Promoting Implementation of Seizure Detection Devices in Epilepsy Care: the PROMISE Study
Phase: NA
Conditions: Epilepsy in Children
Sponsor: Stichting Epilepsie Instellingen Nederland

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RESEARCH PROTOCOL  
PROMISE study 
(April 2018) 
 
 
 
 
 

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PROTOCOL TITLE : 
“Promoting implementation of seizure detection devices in epilepsy care: 
the PROMISE study.” 
Short title 
The PROMISE study 
Version 
3.0 
Date 
April 19, 2018 
Coordinating investigator/project leader 
 
A. van Westrhenen, MD, PhD candidate 
Stichting Epilepsie Instellingen Nederland 
(SEIN) 
Achterweg 5 
2103 SW Heemstede 
Phone 023 558 8975 
Email: Avwestrhenen@sein.nl 
 
 
Principal investigator(s) (in Dutch: 
hoofdonderzoeker/ uitvoerder) 
 
R.D. Thijs, MD, PhD 
Stichting Epilepsie Instellingen Nederland 
(SEIN)  
Achterweg 5  
2103 SW Heemstede  
Phone 023-558 8948 
Fax 023-558 8159 
Email: rthijs@sein.nl 
 
Multicenter research 
Center: Academic Centre of Epileptology 
Kempenhaeghe  
Investigator: R.H.C. Lazeron, MD, PhD 
 
Center: University Medical Center Utrecht 
Investigator: F.S.S. Leijten, MD, PhD 
JCA Trappenburg, PhD (The Healthcare 
Innovation Centre (THINC)) 
Sponsor (in Dutch: 
Stichting Epilepsie Instellingen Nederland 
(SEIN) 

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verrichter/opdrachtgever) 
Subsidising party 
Health Holland 
Independent expert  
Neurologist R. Fronczek, MD, PhD 
Stichting Epilepsie Instellingen Nederland 
Achterweg 5 
2103 SW Heemstede 
Phone: 023 - 558 8900 
Email: r.fronczek@sein.nl  
 
 
 
 
 

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PROTOCOL SIGNATURE SHEET 
 
Name 
Signature 
Date 
Sponsor or legal representative: 
Stichting Epilepsie Instellingen Nederland 
(SEIN), Heemstede.  
Research Department.  
Head of Department: 
Prof. JW Sander, MD, PhD 
 
 
 
 
19-04-2018 
 
[Coordinating Investigator/Project 
leader/Principal Investigator]: 
RD Thijs, MD, PhD 
 
 
19-04-2018 
 
 

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TABLE OF CONTENTS 
 
SUMMARY 
 
 
 
 
 
 
 
 
 
 
       8 
1. 
INTRODUCTION AND RATIONALE .............................................................................. 9 
2. 
OBJECTIVES ................................................................................................................10 
3. 
STUDY DESIGN ...........................................................................................................11 
4. 
STUDY POPULATION ..................................................................................................13 
4.1 
Population (base) ...................................................................................................15 
4.2 
Inclusion criteria .....................................................................................................15 
4.3 
Exclusion criteria ....................................................................................................15 
4.4 
Sample size calculation ..........................................................................................16 
5. 
TREATMENT OF SUBJECTS .......................................................................................16 
5.1 
Investigational product/treatment ............................................................................16 
5.2 
Use of co-intervention (if applicable) ......................................................................16 
5.3 
Escape medication (if applicable) ...........................................................................16 
6. 
INVESTIGATIONAL PRODUCT ....................................................................................16 
6.1 
Name and description of investigational  product(s) ...............................................16 
6.2 
Summary of findings from non-clinical studies ........................................................16 
6.3 
Summary of findings from clinical studies ...............................................................16 
6.4 
Summary of known and potential risks and benefits ...............................................16 
6.5 
Description and justification of route of administration and dosage .........................16 
6.6 
Dosages, dosage modifications and method of administration ...............................16 
6.7 
Preparation and labelling of Investigational Medicinal Product ...............................16 
6.8 
Drug accountability .................................................................................................16 
7. 
NON-INVESTIGATIONAL PRODUCT ...........................................................................16 
7.1 
Name and description of non-investigational product(s) .........................................16 
7.2 
Summary of findings from non-clinical studies ........................................................16 
7.3 
Summary of findings from clinical studies ...............................................................16 
7.4 
Summary of known and potential risks and benefits ...............................................16 
7.5 
Description and justification of route of administration and dosage .........................16 
7.6 
Dosages, dosage modifications and method of administration ...............................16 
7.7 
Preparation and labelling of Non Investigational Medicinal Product ........................16 
7.8 
Drug accountability .................................................................................................16 
8. 
METHODS ....................................................................................................................20 
8.1 
Study parameters/endpoints ...................................................................................20 
8.1.1 
Main study parameter/endpoint .......................................................................20 
8.1.2 
Secondary study parameters/endpoints (if applicable) ....................................20 
8.1.3 
Other study parameters (if applicable) .............................................................20 
8.2 
Randomisation, blinding and treatment allocation ..................................................24 
8.3 
Study procedures ...................................................................................................24 
8.4 
Withdrawal of individual subjects ............................................................................26 
8.4.1 
Specific criteria for withdrawal (if applicable) ...................................................26 
8.5 
Replacement of individual subjects after withdrawal ...............................................26 
8.6 
Follow-up of subjects withdrawn from treatment .....................................................26 
8.7 
Premature termination of the study .........................................................................26 
9. 
SAFETY REPORTING ..................................................................................................27 
9.2 
AEs, SAEs and SUSARs ........................................................................................27 
9.2.1 
Adverse events (AEs) ......................................................................................27 

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9.2.2 
Serious adverse events (SAEs) .......................................................................27 
9.2.3 
Suspected unexpected serious adverse reactions (SUSARs)…………………27 
9.3 
Annual safety report……………………………………………………………………...27 
9.4 
Follow-up of adverse events ...................................................................................27 
9.5 
[Data Safety Monitoring Board (DSMB) / Safety Committee] ..................................28 
10. 
STATISTICAL ANALYSIS ..........................................................................................29 
10.1 Primary study parameter(s) ....................................................................................29 
10.2 Secondary study parameter(s) ...............................................................................29 
10.3 Other study parameters ..........................................................................................31 
10.4 Interim analysis (if applicable) ................................................................................32 
11. 
ETHICAL CONSIDERATIONS ...................................................................................33 
11.1 Regulation statement .............................................................................................33 
11.2 Recruitment and consent........................................................................................33 
11.3 Objection by minors or incapacitated subjects (if applicable) ..................................33 
11.4 Benefits and risks assessment, group relatedness .................................................33 
11.5 Compensation for injury .........................................................................................35 
11.6 Incentives (if applicable) .........................................................................................35 
12. 
ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION .........................36 
12.1 Handling and storage of data and documents ........................................................36 
12.2 Monitoring and Quality Assurance ..........................................................................36 
12.3 Amendments ..........................................................................................................37 
12.4 Annual progress report ...........................................................................................37 
12.5 End of study report .................................................................................................38 
12.6 Public disclosure and publication policy ..................................................................38 
13. 
STRUCTURED RISK ANALYSIS...............................................................................39 
13.1 Potential issues of concern .....................................................................................39 
13.2 Synthesis ...............................................................................................................39 
14. 
REFERENCES ..........................................................................................................40 

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LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS  
 
ABR 
ABR form, General Assessment and Registration form, is the 
application form that is required for submission to the accredited 
Ethics Committee (In Dutch, ABR = Algemene Beoordeling en 
Registratie) 
AE 
Adverse Event 
AR 
Adverse Reaction 
CCMO 
Central Committee on Research Involving Human Subjects; in 
Dutch: Centrale Commissie Mensgebonden Onderzoek 
DSMB 
Data Safety Monitoring Board 
EEG 
EU 
Electroencephalography 
European Union 
EudraCT 
European drug regulatory affairs Clinical Trials  
FNAR 
False negative alarm rate 
GCP 
Good Clinical Practice 
IB 
Investigator’s Brochure 
IC 
Informed Consent 
Kempenhaeghe Academic Centre of Epileptology Kempenhaeghe 
METC  
Medical research ethics committee (MREC); in Dutch: medisch 
ethische toetsing commissie (METC) 
QoL 
(S)AE 
SDD 
Quality of Life 
(Serious) Adverse Event  
Seizure Detection Device 
Sponsor 
 
 
 
 
 
The sponsor is the party that commissions the organisation or 
performance of the research, for example a pharmaceutical 
company, academic hospital, scientific organisation or investigator. 
A party that provides funding for a study but does not commission it 
is not regarded as the sponsor, but referred to as a subsidising 
party. 
SEIN 
Stichting Epilepsie Instellingen Nederland 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
UMCU 
University Medical Center Utrecht 
Wbp 
Personal Data Protection Act (in Dutch: Wet Bescherming 
Persoonsgevens) 
WMO 
Medical Research Involving Human Subjects Act (in Dutch: Wet 

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Medisch-wetenschappelijk Onderzoek met Mensen) 
SUMMARY 
Rationale: Various remote and wearable sensor devices have become available for the 
detection of potentially dangerous seizures, with limited impact on epilepsy care so far. Both 
our remote and our wearable seizure detection devices (SDDs) have been extensively tested 
and proven highly sensitive. Yet the home performance in children, an important target 
population, had been insufficiently studied.  
Objective:  
1. To test the performance of the wearable SDD (NightWatch) prospectively and the remote 
SDD (automated video and audio analysis) retrospectively in children in a family home 
setting. 2. To assess the feasibility, cost-effectiveness and cost-utility of NightWatch in 
children.   
Study design: A multicenter home-based medical device intervention study with prospective 
validation of our wearable SDD.  
Study population: 60 children (ages 4-16 years) with refractory epilepsy (≥1 major nocturnal 
seizure per week) recruited from the outpatient clinics of one of the participating epilepsy 
centers (Stichting Epilepsie instellingen Nederland (SEIN), Academic Centre of Epileptology 
Kempenhaeghe (Kempenhaeghe), University Medical Center Utrecht (UMCU)).  
Intervention (if applicable): Phase I: Two months of baseline (usual care); Phase 2: Two 
months of nocturnal seizure monitoring at home, using NightWatch and the remote SDD. 
Main study parameters/endpoints: The diagnostic performance of NightWatch and the 
remote SDD algorithms, i.e. sensitivity, positive predictive value, false alarm rate and % time 
with uninterrupted signal output. We will evaluate feasibility of NightWatch through surveys 
on quality of life, sleep, parental strain, interviews with parents/guardians and neurologists, 
and a value sensitive design group session. We will also perform a cost-effectiveness and 
cost-utility analysis by medical consumption and costs questionnaires. 
Nature and extent of the burden and risks associated with participation, benefit and 
group relatedness: Implementing SDDs will not pose any direct or substantial risk. Study 
participation can be a burden though, due to impact of the devices on privacy, number of 
false alarms and time spent on the questionnaires and interviews. Application of the SDDs, 
however, might offer better insight into the actual number of nocturnal seizures in a child, 
change in medical management and facilitate appropriate interventions in major motor 
seizures. If reliable, SDDs may improve the night rest of both patient and parents/guardians.  
 
 

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1. INTRODUCTION AND RATIONALE 
Epilepsy impacts ~180.000 people in the Netherlands [1]. Despite advances in treatment, 
one third of all people with epilepsy continue to have seizures [2] that adversely affect quality 
of life (QoL) [3,4]. Poor seizure control is the major determinant of impaired QoL. Seizures 
impact not only individuals with epilepsy but also their guardians [5-7] as seizures are (1) 
unpredictable, (2) may cause loss of control and (3) cause life threatening situations, 
including injuries, status epilepticus and sudden unexpected death in epilepsy [8]. Convulsive 
seizures carry the greatest mortality risk, particularly those occurring at night, as these are 
often unwitnessed [9]. Childhood epilepsy has also a severe impact on parental QoL [10] and 
monitoring devices can help to improve parental anxiety levels, quality of sleep, and QoL 
[11]. Various non-EEG based signals have been assessed for the detection of potentially 
dangerous seizures [12]. Seizure detection devices (SDDs) have had, however, limited 
impact on epilepsy care so far. Barriers to SDD implementation include lack of external 
validation and high rate of false alarms. Most SDDs rely on a single modality. This approach 
likely explains limited sensitivity and specificity [12]. Previous studies validated multimodal 
algorithms for wearable sensors (accelerometry & heart rate) and demonstrated the 
feasibility of remote sensors (audio & video) to detect seizures [13-17].  
Preliminary results indicate that the performance of the NightWatch is superior to a 
commonly used bed sensor, the Emfit. Our multicenter prospective trial in a residential 
population of adults with epilepsy and learning disabilities (LICSENSE trial, NTR4115) shows 
a median sensitivity per person of 85.7% with a positive predictive value of 49.3% and a 
median false negative alarm rate of 0.04 per person per night [18]. The interim analysis of 
our recent trial in 21 children (LICSENSE phase III) indicated that the algorithms needed an 
adjustment as in children higher heart rates are more common and less specific features for 
epilepsy appear thus increasing the number of false alarms. In response we updated our 
algorithm (with less emphasis on heart rate changes and more weight on movement 
changes). This approach still reach 80% sensitivity and 50% PPV in the majority (80%) of 
subjects (adults and children). This current prospective home-based trial is needed as a final 
validation step for the new algorithm in children and to evaluate feasibility of NightWatch. 
Former trials were performed without actual alarms. The current trial also enables us to get 
insight in the real life situation of children and their parents/guardians by focusing on 
feasibility. The literature has so far only discussed these needs with questionnaires but 
without insight into the home situation [19].  
Remote SDDs may provide an alternative for wearable sensors, especially when they are not 
tolerated. We recently demonstrated the feasibility of video algorithms to detect convulsive 
seizures in a small clinical cohort (a learning set of 50 subjects with 72 convulsive seizures 
and a test set of 12 individuals and 50 seizures). Performance analysis resulted in 100% 

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sensitivity of detecting tonic-clonic seizures and 57% of detecting non-vital minor seizures. 
67% of latencies were ≤ 10 seconds and the median false detection rate was 0.78 per night 
[13]. A previous study found a sensitivity of audio detection of 81% by analyzing seizure 
specific sounds in 10 subjects with 112 major seizures [15]. All false positive alarms (mean 
value: 1.29 per night) were due to minor seizures and 4 seizures (3%) were missed because 
of lack of sound and 10 (9%) because of sounds below the system’s threshold. The company 
CLB Acoustic Monitoring has developed several acoustic monitoring devices for use in health 
care. They collected a large database of distinct sounds, including seizure related ones. For 
both remote SDD components (video and audio) long-term databases are needed to 
determine false alarm rates.  
The current study will test (1) the performance of NightWatch with a fixed algorithm and (2) 
optimize the algorithms for the remote SDD (video and audio).  
All studies on any SDD have been performed in a clinical (hospital/institution) setting. These 
study populations do not represent the general epilepsy population, and (sleep) settings in 
the hospital clearly differ from at home. Our study will test the SDDs in a family home setting 
and will be the first real field SDD implementation study. By focusing on the patient and 
family perspective, we will obtain crucial feedback on which performance is feasible for them 
and in which way parents/guardians experience support from an SDD. This study design will 
comply with the concepts of the Dutch Health Board’s recommendations for novel devices 
[20]. 
 
 
 

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2. OBJECTIVES 
 
Primary Objective:  
Diagnostic performance of our wearable multimodal SDD (NightWatch) to detect major 
nocturnal motor seizures in children at home. Diagnostic performance of NightWatch will be 
measured prospectively by means of sensitivity, positive predictive value, false alarm rate 
and % time with uninterrupted signal output.   
 
Secondary Objectives:  
- Diagnostic performance of our remote SDD (video and audio) to detect major nocturnal 
motor seizures in children at home. Diagnostic performance will be measured retrospectively 
by means of sensitivity, positive predictive value and false alarm rate and % time with 
uninterrupted signal output.  
- Feasibility of NightWatch with a mixed methods approach focusing on Acceptability, 
Demand, Implementation, Practicality, Expansion and Limited-efficacy testing (caregiver 
strain (CSI), sleep (PSQI), QoL (EQ-5D-5L)) and impact of the SDD on parents/guardians 
and children (interview).  
- Economic evaluation from a societal prospective of NightWatch involving a combination of a 
cost-effectiveness analysis (CEA) and a cost-utility analysis (CUA). (See 8.1.2. Methods) 
 
 

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3. STUDY DESIGN 
 
This is a home-based medical device intervention study, with prospective validation of our 
wearable device, including 60 children with refractory epilepsy (≥1 major nocturnal seizure 
per week) from three epilepsy centers (SEIN, Kempenhaeghe, UMCU). Subjects will receive 
usual care during the first two months (non-exposure period), followed by home-based 
nocturnal monitoring for two months (exposure period) [See Figure 1]. In both periods 
parents/guardians will be invited to keep a seizure diary. The NightWatch wirelessly 
transmits sensor outputs to a monitor in the parents/guardians room to alert them in case of 
a suspected seizure [See Figure 2]. Simultaneous video and audio recordings will be stored 
and analyzed offline.[21] Both algorithms will generate marks in dataflow, but these marks 
will not be used to alert the parents/guardians and will only be examined by the 
researchers.[See figure 3] The video material will also be used to screen for false negative 
alarms and to improve the algorithm when necessary (comparable with the LICSENSE study 
design, NTR4115).  
Trial nurses will check the validity of the generated alarms and marks in a blinded way and 
screen 5% of the nocturnal video recordings without alarms. The LICSENSE trial 
demonstrated a median false negative alarm rate (FNAR) of 0,03 per subject per night with 
10% screening of all nights. We believe that 5% screening will also be feasible, but we will 
perform an interim analysis after inclusion of 20 subjects to see whether FANR is still 
reasonably low (below 0,1 per night). If this is not the case, we will increase screening to 
10% of all nights. The LICSENSE trial found a high Cohen’s kappa (0.77) for inter-observer 
agreement between trial nurses and neurologists. Therefore, this expert review of the 
nocturnal video recordings by the trial nurses will serve as the gold standard. Cases of doubt 
will be discussed with a neurologist. Seizures will be stratified according to type (tonic-clonic, 
>30 seconds tonic, hyper motor and major) and severity (minor/major). 
Parents/guardians will be invited to articulate their user experiences at focus meetings. Video 
tracings of detected seizures of their child will be shown to the parents/guardians who will be 
asked to indicate whether they would want to be alerted for these events or not. Results from 
these meetings will be included in the discussion on which type of seizures should be 
alarmed by SDDs.   
To evaluate SDD feasibility, we will compare parental strain, quality of sleep and QoL during 
the non-exposure period and exposure period [22]. Based on a survey after the exposure 
period, we will calculate retention rate.  
 
After the exposure period, we will offer the parents/guardians and children ≥12 years of age 
two options, based on the diagnostic performance of the NightWatch in their child.  

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Non-exposure period 
Exposure period 
Good performance 
Keep NightWatch 
Bad performance 
Tailoring#  
1. In case of bad performance, , we will offer a second-2-month period of monitoring in 
case we noted that an individualized adjustment of the algorithm (i.e. threshold 
adjustments for heart rate & accelerometry settings) using the data from the exposure 
period results in a substantial improvement. We will prospectively test the diagnostic 
performance of the adjusted algorithm prospectively and compare results between 
both periods. 
2. In case of good performance, we will offer the parents/guardians the possibility to 
keep the NightWatch for further use, under certain conditions. (See 11.4 Ethics)   
 
 
 
 
 
 
 
Figure 1: Study design.  
# If this results in a substantial improvement of the NW performance 
 
 
 
 
 
 
 
 
 
Figure 2: NightWatch around upper arm.  
Figure 3:  alarm system (left) and 
NightWatch (right). 
 
 
 
 
 
T0 
-- 2 Months -- 
-- 2 Months -- 
T2
T1
-- Optional 2 Months -- 

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Figure 4: Overview of SDDs in study.  
 
 
 
 
 
 

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4. STUDY POPULATION 
4.1 Population (base)  
Around 20,000 children carry the diagnosis of epilepsy in the Netherlands [23]. Most children 
with severe or difficult to treat epilepsy are under specialized epilepsy care in SEIN, 
Kempenhaeghe or UMCU. This study will include 60 children with refractory epilepsy (≥1 
major nocturnal seizure per week) from one of the above epilepsy care facilities. There will 
be no restrictions on seizure etiology.  
4.2 Inclusion criteria 
In order to be eligible to participate in this study, a subject must meet all of the following 
criteria: 
 
Age 4-16 years 
 
Diagnosis of refractory epilepsy with ≥1 major nocturnal motor seizure per week. 
 
Treated at one of the following epilepsy centers: SEIN, Kempenhaeghe or UMCU. 
 
Written informed consent by legal representatives (mostly parents) and also by the 
subject when aged ≥12 years and capable of signing informed consent. 
4.3 Exclusion criteria 
A potential subject who meets any of the following criteria will be excluded from 
participation in this study: 
 
Intensive non-epileptic movement patterns such as severe choreatiform movements, 
intensive sleep walking, or frequent night terrors (> 1/week).  
 
Minor motor seizures only, i.e. non-generalized or short (< 10 sec.) tonic seizures or 
isolated myoclonias that are self-limited and do not require intervention.  
 
Presence of a pacemaker or cardiac arrhythmias that may generate false alarms (e.g. 
supraventricular tachycardia). 
 
Inability to comply to the trial procedure.  
 
Skin characteristics (e.g. dark skin color or tattoo) that may affect 
photoplethysmography and thereby influence performance of the NightWatch.   
 
Dependence on another SDD (e.g. Emfit or saturation monitor). Simultaneous use of 
a baby phone (or other types of microphones) is permitted. 
 
Subjects who are not sleeping alone in the bed (i.e. co-sleeping in the 
parents’/guardians’ bed influences the remote SDD). We do not allow subjects and 
parents/guardians to change their sleeping habits for the duration of the study only.     
 

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4.4 Sample size calculation 
 
If 60 subjects  are monitored for two months at minimal seizure frequency of 1 per week 
we will likely obtain around 540 seizures. To assess the diagnostic performance of the 
NightWatch this sample size seems sufficient. The detection algorithms aim to reach a 
sensitivity of 80% and a PPV of 50%. A sample size of 384 would be sufficient to reach a 
confidential interval of 5% (given a confidence level of 95%) [24]. A sample size of 60 
subjects will allow us to intercept a drop-out rate of approximately 30% for the feasibility 
study.    
 
              
 
 

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5 TREATMENT OF SUBJECTS 
Not applicable 
5.1 Investigational product/treatment 
 
Not applicable 
5.2 Use of co-intervention (if applicable) 
 
Not applicable 
5.3 Escape medication (if applicable) 
 
Not applicable 

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6 INVESTIGATIONAL PRODUCT  
Not applicable 
  
6.1 Name and description of investigational  product(s) 
 
Not applicable 
 
6.2 Summary of findings from non-clinical studies 
 
Not applicable 
 
6.3 Summary of findings from clinical studies 
 
Not applicable 
6.4 Summary of known and potential risks and benefits 
 
Not applicable 
6.5 Description and justification of route of administration and dosage 
 
Not applicable 
 
6.6 Dosages, dosage modifications and method of administration 
 
Not applicable 
 
6.7 Preparation and labelling of Investigational Medicinal Product 
 
Not applicable 
 
6.8 Drug accountability 
 
Not applicable 
 

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7 NON-INVESTIGATIONAL PRODUCT 
Not applicable 
  
7.1 Name and description of non-investigational product(s) 
 
Not applicable 
 
7.2 Summary of findings from non-clinical studies 
 
Not applicable 
 
7.3 Summary of findings from clinical studies 
 
Not applicable 
7.4 Summary of known and potential risks and benefits 
 
Not applicable 
7.5 Description and justification of route of administration and dosage 
 
Not applicable 
 
7.6 Dosages, dosage modifications and method of administration 
 
Not applicable 
 
7.7 Preparation and labelling of Non Investigational Medicinal Product 
 
Not applicable 
 
7.8 Drug accountability 
 
Not applicable 
 

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8 METHODS 
8.1 Study parameters/endpoints 
8.1.1 Main study parameter/endpoint 
Performance of the NightWatch: 
 
Sensitivity; 
 
Positive predictive value; 
 
False alarm rate; 
 
% Time with valid signal allowing proper detection.  
 
8.1.2 Secondary study parameters/endpoints (if applicable) 
1. Validation of remote SDDs (video and audio): 
 
Sensitivity; 
 
Positive predictive value; 
 
False alarm rate; 
 
% Time with valid signal allowing proper detection.  
 
2. The feasibility of the NightWatch focusing on Acceptability, Demand, Implementation, 
Practicality, Expansion and Limited-efficacy testing [22]. 
 
Acceptability  
The parameter Acceptability is defined as:  
The extent in which the NightWatch is judged as suitable, satisfying, or attractive for people 
with epilepsy and their parents/guardians.  
Focusing on: 
 
Intent to continue use (survey T0) 
 
Expectations (survey T0) 
 
Satisfaction (Survey T2 and semi-structured interview with parents/guardians and 
subjects) 
 
Demand 
The parameter Demand is defined as:  
The extent in which the NightWatch is likely to be used.  
Focusing on: 
 
Perceived demand (Survey T0) 

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 
Actual use (Diary and semi-structured interview with parents/guardians and subjects) 
 
Implementation 
The parameter Implementation is defined as:  
The extent in which the NightWatch can be successfully delivered to people with epilepsy 
and their parents/guardians.  
Focusing on: 
 
Degree of execution, (Diary, semi-structured interview with parents/guardians and 
subjects and survey T2) 
 
Success or failure of execution (semi-structured interview with parents/guardians and 
subjects and survey T2) 
 
Amount, type of resources needed to implement (semi-structured interview with 
parents/guardians and subjects)  
 
Practicality 
The parameter Practicality is defined as:  
The extent in which the NightWatch device can be carried out in people with epilepsy and 
their parents/guardians using existing means, resources, and circumstances and without 
outside intervention? 
Focusing on: 
 
Factors affecting implementation ease or difficulty (semi-structured interview with 
parents/guardians and subjects and survey T2) 
 
Positive/negative effects on people with epilepsy and their family members (semi-
structured interview with parents/guardians and subjects and survey T2) 
 
Ability of parents/guardians to carry out intervention activities (semi-structured 
interview with parents and subjects and survey T2) 
Expansion 
The parameter Expansion is defined as:  
The extent in which the NightWatch can provide a new service to people with epilepsy and 
their parents/guardians.  
Focusing on: 
 
Fit with organizational goals and culture treatment of people with epilepsy (group 
session* and interview with neurologists)  
 
Disruption due to expansion component (group session* and interview with 
neurologists) 
 

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*At the end of the study, we will evaluate the NightWatch by inviting a group of 
parents/guardians and professionals to a group session using the value sensitive design 
methodology.[26] 
 
Limited-efficacy testing 
The parameter Limited-efficacy testing is defined as:  
The extent in which the NightWatch shows a promise of being successful on key 
intermediate variables (quality of life, stress, sleep, and strain) in people with epilepsy and 
their parents/guardians.   
Focusing on Intended effects of the NightWatch on key intermediate: 
 
Health-related QoL in people with epilepsy and their parents/guardians, including 
EQ-5D-5L [27] (Survey T0 and T2) 
 
Strain and sleep, including Caregiver Strain Index (CSI) [28] and Pittsburgh Sleep 
Quality Index (PSQI) [29] (Survey T0 and T2).  
 
3. Economic evaluation of NightWatch 
To evaluate the costs and effectiveness/utility of NightWatch for children and their 
parents/guardians from a societal perspective.   
 
Medical Consumption Questionnaire (MCQ) – adjusted version (T0 and T2)  
- Questions regarding the subject (to be completed by one or two 
parent(s)/guardian(s) together) 
- Questions regarding the parent/guardian (to be completed by one or both 
parent(s)/guardian(s) separately) 
 
Productivity Costs Questionnaire (PCQ) – adjusted version (T0 and T2) 
- To be completed by one or two parent(s)/guardian(s) separately.  
 
4. Other secondary study parameters are: 
- Compliance as indicated by frequency of use, i.e. hours per night that NightWatch is ‘on’.  
- Number and nature of interventions due to alarms. 
- Effect of algorithm tailoring on performance of the NightWatch.   
 
 
 
 
 

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Table 1: Time schedule of surveys, questionnaires and interviews and feasibility domains.  
 
T0 = Before implementation of the SDDs;  
T1 = Intervention (2 months);  
T2= After implementation of the SDDs.  
 
 
Time 
period 
Method 
Duration 
Topic 
T0  
 
Surveys T0 
10 
minutes 
- 
Personal/medical information subject and family (baseline) 
- 
MCQ and PCQ  
- 
Acceptability:  
- 
Intent to continue use; 
- 
Expectations  
Demand 
- 
Perceived demand  
Questionnaires  
30 
minutes 
Limited-efficacy testing 
- 
CSI: Parental strain/stress  
- 
PSQI: Parental quality of sleep 
- 
EQ-5D-5L: Parental and child quality of life 
T1  
 
Diary 
 
Demand 
- 
Actual use  
Implementation  
- 
Degree of execution  
Interview 
(subgroup) 
60 
minutes 
Acceptability  
- 
Satisfaction 
Demand 
- 
Actual use  
Implementation 
- 
Degree of execution 
- 
Success or failure of execution 
- 
Amount, type of resources needed to implement 
Practicality 
- 
Factors affecting implementation ease or difficulty 
- 
Positive/negative effects on patients with epilepsy and their 
family members 
- 
Ability of parents/guardians to carry out intervention 
activities 
T2  
Surveys T2 
10 
minutes 
- 
MCQ and PCQ 
Acceptability  
- 
Satisfaction 
Implementation 
- 
Degree of execution 
- 
Success or failure of execution 
- 
Amount, type of resources needed to implement 
Practicality  
- 
Factors affecting implementation ease or difficulty 
- 
Positive/negative effects on patients with epilepsy and their 
parents/guardians 
- 
Ability of parents/guardians to carry out intervention 
activities 
Questionnaires 
30 
minutes 
Limited-efficacy testing 
- 
CSI: Parental strain/stress  
- 
PSQI: Parental quality of sleep 
- 
EQ-5D-5L: Parental and child quality of life 
Optional 
Group session 
120 
minutes 
Expansion 
- 
Value sensitive design group session  

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Table 2: Overview of questionnaires 
 
Questionnaire 
Domains 
No. of items  
CSI 
Strain related to care provision.  
Major domains: Employment, Financial, Physical, Social 
and Time 
13 
PSQI 
Quality of sleep. 
Major domains: subjective sleep quality, sleep latency, 
sleep duration, habitual sleep efficiency, sleep 
disturbances, use of sleep medication, and daytime 
dysfunction.  
10 
EQ-5D-5L 
Quality of Life. 
Major domains: Mobility, self-care, usual activities, 
pain/discomfort, anxiety/depression.  
5 
 
8.1.3 Other study parameters (if applicable) 
Not applicable. 
8.2 Randomisation, blinding and treatment allocation 
Not applicable 
 
8.3 Study procedures 
Inclusion & consent 
(See 11.2 Recruitment and consent)  
 
Run in period 
During the first two months, there will be no home-based monitoring. Parent(s)/ 
representative(s) will complete the questionnaires and a subgroup will be 
interviewed.  
 
Intervention 
After two months, the researcher will visit the home to install the equipment. A 
camera and microphone will be placed on a pole, secured between floor and ceiling, 
next to the subject’s bed. A suitcase containing a MacBook laptop and an external 
hard drive for data storage will be placed in the subject’s room. The subject will be 
instructed to wear the NightWatch bracelet every night around the upper arm.  When 
NightWatch is removed from its docking station, it will start running automatically. All 
recorded data (NightWatch, video and audio) will be stored automatically to the 

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MacBook and copied on hard drive. The researchers will replace the hard-drive 
every 2 weeks and store all recordings safely at SEIN or Kempenhaeghe for 
analysis. During the first weeks, the hard drive will be switched more often, in order 
to detect systematic errors in time.  
In the morning, NightWatch must be connected to the docking station, when this 
happens, recordings stop automatically. During the study, subjects (or 
parent(s)/guardian(s)) do not have to switch any on/off button for the recordings.   
When NightWatch detects a seizure, it generates an alarm to the alarm station part 
of the NightWatch system at the parent(s)/guardian(s) bedroom. When the alarm 
goes off, the responding parent/guardian will check on their child and act upon the 
situation. He/she will keep a diary of all events.  The SDD intervention period will 
last two months. 
In case of technical problems, parent(s)/guardian(s) can contact the technical trial 
coordinator. If the parent(s)/guardian(s) give their consent, the coordinating 
investigator will be able to look into the study Macbook at their home from a distance 
true a secured program to solve technical problems. If the problem is not solved, the 
technical trial coordinator will visit the participant’s home.       
 
Questionnaires & interviews 
During the study (T0 and T2), parent(s)/guardian(s) will be asked to complete 
several questionnaires about their experiences with NightWatch, quality of life, 
stress and quality of sleep. This will take 40 minutes for each time period (T0 and 
T2). The questionnaires will be presented in an online tool. Parent(s)/guardian(s) will 
give their consent to use their email address for access to this tool. A subgroup of 
parent(s)/guardian(s) will be invited to participate in a semi-structured interview 
focusing on feasibility of NightWatch and the impact of the SDD on family life. This 
interview will take one hour. Parent(s)/guardian(s) can indicate their availability to 
participate on the informed consent form. Based on all evaluations, researchers will 
decide which perspective will gain deeper understanding about the feasibility and 
impact of NightWatch. The researchers will select parents/guardians based on 
maximum variation.  
 
Optional phase  
Depending on the performance of NightWatch, parent(s)/guardian(s) will have 
different options. In case of bad performance, the researchers will offer them a 
second-2-month period of monitoring if an individually tailored adjustment of the 
algorithm could substantially improve  performance. In case of good performance, 

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researchers we will offer the parent(s)/guardian(s) the possibility to keepNightWatch 
for further use. They can buy NightWatch at a 50% reduced rate of €750,-.  
 
8.4 Withdrawal of individual subjects 
Subjects can terminate the study at any time for any reason if they wish to do so 
without any consequences. The investigator can decide to withdraw a subject from 
the study for urgent medical reasons or important unforeseen events (e.g. material 
deficiencies). If the subject shows any signs of resistance to wear the device, the 
investigators are obliged to withdraw the subject from the study.  
Researchers will ask for the reason of withdrawal, because this can give them 
information about the feasibility. Subjects and their parent(s)/representative(s) are 
not obliged to answer this question.  
8.4.1 Specific criteria for withdrawal (if applicable) 
8.5 Replacement of individual subjects after withdrawal 
If a subject is withdrawn from the study within two weeks from inclusion, the subject 
will be replaced. After this time period, subjects will not be replaced.     
8.6 Follow-up of subjects withdrawn from treatment 
Not applicable. 
8.7 Premature termination of the study 
Not applicable.  
 
 

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9 SAFETY REPORTING 
9.1 Temporary halt for reasons of subject safety 
Not applicable 
9.2 AEs, SAEs and SUSARs 
Our wearable sensor (NightWatch) has been developed in cooperation with Livassured 
and a group of researchers, the Dutch Teleconsortium. After production of a prototype, 
different usability tests have been performed to examine the product. Special attention 
has been paid to patient safety.  
NightWatch is CE certified as a Medical Device Class I.  
 
9.2.1 Adverse device events (ADEs) 
Adverse device events (ADEs) are defined as any undesirable experience occurring 
to a subject during the study, causally related to the study device. All adverse device 
events reported spontaneously by the subject or observed by the investigator or his 
staff will be recorded. 
9.2.2 Serious adverse events (SAEs) 
A serious adverse (device) event (SA(D)E) is a serious (leading to hospitalization or 
(near)-death) unfavorable and unintended sign (including an abnormal finding), 
symptom, or disease temporally associated with the clinical trial whether or not 
related to a failure of the device to alarm. A SAE will be reported within 7 days to the 
METC . All subjective or presumed complaints will be reported. We do not expect 
serious adverse events causally related to NightWatch (SADE). Previous trials 
(LICSENSE Phase I-III) have indicated that the NightWatch is tolerated well with 
respect to comfort and skin reactions.  
 
 
 
 
 
9.2.3  Suspected unexpected serious adverse reactions 
(SUSARs) 
 
Not applicable. 
 
9.3 Annual safety report 
 
Not applicable.  
 

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9.4 Follow-up of adverse events 
All AEs will be followed until they have abated, or until a stable situation has been 
reached. Depending on the event, follow up may require additional tests or medical 
procedures as indicated, and/or referral to the general physician or a medical specialist. 
 
9.5 [Data Safety Monitoring Board (DSMB) / Safety Committee] 
 
Not applicable.  

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10 STATISTICAL ANALYSIS 
10.1 
Primary study parameter(s) 
Performance of the algorithms ( sensitivity, positive predictive value, false alarm rate and % 
time with valid signal allowing proper detection) will be expressed using descriptive statistics.  
 
10.2 
Secondary study parameter(s)  
Methods triangulation will be conducted for this study, which means that there will be two 
or more research methods applied in one study [30,31]. After analysis the results will be 
combined, leading to a deeper understanding concerning the feasibility parameters. 
 
Feasibility and utility of the NightWatch will be presented, using descriptive statistics (see 
table 3). To calculate differences in pre- and post-measurements, a paired samples T-test 
will be applied (in case of normal distribution). Multiple imputation test will be applied in 
case of missing data. Differences in outcome will be tested through a post-hoc test.  
 
Semi-structured interviews 
Data from the semi-structured interviews will be analyzed using a thematic analysis 
approach [32]. Thematic analysis is a flexible method for identifying and analyzing 
patterns within data.  All interviews will be audiotaped, and transcribed verbatim; NVivo 
software (QSR International Pty Ltd, 2012) will be used in the analysis process. Thematic 
analysis consist of six steps: getting familiar with the data, generating codes, searching 
for themes, reviewing themes, defining theme, and representing results [32].  
 
Group session 
A focus group session with subjects, parents/guardians and professionals will be 
organized. After consent of the participants, the session will be recorded on video and 
transcribed verbatim will be used for further thematic analysis.  
 
 

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Table 3. Analysis for feasibility parameters  
Feasibility parameter 
Source 
Analysis 
Acceptability 
  
  
Satisfaction 
  
- Survey T2 
- Interview  
- Descriptive statistics1 
- Thematic analysis 
Intent to continue use 
- Survey T0 
- Interview 
- Descriptive statistics1 
- Thematic analysis 
Expectations 
- Survey T0 
- Descriptive statistics1 
Demand 
  
  
Actual use 
- Diary 
- Interview  
- Descriptive statistics2 
- Thematic analysis 
  
Perceived demand 
- Survey T0 
- Survey T2 
- Descriptive statistics1 
- Descriptive statistics1 
Implementation 
  
  
Degree of execution 
- Diary 
- Interview 
- Survey T2 
  
- Descriptive statistics2 
- Thematic analysis 
- Descriptive statistics1 
Success or failure of execution 
- Interview 
- Survey T2 
- Thematic analysis 
- Descriptive statistics1 
Amount, type of resources needed to 
implement 
- Interview 
- Thematic analysis 
Practicality 
  
  
Factors affecting implementation ease or 
difficulty 
- Interview 
- Survey T2 
- Thematic analysis 
- Descriptive statistics1 
Positive/negative effects on people with 
epilepsy and their family members 
- Interview 
- Survey T2 
- Thematic analysis 
- Descriptive statistics1 
Ability of parents/guardians to carry out 
intervention activities 
- Interview 
- Survey  T2 
- Thematic analysis 
- Descriptive statistics1 
Expansion 
  
  
Fit with organizational goals and culture 
treatment of people with epilepsy 
- Group session 
- Videotaped and thematic analysis 
Disruption due to expansion component 
- Group session 
- Interview neurologist 
- Videotaped and thematic analysis 
- Thematic analysis 
Limited-efficacy testing 
  
 
Health-related QoL 
- EQ-5D-5L 
- Check on normally distributed data 
- Descriptive statistics3 
- Paired samples T-test 
Caregiver Strain Index (CSI) 
- CSI 
- Check on normally distributed data 
- Descriptive statistics3 
- Paired samples T-test 
Pittsburgh Sleep quality index (PSQI) 
- PSQI 
- Descriptive statistics3 

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- Repeated measures ANOVA (if 
necessary multiple imputation) 
- post-hoc test (Turkey’s HSD) 
 
 
 
1 = Median, mode, range, highest and lowest value 
2 = Sensitivity, positive predictive value, false alarm rate (compared with results NightWatch analysis) 
3 = Mean (with SD) or median (with IQR), mode, variance and range 
 
10.3 
Other study parameters 
Economic evaluation NightWatch 
This economic evaluation will involve a combination of a cost-effectiveness analysis (CEA) 
and a cost-utility analysis (CUA). Additional costs and additional outcomes will be compared 
before and after implementation of NightWatch in a family home.  
 
In the CEA, effects are presented in clinical outcomes and the incremental cost-effectiveness 
ratio (ICER). The primary outcomes measure for the cost-utility analysis will be QALYs, 
based on the EuroQol utility scores.[33] 
 
We will assess intervention costs, healthcare costs, patient and family costs, and costs 
outside the health care sector. We have developed an adjusted version of the Medical 
Consumption Questionnaire (MCQ) and the Productivity Costs Questionnaire (PCQ) 
especially designed for parents or representatives of children with epilepsy.  
The valuation of healthcare costs, patient and family costs will be based on the updated 
Dutch manual for cost analysis in healthcare research. This manual recommends using 
standardized cost prices.[34]  
 
A baseline analysis will be performed to examine the comparability of groups at baseline for 
both costs and outcomes. If necessary, methods will be applied to control for differences in 
base. To investigate whether data are normally distributed a Kolmogorov-Smirnov test will be 
performed. Depending on the results either parametric (t-tests) or bootstraps will be used.  
The uncertainty of the Increment Cost Effectiveness Ratio (ICER) will be checked by non-
parametric bootstrapping. The bootstrapped cost-effectiveness ratios will be subsequently 
plotted in a cost-effectiveness plane. The choice of treatment depends on the maximum 
amount of money that society is prepared to pay for a gain in effectiveness, which is called 
the ceiling ratio. Therefore, the bootstrapped ICERs will also be depicted in a cost-
effectiveness acceptability curve showing the probability that NightWatch is cost-effective 
using a range of ceiling ratios. Additionally, to demonstrate the robustness of our base-case 
findings a multi-way sensitivity analyses will be performed.   

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10.4 
Interim analysis (if applicable) 
Not applicable.  

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11 ETHICAL CONSIDERATIONS 
11.1 
Regulation statement 
The study will be conducted according to the principles of the Declaration of Helsinki 
(most recent version, date19-10-2013) and in accordance with the Medical Research 
Involving Human Subjects Act (WMO).  
 
11.2 
Recruitment and consent 
Subjects will be recruited in one of the epilepsy centers (SEIN, Kempenhaeghe, UMCU). 
The principal investigator will inform the neurologists from these centers about the study, 
before recruitment. After reviewing in- and exclusion criteria, the subject and/or parent(s) 
or guardian(s) will be informed about the study by their neurologist. All subjects and 
parent(s)/guardian(s) will receive an information letter with extensive information on the 
study, adjusted to age. Subjects and parent(s)/guardian(s) will be approached by 
researchers after a minimum of one week, to answer all questions and schedule an 
informed consent meeting (in person or by telephone) if they show interest. During this 
meeting, the researcher will explain everything about the study and parent(s)/guardian(s) 
can sign informed consent (with the researcher or at home, which will then be send to the 
researcher). Subjects between 12 and 16 years will give a co-consent in addition to the 
informed consent of their parents/guardians, if they are able to do so.   
11.3 
Objection by minors or incapacitated subjects (if applicable) 
We will make sure that a minor or incapacitated subject will never be forced to participate 
in our trial. Subjects aged 12-16 must give a co-consent in addition to the informed 
consent of their parent(s)/representative(s). The subject can only participate if both 
parties have given consent. Younger subjects (age 4-12) will be informed about the study 
in the best way we can (by means of a specific information letter, adjusted by age). If a 
minor or incapacitated subject gives any objection against participation, the subject will 
not be included in the study. Next to that, all subjects will be able to stop participating in 
the study, at any moment during the study. When the subject is able to communicate this 
(non)verbally, the wish of the subject will be honored. If the NightWatch is experienced as 
a nuisance, or makes the subject uncomfortable, the device will be removed in 
consultation with the parent(s)/representative(s).  
11.4 
Benefits and risks assessment, group relatedness 
Implementing SDD is not considered to pose any substantial risks. Study participation 
can be a burden for the family (especially the parents/guardians) though, due to impact 
of the devices on privacy, impact of false alarms and time spent on the questionnaires & 

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interviews. Participation does, however, also offer better insight for the 
parents/guardians in the actual nocturnal seizure activity of their child, demonstrates the 
added value of the NightWatch and may help them to timely alert to a major seizure. 
When actual seizure activity is not consistent with the parent’s expectations, this 
information can be confronting. All study results will be shared with the attending 
neurologists, so parents/guardians will be able to discuss this problem.    
 
We will inform subjects and parent(s)/guardian(s) as good as possible on the impact of 
the study design on their privacy. It can be quite a burden to have a camera running in 
your (child’s) room every night. To minimize this burden, we will give the subject and 
parent(s)/guardian(s) the opportunity to delete sensitive video or audio material from the 
storage data before it is send to the researchers. To prevent the risk of data getting lost, 
we do not allow subjects or parent(s)/guardian(s) to delete the material themselves. 
Every 1-2 weeks, when a trial nurse comes to their home to switch the external hard disk 
for an empty one, they are able to delete any footage they want, without any 
consequences. If subjects of parent(s)/guardian(s) do not want the trial nurse to see or 
hear the sensitive material, they can simply refer to a specific night, or time-window 
during a night, which will then be deleted by the trial nurse. If they wish to stop the 
recordings, they can contact the researcher to discuss which recordings should be 
stopped and those will be switched off immediately.  
If a high frequency of false alarms causes a big burden on parent(s)/guardian(s), they 
can contact the researcher to discuss this problem. The researcher can then offer them 
the possibility to switch off the audible alarms. Because the annotation process takes 
some time, we are not able to give feedback on the reason for these false alarms, and if 
they are really false alarms, at that time. When the analyzation process is completed, the 
researchers will give the parent(s)/guardian(s) the opportunity to look at the recordings of 
their child to learn more about their seizures and reasons for false alarms. 
 
At the end of the study, we will  share the performance data of NightWatch with the 
subject’s neurologist. He/she will invite the subject and/or his/her parent(s)/guardian(s) to 
discuss this performance and user experiences. As an objective third party, the 
neurologist can then advise them to keep NightWatch for further use or might advise to 
use another seizure detection device.  
According to the performance of NightWatch, we will offer the following options at the end 
of the study:  

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In case of good performance, combined with satisfying use, NightWatch can give the 
family a benefit. In these cases, we would like to offer them the possibility to keep 
NightWatch for further use. We believe that offering NightWatch for free or a small 
amount of money can give an undesirable financial incentive to participate. It should be 
noted that currently none of the seizure detection devices are reimbursed. The most 
frequently sold seizure detection device (bed sensor) that was shown to have a poorer 
performance in our previous trial (LICSENSE NTR4115) has a higher cost price (€1700,-) 
compared to the NightWatch (€1500,-). For the above reasons, we found a 50% reduced 
rate of €750,- to be reasonable, since this is equal to the production costs. Besides, 
Livassured will offer a two year guarantee for the service and support of the device.   
  
In case of bad performance, we will  assess whether better performance can be 
obtained using a tailored algorithm. To this end we will review all trial data of the 
participant and evaluate the effects of altering the algorithm thresholds. If this is likely to 
result in a substantial improvement, we will offer participants a second 2-month 
intervention period with a tailored NightWatch algorithm. At the end of this trial we will 
once again share the results with the family and the treating neurologist. If the 
performance has improved we will offer the NightWatch at reduces rate of € 750,-. 
 
 
Compensation for injury 
The investigator has a liability insurance which is in accordance with article 7 of the WMO. 
  
SEIN has an insurance with HDI Global SE, the Netherlands, which is in accordance with 
the legal requirements in the Netherlands (Article 7 WMO). This insurance provides cover 
for damage to research subjects through injury or death caused by the study. 
The insurance applies to the damage that becomes apparent during the study or within 4 
years after the end of the study. 
 
11.5 
Incentives (if applicable) 
There will be no financial compensation for participation.  
In case of good performance of NightWatch, we will offer participants NightWatch at a 
reduced rate of €750,-. (See explanation above, 11.4)

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ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION 
11.6 
Handling and storage of data and documents 
The processing of personal data in pursuit of this trial will be limited to those data that are 
reasonably necessary to investigate the efficacy, safety, quality and utility of the seizure 
detection sources used in this trial. The collected data contains not only figures and 
written observations, but also video-images. Subjects or their parents/guardians have the 
possibility to remove privacy-sensitive video-images from  the trial data. They can 
indicate whether they want to remove video-images every time one of the researchers 
comes to their home to change the external hard-disk. The investigators will process the 
video-fragments with adequate precautions to ensure confidentiality and to protect the 
privacy. 
All recordings will be stored safely at SEIN Heemstede and Kempenhaeghe for further 
analysis and a back-up of all data will be stored at SEIN Heemstede for 15 years after 
closure of the trial. Patient files will be coded and only the coordinating and principal 
investigator will have the key to this code.   
No medical records will be shared with the sponsor or subsidizing parties. Only coded 
data from the study will be shared with LivAssured (the provider of the NightWatch) and 
CLB (provider of the audio algorithms) to optimize their algorithms.    
The trial team ensures that the personal data are:   
- collected for a specified and legitimate purpose;  
- processed fairly and lawfully; 
- accurate and up to date; 
- not published or shown without prior explicitly written consent.   
The trial team ensures that any audio fragments that could de-identify the subject (e.g. 
spoken language) will not be used for audio analysis by CLB. Prior to data exchange all 
audio fragments will be checked by the researchers. 
 
Explicit consent for the processing of personal data will be obtained from the participating 
subject (or his/her legally acceptable representative) prior to any processing of personal 
data.  All personnel whose responsibilities require access to personal data agree to keep 
the identity of trial subjects confidential.  This confidentiality will be maintained throughout 
the complete data processing. Trial subjects will be entitled to request confirmation of the 
existence of personal data in the database and will have the right to rectify erroneous or 
inaccurate data. 

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11.7 
Monitoring and Quality Assurance  
We will ask the Julius Center to monitor the trial according to the current Standard of 
Good Clinical Practice. One initiation, two monitoring, and one close out visit to both 
analyzing sites (SEIN and Kempenhaeghe) will be performed. Monitoring activities 
include: 1) monitoring rate of inclusion and dropout; 2) Checking availability and 
completeness of trial master file, informed consent forms, all SEAs, in- and exclusion 
criteria of a sample of subjects, query process and the presence of instructions for the 
execution of study procedures and if study personnel has been properly trained; 3) 
Verification of existence and identity of subjects and endpoints.  
 
11.8 
Amendments  
Amendments are changes made to the research after a favorable opinion by the 
accredited METC has been given. All amendments will be notified to the METC that gave 
a favorable opinion.  
 
A ‘substantial amendment’ is defined as an amendment to the terms of the METC 
application, or to the protocol or any other supporting documentation, that is likely to 
affect to a significant degree: 
- the safety or physical or mental integrity of the subjects of the trial; 
- the scientific value of the trial; 
- the conduct or management of the trial; or 
- the quality or safety of any intervention used in the trial. 
 
All substantial amendments will be notified to the METC and to the competent authority. 
 
Non-substantial amendments will not be notified to the accredited METC and the 
competent authority, but will be recorded and filed by the sponsor.  
 
11.9 
Annual progress report 
The sponsor/investigator will submit a summary of the progress of the trial to the 
accredited METC once a year. Information will be provided on the date of inclusion of the 
first subject, numbers of subjects included and numbers of subjects that have completed 
the trial, serious adverse events/ serious adverse reactions, other problems, and 
amendments.  
 

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11.10 Temporary halt and (prematurely) end of study report 
The investigator/sponsor will notify the accredited METC of the end of the study within a 
period of 8 weeks. The end of the study is defined as the end of the monitoring period of 
the last included subject (except for subjects with early withdrawal).  
 
The sponsor will notify the METC immediately of a temporary halt of the study, including 
the reason of such an action.  
    
In case the study is ended prematurely, the sponsor will notify the accredited METC 
within 15 days, including the reasons for the premature termination. 
 
 Within one year after the end of the study, the investigator/sponsor will submit a final 
study report with the results of the study, including any publications/abstracts of the study, 
to the accredited METC.  
 
11.11 Public disclosure and publication policy 
The study will be registered at cliniclatrials.gov.  
For the disclosure of the results, we will submit our results for publication in peer-
reviewed scientific journal. Involved companies will not have a say in the publication.   
 
 

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12 STRUCTURED RISK ANALYSIS  
12.1 
Potential issues of concern 
12.2 
Synthesis 
Implementation of our wearable sensor device (NightWatch) is not considered to pose any 
substantial risk. Since the efficacy of NightWatch has not yet been proven in children in a 
family home setting, we cannot guarantee that subjects and parents/guardians can rely 
completely on this device. There is a chance that parent(s)/guardian(s) will become less 
alert during the study. To minimize this risk, we will give them extensive information that 
especially emphasizes this matter. 
Study participation can be a burden for the family, due to the impact of the devices on 
their privacy, the impact of false alarms and the time spend on completing questionnaires, 
interviews and a diary. It does, however, also give the families better insight in seizure 
behavior of their child and shows them the possible utility of seizure detection.      
If the NightWatch becomes uncomfortable or causes any distress, the wearable device 
will be removed and the subject will be withdrawn from the study. In case of alarm fatigue, 
the parents/guardians can stop the NightWatch measurements and contact the researcher 
to switch off the alarms. If the subject or parents/guardians wish(es) to stop the video 
registration for any reason, they can contact the researchers to switch off the video 
recordings or even all recordings.  
 
 
 

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