 23.6%) and was statistically significant (p = 0.000).
This secondary effectiveness endpoint was met. This data is based on
the 67 of 67 (100%) subjects who were able to be tested in the
preoperative Acoustic-only condition and the postoperative Electric-
only condition and condition at the 12-month interval.

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 3. Subgroup Analyses

Effectiveness Data Stratified by Performance

Table 10 displays the proportion of subjects who performed poorer, similar,

and better for the primary endpoint (CUNY post EAS- pre A) and two secondary
endpoint metrics (CUNY post EAS – post E and CNC post E-pre A) at the 12-month
interval. Over 87% of the subjects exhibited similar or better performance on
all three metrics. However, there were small proportions of subjects who
performed poorer for CUNY post EAS- pre A (7.8%), CUNY post EAS – post E (13.4%),
and CNC post E-pre A (11.9%), respectively, at the 12-month interval.

Table 10. Proportion of subjects who performed poorer, similar, or better in

the post-operative EAS or Electric-only condition versus the (ipsilateral) pre-
operative Acoustic-only condition at 12 months
Time Point Better (SE) Similar Worse
CUNY post EAS- pre A 12 Month 56/66 (84.85%) 5/66 (7.58%) 5/66 (7.58%)
CUNY post EAS – post E 12 Month 47/67 (70.15%) 11/67 (16.42%) 9/67 (13.43%)
CNC post E-pre A 12 Month 45/67 (67.16%) 14/67 (20.90%) 8/67 (11.94%)

Exploration of Effects of Baseline Characteristics on Device Effectiveness

Regression analyses were performed on CUNY and CNC scores as a function of
the following baseline demographics: sex, age, duration of hearing impairment,
pre-operative low-frequency hearing loss, and baseline speech score. Multivariate
Analyses were completed for the above baseline characteristics as categorical
(e.g., >/< mean) and continuous variables, when applicable. Results for CUNY
and CNC improvement are presented below in Tables 11 and 12 (respectively) as
a function of baseline demographics. Both sets of analyses show general
improvement in all subgroups and yield no statistically significant differences in
outcome.

Table 11. CUNY Results as a Function of Baseline Demographics

Coefficient P-
Variable (SE) Value
Intercept 9.25 0.68
(22.50)
SEX (Female) -7.39 (6.16) 0.23
AGE 0.07 (0.24) 0.79
HLDURL -5.24 0.65
(11.51)

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 Coefficient P-
Variable (SE) Value
HLDURR 5.39 0.64
(11.51)
Pre-Op Low Frequency 0.21 (0.25) 0.42
Hearing Loss
Baseline Speech Scores -0.12 (0.10) 0.24

Table 12. CNC Results as a Function of Baseline Demographics

Coefficient P-
Variable (SE) Value
Intercept 72.11 0.00
(21.49)
SEX (Female) 3.41 (5.40) 0.53
AGE 0.04 (0.21) 0.83
HLDURL 0.18 (9.85) 0.99
HLDURR -0.33 (9.85) 0.97
Pre-Op Low Freq Hearing -0.05 (0.24) 0.85
Loss
Baseline Speech Scores -1.11 (0.20) 0.00

Exploration of Residual Hearing as a Function of Site

Outcomes related to postoperative residual hearing were investigated across sites

to determine the amount of pre-to-post operative threshold shift. Results are
presented below in Table 13. No statistically significant site effects were
demonstrated.

Table 13. Pre-to-post Operative Thresholds Shift as a Function of Site

Source DF Type III SS Mean Square F Value P-Value
SITENO 13 4496.524525 345.886502 1.46 0.1632

PMA P000025/S084: FDA Summary of Safety and Effectiveness Data Page 30

 E. Financial Disclosure

The Financial Disclosure by Clinical Investigators regulation (21 CFR 54) requires
applicants who submit a marketing application to include certain information
concerning the compensation to, and financial interests and arrangement of, any
clinical investigator conducting clinical studies covered by the regulation. The
pivotal clinical study included 107 investigators of which none were full-time or part-
time employees of the sponsor and 3 investigators had disclosable financial
interests/arrangements as defined in 21 CFR 54.2(a), (b), (c) and (f) and described
below:

 Compensation to the investigator for conducting the study where the value
could be influenced by the outcome of the study: 0
 Significant payment of other sorts: 3
 Proprietary interest in the product tested held by the investigator: 0
 Significant equity interest held by investigator in sponsor of covered study: 0

The applicant has adequately disclosed the financial interest/arrangements with

clinical investigators. Statistical analyses were conducted by FDA to determine
whether the financial interests/arrangements had any impact on the clinical study
outcome. The information provided does not raise any questions about the reliability
of the data.

XI. SUMMARY OF SUPPLEMENTAL CLINICAL INFORMATION

The applicant included test results on the following additional tests in their PMA: the
Abbreviated Profile of Hearing Aid Benefit (APHAB) and Hearing Device Satisfaction
Scale (HDSS) questionnaires. The comparisons of the APHAB and HDSS questionnaire
scores between the postoperative EAS and the preoperative Acoustic-only conditions
were conducted to determine patients’ subjective perception of the device benefit.
Subjects were not instructed to ignore the contralateral ear and, therefore, the
comparisons were between the preoperative, bilateral Acoustic condition and the
postoperative, everyday listening condition (Electric + bilateral Acoustic). Results from
these tests are briefly summarized below.

The Abbreviated Profile of Hearing Aid Benefit (APHAB) – The APHAB (Cox and
Alexander, 1995), a self-report questionnaire that is used to qualify the impact of a
hearing problem on an individual’s daily life, was adopted to assess subjects’ perception
of hearing disability. The APHAB consists of multiple domains of hearing: hearing in the
presence of background noise, hearing in reverberant surroundings, ease of
communication, and aversion to sounds. The global sore quantifies, across all domains,
the frequency of problems before and after the implantation of the MED-El EAS system.
Lower scores correspond to lower disability. A mean reduction of APHAB global score
with 95% confidence intervals was 30.2% (-69%, 41%) and was statistically significant
(p < 0.001). This data is based on the 59 of 67 (88%) subjects who were able to be tested
at the baseline and the 12-month interval. The data indicates significant improvement in
PMA P000025/S084: FDA Summary of Safety and Effectiveness Data Page 31
 subjects’ perception of hearing disability from preoperative baseline to 12 months after
implantation.

The Hearing Device Satisfaction Scale (HDSS) – The HDSS is a self-assessment

questionnaire that assesses subjects’ satisfaction with various aspects of the amplification
system. Subjects rated their satisfaction level with their hearing aids at the baseline and
with their contralateral hearing aid + MED-EL EAS system at the 12-month interval as:
“Very Satisfied”, “Satisfied”, “Neutral”, “Dissatisfied”, “Very Dissatisfied”, or “Does
Not Apply” in a variety of listening environments. There are 21 sub-categories in total
e.g. overall fit/comfort, sound quality of my own voice, effectiveness in background
noise, handling/manipulation etc. Increase of satisfaction was defined as improvement in
a rating scale for at least one category. The proportion of subjects experiencing no
change, decreasing, or increasing satisfaction is displayed below in Table 14. Of all
subjects completing the HDSS, 86% indicated an increase in satisfaction at the 12 months
follow-up interval. This data is based on the 59 of 67 (88%) subjects who were able to be
tested at the baseline and the 12-month interval.

Table 14. Hearing Device Satisfaction Scale (HDSS)

Visit No Change Decrease Increase
12 Months 7/59 (11.86%) 1/59 (1.69%) 51/59 (86.44%)

XII. PANEL MEETING RECOMMENDATION AND FDA’S POST-PANEL ACTION

In accordance with the provisions of section 515(c)(3) of the act as amended by the Safe
Medical Devices Act of 1990, this PMA was not referred to the Ear, Nose, and Throat
Devices Panel, an FDA advisory committee, for review and recommendation because the
information in the PMA substantially duplicates information previously reviewed by this
panel.

XIII. CONCLUSIONS DRAWN FROM PRECLINICAL AND CLINICAL STUDIES

A. Effectiveness Conclusions
One primary and two secondary effectiveness endpoints were defined. For all
endpoints, performance at 12 months post implantation was compared to pre-
operative baseline. Performance was measured using the MED-EL EAS system (at 12
months) and compared to the preoperative, hearing aided performance in the ear-to-
be-implanted (at preoperative baseline). The primary effectiveness endpoint was
defined as a mean improvement in CUNY sentence-in-noise scores (CUNY post EAS- pre
A). Two secondary effectiveness endpoints were defined as 1) a comparison of CUNY
sentence-in-noise scores between the postoperative EAS condition and the
postoperative E Alone condition (CUNY post EAS – post E); and 2) a comparison of CNC
word scores between the postoperative Electric-only condition and the preoperative
Acoustic-only condition (CNC post E-pre A).

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 Primary Endpoint Results: The mean improvement in CUNY sentences (CUNY post
EAS- pre A) was 42.4% with 95% confidence intervals of (33.6%, 51.2%). The
improvement was statistically significant (p = 0.000), and it was thus concluded that
the primary endpoint was met.
Secondary Endpoint Results: The mean improvement in CUNY sentences (CUNY post
E – pre A)
was 18.4% with 95% confidence intervals of (-19%, 77%). The mean
improvement in CNC words (CNC post E-pre A) was 17.9% with 95% confidence
intervals of (12.5%, 23.6%). Both secondary endpoints were met.
Overall, the data supports that the MED-EL EAS system provides significant benefit
compared to the preoperative Acoustic-only condition, and that electric stimulation
alone also provides benefit over the preoperative Acoustic-only condition. Because
the majority of subjects (66 out of 67) were tested in the ipsilateral EAS condition, it
is expected that subjects would be able to achieve even greater EAS benefit when
combining electric hearing and bilateral acoustic hearing together, i.e., the bilateral
EAS condition in which patients would typically experience with their CI and HA(s)
in daily life.
Other effectiveness measures and analyses
Analysis by study site: The consistency of the postoperative residual hearing was
examined across 14 investigational sites by testing for an effect of site in an ANOVA
model, based on 67 subjects who completed the 12-month interval evaluation. The
results indicated no evidence of site effects on the primary effectiveness endpoints.
Other Effectiveness Measures:
The APHAB Questionnaire: The results from 59 subjects showed a mean 30.2%
reduction in the APHAB global score with 95% confidence intervals of (-69%, 41%)
indicating significant improvement in subjects’ perception of hearing disability from
preoperative baseline to 12 months after implantation.
The HDSS Questionnaire: The results from 59 subjects showed that 86% subjects
indicated an increase in satisfaction with their MED-EL EAS system at the 12 months
follow-up interval compared to that with their preoperative amplification at the
preoperative baseline.

B. Safety Conclusions

The risks of the device are based on the data collected in the clinical study conducted
to support PMA approval as described above.

The primary safety objective was to report all surgical and/or device-related events,
as the number and proportion of individuals experiencing an adverse event.

Profound/total loss of residual low-frequency hearing and conductive
hearing loss were the most frequently observed anticipated unresolved
adverse event. Total loss of residual hearing was observed in 8 of 73
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 subjects (11%). Conductive hearing loss was observed in 6 of 73 subjects
(8%).

 Type B or C tympanogram and pain at site were the most frequently

observed resolved adverse events and occurring at a rate of 8 and 4%,
respectively, in the 73 enrolled and implanted subjects.

 Explantation and reimplantation with a standard/FLEX24 electrode array

occurred in 2/73 (3%) of subjects due to electrode lead breakage and
electrode migration.
The adverse event rate (40%) exceeded the safety endpoint (8.5%) pre-specified in
the IDE study protocol (G040002). However, observed adverse events that were
resolved were consistent with those seen with approved cochlear implant systems.
Profound/total loss of hearing is the most frequently observed anticipated unresolved
adverse event. No subjects who lost the residual hearing in the implanted ear were
explanted or reimplanted with a standard electrode array due to dissatisfaction or poor
performance with the MED-EL EAS system. Therefore, the adverse event rate
observed in the pivotal study is acceptable. It is yet to be determined over the long-
term how many additional subjects will experience total loss of residual hearing. The
post approval study specified in the approval order is designed to assess the time
course of residual hearing loss. Based on the results of this post approval study, the
labeling for the MED-EL EAS system will be updated accordingly.

C. Benefit-Risk Conclusions

The probable benefits of the device are also based on data collected in a clinical study
conducted to support PMA approval as described above. The clinical study results for
the MED-EL EAS system demonstrated a statistically and clinically significant
benefit (average 42% improvement) from use of the device (EAS condition) at the
study endpoint interval (12-month) in speech-in-noise recognition over the
preoperative HA performance using the CUNY sentence in noise for speech
recognition. 85% of the subjects exhibited better performance on speech recognition
at the 12-month interval compared to the preoperative baseline (e.g., CUNY post EAS- pre
A). Therefore, the MED-EL EAS system is expected to improve speech recognition in
terms of CUNY sentences and CNC words for a majority of the indicated population.

The safety data from this clinical study suggests that the patients tolerated the risks
well, especially since most adverse events were device/procedure related to cochlear
implantation surgery and were resolved postoperatively. The profound and possibly
also total loss of low-frequency hearing that occurred in 8/73 (11%) of subjects at the
12-month follow-up visit is the most frequent, unresolved risk. Among the eight
subjects, two subjects experienced total loss and only used the electrical unit of the
MED-EL EAS system; six subjects experienced a profound loss of hearing but were
still able to use the acoustic unit based on at least one low-frequency threshold better
than 80 dB HL. No subjects who had profound/total loss of the residual hearing in
the implanted ear were explanted or reimplanted with a standard electrode array due

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 to dissatisfaction or poor performance with the MED-EL EAS system. Therefore,
even for those who experienced permanent residual hearing loss, they still generally
obtained greater benefit than the alternative treatments (i.e., hearing aids), suggesting
that the risks were tolerable relative to the benefits. The long-term rate of
profound/total loss of residual hearing is being studied in a post-approval follow-up
study.

Additional factors to be considered in determining probable risks and benefits for the
MED-EL EAS system included patient’s perspectives on the device benefit.

1. Patient Perspectives

Patient perspectives considered during the review included: subjective measures

of benefit and satisfaction. The majority of subjects demonstrated improvements
in benefit and satisfaction evaluated by both APHAB and HDSS questionnaires
regarding the ease of communication, especially in difficult listening conditions,
and improvement in quality of life (i.e., social, emotional, physical). The large
magnitude of benefit and satisfaction improvement demonstrated through the
responses on both APHAB and HDSS questionnaires (e.g., 30.2% improvement
score on APHAB) indicated that patients were able to experience the EAS benefit
in their daily lives from the MED-EL EAS system, compared to their
preoperatively used hearing aids.

In conclusion, given the available information above, the data support that the overall
hearing benefits of the device outweigh the risks for patients who do not benefit from
traditional hearing aids and meet the criteria specified in the proposed indication.

D. Overall Conclusions
The data in this application support a reasonable assurance of safety and effectiveness
of this device when used in accordance with the proposed indications for use. The
preclinical testing provided for the device was acceptable. Based on the clinical study
results, it is reasonable to expect clinical benefits with use of the MED-EL EAS
system in terms of improvement in speech understanding in quiet and noise since the
average performance of the study population showed statistically significant
improvements in one primary and two secondary endpoint measures. The risks
associated with the device, including residual low-frequency hearing loss and
conductive hearing loss should therefore be carefully considered by potential
candidates and their hearing health-care providers. However, FDA believes that the
available data demonstrate that the benefits outweigh these risks in the pivotal study
patient population, particularly since the device provided speech-understanding
benefit for most subjects, including those individuals who lost residual hearing to the
profound levels.

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XIV. CDRH DECISION

CDRH issued an approval order on September 15, 2016. The final conditions of approval
cited in the approval order are described below.

MED-EL EAS Extended Follow-up Study: This study is an extended follow-up of the
subjects who were enrolled in the pivotal study to assess long-term safety and device
performance. The study will be conducted as a prospective, non-controlled, non-
randomized, multicenter study at the 14 sites. All 68 available subjects who were enrolled
in the pivotal study will be invited to participate in the extended follow-up. Study
subjects will be followed for a minimum of 5 years post- implantation of the device. The
primary safety endpoint is the number and proportion of subjects experiencing device-
related adverse events throughout the duration of the post-approval study. The secondary
safety endpoint includes measures of residual hearing at a minimum of 5 years post-
implantation, which will provide an estimation of the proportion of subjects with residual
hearing loss at 5 years post-implantation. The effectiveness endpoints will include the
within-subject differences for the two speech recognition tests, i.e., word recognition in
quiet as evaluated with the Consonant-Nucleus-Consonant (CNC) test, and sentence
recognition in noise as evaluated with the CUNY test. The stability of perceived hearing
benefits over time will be assessed by employing the APHAB questionnaire. Subjects
will be followed on an annual basis until reaching 60 months post-activation; for those
who are already outside the 60-month window, one additional visit will be required.
Every explanted device will be tested to determine the reason for device failure, and
device explantations will be reported as serious adverse events.  

XV. APPROVAL SPECIFICATIONS

Directions for use: See device labeling.

Hazards to Health from Use of the Device: See Indications, Contraindications,

Warnings, Precautions, and Adverse Events in the device labeling.

Post-approval Requirements and Restrictions: See approval order.

XVI. REFERENCES
 
Cox, R.M. and Alexander, G.C. (1995). The abbreviated profile of hearing aid benefit.
Ear & Hearing, 16:176-186.

Peterson, F. and Lehiste, I. (1962). Revised CNC lists for auditory tests. Journal of
Speech and Hearing Disorders, 27(1):62-70.

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