Telemedically Assisted Sampling of COVID-19 Patients - Is the Sampling Quality Sufficient: An Interventional Randomized Method Comparison Study
Phase: NA
Conditions: Telemedicine, Pharynx, COVID-19
Sponsor: Teststation Praxis Dr. med Bielecki

Telemedically assisted sampling of COVID-19 patients -
Is the sampling quality sufficient? An interventional
randomized method comparison 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 according to HRO Art.7
Project Leader:
PD Dr. med. Walter Zingg, Leitender Arzt Klinik für
Infektionskrankheiten und Spitalhygiene, Universitätsspital Zürich,
Rämistrasse 100, 8091 Zürich
Walter.Zingg@usz.ch, +41 76 419 40 18
Co-Investigators:
Dr. med. Christian Eisenring (local investigator)
Dr. med. Michel Bielecki
Dr. med. Thibault Lovey
Dr. med. Fabian Kraxner
Charles Winiarski, PhD
Version Nr
Version date
Modified
without version
change
Description, comments
Control
3.0
14.04.2022
Revised version
CE
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1

PROTOCOL SIGNATURE FORM
Study Title
Telemedically assisted sampling of COVID-19 patients - Is
the sampling quality sufficient? An interventional
randomized method comparison study
The project leader and Principle Invistigator have approved the protocol version 1 (dated
25.12.2021) and version 2 (dated 10.01.2022) and version 3 (dated 14.04.2022) 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
and procedures for integrity in scientific research involving human beings.
Sponsor and Project leader:
PD Dr. med. Walter Zingg
Date:    14.04.2022
Signature:
Principle and local Investigator
Name:  Dr. med. Christian Eisenring
Date:      14.04.2022
Signature:
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2

TABLE OF CONTENTS
Table of Contents
3
GLOSSARY OF ABBREVIATIONS
4
BACKGROUND and project rationale
5
project OBJECTIVES and Design
7
2.1 Hypothesis and primary objective
7
2.2 Primary and secondary endpoints
7
2.3 Project design
8
PROJECT POPULATION and Study procedures
11
3.1 Project population, inclusion and exclusion criteria
11
3.2 Recruitment, screening and informed consent procedure
11
3.3 Study procedures
12
3.4 Withdrawal and discontinuation
12
STATISTICS AND METHODOLOGY
13
4.1. Statistical analysis plan
13
4.2. Handling of missing data
14
5 Regulatory Aspects AND SAFETY
14
5.1 Local regulations / Declaration of Helsinki
14
5.2 Notification of safety and protective measures (HRA Art. 15, HRO Art. 20)
14
5.3 Serious events (HRO Art. 21)
14
5.4 Amendments
14
5.5 End of project
15
5.7 Insurance
15
6 FURTHER Aspects
15
6.1 Overall ethical considerations
15
6.2 Risk-Benefit Assessment
15
7 Quality CONTROL AND Data protection
16
7.1 Quality measures
16
7.2 Data recording and source data
16
7.3 Confidentiality and coding
16
7.4 Retention and destruction of study data and biological material
17
8  Funding / Publication / declaration of Interest
17
REFERENCES
17
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GLOSSARY OF ABBREVIATIONS
AES
Advanced Encryption Standard
BASEC
Business Administration System for Ethical Committees
CRF
case report form
Ct
cycle threshold
EBPI
Institut für Epidemiologie, Biostatistik und Prävention
FOPH
Federal Office of Public Health
GSS
guided self-sampling
H0
null hypothesis
H1
alternative hypothesis
HCP
healthcare professional
HRA
Human Research Act
HRO
Ordinance on Human
NP
nasopharyngeal
OP+N
oropharyngeal and nasal
PCR
polymerase chain reaction
RT
realtime
SD
standard deviation
SOP
standard operating procedure
TLS
Transport Layer Security
USS
unsupervised self sampling
VOC
variant of concern
μs
mean in the standard treatment group
μe
mean in the experimental treatment group
d
non-inferiority limit
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1
BACKGROUND AND PROJECT RATIONALE
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) pandemic has resulted
in more than 3.8 billion registered tests, 275 million positive cases, and 5 million deaths
worldwide.4,5 It will most likely remain for months or years.6,7 Early and regular testing has been
an important pillar of secondary prevention, since the beginning.8 The current global
emergence of the Omicron variant of concern (VOC), is rewriting the pandemic history because
of the increased viral load and transmission. 9 Current projections indicate that COVID-19
hospitalizations are likely to be higher in the next six months than in the last six months.10 Low
vaccination rates foster new mutations and thus, reduce the effectiveness of vaccination. This
puts older generations again at higher risk11 and shifts the timeline of the pandemic by at least
several months. 12,13
As a consequence of the spreading of Omicron VOC, the 2G+ rule has been in effect in
Switzerland, since December 20, 2021, meaning that in all publicly accessible cultural, sports,
recreational, and entertainment areas, even double vaccinated and individuals who recovered
more than four months ago are obliged to present a negative test, to be exempted from the
mask requirement indoors.14 The new measures taken by Switzerland in response to the
increasing number of omicron cases place an additional burden on the testing infrastructure,
patience, and satisfaction of dually vaccinated, asymptomatic individuals as they adjust their
daily lives as best they can to the circumstances with regular testing.
Regular testing is therefore expected to become a part of our lives to allow public operations.8
The testing infrastructure is currently costly to operate and maintain. In addition, the lack of
availability of adequately trained personnel and insufficient accuracy and quality of testing
urged some test centers to halt operations.15 This situation has exacerbated in decentralized,
rural areas where the density of test centers results in longer travel distances and inherent
transmission risks on public transport.16 However, this pandemic has also fostered solutions in
the form of e telemedicine with enormously increased applicability, especially rural areas.17
Several emerging issues, such as the use of technology by older adults, the availability of
high-capacity Internet access, and support for telemedicine, can be overcome in the near
future to increase the benefits of telemedicine.18,19
In Israel, the uptake of regular testing increased with the introduction of rapid home and
self-testing. Especially in areas of high viral activity, self- and home-tested children allowed the
schools to continue operating.20,21 Also, other Western countries, including the United Kingdom,
the United States of America22 and Switzerland, introduced video-assisted sampling as a
self-testing strategy.23,24 In Switzerland, this has been well received by broad segments of the
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population; however, only polymerase chain reaction (PCR) tests had been medically approved
to generate a certificate.25 The advantages are obvious: less exposure of symptomatic to
healthy individuals in test centers, increased low-risk accessibility for e.g.
immunocompromised people, consistent implementation of isolation and quarantine
obligations without interruption for early termination based on negative testing26. The available
private information technology and communication infrastructure with smart devices reduce the
provision of costly state infrastructure.
Studies comparing self-sampling were published, but none compared autonomous self-testing
with guidance by healthcare specialists to sampling by healthcare professionals in a
randomized controlled trial.27–30 Non-inferiority of oral + nasal vs. nasopharyngeal sampling has
been proven31. However, the question of whether telemedically supervised testing with
SARS-CoV-2 Rapid Antigen Tests is non-inferior to the same tests being carried out by trained
personnel in test centers is still open for debate.
With this study, we aim to compare and evaluate the reliability and sampling quality of
self-performed rapid tests for professional use compared to professional sampling by
healthcare personnel. This will be done by comparing cycle threshold (Ct) values of both
housekeeping genes and SARS-CoV-2.32
A solution that builds on the capacity of existing laboratories may be implemented with a high
level of safety and minimizes the risk of transmission in rural areas.
This fuels hope that medical personnel will be relieved of the burden of jointly managing the
pandemic as a national and global challenge.
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2
PROJECT OBJECTIVES AND DESIGN
2.1 Hypothesis and primary objective
Our hypothesis is that, applying a strict standard operating procedure (SOP, attached), guided
oropharyngeal + nasal (OP+N) self-sampling (GSS) is non-inferior to nasopharyngeal (NP) or
OP+N sampling performed by health care professionals (HCP), and that guided OP+N
sampling is superior to unsupervised OP+N self-sampling (USS).
Figure 1: Anatomy of Larynx/Pharynx33
●
OP+N GSS is non-inferior to nasopharyngeal (NP) sampling performed by HCP
●
OP+N GSS is non-inferior to OP+N performed by HCP
●
OP+N GSS is superior to unsupervised OP+N USS
We are also interested to know if the difference between the sampling techniques is the same
depending on the SARS-CoV-2 viral load (low, medium, high).
Another secondary endpoint will be in how many people a correctly executed nasopharyngeal
sampling is possible. Due to lack of comfort, deviation of septum, as well as nasal polyps in a
small percent of the population, we hypothesize that in a majority of people it is not possible to
correctly execute a nasopharyngeal sampling.
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2.2 Primary and secondary endpoints
The Ct-value is defined as the number of cycles required for a signal to cross the detection
threshold and can be used as a surrogate for sampling quality, as it allows to quantify the
amount of material that is being extracted.
Primary endpoints:
●
Concordance of positive/negative samples in antigen tests with GSS, USS, and
HCP-based samples.
Secondary endpoints:
●
Housekeeping gene Ct comparison based on sampling method between samples
based on GSS, USS, or HCP
●
ORF1ab/RdRp-, E-, N-, and S genes Ct value comparison based on sampling method
between samples based on GSS, USS, or HCP
●
Qualitative analysis of perceived sampling accuracy established with a short form
●
Detected variant of concern
●
Case report form (CRF) assessing basic demographics and variables of interests as
indicated separately in the CRF form
●
Prevalence of variants of concern
●
Immunization status
●
Travel destinations in the passed three months
●
n of people in which a nasopharyngeal sampling is possible correctly (ratio)
2.3 Project design
This is a single-center, randomized, controlled study at a Swiss test station.
2.3.1 Piloting
In order to assess the sampling quality by HCP or telemedically guided self-sampling, Ct
values obtained in RT-PCR analysis of a COVID-19 assay, a housekeeping gene can be used
for reference.
Hence, for the first part of the study, we will recruit 10 people in which we will perform an
OP+N sampling at two-time points, 15 minutes apart, and compare the Ct values of these two
values to calculate the standard deviation and see if the produced SD*1.96/√(Sample size)
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equals the margin of error. Our 95% confidence interval (CI) will be standard deviation (SD)+/-
the margin of error.
Alternatively, we will pool confirmed RT-PCRs of two/three swab samples into one and spike
them with SARS-CoV-2 standard. Next, we do as many repeats of the same sample on
RT-PCR comparing housekeeper and SARS-CoV-2 genes. The advantage here is that we will
have controlled starting biological material and the resultant SD / 95% CI will concern only the
analytical and laboratory process variability. With the first approach, we will test SD of the swab
procurer too, along with the interference coming from the analytical process (lab, instruments,
sample storage).
2.3.2. Randomized telemedical and HCP sampling
After giving informed consent by signing the consent form, patients will be randomized to either
OP+N GSS - or to OP+N USS.
After performing either procedure, they will continue to be sampled by HCP OP+N and HCP
NP.
We will start the assessment with the self-sampling methods in order to reduce bias that could
occur if they experience the HCP’s sampling.
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Written instructions on how to perform a self-test will be provided, representing the instructions
that come along with a commercially available rapid test set. An instructional online video
tutorial or similar would also account as the latest state of the art.30 However, this has not yet
been implemented comprehensively with all available test sets that are currently being
distributed across Switzerland.
Furthermore, to avoid bias in the sampling procedure, exclusively one HCP at the testing
station will be designated as the study's sampling expert. The HCP will perform the NP and
OP+N sampling sequentially in a previously randomized order.
The telemedical guidance will be exclusively done by the same HCP in order to minimize
interoperability differences. The standardized telemedical sampling will be conducted at the
same test station, in a separate empty room in which a computer will be placed with
instructions on how to connect for the telemedical consultation.
Figure 1: Study chart
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During each sampling procedure, the patients will either undergo OP+N GSS or OP+N USS for
PCR analysis, as well as for antigenic testing. This means each participant will be sampled a
total of six times within 15 minutes from different locations in the upper respiratory tract.
Concordance of results between sampling by GSS vs. USS vs. HCPs will be assessed.
As the difference in time between the samplings can influence the Ct value, the sampling
process will only be started when the HCP and the telemedical supervisor are ready. The three
different samples will be stored in the test station refrigerator between 2°C-8°C before
transport.
A grouping of samples will ensure that temperature changes are consistent between samples
from the same participant.
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3
PROJECT POPULATION AND STUDY PROCEDURES
3.1 Project population, inclusion and exclusion criteria
All patients, regardless of symptoms, who present themselves at the Test-station SARS-CoV-2
testing will be offered to participate in the study.
Study inclusion criteria;  
●
Written informed consent 
●
Patients visiting the test-station for a SARS-CoV-2 test
●
Consent to comply with the study protocol 
●
Age of 18 or older
List the study exclusion criteria:
●
Refusal to comply with the study protocol
●
Digital illiteracy
(i.e. patients who would never use telemedicine as they do not feel
competent enough to use the necessary tools)
●
Not German or English speaking
●
People trained in the use of rapid diagnostic tests (HCP, biologists) will be excluded to
reduce bias30
3.2 Recruitment, screening and informed consent procedure
The participating test station in Olten receives approximately 100 patients per day for PCR
and/or antigen testing. The population is mixed as both asymptomatic people, as well as
symptomatic people, frequent the facility for SARS-CoV-2 testing. The recruitment will happen
by the local investigator in daily clinical practice. All costs for tests performed within the
framework of the study will be financed by the study. A payable travel certificate will be issued for
unchanged costs. Participation in the study and spending time on it is voluntary, free of charge and
at no cost to the study participants. However, each study participant will receive a voucher for free
PCR testing at a later date.
Patients who wish to have a COVID test can register online at least one day in advance for
predefined time slots for appointments (via the Onedoc-Software, Geneva, Switzerland).
Immediately after registration, the potential test participants will be informed about the study
either by telephone or by e-mail based on their contact details, with delivery of the written
study material if they are interested, giving them more than 24 hours to contemplate whether
they want to participate.
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At the consultation, a personal oral and written briefing about the study goals and study
design, as well as the informed consent form will be given to the participants. They are invited
to date and sign if they are willing to participate and have no further questions, and express to
have understood the content and do agree with it. A copy of the signed document will be given
to the study participant. The consent form will be stored as part of the study records.
Participants will not receive financial compensation for the participation in this study. However,
each study participant will receive a voucher for free PCR testing at a later date.
We shall end recruiting either when reaching the necessary sample size or no later than
October 30th, 2022.
3.3 Study procedures
-
The recruitment phase will start immediately after the approval of this study by the
cantonal ethical committee.
-
Sampling will be performed by a licensed and trained HCP.
-
The telemedical supervision will be guided by a licensed medical doctor.
-
The three different samplings will occur randomly in sequence (NP and OP+N by HCP
and either OP+N USS or OP+N GSS by the participant)
-
To ensure comparable results and reduce biases, all procedures will happen in the same
testing premises. The HCP will always sample the participants. The same doctor will
always guide the participants through self-sampling.
-
Registration starts at least 24 hours before the telemedical consultation. The
consultation will take about 10 minutes, sampling will take place at two time points, 15
minutes apart, and filling of the final questionnaire will take another 15 minutes. The
rapid test result is announced immediately and the COVID-19 certificates will be issued
according to cantonal guidelines. The PCR test evaluation takes a maximum of 24
hours and test results will be automatically communicated to the participant after
analysis. Positive results and symptomatic people will be reported to the federal office
of public health (FOPH) through the online reporting tool. The whole process from
registration to the communication of the final PCR result will take approximately 48
hours for each patient.
-
In case of a positive rapid test result, the FOPH is informed by the HCP on site through
the online reporting system. In case of a positive PCR test, the FOPH and cantonal
authorities are automatically informed by the analyzing laboratory.
-
We aim to finalize the study by December 31st, 2022.
-
Multiple laboratories have been contacted for participation in the study and the best fit
is currently being evaluated.
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Possible biases include mainly sampling bias and selection bias which are accounted for in the
study design via randomization and through tight exclusion criteria. A list of possible
confounders can be found in table 1 (Appendix).
3.4 Withdrawal and discontinuation
Participants are free to withdraw their consent at any time without giving any reason. In
case of withdrawal of consent, their sample will be destroyed and their data will be
deleted from the database.
4
STATISTICS AND METHODOLOGY
4.1. Statistical analysis plan
4.1.1 Randomization
To ensure allocation concealment, randomization will be performed with a block of 170 in a 1:1
allocation ratio by a web-based independent randomization software (Random Allocation
version 1.0). Patients will be randomly assigned to either OP+N GSS or to OP+N USS.
Instruction on the assigned procedure will be kept in sealed opaque envelopes labeled with
sequential study numbers and opened right before swab-testing.
4.1.2 Sample size
The SD of the mean of Ct values for RT-PCR analysis of multiple samples is not clearly defined
in the literature and varies between studies.34,35
If there is truly no difference between the standard and experimental treatment, then 85
patients per group are required to be 90% sure that the lower limit of a one-sided 97.5%
confidence interval (or equivalently a 95% two-sided confidence interval) will be above the
non-inferiority limit of -3.
We, therefore, estimated a standard error of six that accounts for this variance. In addition, the
limit of non-inferiority was set at three according to clinical significance.
Results will be stratified by symptom status, age, and sex.
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4.1.3 Hypothesis
Primary outcome
NP HCP vs OP+N HCP
H0: μe − μs ≤ -d  -> μ(NP HCP ct) - μ(OP+N HCP ct) ≤ -3
H1: μe − μs > -d ->  μ(NP HCP ct) - μ(OP+N HCP ct) > -3
OP+N HCP vs OP+N GSS
H0: μe − μs ≤ -d  -> μ(OP+N HCP ct) - μ(OP+N GSS ct) ≤ -3
H1: μe − μs > -d ->  μ(OP+N HCP ct) - μ(OP+N GSS ct) > -3
OP+N HCP vs OP+N USS
H0: μe − μs ≤ -d  -> μ(OP+N HCP ct) - μ(OP+N USS ct) ≤ -3
H1: μe − μs > -d ->  μ(OP+N HCP ct) - μ(OP+N USS ct) > -3
Secondary outcome:
We will stratify the primary outcome by viral load (low, medium, high).
4.1.4. Statistical test
A variant of a paired student t test or Wilcoxon test (if non-normal distribution) with exchange of
null and alternative (relaxed) hypotheses will be used as a non-inferiority test to assess
differences in cycle threshold (Ct, considered as a log2-transformed measure of the amount of
viral RNA load) between the NP and OP/N samples (HCP and GSS). Stratification for possible
confounders will be done using logistic regression.
In order to show agreement between the approaches and estimate the limits of agreement and
those are not too large, different graphical methods, such as Bland Altman diagrams will be
used to show agreement between the approaches.
4.2. Handling of missing data
Analysis is based on intention-to-treat assumption. Collected data until drop-out will be
included for further analysis.
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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
Helsinki3, the principles of Good Clinical Practice, the Human Research Act (HRA)2 and the
Human Research Ordinance (HRO)1 as well as other locally relevant regulations. The Project
Leader and the Sponsor both acknowledge their responsibilities.
5.2 Notification of safety and protective measures (HRA Art. 15, HRO Art. 20)
If, during the research project, circumstances arise which could jeopardize the safety or health
of the participants or lead to a disproportionate relationship between the risks and burdens and
the benefits, all the measures required to ensure protection are to be taken without delay.
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)
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. 211.
5.4 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.
5.5 End of project
Upon project completion or discontinuation, the Ethics Committee is notified within 90 days. All
biological materials and health-related data are anonymized upon the termination of data
analysis.
5.7 Insurance
In the event of project-related damage or injuries, the Sponsor will be liable, except for
damages that are only slight and temporary; and for which the extent of the damage is no
greater than would be expected in the current state of scientific knowledge, except for claims
that arise from misconduct or gross negligence. (Art. 12 HRO).
1 A serious event is defined as any adverse event where it cannot be excluded, that the event is attributable to the
sampling of biological material or the collection of health-related personal data, and which:
a. requires inpatient treatment not envisaged in the protocol or extends a current hospital stay;
b. results in permanent or significant incapacity or disability; or
c. is life-threatening or results in death.
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6
FURTHER ASPECTS
6.1 Overall ethical considerations
Already before the COVID-19 pandemic, the Swiss healthcare system has been undergoing a
digital transformation. Digitalization enables decentralized living, e.g., in a home office, making
life in remote areas more attractive. The desire for proximity to green nature, sufficient living
space and a garden of one's own has continuously gained in importance. On the one hand, the
population assesses Switzerland's healthcare system as particularly well equipped for
digitalization; on the other hand, deficits in implementation are also perceived, especially in
rural areas.36
Rural areas of Canada, Finland, Ireland, Sweden, Scotland, Northern Ireland, Faroe Islands,
Iceland, Greenland and Norway are also very positive about decentralized living. It allows
progress, optimizes organization, and responds effectively to healthcare challenges with
favorable economic outcomes.37 Similarities with Switzerland are that access to healthcare and
schooling are capable of turning rural areas more attractive for young families to build resilience
and encourage them to stay. This process is facilitated through digitalization.38 From a global
perspective, digitalization of healthcare is on the rise, in keeping with increased testing
capacities for COVID-19, which has proven essential to successful management of the
pandemic.39
In rural Australian areas, pending test results restrict everyday life. Emergency and family visits
are denied in case of a pending COVID-19 test result and quarantine occurs when there is a
suspected case of COVID transmission, while waiting for test results.40 Cumbersome testing is
a global challenge especially in rural regions.41 Challenges comprise diagnostic insufficiency
and low testing capacity since COVID-19 testing as well as treatment centers, are mainly
situated in the urban areas.42,43 Lack of easily applicable testing capacity leads vulnerable
groups to delay testing and seek medical care only at advanced stages of the disease,
resulting in poorer outcomes.44 There is clearly a local and global desire for large-scale testing
through fast, accurate and affordable diagnostic. A proven strategy to increase testing
capacities is to foster public-private partnerships.42
The use of self-testing with reactive antigen SARS-CoV-2 home tests is instrumental in
enabling governments around the world to relieve some restrictions to a reasonable degree and
open their economies and societies despite the advancing pandemic. Effective testing can also
be critical during a rapid surge in cases, as evidenced in India and USA, with governmentally
authorized reactive antigen SARS-CoV-home tests.45 Self-administered nasal swab rapid tests
are on the rise and bring relevant profits worldwide in the healthcare sector such as less
personnel effort, infrastructure, protective equipment and exposure of healthcare workers,
healthy individuals and symptomatically ill individuals. This brings about not only positive
impact on the health of each individual but also on a larger scale with advantageous social and
economic outcomes.45
The collected genetic study data will be handled as described above and the participants are
not exposed to additional risks compared to standardized testing as described below. This, in
keeping with the freely provided test-result and certificate suggests a fair balance for the study
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participant, also from a public health and economic point of view. Incidental findings would in
case of appearance be discussed with the study team and if need be with the Ethics
Committee. Study participation is voluntary and may be revoked without explanation as
described above.
6.2 Risk-Benefit Assessment
Self-sampling is already a common practice in Switzerland, in many European countries and in
many countries around the world. There are no additional risks to standardized OP+N
swab-testing to the study participants. The risk of each swab is already minimal and will be
kept minimal through professional instruction and supervision by specifically trained HCP.
However, the testing takes place six times on the same day, that means that possible
inconveniences such as local pain or discomfort is six times more likely.
No financial compensation is provided, but the cost of testing will be compensated. The
individual study participant will not have a direct profit of this clinical study to compare different
testing modalities. However, in the long term the participants and future patients may
contribute to acquisition of results concerning a simplified and less invasive testing method
that may be well integrated into everyday life. Future patients may benefit from a better
understanding of COVID-19 disease diagnostics.
7
QUALITY CONTROL AND DATA PROTECTION
7.1 Quality measures
To reduce biases strict SOPs will be implemented.
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.
The procedures will be done by specially trained physicians and scientists as health care experts
from the Teststation.
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7.2 Data recording and source data
The source data will consist of the study CRF, a baseline questionnaire. Clinical data will be
entered into  REDCap, an online CRF. Access is only possible with a username and password.
De-indentified data will be downloaded after study completion and stored for ten years on
University Hospital Zurich (USZ) secure server. This server is behind the institutional firewall.
The project data will then be transferred and stored permanently on REDCap in the REDCap
secure database.
Patient data will be stored in the REDCap database, behind the University of Alberta firewall,
and institutional data protection standards of University of Alberta, Canada will apply. This is a
password protected, secure database that can track changes. The server has an SSL security
certificate that allows encrypting the data that is transferred between the client and the server.
Regular back-ups of data can be created from REDCap database.
7.3 Confidentiality and coding
Project data will be handled with uttermost discretion and is only accessible to the
above-mentioned investigators 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 participant number. The document containing the keys linking the ID and
the patient will be encrypted and accessible only by the principal investigator.
Biological material in this project is not identified by participant name but by a unique
participant number. Biological material is appropriately stored in a restricted area only
accessible to authorized personnel.
All identifiable data will be uploaded to REDCap and once the project is archived at the
REDCap Server in Alberta-Canada, only the data manager at the Clinical Trials Center of the
Universitätsspital Zürich, Ashlesha Sonpar, will have access.
7.4 Retention and destruction of study data and biological material
Samples will not be kept after analysis, they will be discarded by the laboratory according to
the internal processes for biohazardous materials. Biological material will be destroyed at the
latest on 31.12.2022.
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The study data will be stored for 10 years after termination of the research project. Access will
be limited to the principal investigator.
8
FUNDING / PUBLICATION / DECLARATION OF INTEREST
This project is privately funded by the local investigator, Dr. med. Christian Eisenring.
There is a conflict of interest between one of the investigators (Dr. med. Michel Bielecki, CEO of
GobiX GmbH) who has a remote diagnostics startup and provides the testing facilities.
9
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25

Appendix
Schedule of assessments
Time
>-1 day
0
+1
Visit
Information
Testing
Results
oral
and
written
Information
+
Written consent
+
check inclusion-/
exclusion criteria
+
Participant
Characteristics
+
Procedures
+
Questionnaire
+
Sampling
+
Result communication
+
+ (PCR)
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26

Shell Table 1: Potential confounders
Confounding  Variables
Type of variable
Age
Continuous
Sex
Binomial
Mobility impairment
Nominal
Occupation
Categorical
Socioeconomic status
Continuous
Highest level of education attained
Ordinal
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27

Financing
Type
Source
Amount in CHF
Percent
public
Privately funded by
local investigator
30‘000
100
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28