Lenire User Experience Group Study - Report 1 - Cohort Analysis 20200131 PDF

Lenire User Experience Group Study – Report 1
Cohort Characteristics and Analysis
@PeterPan
TinnitusHub
31st January 2020
Introduction
The Lenire User Experience Group (LUEG) Study is a patient-lead study aimed at helping to
understand the effectiveness of a recently released device for treating tinnitus known as the Lenire.
Lenire is a “bi-modal” device meaning that it delivers both sounds and electrical impulses to patients
as its method of action in treating tinnitus. It is sold by Neuromod devices, a small company with a
head office located in the Republic of Ireland. Neuromod have conducted their own extensive trials
on the efficacy of the device, and information about the design of these trials may be found in [6]
and [7]. The results of the trials have, at the time of writing, not been published.
Data for this LUEG study has been mostly obtained from members of TinnitusTalk, a popular tinnitus
forum, who have purchased the device and volunteered to share their treatment experience in an
objective way. Participants have been asked to complete an online questionnaire that captures their
baseline characteristics at the commencement of the treatment and their experiences at 6 and 12
weeks from this date. The study is being conducted over the period between July 2019 to April 2020
and consists of 43 patients. Data from patients continues to be collected beyond April 2020, and
these reports may be updated from time to time as more data is received.
This report (Report 1) looks at the characteristics of the study participants (the patients), and
mainly represents an analysis of pre-treatment “day 0” data.
The next report (Report 2) will examine the effects of the Lenire treatment on the patient’s tinnitus
at the treatment milestones and is anticipated to be completed around April 2020. Report 1 will be
of assistance in understanding the second report on treatment effects.
The intended audience for these reports is TinnitusTalk members and others interested in tinnitus,
particularly persons afflicted with tinnitus. This report does include statistical techniques that may
be difficult to understand for those without a statistics background, and as such, we recommend:
• Those readers who would just like see the summary of the report findings, can just read
Section 1: Executive Summary.
• Those readers who would like some additional information about the patient characteristics
but who do not feel comfortable with statistics can also read Section 3. This section
describes the questionnaire and provides the results in the form of charts. We do mention
means and standard deviations1 in this section.
• Those who would like to tackle the statistics sections in order to get a better understanding
of the statistical significant results mentioned in the Executive Summary, you can read
sections 4 and 5. If you do not have a statistics background, to get the most out of these
sections we recommend you read Appendix 2 and the references in Appendix 4 in advance.
While this series of reports mainly focuses on a statistical approach to understanding the
effectiveness of the Lenire, there are alternatives. This thread on the TinnitusTalk forum provides
1
The standard deviation of a sample is a measure of the sample spread. If the sample is from a normal
distribution, 68% of the values will typically fall within the mean +/- one standard deviation and 95% within 2
standard deviations either side of the mean. A normal distribution is bell shaped and used to model a wide
variety of phenomena.
1
subjective feedback from users of the device and is also a useful resource as it provides a different
perspective on the effectiveness of the Lenire .
This study is managed and staffed by volunteers from TinnitusHub, a not-for-profit patient
organization that is passionate about improving the lives of tinnitus patients.
2
Contents
Introduction ........................................................................................................................................ 1
Table of Figures ................................................................................................................................... 4
Tables .................................................................................................................................................. 5
Thanks ................................................................................................................................................. 5
Section 1: Executive Summary ............................................................................................................ 7
Section 2: Some Terminology ............................................................................................................. 9
Section 3: Results from the Questionnaire ....................................................................................... 10
Section 4: Tinnitus and patient characteristics ................................................................................. 39
Section 5: Relationships between patient characteristics ................................................................ 42
Section 6: A Word on the Next Report ............................................................................................. 47
References ........................................................................................................................................ 49
Appendix 1 - Summary of Factors Studied........................................................................................ 50
Appendix 2 - Statistical Techniques .................................................................................................. 51
Appendix 3 – Report Caveats ............................................................................................................ 53
Appendix 4 – Suggested Viewing - Statistics..................................................................................... 54
3
Table of Figures
Figure 1 - TFI Distribution at Baseline ................................................................................................... 11

Figure 2 - Country of origin for patients ............................................................................................... 12
Figure 3 - TFI Versus Age Scattergram .................................................................................................. 13
Figure 4 - Age and TFI Bar chart ............................................................................................................ 14
Figure 5 - TFI Versus Gender Scattergram ............................................................................................ 15
Figure 6 - Gender and TFI Bar chart ...................................................................................................... 15
Figure 7 - TFI Versus Duration Scattergram .......................................................................................... 16
Figure 8 - Duration and TFI Bar Chart ................................................................................................... 17
Figure 9 - Cause of Tinnitus................................................................................................................... 18
Figure 10 - TFI Versus Self-Assessed Severity Rating Scattergram ....................................................... 19
Figure 11 – Self Assessed Tinnitus Severity Rating and TFI Bar chart ................................................... 19
Figure 12 - TFI Versus Loudness Scattergram ....................................................................................... 20
Figure 13 - Tinnitus Loudness and TFI Bar Chart................................................................................... 20
Figure 14 - TFI Versus Intermittency Scattergram ................................................................................ 21
Figure 15 - Intermittency and TFI Bar Chart ......................................................................................... 21
Figure 16 - TFI Versus Hyperacusis Scattergram ................................................................................... 23
Figure 17 - Hyperacusis and TFI Bar Chart ............................................................................................ 24
Figure 18 - TFI Versus Hearing Loss Scattergram .................................................................................. 25
Figure 19 - Hearing Loss and TFI Bar Chart ........................................................................................... 26
Figure 20 - TFI Versus Somatic Modulation Scattergram ..................................................................... 26
Figure 21 - Somatic Modulation and TFI Bar Chart ............................................................................... 27
Figure 22 - TFI Versus Source Scattergram ........................................................................................... 28
Figure 23 - Source and TFI Bar Chart..................................................................................................... 28
Figure 24 - TFI Versus Reactivity Scattergram ...................................................................................... 29
Figure 25 - Reactivity and TFI Bar Chart ................................................................................................ 29
Figure 26 - TFI Versus Variation within a Day Scattergram .................................................................. 30
Figure 27 - Variation within a Day and TFI Bar Chart ............................................................................ 30
Figure 28 - TFI and Variation Between Days Bar Chart ......................................................................... 31
Figure 29 - TFI and Variation Between Days Bar Chart ......................................................................... 31
Figure 30 – Type of Tinnitus Sound....................................................................................................... 32
Figure 31 - TFI Versus Pitch Scattergram .............................................................................................. 33
Figure 32 - Pitch and TFI Bar Chart........................................................................................................ 33
Figure 33 - Other Treatments ............................................................................................................... 35
Figure 34 - Lenire and Patient Monthly Income ................................................................................... 36
Figure 35 - Neuromod Satisfaction ....................................................................................................... 37
Figure 36 - Example ANOVA .................................................................................................................. 39
Figure 37 - Example Linear Regression/Pearsons Correlation .............................................................. 42
Figure 38 – Loudness versus TFI with confidence intervals .................................................................. 43
4
Tables
Table 1 – Classifying Tinnitus Duration ................................................................................................. 16

Table 2 - Classifying Hearing Loss ......................................................................................................... 25
Table 3 - Classifying Source of Tinnitus ................................................................................................. 27
Table 4 - Tukey HSD - Average TFI and Loudness ................................................................................. 40
Table 5 - One-Way Anova Results ......................................................................................................... 40
Table 6 - Linear Regression p-values for between-factor regressions .................................................. 44
Table 7 - Linear Regression R2 values for between-factor regressions ................................................ 44
Table 8 - Linear Regression Slope Coefficient values for between-factor regressions ......................... 45
Table 9 - Summary of Factors Studied .................................................................................................. 50
5
Thanks
TinnitusHub would like to offer thanks to the following personnel who contributed to this report:
@Hazel and @Markku: Hazel and Markku participated in the design of the questionnaire, invited
university researchers to review the questionnaire prior to release, helped with reminding members
to complete their surveys, and provided overall guidance and assistance.
TinnitusTalk forum members: for offering their valuable time to respond to the survey and share
their experiences.
University Researchers for reviewing the questionnaire and providing valuable feedback.
Expert Forum Members and their relations who have donated their valuable time in reviewing the
statistical component of this report.
@PeterPan: Yours truly, the author of this report and project manager of the study.
6
Section 1: Executive Summary

It is important to note that this report does NOT look at the effectiveness of the Lenire in any way.
Report 2 will serve this function.
There are many caveats related to this study. Refer to Appendix 3 for details.
This study is useful to read as a pre-cursor to the second report and enables the reader to become
familiar with the questionnaire we used, the terminology used, some of the statistical techniques
used in the next report, and the characteristics of the patients participating in the study. Here are
our findings on our patient sample:
• A total of 43 patients signed-up for the study and provided baseline tinnitus data. The
average age of the patients was 41.6 and the standard deviation was 11.5. The youngest was
21 and the oldest 68. The average duration of tinnitus was 6.3 years, and the duration
standard deviation was 7.6. 58% of patients originated from either the UK, the US or Ireland.
• The sample size is quite small and may make it difficult to arrive at reliable statistical
conclusions relating to changes as a result of treatment.
• Of the 43 patients, 40 provided a TFI score at baseline. TFI is a popular method of capturing
tinnitus severity and was optional in this survey.
• The average TFI rating for the patients who provided it was 45.9, and the standard deviation
19.0. The lowest was 9.8 and the highest 96. Patients reported a variety of causes for their
tinnitus, with the most common being related to acoustic trauma or noise-induced hearing
loss.
• We had many more males (34) respond to the questionnaire than females (9). Female
tinnitus severity showed a much higher average value and a much higher variability than
male responses. More details here and section 4.
• The questionnaire we used to capture patient information was well designed in the sense
that in most cases there was a reasonably even distribution of question responses across the
possible options presented to the patients. More details in section 3.
• Patients’ experience with Neuromod during their initial appointments was positive, with an
overall experience rating of 4.4/5. More details here.
• When comparing the TFI group (e.g Male, Female) means within a factor (e.g. Gender) these
means were statistically significantly2 different within the “Gender”, “Loudness” and
“Severity” factors and no others. For more details refer to section 4 and for a list of all
factors considered refer to Appendix 1.
• When comparing the patient characteristics (factors) with each other and with their TFI
score, we saw some statistically significant correlations:
2
It’s important to distinguish between “Statistical Significance” and “Clinical Significance”. A result with
Statistical Significance means that the result would have a small probability of occurring due to random
chance. A result can have statistical significance but be too small to have any practical value. A clinically
significant result is one which makes a difference to the patient. The smallest amount that would make a
difference is called the minimally clinically important difference or MCID. The smallest amount of difference in
tinnitus that would make a difference is discussed further in the report.
7
o Reduced intermittency was correlated with a higher TFI, increased duration,

increased age, higher pitch, increased perceived loudness and increased perceived
severity.
o Hearing Loss was correlated with age.
o Higher pitch was correlated with increased loudness and severity.
o Increased loudness and severity were correlated with higher TFI and with each
other.
These relationships can be further investigated in section 5. These relationships will be

important to consider when we look at any relationships between factors and TFI changes in
the next report.
8
Section 2: Some Terminology
This report frequently mentions factors and groups, and it is important to understand how they are
used.
A factor is a characteristic of the patient population that is of interest. In this report, examples of
factors are age, tinnitus duration, gender, hyperacusis etc.
Within each factor, patients are divided into groups, dependent on how they respond to
questionnaires, or how we have divided them up as part of this study. Thus, for example, within the
“Gender” factor there are Male and Female groups. Within the “Hyperacusis” factor there are None,
Mild, Moderate, Severe groups. For the “Age” factor, we have, for the purposes of some tests,
divided patients into <30, 30-39, 40-49, >50 groups.
Understanding how these terms are used should help with interpreting this (and the next) report.
9
Section 3: Results from the Questionnaire

In this section we examine the response to each of the relevant survey questions and the TFI
characteristics of the patient groups defined by the possible survey responses. TFI, or Tinnitus
Functional Index, is an established measure of the severity of tinnitus. More information about the
TFI may be found in [3] and in the text box below.
We asked a series of questions designed to capture TFI near the end of the day-0 survey. We present
the response to these questions first, and then the remainder of the questions relevant to this study
in accordance in the order in which they were asked. We do this because subsequent analysis for
each question discusses TFI.
When capturing TFI information, we firstly asked the question below:
Are you willing to complete the Tinnitus Functional Index? This will take about 5
minutes. It consists of 25 simple questions to get a more detailed assessment of your
tinnitus severity. If you complete this section now, you will be asked to repeat the TFI
again mid- and post-treatment; this will help us to assess how your severity has
changed due to the treatment
If the patient agreed to complete the TFI, they were then presented with the 25 questions
representing the standard Tinnitus Functional Index questionnaire. You can see the TFI
questionnaire here. An analysis of the responses can be used to generate the TFI score of between 0
and 100. This score is an indicator of tinnitus severity.
The patient could elect not to answer the TFI questions. The TFI questions were made optional in
order to help with reducing the drop-out rate. Of the 43 responses we received, 40 provided TFI
responses. A compulsory question on tinnitus severity described later in this report was included in
the questionnaire with the intention that this could be used instead of TFI if necessary.
In order to improve the quality of the response at subsequent checkpoints, when this question was
asked at these checkpoints, we asked patients not to refer back to their original responses:
“When filling in this section, please DO NOT look back to your answers from Part 1, as this may
influence your answers for Part 2.”
10
More information on TFI
TFI is used throughout these studies so it is important to get a good understanding of what it
measures and its characteristics. TFI is designed to measure the severity of tinnitus. According to
[3], the TFI correlates well with the THI (an alternate measure of tinnitus severity and also used in
the Neuromod studies). In addition, in the study completed by the TFI authors, patients’ responses
to this query “How much of a problem is your tinnitus” averaged the following TFI scores:
Response Mean TFI Standard Deviation

Not a problem 14 12
A small problem 21 10
A moderate problem 42 16
A big problem 65 15
A very big problem 78 16
This gives an idea of the meaning of a TFI score. The authors also report another way to interpret
the TFI: A score of 25 or less indicates relatively mild tinnitus and little need for intervention, 25-50
significant problems with tinnitus and possible need for intervention, and 50 or greater indicates
“tinnitus severe enough to qualify for more aggressive intervention”.
In Report 2, for some of the tests, we want to know if a meaningful reduction in tinnitus severity
has occurred. According to [3], “After careful evaluation, a 13-point reduction was considered a
preliminary criterion for meaningful reduction in TFI outcome scores.”. We use this “meaningful
reduction” criterion when considering if a patient has had a change in their tinnitus.
Here is the distribution of responses to the TFI question at baseline:
TFI Distribution at Baseline

12
10
8
Frequency
6
Baseline
4
0
0-12.5 12.5-25 25-37.5 37.5-50 50-62.5 62.5-75 75-87.5 87.5-100
TFI
Figure 1 - TFI Distribution at Baseline
11
Note that 0-12.5, for example, means greater than equal to 0 and less than 12.5.
The average TFI score is 45.9, the 25th percentile is 37.0, the 75th percentile is 52.8 and the standard
deviation is 19.0. According to the TFI authors, the average of 46 can best be described as a
“moderate problem”.
Here are the remainder of the study-relevant questions and their responses, in the order in which
they are asked:
In which country do you live?
Figure 2 - Country of origin for patients
Most patients originate from the UK and approximately 58% originated from either the US, the UK or
Ireland. At present the only place in the world to get access to Lenire is in Dublin, Ireland. Each
patient must travel to Ireland four times to get the benefit of the full treatment.
What is your Age?
Patients were asked to provide their actual age (rather than an age range).
12
TFI versus Age

100
90
80
70
60
TFI
50
40
30
20
10
0
0 10 20 30 40 50 60 70 80
Age
Figure 3 - TFI Versus Age Scattergram
This scatter plot contains a dot for each patient response. So, for example, the dot highlighted in red
above represents a patient who is 23 years of age and has a TFI of about 18. You can see there
doesn’t appear to be much relationship between age and TFI in our sample3.
The average age of patients in the cohort is 41.6 and the standard deviation is 11.5. The youngest
was 21 and the oldest 68.
We classified Age into four categories to assist with performing some of the statistical tests (and
used the raw age for others).
3
It’s important to note that a lack of a relationship between tinnitus and age in our sample does not provide
support for the hypothesis that there is no relationship between tinnitus and age for the general tinnitus
sufferer. This is because we are drawing our sample from people who have severe enough tinnitus to decide to
use the Lenire. This could introduce many biases in the sample. For example, different age groups may have
different motivation levels to remedy their condition or may have different income levels and differing levels
of ability to purchase the Lenire. More importantly, only those people with more severe tinnitus are likely to
be motivated to seek this type of treatment so less severe sufferers in each age group will be likely to be
filtered out. In order to determine if there is a relationship in general, we would need to survey the general
population (something which some studies have attempted to do). The same can be said of any other factors
in the study. More information on relationships in the general population can be found in [1], [4] and [5].
13
Age and TFI

70
75th Percentile
60
25th Percentile
50
40
TFI
30
20
10
0
< 30 30-39 40-49 >50
TFI 53.4 41.0 47.3 44.4
N 7 9 13 9
Figure 4 - Age and TFI Bar chart
The diagram shows the average TFI for each of four age categories. It also shows the number in each
category (“N”) and the 25th and 75th percentiles for the TFI.
Thus, for example, for the group highlighted in red above, we had 14 people between 40 and 49
inclusive, the average TFI was 47.8, the 25th percentile for this group (the lower part of the error bar)
is 40.1 and the 75th (the upper part of the error bar) is 56.49. Note that the 25th percentile is the
lowest value below which at least 25% of patients may be found (with a similar definition for 75th
percentile).
14
What is your gender?
TFI versus Gender

100
90
80
70
60
TFI
50
40
30
20
10
0
Male Female
Gender
Figure 5 - TFI Versus Gender Scattergram
Gender and TFI

80
70
60
50
TFI
40
30
20
10
0
Male Female
TFI 41.71 63.25
N 30 8
Figure 6 - Gender and TFI Bar chart
There were many more male patients than females, and the TFI rating and variation for females was
considerably higher than for males. Tinnitus in general is more prevalent in males and this may be
due to occupational hazards.
15
How long have you had tinnitus?
Patients were asked to select one of the items in the first column below in response to this query.
For the purpose of the statistical analysis in Section 3, people were moved into one of the four
groups in the second column below. For the purpose of the statistical analysis in Section 4, the
midpoint of the original interval, as per the third column below, was used. Report 2 also uses these
statistical techniques.
Questionnaire Section 3 Section 4

Up to 3 months 0-12 Months 0.13
4-6 months 0-12 Months 0.42
6-12 months 0-12 Months 0.75
1-2 years 1-3 Years 1.50
5-10 years 5 Years or More 7.50
10-20 years 5 Years or More 15.00
More than 20 years 5 Years or More 25.00
Table 1 – Classifying Tinnitus Duration
TFI versus Duration

100
90
80
70
60
TFI
50
40
30
20
10
0
< 1 Year 1-3 Years 3-5 Years > 5 Years
Duration
Figure 7 - TFI Versus Duration Scattergram
16
Duration and TFI

70
60
50
40
TFI
30
20
10
0
< 1 year 1-3 years 3-5 years > 5 years
TFI 54.29 38.45 40.32 44.91
N 12 6 5 15
Figure 8 - Duration and TFI Bar Chart
The average duration of tinnitus was approximately 6.3 years, and the standard deviation was 7.6.
There doesn’t seem to be much relationship between the severity of tinnitus and duration in our
sample. We can see that the TFI in the first year seems to be quite high.
What do you believe is the cause of your tinnitus?
Patients were asked to select a response indicating the cause of their tinnitus. Patients could select
more than one.
17
18
Other (please specify)

Virus (ear infection, flu, cold)
TMJ (issues with the jaw)
Sudden hearing loss
Psychological (stress, anxiety, depression)
Ototoxic (from drugs or medication)
Otosclerosis
Noise-induced hearing loss (continued noise exposure, occupational noise)
Figure 9 - Cause of Tinnitus

Cause of Tinnitus
Metabolic (diabetes, thyroid, B12, hyperlipidaemia etc.)

Meniere's
Head or neck injury
Ear wax procedure (syringing, candling or other related procedure)
Ear wax build up
Dental treatment
Barotrauma (due to change in barometric or water pressure)
Allergy
Age-related hearing loss
Acoustic trauma (explosion, exposure to gunfire or extremely loud, sudden…
40% Don't know the cause
35%
30%
25%
20%
15%
10%
5%
0%
How do you rate the Severity of your Tinnitus?
This is the question which provides an alternative severity measure to the TFI questionnaire. Patients
were asked to select one of Borderline Tinnitus, Mild Tinnitus, Moderate Tinnitus, Severe Tinnitus,
Substantial Tinnitus or Catastrophic Tinnitus.
TFI versus Tinnitus Severity Rating

100
90
80
70
60
TFI
50
40
30
20
10
0
Borderline Mild Moderate Substantial Severe Catastrophic
Tinnitus
Rating
Figure 10 - TFI Versus Self-Assessed Severity Rating Scattergram
Tinnitus Severity Rating and TFI

120
100
80
TFI
60
40
20
0
Borderline Moderate Substantial Catastrophic
Mild Tinnitus Severe Tinnitus
Tinnitus Tinnitus Tinnitus Tinnitus
TFI 0.00 40.16 35.27 49.29 55.21 96.00
N 0 3 13 13 8 1
Figure 11 – Self Assessed Tinnitus Severity Rating and TFI Bar chart
19
Note that we cannot see the percentile bars for borderline, mild and catastrophic tinnitus as there is
insufficient data. You can also see there appears to be a relationship between TFI and severity rating
in our sample (which we would expect), however there are some anomalies which suggest that the
descriptors may not be a good means of capturing severity on an ordinal scale.
How do you rate the loudness of your Tinnitus over the last week?
Patients were asked to select one of these responses: Very Quiet, Quiet, Moderate, Loud, Very Loud.
TFI Versus Loudness

100
90
80
70
60
TFI
50
40
30
20
10
0
Quiet Moderate Loud Very Loud
Loudness
Figure 12 - TFI Versus Loudness Scattergram
Tinnitus Loudness and TFI

90
80
70
60
50
TFI
40
30
20
10
0
TFI 23.42 41.62 50.23 81.44
N 4 16 15 3
Figure 13 - Tinnitus Loudness and TFI Bar Chart
20
TFI appears to be closely related to loudness in our sample. That is, if your tinnitus is perceived as
loud, you are likely to report a high TFI score. Note that no-one reported “Very Quiet” tinnitus.
How often did you hear your Tinnitus in the last week?
TFI Versus Intermittency

100
90
80
70
60
TFI
50
40
30
20
10
0
I did not I heard it I heard it about I heard it I heard it all
hear it occasionally 50% of the time most of the… the time
Most Intermittent to least intermittent
Figure 14 - TFI Versus Intermittency Scattergram
Intermittency and TFI

70
60
50
40
TFI
30
20
10
0
I heard it I heard it about I heard it most of I heard it all the
I did not hear it
occasionally 50% of the time the time time
TFI 0.00 31.04 37.87 46.68 53.54
N 0 2 10 11 15
Figure 15 - Intermittency and TFI Bar Chart
21
In our sample, it appears that Tinnitus severity increases with reduced intermittency.
Please provide some feedback about how your experience of tinnitus during the last
week and how it is affecting your life.
Some responses to this question are shown below:
“As always, over everything else, loud and bothering. It s impossible to mask it totally but I m always
using cricket sounds to ease the stress.”, Male, 45
“Tinnitus is a constant, worse when going to sleep and upon awakening. Only time it is better is when
I concentrate on other things and try to forget about it. I generally strive to not let it affect me, but
this it is still a constant source of irritation.”, Male, 49
“Not nearly as annoying now as it was when it worsened in May 2019. it's now most bothersome
when I want to listen to music or a movie and thus am concentrating on listening. I also hear it in bed
of course, and sitting in a quiet meeting room.”, Male, 35
“If I don't mask it with specific sounds i hear it almost everywhere.”, Male 27
“I have generally adapted to it pretty well all things considered, but it is loud, distracting, constant. It
limits some of my social interaction, patience, and consecration. When it get bad I have trouble
hearing.”, Male, 49
“It is usually at its highest during mid-afternoon and generally settles down a bit in the evening.”,
Male, 61
“The tinnitus is always there, it makes me afraid that it may get worse.”, Female, 58
“I find it very difficult to think about anything else than my tinnitus. While not very loud during the
day it is very difficult to mask and I have not yet habituated after last year's worsening.”, Male, 44
“Tinnitus implies distraction and anxiety (not always though i have periods of time without anxiety).
It messes up with my thinking pattern, I have OCD around tinnitus, I think about it whole day even
when I don't hear it. I need to be actively engaged in other activity/task to refocus my attention and
thoughts away from it”, Male, 40
“Tinnitus affects my life greatly. I think about it all the time and it has affected many relationships in
my life.”, Male, 41
“It’s difficult for me to deal with tinnitus. The intensity can vary depending on the days...”, Female, 34
“During working hours my I don’t notice my tinnitus. I am able to forget I have it when I am
concentrating on work. Out of working hours I find it difficult to relax and not concentrate on my
tinnitus. Some days I find it easier, others are more difficult.”, Male, 24
“My tinnitus is always the same, I tend to focus on it in quiet environments and consequently at
night, before going to sleep.”, Male, 57
22
“Screaming - feeling concerned about the future and unable to work.”, Female, 44
“Fluctuates. When its good, I'm good. When its bad, life is a nightmare I no longer want to be a part
of.”, Male, 51
“Tinnitus is always there, in and around the house, out the house in the garden or trips to shops. In a
lot of cases I can ignore it and my attention is drawn away from the ringing but it frequently spikes
for no reason for a number of seconds at a time which brings my attention back to it. Can be very
distracting and very uncomfortable when trying to sleep. Previous week it has been relatively quiet
with no major spikes which is a vast improvement on the week before. Unsure as to what has
contributed to this.”, Female, 58
“All-consuming, getting louder to the point that conversations are hard to focus on and mis words.”,
Male, 50
Do you have hyperacusis (reduced tolerance or increased sensitivity to everyday

sounds)?
TFI Versus Hyperacusis

100
90
80
70
60
TFI
50
40
30
20
10
0
No Mildly Moderately Severely
Hyperacusis Severity
Figure 16 - TFI Versus Hyperacusis Scattergram
23
Hyperacusis and TFI

100
90
80
70
60
TFI
50
40
30
20
10
0
None Mildly Moderately Severely
TFI 42.43 43.76 61.10 86.32
N 13 20 4 1
Figure 17 - Hyperacusis and TFI Bar Chart
There doesn’t seem to be a strong relationship between TFI and hyperacusis in our sample.
Hyperacusis should makes tinnitus more unpleasant, but this isn’t coming out in the numbers
(maybe those who have hyperacusis have less severe tinnitus, or maybe we don’t have enough
data.).
How is your hearing in your right ear? If you're not sure, just give us your best
approximation.
How is your hearing in your left ear? If you're not sure, just give us your best
approximation.
We asked two questions about the severity of hearing loss, one about each ear. Patients were asked
to respond with No hearing loss, Mild Hearing Loss, Moderate Hearing Loss or Severe Hearing Loss.
This question is self- assessed and definitely could have benefited from being captured in a clinical
setting, but unfortunately this was not possible.
Because hearing loss is quite a critical component of this study, I came up with a figure for hearing
loss in four different ways. All of them involved assigning a 1 to no hearing loss, 2 to mild hearing
loss, 3 to moderate hearing loss and 4 to Severe Hearing Loss. Different methods will be used in
different statistical tests.
24
# Description Method
1 Average and Add up left and right scores, divide by 2 and
then round up round up.
2 Average Add up left and right scores, divide by 2
3 Maximum Take the maximum of the left and right
score. This corresponds to the worst ear.
4 Minimum Take the minimum of the left and right
score. This corresponds to the best ear.
Table 2 - Classifying Hearing Loss
We present the results here using method 1.
TFI Versus Hearing Loss

100
90
80
70
60
TFI
50
40
30
20
10
0
No Hearing Mild Hearing Moderate Severe Hearing
Loss Loss Hearing Loss Loss
Hearing Loss Severity
Figure 18 - TFI Versus Hearing Loss Scattergram
25
Hearing Loss and TFI

70
60
50
40
TFI
30
20
10
0
Moderate Hearing Severe Hearing
No Hearing Loss Mild Hearing Loss
Loss Loss
TFI 49.84 45.12 40.53 0.00
N 12 23 3 0
Figure 19 - Hearing Loss and TFI Bar Chart
In our sample, there doesn’t seem to be much relationship between hearing loss and TFI.
Are you able to change the volume or pitch of your Tinnitus via somatic modulation (e.g.
jaw or neck movement)?
Patients were asked to respond with yes or no.
TFI versus Somatic Modulation

100
90
80
70
60
TFI
50
40
30
20
10
0
Somatic Non Somatic
Tinnitus Type
Figure 20 - TFI Versus Somatic Modulation Scattergram
26
Somatic and TFI

70
60
50
40
TFI
30
20
10
0
Somatic NonSomatic
TFI 43.73 53.29
N 28 10
Figure 21 - Somatic Modulation and TFI Bar Chart
Where does your tinnitus appear to (mostly) come from?
Patients were asked to respond with one of Left Ear, Right Ear, Both Ears, Inside my Head, Inside my
Head and From my Ears, Other (please specify). For the purpose of analysis, these were further
classified as per the below:
Original Question Classification

Left Ear Single Ear
Right Ear Single Ear
Both Ears Both Ears
Inside my Head Inside Head
Inside my head and from my ears Inside Head
Other (please specify) Other
Table 3 - Classifying Source of Tinnitus
27
TFI Versus Source

100
90
80
70
60
TFI
50
40
30
20
10
0
Single Ear Both Ears Inside my Head Other
Source of Tinnitus
Figure 22 - TFI Versus Source Scattergram
Source and TFI

80
70
60
50
TFI
40
30
20
10
0
Single Ear Both Ears Inside my Head Other
TFI 43.60 44.90 46.35 58.54
N 16 6 12 4
Figure 23 - Source and TFI Bar Chart
For those who reported that tinnitus was from a single ear, 14 reported the left ear and 4 the right
ear.
28
Is your Tinnitus reactive to noise?
TFI Versus Reactivity

100
90
80
70
60
TFI
50
40
30
20
10
0
Some sounds
Some sounds Sounds don’t Mixture - some Some sounds Some sounds
make it a lot
make it a little really affect me sounds make it make it a little make it a lot
worse
worse better and some better better
worse
Tinnitus Reactivity
Figure 24 - TFI Versus Reactivity Scattergram
Reactivity and TFI

80
70
60
50
TFI
40
30
20
10
0
Mixture - some
Some sounds Some sounds Some sounds Some sounds
Sounds don’t sounds make it
make it a lot make it a little make it a little make it a lot
really affect me better and some
worse worse better better
worse
TFI 57.19 51.69 38.91 37.25 41.60 23.44
N 11 8 10 7 1 1
Figure 25 - Reactivity and TFI Bar Chart
29
Is your Tinnitus different at different times of the day?
TFI versus Variation within a Day

100
90
80
70
60
TFI
50
40
30
20
10
0
It doesn’t It's less It's less It fluctuates but
bothersome in bothersome Other (please
change at all there is no
the morning in the evening specify)
pattern
Ttinnitus Variation within a Day
Figure 26 - TFI Versus Variation within a Day Scattergram
Variation within a Day and TFI

70
60
50
40
30
20
10
0
It's less It's less It fluctuates but
It doesn’t change Other (please
bothersome in bothersome in there is no
at all specify)
the morning the evening pattern
TFI 45.11 42.57 37.24 47.75 50.39
N 7 9 1 14 7
Figure 27 - Variation within a Day and TFI Bar Chart
30
Does your Tinnitus vary from one day to the next?
TFI versus Variation Between Days
100
90
80
70
60
TFI
50
40
30
20
10
0
No, it's constant Some Variation Significant
all the time from Day to Day Variation from
Day to Day
Tinnitus Variation Between Days
Figure 28 - TFI and Variation Between Days Bar Chart
Variation Between Days and TFI

70
60
50
40
TFI
30
20
10
0
No, it's constant all the Some Variation from Day Significant Variation from
time to Day Day to Day
TFI 52.81 43.86 42.75
N 11 20 7
Figure 29 - TFI and Variation Between Days Bar Chart
31
How would you describe your tinnitus sound? Check all that apply.
Patients were asked to select the type of tinnitus sound they experience. Patients could select more
than one.
Type of Tinnitus Sound

70%
60%
50%
40%
30%
20%
10%
0%
Figure 30 – Type of Tinnitus Sound
32
What is the pitch (frequency) of your tinnitus?
TFI Versus Pitch
120
100
80
TFI
60
40
20
Very High High Medium Low I don't know

Pitch (Very High to Low)
Figure 31 - TFI Versus Pitch Scattergram
Pitch and TFI

70
60
50
40
TFI
30
20
10
0
Very High High Medium Low I don't know
TFI 49.95 44.04 38.75 0.00 46.82
N 15 16 3 0 4
Figure 32 - Pitch and TFI Bar Chart
33
Tinnitus appears to be worse with higher pitch. No-one has a low pitch.
Besides Lenire, have you tried any other treatments for your tinnitus? Check all that
apply.
Patients were asked to indicate if they had used any other treatments prior to using the Lenire.
Patients could select more than one.
34
Other (please specify)
35
Vagus Nerve Stimulation

TRT (Tinnitus Retraining Therapy
Transcranial Stimulation Treatments (rTMS, tDCS, tACS)
TMJ treatment
Tinnitus cure eBooks
Tinnitus Activities Treatment (TAT)
Surgical procedure
Steroids
Stem Cell Treatment
SoundCure
Self-administered sound therapy (masking, nature sounds)
Retigabine (Trobalt / Potiga)
Psychologist
Psychiatrist
Progressive Tinnitus Management (PTM)
Platelet Enriched Plasma (PRP)
Other Treatments
Physiotherapy
Figure 33 - Other Treatments

Off-label medication (e.g. retigabine, betaserc, lidocaine)
Notched music therapy
Neuromonics
Mindfulness / MBCT
Low-Level Laser Treatment (LLLT)
Levo Device
In-ear sound generator
Homeopathic treatment
Hearing aid
HBOT (Hyperbaric Oxygen Therapy)
GABA type drugs
Dietary supplements / herbal medicines
Deep Brain Stimulation
Chiropractor
CBT (Cognitive Behavioural Therapy)
Cannabis / Marijuana or CBD Oil
Brain Surface Implants
Bio / Neuro feedback
Antidepressants
Anti-anxiety (Benzos)
Acupuncture
Acoustic Neuromodulation
Acceptance and Commitment Therapy (ACT)
None
45%
40%
35%
30%
25%
20%
15%
10%
5%
0%
Optional - What multiple of your monthly income after tax does the outright purchase
(EUR 2,150) of the device represent? (e.g. 0.5 would mean the device is half your
monthly income, 2 would mean the device is twice your monthly income)
Lenire Cost as Mutliple of Monthly income

8
0
0-0.25 0.25-0.5 0.5-0.75 0.75-1 1-1.25 1.25-1.5 1.5-1.75 1.75-2 2-100
Figure 34 - Lenire and Patient Monthly Income
We saw a large variation in responses to this question. It seems that patients have quite a wide
range of incomes. The cost of the device is €2150 if paid for at commencement, and €2500 in
instalments. Using the former figure and our data, the approximate average after tax income for
patients was €4,501.
How do you rate your experience with Neuromod during this appointment?
Patients were asked to rate their experience with Neuromod from 1-5 with 5 being best and 1 worst.
We weren’t specific if this rating applied to the initial assessment or the device fitting appointment.
36
Neuromod Satisfaction
20
18
16
14
12
Count
10
8
6
4
2
0
1 2 3 4 5
Satisfaction Rating
Figure 35 - Neuromod Satisfaction
The average satisfaction score was 4.4. Patients were, in general, satisfied with their experience at
Neuromod.
Any other feedback about your appointment?
Some responses are provided below:
“The folks at Neuromod were excellent. Haviing travelled from Canada, they made me feel important
by explaining every aspect of the treatment and accepting of my questions. They seem to be
genuinely interested in making my experience worthwhile, however, they cautioned me that the
treatment is not guaranteed. I appreciated their candure.”
“Neuromod Staff is kind and willing to help and it seems they truely believe the treatment can be
effective”
“Neuromod's been wonderful and professional all along.”
“very friendly staff, a little bit vague on certain things, as i guess they cant guarantee anything”
“Very good feeling of my appointment. Caroline was very professional and qualified”
“They were friendly and helpful.”
“Very professional and competent staff. No pushing or hard selling for the device.”
“i was informed that they plan to open a clinic in germany in 2020. also, i was informed that there
was no plans to open a clinic in usa in 2020.”
“My initial consultation was quite in-depth and turned into an almost counseling like session. It was
great to find out the number of decibels needed to mask my tinnitus and to have my hearing
checked. In my follow up fitting appointment my audiogram was explained to me and the treatment
37
process was explained a little bit (I'm not a scientific person but they explained as best they could).
My masking levels were tested again and had dropped by 6 decibels (from 26db to 20db).
Throughout the process, I was made to feel confident that I could very well benefit from the
treatment as I was a less complicated case. All the staff were very friendly and accommodating. I
have sent multiple emails and questions which they have always replied to.”
38
Section 4: Tinnitus and patient characteristics

**WARNING** Now Entering the Statistics Zone **WARNING**
In this section we look at trying to find a relationship between the TFI score between groups (e.g.
Male, Female) within a factor (e.g. “gender”) using one-way ANOVA. Specifically, we would like to
know if the TFI group means are different within each factor. This will help with better
understanding the patient cohort and will introduce the reader to some of the statistical techniques
used in the second report (in the second report we look at the changes in TFI at each treatment
milestone in each group, rather the actual value as we do here).
Let’s look at a practical example. Here is our Loudness and TFI chart from earlier in the report:
Tinnitus Loudness and TFI

90
80
70
60
50
TFI
40
30
20
10
0
TFI 23.42 41.62 50.23 81.44
N 4 16 15 3
Figure 36 - Example ANOVA
We would like to know if there are any statistical differences in the mean TFIs in each group. From
the above chart, it looks like there could be differences between all the means except between the
Moderate and Loud groups. One way to tell if this is correct is to run an ANOVA test.
If we do this, we get an ANOVA p = 0.00005, which is very significant (generally if p<0.05 we can
confidently conclude there is a significant difference). ANOVA is telling us that we can reject the null
hypothesis that the group means are the same at the 99.995% level of confidence.
To see which group means are different, we run Tukey HSD and we get the below p values:
39
group 1 group 2 p-value

Quiet Moderate 0.03
Quiet Loud 0.01
Quiet Very Loud 0.00
Moderate Loud 0.74
Moderate Very Loud 0.00
Loud Very Loud 0.00
Table 4 - Tukey HSD - Average TFI and Loudness
The p values which are significant are those below .05 and are highlighted in green. Tukey is telling
us pretty much as we expected (i.e. all means are different except Moderate to Loud). The Tukey
test can also give us confidence intervals for differences in the means (and we do this for gender
below).
Now we can run the ANOVA for all the factors to see if there are any differences in the means of
groups within the factor.
If we do this, we see few associations.
Factor One Way Anova p score

Severity Rating 0.03
Loudness 0.00
Hyperacusis 0.04
Duration 0.28
Age 0.51
Hearing Loss 0.78
Pitch 0.63
Intermittency 0.13
Source 0.56
Reactivity to Noise 0.05
Gender 0.00
Somatic Modulation 0.17
Variation within a Day 0.90
Variation between Days 0.37
Table 5 - One-Way Anova Results
It’s worthwhile noting that our sample is drawn from people who mostly have severe tinnitus and
this fact will tend to reduce differences between groups.
For Severity Rating, we only saw differences in means between Moderate and Severe (catastrophic
excluded as only one data point), which is a little surprising.
For Hyperacusis, Tukey HSD had no p-values less than 0.05, so we cannot reject the hypothesis that
there are differences.
40
The relationship between gender and TFI was also surprising. We saw a difference in means of 21.3
and a 95% confidence interval for the difference in means of [6.9,35.7].
Also note that we are not finding differences between groups in the hearing loss factor.
41
Section 5: Relationships between patient characteristics

**WARNING** Now Entering the Statistics Zone **WARNING**
In this section, we use Linear Regression to examine relationships between various factors
considered in this study. We would like to know if there are any relationships between these factors
(rather than within the factors which was the subject of the previous section). The reason this is of
interest is that will help understand any results we see in Report 2. If we are seeing relationships
between TFI reduction and various factors, it may be because the factor is related to another one.
For example, if there is:
• A relationship between age and reduction in tinnitus after treatment,

• A relationship between hearing loss and reduction in tinnitus after treatment
• A strong relationship between age and hearing loss
Then it may be possible that it’s the hearing loss that is the cause of the relationship between the
reduction in tinnitus and age rather than age.
Let’s look at two factors, age and hearing loss. We might expect hearing loss to increase with Age.
We can see if we can uncover this relationship and see if there are any others.
Below is the plot of average hearing loss and age.
Age Versus Hearing Loss

3.5
3 y = 0.02x + 0.873
R² = 0.1901
Ave Hearing Loss
2.5
1.5
0.5
0
15 25 35 45 55 65 75
Age
Figure 37 - Example Linear Regression/Pearsons Correlation
We can see that in our sample as age increases, so does, as might be expected, hearing loss. The
slope of the line is about 0.02 and tells us the extent of hearing loss per extra year of age. We can
perform a statistical analysis on the slope to determine if we can reject the null hypothesis that is it
zero (which would mean no relationship). If we do this the “p” value is 0.004, which is less than .05,
which means we can reject the hypothesis that the slope is not zero with 95% level confidence. We
can also see that R2 is about 0.19, which means 19% of the variation in hearing loss is explained by
42
the model. Note that a R2 of 1.0 means a perfect linear plot of the dependent variable against the
independent variable and that all the variation in the dependent variable is explained by the model.
We can also use the model to predict hearing loss given a particular age (by using the straight line
fit), and also work out the confidence interval of the prediction. In this particular case, the
confidence intervals are very wide due to the weak relationship. For the sake of illustration, the
diagram below shows TFI and loudness and the 95% Confidence intervals for the predictors:
Loudness versus TFI

120
100
80 Patients
Lower 95% CI
60
Upper 95% CI
TFI
Series4
40
Linear (Patients)
Poly. (Lower 95% CI)
20
Poly. (Upper 95% CI)
Very Quiet Quiet Moderate Loud Very Loud

-20
Loudness
Figure 38 – Loudness versus TFI with confidence intervals
You can see that all samples fall inside the confidence intervals except one. So, if someone gave me
their self-assessed loudness (say, for example moderate), I could make a prediction on their TFI
score (in this case 38.9 +/- 14.9) and be correct most of the time.
We may use this idea in the next report when trying to predict TFI changes based on patient
characteristics (and may use more than one independent variable).
Below are tables showing the p value, the R2 values and the slopes for each of the possible
combinations of relationships between (at least ordinal) factors used in the study. I have also
included “TFI” as a factor. The text highlighted in red corresponds to the parameter in the above
“Age Versus Hearing Loss” chart. The p-values highlighted in green are the significant values showing
there is a relationship. Refer to the Appendix on Linear Regression for more information on these
values.
43
Hearing Loss
TFI Hyperacusis Age Duration Intermittency (Ave) Pitch Loudness
Hyperacusis 0.98
Age 0.87 0.83
Duration 0.28 0.73 0.53
Intermittency 0.02 0.32 0.02 0.02
Hearing Loss (Ave) 0.47 0.87 0.00 0.22 0.17
Pitch 0.35 0.57 0.68 0.19 0.07 0.58
Loudness 0.00 0.40 0.07 0.56 0.00 0.11 0.01
Severity 0.00 0.79 0.11 0.20 0.00 0.22 0.04 0.00
Table 6 - Linear Regression p-values for between-factor regressions
Hearing Loss
Hyperacusis 0.00
Age 0.00 0.00
Duration 0.03 0.00 0.01
Intermittency 0.14 0.02 0.12 0.12
Hearing Loss (Ave) 0.01 0.00 0.19 0.04 0.04
Pitch 0.02 0.01 0.00 0.04 0.08 0.01
Loudness 0.42 0.02 0.08 0.01 0.37 0.06 0.18
Severity 0.28 0.00 0.06 0.04 0.44 0.04 0.10 0.45
Table 7 - Linear Regression R2 values for between-factor regressions
44
Hearing Loss
Hyperacusis 0.00
Age -0.02 0.60
Duration -0.07 -0.63 0.07
Intermittency 0.02 -0.22 0.03 0.04
Hearing Loss (Ave) 0.00 0.02 0.02 0.01 0.12
Pitch 0.00 0.09 0.00 0.02 -0.19 0.10
Loudness 0.03 0.15 0.02 -0.01 0.50 0.35 -0.50
Severity 0.03 -0.07 0.02 0.03 0.71 0.36 -0.49 0.88
Table 8 - Linear Regression Slope Coefficient values for between-factor regressions
45
You can see that, in our sample, that:
o Reduced intermittency was correlated with a higher TFI, increased duration,

increased age, higher pitch, increased perceived loudness and increased perceived
severity.
o Hearing Loss was correlated with age.
o Higher pitch was correlated with increased loudness and severity.
o Increased loudness and severity were correlated with higher TFI and with each
other.
Interestingly there are no relationships with Hyperacusis.
46
Section 6: A Word on the Next Report

The next report will mostly look at the differences in TFI encountered from 0 to 6 weeks and 0 to 12
weeks of treatment and we will be using many of the techniques used in this report, as well as
others, to try to uncover relationships. We will look at:
• Overall differences in TFI between 0 and 6 weeks, 0 and 12 weeks, and 6 and 12 weeks
across the cohort and their significance. That is, we will determine if we are experiencing a
statistically significant change in patient TFI as treatment progresses.
• Changes in TFI between groups of a given factor at 0, 6 and 12 weeks. That is, is there a
difference in the mean TFI change between groups within a factor as treatment progresses?
This will help identify patient characteristics that are associated with greater of lesser
efficacy of the device. This is the same type of test we did in Section 4, but this time with TFI
changes, rather than TFI itself.
• Correlation between TFI changes and ordinal factors. This is the same TFI/ordinal factor
correlation tests we did in Section 5, except this time with TFI changes, rather than TFI itself.
• Changes in the patient-described severity score at 0, 6 and 12 weeks.
• Testing to see if group membership within a factor and a successful outcome using the
Lenire (a reduction of 13 or more points) are dependent of independent. Dependency
implies a relationship.
• The feasibility of using multiple regression to model TFI changes, and the possibility of using
it as a predictor for TFI reduction. That is, is it possible for us to predict the likely changes in
tinnitus given certain patient characteristics.
• Lessons Learned during the study and how these could be used to improve subsequent
similar studies.
We will also provide:
• Information on the number of drop-outs and the cause of drop-outs.

• Scatter plots for TFI at commencement versus TFI at 6 and 12 weeks.
• Bar charts showing changes in loudness and bothersomeness at 6 and 12 weeks.
• Tables showing the self-assessed severity prior to the treatment versus self-assessed
severity at 6 and 12 weeks.
• Where there is a statistically significant change relating to a factor at 6 or 12 weeks:
o Scatter-plots showing TFI at commencement versus TFI at the 6 or 12 week
milestone with each data item labelled according to the group within the factor.
o Average TFI change for each group within the factor, with percentiles.
o % of patients with significant TFI improvement (>13 points) for each group within
the factor.
Once again, we should point out our sample size is small, and we are not measuring things such as
hearing loss in a clinical environment.
Notwithstanding the above, the analysis in the next report should help to point the way on what
might be possible in a larger study. The supplier of the device has conducted very large trials and is
presently capturing data from post-trial customers. They very likely have large quantities of high-
47
quality data which could be used to generate statistical information such as that generated in the
next report. Making this available to the tinnitus community would be of great benefit as it would
allow potential customers to determine the likelihood of success for their situation.
48
References
[1] The impact of gender, age and hearing loss on tinnitus severity, Patricia Ciminelli Linhares Pinto
et al, February, 2010.
[2] Significant p-values in small samples, 25th Jan, 2012, Allen Fleishman.
[3] The Tinnitus Functional Index: development of a new clinical measure for chronic, intrusive
tinnitus, Meikle et al, May 2012.
[4] Gender and Chronic Tinnitus: Differences in Tinnitus-Related Distress Depend on Age and
Duration of Tinnitus, Seydel et al, September 2013.
[5] Tinnitus—a study of its prevalence and characteristics, Axelsson et al, March, 1988.
[6] Bi-modal stimulation in the treatment of tinnitus: a study protocol for an exploratory trial to
optimise stimulation parameters and patient subtyping,, BMJ, D’Arcy Et al, 25th October, 2017.
[7] Noninvasive Bimodal Neuromodulation for the Treatment of Tinnitus: Protocol for a Second
Large-Scale Double-Blind Randomized Clinical Trial to Optimize Stimulation Parameters, Conlon et al,
JIMR Prptoc 2019; 8(9)
49
Appendix 1 - Summary of Factors Studied
Factor Option 1 Option 2 Option 3 Option 4 Option 5 Option 6 Option 7 Option 8 Option 9
Age
Gender Male Female
Duration < 3 months 4-6 months 6-12 months 1-2 years 2-3 years 3-5 years 5-10 years 10-20 years > 20 years
Severity Rating Borderline Mild Moderate Substantial Severe Catastrophic
Loudness Very Quiet Quiet Moderate Loud Very Loud
Intermittency Occasional 50% Mostly All the time
Hyperacusis None Mild Moderate Severe
Hearing Loss (R) None Mild Moderate Severe
Hearing Loss (L) None Mild Moderate Severe
Somatic Somatic Non Somatic
Source Left Ear Right Ear Both Ears Inside Head Inside + ears Other
Reactivity to Noise Lot Worse Little worse No effect Little Better Lot Better
Variation within a Day No change Less in AM Less in PM No pattern Other
Variation between Days Constant Some Significant
Pitch Very High High Medium Low
Table 9 - Summary of Factors Studied
50
Appendix 2 - Statistical Techniques
One Way Anova
ANOVA is a statistical technique that compares variation between and amongst groups to analyse
the differences in group means in a sample. It tells us if we should reject the null hypothesis that
group means are identical, at a given level of confidence. It’s important to note that ANOVA only
tells us if there is a difference between groups, and to find out which groups are different, we need
to execute another test (we chose the Tukey HSD for this). An example of using ANOVA may be
found here.
We should point out that the sample size we are using in this study is very small, and the sample
is not randomized but self-selected. As such, any conclusions we come to regarding differences in
means between groups should be approached with caution. For an introduction to the subject of
small sample sizes and statistical significance refer to [2].
Linear Regression
Linear regression is a statistical technique that used to model a dependent variable on one or more
independent (or explanatory) variables. In this report we use one independent variable only,
although in the next we may use several.
The linear regression process involves fitting a straight line to data plots of a dependent variable
against an independent variable. The straight line which minimizes the sum of the squares of the
differences to the line is the linear regression plot. The slope of the line is an indicator of the linear
nature of the relationship. For example, a slope of 2 would indicate that, using the fitted line, the
dependent variable changes by twice the value of the change in the independent variable. We are
often interested in determining if the slope of the line is different than zero (a zero slope indicates
no relationship). We can use statistical tests to determine if the slope is zero or not and the result is
a “p” value. A “p” value less than 0.05 indicates that we can reject the null hypothesis that the slope
is zero with a 95% level of confidence. More information here.
The other statistic that is often mentioned in relation to linear regression is R2. R2 represents the
percentage of the dependent variable that is explained by a linear model. In general, the higher the
R2, the better the model fits the data. More information here. R is also known as the Pearson
Correlation Coefficient.
Normally the independent and dependent variables used in linear regressions should be
continuous (e.g. Age, Duration or similar), however it is common practice to also use linear
regression when the independent variable has a Likert type scale outcome (e.g. Borderline, Mild,
Moderate, Substantial, Severe) and we do this here. More information, for example, may be found
here. Alternative tests (“non-parametric tests”) which do not require these variables to be
continuous are available (e.g. Spearman’s Rank Correlation, or Kendall’s Tau). These test for a
monotone relationship rather than a linear one. These tests often result in very similar results to the
51
Pearson test. See the below table for Pearson versus Spearman and Kendall for the “Pitch versus
Loudness” p-value and correlation coefficients:
p-value Correlation Coefficient

Pearson 0.005 0.419
Spearman 0.004 -0.455
Kendall 0.005 -0.417
(Note: The Spearman and Kendall coefficients are negative if the relationship is a negative one).
There are many rules of thumb for the minimal sample size required for multiple linear
regression. For example (Green 1991) indicated a sample size N > 50 + 8m, where m is the number of
independent variables (1 in linear regression), and N > 104 + m for individual predictors. Harris
(1985) states the number of participants should be at least 50, Van Voothis & Morgan states that for
6 predictors, the absolute minimum number of participants should be 10, but it is better to have 30
per variable. We have 43 participants here for m = 1, so the results should be treated with caution.
52
Appendix 3 – Report Caveats

It’s important that we point out the caveats that apply to this and the second study These caveats
should be considered when reading these Lenire User Experience Group reports.
• We are trying to estimate statistics for the general population of people who are eligible for
use of the Lenire and likely to purchase it. The sample we are using is self-selected from
TinnitusTalk forum members who have purchased the device and volunteered to provide
their experiences. This may not be a representative sample of the population mentioned
above (For example, participants from the TT forum may have more severe tinnitus,
especially early adopters). As such, the conclusions of this report may not be valid for the
population who are likely to use the Lenire in the future.
• Survey responses such as the extent of hearing loss are self-reported and not measured
independently. One person's moderate hearing loss may be another person's mild hearing
loss.
• The sample size is not large (43). It is difficult to make conclusions about the significance of
statistics with small sample sizes. In small samples, statistically significant results tend to be
fragile and subject to change as a result of a small change in the sample. In addition, smaller
samples may fail to reject null hypotheses that would be rejected by larger samples.
• This is an observational study. There is no control group. We can't be sure that the effects
we are observing in the treatment stage would not have been experienced in part or full by
a control group undertaking a placebo treatment. That is, we cannot say that the Lenire is
the cause of any observed improvements or changes.
• It is known that tinnitus is more likely to spontaneously resolve for people who have been
afflicted for a short duration than those who have been afflicted for a longer period. As
there is no control, we can't be sure that improvements for people with short duration
tinnitus is related to the use of the Lenire.
• Correlation does not imply causation. If an independent variable is correlated with a tinnitus
change, it does not mean it is the cause of the change.
• The staff performing the data collection and analysis are not professional researchers. While
we are trying to minimise errors by leveraging the experience of the members of the forum,
performing reviews of the results by experts, and also making use of university researchers
who have agreed to collaborate, a more ideal scenario would involve the use of professional
researchers.
• Patients are providing information anonymously over the Internet. While some patients are
well known on the TinnitusTalk forum and have been contributing for years, others are
relatively new and have no previous history of contributing. While we have asked
contributors to provide photos of the device to establish their bona-fides, this has not
always been done.
• Communication with patients is with email and the forum messaging only. The native
language of some patients is not English. In a small number of cases this has led to
communication problems and ambiguities and to an overall reduction in quality of the data.
• In a small number of cases, we have accepted surveys from people who, due to unexpected
issues, have already started using the device.
53
Appendix 4 – Suggested Viewing - Statistics
Understanding p-values
Understanding the p-value – Statistics Help
Anova
Introduction to One-way Anova
Linear Regression
Introduction to Simple Linear Regression
54

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Lenire User Experience Group Study – Report 1

Cohort Characteristics and Analysis

Figure 1 - TFI Distribution at Baseline ................................................................................................... 11

Table 1 – Classifying Tinnitus Duration ................................................................................................. 16

Section 1: Executive Summary

o Reduced intermittency was correlated with a higher TFI, increased duration,

These relationships can be further investigated in section 5. These relationships will be

Section 2: Some Terminology

Section 3: Results from the Questionnaire

When capturing TFI information, we firstly asked the question below:

More information on TFI

Response Mean TFI Standard Deviation

Here is the distribution of responses to the TFI question at baseline:

TFI Distribution at Baseline

Figure 1 - TFI Distribution at Baseline

In which country do you live?

Figure 2 - Country of origin for patients

What is your Age?

TFI versus Age

Figure 3 - TFI Versus Age Scattergram

Age and TFI

Figure 4 - Age and TFI Bar chart

What is your gender?

TFI versus Gender

Figure 5 - TFI Versus Gender Scattergram

Gender and TFI

Figure 6 - Gender and TFI Bar chart

How long have you had tinnitus?

Questionnaire Section 3 Section 4

Table 1 – Classifying Tinnitus Duration

TFI versus Duration

Figure 7 - TFI Versus Duration Scattergram

Duration and TFI

Figure 8 - Duration and TFI Bar Chart

What do you believe is the cause of your tinnitus?

Other (please specify)

Figure 9 - Cause of Tinnitus

Metabolic (diabetes, thyroid, B12, hyperlipidaemia etc.)

How do you rate the Severity of your Tinnitus?

TFI versus Tinnitus Severity Rating

Figure 10 - TFI Versus Self-Assessed Severity Rating Scattergram

Tinnitus Severity Rating and TFI

TFI Versus Loudness

Figure 12 - TFI Versus Loudness Scattergram

Tinnitus Loudness and TFI

Figure 13 - Tinnitus Loudness and TFI Bar Chart

TFI Versus Intermittency

Most Intermittent to least intermittent

Figure 14 - TFI Versus Intermittency Scattergram

Intermittency and TFI

Figure 15 - Intermittency and TFI Bar Chart

Some responses to this question are shown below:

Do you have hyperacusis (reduced tolerance or increased sensitivity to everyday

TFI Versus Hyperacusis

Figure 16 - TFI Versus Hyperacusis Scattergram

Hyperacusis and TFI

Figure 17 - Hyperacusis and TFI Bar Chart

Table 2 - Classifying Hearing Loss

We present the results here using method 1.

TFI Versus Hearing Loss

Figure 18 - TFI Versus Hearing Loss Scattergram

Hearing Loss and TFI