Continuous Monitoring of Health Data With a Wearable Device in Pediatric Patients Undergoing Chemotherapy for Cancer - a Feasibility Pilot Study
Conditions: Pediatric Cancer, Febrile Neutropenia, Chemotherapy-induced Neutropenia, Oncology
Sponsor: Insel Gruppe AG, University Hospital Bern

 
 
Bern 2019 WD Pilot 
 
 
Continuous monitoring of health data with a wearable device in 
pediatric patients undergoing chemotherapy for cancer – a feasibility 
pilot study 
 
 
 
 
Research legislation: 
 Ordinance on human research with the exception of Clinical trials 
(HRO) [1]. 
 
 
Type of Research Project: 
Research project involving human subjects  
 
 
Risk Categorisation:  
Risk category A acc. to ordinance HRO Art.7 
 
 
Project Leader: 
 
Eva Brack, MD 
Pediatric Hematology/Oncology, Department of Pediatrics,  
University of Bern,  
Freiburgstrasse 
Inselspital, Bern University Hospital, CH-3010 Bern, 
Switzerland. 
phone +41 31 632 21 11; fax +41 31 632 95 07 
eva.brack@insel.ch 
 
Study Committee 
 
Eva Brack, MD, PhD  
Pediatric Hematologist/Oncologist 
 
 
 
 
Christa Koenig, MD  
Physician, cand. MD-PhD 
 
 
 
 
Roland A Ammann, MD 
Pediatric Hematologist/Oncologist 
 
 
 
 
Jochen K Roessler, MD 
Pediatric Hematologist/Oncologist 
 
 
 
 
 
 
 

 
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PROTOCOL SIGNATURE FORM    
 
 
Study Title 
Continuous monitoring of health data with a wearable 
device in pediatric patients undergoing chemotherapy for 
cancer – a feasibility pilot study 
 
The project leader has approved the protocol version [0.7 (dated 29.10.2019)], and confirms 
hereby to conduct the project according to the protocol, the Swiss legal requirements [1, 2], 
current version of the World Medical Association Declaration of Helsinki [3] and the principles of 
Good Clinical Practice.  
 
Project leader and Sponsor: 
 
Site: Pediatric Hematology/Oncology, Department of Pediatrics, University of Bern, Inselspital, 
Bern University Hospital, CH-3010 Bern, Switzerland. 
 
Name: Eva Brack 
Date: 
29.10.2019                                    Signature:  
 

 
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TABLE OF CONTENTS 
TABLE OF CONTENTS 
3 
GLOSSARY OF ABBREVATIONS 
4 
1 BACKGROUND AND PROJECT RATIONALE 
5 
1.1 Clinical Evidence to Date 
5 
2 PROJECT OBJECTIVES AND DESIGN 
6 
2.1 Primary objective 
6 
2.2 Secondary objectives 
6 
2.3 Choice of WD 
6 
2.4 Signals and scores collected 
6 
2.4 Primary and secondary endpoints 
7 
2.5 Project design 
8 
3 PROJECT POPULATION AND STUDY PROCEDURES 
8 
3.1 Project population, inclusion and exclusion criteria 
8 
3.2 Recruitment, screening and informed consent procedure 
9 
3.3 Study procedures 
10 
3.1.1 
Study visit 
10 
3.1.2 
Study period 
10 
3.1.3 
Follow-up 
11 
3.4 Withdrawal and discontinuation 
11 
4 STATISTICS AND METHODOLOGY 
11 
4.1 Statistical analysis plan 
11 
4.2 Handling of missing data 
12 
4.3 Planned Timetable 
12 
5 REGULATORY ASPECTS AND SAFETY 
12 
5.1 Local regulations / Declaration of Helsinki 
12 
5.2 Notification of safety and protective measures (HRO Art. 20) 
12 
5.3 Serious events (HRO Art. 21) 
12 
5.4 Procedure for investigations involving radiation sources 
13 
5.5 Amendments 
13 
5.6 End of project 
13 
5.7 Insurance 
13 
6 FURTHER ASPECTS 
13 
6.1 Overall ethical considerations 
13 
6.2 Risk-Benefit Assessment 
13 
6.3 Rationale for the inclusion of vulnerable participants 
14 
7 QUALITY CONTROL AND DATA PROTECTION 
14 
7.1 Quality measures 
14 
7.2 Data recording and source data 
14 
7.3 Confidentiality and coding 
15 
7.4 Retention and destruction of study data and biological material 
15 
8  FUNDING / PUBLICATION / DECLARATION OF INTEREST 
15 
9 REFERENCES 
16 
Appendix 1: Fitzpatrick Scale 
18 

 
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GLOSSARY OF ABBREVATIONS 
BASEC 
Business Administration System for Ethical Committees 
CRF 
Case report form  
FOPH 
Federal Office of Public Health 
HRA 
Human Research Act 
HRO  
Ordinance on Human 
WD 
 
Wearable device 
 
 
 
 
 

 
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1 
BACKGROUND AND PROJECT RATIONALE  
Pediatric patients with cancer and chemotherapy-induced neutropenia are at great risk to 
develop severe and potentially life threatening infections. Initially, fever is often the only clinical 
detectable sign of such an infection. Therefore, fever in neutropenia is treated as an 
emergency, including hospitalization, start of intravenous empirical broad-spectrum antibiotics 
and close monitoring.  
Several clinical decision rules have been established to distinguish between severe and less 
severe infections, based on the patient’s history, clinical appearance and laboratory signs [4, 5], 
but with the exception of fever, vital signs are hardly explored. Delay of diagnosis and treatment 
can result in increased mortality [6], more intensive treatment [7] and more adverse events [8]. 
Time from hospital admission to antibiotics has been shown to influence clinical outcomes [8].  
Wearable devices (WD) are already frequently used by athletes to monitor their activities and 
vital signs. Those devices are becoming smaller, more powerful and sophisticated and allow 
continuous recording of health data nearly everywhere and under any condition. Also in medical 
settings, WD are increasingly used for continuous measurements of patients’ health data [9, 
10]. Non-invasive on-skin wearable monitoring devices offer a broad set of health data that is 
recorded continuously [11]. 
It is hypothesized that continuous health data monitoring will provide more detailed information, 
and an more exact representation of the patient’s health status than discrete measurements.  
Specifically it has been shown, that infections trigger changes of vital-signs very early in their 
course. For example heart-rate variability has been identified to change before clinical 
symptoms are detectable in neonates with sepsis [12] and in adults who underwent bone 
marrow transplant [13, 14]. Using a WD therefore opens the possibility to identify health data 
patterns that might be used as an additional diagnostic tool or a tool predicting imminent fever 
or infection in the near future. This may lead to earlier diagnosis and shorter time to antibiotics 
in patients at high risk for severe infection and the distinction from patients at lower risk.  
1.1 Clinical Evidence to Date 
Continuous monitoring with wrist-worn WDs has been shown to be possible for heart rate (Fitbit 
Charge HR©) [15] and physical activity (GENEActiv accelerometer) [16, 17] in healthy children. 
Several studies have assessed physical activity in pediatric patients undergoing chemotherapy 
with WDs worn on the ankle (StepWatch 3TM Activity Monitor) [18], waist (MTI Actigraph 
accelerometer) [19]; (Actical activity monitor) [20] or clothes (FitBit®) [21]. But no study has 
proven feasibility of continuous monitoring of other health data or vital signs with any WD in 
pediatric patients undergoing chemotherapy for cancer (search in PubMed, using 
(Accelerometer OR Wearable Electronic Devices/ OR wearable OR sensor OR tracker*) AND 
(child OR children OR pediatric OR paediatric) AND (cancer/ OR cancer OR oncology), 
performed on June 20, 2019). It is not known if children tolerate a WD worn on the upper arm or 
thigh and if data quality sustains. Neither is it known if parents and patients can and are willing 
to handle a device in outpatient settings.   
We know of a currently ongoing pilot study in pediatric inpatients aged 4 to 16 years with 
perforated appendicitis, osteomyelitis or septic arthritis, investigating the feasibility of continuous 
vital sings assessment with the Everion® at the University of Basel Children’s Hospital (BASEC 
ID 2018-01926). In contrast to the present study, the Basel study excludes outpatients and 
patients below 4 years of age. Besides, the setting for children and adolescents undergoing 
chemotherapy for cancer is not comparable to patients receiving antibiotics for infections. 

 
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Additionally Everion® is currently investigated as one of five devices in an ongoing study trying 
to assess changes in physiological signals before and during seizures in children with epilepsy 
(NCT03745118). 
2 
PROJECT OBJECTIVES AND DESIGN  
2.1 Primary objective  
To assess the feasibility of continuous monitoring of heart rate in pediatric patients undergoing 
chemotherapy for cancer using the WD.  
2.2 Secondary objectives 
Secondary objectives are related to:  
A. Further feasibility aspects  
B. Comparison of continuously recorded data with results of discrete measurements performed 
for clinical routine care 
C. Exploration for specific patterns in continuously recorded data before and during episodes of 
fever and infection 
2.3 Choice of WD  
The WD investigated in this study is the Everion® by Biovotion, Zurich, Switzerland. To 
continuously monitor health data in children, a light and easy wearable device is needed, that 
does not hamper the child in any way during daily activities. The handling should be easy for the 
patients and/or parents to minimize the additional burden during the intensive treatment phases 
of chemotherapy. The Everion® is light (approximately 40g), without buttons and cables, and 
can be worn with an elastic band. Once the band is put on, the patient cannot tighten the band 
any further, as the size can only be adjusted by choosing the appropriate band size. This is 
more secure than an adjustable band for young children. As it is not known yet how to interpret 
the recorded data, it is necessary that the patients, parents and treating personnel do not have 
direct access to the data, as there is a risk for misinterpretation. In contrast to other WD, as 
smart-watches, the recorded data is not displayed on this WD. The Everion® is designed to 
measure with medical grade quality and provides a quality indicator for all calculated signals. It 
is CE-certified (CE 0123), medical device class IIa and FDA 510(k) exempt listed. Regulatory 
information: CE0123 ; MD Directive 93/42/EEC; RoHS Ro2011/65EU; Radioequipment 
Directive 2014/53/EU; Low Voltage Directive 2006/95/EC; WEE 2012/19/EU; EMC 2014/30 EU.  
One WD will be used for several patients, the WD is disinfected between different patients. For 
each patient a new elastic band will be used.  
2.4 Signals and scores collected  
Everion® generates signals as vital signs or scores at a frequency of one per second. For this 
study aggregates will be used. Aggregates are filtered or averaged versions of signals and will 
be calculated every minute. Aggregates are calculated as quality-weighted average considering 
all signals whose quality is >50 and then weights each signal by the quality-30. The associated 
quality score is the average of all quality values >50, if more than 10% of quality values are >50, 
else it is the average of all quality values <50. For signals without quality scores aggregates are 
calculated as median value for all signals in the aggregation period of three minutes.  
 
 

 
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Description of Aggregates  
unit 
range 
ID 
Quality 
Score 
 
name 
ID 
Signals comparable with discrete measurements 
 
 
S.1 HEART RATE  
bpm 
30-240 
6 
Q.1 
HEART RATE QUALITY 
68 
S.2 OXYGEN SATURATION 
% 
60-100 
7 
Q.2 
OXYGEN SATURATION 
QUALITY 
69 
S.3 RESPIRATION RATE        
bps 
2-60 
12 
Q.3 
RESPIRATION RATE QUALITY 
75 
S.4 CTEMP (Core temperature) 
°C 
21-46 
15 
Q.4 
CTEMP QUALITY 
76 
S.5 TEMPERATURE OBJECT 
(skin temperature) 
°C 
-10-40 
118 
- 
- 
- 
 
Signals for general performance 
 
 
 
 
 
 
S.6 HEART RATE VARIABILITY 
ms 
2-140 
11 
Q.6 
HEART RATE VARIABILITY 
QUALITY 
74 
S.7 PERFUSION INDEX 
- 
0-5 
8 
Q.7 
PERFUSION INDEX QUALITY 
133 
S.8 HEALTH SCORE 
- 
0-100 
22 
- 
- 
- 
S.9 GSR (Galvanic skin response) 
kOhm 
0-5 
21 
- 
- 
- 
 
Quality Scores 
Q.1 to Q.4 and Q.6: Quality scores for Signals S.1 to S.4 and S.6 [0 to 100; ≥50 indicates at 
least acceptable quality] 
Q.7 Quality score for Signal S.7, perfusion of the skin [0 to 5.2;  Higher values indicate better 
perfusion leading to better overall quality measurements; no limit defined for acceptable quality] 
2.4 Primary and secondary endpoints 
The primary outcome is defined  as at least acceptable (≥50) quality score Q.1 (see 2.3) of 
heart rate S.1 during a cumulative duration of ≥18/24h per day (midnight to midnight), during ≥7 
consecutive days within the 14 days of study duration (binary outcome, measured once).  
 
A. Secondary feasibility-related outcomes:  
A1) At least acceptable quality scores (Q.2 to Q.4 and Q.6/7) of further signals (S.2 to S.4 and 
S.6/7 (see 2.3) during a cumulative duration of ≥18/24h per day (midnight to midnight), during 
≥7 consecutive days within the 14 days of study duration (binary outcomes, measured once).  
A2) Cumulative length of time with at least acceptable quality scores Q.1 to Q.4 and Q.6/7 (see 
2.3) per study day (continuous outcomes, measured daily).  
A4) Primary outcome and secondary outcomes A1 and A2 by skin type according to the 
Fitzpatrick scale [22] (Appendix 1). 
A4) Primary outcome and secondary outcomes A1 and A2 by activity reported by parents and 
patients if applicable. 
A5) Proportion of patients and parents indicating that continuous monitoring with the WD is 
acceptable per day and per entire study duration (binary outcome, measured daily plus once).  
A6) Reasons not to wear the device as reported by parents and by patients if applicable 
(categorical outcome, measured daily). 
A7) Side effects reported by parents and patients, if applicable (categorical outcome, measured 
daily) 
A8) Effort (cumulative number and duration of contacts) per study day for the investigators 
(continuous outcomes, measured daily).  
 

 
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B) Secondary comparison-related outcomes: 
B1) Difference between discrete measurements performed for clinical routine cares of heart rate 
and the mean of continuously measured signal S.1 (heart rate) within +/-10min at times of the 
discrete measurement (continuous outcomes, measured potentially multiple times).  
B2) Like B1, for percutaneously measured blood oxygenation and signal S.2 (Oxygen 
Saturation). 
B3) Like B1, for respiration rate and signal S.3 (respiration rate). 
B4) Like B1, for ear temperature and signal S.4 (core temperature). 
B5) Like B1, for ear temperature and signal S.5 (skin temperature). 
 
C) Secondary outcomes for the exploration of specific patterns 
C1) Exploration of potential changes in or specific patterns of the measured signals S.1 to S.9 
and quality scores Q.1 to Q.6, within 48 hours before and after clinical diagnosis of fever (ear 
temperature of ≥39.0°C, or ≥38.5°C if fever is declared for clinical reasons) with or without 
neutropenia and microbiologically or clinically defined infections, if applicable. 
C2) Like C1) for further signals collected with the WD.  
2.5 Project design  
This is an investigator-initiated, single-center observational pilot study on the feasibility of 
continuous monitoring of health data with a WD in pediatric patients undergoing chemotherapy 
of cancer. For patients with cancer, the risk for severe infections is the highest during phases 
with chemotherapy induced neutropenia. Neutropenia normally last about 10 to 14 days. To 
detect severe infections earlier, this expected time period with neutropenia, is the period, in 
which continuous monitoring of health data does make most sense. Therefore, in this study the 
WD will be studied in the patients for 14 days.  
A total of 20 patients will be included, including at least 4 patients <6 years. As this is a 
feasibility study, a formal sample size calculation has not been performed. However, this 
sample size allows to assess the primary outcome with clinically meaningful precision and to 
roughly assess the primary outcome in the group of patients <6 years of age. 
3 
PROJECT POPULATION AND STUDY PROCEDURES 
3.1 Project population, inclusion and exclusion criteria  
Inclusion criteria: 
 
Chemotherapy treatment because of any malignancy, expected to last ≥1 month at time 
of recruitment for myelosuppressive therapy; or at least one cycle of myeloablative 
therapy requiring autologous hematopoietic stem cell transplantation. 
 
Age from 1 month to 17.99 years at time of recruitment 
 
Written informed consent from patients and/or parents 
 
Exclusion criteria:  
 
Local skin diseases prohibiting wearing of the WD. 
 
Denied written informed consent from patients and/or parents 
 

 
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3.2 Recruitment, screening and informed consent procedure 
This study will be conducted at the Inselspital, Bern University Hospital. Recruitment will take 
place at the Department of Pediatrics, in the Division of Pediatric Hematology/Oncology. 
Patients will be screened for eligibility and recruited by a study investigator or treating physician. 
No specific screening procedures except verifying inclusion/exclusion criteria are needed. 
Patients will be assessed during a routine outpatient visit, or during hospitalization. Patient 
recruitment will stop when the aimed number of twenty patients is reached. 
No payment or compensation will be given to study patients or their parents. 
 
The investigators will explain to the parents/legal representative and the patient if applicable, 
the nature of the study, its purpose, the procedures involved, the expected duration, the 
potential risks and benefits and any discomfort it may entail. The parents/legal representative 
and the patient if applicable, will be informed that the participation in the study is voluntary and 
that he/she may withdraw from the study at any time and that withdrawal of consent will not 
affect the subsequent medical assistance and treatment.  
The parents/legal representative and the patient if applicable, must be informed that the medical 
records may be examined by authorized individuals other than their treating physician. 
The parents/legal representative and the patient if applicable, will be provided a patient 
information sheet and a consent form describing the study and providing sufficient information 
for parents and patients to make an informed decision about their participation in the study. 
Sufficient time will be given to make the decision. 
The formal consent of the parents/legal representative and the patient if applicable, using the 
approved consent form, must be obtained before the patient is submitted to any study 
procedure.   
If a minor and/or patient under tutelage is capable of judgment, his/her assent is collected 
(required from the age of 14 years) in addition to the consent of the parents/legal representative 
on the informed consent form.  
The parents/legal representative and the patient if applicable, should read and consider the 
statement before signing and dating the informed consent form, and should be given a copy of 
the signed document. The consent form must also be signed and dated by the investigator (or 
his designee) at the same time as the patient sign, and it will be retained as part of the study 
records. 
 
 

 
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3.3 Study procedures 
 
Study Periods 
  
Screening 
Study visit 
Study period 
Follow-up 
Time (day) 
0, 1 or 
before 
0 or 1 
1 -14 
15 to 17 
In- /Exclusion Criteria 
x 
 
 
 
Patient Information and 
Informed Consent 
x 
 
 
 
Further patient 
characteristics 
x 
 
 
 
WD distribution 
 
x 
 
 
WD instructions 
 
x 
x 
 
Wearing the WD 
 
x 
x 
 
Primary outcome 
 
x 
x 
 
Secondary outcomes 
 
x 
x 
x 
Side effects 
 
x 
x 
x 
3.1.1 Study visit 
The study visit will be done during a routine outpatient visit, or during hospitalization. One of the 
study investigators will distribute the WD, the charger, and if needed the mobile phone to the 
parents or patient. Parents and/or patients, with no suitable mobile phone, will be provided with 
a phone for the study time. This phone will not be usable for other purposes than data transfer. 
Basic characteristics as age, height, weight, thigh and arm circumference and skin type will be 
assessed at the study visit. 
The WD is fitted using body size-appropriate elastic bands and the fitting is controlled by the 
investigator. Parents and patients if applicable, will be instructed in the handling and charging of 
the WD. For instructions, the pictures and descriptions provided by the manufacturer on the 
website, in the “instructions for use” handbook and the information in the study information form 
will be used. Instruction on how to install the mobile phone app for data transfer will be provided 
(see 7.2). The WD will be put on the upper arm or, if anatomically reasonable, on the upper leg.  
 
3.1.2 Study period 
There will be no additional examinations or procedures performed for this study, specifically no 
additional discrete measurements of vital signs will be undertaken unless the clinically indicated 
measurements. Daily activities and temperature measurements if taken during outpatient stay 
will be recorded on case report forms (CRF) by parents and/or by patients. Questionnaires will 
be used for the assessment of WD acceptance, side effects and reasons not to wear the device.  
Parents, patients and members of the treating staff will not be able to access the continuously 
measured data, in order to avoid any influence on clinical decision making due to these data. 
 
During the measurement period of 14 days no extra visits are planned. During the whole study 
period, one of the investigators will do a daily data-check, to see if data is recorded properly or 
not. If no data is recorded or if there are signs for reduced data quality, the parents and/or 
patients will be contacted by phone. Possible reasons for non-recording or reduced data quality 

 
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will be discussed on the phone and instructions will be given to parents and/or patients. During 
hospital visits calls may be replaced by on ward visits.  
 
Parents and/or patients can contact the study site by phone  any time by calling the pediatric 
oncology ward (24h emergency number) or outpatient ward and ask for assistance with the WD. 
Investigators are allowed to additionally check data recording, when contacted by parents or 
patients. Date, number, duration and reason of phone contacts and visits will be noted. 
 
During the study period, parents and/or patients will be in charge for battery charging (approx.2 
hours each day) and data upload via mobile phone app. Parents and/or patients will fill out a 
CRF daily and note time of charging, connection to the mobile phone, reasons for not wearing 
the WD, any side effects, activities and temperature measurements, if applicable.  
 
During hospitalization treating staff will perform discrete measurements as clinically indicated 
and note them in the patient chart. Parents and/or patients will continue to fill out the CRF daily. 
The charts will be assessed by the investigators to match the recorded data with the data from 
the WD.  
The study period ends regularly for each patient after the planned period of 14 days, in case of 
intensive care unit admission or at the day of death from any cause, unrelated to the study. 
3.1.3 Follow-up 
Follow-up period covers 24hours after the end of the study period. The respective follow-up 
interview by phone or if applicable during a routine hospital visit will take place 1 to 3 days after 
the end of the study period. 
3.4 Withdrawal and discontinuation 
Non-compliance, mainly not wearing or charging the WD, will not lead to exclusion from the 
study, as this is directly linked to the primary outcome.  
In case of withdrawal of informed consent no data will be collected beyond the date of 
withdrawal except for tracking of side effects for 24 hours after the last time the WD has been 
worn. The information collected until this date will be used for analysis. This information will be 
fully anonymized after analysis.  
4 
STATISTICS AND METHODOLOGY 
4.1 Statistical analysis plan 
For the primary outcome the proportion of patients and its exact 95% CI will be calculated.  
Feasibility of continuous monitoring of heart rate in pediatric patients under chemotherapy will 
be claimed if 15 of 20 patients (75%) fulfil the primary outcome. 
For all outcomes, descriptive statistics using standard methods, including graphical methods, 
will be performed and exact 95% CI for proportions and estimates, where applicable, will be 
calculated.  
For exploratory analyses different methods adapted to data types will be used.  
The analyzed dataset contains all included patients. The current version of the R software [23] 
will be used for analysis. 

 
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4.2 Handling of missing data  
There will be no imputation for missing data. No replacement of drop-outs is done, because the 
target assessed primary outcome will include drop-outs. 
4.3 Planned Timetable  
There are at least 20 patients under chemotherapy in the study site at any given time point and 
about 40 patients with newly diagnosed cancer per year. We expect a participation rate of about 
75% and thus a study duration of three to four months. We will use ten to twenty in parallel 
usable WDs. 
 
2019, June 
Submission to pediatric IRB Bern 
2019, August 
Submission to CEC 
2019, December 
Recruitment of first patient 
2020, March 
Last patient out 
2020, May 
Data closure, clean data 
2020, July 
Data analyzed 
2020, October 
Manuscript with main results submitted 
 
5 
REGULATORY ASPECTS AND SAFETY 
5.1 Local regulations / Declaration of Helsinki 
This research project will be conducted in accordance with the protocol, the Declaration of 
Helsinki [3], the principles of Good Clinical Practice, the Human Research Act (HRA) and the 
Human Research Ordinance (HRO) [1] as well as other locally relevant regulations. The Project 
Leader acknowledges his responsibilities as both the Project Leader and the Sponsor. 
5.2 Notification of safety and protective measures (HRO Art. 20) 
The project leader is promptly notified (within 24 hours) if immediate safety and protective 
measures have to be taken during the conduct of the research project. The Ethics Committee 
will be notified via BASEC of these measures and of the circumstances necessitating them 
within 7 days. 
5.3 Serious events (HRO Art. 21) 
A serious event is defined as any adverse event where it cannot be excluded, that the event is 
attributable to the collection of health-related personal data using the WD, and which: 
 
requires inpatient treatment not envisaged in the treatment protocol or extends a current 
hospital stay; 
 
results in permanent or significant incapacity or disability; or 
 
is life-threatening or results in death. 
If a serious event occurs, the research project will be interrupted and the Ethics Committee 
notified on the circumstances via BASEC within 7 days according to HRO Art. 21 [1]. The 
project leader will submit a report to the responsible Ethics Committee which evaluates the 
relationship between the event reported and the methods of collecting health related personal 
data within the project, and propose how to proceed with the project. 

 
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During this study the included patients are undergoing clinical procedures as per standard of 
care for their cancer diagnosis, which will cause side events unrelated to the study procedures 
and will not be reported.  
5.4 Procedure for investigations involving radiation sources 
No radioactive sources are used in this research project. 
5.5 Amendments 
Substantial changes to the project set-up, the protocol and relevant project documents will be 
submitted to the Ethics Committee for approval according to HRO Art. 18 before 
implementation. Exceptions are measures that have to be taken immediately in order to protect 
the participants.  
5.6 End of project 
Upon project termination, the Ethics Committee is notified within 90 days. All health-related data 
are anonymized upon termination of data analysis. Records and documents pertaining the 
conduct of this study, including source documents, CRFs and consent forms will be retained for 
10 years. 
5.7 Insurance 
In the event of project-related damage or injuries, the liability of the Inselspital Bern provides 
compensation, except for claims that arise from misconduct or gross negligence.  
6 
FURTHER ASPECTS 
6.1 Overall ethical considerations 
The research project will be carried out in accordance to the protocol and the Declaration of 
Helsinki, the guidelines of Good Clinical Practice (GCP) and the ISO Norm 14155, the Swiss 
Law and Swiss regulatory authority’s requirements. The CEC will receive annual safety reports 
and will be informed about study stop/end in agreement with local requirements. 
The study can only begin once approval from all required authorities has been received. Any 
additional requirements imposed by the authorities shall be implemented. 
6.2 Risk-Benefit Assessment  
For the participants this study has minimal risks:  
 
Pressure: If the WD is attached too tight, this can result in pressure and stasis injuries. 
 
Skin reactions: Allergic reactions to the materials used, skin reactions because of 
moisture or dirt between the skin and the device, or skin reactions to friction of the 
device against the skin may occur. 
 
Child distress: Young children may not understand the purpose of this study and of 
wearing the WD. Therefore, they could show symptoms of distress as persisting crying 
and resistance against attachment of the WD. 
Training and information of parents and of patients if applicable, will minimize these risks. The 
WD is fitted using body size-appropriate elastic bands. After fitting, the size of the band cannot 

 
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by tightened any further by the patient. Regular cleaning of the skin underneath the device and 
of the device itself will be instructed.  
 
In this study, there are no direct benefits for the patients. The knowledge gained from this study, 
and potential future studies building upon the results of this study may help to provide better 
care for future pediatric patients, including pediatric patients undergoing chemotherapy for 
cancer. 
6.3 Rationale for the inclusion of vulnerable participants  
Health data in children and adolescents is known to differ in many core characteristics from 
health data in adults and can therefore not be extrapolated from adults. To assess feasibility of 
continuous monitoring of health data in pediatric patients specifically, children and adolescent 
need to be studied themselves, despite them being especially vulnerable study participants.  
7 
QUALITY CONTROL AND DATA PROTECTION 
7.1 Quality measures  
For quality assurance the Ethics Committee may visit the research sites. Direct access to the 
source data and all project related files and documents must be granted on such occasions. All 
staff involved are trained in project related procedures and all important aspects. 
7.2 Data recording and source data 
Baseline patient data and information on disease and treatment, where relevant, will be 
extracted from electronic medical records. Investigators and staff of the study site delegated to 
complete CRFs will record study-related information on patients.  
Data recorded by the WD will be transferred to the mobile phone via Bluetooth and then 
uploaded in a pseudonymized fashion to a web-based password-protected dashboard. The WD 
cannot be linked with other devices and recorded data cannot be read by third parties, nor by 
the parents and patients. Biovotion is ISO 13485 certified [24] and guarantees data security in 
compliance with the EU General Data Protection Regulation. Biovotion will provide an 
application programming interface, so that the investigators can download the data themselves. 
Access and retrieval of the data from the dashboard is secured by a password. All data are 
transferred and stored using encryption (TLS, https).  
 
Source documents include the patients’ charts (electronic as well as paper), which are stored at 
the site-specific usual location for charts. Data recorded by the WD will be downloaded by the 
investigators and stored electronically in a SharePoint Databased provided by the CTU Bern. 
This database will be used as source document for the WD data, as the web-based dashboard 
is not convenient for long term data storage.  
If parents and patients if applicable consent, collected data will be published in anonymized 
form. Study-specific documents (Informed Consent Forms, screening form, patient identification 
list and relevant correspondence) are filed in the Investigator Site File. The Investigator Site File 
is stored in a closed location of the “study center”. 
 

 
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7.3 Confidentiality and coding 
Project data will be handled with uttermost discretion and is only accessible to authorized staff 
who require the data to fulfill their duties within the scope of the research project. On the CRFs 
and other project specific documents, participants are only identified by a unique patient number 
(ID). The patient identification list will be stored by the project leader. 
 
Confidentiality of the patients will be maintained by assigning a unique patient number (ID), 
keeping identifiers separate from the data and storing data in a locked file with password access 
and secure computer database in line with Swiss legal requirements. Scientific reports 
generated from the study will not contain information that would identify the participating 
children. Biovotion Zurich signed a data processing agreement and agrees not to try to re-
identify the pseudonymized data and to maintain confidentiality about all information. 
7.4 Retention and destruction of study data and biological material 
Source documents and documents pertaining to the conduct of this study, including CRFs, and 
consent forms, are archived for a minimum of 10 years after the completion or premature 
termination of the study. 
8  FUNDING / PUBLICATION / DECLARATION OF INTEREST 
Funding for this study will be searched by grant applications to the “Batzebär” foundation and, 
for backup, to the “Berner Stiftung für Krebskranke Kinder und Jugendliche”. These institutions 
will have no influence on the study design, data collection and analysis, decision to publish, or 
preparation of the manuscript. 
 
The main results of this study will be communicated to the parents and the patients if applicable, 
and the treating staff involved in a letter written in lay language. 
The detailed study results will be submitted for publication in peer-reviewed journals. The 
current version of the ICMMJE recommendations regarding authorship eligibility is applicable. 
The use of professional writers is not planned. 
The protocol is not confidential; it is intended to be made publicly available. 
There is no conflict of interest for the Sponsor-Investigator and for all study investigators. 
 
 

 
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Appendix 1: Fitzpatrick Scale 
The Fitzpatrick skin type classification denotes six different skin types [22, 25]. The scale is based 
on a questionnaire related to an individual’s genetic constitution, reaction to sun exposure and 
tanning habits. The response to all questions are added to get the final score (all tables from: 
Sachdeva S. Fitzpatrick skin typing: Applications in dermatology. Indian J Dermatol Venereol 
Leprol 2009 [25]) 
 
Table A1: Genetic disposition, total score 0-16 
Table A2: Reaction to sun exposure, total score 0-16 
Table A3: Tanning habits, total score 0-8 
Table A4: Total score of table A1 to A3 corresponding to Fitzpatrick skin Type