Production of a Device to Obtain Continuous Ambulatory Vestibular Assessment (CAVA) - Healthy Volunteer Trial
Conditions: Optokinetic Nystagmus
Sponsor: Julie Dawson

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CONFIDENTIAL 
 
CAVA: Healthy Volunteer Trial 
Clinical Investigation Plan 
 
 
 
 
 
Full title of project:  
Production of a device to obtain continuous ambulatory 
 
 
 
vestibular assessment (CAVA) – healthy volunteer trial 
 
Short title of project:  
CAVA – Healthy Volunteer Trial 
 
MRC reference:  
MR/P026265/1 
 
IRAS ID: 
 
240847 
 
Version number: 
2.5 
 
Date: 
 
 
20th September 2018 
 
Authors: 
 
Mr John Phillips (JP) 
- Principal Investigator 
 
 
Prof Stephen Cox (SC) - Co Principal Investigator 
Dr Jacob Newman (JN) - Research Associate 
 
Sponsor: 
 
Norfolk & Norwich University Hospitals NHS Foundation Trust 
 
 
 
Department of Otolaryngology 
 
 
 
Colney Lane 
 
 
 
Norwich 
 
 
 
Norfolk 
 
 
 
NR4 7UY 
 
 
 
United Kingdom 
 
 
 
 
 
 
 
 
 
 

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1 
INTRODUCTION 
 
1.1 
In 2017, the Medical Research Council awarded a grant as part of their Biomedical Catalyst: 
Development Pathway Funding Scheme to Mr John Phillips and his team at the University of 
East Anglia, to develop a medical device to aid diagnosis in individuals experiencing dizziness, 
vertigo and balance problems.  This grant is to develop an early prototype, and then to 
formally test it in healthy volunteers, and then later, in individuals who experience vertigo. 
 
1.2 
This document outlines the clinical investigational plan for the first of two formal clinical trials.  
This clinical investigation plan is for a healthy volunteer trial. 
 
2 
SCIENTIFIC RATIONALE 
 
2.1 
In England and Wales, eight out of every 1,000 patients are likely to consult with their General 
Practitioner complaining of dizziness every year.  Symptoms of dizziness or imbalance are 
experienced by 30% of the population by the age of 65 years (Roydhouse 1974).  One in four 
in the community have ‘significant’ dizziness at any given time (Nazareth 1999). 
 
2.2 
Eye movements are key in assessing the function of the inner ear and the vestibular system 
(Huh 2013).  There is a dipole potential (the corneo-retinal potential) between the front and 
the back of the eyeball that allows eye movements to be measured electronically.  The 
intimate relationship between eye movements and the inner ear is mediated by a neural 
reflex called the vestibulo-ocular reflex (VOR).  The main purpose of this reflex is to stabilise 
images on the retina during head movements. This reflex is administered in a manner whereby 
the eyes move in the opposite direction to the direction of the head movement.  The VOR 
does not require visual input and so is active both in total darkness and when the eyes are 
closed.  As this is a brainstem reflex, it is also active when a subject is asleep or in a coma, and 
as such is used clinically to diagnose brainstem death.  
 
2.3 
The common causes of vestibular dysfunction occur momentarily, and by the time a patient 
presents to a specialist, they are asymptomatic (Molnar 2014).  Two conditions which 
particularly attract considerable attention in the clinical and research communities are 
Meniere’s disease and Vestibular Migraine.  The causes of these conditions are not fully 
understood and their assessment is challenging (Phillips 2010).  Both of these conditions may 
result in dizziness lasting for many hours, but because patients may be asymptomatic for days, 
weeks or even months between attacks, it is often the case that there are few findings to be 
identified when the patient is assessed.  Meniere’s disease and Vestibular Migraine are 
provided as examples, but these conditions are not unique in their mode of presentation, as 
the majority of balance disorders present in this manner.  
 
2.4 
There are many traditional and contemporary balance tests available, but they still provide 
only a snapshot of vestibular function when performed in the absence of an actual 'dizzy 
attack' (Phillips 2011).  By developing a device that can capture the characteristic eye 
movements (nystagmus) that are produced during a 'dizzy attack', we will be able to identify 
the aetiology of these episodes of imbalance.  Parallels can be drawn between our device and 
the 24-hour ECG tape that is used to identify cardiac arrhythmias. 
 
2.5 
Nystagmus is a clinical sign which is often specific to the inner ear.  However, a number of 
patterns of nystagmus are produced as a consequence of conditions that are not caused solely 
by a malfunction of the inner ear (Serra 2002). Therefore, the identification of nystagmus will 
not only allow us to differentiate between the many vestibular causes for a ‘dizzy attack’, but 

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would also allow us to understand the role of different types of nystagmus as a consequence 
of certain other nervous system pathologies. 
 
2.6 
The assessment of the dizzy patient can be challenging for all clinicians involved in managing 
their care. John Phillips has been commissioned by the British Medical Journal to write a 
learning module to help clinicians understand how to assess these patients (Phillips 2015). 
This module outlines the processes and pathways to differentiate inner ear dizziness from non 
inner ear dizziness from the outset. This essential first step would be refined significantly by 
the introduction of our proposed device.  
 
2.7 
A recent Royal College of Physicians working party report confirms our expectation that 
detailed occulomotor assessment will ‘frequently enable an appropriate diagnosis to be made 
without the use of expensive resources’ (RCP 2007, Halmaghi 2005). According to the RCP 
report, balance services in the UK have been ‘particularly neglected due to limited training, 
resources and manpower’, so our proposal will fulfill a significant unmet clinical need. ‘Dizzy 
patients’ present via a variety of routes: A&E departments, general practitioners, self-referral 
to ENT, cardiologists, neurologists or audiovestibular physicians. The Department of Health 
have proposed a referral pathway to allow treatment within an 18-week target. However, due 
to the complexity in the manner that these patients present, and the overlap of aetiologies 
between multiple specialties, patients are often seen by several clinicians from different 
disciplines before a diagnosis is made. The US National Institutes of Health report that the 
mean number of physicians a patient with vertigo visits before receiving a correct diagnosis is 
4.5, and a similar finding is reported from specialist balance centres in the UK (RCP 2007). Our 
proposed device could be made available at the point of initial referral to avoid delay in 
diagnosis and ensure cost-effective use of appropriate resources. This is particularly 
significant as the cost of falls to the NHS and social services in people over 60 years old in 1999 
was £981 million (Scuffham et al, 2003). Another consideration is that in 80% of affected 
individuals, vertigo results in a medical consultation, interruption of daily activities, or sick 
leave (Neuhauser et al, 2005). 
 
3 
THE DEVICE 
 
3.1 
The device is composed of two components: a bespoke single-use sensor array that adheres 
to the participant’s face, and a small reusable module that contains a battery, microcomputer, 
data storage facility, battery and connection port.  A series of preliminary prototype devices 
have been manufactured and tested as part of a preliminary programme of work aimed at 
developing the overall project to this stage.  This work has been completed by the primary 
research team in collaboration with a design agency (Wright Design Limited).  The device is a 
lightweight, durable, body-worn monitoring device that can be worn day and night.  It will be 
worn on the face and head but will minimally intrude into the patient’s normal lifestyle. 
 
3.2 
Preliminary prototype devices have been developed to be able to record the maximal ocular 
excursions and velocities that are observed in clinical practice.  These preliminary prototype 
devices have consistently, accurately, precisely and reliably identified periods of physiological 
nystagmus in subjects both stationary and in motion and have produced consistent signals at 
the beginning and end of each trial period.  The sensor array has been reported to be 
comfortable and there have been no adverse skin reactions.  The evolved device that will be 
used for this trial, will be provided to a participant for a 30 day period at a time and will include 
an ‘event marker’ button. Although not relevant to this first trial, actual dizzy patients would 
depress this button during an episode of dizziness.  The absence of any nystagmus during this 
period would indicate a cause of dizziness that is not related to a malfunction affecting the 

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VOR. To further clarify subject activity during episodes of either nystagmus and/or dizziness, 
the final device will contain an accelerometer which will enable retrospective correlation 
between activities that may be implicated in the cause of dizziness and/or variation in the 
signal produced.  
 
3.3 
Independent market research 
We have commissioned some independent market research which has provided further 
insight into other uses for the device.  Currently, clinical trials into the use of new treatments 
for dizziness rely on the participant completing questionnaires or diaries.  The use of the 
device, would enable an objective measure of the frequency of vertigo in these patients.  
There is increasing interest in the use of ambulatory telemetry for individuals with other 
primary neurological conditions; as such, our device might be of interest in the field of stroke 
medicine. 
 
3.4 
Patient and public involvement 
Early on in the design process, a focus group was formed to allow the design company to 
interact with potential users of this device.  This was a very useful exercise, and allowed all 
participants to provide input to the device design, and the format of the device trials. 
 
4 
AIMS AND OBJECTIVES 
 
4.1 
The overall aim of this trial is to further develop and test a fully evolved device for the 
continuous recording of eye movements over a prolonged period of time.  For the purpose of 
this study, the monitoring period is 23 hours a day, for 30 days. 
 
4.2 
The overall trial objectives and how we will present the data relating to them, are as follows: 
 
i. 
The device produces data that allows recognition of nystagmus with a diagnostic 
sensitivity of 95% or greater. 
 
We will report the sensitivity and specificity of the computer algorithm’s classification 
results. This will be calculated from the number of true positives, false positives, true 
negatives, and false negatives. These values are produced by applying the trial data 
to computer algorithms developed by the project’s Research Associate. For clarity, we 
will also present these values. 
 
ii. 
The device produces data that allows recognition of nystagmus with a diagnostic 
specificity of 95% or greater. 
 
As in point i. 
 
iii. 
The device provides less than 5% non-useful data and less than 5 drop-outs for each 
single day of the trial for each participant. 
 
In a tabular format, we will present the proportion of non-useful data for each 
participant, for each day, and the number of drop-outs for each person, for each day. 
Non-useful data will be determined from missing data which is not reported as a 
compliance issue. Drop outs will be defined as any periods of missing data which are 
at least an hour apart. 
 
iv. 
The device provides less than 5% non-useful data and less than 60 drop-outs for the 
entirety of the 30-day trial for each participant. 

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In a tabular format, we will present the proportion of non-useful data for each 
participant, across the entire period that they were supposed to be wearing the 
device during the trial. Non-useful data and drop outs will be defined as in iii. 
 
v. 
There is a minimum of 80% compliance with wearing the device for each single day 
of the trial for a minimum of 80% of participants. 
 
In a tabular format, we will present the proportion of compliance for each participant, 
for each day of their involvement in the trial. This data will be determined from the 
trial diaries. From this table, we will calculate the proportion of participants who 
demonstrated a minimum of 80% compliance for each single day. 
 
vi. 
There is a minimum of 80% compliance with wearing the device for the entirety of 
the 30-day trial for a minimum of 80% of participants. 
In a tabular format, we will present the proportion of compliance for each participant, 
across the entire period that they were supposed to wear the device during the trial. 
This data will be determined from the trial diaries. Additionally, we will present the 
proportion of these participants who demonstrated a minimum of 80% compliance. 
 
vii. 
The device’s event-marker, timestamping hardware and accelerometer function 
correctly. 
 
We will present a report detailing the results of tests performed to evaluate this 
objective. The results of the event marker function test will consist of the approximate 
time that the button was pressed, the time that the device reported that the button 
was pressed, and a pass or fail indication, based on whether the button press was 
registered. The timestamping hardware test result will consist of the time difference 
(in dd:hh:mm:ss) between the time logged on the device following the activation of 
the event marker, and that of a real-time clock on a desktop computer. The 
accelerometer test will consist of a table listing the head movements performed and 
whether they could be identified manually from the accelerometer data. We will 
present all data for each device, as well as averaging and calculating the proportion 
of tests passed from the total pool of devices. 
 
viii. 
To derive further user reported data regarding the day to day experience of using 
the device and to acquire further safety data regarding the device. 
 
We will write a report which details the results of the post-trial questionnaires filled 
in by each participant, summarising the conclusions of the report. This report will 
cover topics such as the safety, usability, tolerability of wear etc. 
 
ix. 
To derive further experimental data using the device whilst being used in a clinical 
testing environment, to enable the correlation between device data, and clinical 
testing data. 
 
We intend to compare data produced by the CAVA device to data captured using 
conventional Videonystagmography (VNG), gathered during a standard balance 
assessment procedure. From the eye movement data captured, we will make 
estimates of the onset, end, beat direction, beat frequency and Short Phase Velocity 
(SPV), and then compare the two systems. 
 
 
 

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5 
METHODOLOGY 
 
5.1 
Overview 
 
Healthy individuals will be recruited from the local area to participate in this trial.  It is 
intended that this trial will be advertised at the University of East Anglia.  Participants will be 
required to wear the device for thirty days.  During this period, they will induce physiological 
nystagmus by viewing optokinetic video footage.  This replicates the typical eye-movements 
observed when watching a passenger on a moving train looking out of a window. 
 
5.2 
We intend to confirm that the device will be able to capture any occurrence, of a minimum 
period of thirty seconds, of artificially induced nystagmus, within a 24-hour period of time.  
Each participant will be provided with the device and enough single-use electrode arrays to 
allow the array to be changed every 24 hours, for thirty days.  Participants will be allowed to 
remove the sensor array for up to 60 minutes each day to allow them to wash and/or 
shower.  On eight of the thirty days for which they wear the array, each participant will be 
required to induce physiological nystagmus by viewing optokinetic video footage.  The 
footage will be viewed on a portable screen (of a deactivated mobile phone) inside a VR 
headset.  These will be issued to the participants at the beginning of the trial. Participants 
will undertake the procedure whilst stationary for the first four days, and whilst walking 
gently on the spot for the remaining four days.  The identity of these days will not be 
revealed to the blinded investigator who will later analyse the data.   At the end of the 
thirty-day trial, the sensitivity and specificity of the device will be determined by assessing 
whether the data can be used to correctly identify the dates that participants induced 
nystagmus. 
 
5.3 
At the end of the thirty-day device trial, the participant will complete a questionnaire 
regarding their experiences using the device.  The participant will then undergo caloric 
vestibular testing, whilst wearing the device. 
 
5.4 
Inclusion criteria 
Adults aged 18 and over 
 
Able to commit to 30 days of continuous wear of the trial device as per the study plan 
 
Own a telephone 
 
5.5 
Exclusion criteria 
Potential participants who have a history of dermatological disease or damage around the 
forehead 
Potential participants who have an allergy to plasters and/or medical adhesives (similarly to 
materials used in the device)  
 
History of dizziness, vertigo, balance disorders, or syncope 
 
History of hypertension or cardiac problems (uncontrolled, acute or de-compensated phase) 
 
History of ear disease, or previous ear surgery 
 
History of psychotic/neurotic disorders or epilepsy 
 
History of eye disease, or previous eye surgery 
 
Pregnant or nursing mothers 
 
Unable to follow the testing protocol 
 
 
 
 

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5.6 
Clinical trial process 
 
i. 
Posters advertising the trial will be placed around the University of East Anglia (UEA). 
The poster will also be distributed internally to staff and students at UEA by email (See 
appendix A for the email template, which includes a copy of the poster). Potential 
participants may request more information about the study by contacting the 
research team through the contact details given on the poster. 
 
ii. 
Potential participants will be provided with a participant information sheet – see 
appendix B. 
 
iii. 
At the consenting visit, the participant information sheet and consent form (see 
appendix C) will be fully discussed, and the potential participant will be invited to ask 
questions. 
 
iv. 
If the participant agrees to be involved with this trial and signs a consent form, 
inclusion and exclusion criteria will be confirmed, and data collection forms will be 
filled in – see appendix D. In addition, if the participant agrees, a letter will be sent to 
the participant’s GP detailing their involvement in the trial – see appendix E. 
 
v. 
The participant will be provided with verbal and written instructions regarding a 
number of processes they are required to follow during the trial. There will be 
instructions provided and training given on how to activate, apply and take care of 
the device – see appendix F.  There will be instructions and training on how to power, 
charge and activate the mobile phone - see appendix G. In addition, they will receive 
instructions on how to view the optokinetic video footage – see appendix H.  A 
practical demonstration of the necessary processes required will also be provided. 
 
vi. 
The participant will be provided with a trial diary – see appendix I. The diary lists the 
eight individual days when he/she will activate the device event marker and run the 
optokinetic video footage, as well as the dates of their face-to-face hospital visits. The 
diary also provides space for participants to record the precise date and time of each 
viewing of the optokinetic video, a space for recording deviations from the trial 
protocol, and for recording any other events that the participant feels could be 
relevant to the trial.  
 
vii. 
A demonstration of all the necessary trial processes will be provided.  The training 
process will follow a strict protocol - see appendix J. The participant will be asked to 
demonstrate that they can follow the protocol correctly.  If they are unable to do this, 
they will be excluded.  See appendix J. Before the participant is released with the 
device, it will be plugged into a computer and a battery will be installed into it. Once 
connected to a computer, it will appear as a portable drive. A blank text file will be 
transferred to the device to synchronise the device’s internal clock. The device will 
start logging once it is detached from the computer. Whilst wearing the device, 
participants will be asked to stand a fixed distance from a wall chart and to look 
between certain positions on the chart. This will provide data which may be useful for 
device calibration, post-trial. 
 
viii. 
On day four or five of the trial, the participant will be invited to return to confirm that 
they are getting on well with the device, there are no issues, the sensor array has been 
applied correctly, and that there have been no skin reactions. The participant will 

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undertake their second viewing of the optokinetic video during this visit, allowing the 
team to check that the protocol is being followed correctly. 
 
ix. 
On day thirteen, the participant will be invited to return to confirm that they are 
getting on well with the device, there are no issues, the sensor array has been applied 
correctly, and that there have been no skin reactions. A member of the research team 
will employ the event marker and record the exact date and time that this activity is 
performed. After the device has been removed from the participant, the device will 
be plugged into a computer to re-synchronise the device’s internal clock, which is 
performed by replacing the provisioning file (blank text file) on the device. Whilst 
plugged into the computer, the device’s battery will be changed.  An interim 
download of the data will be performed and submitted to the un-blinded investigator 
(SC), to confirm that the study protocol has be followed as instructed.  If there is 
evidence that the participant has not been complying with the study protocol as 
instructed, future participant involvement in the trial will be terminated. 
 
x. 
On day thirty-two (thirty-two to thirty-six), the participant will be invited to return the 
device, mobile phone and all accessories.  At this point, the participant will: 
 
a. 
Complete a questionnaire regarding their experiences using the device – see 
appendix K.  We will use a predefined questionnaire that assesses a broad 
range of parameters related to user acceptability; both quantitative data as 
well as qualitative data will be acquired.  
 
b. 
Perform three specific head movements; one in each plane of axis with the 
device in place – see appendix L. 
 
c. 
Undergo caloric vestibular testing whilst wearing the device.  Caloric testing 
will be completed according to British Society of Audiology recommended 
procedures (BSA 2010). 
 
d. 
Whilst wearing the device, participants will be asked to stand a fixed distance 
from a wall chart and to look between certain positions on the chart. This will 
provide data which may be useful for device calibration, post-trial. 
 
5.7 
Dry run participant 
A dry run of all trial processes will be conducted using the first participant recruited for the 
trial. This participant will undergo the same trial processes as the remaining participants, for 
example: recruitment, device and VR headset training, wearing the device for 30 days and 
return hospital visits. The device data recorded during the dry run will also be subject to the 
same processing steps as the data captured by the remaining 15 participants, such as: data 
download, re-segmentation, randomisation and nystagmus identification. 
 
The purpose of the dry run is to test all trial procedures in a manner which is representative 
of how they will be performed by the remaining 15 participants. This test is important as the 
duration of the trial and the amount of data captured cannot be realistically simulated in 
advance. The dry run will provide an opportunity for the research team to refine their 
technique for executing the study protocol and to simultaneously confirm the functionality of 
the computer software used in a number of trial processes. In the event that any easily 
overcome, yet trial threatening issues are identified during the dry run (e.g. device bugs), the 
device’s firmware may be updated prior to the remaining participants starting the trial. The 

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dry run participant will be subject to the same safety and ethical considerations as the 
remaining participants. For example, the same safety stopping criteria will apply and they will 
have the right to withdraw from the trial without providing a reason. 
 
None of the research team will be blinded from the true identity of the randomised data 
derived from the dry run participant’s data. Therefore, the identity of the data files containing 
nystagmus will be known to all members of the research team. This will allow the team to 
extensively examine the data to confirm that the software-dependent procedures and the 
device itself are functioning as intended. As a main objective of the trial requires the blinded 
investigator to process randomised trial data through a nystagmus detection algorithm, the 
eye movement data captured by the first participant will be excluded from the data used to 
measure the sensitivity and specificity of that algorithm. However, the participant’s remaining 
data (e.g. safety data and caloric testing data) will be included in our final analysis. 
 
5.8 
Optokinetic Video Footage 
An optokinetic video stimulus will be viewed by trial participants in order to induce 
physiological nystagmus. The footage consists of a black dot rolling across the screen. To 
ensure that the CAVA device is capable of recording a variety of eye movement characteristics, 
the speed and direction of the rolling dot will vary by participant. During enrolment, each 
participant will be assigned a specific video for use throughout the trial. 8 out of the 15 
participants will be assigned rightward rolling dots (inducing left-beating nystagmus), and 7 
will be given leftward rolling dots (inducing right-beating nystagmus). Three separate speeds 
will also be used (slow, medium and fast), with 5 participants assigned to each speed. In 
summary, the videos will be distributed as follows: 
 
i. 
3 participants assigned rightward rolling dots at a slow speed. 
 
ii. 
2 participants assigned leftward rolling dots at a slow speed. 
 
iii. 
3 participants assigned rightward rolling dots at a medium speed. 
 
iv. 
2 participants assigned leftward rolling dots at a medium speed. 
 
v. 
2 participants assigned rightward rolling dots at a fast speed. 
 
vi. 
3 participants assigned leftward rolling dots at a fast speed. 
 
5.9 
Data handling protocol 
 
Once the device has been returned, the device data will be downloaded by the blinded 
investigator (JN). JN will use software to parse and re-segment the data into 30 full calendar 
days’ worth of data and will upload the data to the University of East Anglia’s research storage. 
The unblinded investigator (SC) will then download a copy of the data.  SC will manually 
review the data to confirm that the device was capturing meaningful data during the trial. The 
success of the trial is determined in part by the sensitivity and specificity of the nystagmus 
detection algorithm used by JN, for which a ground-truth labelling of the data is required (i.e. 
whether nystagmus is present or not). In the event that a participant does not wear their 
device or does not view the optokinetic video, their diary may indicate the presence of 
nystagmus, when in fact it is absent from the data. The detection algorithm may then be 
incorrectly judged as having failed to identify a period of nystagmus. For this reason, it would 
be inappropriate to include non-meaningful data in the pool of randomised data passed to JN. 
 

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SC will judge whether data is meaningful by manually reviewing it for evidence that the device 
has been recording an informative signal (i.e. not simply a flat line), and in so doing determine 
if the device has been worn by the participant. SC will also examine the recorded signals for 
any evidence of the characteristic nystagmus waveform on the dates and times logged in the 
participant’s trial diary. An absence of any nystagmus, irrespective of its quality, would 
suggest that the participant had not viewed the optokinetic video, despite having claimed to 
have done so. A false claim would be grounds for all of the participant’s data to be deemed 
non-meaningful. All non-meaningful data will be excluded from further analysis. 
 
After SC has confirmed that the device data is meaningful, he will assign each of the individual 
‘days of data’ a unique identifier, and then reorder the files into a random order.  Using a 
coding sheet only the un-blinded investigator (SC) will be able to determine the origin 
(participant and date) for each ‘day of data’.  The data will then be analysed off-line by the 
blinded investigator (JN). JN will apply a computer algorithm to the data files, which has been 
developed as part of the scientific research element of this MRC funded project. This 
algorithm will produce a list of the files which it has identified as containing nystagmus. The 
accuracy of this algorithm will be determined by SC, who will compare the predicted dates 
generated by JN to the ground-truth dates from the trial diaries. A document detailing the 
data download processes can be found in appendix M. 
 
 
Trial participants will wear the device for 30 days in total. However, the first and last days of 
the trial (days 1 and 31, respectively) will be half days, as the device will be applied in the 
morning of day 1 and removed for the last time on the morning of day 31. During the re-
segmentation process, the blinded investigator (JN) will append the data from day 31 to the 
end of the file from day 1, making 1 full day. Additionally, when the device is disconnected 
from a computer (e.g. during day 13’s face to face visit), the device will start logging to a new 
data file. Therefore, where days comprise multiple data files, such files will also be joined 
together. Finally, the device’s internal clock does not account for British Daylight Saving Time 
(DST), and so the re-segmenting procedure will also include adjustments for DST. Any periods 
of time where the device was not worn for a legitimate reason (e.g. during the face-to-face 
visits) will be excluded from calculations of user compliance and device functioning. 
 
5.10 
For each participant, the un-blinded investigator (SC) will submit the following anonymized 
data for statistical analysis by the project statistician: 
 
 
i. 
Number of true positive days. 
 
 
ii. 
Number of false positive days. 
 
iii. 
Number of true negative days. 
 
iv. 
Number of false negative days. 
 
 
v. 
Duration of use for each day of the trial for each participant 
 
 
5.11 
Verification of correct time-stamping, and correct event-marking 
 
Confirmation of correct time-stamping and event-marker function will be achieved by 
comparing the written record of when the event marker was employed with the downloaded 
record of when the event-marker was employed.  
 

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5.12 
Verification of correct accelerometer functioning 
 
This will be confirmed by reviewing data from day thirty-two of the trial. 
 
5.13 
Study activities and evaluations 
 
 
Each participant’s involvement in the trial will follow a predetermined schedule, as defined 
below. A detailed description of each activity can be found in the Clinical Investigation 
Flowchart (See appendix N). 
 
 
Day 
Activity  
 
 
 
 
Location 
Staff Member 
 
 
- >7 
PIS sent to potential participant  
 
Home  
R. Nurse / RA 
 
 
0 
Consent, enrolment and introduction 
 
NNUH  
JP 
 
 
0 
Device & headset training 
 
 
NNUH  
RA 
 
 
0 
Wall chart exercises 
 
 
 
NNUH  
RA 
 
 
4-5 
Face to face review 
 
 
 
NNUH  
R. Nurse / RA 
 
 
13 
Face to face review, battery change, 
 
 
timestamp and event marker test 
 
NNUH  
R. Nurse / RA 
 
 
32-36 Trial hardware returned 
 
 
NNUH  
R. Nurse / RA 
 
 
32-36 Questionnaire completed 
 
 
NNUH  
R. Nurse / RA 
 
 
32-36 Accelerometer tests 
 
 
 
NNUH  
RA 
 
 
32-36 Wall chart exercises 
 
 
 
NNUH  
RA 
 
 
32-36 Caloric testing  
 
 
 
NNUH  
R. Nurse / RA / JFG 
 
 
32-36 End of study 
 
 
 
 
NNUH  
R. Nurse / RA 
 
 
0-36 
Optional interim review  
 
 
NNUH  
R. Nurse / RA / JP 
 
 
 
 
RA = Research Associate 
 
JFG = Dr John Fitzgerald (Consultant Clinical Scientist) 
 
5.14 
Adverse event reporting 
Timely, accurate, and complete reporting and analysis of safety information from this trial 
will be conducted in accordance with Good Clinical Practice.  We will assess skin reactions 
according to the International Contact Dermatitis Research Group scoring system. 
 
5.15 
Policy for reimbursement of participant costs and expenses 
Participants will be reimbursed for the inconvenience endured as a result of participating in 
this trial.  This reimbursement will be staged according to the length of their involvement as 
detailed below.  All payments will be provided at the end of the trial.  Travelling expenses 

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and parking charges will be fully reimbursed.  Payment may be withheld if the study 
materials are damaged or lost. 
 
Drop out after one week 
 
 
 
 
 
 
£100 
 
Drop out or termination after two weeks 
 
 
 
 
£200 
 
Drop out after three weeks 
 
 
 
 
 
 
£300 
 
Drop out after four weeks (caloric testing not completed) 
 
 
£400 
 
Completion of the whole trial (4 weeks with caloric testing completed)  
£500 
 
5.16.1 Early participant termination procedure and policy 
The purpose of early termination is to: 
1. 
Allow early identification of poor participant compliance.   
2. 
Allow early identification of device failure. 
3. 
Allow early identification of safety issues. 
 
Early termination would allow mitigation of valuable wasted time and resources. 
 
5.16.2 Process 
- 
At 13 days, device data will be downloaded, but not erased from the device. 
- 
Data would be assessed by SJC. 
- 
A decision for termination will be provided within 24 hours. 
- 
A decision for early participant termination would be determined to be the -
consequence of poor participant compliance in circumstances where data is being 
recorded, but there is a persistent period of eye or head inactivity during the day. 
- 
A decision for early participant termination would be determined to be the 
consequence of poor participant compliance in circumstances where the device data 
shows that the device’s electrodes have not been applied correctly to the face. 
- 
A decision for early participant termination would be determined to be the 
consequence of poor participant compliance in circumstances where the trial diary 
has not been completed. 
- 
A decision for early participant termination would be determined to be the 
consequence of poor participant compliance in circumstances where the trial diary 
or data captured indicates that the participant has repeatedly worn the device for 
periods exceeding 24 hours. 
- 
A decision for early participant termination would be determined to be the 
consequence of device failure in circumstances where no data is recorded. 
 
5.16.3 Policy 
In cases of poor participant compliance, participant data would be omitted from final 
analysis.  In cases of device failure, participant data would be submitted for final analysis. 
 
5.16.4 Safety stopping criteria 
If any evidence of skin irritation is visible during any of the return visits of a participant, 
including during any additional visits, then that participant’s involvement in the investigation 
will cease. Additionally, if a participant reports an adverse event which has affected their 
safety and which could conceivably be linked to the use of the CAVA device, that 
participant’s involvement in the investigation will cease. Data captured up until the point of 

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exclusion will be submitted for final analysis unless the safety issue in question is deemed to 
have affected the quality of the signal recorded. 
 
5.16.5 Other circumstances 
In cases of device misuse causing damage to the device, e.g. accidental exposure to water, 
trauma to the device, etc; participants will be terminated early from the trial, and data 
would be submitted for final analysis. 
 
5.17.1 Early study termination procedure and policy 
The purpose of early study termination is to: 
1. 
Allow early identification of a consistent pattern of device failure. 
2. 
Allow early identification of safety issues. 
 
5.17.2 Process 
- 
Participants will be encouraged to report any unusual device operations or safety 
concerns throughout their involvement in the trial, both in their trial diary and by 
contacting the research team. 
- 
Adverse event reporting will be used to track and assess the risks identified. 
- 
The safety stopping criteria (5.17.4) will determine whether the trial will be 
terminated on the basis of safety. 
- 
Early study termination would be determined to be the consequence of a consistent 
pattern of device failure if 2 or more devices are found to have recorded no data, 
during any of the return visits. 
5.17.3 Policy 
In cases of device failure, participant data would be submitted for final analysis. For 
termination due to safety issues, data captured up until the point of exclusion will be 
submitted for final analysis unless the safety issue in question is deemed to have affected 
the quality of the signal recorded. 
 
5.17.4 Safety stopping criteria 
The study will be terminated if we identify any unforeseen safety issues which apply to the 
use of the CAVA device, and which constitute a likely and significant hazard to participant 
safety. 

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6 
OUTCOMES & DATA ANALYSIS 
 
6.1 
Nystagmus identification 
 
This will be derived for each participant by comparing the actual nystagmus data and the 
device-derived nystagmus data.  Data will be collated to calculate an overall value for 
sensitivity and specificity for all participants – see appendix O. 
 
6.2 
Signal production 
 
This will be calculated for each participant by appraising the percentage of non-useful data 
and number of drop-outs for each day of device usage, as well as for the entire thirty-day trial.  
Data will be collated to calculate an overall value for device reliability for all participants. 
 
6.3 
Device compliance 
 
This will be calculated for each participant by appraising the percentage of time the device 
was worn for each day of the trial usage, as well as for the entire thirty-day trial.  Data will be 
collated to calculate an overall value for device compliance for all participants. 
 
6.3 
Event-marker, timestamping hardware and accelerometer 
 
For each participant, data derived during return visits will be assessed to confirm that the 
event-marker functions, that the timestamping hardware is accurate, and that the 
accelerometer provides appropriate data. 
 
6.4 
Appraisal of satisfaction questionnaires and safety information 
A questionnaire will be completed by each participant at the end of trial to assess the comfort 
and acceptability of the device.  Safety information will also be acquired throughout each 
participant trial.  All data collected will be analysed using qualitative methods. 
 
6.5 
Appraisal of data from caloric vestibular testing 
 
Data recorded using traditional caloric testing techniques will be compared visually to the data 
recorded by the device. 
 
 

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7 
REFERENCES 
 
Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of 
therapy in Menière's disease. American Academy of Otolaryngology-Head and Neck 
Foundation, Inc. Otolaryngol Head Neck Surg. 1995;113(3):181-5. 
 
British Society of Audiology.  Recommended procedures: The Caloric test. April 2010 
 
Halmagyi GM. Diagnosis and management of vertigo. Clin Med 2005;5(2):159–65. Huh YE, 
Kim JS. Bedside evaluation of dizzy patients. J Clin Neurol. 2013;9(4):203-13  
 
Molnar A, McGee S. Diagnosing and Treating Dizziness. Med Clin North Am. 2014;98(3):583-
596  
 
Phillips JS, Mallinson AI. Vertigo: diagnosis and management. BMJ Learning. 
http://learning.bmj.com/learning/module-intro/.html?moduleId=10016740. Accessed 1st 
March 2015.  
 
Phillips JS, Mallinson AI, Hamid MA. Cost-effective evaluation of the vestibular patient. Curr 
Opin Otolaryngol Head Neck Surg. 2011.  
 
Phillips J, Longridge N, Mallinson A, Robinson G. Migraine and vertigo: a marriage of 
convenience? Headache. 2010;50(8):1362-5.  
 
Rauch S. Ambulatory Vestibular Monitoring. New Dimensions in Designing Medical Devices. 
2008  
 
Royal College of Physicians. Hearing and balance disorders: achieving excellence in diagnosis 
and management. Report of a Working Party. London: RCP, 2007.  
 
McCaslin D. Electronystamography/Videonystagmography. Plural Publishing, 2012 
 
Nazareth I, Yardley L, Owens N, Luxon LM. Outcome of symptoms of dizziness in a general 
practice community sample. Family Practice 1999;16(6):616–19.  
 
Neuhauser NK, von Brevern M, Radtke A, Lezius et al. Epidemiology of vestibular vertigo. A 
neurotologic survey of the general population. Neurology 2005;65:898–904.  
Roydhouse N. Vertigo and its treatment. Drugs 1974;7:297–309.  
 
Serra A, Leigh RJ. Diagnostic value of nystagmus: spontaneous and induced ocular 
oscillations. Neurol Neurosurg Psychiatry. 2002;73(6):615-8.  
 
Scuffham P, Chaplin S, Legood R. The incidence and cost of unintentional falls in older 
people in the United Kingdom. J Epidemiol Community Health 2003;57:740 
 
Zimetbaum P, Goldman A. Ambulatory arrhythmia monitoring: choosing the right device. 
Circulation. 2010;122(16):1629-36. 
 
 
 
 
 

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7 
APPENDICES 
 
7.1 
APPENDIX A: EMAIL TEMPLATE AND POSTER 
 
Dear Department Manager, 
 
My name is Jacob Newman and I am a research associate in the School of Computing Sciences. I am 
working on a project to develop a wearable medical device, which is hoped will aid the treatment of 
patients suffering from dizziness.  
 
We are currently seeking healthy volunteers to take part in a clinical trial to evaluate our device. 
More information about the study, including details of how to get involved, can be found in the 
attached poster. 
 
I would be most grateful if you could forward this email (including the poster) to the staff and 
students in your department. If you have any questions about this project, please get in touch. 
 
Yours sincerely, 
 
Jacob Newman 
 
 
 
 
 
IRAS ID: 240847 
Version 2.0, 1st May 2018, Page 1 of 1 
 
HEALTHY VOLUNTEERS NEEDED 
for a clinical trial 
 
 
 
 
 
 
 
 
 
The Norfolk and Norwich University Hospital is seeking 
volunteers to participate in a clinical trial to evaluate a wearable 
medical device. It is hoped that the device will aid the treatment 
of patients suffering from dizziness. 
 
 
Participation in the study requires you to wear a medical device 
on your face for up to thirty days. At the end of the trial, you would 
be asked to undergo a routine balance assessment test, known 
as a caloric test. 
 
You may be eligible to take part if: 
• You are aged 18 or over. 
• You can to commit to wearing a medical device for 30 days. 
• You are in good health. 
 
You will receive up to £500 for taking part, and 
your travel expenses will be paid. 
 
For more information, call 
(01603) 593054 or visit 
www.cava-project.org 

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7.2 
APPENDIX B: PARTICIPANT INFORMATION SHEET 
 
 
 
This document has been produced as an independent standalone document. 
 
7.3 
APPENDIX C: CONSENT FORM 
 
 
This document has been produced as an independent standalone document. 
 
7.4 
APPENDIX D: DATA COLLECTION FORMS 
 
 
This document has been produced as an independent standalone document. 
 
7.5 
APPENDIX E: GP LETTER 
 
 
This document has been produced as an independent standalone document. 
 
 
 

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7.6 
APPENDIX F: INFORMATION REGARDING THE USE OF THE DEVICE 
 
Please note: The following instructions are extracts from the full “Trial Instructions for Participants” 
document supplied to each trial participant. 
 
Introduction 
 
These instructions explain every aspect of using the device and its accessories during the 30-day trial. 
Dr Jacob Newman (Research Scientist) will go through this information with you and instruct you on 
everything you will be expected to do during the trial. If you have any questions, please ask him. 
 
Please remember: 
• 
You are required to wear the device for 23 hours a day, for a period of 30 days. 
• 
We hope that you will take part in the entire trial, however you are free to withdraw from the 
trial at any time. The longer you participate in the trial, the more money you will receive at 
the end. You can receive up to a maximum of £500 if you complete the entire trial, including 
the balance assessment at the hospital. 
• 
We request that if you already know of any reason why you will have to withdraw from the 
trial prematurely, please inform the research team as soon as possible. 
 
Please familiarise yourself with the CONTACT INFORMATION presented in the Important Information 
section at the end of this document. It explains what you should do in the event of an emergency and 
how to contact the research team. 
 
You have been given a trial pack which contains the following items: 
1 x trial instructions for participants (this document) 
1 x instructions for use 
1 x device logging module 
35 x sealed electrode arrays (35 each of left and right mounts) 
1 x medical adhesive remover 
1 x mobile phone 
1 x mobile phone charging cable 
1 x mobile phone charging adapter 
10 x mobile phone screen cleaning wipes 
1 x pack of antibacterial wipes for the VR headset 
1 x virtual reality (VR) headset 
1 x trial diary 
1 x ballpoint pen 
 
 
 

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General Trial Instructions 
 
DURING the trial, you should follow these rules and procedures: 
• 
You should go about your normal daily activities whilst wearing the device. 
• 
You should avoid looking out of the side window of a moving vehicle (car or train) as a 
passenger for a prolonged period of time.  If you do, please record this activity in your trial 
diary. 
• 
You should not use a swivel chair or spin yourself excessively. If you do, please record this 
activity in your trial diary. 
• 
You may drink alcohol during the trial, however we request that you do not drink to the 
extent that you might experience a hangover and feel dizzy as a result. If you do experience 
dizziness as a result of alcohol consumption, please record this activity in your trial diary. 
• 
You should not immerse the device in water (i.e. no swimming or showering whilst wearing 
the device. Avoid exposing the device to rain). If the device is accidentally or unavoidably 
exposed to water, you should make a note in your trial diary and contact a member of the 
research team for further assistance. 
• 
You should remove the device once a day, for an hour, to allow you to clean and shower 
(see guide, Removing the Device). 
• 
After washing, you should make sure that your skin is completely dry before reapplying the 
device and a new sensor array (see guide, Putting on the Device). 
• 
You should only view the optokinetic stimulus on the 8 separate days listed in your trial 
diary (see guide, Optokinetic Video Stimulus). On the first 4 of these days you should watch 
the video while sitting or standing still. On the last four you should watch the video while 
walking gently on the spot. When you watch the video, you should make sure that you are in 
an open space, free from physical obstacles and psychological distractions. You should not 
view the optokinetic stimulus at any other time during the trial. 
• 
You should make notes in your trial diary indicating the date and time of when you viewed 
the optokinetic stimulus. Also make note of any times you accidentally looked out of the 
window of a moving vehicle as a passenger, or of any unexpected events that occur during 
the trial 
• 
If you have to charge the mobile phone, you should make a note in your trial diary, listing 
the date and time. 
• 
You should also take note in your diary of any unusual device or sensor operation, or any 
other unexpected events that occurred during the trial. 
 
At the END of the trial, the following activities will take place: 
• 
On day 35 you will return to the clinic with the device, its accessories and all used and 
unused sensor arrays. 
• 
We will ask you to complete a questionnaire on your experiences of using the device. 
• 
We will ask you to perform some simple head movements whilst wearing the device. 
• 
A medical scientist will perform a balance assessment on you (caloric testing) whilst wearing 
the device. 
• 
You will be debriefed from the trial. 
 
 
 

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Device Instructions 
 
The CAVA device is comprised of three main components: Two single-use electrode mounts that 
adhere to either side of your face, and an electronic, reusable logging module which stores the 
signal from the electrodes, and which rests behind the ear (Diagrams 1 and 2). 
 
 
 
Diagram 1 - CAVA device components: Electrode mounts and logging unit. 
 
 
 
Diagram 2 - CAVA device positioning on the head. 
 
 
 

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Putting on the Device 
 
• You do not need to switch the device on or off. It will remain powered throughout the 
trial. 
• You should not reapply the same electrode mount more than once. Always use a new 
mount. 
• The electrodes should be applied to clean skin, free from oils or lotions. Use soap and 
water to clean the areas where they will be applied. Make sure your skin is completely 
dry in the areas where the electrode’s adhesive pads will attach to your face. 
• You should use a mirror to help you apply the device to your face. 
• If you wear spectacles, you should remove them until you have put the device on 
successfully. 
• If you make a mistake which means that the electrodes won’t be applied to the right 
place or will not stay in place, you should remove them and then start again with a 
new electrode array. 
• Diagram 3 shows what to do before you apply the device and Diagram 4 shows how 
to apply the device to your face 
• Once you have applied the device to your face, you should check the status of the 
device to ensure that it is functioning correctly. See the guide, Checking the Status of 
the Device, for instructions on this process. 
 
 
 
Diagram 3 – Before applying the device. 

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Diagram 4 – Putting on the device. 
 
 
 

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Checking the Status of the Device 
 
• 
You can check the status of the CAVA device by pressing and holding the event marker 
button for 2 seconds. You will need to use a mirror to see the status LED on the device. See 
Diagram 5 below for a guide to this process. 
• 
The device has four possible LED patterns: steady green (device/battery OK), flashing green 
(low battery), steady red (battery/device problem), flashing red (electrode disconnection). 
• 
When you have attached the device to your face, you should check the status of the device. 
You will need to use a mirror see the status LED. If the device is connected and functioning 
correctly, a steady green LED will illuminate for 10 seconds. If any other pattern of LED is 
displayed please refer to the Troubleshooting guide in the Maintenance section of this 
document. 
 
 
 
 
Diagram 5 – Checking the status of the device. 
 
 
 

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Removing the Device 
 
• 
Once a day you should remove the logging unit and the electrode array for up to an hour to 
clean or shower yourself, being sure to clean your face. 
• 
This hour may be in the morning or in the evening, but once you have selected a time you 
should try to stick to it, as you should not wear the device for more than 23 hours at a time. 
• 
Once you have unplugged the electrode mounts from the logging unit, you should use the 
medical adhesive remover to help remove the electrodes. 
• 
When removing each electrode from your face, you should support the skin next to the 
electrode so that it is under tension, before slowly rolling each electrode back onto itself. 
• 
To remove the device, you should follow the instructions in Diagram 6, below. 
• 
Once removed, you should detach the electrode mounts from the logging unit and store 
them in the bag provided. You will need to return them to the clinic at the end of the trial. 
 

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Diagram 6 – Removing the device. 
 

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Cleaning Information 
 
• 
Only clean the main sensor unit using a lightly damp cloth or non-alcohol containing cleaning 
wipe. 
• 
Allow to dry before re-applying. 
• 
On no account use a bleach or alcohol-based detergent on the unit. 
• 
Before viewing the optokinetic footage, ensure that the phone screen and VR headset lenses 
are clean by using one of the Zeiss lens cleaning wipes you have been supplied with. 
• 
After use, the cushioning on the VR headset should be cleaned using one of the antibacterial 
wipes supplied to you, and then wiped dry with a paper towel. 
 
Charging the Mobile Phone 
 
• 
The mobile phone should only be turned on for the purpose of viewing the optokinetic video 
stimulus. It should be switched off after you have finished viewing the video. The battery in 
the mobile phone should stay charged sufficiently to use it on 8 occasions during the trial. 
However, if the battery charge falls below 20%, you should recharge the phone as follows. 
• 
You should insert one end of the phone charging cable into the bottom of the phone and the 
other end into the phone’s wall adapter. 
• 
You should plug the wall adapter into a plug socket and turn the socket on. 
• 
Ensure that the charging icon is visible next to the battery indicator. If it is not, ensure that 
the previous steps have been followed correctly.  
• 
The phone should charge to about 90% in less than 2 hours. 
• 
Once the charge reaches over 90%, you should switch off the plug socket, unplug the cables, 
and resume the Optokinetic Video Stimulus steps where necessary. 
• 
If the phone will not turn on at all or will not charge, you should contact the research team 
at the hospital (See CONTACT INFORMATION in the Important Information section at the 
end of this document). 
 
Troubleshooting 
 
• 
If, when checking the status of the device, the steady green LED does not illuminate, check 
that all the cable connectors are inserted correctly and that the electrodes are applied 
correctly to your face. When you recheck the status, if the green LED still fails to show, 
remove the device and repeat the procedure for putting on the device. 
• 
If the green LED flashes or shows a red light, you should contact the research team (See 
CONTACT INFORMATION in the Important Information section at the end of this document). 
• 
If the steady green LED does not show after following these instructions, you should contact 
the research team at the hospital for advice (See CONTACT INFORMATION). 
 
 
 

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Important Information 
 
During the trial, please follow these rules: 
 
• 
Please AVOID looking out of a side-facing window in a moving car or train as a passenger for 
a prolonged period of time.  However, if this situation is unavoidable, please make precise 
notes in your diary of the dates and times that these events occurred. 
• 
You may drink alcohol during the trial, however we request that you do not drink to the extent 
that you might experience a hangover and feel dizzy as a result. If you do experience dizziness 
as a result of alcohol consumption, please make precise notes in your diary of the dates and 
times that the dizziness occurred. 
• 
Please DO NOT use a swivel chair during the trial or otherwise spin yourself excessively. As 
above, if this situation is unavoidable, please make notes in your diary. 
• 
Please DO NOT view the optokinetic stimulus on days other than the 8 days listed in your trial 
diary. 
 
The followings warnings apply to using the CAVA device. Failure to follow these practices may lead to 
injury or harm. 
 
WARNINGS 
 
• 
Only to be used by trial participant under the guidance of medical personnel. 
 
The device should not be used by: 
 
• 
Users with a history of skin sensitivities / allergic reactions to materials used in the device or 
similar items such as plasters or medical adhesives. 
• 
Users with inflamed or broken skin where the sensor is worn.   
• 
Users who experience rashing or irritation should discontinue use and seek medical advice.  
• 
Children and young adults less than 18 years old.  
• 
Only connect the provided sensors to the main unit. On no account should the unit be 
connected to other devices such as USB chargers, laptops etc. 
• 
Only clean the device using the instruction provided in this manual. 
• 
Users engaged in activities which require the user of a safety personal protective equipment 
(e.g.: cycle helmet) must remove this device if it interferes with the safe operation of the 
protective equipment. 
• 
Remove this device if you are passing through equipment which uses electromagnetic energy 
to screen or monitor people. This includes MRI, X RAY or CT scanners and devices like airport 
security scanners. 
• 
Always make your healthcare carers aware of the fact you are wearing the trial equipment 
when attending clinics etc. A description card is provided at the end of the manual which can 
be used for this purpose. 
 
The following cautions apply to using the CAVA device. Failure to follow these practices may affect the 
performance of the device. 
 
CAUTIONS 
 
• 
Avoid exposure to moisture and water. The device should be removed before bathing or 
washing. 
• 
No user serviceable parts – The device should not be opened or disassembled 

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CONTACT INFORMATION 
 
If you have a medical issue or medical question concerning the trial, please contact: 
 
Ms Catherine Wright (Research Nurse) or Mr John Phillips (Surgeon) 
Norfolk & Norwich University Hospitals NHS Trust 
Colney Lane 
Norwich 
NR4 7UY 
Tel: (01603) 286286 
 
If you need to speak to the research team for any non-medical reason during the trial, please contact: 
 
Dr Jacob Newman (Research Scientist) 
University of East Anglia 
Norwich Research Park 
NR4 7TJ 
Tel: (01603) 593054 
 
Following is a list of example scenarios in which you should contact the research team:  
 
§ 
In the event of any unexpected issues or complications arising from wearing the device, 
immediately contact Catherine Wright (Research Nurse) or another member of the Research 
team. 
§ 
If you experience skin irritation or any other unexpected side effects whilst wearing the 
device, remove the device and immediately contact Catherine Wright (Research Nurse) or 
another member of the Research team. 
• 
If the device will not turn on or will not display a steady green LED when applied to your face, 
contact Dr Jacob Newman (Research Scientist). 
• 
If you have issues related to the mobile phone, including using or charging the phone, please 
contact Dr Jacob Newman (Research Scientist). 
• 
If you have any other questions or concerns during or after the trial, do not hesitate to contact 
any member of the research team. 
 
 

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7.7 
APPENDIX G: INFORMATION REGARDING THE USE OF THE MOBILE PHONE 
 
Please note: The following instructions are extracts from the full “Trial Instructions for Participants” 
document supplied to each trial participant.  
 
Notes on the Mobile Phone and VR Headset 
 
The mobile phone supplied to you does not contain a sim card and is set to “airplane mode”, which 
means that it cannot access Wi-Fi or Bluetooth. The phone is not intended to be used for any purpose 
other than viewing the optokinetic stimulus on the 8 days listed in your trial diary. The phone is fixed 
to the removable tray in the VR headset (Diagram 7). As described in the guide, Optokinetic Video 
Stimulus, the phone should only be turned on for the purpose of viewing the stimulus and should be 
turned off at all other times. The battery in the phone should remain charged for the duration of the 
trial, however, if its charge falls below 20% you should follow the steps in the guide, Charging the 
Mobile Phone, in the Maintenance section of this document. 
 
 
Diagram 7 - VR headset with headset tray partially inserted. 
 
Before using the phone and headset, you should ensure that the phone screen and VR headset lenses 
are clean, using the lens wipes supplied to you. Instructions on how to view the optokinetic stimulus 
using the phone and headset can be found in the guide, Optokinetic Video Stimulus. These instructions 
also state that you should use the lens adjustment controls (Diagram 7) if the calibration image 
appears to be blurry or if you can see a double image. Sliding the controls forwards and backwards 
adjusts the focus, while left and right adjusts the distance between the lenses. Once you have viewed 
the video stimulus, you should wipe the cushioning on the VR headset using one of the antibacterial 
wipes supplied to you, and then wipe it dry with a paper towel. Remember to turn the phone off and 
store the tray inside the VR headset when it is not in use. 
 
 

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7.8 
APPENDIX H: FOLLOWING THE NYSTAGMUS TESTING PROTOCOL USE OF THE DEVICE 
 
Please note: The following instructions are extracts from the full “Trial Instructions for 
Participants” document supplied to each trial participant. 
 
 
Please thoroughly familiarise yourself with these instructions before you attempt to watch the video 
stimulus. 
• 
The optokinetic video stimulus is a 55-second video containing three segments. The video 
starts with a 20-second on-screen countdown, followed by the optokinetic stimulus, which is 
a 30-second video showing black dots rolling across the screen.  Finally, the video ends by 
displaying a green background for 5 seconds. 
• 
You should view the optokinetic video stimulus on 8 separate days of the 30-day trial. These 
dates are listed in your trial diary, provided to you by the research team. 
• 
You should make a note in your trial diary of the dates and times that you viewed the 
optokinetic stimulus. You must also press and hold the event marker button on the device (for 
1 second) at the start and the end of viewing the stimulus (Diagram 8).  
• 
On each of the 8 days, you should use the VR headset and mobile phone to watch one play of 
the entire optokinetic video. On the first 4 of these days you will watch the video while 
remaining still, and on the last 4 you will walk gently on the spot. 
• 
When you watch the video, you should make sure that you are in an open space, free from 
physical obstacles and psychological distractions. 
• 
You should watch the video at some time between 10am and 12pm (midday). 
• 
You should only watch the video if you have been wearing the device for at least 10 minutes. 
• 
If you attempt to view the stimulus but you are unable to or something goes wrong, please 
contact Dr Jacob Newman (see CONTACT INFORMATION in the Important Information 
section), who will advise you on how to fix the issues you are having. If the delay stops you 
from viewing the stimulus between 10am and midday, you will be instructed you to view the 
stimulus in the afternoon or during the following day.  
 
 
 
Diagram 8 – Activating the event marker. 
 
 
 
 

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Version 2.5, 20th September 2018, Page 32 of 43 
To view the optokinetic video, you should follow these 13 steps: 
 
1. Check the status of the device (See the guide, Checking the Status of the Device). If the status 
LED is red or flashing, you should contact the research team (See CONTACT INFORMATION). 
2. Take the tray out of the VR headset. 
3. Ensure that the phone screen and VR headset lenses are clean by using one of the Zeiss lens 
cleaning wipes you have been supplied with. 
4. Turn the mobile phone on by holding the power button on the right-hand side until the screen 
turns on. Wait until the lock screen is displayed. Swipe upwards from the middle of the screen 
to unlock the phone, revealing the home screen. 
5. If the phone has less than 20% battery power remaining, follow the steps in the Charging the 
Mobile Phone guide, in the Maintenance section of this document. 
6. Open the Kodi app on the phone, then tap Favourites. 
7. If you wear glasses, you should remove them now. 
8. Tap on calibration.png and slide the tray back into the VR headset. Look at the image through 
the headset. If it is blurred, adjust the controls on the headset until it is clear. You may only 
have to follow this step once as the headset should remain calibrated. When complete, 
remove the tray from the headset and exit the image by pressing the screen for two seconds. 
9. You are almost ready to view the optokinetic video, but before you do, you should read the 
following information and instructions: 
§ 
The video will start with a 20-second countdown, giving you time to slide the 
tray back into the headset and to look through the eyepieces. 
§ 
If the countdown starts but you are not ready to view the optokinetic footage, 
do not look at the phone until at least 1 minute has passed, then replay the 
video if necessary. 
§ 
After the countdown, the stimulus will be shown. It is a 30-second clip of dots 
rolling across the screen. 
§ 
On the first 4 days that you watch the video, you should stay still (sitting or 
standing) while watching the video. 
§ 
On the last 4 days that you watch the video, you should walk gently on the 
spot while watching the video. 
§ 
You should make sure that you are in an open space, free from physical 
obstacles and psychological distractions. 
§ 
The video will end by displaying a green screen for 5 seconds. 
§ 
You should try to follow every dot across the screen with your eyes. 
§ 
You should not shut your eyes or look at the edge of the video. 
10. When you are ready to watch the video, you should make a note of the date and time in your 
trial diary and press the event marker on the CAVA device (Diagram 5). 
11. To watch the optokinetic video, tap on opto_video.mp4, slide the tray back into the headset, 
look through the eyepieces and wait for the rolling dots clip to begin. When the green screen 
is displayed, you may stop watching the video and move the headset away from your face. 
12. When you have finished watching the video, remove the tray from the headset and turn the 
phone off by holding the power button until a button appears on the screen saying “Power 
off”. Press this button and then the “Touch to power off” button which follows it. You should 
slide the tray back into the VR headset. 
13. The cushioning on the VR headset should be cleaned using one of the antibacterial wipes 
supplied to you, and then wiped dry with a paper towel. 
 
 

CONFIDENTIAL - IRAS ID: 240847 
Version 2.5, 20th September 2018, Page 33 of 43 
7.9 
APPENDIX I: TRIAL DIARY 
 
 
 
 
 
PARTICIPANT ID:______________ 
 
 
CONFIDENTIAL - IRAS ID: 240847 - Version 1.2, 13th July 2018, Page 1 of 5 
Trial Diary 
Please fill in this diary daily. Please use this diary to record the times you carried out each trial activity and to list any unexpected events that occurred. 
 
Day 
Date 
(dd/mm) 
Trial Event 
Time device 
taken off 
hh:mm 
am/pm 
Time device 
put on 
hh:mm 
am/pm 
Optokinetic 
video day 
Time video 
viewed 
hh:mm 
am/pm 
Accidental activities (looking 
out of train window, spinning 
on chair etc) 
All other events (Discomfort, 
device won’t turn on, electrodes 
won’t stick etc) 
1 
 
First day 
wearing 
device 
- 
 
YES 
(STANDING OR 
SITTING STILL) 
 
 
 
2 
 
- 
 
 
NO  
 
 
 
3 
 
- 
 
 
NO 
 
 
 
4 
 
Face to face 
review at 
hospital 
 
 
NO 
 
 
 
5 
 
Face to face 
review at 
hospital 
 
 
YES 
(STANDING OR 
SITTING STILL) 
 
 
 
6 
 
- 
 
 
NO 
 
 
 
7 
 
- 
 
 
NO 
 
 
 
Day 
Date 
(dd/mm) 
Trial Event 
Time device 
taken off 
hh:mm 
am/pm 
Time device 
put on 
hh:mm 
am/pm 
Optokinetic 
video day 
Time video 
viewed 
hh:mm 
am/pm 
Accidental activities (looking 
out of train window, spinning 
on chair etc) 
All other events (Discomfort, 
device won’t turn on, electrodes 
won’t stick etc) 
 
PARTICIPANT ID:______________ 
CONFIDENTIAL - IRAS ID: 240847 - Version 1.2, 13th July 2018, Page 2 of 5 
8 
 
- 
 
 
YES 
(STANDING OR 
SITTING STILL) 
 
 
 
9 
 
- 
 
 
NO 
 
 
 
10 
 
- 
 
 
NO  
 
 
 
11 
 
- 
 
 
NO 
 
 
 
12 
 
- 
 
 
YES 
(STANDING OR 
SITTING STILL) 
 
 
 
13 
 
Face to face 
review at 
hospital 
 
 
NO 
 
 
 
14 
 
- 
 
 
NO  
 
 
 
15 
 
- 
 
 
YES 
(WALKING 
GENTLY ON THE 
SPOT) 
 
 
 

CONFIDENTIAL - IRAS ID: 240847 
Version 2.5, 20th September 2018, Page 34 of 43 
 
 
 
 
 
 
Day 
Date 
(dd/mm) 
Trial Event 
Time device 
taken off 
hh:mm 
am/pm 
Time device 
put on 
hh:mm 
am/pm 
Optokinetic 
video day 
Time video 
viewed 
hh:mm 
am/pm 
Accidental activities (looking 
out of train window, spinning 
on chair etc) 
All other events (Discomfort, 
device won’t turn on, electrodes 
won’t stick etc) 
 
PARTICIPANT ID:______________ 
CONFIDENTIAL - IRAS ID: 240847 - Version 1.2, 13th July 2018, Page 3 of 5 
16 
 
- 
 
 
NO 
 
 
 
 
 
 
17 
 
- 
 
 
NO 
 
 
 
18 
 
- 
 
 
NO  
 
 
 
19 
 
- 
 
 
YES 
(WALKING 
GENTLY ON THE 
SPOT) 
 
 
 
20 
 
- 
 
 
NO 
 
 
 
21 
 
- 
 
 
NO 
 
 
 
22 
 
- 
 
 
YES 
(WALKING 
GENTLY ON THE 
SPOT) 
 
 
 
23 
 
- 
 
 
NO 
 
 
 
Day 
Date 
(dd/mm) 
Trial Event 
Time device 
taken off 
hh:mm 
am/pm 
Time device 
put on 
hh:mm 
am/pm 
Optokinetic 
video day 
Time video 
viewed 
hh:mm 
am/pm 
Accidental activities (looking 
out of train window, spinning 
on chair etc) 
All other events (Discomfort, 
device won’t turn on, electrodes 
won’t stick etc) 
 
PARTICIPANT ID:______________ 
CONFIDENTIAL - IRAS ID: 240847 - Version 1.2, 13th July 2018, Page 4 of 5 
24 
 
- 
 
 
NO 
 
 
 
25 
 
- 
 
 
NO 
 
 
 
26 
 
- 
 
 
YES 
(WALKING 
GENTLY ON THE 
SPOT) 
 
 
 
27 
 
- 
 
 
NO 
 
 
 
28 
 
- 
 
 
NO 
 
 
 
29 
 
- 
 
 
NO 
 
 
 
30 
 
Last full day 
wearing 
device 
 
 
NO 
 
 
 
31 
 
Last day 
wearing 
device 
 
- 
NO 
 
 
 

CONFIDENTIAL - IRAS ID: 240847 
Version 2.5, 20th September 2018, Page 35 of 43 
 
 
 
 
 
 
 
 
 
PARTICIPANT ID:______________ 
 
 
CONFIDENTIAL - IRAS ID: 240847 - Version 1.2, 13th July 2018, Page 5 of 5 
 
If an entry will not fit in the diary table, please use this box instead. Please date your comments.   
 

CONFIDENTIAL - IRAS ID: 240847 
Version 2.5, 20th September 2018, Page 36 of 43 
7.10 
APPENDIX J: CLINICAL TRIAL TESTING PROTOCOL TRAINING 
 
Device training 
- 
Applying the device 
- 
Removing the device 
 
Mobile phone training 
- 
Optokinetic video preparation 
- 
Viewing of the optokinetic stimulus 
- 
Maintenance of the mobile phone 
 
Trial training 
- 
Looking after the device 
- 
When to view the nystagmus 
- 
Using the trial diary 
- 
When to visit the hospital 
 
Dr Jacob Newman (JN) will demonstrate all aspects of the mobile phone training and device training 
to the participant. Following an initial attempt, during which they may ask questions and ask for 
assistance, they must demonstrate the procedures unaided in 2 consecutive attempts. Participants 
will be provided with written instructions describing the trial training, which they must read and 
explain to JN. They must show a clear understanding of the tasks that have to be performed during 
the trial. 
 
Early termination criteria 
All training procedures, except viewing of the optokinetic stimulus, will be judged visually. For 
example, it is clear visually whether the device training procedures (applying and removing the 
device) are being demonstrated correctly. Viewing of the optokinetic stimulus will be judged 
according to the quality of the nystagmus signal captured by the CAVA device, and by watching the 
participant’s eyes while they observe the optokinetic stimulus on a screen. The instructions provided 
to the participants aim to elicit a “look” nystagmus response, which should produce a regular and 
visually identifiable nystagmus signal. Participants will be judged to have not followed the viewing 
instructions if nystagmus is either not present, or if it changes in a way which suggests a “stare” 
response is being produced. Failure to understand the trial training will be judged on the 
participant’s ability to consistently read and explain the activities that they must perform during the 
trial. 
 
Criteria: 
• 
Failure to demonstrate the device and mobile phone training procedures correctly on 2 
consecutive attempts. 
• 
3 consecutive failed attempts to demonstrate the device and mobile phone training 
procedures. 
• 
Failure to accurately recite the trial training procedures on 3 consecutive attempts. 
• 
A clear and repeated misunderstanding of the trial procedures. 
 
 
 

CONFIDENTIAL - IRAS ID: 240847 
Version 2.5, 20th September 2018, Page 37 of 43 
7.11 
APPENDIX K: PARTICIPANT EXPERIENCE QUESTIONNAIRE 
 
 
 
Thank you for taking part in our study. Please fill in this short questionnaire to share your experiences 
of using the device. It should take about 10 minutes to complete. There is a space below each question 
where you can provide additional information if you’d like to.  We may use your answers anonymously 
for research or promotional purposes – please let the team know if you are not happy for us to use 
the data in this way. 
 
1 - How easy did you find putting on the device and sensors? 
Very Hard 
1 
 
2 
 
3 
 
4 
Very Easy 
5 
 
 
 
 
 
Comments: 
 
 
 
 
2 - How easy did you find taking off the device and sensors? 
Very Hard 
1 
 
2 
 
3 
 
4 
Very Easy 
5 
 
 
 
 
 
Comments: 
 
 
 
 
3 - How easy did you find sleeping whilst wearing the device and sensors? 
Very Hard 
1 
 
2 
 
3 
 
4 
Very Easy 
5 
 
 
 
 
 
Comments: 
 
 
 
 
4 - How comfortable did you find the sensors on your face? 
Very 
Uncomfortable 
1 
 
2 
 
3 
 
4 
Very 
Comfortable 
5 
 
 
 
 
 
Comments: 
 
 
 
 
5 - How comfortable did you find the device on your ear? 
Very 
Uncomfortable 
1 
 
2 
 
3 
 
4 
Very 
Comfortable 
5 
 
 
 
 
 

CONFIDENTIAL - IRAS ID: 240847 
Version 2.5, 20th September 2018, Page 38 of 43 
Comments: 
 
 
 
6 - How much did the device interfere with your normal daily activities? 
A lot 
1 
 
2 
 
3 
 
4 
Not at all 
5 
 
 
 
 
 
Comments: 
 
 
 
 
7 – During an average day, how aware were you of the device and sensors on your face? 
Very Aware 
1 
 
2 
 
3 
 
4 
Not at all aware 
5 
 
 
 
 
 
Comments: 
 
 
 
 
8 - By the end of the trial, how self-conscious did you feel wearing the device? 
Very self-
conscious 
 
1 
 
 
2 
 
 
3 
 
 
4 
Not at all self-
conscious 
5 
 
 
 
 
 
Comments: 
 
 
 
 
9 - Can you think of any ways that we could improve the device and sensors? 
Comments: 
 
 
 
 
10 - Please detail any other experiences or opinions you have relating to the device. 
Comments: 
 
 
 
 
 
 
 
 
 
Thank you for answering the questionnaire. Please hand it back to a member of the research team. 

CONFIDENTIAL - IRAS ID: 240847 
Version 2.5, 20th September 2018, Page 39 of 43 
7.12 
APPENDIX L TESTING PROTOCOL FOR THE ACCELEROMETER 
 
Introduction 
After each participant has completed the 30-day trial, they will visit the clinic to return the device and 
its accessories, and to formally debrief from the clinical trial. During their visit, they will perform a 
number of simple head movements in order to provide data that will be used to evaluate the 
performance of the accelerometer on the CAVA device. The participants will receive instruction and 
supervision from the research team (The Research Nurse and Research Associate) during this exercise. 
This document outlines the testing procedure for evaluating the accelerometer. 
 
Testing Procedure 
During their visit to the clinic, participants will be asked to perform three types of head movement 
activities (Figure 1): A head shaking motion (A), a head nodding motion (B) and a head tilting motion 
(C). These actions will be used to assess the accelerometer’s capability to track motion in the yaw, 
pitch and roll axes. Each participant will perform these activities first at a “slow” speed and then at a 
“fast” speed. “Slow” means completing one instruction (e.g. look left) within approximately 4 seconds. 
“Fast” means completing one instruction within approximately 1 second.  
 
(A) Head shaking: 
 
i) Look forwards 
 
ii) Look left 
 
iii) Look forwards 
 
iv) Look right 
 
v) Look forwards 
(B) Head nodding: 
 
i) Look forwards 
 
ii) Look down 
 
iii) Look forwards 
 
iv) Look up 
 
v) Look forwards 
(C) Head tilting: 
 
i) Look forwards 
 
ii) Tilt left 
 
iii) Look forwards 
 
iv) Tilt right 
 
v) Look forwards 
Figure 1: The instructions for the three head movement activities. 
 
The three activities (A, B & C) comprise 5 separate instructions (i to v), and each activity will be 
repeated three times. Participants will be given time to practice each head movement and a member 
of the research team will be on hand to demonstrate the required movements. During data collection, 

CONFIDENTIAL - IRAS ID: 240847 
Version 2.5, 20th September 2018, Page 40 of 43 
these instructions will be recited to the participant by a member of the research team, after which 
they must perform the associated action. Between instructions, each participant will confirm when 
they are ready to proceed. Prior to performing each instruction, the participant will press the event 
marker on the device, to allow each head movement to be correlated with the data captured by the 
device. A member of the research team will also record notes on the order of activities performed and 
any other details relevant to the procedure. The 3 activities and their 5 instructions are as shown in 
Figure 1. 
 
The accelerometer will be evaluated based on whether a broad correlation is observed between the 
data captured and the head movements performed. The research associate will visually compare the 
data for this task. For example, if the participant moved their head to look left, then the research 
associate will look for evidence of a turn to the left in the accelerometer data. The performance 
characteristics of the accelerometer have been extensively tested and documented by its 
manufacturer, therefore we only seek to verify correct functioning of the device rather than its 
reported degree of accuracy. 
 
 
 
 

CONFIDENTIAL - IRAS ID: 240847 
Version 2.5, 20th September 2018, Page 41 of 43 
7.13 
APPENDIX M: DATA DOWNLOAD PROCESSES 
Data Download 
Once a participant has ﬁnished their involvement in the trial, the data from their device will be 
downloaded, transferred and processed as detailed by the following ﬂowcharts.  
* PDOS = Participant Dates of Nystagmus. 
JN is blinded from the Actual PDOS. These dates are 
known to SJC, who produced the Randomised EYES 
data. 
Data ﬁles summary 
• System report: Contact time/uptime/battery status 
• Eye measurements 
• Event marker 
• Accelerometer
to download and send as follows 
1 - Eyes 
 
2 - Event marker 
 
3 - Diary 
 
4 - Predetermined dates 
IN
JN
SJC
ALL 
DATA
EVENT 
MARKER
DIARY
PREDETERMINED 
DATES
JN
Parsed & 
Resegmented
Actual 
PDOS*
JN
Predicted 
PDOS*
SJC
Randomised 
EYES
Non-meaningful 
data excluded
Randomised 
EYES
University of East Anglia’s 
Research Storage
True Positives, 
False Positives, 
True Negatives, 
False Negatives 
Algorithm Sensitivity 
and Speciﬁcity 
to download 
1 - System report (battery & lead-oﬀ) 
2 - Accelerometer test 
3 - Event marker / time stamp test 
4 - Caloric data 
————————————————- 
JN to collate 
5 - Assess questionnaire responses 
6 - AE
JN

CONFIDENTIAL - IRAS ID: 240847 
Version 2.5, 20th September 2018, Page 42 of 43 
7.14 
APPENDIX N: CLINICAL INVESTIGATION FLOWCHART 
 
 
 
 
 
 
Clinical Investigation 
Flowchart 
 
 
 
Enquiry / PIS Sheet 
 
 
 
 
▼ 
Day 0: Thu 
 
Consent / Enrolment  
◀ 
 
 
 
 
Device & Headset Training 
 
 
 
 
▼ 
Day 1: Fri 
 
Start Wearing Device 
 
 
 
 
▼ 
 
Day 4-5: Mon/Tue
Face to Face Review  
◀ 
 
 
 
 
▼ 
 
 
Day 13: Wed  
Face to Face Review   
◀ 
 
 
 
Battery Change 
 
 
 
 
▼ 
Day 31: Sun  
Stop Wearing Device 
 
 
 
 
▼ 
 
Day 32-36: Mon-Fri Trial Hardware Returned 
◀ 
 
 
Questionnaire 
 
 
 
Caloric Testing 
 
 
 
Device Testing 
1.
Q&A Re PIS 
2.
Consent 
3.
Check inclusions & exclusions 
4.
Educate on: 
A. Device  
B. Smartphone 
C. Test protocol 
5.
Wall chart eye exercises for calibration 
6.
Check can follow protocol. If not, exclude 
7.
Provide list of dates to invoke nystagmus 
8.
Provide dates for activities, e.g. calorics 
9.
Sync device clock and make sure battery 
is new
1.
AE and Q&A
1.
AE and Q&A 
2.
Press event marker and record 
date and time 
3.
Battery change 
4.
Sync device clock 
5.
Check data (send to SJC to check, to 
respond within 24 hours)
1.
Return hardware 
2.
Questionnaire 
3.
Calorics 
4.
Accelerometer 
5.
Wall chart eye exercises for calibration 
6.
Send device to SJC to download data 
(see SJC Data Download)
JP 
JN 
(APB)
JN
JN
JN

CONFIDENTIAL - IRAS ID: 240847 
Version 2.5, 20th September 2018, Page 43 of 43 
7.15 
APPENDIX O: STATISTICAL METHODS TO DERIVE SENSITIVITY AND SPECIFICITY VALUES 
 
 
The success of a diagnostic device to diagnose disease can be appraised by calculating values 
for sensitivity and specificity.  This trial has been designed to exceed the minimum number of 
nystagmus days and minimum number of total days required to demonstrate with statistical 
significance a sensitivity and specificity of over 95%.  This standard was determined from data 
in the field of ambulatory cardiac monitoring (Zimetbaum 2010).  The calculations below were 
performed by a medical statistician to determine the minimum number of independent tests 
required for each milestone. 
 
 
 
 
Device 
 
 
  
Positive 
Negative 
Total 
Participant 
TRUE 
83(97.7) 
2(2.3%) 
85 
FALSE 
2 (2.3%) 
83 (97.7%) 
85 
 
Total 
85 
85 
170 
  
 
 
N for specificity =1.96^2 * specificity * (1- specificity)/ Margin error^2 
 
N for sensitivity =1.96^2 * sensitivity * (1-sensitivity)/ Margin error^2 
 
The minimum sample size was calculated using the formulae above. All that is required to 
calculate the minimum sample size is the sensitivity or specificity, and the margin of error. For 
a sensitivity and specificity of 98% with a maximum marginal error of 3%, for constructing the 
95% confidence interval (0.9442 to 1.000), a sample size producing a minimum of 83.6 positive 
events is required. This is rounded up to 85 events.  Therefore, a total sample size of 170 
events will be required to test both a specificity and sensitivity of 98% with a marginal error 
of 3% for both.  We define each separate day as an independent test.  Each participant will 
artificially induce nystagmus on eight occasions.  Twelve participants will provide 96 artificially 
induced participant positive events (12x8=96).  Twelve participants will provide a total of 360 
testing events (12x30=360).  We will need to see the following outcome (table below), which 
will provide a 95% CI for sensitivity of 0.9506 to 1.000 and for specificity a 95% CI of 0.9646 to 
0.9975. We have decided to recruit fifteen participants to allow for drop-outs. 
 
 
 
Device 
 
 
  
Positive 
Negative 
Total 
Participant 
TRUE 
94(97.92) 
2(2.08%) 
96 
FALSE 
5 (1.89%) 
259 (98.11%) 
264 
 
Total 
99 
261 
360