Autism Spectrum Disorder and Attachment. An Explorative Study of Attachment Styles in Adults With Autism Spectrum Disorder
Conditions: Autism Spectrum Disorder
Sponsor: Parnassia Groep

NL85075.018.23 Autism Spectrum Disorder and Attachment (ASDA study) 
C1 Research Protocol Version: 1.0  Date: October 19th 2023 
  
 
 
 
 
 
 
 
 
 
RESEARCH PROTOCOL 
Autism Spectrum Disorder and Attachment 
 
AN EXPLORATIVE STUDY OF ATTACHMENT STYLES IN 
ADULTS WITH AUTISM SPECTRUM DISORDER 
(October 2023) 
 
 
 

NL85075.018.23 Autism Spectrum Disorder and Attachment (ASDA study) 
C1 Research Protocol Version: 1.0  Date: October 19th 2023 
  
PROTOCOL TITLE An explorative study of attachment styles in adults with autism 
spectrum disorder 
 
Protocol ID 
NL85075.018.23 
Short title 
Autism Spectrum Disorder and Attachment 
EudraCT number  
Not applicable 
Version 
1.0 
Date 
19.10.2023 
Coordinating investigator/project 
leader 
 
E.M.A. (Stephanie) Bohnen, Health Care 
psychologist in post graduate training to become 
a Clinical Psychologist and Psychotherapist 
s.bohnen@anteszorg.nl 
 
Dr. R. (Richard) Vuijk, Clinical Psychologist & 
Supervisor 
r.vuijk@anteszorg.nl 
Principal investigator(s) (in 
Dutch: hoofdonderzoeker/ 
uitvoerder) 
Monocenter Study 
E.M.A. (Stephanie) Bohnen 
Sponsor (in Dutch: 
verrichter/opdrachtgever) 
Parnassia Groep  
Antes Rotterdam 
Subsidising party 
None 
Independent expert (s) 
Mw. T. Brandsma, manager SARR, Clinical 
Psychologist 
Laboratory sites 
Not applicable 
Pharmacy 
Not applicable 

NL85075.018.23 Autism Spectrum Disorder and Attachment (ASDA study) 
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PROTOCOL SIGNATURE SHEET 
 
Name 
Signature 
Date 
Head of Department: 
 
Dr. R. (Richard) Vuijk 
 
 
 
[Coordinating Investigator/Project 
leader/Principal Investigator]: 
E.M.A. (Stephanie) Bohnen 
 
 
 
 
 

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TABLE OF CONTENTS 
 
1. 
INTRODUCTION AND RATIONALE .............................................................................. 8 
2. 
OBJECTIVES ................................................................................................................10 
3. 
STUDY DESIGN ...........................................................................................................10 
4. 
STUDY POPULATION ..................................................................................................11 
4.1 
Population (base) ...................................................................................................11 
4.2 
Inclusion criteria .....................................................................................................11 
4.3 
Exclusion criteria ....................................................................................................11 
4.4 
Sample size calculation ..........................................................................................11 
5. 
TREATMENT OF SUBJECTS .......................................................................................12 
5.1 
Investigational product/treatment ............................................................................12 
5.2 
Use of co-intervention (if applicable) ......................................................................12 
5.3 
Escape medication (if applicable) ...........................................................................12 
6. 
INVESTIGATIONAL PRODUCT ....................................................................................13 
6.1 
Name and description of investigational  product(s) ...............................................13 
6.2 
Summary of findings from non-clinical studies ........................................................13 
6.3 
Summary of findings from clinical studies ...............................................................13 
6.4 
Summary of known and potential risks and benefits ...............................................13 
6.5 
Description and justification of route of administration and dosage .........................13 
6.6 
Dosages, dosage modifications and method of administration ...............................13 
6.7 
Preparation and labelling of Investigational Medicinal Product ...............................13 
6.8 
Drug accountability .................................................................................................13 
7. 
NON-INVESTIGATIONAL PRODUCT ...........................................................................14 
7.1 
Name and description of non-investigational product(s) .........................................14 
7.2 
Summary of findings from non-clinical studies ........................................................14 
7.3 
Summary of findings from clinical studies ...............................................................14 
7.4 
Summary of known and potential risks and benefits ...............................................14 
7.5 
Description and justification of route of administration and dosage .........................14 
7.6 
Dosages, dosage modifications and method of administration ...............................14 
7.7 
Preparation and labelling of Non Investigational Medicinal Product ........................14 
7.8 
Drug accountability .................................................................................................14 
8. 
METHODS ....................................................................................................................15 
8.1 
Study parameters/endpoints ...................................................................................15 
8.1.1 
Main study parameter/endpoint .......................................................................15 
8.1.2 
Secondary study parameters/endpoints (if applicable) ....................................16 
8.1.3 
Other study parameters (if applicable) .............................................................16 
8.2 
Randomisation, blinding and treatment allocation ..................................................16 
8.3 
Study procedures ...................................................................................................16 
8.4 
Withdrawal of individual subjects ............................................................................16 
8.5 
Replacement of individual subjects after withdrawal ...............................................16 
8.6 
Follow-up of subjects withdrawn from treatment .....................................................16 
8.7 
Premature termination of the study .........................................................................16 

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9. 
SAFETY REPORTING ..................................................................................................17 
9.1 
Temporary halt for reasons of subject safety ..........................................................17 
9.2 
AEs, SAEs and SUSARs ........................................................................................17 
9.2.1 
Adverse events (AEs) ......................................................................................17 
9.2.2 
Serious adverse events (SAEs) .......................................................................17 
9.2.3 
Suspected unexpected serious adverse reactions (SUSARs) .........................18 
9.3 
Annual safety report ...............................................................................................18 
9.4 
Follow-up of adverse events ...................................................................................18 
9.5 
Safety Committee ...................................................................................................18 
10. 
STATISTICAL ANALYSIS ..........................................................................................19 
10.1 
Primary study parameter(s) ....................................................................................19 
10.2 
Secondary study parameter(s) ...............................................................................19 
10.3 
Other study parameters ..........................................................................................19 
10.4 
Interim analysis (if applicable) ................................................................................19 
11. 
ETHICAL CONSIDERATIONS ...................................................................................20 
11.1 
Regulation statement .............................................................................................20 
11.2 
Recruitment and consent........................................................................................20 
11.3 
Objection by minors or incapacitated subjects (if applicable) ..................................20 
11.4 
Benefits and risks assessment, group relatedness .................................................20 
11.5 
Compensation for injury .........................................................................................20 
11.6 
Incentives (if applicable) .........................................................................................20 
12. 
ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION .........................21 
12.1 
Handling and storage of data and documents ........................................................21 
12.2 
Monitoring and Quality Assurance ..........................................................................21 
12.3 
Amendments ..........................................................................................................21 
12.4 
Annual progress report ...........................................................................................21 
12.5 
Temporary halt and (prematurely) end of study report ............................................21 
12.6 
Public disclosure and publication policy ..................................................................22 
13. 
STRUCTURED RISK ANALYSIS...............................................................................23 
13.1 
Potential issues of concern .....................................................................................23 
13.2 
Synthesis ...............................................................................................................23 
14. 
REFERENCES ..........................................................................................................23 

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LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS  
 
 
 
AE 
Adverse Event 
AR 
Adverse Reaction 
ASD 
Autism Spectrum Disorder 
ASQ 
Attachment Style Questionnaire 
ECR-R 
Experiences in Close Relationships Revised 
EU 
European Union 
EudraCT
European drug regulatory affairs Clinical Trials  
HSL 
Hechtingsstijllijst 
METC  
Medical Research Ethics Committee (MREC); in Dutch: medisch-ethische 
toetsingscommissie (METC) 
RDM 
Research Data Management 
RSQ 
Relationship Scales Questionnaire 
(S)AE 
(Serious) Adverse Event  
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. 
SRS-A 
Social Responsiveness Scale – Adult version 
SUSAR  
Suspected Unexpected Serious Adverse Reaction 
UMC 
University Medical Center 
WMO 
Medical Research Involving Human Subjects Act; in Dutch: Wet Medisch-
wetenschappelijk Onderzoek met Mensen 
 
 

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SUMMARY 
 
Rationale: Previous research on autism spectrum disorder (ASD) and attachment has 
improved understanding of the aetiology and development of the disorder. Research on 
adults with ASD, however is scarce. In the current study, we focus on attachment in adults 
with ASD.  
Objective: The aim of the current study is to explore attachment styles of adults with ASD 
and examining the relationship between attachment and ASD.  
Study design: Cross-sectional design: data will be analysed at a specific point in time. 
Study population: Adults (>18 years) with ASD, and without intellectual disability. 
Participants will be recruited from SARR Autism Rotterdam and Antes, both part of Parnassia 
Group in the Netherlands. SARR Autism Rotterdam is specialized in psychodiagnostic 
assessments and interventions for children, adolescents, and adults with ASD. Antes and 
Parnassia Group are multisite mental health institutes specialized in psychodiagnostic 
assessments and interventions for adults with a broad range of psychiatric disorders, 
including ASD. The study requires 60 participants. 
Intervention (if applicable): not applicable 
Main study parameters/endpoints: Main study parameters are SRS-A score (ASD 
characteristics), ASQ (attachment style) and ECR-R (attachment anxiety and attachment 
avoidance).  
Nature and extent of the burden and risks associated with participation, benefit and 
group relatedness: Participants are asked to complete three online questionnaires, each 
taking no more than 15 minutes to complete. The questionnaires collect participants’ 
information on their ASD characteristics and their experiences of interpersonal relationships. 
We do not expect this to be burdensome, as they are already familiar with diagnostic 
assessment. For individuals with ASD, the principal psychological benefit of knowing their 
attachment style may be that in those with insecure attachment this knowledge may function 
as a means of treatment.  
 
 
 

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1. INTRODUCTION AND RATIONALE 
 
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with early onset, and 
typical characteristics throughout one’s lifetime. It is called a spectrum disorder because of 
variety in phenotypic presentation and severity of symptoms (Lai et al., 2013). Kanner (1943) 
described ASD as an inability to form effective contact with others. In the late 1970s, lack of 
attachment was mentioned as one of the characteristics of ASD (Rutter, 1978). DSM-III 
American Psychiatric Association, 1980) described ASD as a failure to develop normal 
attachment behaviour. However, recent research indicates that individuals with ADS are able 
to form secure attachment, albeit at lower rates and with more challenges (Chandler & 
Dissanayake, 2014; Giannotti & de Falco, 2021; Rutgers et al., 2004; Teague et al., 2017). 
In DSM-5-TR (American Psychiatric Association, 2022). Core features are persistent deficits 
in social communication, social interaction, and restricted, repetitive patterns of behaviour, 
interests, or activities. The social disability is multifaceted with deficits in social-emotional 
reciprocity, social non-verbal communication, and developing, understanding, and 
maintaining relationships. Both ASD and insecure attachment affect social functioning and 
relationships and little is known about attachment in adults with ASD and the relationship 
between ASD and attachment in adults.   
 
For more than over 60 years, the concept of attachment is one of the most and well-
known concepts in the field of clinical psychology. John Bowlby (1969; 1973; 1980), the first 
attachment theorist, formulated his attachment theory which has led to one of the major 
theories of affect regulation, interpersonal functioning, and psychopathology. Development of 
attachment begins in early infancy: children establish attachment bonds with their caregivers, 
serving as an evolutionary function keeping the child close to the caregiver in times of stress 
to increase chance of survival. During child development, attachment behaviours adapt. In 
infants, toddlers, and pre-schoolers, attachment behaviours are: crying, clinging to 
caregivers, wariness of strangers, preference for a specific caregiver, and using the 
caregiver as a safe-base to return when exploring the environment (Bowlby, 1969). In middle 
childhood (between 6 and 12 years of age), attachment behaviours become less dependent 
on the their physical proximity to caregivers. Instead, caregivers’ unconditional availability 
and responsiveness, influence attachment behaviours (Kobak et al., 2005). 
Ainsworth and colleagues (1978) extended Bowlby’s attachment theory by delineating 
individual differences in attachment patterns through observation of behaviour of infants of 
12 to 24 months approximately in response to separation from and reunion with the caregiver 
(i.e., the well-known Strange Situation procedure (Ainsworth et al., 1978). Three different 
patterns of interaction and behaviour shown by infants towards their caregiver were 
discovered: secure, anxious, and avoidant. Securely attached children were distressed 

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during separation, but recovered quickly, showing joy, affection, easily soothed upon reunion, 
and more openness and flexibility towards exploring the environment. Anxious attached 
children were highly distressed during separations, showing anger and resistance upon 
reunion,  yearning for physical contact and comfort with contradictory and ambivalent 
responses towards the mother, highly sensitive to potential unavailability, maximizing their 
efforts to remain in close contact with the caregiver. Avoidant attached children showed little 
distress when separated, avoiding proximity upon return, suppressing their needs and 
feelings of distress and giving up their proximity-seeking efforts (Ainsworth & Bell, 1970). A 
fourth attachment style was added, which is called the disorganized attachment style (Main & 
Solomon, 1986). Children with this style show chaotic, contradictory behavior (indifferences 
upon mother’s return after excessive distress during separation), misdirected (seeking 
proximity to a stranger instead of a parent after separation) or stereotypical behavior (pulling 
hair with dazed expression, even though the parent is available), stilling and freezing (unable 
to choose between proximity or avoiding the parent, stops moving as in trance, dissociated 
from regular thought processes) for a substantial amount of time, or they even fear the 
parent in stressful circumstances. Their behaviour is bizarre and incoherent, indicating stress 
and anxiety the child cannot resolve because the parent is source of fright as well as the only 
potential haven of safety (Main & Solomon, 1986; Van IJzendoorn et al., 1999). 
Bowlby (1980) argued that attachment processes continue to influence close 
relationships across the life span. In adulthood, internal working models of attachment are 
generally conceptualized as sets of global beliefs about self and others, resulting in a 
combination of four attachment styles (secure, preoccupied, dismissing and fearful) 
(Bartholomew & Horowitz, 1991; Griffin & Bartholomew, 1994). Individuals with a secure 
attachment style have positive views of self and others, and are at ease in becoming 
emotionally close and depending to others. Preoccupied attached individuals have a positive 
view on others, but a negative view on self, desiring extreme intimacy with others who do not 
meet their attachment needs. Avoidant – dismissing individuals have a positive self-model 
and a negative other-model, feeling comfortable without close emotional relationships. 
Intimacy is avoided because independence, self-reliance and maintaining autonomy is very 
important for them. The Avoidant – Fearful individuals have a negative view on both self and 
others, avoiding intimacy for the fear to be hurt.  
 
Until now, studies examining attachment in ASD mainly focused on children 
(Bauminger et al., 2010; Capps et al., 1994; Davidson et al., 2022; Davidson et al., 2015; 
Dissanayake & Sigman, 2001; McKenzie & Dallos, 2017; Minnis et al., 2020; Rutgers et al., 
2004; Sivaratnam et al., 2018; Teague et al., 2017; Van IJzendoorn et al., 2007; Willemsen-

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Swinkels et al., 2000). A review study on ASD and attachment showed 40%-63% children 
with ASD are securely attached to their caregiver, comparable to children without ASD.  
Secure attachments appear to act as a protective factor in the social and cognitive 
development of children with ASD (Teague, 2017).  When demonstrating secure attachment, 
children with ASD show more complex play behaviours (Naber et al., 2008), more joint 
attention (Naber et al., 2007), improved social skills and educational opportunities and 
outcomes (Bauminger et al., 2010. These findings are consistent with observations from the 
typically developing literature and with predictions from attachment theory (Teague, 2017). 
The severity of ASD and developmental delay are both associated with less secure 
attachments (Naber et al., 2006), but there is a lack of consensus on the extent to which 
attachment insecurity is a function of either developmental delay or the severity of autism 
symptoms. To the best of our knowledge, research on attachment in adults with ASD is 
scarce. To date, only one study on attachment in adults with high functioning ASD (N=20) 
found a minority (15%) to be securely attached comparable with a general clinical sample 
and lower than non-clinical samples, and attachment security was found not to be related to 
ASD characteristic and IQ (Taylor et al., 2008). 
Very little research has investigated the relationship between attachment and 
behaviour and emotional problems in children with ASD (Teague et al., 2017).  The aim of 
this study is to explore attachment styles in adults with ASD and examining the relationship 
between attachment and ASD. For individuals with ASD, the principal psychological benefit 
of knowing their attachment style may be that in those with insecure attachment this 
knowledge may function as a means of treatment. 
 
2. OBJECTIVES 
 
Primary Objective: Exploring the relationship between ASD and attachment by describing 
how attachment styles are distributed in an adult population with ASD. We calculate 
correlations between ASD characteristics based on the SRS-A and attachment styles, 
attachment anxiety and attachment avoidance, as well as between attachment and level of 
education and having a relationship. 
 
3. STUDY DESIGN 
A cross sectional design will be used (outcomes on SRS-A, ASQ, and ECR-R). 
 

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4. STUDY POPULATION 
4.1 Population (base)  
Adults (>18 years) with ASD, and without intellectual disability. Participants will be 
recruited from SARR Autism Rotterdam and Antes, both part of Parnassia Group in the 
Netherlands. SARR Autism Rotterdam is specialized in psychodiagnostic assessments 
and interventions for children, adolescents, and adults with ASD. Antes and Parnassia 
Group are multisite mental health institutes specialized in psychodiagnostic assessments 
and interventions for adults with a broad range of psychiatric disorders, including ASD. 
The study requires 60 participants. 
 
4.2 Inclusion criteria 
Inclusion criteria are: a DSM-5 ASD diagnosis, age 18-65 years and no intellectual 
disability (IQ >80). 
 
4.3 Exclusion criteria 
Exclusion criteria are: acute psychosis, acute suicidality, psychotic disorder, intellectual 
disability (IQ < 80) 
 
4.4 Sample size calculation 
A priori power analysis was conducted using G*Power version 3.1.9.7 (Faul et al., 2007) 
to determine the minimum sample size required to test the relationship between ASD 
(SRS-A score) and attachment (ASQ and ECR-R scores). To examine the relationship 
between SRS-A and attachment, Spearman correlation coefficients are computed. 
Sample size for Spearman correlation was determined using power analysis in G*Power 
version 3.1.9.7 (Faul et al., 2007), using an alpha of 0.05, a power of 0.80, and an effect 
size of .5  for a two-tailed test. Because Spearman’s rank correlation coefficient is 
computationally identical, power analysis was conducted using software for estimating 
power of a Pearson’s correlation. Based on the aforementioned assumptions, the required 
sample size was determined to be 56. To prevent the hypotheses from being 
underpowered, we included a total of 60 participants for each hypothesis. 
 

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5. TREATMENT OF SUBJECTS 
This chapter is only applicable for intervention studies:  
Not applicable 
 
5.1 Investigational product/treatment 
Not applicable 
5.2 Use of co-intervention (if applicable) 
Not applicable 
5.3 Escape medication (if applicable) 
Not applicable 

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

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

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8. METHODS 
8.1 Study parameters/endpoints 
8.1.1 Main study parameter/endpoint 
Main study parameters are the SRS-A score, the ASQ and ECR-R. 
 
The Social Responsiveness Scale – Adult version (SRS-A)  (Constantino, 2005; 
Dutch translation: Noens et al., 2012), a screening tool for identifying possible ASD 
characteristics in adults suspicious for ASD, is 64-item self-report questionnaire 
measuring various dimensions of interpersonal behavior, communication, and rigid, 
repetitive behaviour and interests, characteristic for adults with ASD. Each item is 
rated on a 1-4 point scale. The SRS-A showed average to good internal consistency 
and test-retest reliability, adequate content validity, and good congruent validity 
(Noens et al., 2012). The Cronbach’s alpha for the SRS-A scales were for Social 
awareness .80, Social communication .82, Social motivation .81, and Restricted 
interests & repetitive behavior .81 (Bezemer et al., 2020). 
 
The Attachment Styles Questionnaire (ASQ; Mosterman & Hofstra, 2015), translation 
of the Dutch Hechtingsstijllijst (HSL) (Oudenhoven et al., 2003), is a questionnaire 
consisting of 24 items based on four vignettes (Bartholomew & Horowitz, 1991) and 
the Relationship Scales Questionnaire (RSQ; Griffin & Bartholomew, 1994). The ASQ 
assesses four attachment styles (secure, preoccupied, fearful, and dismissing). The 
5-point rating scale ranges from 1 (strongly disagree) to 5 (strongly agree). The 
internal consistencies (Cronbach’s alpha) were 0.75 for the secure style, 0.80 for the 
preoccupied style, 0.79 for the fearful style, and 0.62 for the dismissing style 
(Mosterman & Hofstra, 2015).  
 
The Experiences in Close Relationships Questionnaire Revised (ECR-R) (Fraley, 
Waller, & Brennan, 2000; Dutch translation by Conradi et al., 2006) measures adult 
attachment within romantic relationships in past and present in 36 items, consisting of 
two subscales of 18 items each (attachment anxiety and attachment avoidance). 
Each item is rated from ‘strongly disagree’ (1) to ‘strongly agree’ (7). The ECR-R is 
currently the most commonly used and recommended self-report measures with good 
psychometric properties (Conradi et al., 2006; Sibley et al., 2005; Sibley & Liu, 2004). 
Cronbach’s alpha was 0.88 for attachment avoidance and 0.86 for attachment 
anxiety. In a validation study of the Dutch version, factor structure could be replicated, 
reliability was stable over time and there was good evidence for its construct validity 

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(Kooiman et al., 2013). Cronbach’s alpha was 0.94 for attachment avoidance and 
0.92 for attachment anxiety. Test–retest reliability of the avoidance subscale was .82, 
and .84 for the anxiety subscale (p < 0.1). 
8.1.2 Secondary study parameters/endpoints (if applicable) 
 
         Not applicable 
8.1.3 Other study parameters (if applicable) 
 
         Not applicable 
 
8.2 Randomisation, blinding and treatment allocation 
 
         Not applicable 
  
 
8.3 Study procedures 
The procedure begins with a screening on inclusion- and exclusion criteria. Written 
informed consent is obtained. Participants are asked to complete three online 
questionnaires (SRS-A, ASQ and ECR-R), by computer each taking no more than 15 
minutes to complete. 
 
8.4 Withdrawal of individual subjects 
Participants’ requests for withdrawal will be granted without repercussions.  
8.5 Replacement of individual subjects after withdrawal 
Not applicable 
 
 
 
 
 
 
8.6 Follow-up of subjects withdrawn from treatment 
Not applicable 
8.7    Premature termination of the study 
The study will be prematurely terminated only when the principal investigator is no longer 
able to perform principal investigator’s duties, and no replacement can be found. 
  
 
 
 
 
 

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9. SAFETY REPORTING 
 
9.1 Temporary halt for reasons of subject safety 
In accordance to section 10, subsection 4, of the WMO, 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.  
 
9.2 AEs, SAEs and SUSARs 
9.2.1 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 product / 
trial procedure/ the experimental intervention]. All adverse events reported 
spontaneously by the subject or observed by the investigator or his staff will be 
recorded. 
9.2.2 Serious adverse events (SAEs) 
A serious adverse 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. 
 
If an adverse event might occur, the sponsor will be notified. Due to the nature of 
our research (questionnaires, online at home) we do not expect these kind of 
SAE’s. 
 
The investigator will report all SAEs to the sponsor without undue delay after 
obtaining knowledge of the events, except for the following SAEs: none        . 

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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. 
9.2.3 Suspected unexpected serious adverse reactions (SUSARs) 
  Not applicable. 
 
9.3 Annual safety report 
 
 Not applicable 
9.4 Follow-up of adverse events 
All AEs will be followed until they have abated, or until a stable situation has been 
reached. Depending on the event, follow up may require additional tests or medical 
procedures as indicated, and/or referral to the general physician or a medical specialist. 
SAEs need to be reported till end of study within the Netherlands, as defined in the 
protocol  
9.5 Safety Committee 
Ethical approval will be obtained from an institutional review board (CWO Parnassia 
Psychiatric Institute Academy – Rotterdam – The Netherlands) and Medical Research 
Ethics Committee Amsterdam UMC. 
 

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10. STATISTICAL ANALYSIS 
10.1 Primary study parameter(s) 
Statistical analyses were performed using Statistical Package for the Social Sciences 
version 27 (SPSS Version 27, IBM, New York, NY, USA). First descriptive statistics were 
used to analyze participants’ demographic data. 
 
Spearman correlation coefficients were used to calculate the correlations between SRS-A 
scores and ASQ scores, and between SRS-A scores and ECR-R scores.  
Multiple regression was used to test whether level of education and having a relationship 
influence a SRS-A score and attachment and whether this is a positive or a negative 
effect.  For the analyses p-value of < .05 was considered statistically significant. 
 
10.2 Secondary study parameter(s)  
None 
10.3 Other study parameters 
None 
10.4 Interim analysis (if applicable) 
Not applicable 

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11. ETHICAL CONSIDERATIONS 
11.1 Regulation statement 
The study will be conducted according to the principles of the Declaration of Helsinki 
(64th WMA General Assembly, Fortaleza, Brazil, October 2013) and in accordance with 
the Medical Research Involving Human Subjects Act (WMO). 
 
11.2 Recruitment and consent 
Recruitment starts with contacting mental health therapists from Sarr Autism Rotterdam 
and Antes, both part of Parnassia Group in the Netherlands. They will be asked to inform 
their patients with ASD about the current study and to see if they are  willing to 
participate. Additionally, adults with ASD included in earlier studies at Sarr Autism 
Rotterdam will also be recruited. Next, participants are screened for eligibility by a health 
care psychologist and clinical psychologists. When participants meet criteria, they will 
receive a letter of informed consent, which details the study (see attachment). They will 
have no deadline for consideration of participation. The SRS-A, ASQ and ECR-R will be 
administered by computer, online, at home. Participants can stop participating anytime, 
without explanation. 
 
11.3 Objection by minors or incapacitated subjects (if applicable) 
Not applicable 
 
11.4 Benefits and risks assessment, group relatedness 
Not applicable 
 
11.5 Compensation for injury 
The sponsor/investigator has a liability insurance which is in accordance with article 7 of 
the WMO. The sponsor (also) has an insurance which is in accordance with the legal 
requirements in the Netherlands (Article 7 WMO). This insurance provides cover for 
damage to research subjects through injury or death caused by the study. 
The insurance applies to the damage that becomes apparent during the study or within 4 
years after the end of the study. 
 
11.6 Incentives (if applicable) 
Not applicable 

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12. ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION 
12.1 Handling and storage of data and documents 
Researchmanager Data Management (RDM) is used for data collection (scores on 
questionnaires) and coding and saving data. 
 
12.2 Monitoring and Quality Assurance  
      Not applicable 
 
12.3 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.  
All substantial amendments will be notified to the METC and to the competent authority. 
Non-substantial amendments will not be notified to the accredited METC and the 
competent authority, but will be recorded and filed by the sponsor.  
 
12.4 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.  
 
12.5 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 visit.  
 
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, 

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to the accredited METC.  
 
12.6 Public disclosure and publication policy 
The data will be used for submitting a manuscript to a peer-reviewed international journal 
focusing on ASD. 

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13. STRUCTURED RISK ANALYSIS  
Not applicable 
 
13.1 Potential issues of concern 
13.2 Synthesis 
 
 
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