Assessing Patient Centered Urological Care for Spina Bifida: a Collaboration Between the EAU-ESPU Pediatric Urology Guidelines Panel and the IFSBH.
Conditions: Spina Bifida
Sponsor: Erasmus Medical Center

QoL in patients with spina bifida 
 
Research protocol 
Version 2.0, 15-12-2022 
 
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RESEARCH PROTOCOL 
Quality of life and organization of care for children and 
adolescents with spina bifida: a European study. 
 
 
 
 
 
 
 
 
 
 
 
 

QoL in patients with spina bifida 
 
Research protocol 
Version 2.0, 15-12-2022 
 
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Full title of protocol  
Quality of life and organization of care for children and 
adolescents with spina bifida: a European study. 
Short title or Acronym 
QoL in patients with spina bifida 
Protocol ID 
OZBS62.22332 
Version 
2.0 
Date 
15.12.2022 
Coordinating investigator/ 
project leader / Principal 
Investigator 
Dr. Lisette ‘t Hoen  
Urologist, fellow Kinderurologie 
Kamer SK-1270, Erasmus MC 
Dr. Molewaterplein 40, 3015 GD Rotterdam 
l.thoen@erasmusmc.nl 
Sponsor (in Dutch: 
verrichter/opdrachtgever) 
European Association for Urology and International 
Federation for Spina Bifida and Hydrocephalus 
Subsidising party 
None 
 
 
Name 
Signature 
Date 
Head of Department of Urology: 
Dr. J.L. Boormans 
 
 
Coordinating Investigator/Project 
leader/Principal Investigator: 
Dr. L. ‘t Hoen 
 
 
 
− 
Coordinating investigator: Investigator who bears the responsibility for the coordination of investigators operating in the 
various centers participating in multicenter research. Not all multicenter research will have a coordinating investigator. There 
is no requirement to appoint one. A project leader has the responsibility to develop a research protocol and to complete the 
study within the predefined goals. 
− 
Principal investigator: Investigator who has the overall responsibility to comply and to complete the study within the 
predefined goals. 
− 
Only for multicenter research: as an alternative only the sites could be mentioned here, investigator names and contact data 
could be included in an appendix    
− 
Sponsor: The party that commissions the organisation or performance of the research, for example a pharmaceutical 
company, academic hospital, scientific organisation or the investigator’s employee. 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. 
− 
Subsidising party: A party that provides funding for a study but does not commission it 
 
 

QoL in patients with spina bifida 
 
Research protocol 
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TABLE OF CONTENTS 
 
List of abbreviations and relevant definitions  
 
 
 
4 
Protocol summary  
 
 
 
 
 
 
5 
1. Introduction and rationale   
 
 
 
 
  
6 
 
2. Objective(s)  
 
 
 
 
 
 
 
6 
 
3. Study type  
 
 
 
 
 
  
 
6 
 
4. Study population 
 
 
 
 
 
 
 
7 
 
5. Methods 
 
 
 
 
 
 
 
 
9 
 
6. Unexpected discoveries 
 
 
 
 
 
 
9 
 
7. Exchange, sharing or transfer of data and/or human 
material and/or images outside the Erasmus MC  
 
 
9 
 
 
8.  Statistical analysis  
 
 
 
 
 
 
10 
 
9.  Recruitment and consent   
 
 
 
 
 
10 
 
10. Handling and storage of data and images   
 
 
 
11 
 
 
11. Amendments  
 
 
 
 
 
 
 
11 
 
12. Publication  
 
 
 
 
 
 
 
11  
 
13. References  
 
 
 
 
 
 
 
11 
 
14. Attachments  
 
 
 
 
 
 
 
12 
 
 
 
 
 
 
 
 
 

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LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS* 
 
CTA  
 
Clinical Trial Agreement 
De novo biobank 
The information of a new data, human material or imaging collection 
DMP  
 
Data Management Plan 
DPIA  
 
Data Protection Impact Assessment 
DTA   
 
Data Transfer Agreement 
EAU  
 
European Association for Urology 
Exception consent  Form Care for data Template , in Dutch: Formulier uitzondering toestemming 
FSFI-6 
 
Female Sexual Function Index – 6  
GCP  
 
Good Clinical Practice 
GDPR  
General Data Protection Regulation in Dutch: Algemene Verordening 
Gegevensbescherming 
IC  
 
 
Informed Consent 
IFSBH 
 
International Federation for Spina Bifida and Hydrocephalus 
IFU   
 
Instruction For Use 
IIEF-5 
 
International Index of Erectile Function – 5  
MTA  
 
Material Transfer Agreement 
NWTC  
 
Non-WMO Review Committee; in Dutch: Niet WMO Toetsingscommissie 
QUALAS 
 
QUAlity of Life Assessment in patients with Spina bifida 
UAVG 
Dutch Act on Implementation of the General Data Protection Regulation; in Dutch: 
Uitvoeringswet Algemene Verordening Gegevensbescherming 
WMO 
Medical Research Involving Human Subjects Act, in Dutch: Wet Medisch-  
wetenschappelijk Onderzoek met Mensen 
*Please delete abbreviations/definitions that are not applicable and add any new ones that are  
used in the research protocol 

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PROTOCOL SUMMARY 
Children with spina bifida require care from various medical and paramedical specialists throughout 
their life. The availability and organization of the care needed differs between the European 
countries. The EAU and IFSBH are both organizations with the aim to improve patient care and 
clinical outcomes for children with spina bifida.  
We have set up a collaboration to evaluate the differences in organization of care and clinical 
treatment received and how this affects outcomes with regard to quality of life and sexuality. 
A digital survey has been constructed which will be distributed among children and adolescents with 
spina bifida and their caregivers. The IFSBH and national patient organizations will send out 
invitations to their members. Children and adolescents from 8 – 18 years of age with spina bifida 
are eligible for inclusion. 
The survey includes a primary survey developed in collaboration between panelmembers of the 
EAU pediatric urology guidelines and patient representatives. The second part includes validated 
questionnaires to evaluate Quality of life with the QUALAS and sexual function with the IIEF-5/FSFI-
6 for boys/girls respectively. 
Primary outcome will be the quality of life in children and adolescents with spina bifida. We will 
evaluate if their demographic differences influence the quality of life and if differences are seen 
between the different European countries. Secondary outcomes include differences in sexual 
function, organization of care, treatment received, treatment options available, with also a focus on 
differences between the different European countries. 
The results of this survey will be evaluated and interpreted within a sounding board group 
consisting of children/adolescents/adults with spina bifida, patient representatives from IFSBH and 
panel members of the EAU Pediatric Urology guidelines panel. Finally, the interpreted results will be 
used to update the EAU Pediatric Urology guidelines to make these more patient centered. 
There are no known risks of participating in the study given the fact that participation includes only 
completion of questionnaires and data about standard of care. Furthermore, the study is completely 
voluntary and the results will be completely anonymous. 
 
 

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1. Introduction and rationale 
Children with spina bifida require care from various medical and paramedical specialists throughout 
their life. The availability and organization of the care needed differs between the European 
countries. It can be expected that this variety results in differences in outcome of care.  
Children with spina bifida have stated that for future research they feel it is important that quality of 
life and sexuality are investigated. [1] 
The EAU Pediatric Urology guidelines panel wants to ensure that patients with spina bifida receive 
the best possible care based on the best available clinical evidence. [2] Additionally, we want to 
improve the clinical guidelines by including patients perspectives. The IFSBH represents patients 
with spina bifida and values the promotion and protection of the human rights of patients with spina 
bifida thereby improving quality of life. 
Together with the IFSBH we have set up a collaboration to investigate how  we can make the 
guidelines more patient centered and thereby improve quality of care and quality of life. 
For this aim we have developed a survey to evaluate the current organization of care, demographic 
features and received treatment. The outcome of this survey will show the exact differences in care 
between European countries. We have included two validated questionnaires to measure the effect 
this has on quality of life and sexuality. The information gathered will be used to adapt the clinical 
EAU Pediatric Urology guidelines. 
 
 
2. Objective(s) 
The main objective is to improve the quality of life of patients with spina bifida by updating the 
guidelines according to the differences found in care and how this impacts patients outcomes. 
We will evaluate the difference in organization of care between different European countries based 
on the outcomes of the primary survey. The baseline quality of life and sexuality reported will be 
evaluated with the QUALAS and the IIEF-5/FSFI-6 questionnaires [3-6]. We will then explore the 
relationship between how care is organized and how this affects quality of life and sexuality. The 
results of this study will be used to update the EAU Pediatric Urology clinical guidelines. Also, it will 
highlight the direction for future research to improve patients care and thereby quality of life and/or 
sexuality, which patients with spina bifida have stated they themselves find important. 
 
 
3. Study type 
 
3.1  Study type:  
  
☐ Retrospective 
☒ Prospective 
☐ Combination Retrospective/Prospective 
 
3.2 Check all the applicable boxes: 
Medical records (re-use of data from healthcare, including AI) 
Case report 
Re-use data from research 
Evaluations of quality of healthcare (retrospective) 

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Research with additional use of residual material from regular healthcare 
Research with re-use of human materials from research or existing biobank 
Research with human materials without biobank 
De novo biobank (human material obtained without burdensome or invasive procedures) 
Post marketing survey research with medical devices 
Phase IV research 
Healthcare evaluation research (prospective) 
Medical devices 
In Vitro Diagnostic Tests 
Other research, describe 
 
 
 

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4. Study population 
 
4.1 Population (base)  
Children with spina bifida aged between 8 and 18 years old. 
 
4.2 Inclusion criteria 
In order to be eligible to participate in this study, a subject must meet all of the following criteria: 
- 
Must have spina bifida 
- 
Must be able to complete the digital survey, with help of caregivers allowed. 
- 
Speak one of the nine available languages:  
o 
English,  
o 
Spanish,  
o 
German,  
o 
Italian,  
o 
French,  
o 
Danish,  
o 
Greek,  
o 
Turkish,  
o 
Dutch 
 
4.3 Exclusion criteria 
A potential subject who meets any of the following criteria will be excluded from participation in this 
study: 
- 
Aged over 18 years or under 8 years of age 
- 
Does not have spina bifida  
 
4.4 Sample size calculation 
Since this is a descriptive study no minimal sample size is required.  
However, our aim is to include 500 patients. 
 
4.5 (Planned) start date 
Depending on the approval of the NWTC. 
Start date 01.01.2023. 
 
4.6 (Planned) end date 
The digital questionnaire will be available for 3 months. 
 
 
 
 

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5 Methods  
 
5.1   A digital survey has been created on Surveymonkey: https://www.surveymonkey.com/r/7WSB9S9 
This digital survey includes a primary survey regarding basic demographic features, medical 
treatment and organization of care. This survey was constructed by the EAU guidelines panel and 
the IFSBH patient representatives. The second part of the digital survey includes two validated 
questionnaires. The QUALAS is a validated questionnaire regarding quality of life in patients with 
spina bifida. There are two different versions for the ages 8-12 and 13-18 years. To evaluate 
sexuality the IIEF-5 (for boys) and the FSFI-6 (for girls) are used. These questionnaires are 
validated and are used in patients with spina bifida to evaluate sexual function as standard of care. 
Only children aged 13 years or older will be asked if they want to answer questions about sexuality 
and if they answer yes they will be asked for which gender they want to answer questions about 
their sexuality. After this they’ll get the IIEF-5 or FSFI-6 questionnaire.  
This digital survey is available in nine languages: English, Spanish, German, Italian, French, 
Danish, Greek, Turkish and Dutch.  
The link to surveymonkey will be distributed by the IFSBH and local patient organizations among 
their members. 
After the data have been collected, the general results of the survey will be evaluated and 
interpreted with a sounding board group. When patients participate with the digital survey they will 
not be involved in the sounding group. This sounding board group will consist of 
children/adolescents/adults with spina bifida who are representatives from the patient organization 
IFSBH and panel members of the EAU. This sounding board group will meet for a day. Finally, the 
results will be used to update the EAU Pediatric Urology guidelines.  
 
5.2 This is a demographic study. Patients will not receive any difference in treatment.  
 
5.3 The survey only has to be completed once and is completely voluntary. The questionnaire will take 
around 15 minutes to complete. It will not influence their own treatment.  
 
5.4 There are no known risks of participating in the study given the fact that involves only the 
completion of questionnaires and data about standard of care. Also, all responses will be 
anonymous and completely voluntary. No personal identifying information will be used when 
reporting the data. 
 
 
6 
Unexpected discoveries 
6.1  Is there a chance of unexpected discoveries? 
 
 
☐ Yes 
 
☒ No  
 
 
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Exchange, sharing or transfer of data and/or human material and/or images outside 
Erasmus MC  
The data will be collected and stored within the Erasmus MC in the Castor program. Only 
anonymous data will be collected and shared with collaborating colleagues from the EAU 
Pediatric Urology guidelines panel from their respective institutions outside the Erasmus MC. The 
institutions are: 
- 
University of Leuven, Leuven, Belgium 

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- 
Medical University of Innsbruck, Innsbruck, Austria 
- 
Hacettepe University, Ankara, Turkey 
- 
University Medical Center Groningen, Rijks University Groningen, Groningen, The 
Netherlands 
- 
Istanbul Biruni University, Istanbul, Turkey 
- 
East of England Deanery, Urology, Cambridge, United Kingdom 
- 
University of Medical Center Mannheim, Heidelberg University, Mannheim, Germany 
- 
Aarhus University, Aarhus, Denmark 
- 
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy 
- 
Pediatric Hospital Bambin-Gesù, Rome, Italy 
- 
Radboud University Medical Center, Nijmegen, The Netherlands 
- 
University of Zurich, Zurich, Switzerland 
- 
Beacon Hospital, Dublin, Ireland  
 
 
 
8 Statistical analysis 
 
8.1Main study parameter/endpoint:  
The primary parameter is to evaluate quality of life in children with spina bifida using the QUALAS 
questionnaire. We will evaluate the differences in quality of life between European countries. Also, 
we will evaluate which demographic parameters are of influence on quality of life. 
Descriptive statistics will be used. 
 
8.2Secondary study parameters/endpoints:  
Secondary parameters will include sexual function using the outcomes of the IIEF-5/FSFI-6 
questionnaires, also in relation to differences between European countries. Other parameters 
include organization of care, treatment received, treatment options available, which will all be 
extracted from the primary survey. Again descriptive statistics will be used. 
 
 
9.Recruitment and consent 
 
9.1   Will the subjects be asked for informed consent? 
 
☐ Yes (Upload Patient Information Letter and Informed Consent) 
☒ No, only anonymous data is used, i.e. the data can never be traced back to an individual 
subject 
☐ No, this research will be performed under the exception consent 
                 (Upload form Care for data Template, in Dutch: Formulier uitzondering toestemming)  
☒ Other (e.g. partly, indirectly) Please describe the situation 
The digital survey that has been constructed by the EAU and IFSBH will be distributed 
through the IFSBH and local patient organizations to their members by email and 
newsletter. A link to the digital survey can be found in this correspondence. 

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A short introduction with the purpose of the survey and  a question whether patients agree 
that their data will anonymously be used for research is the start of the digital survey. When 
patients answer no to this question, the digital survey is immediately ended. The data 
gathered cannot be traced back to the individual respondents. 
 
 
9.2 If no, exception consent: Participation is voluntary, people that do not want to participate will not  
complete the questionnaire. They can withdrawal at any time and the responses will be deleted. 
 
10. Handling and storage of data and images 
 
10.1   The data is collected anonymous and it will not be possible to trace back to one specific 
patient. 
10.2   The data will be stored in the Castor information system. Only anonymous data will be used, so 
it will not be possible to trace back to an individual patient.  
 
11.  Amendments 
Amendments are changes made to the research after a favourable opinion by the NWTC has been 
given.  All amendments will be submitted to the NWTC that gave the favourable opinion.  
Substantial amendments must be approved by the NWTC before they can be implemented. 
 
 
12. Publication 
 
Do you have the intention to submit the study results in a manuscript for publication in a journal: 
 
☒ Yes  
☐ No, please motivate 
 
 
13. References 
1. Dogan HS, Stein R, 't Hoen LA, Bogaert G, Nijman RJM, Tekgul S, Quaedackers J, Silay MS, 
Radmayr C. Are EAU/ESPU pediatric urology guideline recommendations on neurogenic 
bladder well received by the patients? Results of a survey on awareness in spina bifida 
patients and caregivers. Neurourol Urodyn. 2019 Aug;38(6):1625-1631. doi: 
10.1002/nau.24024. 
2. Radmayr C, et al: EAU Pediatric urology guidelines, EAU Guidelines. Edn. presented at the 
EAU Annual Congress Amsterdam 2022. ISBN 978-94-92671-16-5 
3. Szymanski KM, Misseri R, Whittam B, Yang DY, Raposo SM, King SJ, Kaefer M, Rink RC, 
Cain MP. Quality of Life Assessment in Spina Bifida for Children (QUALAS-C): Development 
and Validation of a Novel Health-related Quality of Life Instrument. Urology. 2016 Jan;87:178-
84. doi: 10.1016/j.urology.2015.09.027. 
4. Szymański KM, Misseri R, Whittam B, Casey JT, Yang DY, Raposo SM, King SJ, Kaefer M, 
Rink RC, Cain MP. Validation of QUALAS-T, a health-related quality of life instrument for 
teenagers with spina bifida. Cent European J Urol. 2017;70(3):306-313. doi: 
10.5173/ceju.2017.1195.  

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5. van Kollenburg RAA, de Bruin DM, Wijkstra H. Validation of the Electronic Version of the 
International Index of Erectile Function (IIEF-5 and IIEF-15): A Crossover Study. J Med Internet 
Res. 2019 Jul 2;21(7):e13490. doi: 10.2196/13490.  
6. Isidori AM, Pozza C, Esposito K, Giugliano D, Morano S, Vignozzi L, Corona G, Lenzi A, 
Jannini EA. Development and validation of a 6-item version of the female sexual function index 
(FSFI) as a diagnostic tool for female sexual dysfunction. J Sex Med. 2010 Mar;7(3):1139-46. 
doi: 10.1111/j.1743-6109.2009.01635.x. 
 
14. Attachments 
 
☐ Patient information letter and Informed consent document 
☐ Care for data Template – Formulier uitzondering toestemming  
☒ Questionnaires 
☐ Data Management Plan 
☐ Data Transfer Agreement  
☐ Material Transfer Agreement 
☐ Clinical Trial Agreement 
☐ Other, please describe