Quality of Recovery After Day Care Surgery With App Controlled Remote Monitoring: a Randomized Controlled Trial
Phase: NA
Conditions: Pain, Nausea, Vomiting
Sponsor: Onze Lieve Vrouwe Gasthuis

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
 
 
 
 
 
 
 
 
Quality of Recovery after day care surgery with 
app controlled Remote Monitoring: a 
randomized controlled trial  
(December  2021) 
 
De kwaliteit van herstel na een dagbehandeling operatie met 
thuismonitoring via een smartphone app 
 
 
 
 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
 
 
 
PROTOCOL TITLE: Quality of Recovery after day care surgery with app controlled 
Remote Monitoring: a randomized controlled trial 
 
Protocol ID 
NL78144.100.21 
Short title 
QuReMo Trial 
EudraCT number  
 
Version 
4 
Date 
15-12-2021 
Coordinating investigator/project 
leader 
 
B. Thiel MPA MSc 
Department of Anaesthesiology 
OLVG Hospital (Oost) 
Mailbox 95500  
Postal Code 1090 HM Amsterdam 
the Netherlands 
e-mail: b.thiel@olvg.nl 
Principal investigator(s) (in 
Dutch: hoofdonderzoeker/ 
uitvoerder 
 
M.B. Godfried MD PhD 
Department of Anaesthesiology 
OLVG Hospital (Oost) 
Mailbox 95500  
Postal Code 1090 HM Amsterdam 
the Netherlands 
e-mail: m.b.godfried@olvg.nl 
 
R.T.M. van Dongen MD PhD 
Department of Anaesthesiology 
Canisius Wilhelmina Hospital (CWZ) 
Weg door Jonkerbos 100 
Postal Code 6532 SZ 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
 
 
 
Nijmegen 
the Netherlands 
e-mail: r.t.m.vandongen@cwz.nl 
 
J.S.H.A. Koopman MD PhD 
Department of Anaesthesiology 
Maasstad Ziekenhuis 
Maasstadweg 21 
Postal Code 3079 DZ 
Rotterdam 
the Netherlands 
e-mail: KoopmanJ@maasstadziekenhuis.nl 
Sponsor: 
OLVG Hospital 
Mailbox 95500  
Postal Code 1090 HM Amsterdam 
 
The Netherlands 
Subsidising party 
- 
Independent expert (s) 
J.E. Steenhuisen MD 
Department of Anaesthesiology 
OLVG Hospital (Oost) 
Mailbox 95500 
Postal Code 1090 HM Amsterdam 
The Netherlands 
Laboratory sites <if applicable> 
Not applicable 
 
 
Pharmacy <if applicable> 
Not applicable 
 
 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
 
 
 
PROTOCOL SIGNATURE SHEET: Quality of Recovery after day care surgery with app 
controlled Remote Monitoring: a randomized controlled trial, NL78144.100.21 
 
 
 
Name 
Signature 
Date 
M.B. Godfried MD PhD 
Anaesthetist 
OLVG Hospital  
 
 
R.T.M. van Dongen MD PhD  
Anaesthetist  
Canisius Wilhemina Hospital 
 
 
J.S.H.A. Koopman MD PhD 
Anaesthetist 
Maasstad Hospital 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
 
 
 
Involved Researchers 
 
C.J. Kalkman MD PhD  
 
Position: Professor anaesthesiology 
Role: Project Supervisor 
Department of anaesthesia and intensive care  
University Medical Centre Utrecht (UMCU 
Mailbox 85500 
Postal Code 3508 GA  
Utrecht, the Netherlands  
e-mail: c.j.kalkman@umcutrecht.nl 
B. Thiel MPA MSc 
Position: Physician assistant / Clinical epidemiologist  
Role: trial coordinator / PhD student 
Department of anaesthesiology 
OLVG Hospital (Oost) 
Mailbox 95500  
Postal Code 1090 HM  
Amsterdam, the Netherlands 
e-mail: b.thiel@olvg.nl 
M.B. Godfried MD PhD 
Position: Anaesthetist 
Role: Principal Investigator OLVG 
Department of anaesthesiology 
OLVG Hospital (Oost) 
Mailbox 95500  
Postal Code 1090 HM 
Amsterdam, the Netherlands 
e-mail: m.b.godfried@olvg.nl  
B.F. Geerts MD PhD MSc MBA 
Position: Anaesthetist/Intensivist 
Role: Investigator 
Spaarne Gasthuis (Zuid) 
Department of Intensive care 
Boerhaavelaan 22 
Postal Code 2035 RC 
Haarlem, the Netherlands 
e-mail: b.geerts@spaarnegasthuis.nl 
L.M. van Vliet PhD 
Position: Psychologist / Researcher 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
 
 
 
Role: Investigator  
University Leiden 
Wassenaarseweg 52 
Postal Code 233 AK 
Leiden, the Netherlands 
e-mail: l.m.van.vliet@fsw.leiden univ.nl 
E. Rümke 
Postition: Master Student 
University Leiden 
Wassenaarseweg 52 
Postal Code 233 AK 
Leiden, the Netherlands 
e-mail: e.w.rumke@umail.leidenuniv.nl 
L.M. Vernooij PhD 
Position: Clinical Epidemiologist 
Role: Investigator 
Department of anaesthesia and intensive care  
University Medical Centre Utrecht (UMCU) 
Mailbox 85500 
Postal Code 3508 GA  
Utrecht, the Netherlands 
e-mail: L.M.Vernooij@umcutrecht.nl 
W. Gerrits MD 
 
Position: Anaesthetist / Pain specialist 
Role: Principal Investigator CWZ 
Department of Anaesthesiology 
Canisius Wilhelmina Hospital (CWZ) 
Weg door Jonkerbos 100 
Postal Code 6532 SZ 
Nijmegen, the Netherlands 
e-mail: w.gerrits@cwz.nl 
R.T.M. van Dongen MD PhD 
Position: Anaesthetist / Pain specialist 
Role: Principal Investigator CWZ 
Department of Anaesthesiology 
Canisius Wilhelmina Hospital (CWZ) 
Weg door Jonkerbos 100 
Postal Code 6532 SZ 
Nijmegen, the Netherlands 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
 
 
 
e-mail: r.t.m.vandongen@cwz.nl 
M. Sundermeijer 
Position: Medical Assistant 
Role: Investigator / Medical Assistant 
Department of Anaesthesiology 
OLVG Hospital (Oost / West) 
Mailbox 95500  
Postal Code 1090 HM  
Amsterdam, the Netherlands 
e-mail: m.sundermeijer@olvg.nl 
P.  Maillé – Wisse 
  
Position: Trainee Nurse Specialist 
Role: Investigator / Student 
Department of Anaesthesiology 
Canisius Wilhelmina Hospital (CWZ) 
Weg door Jonkerbos 100 
Postal Code 6532 SZ 
Nijmegen, the Netherlands 
e-mail: p.maille@cwz.nl 
L. van Leeuwen 
Position: Trainee Nurse Specialist 
Role: Investigator  / Student 
Canisius Wilhelmina Hospital (CWZ) 
Weg door Jonkerbos 100 
Postal Code 6532 SZ 
Nijmegen, the Netherlands 
e-mail: l.vanleeuwen@cwz.nl 
J.S.H.A. Koopman MD PhD 
Position: Anaesthetist 
Role: Principal Investigator Maasstad Hospital 
Department of Anaesthesiology 
Maasstad Ziekenhuis 
Maasstadweg 21 
Postal Code 3079 DZ 
Rotterdam 
the Netherlands 
e-mail: KoopmanJ@maasstadziekenhuis.nl 
 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
 
 
 
TABLE OF CONTENTS 
 
1. 
INTRODUCTION AND RATIONALE .............................................................................12 
2. 
OBJECTIVES ................................................................................................................14 
3. 
STUDY DESIGN ...........................................................................................................15 
4. 
TREATMENT OF PATIENTS ........................................................................................17 
a. 
Investigational product/treatment ...............................................................................17 
b. 
Use of co-intervention (if applicable) ..........................................................................18 
c. 
Escape medication (if applicable)...............................................................................18 
5. 
INVESTIGATIONAL PRODUCT (Not applicable) ..........................................................19 
a. 
Name and description of investigational product(s) ....................................................19 
b. 
Summary of findings from non-clinical studies ...........................................................19 
c. 
Summary of findings from clinical studies ..................................................................19 
d. 
Summary of known and potential risks and benefits...................................................19 
e. 
Description and justification of route of administration and dosage ............................19 
f. 
Dosages, dosage modifications and method of administration ...................................19 
g. 
Preparation and labelling of Investigational Medicinal Product ...................................19 
h. 
Drug accountability ....................................................................................................19 
6. 
NON-INVESTIGATIONAL PRODUCT ...........................................................................20 
a. 
Name and description of non-investigational product(s) .............................................20 
b. 
Summary of findings from non-clinical studies ...........................................................20 
c. 
Summary of findings from clinical studies ..................................................................20 
d. 
Summary of known and potential risks and benefits...................................................20 
e. 
Description and justification of route of administration and dosage ............................20 
f. 
Dosages, dosage modifications and method of administration ...................................20 
g. 
Preparation and labelling of Non Investigational Medicinal Product ...........................20 
h. 
Drug accountability ....................................................................................................21 
7. 
METHODS ....................................................................................................................22 
a. 
Study parameters/endpoints ......................................................................................22 
i. 
Main study parameter/endpoint ..............................................................................22 
ii. 
Secondary study parameters/endpoints (if applicable) ...........................................22 
iii. 
Other study parameters (if applicable) ....................................................................23 
b. 
Randomisation, blinding and treatment allocation ......................................................23 
c. 
Study procedures .......................................................................................................24 
d. 
Withdrawal of individual subjects ...............................................................................25 
f. 
Replacement of individual subjects after withdrawal ..................................................25 
g. 
Follow-up of subjects withdrawn from treatment ........................................................25 
h. 
Premature termination of the study ............................................................................25 
8. 
SAFETY REPORTING ..................................................................................................26 
a. 
Temporary halt for reasons of subject safety .............................................................26 
b. 
AEs, SAEs and SUSARs ...........................................................................................26 
i. 
Adverse events (AEs) .............................................................................................26 
ii. 
Serious adverse events (SAEs) ..............................................................................26 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
 
 
 
iii. 
Suspected unexpected serious adverse reactions (SUSARs) ................................27 
c. 
Annual safety report ...................................................................................................27 
d. 
Follow-up of adverse events ......................................................................................27 
e. 
[Data Safety Monitoring Board (DSMB) / Safety Committee] ......................................27 
9. 
STATISTICAL ANALYSIS .............................................................................................28 
a. 
Primary study parameter(s)........................................................................................28 
b. 
Secondary study parameter(s) ...................................................................................28 
10. 
ETHICAL CONSIDERATIONS ...................................................................................31 
a. 
Regulation statement .................................................................................................31 
b. 
Recruitment and consent ...........................................................................................31 
c. 
Objection by minors or incapacitated subjects (if applicable) .....................................31 
d. 
Benefits and risks assessment, group relatedness ....................................................31 
e. 
Compensation for injury .............................................................................................31 
f. 
Incentives (if applicable) ............................................................................................31 
11. 
ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION .........................32 
a. 
Handling and storage of data and documents ............................................................32 
b. 
Monitoring and Quality Assurance .............................................................................32 
c. 
Amendments .............................................................................................................33 
d. 
Annual progress report ..............................................................................................33 
e. 
Temporary halt and (prematurely) end of study report ...............................................33 
f. 
Public disclosure and publication policy .....................................................................33 
12. 
STRUCTURED RISK ANALYSIS...............................................................................34 
a. 
Potential issues of concern ........................................................................................34 
b. 
Synthesis ...................................................................................................................34 
13. 
REFERENCES ..........................................................................................................35 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
10 of 36 
LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS  
 
ABR 
General Assessment and Registration form (ABR form), the application 
form that is required for submission to the accredited Ethics Committee; in 
Dutch: Algemeen Beoordelings- en Registratieformulier (ABR-formulier) 
ACWO 
Advies Commissie Wetenschap en Onderzoek 
AE 
Adverse Event 
App 
(smartphone) Application 
AR 
Adverse Reaction 
ASA 
American Society of Anaesthesiologists 
CCMO 
Central Committee on Research Involving Human Subjects; in Dutch: 
Centrale Commissie Mensgebonden Onderzoek 
CV 
Curriculum Vitae 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation; in Dutch: Algemene Verordening 
Gegevensbescherming (AVG) 
IC 
Informed Consent 
NRS 
Numerical Rating Scale (for pain) 
NVA 
Nederlandse vereniging voor Anesthesiologie 
METC  
Medical research ethics committee (MREC); in Dutch: medisch-ethische 
toetsingscommissie (METC) 
PDNV 
Post Discharge Nausea and Vomiting 
PDMS 
Patient Data and Management System  
POP 
Post Operative Pain 
(S)AE 
(Serious) Adverse Event  
SPC 
Summary of Product Characteristics; in Dutch: officiële productinformatie 
IB1-tekst 
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. 
SUSAR  
Suspected Unexpected Serious Adverse Reaction 
UAVG 
Dutch Act on Implementation of the General Data Protection Regulation; in 
Dutch: Uitvoeringswet AVG 
WMO 
Medical Research Involving Human Subjects Act; in Dutch: Wet Medisch-
wetenschappelijk Onderzoek met Mensen 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
11 of 36 
SUMMARY 
Rationale: To date the majority of surgical interventions is performed in day care and 
patients are being discharged soon after the first critical postoperative period. At home, 
patients have limited options to contact the hospital in case of severe pain and nausea. We 
have provided day care surgical patients with a smartphone application for remote monitoring 
that is configured to self-record postoperative pain and nausea after being discharged from 
hospital. Furthermore, it provides a messaging service  to contact the hospital in case of 
(severe) pain or nausea. Despite the promising initial patient experiences of such an 
application, we do not know whether remote monitoring with a  smartphone application 
improves the patient’s experience during the recovery period.     
Objective: To evaluate the experienced quality of recovery after day care surgery between 
patients provided with a smartphone application for remote monitoring and patients receiving 
standard of care (no remote monitoring).  
Study design: (Non-blinded) randomized controlled trial with mixed methods design 
Study population: Adult patients (aged 18 years or older) scheduled for day care surgery 
Intervention (if applicable): The intervention group receives the smartphone application for 
remote monitoring during weekdays from 8 am to 17 pm up to 7 days after surgery. With this 
application, patients are able to record experienced pain and nausea. In addition, they can 
send messages to the hospital. Daily monitoring is performed by an anaesthesia professional 
who will contact the patient in case severe pain or nausea is reported in the app. The control 
group receives standard of care (with post-discharge verbal and paper instructions).    
Main study parameters/endpoints: The main study endpoint is the difference between 
patients using remote monitoring and patients not using remote monitoring in perceived 
quality of recovery measured with the QoR-15 questionnaire on the 7th day after day care 
surgery.  Secondary endpoints are 1) the overall score on the Quality of Recovery-15 at day 
1, 4 and 7 post discharge, 2) the perceived quality of hospital aftercare and 3) experienced 
psychological effects of remote monitoring during postoperative recovery from day care 
surgery. 
Nature and extent of the burden and risks associated with participation, benefit and 
group relatedness: Participating in this study does not pose any additional risks either for 
patients allocated to the intervention group with remote monitoring or for patients allocated to 
the standard of care group. Patients in the remote monitoring group are being asked to use a 
smartphone application to record pain and nausea daily for up to 7 days post discharge. 
Recording pain and nausea will take 2 minutes daily. Patients from both groups are being 
asked to fill in the validated QoR-15 questionnaire one day before admission and on the 1st, 
4th and 7th day post discharge and this will take 2.5 minutes. No extra hospital visits, physical 
examinations or tests are required. Patients in the remote monitoring group could benefit 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
12 of 36 
from participating in the study because they are monitored daily by a healthcare professional. 
Therefore, severe pain, nausea and possibly other complications can be noticed and 
managed earlier.  
1. INTRODUCTION AND RATIONALE 
To date the majority of patients receiving minor or intermediate surgical interventions are 
being discharged as soon as the critical post-operative phase is passed and vital signs and 
physical wellbeing have been stabilized. In general patients will leave the hospital within 4 to 
5 hours after the intervention usually without further monitoring (1). Most hospitals provide 
their patients with verbal and paper instructions on what to do in case of severe pain, nausea 
and alleged surgical complications. The usual advice is to contact the surgical or anesthesia 
outpatient department during office hours and if not available, patients are advised to contact 
their general practitioner or the hospitals’ emergency department. For patients whilst being in 
pain, nauseous or worried about physical wellbeing, contacting the hospital can be a 
challenging task. Answering machines and gatekeepers (e.g., secretaries who may or may 
not connect you with the doctor) stand between the patient and their healthcare professional 
in order to prevent for improper contact. In addition, doctors and nurses have ongoing clinical 
obligations, which makes it unrealistic to expect that they are available on-demand.  
Maintaining and improving high quality and cost-effective healthcare for outpatients is a 
hospital priority. The volume and complexity of outpatient surgical procedures continues to 
increase, with a wider range of patients now considered suitable for day care surgery (2). In-
addition, recent drives to reduce the length of hospital stay because of the Covid-19 
pandemic emphasize that day care surgery is fundamental to modern patientcare. For 
example, in the Netherlands in 2012, 54% of the patients are treated via day care surgery 
versus 25% in 1993 (3), considering 1.4 million surgical procedures annually (4). To realize 
the aims of improving recovery after outpatient surgery, it is especially important to optimize 
management of postoperative pain (POP) and post discharge nausea and vomiting (PDNV). 
Even today, 40% to 75% of the patients experience moderate-to-severe POP (5, 6) and 28% 
to 57% experience PDNV (7-10).  
eHealth interventions are currently broadly applied in perioperative care (e.g. remote 
monitoring, educational websites and tele-rehabilitation) (11, 12). In a similar way, we 
configured an existing and already applied remote monitoring application to enable follow up 
of patients after day care surgery with the objective to improve the efficiency and quality of 
postoperative recovery. In order to do so, we have provided patients a smartphone 
application to record postoperative pain and nausea and to be in contact with a healthcare 
professional when worried about their physical well-being after day-care surgery. Despite the 
promising first results from a proof of concept study with a similar application amongst 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
13 of 36 
clinically admitted patients we do not know to what extend it improves the patient’s recovery 
after day care surgery (13). A recent systematic review showed that the overall primary 
purpose of ‘pain related’ apps is education and pain self-management and to the lesser 
extend remote monitoring . More importantly, many applications lacked a direct feedback 
loop between the patient and their healthcare professionals (14, 15).  
We hypothesized that the realization of being monitored remotely and receiving feedback 
from healthcare professionals during the postoperative recovery period will improve patient 
experienced recovery. In a non-blinded randomized controlled trial with mixed methods 
design, we propose to answer the following research question: What is the difference in 
experienced quality of recovery between patients provided with a smartphone app-based 
remote monitoring tool and patients without remote monitoring (standard care) after day care 
surgery? 
 
 
 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
14 of 36 
2. OBJECTIVES 
a. Primary Objective 
b.  Primary outcome is to assess the difference between patients using remote 
monitoring and patients not using remote monitoring in perceived quality of 
recovery measured with the QoR-15 questionnaire on the 7th day after day 
care surgey. 
c. Secondary Objective(s) 
To assess the experienced postoperative pain (POP) between patients provided with a 
smartphone application for remote monitoring and patients receiving standard of care (no 
remote monitoring) after day care surgery.  
To assess the experienced post discharge nausea and vomiting (PDNV) between 
patients provided with a smartphone application for remote monitoring and patients 
receiving standard of care (no remote monitoring) after day care surgery. 
To assess the difference in the number of surgical complications rated with the Clavien 
Dindo classification of surgical complication between patients provided with a smartphone 
application for remote monitoring and patients receiving standard of care (no remote 
monitoring) after day care surgery. 
To assess the difference in the number of re-admissions between patients provided with 
a smartphone application for remote monitoring and patients receiving standard of care 
(no remote monitoring) after day care surgery. 
To assess the difference in the number of hospital contacts / general practitioner between 
patients provided with a smartphone application for remote monitoring and patients 
receiving standard of care (no remote monitoring) after day care surgery. 
To assess the difference in experienced quality of communication with the hospital staff 
between patients provided with a smartphone application for remote monitoring and 
patients receiving standard of care (no remote monitoring) after day care surgery.  
 
 
To assess the experienced psychological effects remote monitoring in patients recovering   
from day care surgery  

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
15 of 36 
3. STUDY DESIGN 
A two-arm multicenter non-blinded randomized controlled trial with mixed methods design 
will be conducted at the day care nursing wards of OLVG Hospital (Locations Oosterpark and 
Jan Tooropstraat), Amsterdam, the Netherlands, Canisius Wilhelmina Hospital, Nijmegen, 
the Netherlands and Maasstad Hospital, Rotterdam, the Netherlands. Surgical specialisms 
involved are gynecology, eye-nose and throat, oral and maxillofacial, orthopedics, general 
and vascular, trauma and urology. Surgical day care patients will be randomly assigned to 
one of the two study arms, remote monitoring with a smartphone application (intervention) or 
standard of care (no remote monitoring) after hospital discharge. Study period is expected to 
run from 1st of February 2022 up to the 31st December 2022.STUDY POPULATION 
a. Population (base)  
For this study, we will enrol 230 consecutive patients admitted to OLVG Hospital, Canisius 
Wilhelmina Hospital or Maasstad Hospital who are scheduled to undergo a surgical 
intervention in day care. In 2020 under the pressure of the covid-19 pandemic over 8000 day 
care surgical interventions were performed therefore, it is likely that the inclusion will be 
achieved within the intended study period. 
b. Inclusion criteria 
In order to be eligible to participate in this study, a subject must meet all of the following 
criteria: 
 
Age: older than or equal to 18 years 
 
Pre-anaesthesia conclusion: ASA I to III 
 
Scheduled for day care surgery for one of the following surgical specialties: 
gynaecology, eye-nose and throat, oral and maxillofacial, orthopaedics, general and 
vascular, trauma and urology 
o  
 
In possession of a smartphone 
c. Exclusion criteria 
A potential subject who meets any of the following criteria will be excluded from participation 
in this study: 
 
Not able to speak or understand the Dutch language 
 
Mentally impaired (e.g. dementia, retardation) 
 
During study: 
 
Patients who experience a unexpected post-operative complication or prolonged 
recovery with the result that discharge on the same day of the surgical intervention is 
not possible will be excluded 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
16 of 36 
d. Sample size calculation 
An 8.0 difference in the overall score in the QoR-15 questionnaire on postoperative day 7 is 
considered a minimal clinically relevant difference (16) with standard deviation of 19.1 (17). 
Group sample sizes of 91 patients achieve 80% power to detect a difference of -8.0 with a 
significance level (alpha) of 0,05 using a two-sided two-sample t-test. Sample Size 
calculation is performed with PASS 2021 Power Analysis and Sample Size Software (2021). 
NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/pass. We plan to include 20% extra 
patients to adjust for dropout or incomplete data. Total sample will be 230 subjects divided 
into two groups.  
 
 
 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
17 of 36 
 
4. TREATMENT OF PATIENTS 
a. Investigational product/treatment 
Patients scheduled for day care surgery within 3 weeks after their pre-anaesthesia workup 
who fit the inclusion criteria and are willing to participate in this study are allocated to 
either remote monitoring with a smartphone application after discharge (the intervention) 
or the standard of care without remote monitoring (control). Both groups will have a pre-
anaesthesia workup  (e.g. online-assessment, telephone assessment or an assessment 
during a physical visit to the anaesthesia outpatient department) according to the 
standards of the Dutch association of Anaesthesiologist and Federation of Medical 
Specialists (18).  
 
During the pre-anaesthesia workup, patients are being notified about the study by an 
anaesthesiologist, physician assistant or medical assistant. If interested they will receive 
the study information and a consent letter. Two days before admission a researcher will 
explain the study during a telephone call and will ask for informed consent. Moreover, 
participating patients are asked to complete the first online QoR-15 questionnaire. 
Patients allocated to the intervention group also receive an invitation e-mail with 
instructions from Thuismeten (Luscii) © to download and install the remote monitoring 
application. This invitation is sent by a healthcare professional through a secured 
connection via the hospitals’ patient data management system (e.g. EPIC ©). During the 
admission patients from both groups receive perioperative anaesthesia care according to 
standards based on the Guidelines for treatment of the Dutch association of 
anaesthesiologists (18, 19).  
 
Patients are regularly asked about their postoperative pain and nausea by either nurses or 
doctors, at least once per perioperative phase (e.g. recovery and day care ward). In case 
of severe pain, the patient is administered paracetamol, NSAID’s, tramadol or opioids. In 
case of nausea, the patient is administered metoclopramide or granisteron. Both, pain- 
and nausea treatment is executed by nurses with the aim of making the patient feel 
comfortable. Postoperative medication is ordered and supervised by the attending 
anaesthetist.   
 
Before discharge, patients from both groups receive verbal and paper (APPENDIX I: 
example discharge information OLVG, in Dutch) care- and recovery instructions from a 
day care ward nurse. In addition, they receive a medication box containing paracetamol, 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
18 of 36 
non-steroid inflammatory drug (NSAID), metoclopramide, pantoprazole and if they 
underwent a surgical procedure with intermediate risk for complications, they also receive 
tramadol or opioids.   
 
In addition to standard care as delineated above, patients in the intervention group 
(remote monitoring after discharge) will have the monitoring application installed on their 
personal smartphone. Once they are back home, they can start recording pain and 
nausea and may ask questions about their recovery within the application. Once a day 
patients receive a push notification to record pain and nausea. The application is 
operational up to 7 days post discharge. After this period the application is disconnected 
from the Thuismeten (Luscii) © server. 
 
In case of recording unbearable pain and nausea or asking a question and being in need 
for help or assistance, an anaesthesia medical assistant will contact these patients during 
office hours from 08:00 to 16:30  by using the applications’ messaging service or by 
telephone. First the medical assistant will perform an initial triage of the patients in need, 
subsequently pain and nausea reports and additional questions that appear as an alert in 
the electronic back office systems of Thuismeten (Luscii) © will be addressed. The alerts 
are set to the in-app question ‘do you want something to be done about your pain or 
nausea?’ or an increase of 3 points numerical rating scale (NRS) for pain and additional 
questions asked in the apps messaging service. During triage, the medical assistant will 
follow a protocolled workflow to assess actions to be taken (APPENDIX II triage workflow, 
in Dutch). If contacting the patient by telephone is necessary, the medical assistant will 
use a call script to assess patients’ pain, nausea and physical status (APPENDIX III, call 
script, in Dutch). The medical assistant will often give appropriate feedback or advice via 
message or telephone. In case of a possible medical alert or a necessary medication 
adjustment, the medical assistant will consult the anaesthetist, trainee nurse specialist or 
physician assistant responsible for remote postoperative pain care. 
b. Use of co-intervention (if applicable) 
Not applicable  
c. Escape medication (if applicable) 
Not applicable 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
19 of 36 
5. INVESTIGATIONAL PRODUCT (Not applicable) 
a. Name and description of investigational product(s) 
Not applicable 
b. Summary of findings from non-clinical studies 
Not applicable 
c. Summary of findings from clinical studies 
Not applicable 
d. Summary of known and potential risks and benefits 
Not applicable 
e. Description and justification of route of administration and dosage 
Not applicable 
f. Dosages, dosage modifications and method of administration 
Not applicable 
g. Preparation and labelling of Investigational Medicinal Product 
Not applicable 
h. Drug accountability 
Not applicable 
 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
20 of 36 
6. NON-INVESTIGATIONAL PRODUCT 
a. Name and description of non-investigational product(s) 
The remote monitoring application for day care patients is a configuration of an already 
existing and applied monitoring platform  by Luscii Healthtech B.V. The configuration for 
postoperative monitoring was commissioned by OLVG hospital. In  this study app versions 
2.43.0 or higher are being used. The application is CE IIa certified. For more information 
about Luscii technical, privacy and security specifications, we refer to 
https://www.notion.so/Security-and-privacy-at-Luscii-fc51e66e21ae4a87a51499a52d4c8db2. 
Information on intended use is available at https://www.notion.so/luscii/Luscii-vitals-
Instructions-for-Use-for-Patients-and-Clinicians-3d5050d94f6f40f9aa6af2e9aa77084d both the 
triage protocol and the call script are developed by the OLVG hospital department of 
anaesthesia (APPENDIX II and III). 
b. Summary of findings from non-clinical studies 
Not applicable 
c. Summary of findings from clinical studies 
The Luscii tele-monitoring platform is currently being used in the care for patients with acute 
and chronic diseases such as hypertension during pregnancy, hearth failure, COPD and 
COVID-19. The different telemonitoring modules are based on a direct feedback loop 
between patients and health care providers and alarming combinations of patient recorded 
results (20, 21). Results show a significant reduction of hospital admissions, days spent in 
hospital and healthcare costs (22, 23). 
 
d. Summary of known and potential risks and benefits 
No potential risk or harm is to be expected from using the Luscii application and remote 
monitoring. Patients using the application and remote monitoring could benefit from being 
monitored daily by an anaesthesia medical assistant as formulated in the study objectives. It 
is expected that in patients receiving remote monitoring the quality of recovery be improved.  
e. Description and justification of route of administration and dosage 
Not applicable 
f. Dosages, dosage modifications and method of administration 
Not applicable 
g. Preparation and labelling of Non Investigational Medicinal Product 
Not applicable 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
21 of 36 
h. Drug accountability 
Not applicable 
 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
22 of 36 
7. METHODS 
a. Study parameters/endpoints 
i. Main study parameter/endpoint 
Quality of recovery measured with the Quality of Recovery questionnaire-15 (QoR-15) (16, 
24) at day 7post discharge between patients with remote monitoring (intervention group) and 
patients without remote monitoring (non-intervention group) after day care surgery. 
ii. Secondary study parameters/endpoints (if applicable) 
Quality of recovery measured with the quality of recovery questionnaire-15 (QoR-15) (16, 24) 
at post discharge day at post discharge day 1, 4 and 7.  
 
Postoperative Pain: Experienced postoperative pain (POP) measured with (in-app) NRS for 
Pain (25) (combined with 11 faces scale) measured at day 1, 4 and 7 post discharge.  
 
Post discharge nausea and vomiting: Experienced post discharge nausea and vomiting 
(PDNV) measured with the Myles’ PDNV assessment scale (21) between intervention and 
non-intervention group. Measured at day 1, 4 and 7 post discharge. 
 
Medication Dosage and Use: the total dosage of administered analgesics will be assessed 
during hospital stay and recorded in the medical record. The total dosage of administered 
analgesics at home after discharge will assessed by asking patients to indicate which pain 
medication they have been using. Measured at day 1, 4 and 7 post discharge.  
 
The number of contacts with the hospital, general practitioner or emergency department. All 
types of contacts (e.g. physically, e-mail, telephone) will be assessed by reviewing the PDMS 
for registered contacts and by asking the patients to indicate the number of contacts. 
Measured at day 1, 4 and 7 post discharge.    
 
The number of surgical complications assessed according to the Clavien Dindo classification 
of surgical complications (26, 27) will be assessed by reviewing the PDMS and by asking the 
patients to indicate the number of complications. Measured at day 1, 4 and 7 post discharge. 
 
The number of readmissions. A readmission is defined as an admission to hospital or 
emergency department for medical care or observation regarding their surgical intervention. 
Readmissions will be assessed by reviewing the PDMS and by asking the patient to indicate 
the number of readmissions. Measured at day 1, 4 and 7 post discharge.     

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
23 of 36 
 
Satisfaction: Patients’ satisfaction with the provided care will be assesses using a 1-item self-
created VAS scale (‘not at all to very much’, 0-10 range). Satisfaction will be measured at 
day 1, 4 and  7 post discharge. 
 
General evaluations regarding provided care after discharge: Patients’ evaluations of their 
experienced care during the 7 day discharge period are measured using two items.  i) How 
likely is it that the patient would recommend this hospital to other day care surgery patients 
(using an adapted item from the CQ index (0-10 ‘would definitely not recommend’ to ‘would 
definitely recommend’) (28, 29). Ii) Their overall rating of the quality of care provided by the 
hospital during the 7 day discharge period, using an item from the CQ index (0-10 scale, 
‘very poor care’ to extremely good care’) (28, 29). Both items will be measured at discharge 
day 1, 4 and 7.  
 
The quality, experiences and communication regarding remote monitoring with this 
application will be assed in one by one semi structured interviews. The perceptions of 20 
participants are considered satisfactory or when data saturation is reached (REF). Prior to 
the interview, participants receive general information concerning the topics and informed 
consent was requested from the interviewee to allow for audio recording of the interview. See 
for interview topics (f1_Interview Topics_version_1_11_2021¬).Furthermore, interviews are 
conducted by telephone or online through Skype, Zoom or FaceTime due to COVID-19 
measures. 
 
iii. Other study parameters (if applicable) 
The following patient baseline characteristics are collected: age, sex, smoking status, body 
mass index, ASA classification, PONV score, preoperative NRS, PONV prophylaxis, 
previous surgical or anaesthesia related  complications, history of (chronic) pain, history of 
motion sickness, surgical specialism, surgical procedure and classification (e.g. laparoscopic 
cholecystectomy, minor), anaesthesiology technique (i.e. general or spinal anaesthesia), 
surgery duration, intraoperative medication, PONV and NRS for pain at recovery ward, 
PONV and NRS for pain at day care ward, duration of admission 
b. Randomisation, blinding and treatment allocation 
Patients will be allocated oto the intervention (remote monitoring) or standard of care group 
(no remote monitoring). To adjust for practice variation between the participating hospitals 
Eligible patients will be randomly assigned to receive remote monitoring with the application 
or the standard of care without remote monitoring. Treatment assignments were performed 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
24 of 36 
centrally according to a computer-generated random schedule (Castor EDC) in permuted 
blocks of four within strata of participating hospitals (OLVG Hospital, Maasstad Hospital and 
Canisius Wilhelmina Hospital). The allocation will be computer-generated with Castor© web 
application (http://castoredc.com/ and https://castorcrf.com, Castor Services are operated by 
Ciwit B.V. and located in the Netherlands).  
c. Study procedures 
Patients are recruited to participate in this study during their appointment for anaesthesia 
pre-assessment (e.g. online assessment, telephone assessment or during visiting the 
anaesthesia outpatient department). An anaesthesiologist, trainee nurse specialist, physician 
assistant or medical assistant will verbally explain the study. If interested, they receive an 
information-letter about the study, and an informed consent form 
(PIF_IC_e1_e2_QuReMo_Versie1_14_7_2021).  
 
Patients who are not informed during the preoperative assessment will be contacted 
afterwards by one of the researchers to explain the study and to ask them to consider 
participation. If interested, they receive an information-letter about the study, and an informed 
consent form (PIF_IC_e1_e2_QuReMo_Versie1_14_7_2021). 
 
The patients are given a reflection period of at least 48 hours, after that a researcher or 
medical assistant will contact the patient if they agree to participate. Patients who have been 
asked to participate are earmarked in the PDMS (e.g. EPIC). A patient who wishes to 
participate is asked to sign the consent form and bring it on the day of admission. Patients 
who, forget to bring their consent form are provided a copy, which is then to be signed on the 
day of admission. Accordingly, both researchers and patients receive a wet ink copy of the 
consent form. 
 
After receiving informed consent, the researchers will record the baseline characteristics to 
the Castor EDC database and perform the randomisation procedure. Moreover, no data is 
recorded that could trace back the identity of the patients. By randomizing, an anonymous 
study identification number is allocated to the patients. The researchers from the participating 
hospitals will keep a secured database in which patient hospital number corresponds with the 
study identification number, stored locally at their own hospital server. Two days before 
admission patients in the remote monitoring group (intervention group) receive an invitation 
e-mail from Luscii © sent by a medical assistant from the anaesthesia outpatient department 
with instructions to download and install the remote monitoring application. Perioperative 
patients from both the intervention group and the standard of care group receive anaesthesia 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
25 of 36 
care according to the standards of the Dutch association of anaesthesiologist (18, 19). Intra- 
and postoperative characteristics and variables will be recorded in Castor EDC by the 
researchers. Before discharge, patients from both groups receive verbal and paper care and 
recovery instructions from a day ward nurse. In addition patients receive a medication box 
with instructions for use, containing paracetamol, naproxen or diclofenac and in case of an 
intermediate surgical risk for complications also tramadol or an opioid.  Once at home, 
patients in the intervention group can start using the smartphone application for recording 
pain and nausea and ask additional questions about their recovery. Subsequently an 
anaesthesia medical assistant will respond appropriately to patients in need following triage 
and assessment protocol. At day 1, 4 and 7 post discharge patients from both groups receive 
an online questionnaire (QoR-15). In case patients do not respond, a researcher or a medical 
assistant will contact the patients from both study arms by telephone to assess the study 
endpoint questionnaire (f1_vragenlijst_QuReMo_English_version_1_16_7_2021  ). 
Thereafter, endpoint data will be recorded in Castor EDC by one of the researchers.    
 
In addition, patients from the remote monitoring group who have given permission for an 
interview to assess the quality of communication with app receive a telephone appointment 
at day 7 postoperative for a 30 minutes semi structured interview with one of the 
researchers.   
d. Withdrawal of individual subjects 
Subjects can leave 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. 
 
e. Specific criteria for withdrawal (if applicable) 
f. Replacement of individual subjects after withdrawal   
In our power calculation, we anticipated for 20% dropout. If data collection is still in 
progress, new subjects will be recruited. 
g. Follow-up of subjects withdrawn from treatment 
There will be no follow up on withdrawn subjects. 
h.   Premature termination of the study 
  Not applicable 
 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
26 of 36 
8. SAFETY REPORTING 
a. Temporary halt for reasons of subject safety 
In accordance to section 10, subsection 4, of the WMO (30), the sponsor will suspend the 
study if there is sufficient ground that continuation of the study will jeopardise subject 
health or safety.  The sponsor will notify the accredited METC without undue delay of a 
temporary halt including the reason for such an action. The study will be suspended 
pending a further positive decision by the accredited METC. The investigator will take 
care that all subjects are kept informed.  
 
b. AEs, SAEs and SUSARs 
i. Adverse events (AEs) 
Adverse events are defined as any undesirable experience occurring to a subject 
during the study, whether or not considered related to the investigational intervention. 
All adverse events reported spontaneously by the subject or observed by the 
investigator or his staff will be recorded. 
ii. Serious adverse events (SAEs) 
A serious adverse event is any untoward medical occurrence or effect that  
- 
results in death; 
- 
is life threatening (at the time of the event); 
- 
requires hospitalisation or prolongation of existing inpatients’ hospitalisation; 
- 
results in persistent or significant disability or incapacity; 
- 
is a congenital anomaly or birth defect; or 
- 
any other important medical event that did not result in any of the outcomes listed 
above due to medical or surgical intervention but could have been based upon 
appropriate judgement by the investigator. 
 
An elective hospital admission will not be considered as a serious adverse event. 
The investigator will report all SAEs to the sponsor without undue delay after 
obtaining knowledge of the events, except for the following SAEs: The sponsor will 
report the SAEs through the web portal ToetsingOnline to the accredited METC that 
approved the protocol, within 7 days of first knowledge for SAEs that result in death or 
are life threatening followed by a period of maximum of 8 days to complete the initial 
preliminary report. All other SAEs will be reported within a period of maximum 15 
days after the sponsor has first knowledge of the serious adverse events. 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
27 of 36 
 
Seen the nature of our intervention, i.e. remote monitoring on top of routine 
postoperative care, no adverse or serious adverse events are expected. 
iii. Suspected unexpected serious adverse reactions (SUSARs) 
 
         Not applicable.  
 
c. Annual safety report 
 
 
 Not applicable. 
d. 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. 
SAEs need to be reported until end of study within the Netherlands, as defined in the 
protocol  
 
e. [Data Safety Monitoring Board (DSMB) / Safety Committee] 
Not applicable 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
28 of 36 
9. STATISTICAL ANALYSIS 
All statistical analyses will be conducted according to the intention–to–treat principle (31, 32) 
considering all patients in the treatment groups to which they were randomly assigned, 
excluding cases lost to follow-up due to withdrawal of consent or cancellation of surgery. 
Continuous distribution of the data will be assessed by visual inspection of histograms and 
normality tests. For both study arms, the baseline characteristics will be reported for the 
intervention and control group and expressed as counts and percentages, means and 
standard deviations (SD), or medians and interquartile ranges (IQR) whenever appropriate. 
Baseline characteristics of patients with and without complete follow up will be compared to 
examine whether selective dropout occurred.  Analyses will be performed using IBM SPSS 
Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp. 
a. Primary study parameter(s) 
The primary outcome, QoR-15 at day 1, 4 and 7, will be compared among patients 
randomized to either the intervention and control group, using Student’s t-test or a 
nonparametric Mann Whitney U test. 
 
Mixed effects linear regression models will be conducted to investigate the effect of the 
smartphone app on QoR-15 over the first week post discharge as a function of the 
randomization assignment (i.e. intervention vs control), time (i.e. measurements before 
surgery, and at day 1, 4 and 7 post discharge), and their interaction term. Random effects, 
i.e. random intercept, will be fitted per individual to account for clustering effects. To adjust 
for practice variation between the participating hospitals, the factor hospital will be added as 
fixed effect to the mixed model. In addition, we will perform a sensitivity analysis if the results 
of the mixed model analysis indicate for bias.  
 
b. Secondary study parameter(s)  
Postoperative pain on post discharge day 1, 4 and 7: Mean, Standard Deviation, Mixed 
effects linear regression models will be conducted to investigate the effect of the smartphone 
app on postoperative pain over the first week post discharge as a function of the 
randomization assignment (i.e. intervention vs control), time (i.e. measurements before 
surgery, and at day 1, 4 and 7 post discharge), and their interaction term. Random effects, 
i.e. random intercept, will be fitted per individual to account for clustering effects 
 
Post discharge Nausea and Vomiting (PDNV) on post discharge day 1, 4 and 7: Mean, 
Standard Deviation and  Mixed effects linear regression models will be conducted to 
investigate the effect of the smartphone app on PDNV over the first week post discharge as 
a function of the randomization assignment (i.e. intervention vs control), time (i.e. 
measurements before surgery, and at day 1, 4 and 7 post discharge), and their interaction 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
29 of 36 
term. Random effects, i.e. random intercept, will be fitted per individual to account for 
clustering effects 
Medication Dosage and usage measured in morfine equivalents on post discharge day 1, 4 
and 7: Mean, Standard Deviation and Mixed effects linear regression models will be 
conducted to investigate the effect of the smartphone app on medication dosage and usage  
over the first week post discharge as a function of the randomization assignment (i.e. 
intervention vs control), time (i.e. measurements before surgery, and at day 1, 4 and 7 post 
discharge), and their interaction term. Random effects, i.e. random intercept, will be fitted per 
individual to account for clustering effects 
 
Difference in the number contacts with the hospital, general practitioner or emergency 
department (on day 7 post discharge): Mean and Standard Deviation and two sample-t-test 
(in case of non-normally distributed data we will report on medians and interquartile ranges 
and differences will be tested using the Mann-Whitney U test)  
 
Difference in the number of surgical complications assessed according to the Clavien Dindo 
classification of surgical complications (on day 7 post discharge): Mean, Standard Deviation 
and two sample-t-test (in case of not normally distributed data we will use the Mann-Whitney 
U test) 
 
Difference in the number of readmissions emergency department (on day 7 post discharge): 
Mean, Standard Deviation and two sample-t-test (in case of not normally distributed data we 
will use the Mann-Whitney U test) 
 
Satisfaction (on day 7 post discharge): Median, Interquartile Range and χ2 tests for equal 
proportion.   
 
General evaluations regarding provided care after discharge (on day 7 post discharge): 
Median, Interquartile Range and χ2 tests for equal proportion.   
 
Experienced quality of communication: Data collection and analysis progression were 
discussed during regular meetings with researchers. A thematic framework will be used to 
analyze the qualitative data. First, the audio recordings of the interviews will be transcribed 
verbatim in Dutch. After familiarization with the data, the transcripts are coded. After coding, 
overarching themes and patterns are identified and labelled within each concept. 
 
c. Cleaning and locking of the database 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
30 of 36 
The database will be locked as soon as all data are entered, and all discrepant or missing 
data are resolved – or if all efforts are employed and we consider that, the remaining 
issues cannot be fixed. At this step, the data will be reviewed before database locking. 
After that, the study database will be locked and exported for statistical analysis. At this 
stage, permission for access to the database will be removed for all investigators, and the 
database will be archived. 
d. Missing data 
No or minimal losses to follow–up for the primary and secondary outcomes are 
anticipated. Missing data will be accounted for with multiple imputation techniques. 
e. Interim analysis (if applicable) 
Not applicable 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
31 of 36 
10. ETHICAL CONSIDERATIONS 
a. Regulation statement 
The study will be conducted according to the principles of the Declaration of Helsinki as 
stated in the current version of Fortaleza, Brazil 2013, in accordance with the Medical 
Research Involving Human Subjects Act (WMO) and comply with Good Clinical Practice 
(GCP) Guidelines and all applicable national (for example WMO for the Netherlands) and 
international regulatory requirements and general data protection regulations (GDPR). 
b. Recruitment and consent 
Patients will be recruited at the anaesthesiology outpatient clinic. Patients will be informed 
verbally by local researchers and by a patient information letter. The patient will be given 
sufficient time to consider their decision and to discuss the decision with their relatives or 
the independent expert. 
c. Objection by minors or incapacitated subjects (if applicable) 
Not applicable  
d. Benefits and risks assessment, group relatedness 
Patient burden is considered minimal  
e. Compensation for injury 
There is no injury expected caused by study participation. Insurance exemption has been 
requested.   
f. Incentives (if applicable) 
Not applicable 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
32 of 36 
11. ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION 
a. Handling and storage of data and documents 
All participating hospitals have signed a data processing agreement with Luscii healthtech 
B.C.  that complies with the general data protection regulations (GDPR) and national 
regulations (e.g. Algemene Verordening Gegevensbescherming (AVG)) that apply in the 
Netherlands. Moreover, all of the patients directly identifying personal data (e.g., name, 
address, etc.) will be separated from the research data (e.g., measurement data, etc.) and 
replaced by an assigned code. The directly identifying data will be only used to contact the 
patients and is only available to the investigators. The handling of personal data complies 
with the general data protection regulations (GDPR) and applicable national regulations 
(e.g. Algemene Verordening Gegevensbescherming (AVG)). For data collection and 
validation, an eCRF, including validation checks and appropriate user access rights, will 
be set up in CASTOR© (www.castoredc.nl). CASTOR© is a GCP compliant and meets 
the standard for information security management. All data will be stored in a secure place 
for 15 years after study end at OLVG Hospital. Electronic files will be archived on the 
OLVG ‘SharePoint wetenschap anesthesiologie’ server in a secure and controlled 
environment to maintain confidentiality. Electronic documents will be controlled with 
password protection according to best practices. Any data leaks that might occur 
regardless of these safety precautions will be reported to all parties within 1 working day 
after discovery of the leak.  
b. Monitoring and Quality Assurance  
All medical specialists, nurses and other hospital personnel involved in perioperative care 
for surgical day care patients receive information an instruction about the study 
procedures either by an information letter (APPENDIX). The conduct of the study will be 
performed according to BROK/GCP standards and follow guidelines on improving and 
standardizing evaluations reports of web-based and mobile health interventions (33).  
Furthermore a clinical data management plan will be used  with the objective of the clinical 
data management plan is to provide high–quality data by adopting standardized 
procedures to minimize the number of errors and missing data, and consequently, to 
generate an accurate database for analysis (APPENDIX). Accuracy and consistency 
checks will be carried out by way of validation, pre-specified and ad hoc checking by the 
researchers. A qualified monitor will be installed to perform study monitoring according to 
the monitoring plan. Monitoring will be performed to signal early aberrant patterns, issues 
with consistency, credibility, and other anomalies.  

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
33 of 36 
c. Amendments  
Amendments are changes made to the research after a favourable opinion by the 
accredited METC has been given. All amendments will be notified to the METC that gave 
a favourable opinion. Non-substantial amendments will not be notified to the accredited 
METC and the competent authority but will be recorded and filed by the sponsor 
 
d. 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.  
e. 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 last patient’s last follow-up. 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.  
f. Public disclosure and publication policy 
The study protocol will be registered before inclusion of the first patient on 
www.clinicaltrials.gov. The results of the study will find their way into (inter–) national 
scientific journals and guidelines. We will submit analyses to scientific journals in the field 
of anaesthesiology. A lay summary of the results will be published as well and send to the 
participants if they are interested. 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
34 of 36 
12. STRUCTURED RISK ANALYSIS  
Not applicable 
a. Potential issues of concern 
 
Not applicable  
 
b. Synthesis 
Not applicable  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
35 of 36 
13. REFERENCES 
1. Zirpe D, Swain SK, Das S, Gopakumar CV, Kollu S, Patel D, et al. Short-stay daycare 
laparoscopic cholecystectomy at a dedicated daycare centre: Feasible or futile. J Minim 
Access Surg. 2016;12(4):350-4. 
2. Bailey CR, Ahuja M, Bartholomew K, Bew S, Forbes L, Lipp A, et al. Guidelines for day-
case surgery 2019: Guidelines from the Association of Anaesthetists and the British 
Association of Day Surgery. Anaesthesia. 2019;74(6):778-92. 
3. Volksgezondheid.info.  [Available from: 
https://www.volksgezondheidenzorg.info/onderwerp/ziekenhuiszorg/cijfers-context/trend-
gebruik#node-trend-ziekenhuisopnamen-voor-drie-chronische-aandoeningen. 
4. (CBS) SN.  [Available from: 
https://opendata.cbs.nl/statline/#/CBS/nl/dataset/80386NED/table?fromstatweb. 
5. Wadensten B, Frojd C, Swenne CL, Gordh T, Gunningberg L. Why is pain still not being 
assessed adequately? Results of a pain prevalence study in a university hospital in Sweden. 
J Clin Nurs. 2011;20(5-6):624-34. 
6. Carr EC, Meredith P, Chumbley G, Killen R, Prytherch DR, Smith GB. Pain: a quality of 
care issue during patients' admission to hospital. J Adv Nurs. 2014;70(6):1391-403. 
7. Apfel CC, Philip BK, Cakmakkaya OS, Shilling A, Shi YY, Leslie JB, et al. Who is at risk 
for postdischarge nausea and vomiting after ambulatory surgery? Anesthesiology. 
2012;117(3):475-86. 
8. Odom-Forren J, Jalota L, Moser DK, Lennie TA, Hall LA, Holtman J, et al. Incidence and 
predictors of postdischarge nausea and vomiting in a 7-day population. J Clin Anesth. 
2013;25(7):551-9. 
9. Bruderer U, Fisler A, Steurer MP, Steurer M, Dullenkopf A. Post-discharge nausea and 
vomiting after total intravenous anaesthesia and standardised PONV prophylaxis for 
ambulatory surgery. Acta Anaesthesiol Scand. 2017;61(7):758-66. 
10.Wallden J, Flodin J, Hultin M. Validation of a prediction model for post-discharge nausea 
and vomiting after general anaesthesia in a cohort of Swedish ambulatory surgery patients. 
Eur J Anaesthesiol. 2016;33(10):743-9. 
11.van der Meij E, Anema JR, Otten RH, Huirne JA, Schaafsma FG. The Effect of 
Perioperative E-Health Interventions on the Postoperative Course: A Systematic Review of 
Randomised and Non-Randomised Controlled Trials. PLoS One. 2016;11(7):e0158612. 
12.Breteler MJM, Numan L, Ruurda JP, van Hillegersberg R, van der Horst S, Dohmen DAJ, 
et al. Wireless Remote Home Monitoring of Vital Signs in Patients Discharged Early After 
Esophagectomy: Observational Feasibility Study. JMIR Perioper Med. 2020;3(2):e21705. 
13.Thiel B, Godfried MB, van Huizen EC, Mooijer BC, de Boer BA, van Mierlo R, et al. 
Patient reported postoperative pain with a smartphone application: A proof of concept. PLoS 
One. 2020;15(5):e0232082. 
14.Wallace LS, Dhingra LK. A systematic review of smartphone applications for chronic pain 
available for download in the United States. J Opioid Manag. 2014;10(1):63-8. 
15.Portelli P, Eldred C. A quality review of smartphone applications for the management of 
pain. Br J Pain. 2016;10(3):135-40. 
16.Kleif J, Waage J, Christensen KB, Gogenur I. Systematic review of the QoR-15 score, a 
patient- reported outcome measure measuring quality of recovery after surgery and 
anaesthesia. Br J Anaesth. 2018;120(1):28-36. 
17.Myles PS, Myles DB, Galagher W, Chew C, MacDonald N, Dennis A. Minimal Clinically 
Important Difference for Three Quality of Recovery Scales. Anesthesiology. 2016;125(1):39-
45. 
18.Specialisten FM. Perioperatief traject. 2020. 
19.Anesthesiologie NVv. Richtlijn Postoperatieve Pijn. 2012. 
20.van den Heuvel JFM, Kariman SS, van Solinge WW, Franx A, Lely AT, Bekker MN. 
SAFE@HOME - Feasibility study of a telemonitoring platform combining blood pressure and 
preeclampsia symptoms in pregnancy care. Eur J Obstet Gynecol Reprod Biol. 
2019;240:226-31. 
21.van den Heuvel JFM, Lely AT, Huisman JJ, Trappenburg JCA, Franx A, Bekker MN. 
SAFE@HOME: Digital health platform facilitating a new care path for women at increased 
risk of preeclampsia - A case-control study. Pregnancy Hypertens. 2020;22:30-6. 

NL78144.100.21 / OLVG WO 21.083 
 
QuReMo Trial 
Version number: 4  ,date 15/12/2021 
 
36 of 36 
22.van der Burg JMM, Aziz NA, Kaptein MC, Breteler MJM, Janssen JH, van Vliet L, et al. 
Long-term effects of telemonitoring on healthcare usage in patients with heart failure or 
COPD. Clinical eHealth. 2020;3:40-8. 
23.Grutters LA, Majoor KI, Mattern ESK, Hardeman JA, van Swol CFP, Vorselaars ADM. 
Home telemonitoring makes early hospital discharge of COVID-19 patients possible. J Am 
Med Inform Assoc. 2020;27(11):1825-7. 
24.Stark PA, Myles PS, Burke JA. Development and psychometric evaluation of a 
postoperative quality of recovery score: the QoR-15. Anesthesiology. 2013;118(6):1332-40. 
25.Breivik EK, Bjornsson GA, Skovlund E. A comparison of pain rating scales by sampling 
from clinical trial data. Clin J Pain. 2000;16(1):22-8. 
26.Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new 
proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 
2004;240(2):205-13. 
27.Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The 
Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 
2009;250(2):187-96. 
28.CQ-index Chronisch Hartfalen. Utrecht: NIVEL; 2015.  Contract No.: ISBN 978-94-6122-
294-7. 
29.CQ-index Ziekenhuisopname: meetinstrument ontwikkeling. Utrecht: NIVEL 2009.  
Contract No.: ISBN 978-90-6905-947. 
30.World Medical A. World Medical Association Declaration of Helsinki: ethical principles for 
medical research involving human subjects. JAMA. 2013;310(20):2191-4. 
31.McCoy CE. Understanding the Intention-to-treat Principle in Randomized Controlled 
Trials. West J Emerg Med. 2017;18(6):1075-8. 
32.Gupta SK. Intention-to-treat concept: A review. Perspect Clin Res. 2011;2(3):109-12. 
33.Eysenbach G, Group C-E. CONSORT-EHEALTH: improving and standardizing evaluation 
reports of Web-based and mobile health interventions. J Med Internet Res. 2011;13(4):e126.