Kintsugi Voice Device Study
Conditions: Depression, Anxiety
Sponsor: Kintsugi Mindful Wellness, Inc.

Protocol Title: Kintsugi Voice Device Pilot Study
Sponsor: Kintsugi Mindful Wellness, Inc.
1569 Solano Avenue No. 365
Berkeley, CA 94707
Principal Investigator: Grace Chang
Co-Investigators: Herbert J. Harman, MD, Roshanak Ramezani, MD
Version, Date: Version 7.0, Dated Sep 7, 2022

Statement of Compliance
The study will be conducted in accordance with the International Conference on
Harmonisation guidelines for Good Clinical Practice (ICH E6), the Code of Federal
Regulations on the Protection of Human Subjects (45 CFR Part 46). All personnel
involved in the conduct of this study have completed human subject’s protection
training.
2

SIGNATURE PAGE
The signature below constitutes the approval of this protocol and the attachments, and provides
the necessary assurances that this trial will be conducted according to all stipulations of the
protocol, including all statements regarding confidentiality, and according to local legal and
regulatory requirements and applicable US federal regulations and ICH guidelines.
Principal Investigator: Grace Chang
Co-Investigators: Herbert J. Harman, MD, Roshanak Ramezani, MD
Signed:
Grace Chang
Date:
Signed:
Herbert J. Harman, MD
Date:
Signed:
Roshanak Ramezani, MD
Date:
3

Table of Contents
Table of Contents
4
Key Roles
5
Abbreviations
9
Glossary
9
Background Information
13
Study Device Description
14
Study Objectives
17
Study Endpoints
17
Effectiveness Endpoints
18
Safety Endpoints
18
Study Duration
18
Study Design and Procedures
18
Study Population
22
Inclusion Criteria
23
Exclusion Criteria
23
Data Collection and Storage
24
Potential Risks and Benefits
25
Potential Risks
26
Potential Benefit
26
Adverse Events Reporting
26
Definitions
27
Recording of AEs/ADEs and SAEs/SADEs
28
Follow-up of Subjects after AEs
28
Data Analysis Plan
28
Study Management
29
Investigator, Clinician, and Research Staff Selection
29
Training and Monitoring
29
Informed Consent
29
Participant Withdrawal Criteria
29
Protocol Amendments
30
Study Discontinuation
30
4

Subject Confidentiality
30
Financial Considerations
30
Subject Compensation:
31
Costs to the Subject:
31
Reference List
31
5

Key Roles
Principal
Investigator
Grace Chang
Kintsugi Mindful Wellness, Inc.
1569 Solano Avenue, No. 365
Berkeley, CA 94707
grace@kintsugihealth.com
(310) 598-1553
Co-Investigator
Herbert Harman, MD
Vituity
Herbert.Harman@Vituity.com
(541) 250-6368
Co-Investigator
Roshanak Ramezani, MD
Vituity
Roshanak.Ramezani@Vituity.com
(858) 414 3774
Research
Coordinator:
Mei-Hsin Cheng, PhD
Kintsugi Mindful Wellness, Inc.
1569 Solano Avenue, No. 365
Berkeley, CA 94707
mace@kintsugihealth.com
(650) 762-5087
Research
Coordinator:
Danielle Faruq
Kintsugi Mindful Wellness, Inc.
1569 Solano Avenue, No. 365
Berkeley, CA 94707
danielle@kintsugihealthhello.com
(305) 215-0299
Research
Coordinator:
Alexa Mazur
Kintsugi Mindful Wellness, Inc.
1569 Solano Avenue, No. 365
Berkeley, CA 94707
alexa@kintsugihealth.com
(610) 724-1431
6

Research
Coordinator:
Do Hyung Kim
Kintsugi Mindful Wellness, Inc.
1569 Solano Avenue, No. 365
Berkeley, CA 94707
david@kintsugihealth.com
(314) 745-2316
Research
Coordinator:
Alice Kim
Kintsugi Mindful Wellness, Inc.
1569 Solano Avenue, No. 365
Berkeley, CA 94707
alice@kintsugihealth.com
Research
Coordinator:
Bhavana Sreeram
Kintsugi Mindful Wellness, Inc.
1569 Solano Avenue, No. 365
Berkeley, CA 94707
bhavana@kintsugihealth.com
Research
Associate:
Rima Seiilova-Olson
Kintsugi Mindful Wellness, Inc.
1569 Solano Avenue, No. 365
Berkeley, CA 94707
rima@kintsugihealth.com
Research
Associate
Irina Vanzhula, PhD
Johns Hopkins School of Medicine
ivanzhu1@jhu.edu
7

Abbreviations
AE:
Adverse Event
AI:
Artificial Intelligence
API:
Application Programming Interface
ASADE:
Anticipated Serious Adverse Device Effect
CFR:
Code of Federal Regulations
DSM-5:
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition
FDA:
Food and Drug Administration
GAD-7:
General Anxiety Disorder-7
GCP:
Good Clinical Practice
HCP:
Healthcare Provider
ICF:
Informed Consent Form
IRB:
Institutional Review Board
MDD
Major Depressive Disorder
PHQ-9:
Patient Health Questionnaire-9
PI
Principal Investigator
SAE:
Severe Adverse Event
SCID:
Structured Clinical Interview for DSM Disorders
USADE:
Unanticipated Serious Adverse Device Event
8

Glossary
Term
Definition
Accuracy
Rate of correct predictions made by the
Device on a set of voice samples. Accuracy is
estimated by using independent data that
was not used at any time during the training
process.
AE
An Adverse Event (AE) is any untoward
medical occurrence, unintended disease or
injury, or untoward clinical signs (including
abnormal laboratory findings) in participants,
users or other persons, whether or not related
to the investigational Device.
Algorithm
A process or set of rules to be followed in
calculations or other problem-solving
operations, especially by a computer.
Anxiety Disorders
Anxiety disorders involve anxiety that does
not go away and can get worse over time.
Symptoms can interfere with daily activities.
There are multiple types of anxiety disorders
including generalized anxiety disorder, panic
disorder, and various phobia-related
disorders.
API
The Application Programming Interface is a
type of software interface offering a service to
other pieces of software. The API can be
electronically interfaced and perform analysis
with data transferred from computer-based
applications.
Case Report Form
Printed or electronic document designed to
record protocol-required information on each
participant in a clinical study.
Device
In this protocol, the Device refers to the
Kintsugi Voice Device.
Device Operator
Individual who operates the Device.
Dropout
After consenting to participation in trial (and
therefore enrolling), a study subject
discontinues participation in the trial (e.g.,
due to lack of interest, medical condition,
9

adverse event). Dropout may simply be lost
to follow up.
DSM-5
Diagnostic and Statistical Manual of Mental
Disorders, Fifth Edition; standard
classification of mental disorders for clinicians
for diagnosis of neurobehavioral and
psychiatric disorders.
Endpoint
Key outcome measure in a clinical study.
GAD-7
General Anxiety Disorder-7, a widely used
rating scale to measure the severity of
anxiety based on participant responses to
seven questions.
GCP
Good Clinical Practice.
Ground Truth
Data assumed to be correct by direct
observation or measurement. In this study,
the clinical Ground Truth involves the clinician
evaluation via SCID.
ICF
Informed Consent Form is used to provide
subjects with the information they need to
make a decision to volunteer for a research
study. ICF will include a summary of the
research, potential risks, and potential
benefits.
Indeterminate
The model does not have high confidence to
classify the participant for depression and / or
anxiety. Up to 20% of the results are
expected to be indeterminate.
IRB
The Institutional Review Board is a group that
has been formally designated to review and
monitor biomedical research involving human
subjects.
MDD
Major Depressive Disorder is a mood
disorder that causes a persistent feeling of
sadness and loss of interest. It affects how
you feel, think, and behave and can lead to a
variety of emotional and physical problems.
Also called clinical depression.
ML
Machine Learning is the study of computer
algorithms that can improve automatically
through experience and by the use of data
instead of being explicitly programmed. It is
10

seen as a part of artificial intelligence.
Machine learning algorithms build a model
based on sample data, known as training
data, in order to make predictions or
decisions without being explicitly
programmed to do so.
Phonemes
Distinct units of sounds.
PHQ-9
Patient Health Questionnaire-9 is a widely
used rating scale to measure the severity of
depression based on participant responses to
nine questions.
PI
A Principal Investigator is the individual
responsible for supervising the conduct of the
clinical investigation, including protecting the
rights, safety, and welfare of participants in a
clinical trial.
PII
Personally Identifiable Information. Any
representation of information that permits the
identity of an individual to whom the
information applies to be reasonably inferred
by either direct or indirect means.
SAE
A Serious Adverse Event is an adverse event
that leads to death or serious deterioration in
the health of the participant.
SCID
Structured Clinical Interview is a
semistructured interview guide for making the
major DSM-5 diagnoses.
Sensitivity
Measure of the proportion of participants truly
having clinically significant depression or
clinically significant depression as verified by
a clinician who are correctly identified by the
Device as Positive for depression or anxiety
(or True Positive Rate).
Sensitivity = (True Positive) / (True Positive +
False Negative)
Specificity
Measure of the proportion of participants truly
not having depression or anxiety as verified
by a clinician who is correctly identified by the
Device as Negative for depression or anxiety
(or True Negative Rate).
Specificity = (True Negative) / (True Negative
11

+ False Positive)
Standard of care
Medical or psychological treatment guideline
that specifies appropriate treatment based on
scientific evidence and collaboration between
medical and/or psychological professionals in
the treatment of a given condition.
Study Survey
A web-based study survey that will be
administered to study participants.
12

Background Information
Major Depressive Disorder (MDD) is the leading cause of disability worldwide.1,2 Depression and
anxiety disorders are among the most prevalent of all mental disorders.3 Approximately eight
percent of adults in the United States reported having at least one major depressive episode
and 18.1% of adults in the US have anxiety disorder.3,4 Depression and anxiety disorders are a
frequent comorbidity for patients suffering from chronic medical diseases, such as diabetes,
cancer, and inflammatory bowel disease.5-7 Multiple studies show a 2-3 fold increase in the cost
of treating these chronic conditions, if their depression goes undiagnosed or untreated. Early
detection of disorders is key to both better health and economic outcomes.8 Diagnosing
depression and anxiety can be challenging since there is no current biomarker test used to
detect the possible presence of these conditions. The PHQ-2 / PHQ-9 screener, which can
either be self-administered or administered by a clinician, is the most commonly used diagnostic
instrument. Even though the US Preventive Services Taskforce and the American Academy of
Family Physicians recommend screening in individuals 12 and older,9,10 with the US primary
care visit averaging 16 minutes, mental health screening is frequently skipped,11 and only an
estimated 4.2% of primary care patients are screened for these conditions.
The DSM-5, the standard classification of mental disorders used by mental health professionals
in the US, has definitions for MDD and anxiety disorders. However, reliability of psychiatric
diagnosis is still low, even among psychiatrists.12 Because psychiatric diagnoses are often
based on inferences derived from observation of patient behavior and patient self-reports,
interrater reliability are moderate, typically ranging between kappa values of 0.4 to 0.6.13
Primary care clinicians provide the majority and an increasing percentage of mental health
care.11 If the agreement between psychiatrists, specialists trained specifically on mental health
care is low - the expectation is that it will be even more challenging for primary care clinicians to
diagnose depression and anxiety. According to a global Lancet study, the General Practitioners’
sensitivity is 47.3%.14 Multiple studies describe the underdiagnosis of depression and anxiety,
which is even more pronounced among the more medically disenfranchised demographic
groups such as the elderly and racial minorities.15
Kintsugi, a digital health technology company based in Berkeley was founded to address these
challenges. Kintsugi initially started by creating a consumer application, a voice journaling
wellness app that is available on the Apple App Store. This app allows users to journal by
speaking, interact with community members who share similar challenges, and track their
wellness and mental health over time to promote mental wellbeing. Based upon their preliminary
work and user engagement, the Kintsugi team applied for and was awarded several National
Science Foundation Small Business Innovation Research (SBIR) grants to develop new Artificial
Intelligence (AI) technologies in healthcare. Most recently, the team is developing an AI-based
algorithm that is able to detect signs of depression and anxiety from short clips of free-form
speech. The Kintsugi Voice Device is the result of these efforts.
Voice biomarker technologies provide a unique way to scale access to mental healthcare by
assisting clinicians with the screening and triage especially in high-volume environments where
administrative burdens are high and mental health conditions are often overlooked.
Researchers have attempted to find objective methods to increase the accuracy of depression
and generalized anxiety disorder diagnoses, and voice-based biomarkers are attractive
because of their non-invasive nature and ability to provide passive monitoring.
13

Study Device Description
The Kintsugi Voice Device (“Device”) is a software API that allows the clinician to upload a voice
sample for analysis from an individual ≥ 22 years old. The API can be electronically interfaced
and perform analysis with data transferred from computer-based applications. The Kintsugi
Voice Device output is adjunct to clinical assessment and provides a sensitive reliable estimate
of the presence of vocal characteristics consistent with a significant depressive episode and/or a
clinically significant anxiety state, which are a necessary condition for the diagnosis of lifetime
mood disorders, such as major depressive disorder and/or generalized anxiety disorder. The
Kintsugi Voice Device is not to be used in-lieu of full patient evaluation or relied upon to make or
confirm diagnosis but offers objective signals in the global assessment of mood and anxiety
disorders.
The Device comprises of the following:
●
An API that can be integrated into different clinical workflows. Input of the API is a
patient voice sample that is at least 60 seconds
●
Underlying machine learning algorithm that drives the Device outputs (“Algorithm”)
●
Depression and Anxiety are separate algorithms
The Device output is the following:
●
For depression:
○
The voice sample contains characteristics of depression (the model has high
confidence that the speaker has depression),
○
The voice sample does not contain characteristics of depression (the model has
high confidence that the speaker does not have depression),
○
Indeterminate (the model doesn’t have high confidence to classify the patient as
depressed or not depressed)
●
For anxiety:
○
The voice sample contains characteristics of anxiety (the model has high
confidence that the speaker has anxiety),
○
The voice sample does not contain characteristics of anxiety (the model has high
confidence that the speaker does not have anxiety),
○
Indeterminate (the model doesn’t have high confidence to classify the patient as
anxious or not anxious)
Principles of Operation
The Kintsugi Voice Device technology is based on a large and growing body of research on
voice biomarkers and their ability to detect and predict various neurological and mental
disorders.16–18 Voice biomarkers are a set of acoustic features extracted from voice signals.19
Producing speech involves coordination of various cognitive and motor processes therefore
samples of speech provide insight into the state of physical and mental health. Speech has
14

been studied for a variety of health conditions including dementia, aphasia, Parkinson’s,
Alzheimer’s disease, and various psychiatric conditions.19–24
There have been studies on the relationship between voice and cognitive behavior since the
1920s. Individuals with depression have been reported to have lower pitch, more monotonous
tone, lower sound intensity, and lower speech rate as well as more hesitations, stuttering, and
whispering.25 Longer speech pause times were correlated with depression and the reduction in
speech pause times was used to identify clinical improvement among both unipolar and bipolar
patients with depression.26,27 More recently, Mundt et al. demonstrated in a landmark study of
105 patients that it was possible to collect speech samples from an automated telephone
system and measure the severity of depression and treatment response by using voice
biomarkers.28 Since then, multiple groups have created models to study the effects of
depression on phonemes, which is the unit of sound that can distinguish one word from
another.29,30 Articulatory-phonetic units of speech can capture the effects of different psychiatric
symptoms and be used to deduce the severity of psychiatric symptoms from the human voice.29
In a review of 1395 studies on using speech to identify the presence or severity of cognitive
disorders, Low et al. 2020 analyzed 127 of these studies and synthesized the features that had
predictive power for multiple cognitive disorders, including depression, anxiety, schizophrenia,
and hypomania (Figure 1).31 As shown in Figure 1, every acoustic feature that had predictive
power for depression also had predictive power for anxiety, which serves as the fundamental
basis for the Device’s operation.31
System or Device Components Description
15

The Device is composed of a neural network-based algorithm that analyzes voice recordings to
screen for signs of depression and anxiety. The audio files that are used as input to the
algorithm are recorded by general use computing platforms (e.g., cellphone, tablet, laptop) and
are stored as uncompressed audio in raw form. It is then pre-processed using the following
process:
●
resample the data to match specifications
●
evaluate the quality of the speech sample
●
normalize the loudness of the audio
●
transcode the audio from the original encoding to linear pulse-code modulation
●
trim the pauses at the beginning and end of the audio file
Once processed, vocal features are extracted from the audio and inputted into the neural
network models. The software interprets the acquired signals using signal processing and an
artificial neural network to quantitatively evaluate voice characteristics for presence of indicators
correlated to depression and anxiety. The Kintsugi Voice Device then generates an output for
signs of depression and anxiety which is displayed to the Device Operator. The Kintsugi Voice
Device output will be positive for depression or negative for depression and positive for anxiety
or negative for anxiety. The outcome can also be “uncertain” or within an “indeterminate range”
if the Device cannot provide a high-confidence result.
Study Objectives
This study seeks to evaluate the ability of the Device to aid clinical assessment for depression
and anxiety by comparing its output with the established diagnostic standard consisting of a
diagnosis made by a specialist clinician based on DSM-5 criteria.
This is a prospective study of up to 100 subjects, ages >22 years of age.
We are striving for a 50%/50% split of subjects who have depression and/or anxiety and
subjects who do not have depression and/or anxiety.
16

Study Endpoints
Effectiveness Endpoints
The primary endpoints of this study are to:
1.
Determine the specificity and sensitivity of the Device in discriminating the presence of a
significant depressive episode using the Structured Clinical Interview for DSM-5 Clinical
Trial Version as the established diagnostic standard (“gold standard”)
2.
Determine the specificity and sensitivity of the Device in discriminating the presence of a
clinically significant anxiety state using the SCID-5-CT as the established diagnostic
standard
The secondary endpoints of this study are:
●
Measurement of the percentage of all adults for whom the Device provided no result
●
Determine the specificity and sensitivity of the Device in discriminating the presence
of a significant depressive episode compared to the PHQ-9
●
Determine the specificity and sensitivity of the Device in discriminating the presence of a
clinically significant anxiety state compared to the GAD-7
Safety Endpoints
Adverse events (AEs) and serious adverse events (SAEs) will be collected and reported from
enrollment, which is determined by informed consent signature, through the completion of the
study.
Study Duration
The study is expected to last up to 8 months. The duration of each individual subject’s
involvement in the study will be approximately 2 hours total consisting of a screening call
followed by a psychiatrist clinical evaluation and online survey. However, participants could be
active on the study for up to 2 weeks to schedule a SCID assessment.
17

Study Design and Procedures
This is a prospective fully remote, decentralized clinical study to measure the sensitivity and
specificity of the Device predictions against clinical ground truth for major depressive disorder
and for generalized anxiety disorder. Up to 100 participants will undergo investigational and
comparator assessments for major depressive disorder and a clinically significant anxiety state.
The research coordinator will schedule a time with the participant for the evaluation. There will
be a two-part evaluation: a web-based study survey and a specialist clinician evaluation via the
SCID assessment. The SCID assessment will include questions about the past medical history
of the participant as well as questions from the Clinical Global Impression - Severity scale.
The order of the two evaluations will be randomized to minimize any potential bias.
The Device output will be positive for depression, negative for depression, or indeterminate for
depression and positive for anxiety, negative for anxiety, or indeterminate for anxiety. PHQ-9
and GAD-7 scores will also be collected through the Study Survey.
Participants will also be evaluated by a specialist clinician via the SCID assessment. The
psychiatrist performing the SCID assessment will be a board-certified psychiatrist. The clinical
evaluation via the SCID assessment will be recorded and the channel-separated audio file of
the participant during this assessment will be used as the Device input. The input for the Device
will be obtained by the clinical research team and will be at least one minute of audio taken from
the SCID assessment where the participant is asked about their current illness history and
treatment history. The results of these assessments will act as the clinical comparator for
comparison with the Device output.
Clinicians and participants will both be blinded to the participant the Device output and the
participant assessment results (SCID, PHQ-9, GAD-7). Further, a SCID reviewer may review the
recorded SCID assessment and standard clinical assessment and completed SCID template to
minimize interrater variability.
Subject Identification and Recruitment, Process of Consent
Subjects may be recruited through various mediums including but not limited to social media,
Craigslist, and/or specialized clinical trial recruitment groups. At the time of enrollment, the
mental status of the participant will not be known. Subjects may be recruited from populations
that self-select as interested in mental health. Potential subjects will be provided with detailed
study information so that they are able to make an informed decision.
If subjects wish to enroll, they will need to answer brief pre-screening questions about the
inclusion/exclusion criteria to determine if they meet the study inclusion/exclusion criteria.
Subjects ineligible for the study will be told they do not qualify. Subjects eligible for the study will
receive an informed consent form if they are interested in participating. Participant identity will
be verified before enrollment.
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Participants will then schedule a time for the SCID assessment and to take the web-based study
survey within the same day. Study participants can choose to end participation in the study at
any time. The clinical research coordinator will also answer any questions on the study that
participants have prior to enrollment.
Participants will also provide basic information such as their physical address, emergency
contact, age, and email. Only the necessary participant information and medical history
required for the study will be collected.
Recruitment will continue until up to 100 participants have SCID results or until the Sponsor
terminates the study. The Sponsor may collate interim results at any time during the study to
determine whether the study should continue.
Process of Consent
The participant will be given access to the informed consent from. The informed consent form
serves to ensure that participants understand the purpose of the study, assessments the
participants will be asked to undertake as part of the study, the risks and benefits of
participating, and the voluntary nature of their participation. The informed consent form will
inform the participants that they will provide a recording of their voice and video as part of the
study. The informed consent form will also inform the participants that their specialist SCID
assessments conducted over a HIPAA-compliant video-conferencing platform will be recorded
for the purposes of the study and research. A copy of the consent form will be provided to the
participant after they consent. A clinical research coordinator will be available to answer
participant questions about the study.
Randomization
The order in which the online survey and SCID assessment occur will be randomized. All
participants will participate in investigational (Kintsugi Voice Device) and comparator
assessments (SCID assessment, PHQ-9, and GAD-7).
19

A schematic of the study steps is illustrated in Figure 2.
Participants will be considered enrolled once they have signed the informed consent form.
Participants will receive instructions on completing our web-based Study Survey. If the audio
sample from the SCID assessment is not scorable (e.g. poor microphone quality, insufficient
length, excessive background noise), the participant may be asked to submit an additional audio
sample. A clinical research team member will run the audio sample through the Device.
Participants will fill out the PHQ-9 and GAD-7 questionnaires as part of the Study Survey. The
Device output, PHQ-9, and GAD-7 results will not be shared with the clinicians. Similarly, the
Device output, the PHQ-9, and GAD-7 results will not be shared with the participants.
Participants will complete a SCID assessment immediately after or immediately before the
web-based Study Survey. A clinical research coordinator will be available to support the
participant if they run into issues with the Study Survey.
The SCID assessment will be conducted by a specialist. Specialists will have board certification
in psychiatry and have at least two years of experience diagnosing depressive and anxiety
disorders. Specialists will also undergo psychiatric assessment scoring training for the SCID
assessment prior to providing diagnoses for the study to minimize discrepancies in scoring.
Participants will complete the SCID assessment through a HIPAA compliant teleconferencing
application such as Zoom Meetings. The meeting will be recorded, and the participant will need
to consent to the recording in order to participate in the study. After the SCID assessment, the
specialists will determine a diagnosis based on whether the participant meets the DSM-5 criteria
for Major Depressive Disorder and Generalized Anxiety Disorder.
20

Once the Study Survey (voice sample, PHQ-9, GAD-7) and the specialist-evaluated SCID are
complete, the participant will receive an Amazon gift card of $50 for their time.
21

Study Population
This study will enroll up to 100 subjects >22 years old. Only subjects who meet all eligibility
criteria and sign the informed consent will be enrolled.
Inclusion Criteria
●
Subjects >22 years of age at the time of informed consent
●
Participant must be able to read, understand and sign the Informed Consent Form
●
Access to a laptop, smartphone, tablet, or other Device with a functioning microphone
●
Participants must be willing to be videotaped as part of the study
●
Stated willingness to comply with all study procedures and availability for the duration of
the study
●
Fluency in English
●
Availability for the duration of the study
●
The participant must reside within the state of California
Exclusion Criteria
Participants with at least one of the following conditions will be excluded:
●
Any impairment that would prevent participants from completing an online survey and/or
engage in clinician assessment interviews (e.g., visual impairment, motor impairment,
hearing impairment, acute intoxication)
●
Any known history of neurodegenerative or Central Nervous System disorders
●
Any known history of schizophrenia, psychosis, or severe cognitive deficits
●
Any known presence of disorders that may lead to false signal of depression or anxiety
including Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Parkinson’s Disease, Stroke,
Traumatic Brain Injury
●
Presence of voice disorders that may impact vocal cords such as acute or chronic
laryngitis, vocal cord paresis or paralysis, or spasmodic dysphonia
●
Any known history of vocal cord injury or cerebrovascular accident or head trauma with
residual dysarthria in the past year
●
Past or active heavy smokers if there is impact on the vocal cords
●
Any known history of congenital deafness
●
Subjects who do not speak English
●
Subjects who do not live in the United States
●
Subjects who have previously participated in any Kintsugi-sponsored study.
22

Data Collection and Storage
Data will be retained in accordance with federal and institutional policies. Participants will be
assigned a unique participant ID for de-identification. All data for analysis will be identified by
participant ID number instead of personal identifiable information (PII).
The recruitment data with participant names, phone numbers, emails, location, and emergency
contact will be password protected and only accessible to the research team.
Authorized representatives of institutions participating in the study, the Sponsor, the reviewing
IRB and other groups or organizations that have a role in the study including reviewers of the
structured interviews, regulatory bodies (e.g. the US Food and Drug Administration (FDA),
Department of Health and Human Services (DHHS) agencies) will have access to and may view
a participant’s study information. They will be subject to regulations protecting patient
confidentiality (e.g. HIPAA).
The data repository for this study includes:
●
Device input
o
Voice sample provided as an audio recording
●
Device output
●
Video recording of the diagnostic assessment for clinically significant depression and
clinically significant anxiety according to the DSM-5 criteria (SCID)
●
Results from the PHQ-9 and GAD-7 questionnaire participant self-assessment
●
Medical history relevant to the inclusion/exclusion criteria
At the conclusion of the study, the data will be retained in accordance with institutional policy.
Identifiable data will be kept for 7 years after the completion of the study. De-identified data will
be kept indefinitely.
23

Potential Risks and Benefits
Potential Risks
Risks related to the study are minimal.
The main potential risk to study participants is loss of confidentiality. Measures to protect the
confidentiality of study participants will be implemented as described in the Data Collection and
Storage section.
Participants may feel discomfort answering questions or being interviewed.
An emergency contact will be collected for each participant, in the rare case that there is
imminent danger to the participant as determined by the psychiatrist and, as stated in the
consent, that 911 may be called if the clinician determines there is an emergency. The clinician
will refer the participant to local resources should there be an emergency but will not provide
ongoing care.
Potential Benefit
Knowledge gained from the study could potentially benefit patients in the future.
Participation in this study might lead to identification of clinically significant depression or
clinically significant anxiety, enabling earlier therapy known to positively impact outcomes.
24

Adverse Events Reporting
Definitions
Term
Definition
Adverse Event (AE)
Any untoward medical occurrence,
unintended disease or injury, or untoward
clinical signs (including abnormal laboratory
findings) in participants, users or other
persons, whether or not related to the
investigational Device (ISO 14155-1).
Serious Adverse Event (SAE)
Adverse event that
a) Led to death, b) Led to serious
deterioration in the health of the participant,
that either resulted in 1) A life-threatening
illness or injury, or 2) A permanent
impairment of a body structure or a body
function, or 3) In-patient or prolonged
hospitalization, or 4) Medical or surgical
intervention to prevent life-threatening illness
or injury or permanent impairment to a body
structure or a body function, c) Led to fetal
distress, fetal death or a congenital
abnormality or birth defect (ISO 14155-1).
Anticipated Serious Adverse Device Effect
(ASADE)
An anticipated serious adverse Device effect
(ASADE) is any SAE on health or safety or
any life-threatening problem or death caused
by, or associated with the Device, if that
effect, problem, or death was previously
identified in nature, severity, or degree of
incidence in the investigational plan, informed
consent, operator manual, other risk analysis
documentation or regulatory application; or
any other serious problem associated with
a Device that relates to the rights, safety, or
welfare of subjects.
Unanticipated Serious Adverse Device Effect
(USADE)
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
25

associated with a Device that relates to the
rights, safety, or welfare of participants
21 CFR 812.3(s).
Recording of AEs/ADEs and SAEs/SADEs
All suspected adverse events (AEs) will be evaluated and recorded in the participant’s study
case report form. The AEs/ADEs/SAEs/SADEs may be observed by the investigator and/or
clinical research staff or volunteered by the subject. All observed and volunteered adverse signs
and symptoms, anticipated or unanticipated, regardless of severity or frequency will be recorded
in the case histories (i.e. case report form). The reports of the AEs/ADEs/SAEs/SADEs will
include the description of the event of symptom, date of onset, date of resolution, severity,
anticipated or unanticipated, the relationship to the study Device, the action taken (if any), and
the outcome. AEs/ADEs will be reported to the IRB only if the study clinicians, Dr. Herbert J.
Harman and Dr. Roshanak Ramezani, determine that the event is possibly or definitely related
to the Device. All SAEs/SADEs, anticipated or unanticipated, must be reported to the sponsor
and reviewed by the IRB as soon as possible, but no later than 10 working days after the initial
event was recorded. The study clinicians, Dr. Herbert J. Harman and Dr. Roshanak Ramezani,
will review all adverse events to determine the severity and relationship to study Device.
Follow-up of Subjects after AEs
All reported AEs/ADEs/SAEs/SADEs should be followed until resolution of the event or until the
subject’s participation in the study ends. Resolutions of the events should be documented in the
appropriate case report form.
26

Data Analysis Plan
This is a prospective study with up to 100 subjects who meet the inclusion criteria and who do
not meet any of the exclusion criteria.
The analysis set includes all enrolled subjects who provide a sample of their voice and are
evaluated by a specialist. Device-related adverse events will be tabulated and analyzed.
Study Management
Investigator, Clinician, and Research Staff Selection
Investigator(s) and research staff will be invited to participate in the study based on their medical
specialty and experience conducting clinical research studies. Specialists will have board
certification in psychiatry and have at least two years of experience diagnosing depressive and
anxiety disorders.
Training and Monitoring
Investigator(s) and research staff, including clinical research coordinators and clinicians, will be
trained on the study procedures. Clinicians administering the assessment will also receive
training for the SCID to minimize discrepancies in scoring.
Informed Consent
An IRB-approved informed consent document will be provided to subjects through an electronic
signature software tool. Subjects must sign the informed consent document before they can
participate in the Study Survey or participate in a clinician evaluation. Clinical research
coordinators will inform the subjects on the purpose of the study, expected duration, potential
risks and benefits from the study, as well as making it clear that participants are free to refuse
participation in this clinical study.
Participant Withdrawal Criteria
Participation in this study is voluntary and participants can withdraw from the study at any time.
In order to withdraw, a participant will need to:
1.
Call or email the research coordinator.
2.
Let the research coordinator know about their intention to withdraw.
A participant that withdraws from the study prior to completion of study will not be paid.
27

A subject will be considered lost to follow up after 2 unsuccessful attempts to contact the
subject.
If a participant withdraws from the study prior to its completion, their data will not be deleted;
they will still be used for the research study.
Protocol Amendments
Any amendments to this study protocol must be communicated clearly in writing, signed, and
dated by the sponsor and the principal investigator. IRB approval will be obtained for all study
amendments.
Study Discontinuation
The study Sponsor has the right to terminate this study at any time.
Subject Confidentiality
This study preserves the confidentiality of all subjects under the Health Insurance Portability and
Accountability Act of 1996 (HIPAA) Privacy Rule. The following safeguards will be in place to
protect the privacy of the individuals who are the subjects of the health information to be used in
the research and the confidentiality of that information: The subjects will be informed by the
investigator or the investigator’s designee that their medical records will be kept as confidential
as possible but may be subject to review by: (1) Kintsugi, or its representative; (2) reviewing
IRB; and/or (3) by appropriate regulatory bodies (e.g. the US Food and Drug Administration
(FDA), Department of Health and Human Services (DHHS) agencies).
Only minimum personal information required for purposes of the study will be collected. The
personal information will be collected and used to ensure subject eligibility for study
participation, to conduct the study, and to provide compensation to participants after completion
of the study requirements. Permission to use or disclose personal information, except for that
has been collected and relied on may be canceled by the subject by written notice. If the subject
is withdrawn from the study, the information collected to that time may still be used to preserve
the scientific integrity of the study. There is no expiration date to this authorization.
Subjects’ identities will be kept confidential. Subjects will be assigned a unique study code that
will not reveal the subjects’ identity, and this code will be used on all study documents.
28

Financial Considerations
Subject Compensation:
The participant will be compensated $50 for their participation upon completion of both the
Study Survey (PHQ-9 and GAD-7) and the specialist clinical evaluation.
Costs to the Subject:
The specialist clinician evaluation will be covered by the Company sponsoring the study. Any
additional services will not be covered by the sponsor.
Clinician / Specialist Compensation:
Specialist clinicians will be compensated by the clinician evaluations / assessments they
complete. Reviewing specialist clinicians will be compensated per independent review of cases.
29

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