Patient reported outcomes that matter to individuals with (genetic) intellectual disabilities: a qualitative study

Abstract

Background

To improve the quality of care and the impact of interventions for individuals with (genetic) intellectual disabilities ((G)ID), it is essential to identify and measure relevant patient reported outcomes (PROs), which represent patient perspective on their health and functioning. Currently, various, and potentially irrelevant PROs are being measured for individuals with (G)ID. The aim of this study is to identify relevant PROs from the perspective of different stakeholders, as one of the first steps towards development of a meaningful PRO set for children and adults with (G)ID.

Methods

A qualitative study was performed using focus groups and interviews with individuals with (G)ID, caregivers, healthcare professionals (HCPs) and European patient representatives. A focus group- and interview guide was developed including two themes: the impact of (G)ID on daily life and important topics to discuss with HCPs. Data collection took place until data sufficiency was reached. All sessions were recorded and transcribed verbatim. Transcripts were analysed by three researchers using a thematic analysis approach. PROs were classified and conceptualized (i.e., describing the content of each PRO in detail) within a conceptual framework.

Results

Ten focus groups and 13 interviews were conducted with a total of 51 participants. In total, seven adolescents and 10 adults with (G)ID, 12 caregivers, 13 multidisciplinary HCPs and nine European patient representatives participated. Data sufficiency was reached. PROs reported by participants were related to all health domains including physical, mental, and social functioning. Themes related to the negative impact of (G)ID were prioritized for discussion during consultations.

Conclusions

This study sheds light on relevant PROs for individuals with (G)ID, marking one of the first steps in developing a meaningful PRO set for (G)ID. Once established, this set will inform care, research agendas, policymaking, and the development of a generic patient reported outcome measure (PROM) set for (G)ID, improving care quality and research impact for this complex and vulnerable population.

Supplementary Information

The online version contains supplementary material available at 10.1186/s11689-025-09647-z.

Background

Intellectual disabilities (ID) are characterized by significant limitations in Both intellectual and adaptive functioning, emerging prior to the age of 18 years [1]. ID affects 1–3% of the general population, with about 50% having an identified genetic cause [2–4]. ID, with and without a genetic cause, henceforward referred to as (genetic) ID ((G)ID), can profoundly impact the daily lives of affected individuals and their families due to the wide range of physical and neuropsychiatric manifestations inherent to the often syndromic nature. These manifestations may include epilepsy, tumour growth, attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder [5–8]. The severity and type of manifestations can be highly variable within and between disorders. For example, individuals with Tuberous Sclerosis Complex (TSC) exhibit a wide range of IQ levels and tumour growth in various organ systems at different life stages [6, 9]. Psychosis is common in young adults with 22q11.2 deletion syndrome [10], while obesity is often observed in individuals with Prader-Willi syndrome and Chung-Janssen syndrome [11, 12]. Despite the heterogeneous and complex manifestations of (G)ID, affected individuals often face similar challenges in their everyday lives, such as anxiety, sleeping problems, difficulty performing daily activities, and participating in society [13–16].

Personalized care for individuals with (G)ID is increasingly available, driven by recognition of their specific and complex healthcare needs [17]. Research involving these individuals is growing as well, leading to the development of more targeted interventions [18], and as this research is growing, the importance of measuring the patients’ perspective on their health is becoming more widely recognized [19]. To enhance care and develop relevant interventions for individuals with (G)ID, measuring and assessing relevant patient reported outcomes (PROs) is crucial [20, 21]. PROs are health aspects, such as anxiety or pain, reported directly by the patient or a proxy (i.e., caregiver) without interference of a clinician or someone else [22]. PROs offer insight into the impact of a condition and its treatment. Relevant PROs for patients, such as anxiety in those with Fragile X syndrome and TSC [23, 24], can inform care, shape research priorities, and influence policymaking in order to better reflect what matters most to them. Gaining insight into these relevant PROs is therefore essential for improving healthcare. To deliver patient-centred, high-quality care and research, it is crucial to understand patients’ perspectives on their health.

PROs can be best measured with patient reported outcome measures (PROMs), which are standardized questionnaires [25]. PROMs can be applied in various settings for multiple purposes. In routine care, they can be used to monitor daily functioning, identify issues, and tailor treatment goals accordingly. PROMs can highlight areas for symptom management and opportunities for improvement [26]. In research, PROMs can be used to collect natural history data, identify treatment targets, and evaluate interventions. The PRO data gathered with PROMs can further inform care, research agendas, and policymaking, as well as drug approval processes and pricing and funding of treatments [21].

Clinical trials involving individuals with (G)ID are increasingly using PROMs to evaluate the impact of interventions on daily life. For instance, the Child Health Questionnaire (CHQ) has been used to measure the effect of Glatiramer acetate on quality of life (among other things) in individuals with Rett syndrome [27]. PROM use is also encouraged by patient organizations, regulatory agencies like the European Medicines Agency (EMA) and the Food and Drug Administration (FDA), and European initiatives such as the European Reference Networks to capture patient perspectives on treatment impact [28–31].

To guide care, research, and policy, and identify suitable PROMs for the whole (G)ID population, relevant PROs must first be identified and selected. This selection process is challenging due to the complex and diverse manifestations of ID with unknown origin, as well as the more than 1500 identified genetic and other aetiologies associated with ID, such as inborn errors of metabolism, brain malformations, and perinatal complications [32, 33]. Recent studies demonstrated that a wide array of PROs are being addressed in clinical trials (66 different PROs) and core outcome sets (22 different PROs) for individuals with (G)ID [34, 35]). This abundance of PROs complicates data aggregation and comparison within and across (G)ID groups, and raises concerns about whether the most relevant PROs are being measured and treated for (G)ID.

To address these issues, harmonization of PROs for (G)ID is needed. Utilizing a meaningful PRO set is essential for delivering patient-centred, high-quality care and research. It also aligns with other efforts in the general population to standardize PROs and PROMs across patient groups, settings, and countries [36]. Therefore, this study aims to identify relevant PROs for (G)ID, all from the perspective of affected individuals, caregivers, healthcare professionals (HCPs), and European patient representatives. This study represents one of the initial steps towards developing a meaningful PRO set for (G)ID [37].

Methods

To identify relevant PROs for individuals with (G)ID, a qualitative study including in-person and digital focus groups and interviews was performed (Fig. 1). The consolidated criteria for reporting qualitative studies (COREQ) checklist was utilized as a reporting framework [38]. The individual with (G)ID, their caregiver, and/or HCP assessed the individual’s ability to participate in a focus group or interview. Individuals with (G)ID and caregivers were selected using purposive sampling based on age, genetic diagnosis, and level of ID (of their child) [1]. HCPs were selected using purposive sampling based on their profession (e.g., ID physician, psychologist, or nurse). European patient representatives were selected using convenience sampling.

Fig. 1.

Steps for developing a meaningful PRO set¹: step 1.3 was undertaken in the current study. PROs, patient reported outcomes; PROM(s), patient reported outcome measure(s); COS(s), core outcome set(s); (G)ID, (genetic) intellectual disabilities. Figure 1: Reproduced/adapted from van Silfhout et al., 2024 [37] under the Creative Commons license (https://creativecommons.org/licenses/by/4.0/). ²Van Silfhout et al., 2025 [35]. *Targeted number of participants

Recruitment

Individuals with (G)ID and caregivers were approached through their HCP at the involved organizations (Amsterdam UMC and ‘s Heeren Loo) and patient organizations dedicated to a specific (G)ID. A call was also placed on social media to recruit affected individuals and caregivers. HCPs were recruited by email at the involved healthcare organizations, and European patient representatives via the European Reference Network on Intellectual Disability, TeleHealth, Autism and Congenital Anomalies (ERN-ITHACA), a patient-centred network that aims to enhance collaboration on rare neurodevelopmental disorders, both with and without biological diagnosis. Upon request, individuals with (G)ID and caregivers could authorize their HCP to share their contact details with the investigator (NvS), allowing the investigator to contact them directly. The investigator provided a detailed overview of the study to interested participants and addressed any questions. Participant eligibility was assessed. In addition, interested participants received a comprehensive information letter about the study. Easy-read versions, using simplified language and pictographs, were provided for individuals with ID.

Inclusion criteria for individuals with (G)ID were a diagnosis of ID with or without a known aetiology, being 12 years or older, having effective communication skills to articulate thoughts and feelings, and exhibiting proficiency in Dutch. The inclusion criterion for caregivers was that they provide care and support to an individual with (G)ID. HCPs were required to have a minimum of five years of experience working with individuals with (G)ID, and European patient representatives needed to have at least five years of experience with a patient organization dedicated to (G)ID.

Procedure

Focus groups were conducted separately with adolescents with (G)ID, adults with (G)ID, caregivers, HCPs, and European patient representatives. Participants could, if preferred, also participate in a one-on-one interview. Informed consent was signed by the participants prior to starting the focus group or interview. Socio-demographic information was collected through a short questionnaire prior or after the focus group or interview. Focus groups and interviews with individuals with (G)ID, caregivers, and HCPs were performed at the Amsterdam UMC in the Netherlands or online. Focus groups with European patient representatives were performed online. Individuals with (G)ID were allowed to have a caregiver present during the focus group or interview if desired. The duration of focus groups was approximately 1.5 h, and that of interviews 30 min. The aim was to include three to six participants in each focus group [39]. All focus groups and interviews were audio recorded. Individuals with (G)ID and caregivers received a gift card of 10 euros after participation.

Focus groups were moderated by a female investigator (NvS) and a female assistant (MvM, MKH, TvG, AG, or SL), all of whom were PhD candidates or post-doctoral researchers with a background in psychology, medicine, or physiotherapy. Interviews were moderated by the investigator (NvS) or an assistant (MKH) if concurrent to another focus group or interview. Moderators had no prior professional relationships with participants. Before the focus groups and/or interviews, assistants received a short training on conducting the sessions. Pictographs were used during focus groups and interviews with individuals with (G)ID to enhance their comprehension. At the beginning of the focus group or interview, the aim of the study was explained. The focus group or interview was divided into two parts:

Part 1 - To help participants explain the impact of (G)ID on daily life, the ‘Complain and Cheer wall’ technique was used [40]. Participants were asked to write down the negative impact of (G)ID on a flip chart (the ‘Complain wall’), and the positive impact of (G)ID on another flip chart (the ‘Cheer wall’) or a digital equivalent. Afterwards, a (group) discussion took place on the identified themes.

Part 2 – To identify which themes were relevant for discussion during consultation with a HCP, the ‘Brainstorming’ technique was used [40]. Participants were asked to write the themes on a flip chart or a digital equivalent under one of the following health domains: physical functioning, mental functioning, and social functioning. Afterwards, a (group) discussion took place on the identified themes.

Analysis

Audio recordings were transcribed verbatim through an external organization (Transcript Online). Transcripts were imported and analysed in MAXQDA (2018) using thematic analysis in psychology [41]: (1) highlighting relevant parts of the transcript, (2) organizing text into meaningful groups and selecting initial codes for these groups, (3) merging the initial codes into themes, (4) revising and refining themes, and (5) defining and structuring the final themes. The first 25% of the transcripts were double coded by two researchers (NvS and TvG, or NvS and MvM). Discrepancies were discussed until consensus was reached on the themes. The remaining transcripts were coded by one researcher (NvS). Data collection continued until data sufficiency was reached (meaning that the collected data was ‘good enough’, as no new themes emerged during the focus groups and interviews), and an adequate sample was included to address the research question [42].

Classifying PROs into a conceptual framework

Themes were assessed to determine whether it constituted a PRO (i.e., health aspect reported by patients) or other outcome (i.e., no health aspects reported by patients). PROs were classified into a conceptual framework previously described in our protocol [37], based on the model from Valderas and Alonso [43] (which combines the model by Wilson and Cleary [44] and the International Classification of Functioning, Disability and Health (ICF) [45]), Patient-Reported Outcomes Measurement Information System (PROMIS) [46], and the Outcome-Based Healthcare Program in the Netherlands [47]. PROs were conceptualized (i.e., describing the content of each PRO in detail) using information from the focus groups and interviews. The assessment of the themes, and the classification and conceptualization of the PROs was performed together with two PROM experts (CT, HvO) and one (G)ID expert (LM) (See Acknowledgements).

Results

Participants

In total, seven adolescents (seven interviews) and 10 adults with (G)ID (two focus groups and four interviews), 12 caregivers (three focus groups and two interviews), 13 HCPs (three focus groups), and nine European patient representatives (two focus groups) participated. Table 1 shows the sociodemographic characteristics of the participants. The participant flowchart of the focus groups and interviews is described in Additional file 1.

Table 1.

Sociodemographic characteristics

Individuals with (G)ID (n = 17)
Adolescents (n = 7)
	Mean (range)
Age	14.8 (13–17)
	Frequency
Gender (female) a	4
Genetic diagnosis
16p11.2 deletion syndrome	3
22q11.2 deletion syndrome	1
Menke-Hennekam syndrome	1
Primrose syndrome	1
4q deletion syndrome	1
Unknown	0
Intellectual functioning
Borderline	0
Mild IDb	5
Moderate IDb	2
Adults (n = 10)
	Mean (range)
Age	30.8 (20–50)
	Frequency
Gender (female) a	5
Genetic diagnosis
Unknown	6
Rubinstein-Taybi syndrome	2
Peters plus syndrome	1
Wiedemann-Steiner syndrome	1
Intellectual functioning
Borderline	3
Mild IDb	6
Moderate IDb	1
Caregivers (n = 12)
	Mean (range)
Age child	20.2 (6–37)
	Frequency
Gender child (female) a	4
Genetic diagnosis
22.q11.2 deletion syndrome	2
Cornelia de Lange syndrome	2
Unknown	2
Fragile X syndrome	1
Tuberous sclerosis complex	1
Pitt-Hopkins syndrome	1
SLC6A1 syndrome	1
Wiedemann-Steiner syndrome	1
Rubinstein-Taybi syndrome	1
Intellectual functioning child
Borderline	0
Mild IDb	5
Moderate IDb	4
Severe IDb	2
Profound IDb	1
Clinical experts (n = 22)
HCPs (n = 13)
	Frequency
Profession
Psychologist	4
Other paramedic (e.g., dietician)	3
Pediatrician	2
ID physician	2
Nurse	1
European patient representatives (n = 9)
	Frequency
Country
Ireland	3
Romania	1
Serbia	1
Italy	1
UK	1
France	1
Belgium	1

ID Intellectual disabilities, (G)ID (Genetic) intellectual disabilities, HCPs Healthcare professionals

^aNone of the individuals with (G)ID identified as a gender other than male or female

^bBased on the classification of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) [1]

Focus groups and interviews

Focus groups and interviews were conducted between January 2023 and July 2023. Part 1 explored the impact of (G)ID on daily life to help participants identify relevant consultation themes for part 2. For that reason, themes from part 1 are aggregated across all participant groups. HCPs and European patient representatives are merged into one participant group; clinical experts. Predominant themes from part 2 are described per participant group and health domain. All themes are described in Table 2.

Table 2.

Main themes emerging from the focus groups and interviews

PROs are written in bold. Overlap: themes mentioned as impact of (G)ID and as important to discuss by one of the participant groups

(G)ID (Genetic) Intellectual disabilities, HCP Healthcare professional, STIs Sexually transmitted infections, ADHD Attention-deficit hyperactivity disorder, ID Intellectual disabilities

¹Theme mentioned once

Part 1 - Impact of (G)ID on daily life

Participants emphasized that (G)ID could impact various health domains both positively and negatively. Examples of predominant themes are described below.

Positive impact

Participants reported that (G)ID could have a positive impact on different health domains, including mental functioning (e.g., positive attitude) and social functioning (e.g., connecting with others). Other reported themes included strong social support for the affected individual and their family, as well as effective expectation management and adjustment by the environment of the affected individual.

Negative impact

Participants reported that (G)ID had a negative impact on all health domains, including physical functioning (e.g., performing activities), mental functioning (e.g., sensory integration), and social functioning (e.g., social skills). Other commonly reported themes were impact on family well-being and not feeling understood or heard by the HCP (both from the perspective of individuals with (G)ID and caregivers).

Part 2 – Wish to discuss with a HCP

Participants highlighted the importance of discussing themes across all health domains (physical, mental, and social functioning) with a HCP. The most frequently mentioned themes are described below.

Individuals with (G)ID

Physical functioning

Individuals with (G)ID frequently indicated that fatigue was an important topic to discuss. Individuals reported feeling easily tired, both physically and cognitively, and frequently experienced daytime fatigue. Pain, such as knee pain or headache, was also often deemed important for discussion.

“I need to consider all activities I am involved in. For instance, when I have a sports game, I must rest the day before and also allow myself a few days for recovery.” [Focus group 5 – January 30, 2024].

Mental functioning

 Individuals with (G)ID predominantly emphasized the importance of discussing mental functioning during consultation. Anxiety frequently emerged as a significant topic to discuss during consultation. Individuals often experienced feelings of panic, stress, nervousness, restlessness, and tension. Individuals also highlighted anger, sensory integration, and their own behaviour such as aggressiveness, as crucial topics to address with a HCP.

“I would like to discuss with a healthcare professional how I can calm down when I am feeling anxious.” [Interview – February 23, 2023].

Social functioning

Difficulties with engaging in and sustaining relationships was frequently mentioned as an important topic by individuals with (G)ID. These relationships encompassed connecting with friends, family, and, in the case of older participants, with a romantic partner. Individuals often experienced a lack of relationships, and felt neglected by friends or family. They faced challenges in trusting others, which consequently detained them from pursuing relationships despite their desire for companionship.

“I would appreciate it when the doctor would carefully ask about my relationships. This way, I do not have to start the conversation, as it is a difficult topic for me.” [Interview – January 19, 2023].

Other

Another topic brought up was communication with HCPs. Individuals with (G)ID reported to feel ignored or not treated as equals by HCPs. Individuals often felt that HCPs assumed they would not understand the information discussed, leading to a preference for communicating with their caregivers instead of directly with them.

“When I am with my caregiver at the doctor’s office, the doctor only talks to my caregiver. I find that so upsetting.” [Focus group 6 – February 7, 2023].

Caregivers

Physical functioning

Epilepsy was reported by caregivers as a significant concern, highlighting the need for guidance on managing seizures and understanding the efficacy and potential side-effects of anti-epileptic drugs. Sexual functioning was notably emphasized by caregivers of adolescents or young adults with (G)ID, who sought information and advice of HCPs on addressing sexual development and inappropriate sexual behaviours, such as masturbating in public.

“He turned out to have small seizures that where invisible from the outside but had a significant impact on his behaviour.”[Focus group 4 – January 23, 2023].

Mental functioning

Caregivers predominantly emphasized the importance of discussing mental functioning during consultation. Behavioural problems and anxiety were for caregivers critical topics for discussion. Many caregivers perceived behavioural problems as the primary burden affecting the entire family. They mainly reported externalizing behaviour, such as annoying others, being aggressive (e.g., screaming, hitting, kicking, pulling hair, biting or throwing things), and self-mutilation. Anxiety was also frequently mentioned, with caregivers emphasizing the difficulty of addressing this issue with their child.

“I wish more attention had been given to behavioural problems. How could I have best helped my child at that time?” [Focus group 4 – January 23, 2023].

Social functioning

Relationships and participation were both mentioned as important topics. Caregivers noted that their child encountered challenges in maintaining relationships (with peers), expressed fear of connecting with others, and at times exhibited a lack of interest in forming relationships. Participating in activities was also a topic of concern, as this needed more supervision, or affected individuals lacked adequate social skills or motivation to actively engage in activities with others.

“He’s not permitted to play soccer with his peers because he does not understand the game. As a mother, that hurts me. I would like to discuss with the HCP how to address this situation.” [Focus group 7 – February 9, 2023].

Other

Caregivers highlighted communication with HCPs as crucial, often feeling unheard, dismissed, or misunderstood. They also emphasized the importance of discussing the impact of (G)ID on the family, reporting that they sometimes felt overlooked by HCPs. Caregivers noted the constant need to adjust to the affected individual’s needs. They also reported feeling stressed due to uncertainties surrounding the disorder, concerns about the future of their child, and frequent hospital visits. They noted that siblings were affected as well, frequently feeling overshadowed by the child with (G)ID.

“What is very important to me is that parents are taken seriously” [Focus group 1 – January 10, 2023].

Clinical experts

Physical functioning

Clinical experts identified sleep as an important topic for discussion, noting that individuals with (G)ID often experienced difficulties falling asleep and sleeping through the night, early awakening, disrupted sleep patterns, restless sleep, and sleep apnoea. Epilepsy was also highlighted as a critical topic.

“For instance, if there are issues during the bedtime routine, we can consider how to provide support and make the bedtime routine as clear as possible.” [Focus group 8 – February 21, 2023].

Mental functioning

Mental functioning was most frequently mentioned by clinical experts, even though they did emphasize the importance of discussing all health domains during consultation. Behaviour was mentioned as an important topic to discuss. Clinical experts reported that individuals with (G)ID often exhibited externalizing behaviour such as aggression, claiming behaviour towards their caregiver or peers, self-mutilation, manipulative behaviour, repetitive behaviour, hyperactivity, impulsivity, impatience, and abnormal eating and drinking behaviour. Internalizing behaviour, such as withdrawal or passivity, was reported as well. Clinical experts also emphasized the importance of addressing anxiety during consultation. They mentioned various types of anxiety, such as fear of sleep, separation anxiety, medical anxiety, or social anxiety.

“I often see patients with challenging behaviour, so this is always an important topic to address.” [Focus group 8 – February 21, 2023].

Social functioning

Clinical experts mentioned participation as an important topic for discussion, noting that affected individuals often face participation limitations, leading to isolation. They particularly expressed concern for adults, who may not receive the same encouragement from caregivers as children do. Relationships were also highlighted as an important topic to discuss, with individuals often experiencing difficulties establishing and maintaining them.

“Numerous activities revolve around children, yet when a 40-year-old man is not coming out of his apartment, people tend to care less.” [Focus group 2 – January 12, 2023].

Other

Impact on the family was also reported as an important topic for discussion. They pointed out that family members adjust to the child with (G)ID, sometimes resulting in challenging family dynamics. Parents often experience fatigue, struggle to accept their child’s condition and its consequences, feel a sense of helplessness, endure a constant state of mourning, perceive a lack of understanding from others, and persistently worry about their child’s future.

“I believe that the greatest impact of (G)ID is on the family. Therefore, we always need to consider how to support the family.” [Focus group 9 – May 30, 2023].

Classifying PROs into a conceptual framework

All themes were assessed to determine whether they were PROs (e.g., anxiety) or other outcomes (e.g., communication with HCP) [48]. In total, 24 unique PROs remained, which were classified into the conceptual framework (Table 3). Information from the focus groups and interviews was used to provide a conceptualization of the PROs within the conceptual framework (Additional file 2).

Table 3.

PROs classified into the conceptual framework

	PRO domain	PRO subdomain
Overarching	Quality of lifea
	1. Perceived health
Functioning	2. Physical functioning/activities	3. Mobility
		4. Self-care
	5. Social functioning/participation	6. Relationships
		7. Participation
	8. Mental functioning	9. Anxiety
		10. Depressive symptoms
		11. Anger
		12. Sensory integration
	13. Cognitive functioning
	14. Communication
	15. Sexual functioning
Symptoms	16. Fatigue
	17. Pain
	18. Sleep
	19. Vision
	20. Hearing
	21. Respiratory symptoms
	22. Chewing and swallowing
	23. Itch
	24. Gastrointestinal symptoms

^a Part of the overall conceptual framework but was not mentioned as a PRO in the focus groups or interviews

Discussion

In this study, relevant PROs were identified for individuals with (G)ID from the perspective of individuals with (G)ID, caregivers, HCPs and European patient representatives (collectively called clinical experts). Together with two scoping reviews [35], this lays a thorough foundation for development of a meaningful PRO set for (G)ID, aiming to harmonize PROs and guiding care, research, and health policy. This meaningful PRO set enables the integration of patient perspectives on their health into care and research studies, and allows for relevant PROs to be combined and compared across (G)ID groups. Identified PROs were related to all health domains, including physical, mental, and social functioning. Themes related to the negative impact of (G)ID were deemed important for discussion during consultation, whereas themes related to the positive impact of (G)ID were generally not.

While individuals with (G)ID and caregivers mostly emphasized mental functioning, clinical experts faced challenges in prioritizing health domains. Nevertheless, all groups acknowledged the importance of addressing mental functioning, in particular anxiety. This is in line with previous studies in which individuals with (G)ID and caregivers stress the importance of addressing mental health problems in care [23, 49, 50], and underscores the ongoing need for research and intervention development in this field [51, 52]. Still, many individuals with (G)ID face challenges in receiving suitable and accessible mental health care due to fragmented ID and mental health services, and a lack of knowledge on how to adapt mental health treatments for those with (G)ID, often resulting in undiagnosed and untreated mental health problems [53, 54].

A PRO particularly addressed by caregivers of adolescents, was sexual functioning. These caregivers sought information and advice from HCPs on addressing their child’s sexual development and sexual inappropriate behaviours. While clinical experts acknowledged the importance of sexual functioning, affected individuals did not, possibly due to the difficulty of discussing it in a focus group or interview. Previous research found that affected individuals often lack knowledge about sexuality, with often limited opportunity for sexual expression and development, increasing their vulnerability to sexual abuse, sexually transmitted diseases, or unwanted pregnancies [55]. Addressing sexual functioning in care may be a crucial first step towards raising awareness and supporting the sexuality of individuals with (G)ID.

Important themes - but no PROs

While numerous important themes emerged, not all of them classified as PROs, as they did not represent health aspects reported by patients (See Table 2) [48]. One of those themes was behaviour, which was often mentioned by both clinical experts and caregivers as a critical topic. Previous studies showed that behavioural problems can significantly impact the individual and the whole family, leading to, for instance, increased stress levels among parents [56, 57]. Although important, behavioural problems are manifestations of underlying health issues, such as anxiety or pain, and should therefore not be classified as a PRO. Moreover, behaviour is generally reported by someone other than the patient (e.g., caregiver) [58].

Another key theme was the impact of (G)ID on the family, primarily mentioned by caregivers and clinical experts. Caregivers often felt overlooked by HCPs, despite the burden of living with and caring for an individual with (G)ID. Previous research indicated that psychological support for parents can improve their mental health, as well as their child’s functioning [59], underscoring the importance of family-centred care. However, the impact on family functioning should not be classified as a PRO, as it does not pertain to the affected individual’s health. Additionally, the impact specifically on parents/caregivers should be classified as a parent reported outcome (ParRO) (or caregiver reported outcome), as it pertains to the health of the parent/caregiver [60].

Both individuals with (G)ID and caregivers emphasized communication with the HCP as crucial, which is a process outcome. They often felt ignored or unheard by HCPs, underscoring the need for discussing PROs with affected individuals or their caregivers during consultations and involving them in healthcare decision-making. This theme pertains to the overall care experience of individuals with (G)ID and their caregivers, and therefore does not classify as PRO [61].

Although these themes did not meet the criteria for PROs, this does not diminish their importance. These outcomes should be considered in the development of a full core outcome set. This core outcome set should include all outcomes relevant to individuals with (G)ID, not only PROs.

Interestingly, participants emphasized specific themes with a negative impact on daily life, while aspects with a positive impact were not considered important to discuss with a HCP. Although (G)ID care often focusses on the strengths and abilities of affected individuals, this finding suggest that discussing aspects with a positive impact during consultations may not be as essential. Additionally, there is insufficient research indicating that patients want to discuss positive health aspects, and measuring this preference in care and research remains difficult [62].

The significance of relevant PROs – towards a meaningful PRO set

Identifying relevant PROs for (G)ID is one of the important first steps towards developing a meaningful PRO set, which can influence care, research, and policymaking to better address the needs of affected individuals. These PROs can guide the development of clinical guidelines and care pathways in- and outside of hospitals, promoting patient-centred care. They also help identify research priorities and treatment targets to ensure relevance to individuals with (G)ID. Additionally, these PROs can inform policy development, ensuring that healthcare policies are tailored to the specific needs of this population.

Strengths and limitations

A strength of this study is its broad sample, incorporating perspectives of affected individuals, caregivers, HCPs, and European patient representatives. Identifying shared PROs and other themes across different conditions enables grouping of these conditions, resulting in more efficient care and research. Another innovative and crucial aspect of the current study is that identified themes were assessed on whether it constituted PROs or other outcomes. PROs were classified and conceptualized into a novel framework, which led to a well-defined set of relevant PROs for the complex patient population with (G)ID, serving as a systematic and solid foundation for future studies.

An important, but inherent, limitation of this study is the bias in age and level of intellectual functioning of participants. Only adolescents and adults with borderline to moderate ID were included in the focus groups and interviews. The perspective of children up to 12 years and affected individuals with severe or profound ID had to be represented by their caregivers, HCPs, and European patient representatives. Moreover, the affected individuals and caregivers who participated may have been more assertive and proactive (and, in the case of caregivers, more highly educated), which potentially leads to a bias, as they not fully represent the broader (G)ID population. Furthermore, although the study sample includes different perspectives, it represents only a small subset of the more than 1500 genetic IDs, and comprises only a small group of Dutch-speaking individuals with (G)ID. Therefore, the generalizability of the study to the whole (G)ID population should be carefully considered. A key next step will be to validate the identified PROs in a larger, more diverse international cohort. This study is also limited by the lack of information on age- or condition-specific PROs. Although this study primarily aimed to identify generic PROs relevant to the whole (G)ID population, future studies should focus on age- or condition-specific PROs to provide additional insights. For instance, loss of hand function is common in Rett syndrome [63], making the PRO ‘upper extremity functioning’ potentially relevant for this specific condition. In addition, certain PROs may be more relevant at specific life stages. For instance, sexual functioning may be of greater significance during adolescence and adulthood than in childhood [23].

Conclusions

This study offers important insights into relevant PROs for individuals with (G)ID and represents one of the first steps towards developing a meaningful PRO set for this population. The results highlight the importance of addressing PROs concerning mental, physical, and social functioning, with a particular emphasis on mental health problems. The next step involves integrating these PROs with those found in the literature, prioritizing them, and establishing a meaningful PRO set [37]. This set will guide care, research, policymaking, and the development of a PROM set for (G)ID. Ultimately, the set of PROMs will facilitate the ability to aggregate and compare the most relevant PROs in both care and research, ensuring the inclusion of the perspectives of the vulnerable patient population with (G)ID.

Abbreviations

ID

Intellectual disabilities

(G)ID

(Genetic) Intellectual disabilities

ADHD

Attention-deficit hyperactivity disorder

TSC

Tuberous Sclerosis Complex

PROs

Patient reported outcomes

PROMs

Patient reported outcome measures

CHQ

Child Health Questionnaire

HCPs

Healthcare professionals

COREQ

Consolidated criteria for reporting qualitative studies

COS(s)

Core outcome sets

ERN-ITHACA

European Reference Network on Intellectual Disability, TeleHealth, Autism and Congenital Anomalies

ICF

International Classification of Functioning, Disability and Health

PROMIS

Patient-Reported Outcomes Measurement Information System

ParRO

Parent reported outcome

Authors’ contributions

The study was designed by NvS, MvM, AvE, and LH. Focus groups and interviews were prepared and conducted by NvS and MvM. Data were analysed by NvS and MvM. The first draft of the manuscript was written by NvS. MvM, CvK, LH, and AvE provided important revisions on the manuscript. All authors read and approved the final manuscript.

Funding 

This study was funded by the ForWis(h)dom foundation and ‘s Heeren Loo. They had no role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript.

Data availability

The data used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The Medical Ethics Review Committee of the Amsterdam UMC declared that the Medical Research Involving Human Subjects Act (WMO) does not apply to this study and that a formal ethical approval was not necessary (W22_345 # 22.413). All participants provided written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.