“It didn’t feel like anything unusual because we had already been through so much”: Disability-Related Research Experiences of Families with Children Enrolled in the Undiagnosed Diseases Network

Abstract

Purpose:

In recent years, researchers have brought attention to the underrepresentation of people with disabilities in biomedical research, including genomics research. However, little is known about how disability-related experiences influence participation in rare disease research. This omission is striking, because rare diseases are associated with disabling phenotypes that affect multiple body systems. As part of a study interrogating the relationship between rare disease status and disability identity, we conducted mixed-methods research to address this knowledge gap.

Methods:

Parents of children enrolled in the UDN (n=25) completed semi-structured interviews to assess disability-related experiences in research participation. Directed content analysis was used to identify common themes.

Results:

Participants’ disability-related research experiences were characterized by: 1) disability-related facilitators to research participation, including benefits of research participation and disability-conscious approaches; 2) disability-related logistical barriers to research participation; and 3) research procedures, and the perception of research as minimally burdensome relative to clinical encounters.

Conclusion:

Parents of children in the UDN make considerable investments of time and resources to accommodate their children’s disabilities to facilitate their participation. Future research should explore these issues in other genomic research studies and practical approaches to mitigating barriers and employing facilitators to disability-related research participation.

Introduction

Approximately 61 million Americans and a billion people worldwide live with a disability affecting one or more major life activities.^{1, 2} In recent years, amidst recognition of the health disparities disability communities confront, researchers have brought attention to the underrepresentation of people with disabilities in genomics research.

Approximately 30 million Americans live with rare diseases, defined as conditions affecting less than 200,000 people in the United States.^{3, 4} Rare diseases are associated with disabling phenotypes that affect multiple body systems. Many individuals with rare diseases have symptoms present in childhood.⁵ These individuals and their families spend an average of five years seeking a diagnosis, a process called the “diagnostic odyssey.”^{6, 7} Research advances in genomics over the last decade increasingly offer individuals with a range of rare conditions a path to diagnosis through advanced genetic testing and comprehensive clinical evaluation. However, little is known about how disability-related experiences influence participation in rare disease research.

As part of a study interrogating the relationship between rare disease status and disability identity, we conducted qualitative research to address this knowledge gap. We define a “disability-related research experience” as any lived experience of disability that directly or indirectly influences an individual’s participation.

Previous work has described several challenges for participation of individuals with disabilities in research. In a national survey of people with disabilities, Maya Sabatello et al. find that a combination of lack of trust and concerns over disability accommodations can create barriers to the participation of disability communities in genomics research.⁸ Notably, Sabatello et al. recruited individuals with disabilities who were not already enrolled in genomics research. Further, a recent report by the NIH’s INCLUDE Project specifically highlighted that parents of individuals with Down syndrome expressed concern over accessibility of study procedures given their child’s cognitive limitations.⁹ The report also recommended that logistical burdens like travel to study sites be minimized in order to promote disability access to clinical trials for Down syndrome.

Exploring whether similar disability-related concerns exist for individuals with rare/undiagnosed diseases and their families is important given the wide range of disabling rare disease phenotypes and the significant burdens these individuals and their families confront in the management of their conditions.¹⁰ Accordingly, this study investigates how the range of disabling phenotypes associated with rare/undiagnosed diseases influences genomic study research participation.

Materials and Methods

Using an interpretivist research paradigm, we conducted qualitative research, including semi-structured interviews of parents of pediatric participants enrolled in the Undiagnosed Diseases Network (UDN).¹¹ Our multidisciplinary expertise allowed the data to be analyzed from multiple lenses, encompassing disability studies, ethics and medical genetics. The research team is composed of bioethicists and ELSI researchers with extensive expertise in qualitative research and rare disease genomic research. In addition, the research team includes members who work with disabled research participants, are parents of a child with a disability or rare disease or have a disability themselves. Research team members also include investigators in the Undiagnosed Disease Network and an emeritus board member of the UDN Foundation.

The UDN is a national multi-site study that uses a multidisciplinary, team-based approach, including tools only available in the research context, to advance scientific understanding of the causes of rare diseases by attempting to identify a diagnosis for participants.¹² Consequently, it offers a valuable opportunity to examine disability-related research experiences because participants have a wide range of disabilities. Applicants to the UDN must be referred by a clinician and provide extensive medical records. If accepted, participants may travel to one of the UDN’s 22 clinical sites across the country to undergo diagnostic evaluations. As of 2025, 3,400+ participants have undergone evaluation with 30% receiving diagnoses.¹³

For the purposes of this study, a disability is defined as any health condition that limits an individual’s ability to perform one or more major life activities. We define disability-related research experiences as any lived experience of disability that directly or indirectly influences an individual’s research participation. This study focused on parents of pediatric participants because we wanted to understand how disability status and rare disease status interact with each other in children.

Individuals were eligible for this interview study if they: 1) self-identified as a primary caregiver of a UDN participant aged 2–17; 2) previously provided consent to be recontacted for future studies in the UDN; and 3) were able to read/speak English. Participants were recruited using recruitment emails to eligible caregivers distributed by UDN staff and the study team, as well as posts to the closed Facebook group for currently enrolled UDN participants and their family members. E.N.A. administered a screening survey to each individual via telephone. Parents were invited to complete two sequential semi-structured interviews of approximately one hour each and an online demographic survey. Interviews were conducted remotely via Zoom from November 2022 through June 2023.

The interview guides focused on: 1) parental views about whether their children had disabilities and 2) how parents understood the impact of those disabilities in various domains, including access to clinical care along the diagnostic odyssey, participation in the UDN, and access to disability services. Interview guides were developed using data and perspectives from published literature on disability inclusion in research participation and related topics.^{8, 14, 15} These guides are available as supplementary materials.

Little data exist on the functional limitations of rare disease research participants. Accordingly, the Child Functioning Module (CFM), a validated instrument developed by the World Health Organization to measure the extent of a child’s functional limitations, was administered in the first interview.¹⁶

Interview guides were pilot tested with three individuals. Based on pilot testing, the procedure for administering the CFM was modified so that participants could see an electronic version of the questions and the possible responses to minimize the burden of participants having to remember the standardized response choices. K.T.M. and E.N.A. conducted all interviews. Interviews were audio-recorded, transcribed verbatim, and de-identified. Individual responses to the CFM were recorded in a REDCap database.^{17, 18}

All study procedures were approved by the Stanford University School of Medicine Institutional Review Board under Protocol #65488. All participants provided informed consent.

Analysis

We analyzed interview transcripts using the software Dedoose.¹⁹ Using directed content analysis,²⁰ research team members (K.T.M., E.N.A., M.K.C., H.K.T.) developed a set of deductive codes based on the domains and questions in the interview guides. Emergent codes were added after team discussion, based on patterns in participants’ responses around disability advocacy and stigma. This paper presents findings based on the deductively-derived codes related to UDN research participation. Data from the emergent codes will be presented in a separate paper on the relationship between rare disease identity and disability identity. Two team members (K.T.M. E.N.A.) independently coded each interview transcript, meeting regularly to resolve discrepancies, with another team member (H.K.T.) resolving any disagreements. The coded excerpts were reviewed by the research team to identify themes associated with disability-related UDN experiences.

Results

Participant Characteristics

A total of 33 individuals met inclusion criteria upon screening. However, one individual declined participation after screening, five individuals did not schedule a first interview after screening and two participants withdrew from the study after the first interview. The remaining 25 participants, all of whom completed at least one interview, were included in the analysis.

Most participants were mothers of children enrolled in the UDN (n=24 participants, 96%, Table 1). Three participants reported receiving a diagnosis from the UDN at the time of the interview. Most participants (n=21, 84%) had private health insurance. About half of participants were seen at the Stanford UDN site while the remaining half were seen across six other UDN sites (Vanderbilt, NIH, Duke, Harvard, Baylor, and Seattle Children’s). Most participants identified as non-Hispanic White, reflecting the demographic patterns of the UDN study population as a whole.²¹

Table 1.

Participants’ Demographics

	# of Participantsa
Gender
Female	20
Male	1
Missing	4
Age, Years
18 to 24	0
25 to 34	1
35 to 44	9
45 to 64	11
>64	0
Missing	4
Child Age, Years
<4	1
5-12	9
12-17	12
Missing	4
Race
White	19
Asian	1
Black or African American	0
Two or More Races	0
Unreported	1
Missing	4
Hispanic/Latino (Ethnicity)
Yes	3
No	18
Missing	4
Household Income
Less than $25,000	0
$25,001 to $50,000	1
$50,001 to $100,000	5
$100,001 to $150,000	4
$150,001 to $200,000	5
>$200,000	5
Prefer not to answer	1
Missing	4
# of People in the Household
2	1
3	7
4	6
5	4
6	3
Missing	4
# of Children
1	6
2	6
3	7
4	2
Missing	4
Highest Level of Education
Some high school	0
High school diploma	1
Some college	2
Associate’s	1
Bachelor’s	8
Advanced degree	9
Missing	4
Relationship to Child
Mother	21
Missing	4
Marital Status
Married/in a domestic partnership	19
Widowed	0
Divorced/separated	2
Never married	0
Missing	4
Employment Status
Full-time	10
Part-time	3
I’m not currently employed outside the home	8
Missing	4
Health Insurance Type
Medicaid	0
Medicare	0
Private	21
Military	0
Uninsured	0
Other	0
Missing	4
Child’s Health Insurance b
Medicaid	11
Medicare	0
Private	20
Military	0
Uninsured	0
Other	1
Missing	4
Diagnosis Received?
Yes	5
No	15
Tentative/Pending	1
I don’t know/Not sure	0
Missing	4

^a21 of 25 participants provided the demographic information in Table 1

^bNote that some participants have more than one type of insurance

Participants in our study described caring for children with a variety of disabilities that impact their functioning in multiple ways (Table 2). The most common functional limitations reported were mobility (84.6%), coping with change (84.6%), and communication (84.6%), followed closely by self-care (80.77%) and emotions (80.77%). All participants reported their children have functional limitations in multiple domains (minimum domains n=4, maximum n=11).

Table 2.

The Range of Functional Limitations Among Participant’s Children

	CFM
Domain	At least “some difficulty” a
	N (N=26)	%
Visual	11	42.31
Hearing	4	15.38
Mobility	22	84.60
Communication	22	84.60
Behavior	17	65.38
Learning	20	76.92
Dexterity	1	0.04
Playing	1	0.04
Self-care	21	80.77
Remembering	18	69.23
Concentrating	11	42.31
Coping with change	22	84.60
Relationships	19	73.08
Domain	At least “monthly”
Emotionsb	21	80.77

^aTwo participants answered “Don’t Know” during the survey. The first for Vision and Hearing, the second for Remembering.

^bWe display the number of participants that reported their children had at least “some” difficulty in all domains using the “no difficulty” to “cannot do at all” scale. For emotions, we display the number of participants who reported that their children appeared anxious or depressed monthly, weekly, or daily.

Themes

Three main themes were identified: 1) disability-related facilitators to research participation; 2) disability-related logistical barriers to research participation; and 3) perception of research burden relative to clinical encounters. Tables 3, 4, and 5 include additional quotes supporting each theme.

Table 3.

Facilitators to Research Participation

Benefits of research participation
The possibility of finding a diagnosis	P0032: Yeah, so I was excited! I thought oh this is great, somebody’s going to dedicate their time and energy to figuring out what is wrong with our child. So we tried not to get our hopes up, but yet any little bit…you know, at that time she was seven, I think, so we’d got seven years without a diagnosis. P0017: …I don’t know if it’s based in reality but I feel like [laughter] being a part of some larger network funded by, you know, the [UDN site] gives me a little bit more hope of like, okay, maybe people are sharing information and that really will increase the odds of us getting an answer.
Affirmation	P0004: I don’t know, you almost kind of feel crazy sometimes. And I know looking back, like once we got the diagnosis we were happy getting that diagnosis, but then like this kind of reality set in and it’s like wait, like we’re happy because she’s got this life long illness that she has to deal with, too. But for us, like I don’t know, it was just so hard coming from where we started and not being taken seriously to like being validated and then going a step further and like really solving the mystery behind everything. Just so many mixed feelings, really. P0029: And then overall, just to mention again, I felt like the attitude of the people that we interacted with was just really affirming to us and, you know, like we’re not crazy and, you know, they like truly were dedicated to what they were doing, so yeah, it was a good experience.
Communitiesof support	P0009: I am thrilled to know that even if we don’t [find] answers with [child’s name], that the next [child’s name] that comes around might because her information is out there. P0034: I think the surprising part for me of joining the UDN was I found their Facebook group, and just being able to communicate or see other peoples’ stories that they go through, either more horrific things than I do, or just different things, that was kind of surprising. I think it was nice to find that there is a community out there that can give you support because, you know, nobody else around, around here, around us, has any clue what it’s like to have a child that has a lot of issues and things going on where there’s not a diagnosis.
Altruism/helping other families	P0021: So if sharing [name]’s story can help just one family, you know, get a diagnosis or find a treatment, or find some answers for their child, then that makes me really happy. P0030: And then another thing that’s really important to our family is future research, so that was our other, you know, goal with this was what can we do to help future families, and so being part of the UDN and helping, you know, in any way to build up the database for medically complex families, we thought that was really important.
Partnerships in the diagnostic odyssey
Relationship with UDN	P0026: So I think it’s been a good approach as far as what we’ve experienced for her, and I feel like, you know, we’ve been made to feel like we’re not just a number in a case study or in a research study, she’s an actual person and patient that has needs and family and, you know, I think too often that can happen in research, and I’m glad the UDN has been supportive the way they have. P0029: I remember just like being there the first couple days and just being like this is exactly where we need to be. Like just the way they treated [child’s name], they spoke about it, the way they like didn’t dismiss anything, you know, were like really eager to get as much information from my husband and I as possible, and you know, even when I went in there with my like, my own research [laughter], they were like oh this is great! You know, they were just lovely, and yeah, I think it’s a great place.
Disability-conscious approaches
Holistic	P0007: I really like the UDN’s approach compared to everybody else because I feel like all these other providers, you know, they’re there the 15 minutes that they see [name], if that, you know, they take a look at her and if the question…if the diagnosis doesn’t pop into their head right away while looking at her or maybe just reviewing her chart a little bit, then that’s where they’ll end… versus the UDN, you know, they don’t have the answers so they’ll really do a lot of in depth digging…they’re like a giant detective that just looks at every single clue. P0029: I think what we appreciated most, or one of the things we appreciated most about the UDN, was the integrated approach. I think something that has been challenging for us is having to go see like 12 different specialists multiple times a year, so that’s just a ton of appointments and, you know, rehashing his story in a slightly different context, and…so we really appreciated how the UDN, it felt more integrated and like they were talking to each other, the specialists are talking to each other, and trying to kind of like put the whole picture together.
Research accommodations	P0009: the UDN staff and everybody was fantastic, totally understanding of what [name]’s needs were and accommodations… always asking, you know, will this time work or, what’s the best way to do this with her, what is her tolerance for waiting, and just I felt like just doing everything possible to make it as easy of a trip as possible for us. P0025: They ask me before we went, we were accepted, before we went they ask me, okay, we are…you’re going to a hotel, do you need a wheelchair, do you need a special access to a room, do you have a special diet, those things they ask me before we went.

Table 4.

Disability-related Logistical Barriers to Research Participation

Medical documentation	P0006: Oh, so once we were accepted to the UDN they said we had an option of I could collect all the records and send them to the UDN, or there was this new company called PicnicHealth that would do it all for me, and I was like oh that sounds lovely, we’ll have PicnicHealth do it all! And that turned out to be a yearlong nightmare of them not doing what they were supposed to do and not getting all the records every time. P0032: I mean, again, I don’t remember the process, but the hardest thing, like I said, is tracking down the records, so like if you could just get…I think once we got like our assignment, like you’re working with [physician] at [institution], and then they had like a neurological counselor, I guess, I don’t remember her exact role, but she helped coordinate everything. But prior to that it would have been nice to have like a personal coordinator to be like what do you need, what can I do. And I’d be like look, I can only, you know, call this hospital so many times, I don’t have time during the day to call ten different hospitals to track down these records. You know, and each hospital does it differently, and some you have to pay for and some you don’t, and some are faxed, some are hard copies, so that kind of stuff would be really helpful to have help with because we just don’t have time for that either.
Travel	P0006: … I realized flying with a person with a disability is a whole other level of planning. And so it was a fun, complicated experience, but I learned so much in the months preparing for the flight of like how do we do all of his feeding tube liquids, how do we do his chair, how do we do boarding, like how do we do all of this. And so it was very stressful even accessing all of the resources that the airlines have. P0032: The harder parts are always just waiting because, again, she’s in diapers, she’s on a specific diet, so being away from home, the fact we never stay in hotels with her and we had to stay in a hotel with her was very difficult.
Site visit schedule	P0009: Well we were there in the summer, and I’m sure that matters, but it would have been great…we asked people what is there to do on this campus at [institution]? You know, we had down time, and literally we asked tons of people and they were like we don’t know, nothing. And so that would be the only thing would be like if there was a better idea of like things that were around that area that we could have partook in… P0032: I mean I think they could have probably squeezed it all into one day so we wouldn’t have had to stay the night, that would have probably been ideal.
Research procedures	P0020: From an emotional standpoint she did great. From a physical standpoint it was very hard on her. I think the muscle biopsy took a lot out of her and, of all things, the swallow study because her gut is such a mess, it just sent her…she started vomiting and having seizures. But mentally she does okay. P0026: She wasn’t a fan, I’ll you that! [laughter] She did well, but for her, she doesn’t like to sit still so, you know, when we wanted her to sit still so we could zoom in on certain body parts and, you know, having her walk and things like that, she was getting frustrated, but you know, she was okay, but it definitely was not her favorite! [laughter]

Table 5.

Research burden relative to clinical encounters and/or daily life

P0024: I mean I think not too different from what his experience, his life experience, was up to that point. I mean he had to have an MRI so he had to have a poke because he was sedated. Of course he didn’t like that! [laughter] But beyond that, like I don’t think…it just…that was his normal. P0034: It definitely was because we had to…it was very odd to…because we were using our laptop so we had to angle it if they wanted to see her walk, they wanted to see like her gait, and then they wanted…you know, like raise your hand, like touch your nose, so again, some of the things she didn’t understand, which that happens in a typical doctor’s office anyway where she’ll just kind of look at me like what?

Facilitators of Research Participation

Benefits of Research Participation

Participants described a variety of benefits arising from their research participation. These benefits appeared to be facilitators of research participation because study participants were motivated by the possibility of gaining further insight into their child’s disabling undiagnosed condition. Some parents viewed the primary benefit of participation to be the possibility of finding a diagnosis.

And so here we were at 16 years old and getting a call, and there was just this feeling like we’re not alone, and we have people that want answers, and so just know I would say how appreciated that is. (P0009)

Other parents said a key benefit was receiving affirmation from UDN researchers about their child’s medical complexity.

Because they said we took your words to heart and we brought it back to the Board… and through that had a discussion about [child] and this variant, and we think you’re right… I’m sure I [wept], because it was the first time that somebody believed me. (P0024)

A subset of parents cited the opportunity to find communities of support, specifically to connect with families of other undiagnosed children, as a key benefit of participation.

…in some ways it is a community of a lot of misfits that we don’t know what’s going on with our children... there’s more hope even just to be like hey there’s some of us out there like this, and there’s people that want the best for us too… (P0002)

Combinations of individual and community-oriented benefits were consistently present in participants’ narratives. For example, in addition to finding a variant of concern, P0028 mentioned that one benefit of participation was being able to meet another family in the UDN whose child had the same “variant of concern”. They found the opportunity affirming.

…when I met that family and I watched our two children together, it made me realize that they look like siblings, their mannerisms were so similar… it made me feel in my gut that this is the variant of concern, and it is going to mean something. And now we know it is, so it was an amazing visit. It was amazing to talk to those parents and other siblings in the other family. (P0028)

They are the only participant who described meeting other families of similarly affected children through UDN participation.

Partnerships and Progress in the Diagnostic Odyssey

Participating parents expressed excitement, hope, and gratitude upon being accepted into the UDN. They often saw their acceptance into the project as a milestone in obtaining insight into a child’s undiagnosed condition after years of feeling dismissed or underserved by clinical care providers.

I was really grateful that we were accepted because it seemed to me like a win for us and for the original geneticist who thought there was something to it… that there was a genetic thing, whereas the second geneticist has all this skepticism… (P0033)

Most participants said that being accepted into the UDN made them feel less isolated or alone in supporting their child, in part because they felt that the UDN study and staff were partners in gaining new insight into a child’s undiagnosed condition.

…I’m in contact with our new geneticist probably like almost every month… We have a really good relationship with our nurse practitioner, so we’re really close with our team, and I really like that because they know a lot about [child], they’ve been through this journey with us, so it’s really nice to know that you’re not alone…that there are people with you that care about you. (P0021)

Disability-conscious Approaches

Participants described how several aspects of their research participation were sensitive to their child’s disabilities. The first aspect was the UDN’s approach to analyzing cases, which participants often understood as comprehensive or holistic.

I really like that [the UDN study staff] meet as a team. They do team case studies, whereas for us here, it was like the neurologist said this, they might communicate with the geneticist, but nobody sits down and says here’s everything, let’s look.…the whole team of geneticist[s], biologists, neurologists…they all sat down and discussed her case to determine what else might need to be done right now. (P0034)

This quote reflects how several participants framed the UDN’s approach as a welcome alternative to their experiences of the perceived fragmented nature of clinical care for a child with an undiagnosed disabling condition.

The second aspect participants praised was the availability of disability-related accommodations. According to several participants, some UDN researchers were aware of and sensitive to their children’s limitations and did an exemplary job accommodating them.

We were seeing a lot of providers one day, and we were taking a break out on a playground outside of the medical center, and the doctor just came out to the playground, and he said there’s no reason I can’t examine your kids right here. …and it was like oh my gosh, that’s amazing, thank you! Because just transitions are hard for us, so that was just a really gracious thing for that doctor to do. (P0019)

Examples of successful accommodations involved researchers, like the one described above, who participants perceived as skilled at working with disabled children. Participants also described practices, like maintaining eye contact with their children, that might not require specialized training in disability accommodations.

Disability-Related Logistical Barriers to Research Participation

Several participants described logistical barriers to participation. One mother with two children in the UDN reported that the process of obtaining necessary medical documentation was particularly burdensome and time-consuming.

Yeah, it was my husband and caregivers. I mean we’ve had an au pair living with us for the last 12 years, and other local caregivers that we bring in, and then when the kids are at school, trying to do all this, or after they’re asleep… just fitting it in when I can. (P0019)

Some participants also described how travel for UDN participation could be burdensome, especially for those whose children have difficulty flying, driving long distances, and/or adapting to changes in routine because of their conditions. For example, one parent described how their child experiences chronic pain that is exacerbated by travel and sleeping in non-orthopedic beds.

We made it, but [child]’s health made it… a barrier to get there… so far away from home with all of her medical conditions, and to stay for a week away from home… And the money was a barrier because they do offer some travel expenses, but not enough to cover everything that is needed… So those were barriers for us… (P0027)

Some participants described preferring either shorter clinical visits or longer visits, depending on the particular disability-related challenges their children confront. For example, another participant described how her child had difficulty with the rigorous schedule of their UDN site visit.

She wasn’t sleeping well while we were there so she had some additional seizures, so that was the main thing is she has… when she sleeps the right amount of hours she does very well, and having her sleep interrupted was tough… (P0030)

Beyond documentation, travel, and scheduling, some participants reported that their children faced difficulties related to the research procedures required to participate in the UDN. One parent said that their child has developed PTSD because of frequent hospital visits along the diagnostic odyssey, and that therefore similar clinical encounters frighten him. She felt that she and the team could have done more to support her child.

I think if [name] and I had had a more thorough conversation ahead of time of what accommodation [child] needed and why, I think he probably would have been able to figure out, okay, we should probably just do all of the testing at the [clinical care institution]’s labs there on site versus at the UDN site because… the pediatric people were just much better at getting all of that done for [child] because he is so complicated to get the labs. (P0006)

Relative Burden of Research Participation to Clinical Care

Several participants emphasized that the procedures their children completed in the UDN seemed no more burdensome than their experiences in clinical care. One parent saw her child as “a trooper” for having endured multiple surgeries at a young age. She described her UDN participation:

It was a little bit overwhelming and hard for a kid to go through being poked and prodded, which is kind of understandable for any child that was going through it, but I don’t remember really any unique challenges… at that point we had already been through so many doctor’s appointments and whatnot that it just kind of felt routine, it didn’t feel like anything unusual because we had already been through so much. (P0004)

Similarly, P0010 described how the blood draws her child underwent for research purposes did not seem burdensome compared to their routine clinical care.

Unfortunately, they were very normal for her. She gets blood work taken often. Urine samples can be hit or miss, but it wasn’t anything out of the ordinary for us. (P0010)

When describing the burdens of research participation in these terms, participants demonstrated determination and patience in providing disability-related support for their children. For example, P0026’s child had difficulty managing their anxiety and following directions while completing a physical exam over Zoom. P0026 saw this as “just part of who she is” and went on to explain how she helped her through the exam.

…well of course talk to her, support her, tell her it’s just for this moment, just take these few steps… show them your arm, that kind of thing, we talk to her through it, but we also will give her…something to kind of distract her from… what’s concerning her. (P0026)

Most parents in our study articulated a similar willingness to help their child complete study procedures and overcome any disability-related barriers in order to participate.

Discussion

Participants in this study were motivated to participate by potential individual and/or collective benefits. The opportunity to gain further insight into a child’s undiagnosed disabling condition and opportunities for altruism and community building appeared to be major facilitators of participation. Praise for the UDN’s team-based approach and disability-conscious approaches to their children’s research participation also contributed to participants’ positive attitudes towards the UDN. However, some participants reported logistical barriers to the research process because of their children’s multiple disabilities. Many participants emphasized that these barriers were minimal compared to the challenges they have confronted in raising a child with an undiagnosed disabling condition. These findings parallel Sabatello et al.’s findings related to genomics research more generally. People with disabilities are willing to participate in research they see as beneficial to themselves or others in their disability communities.

Previous literature has brought attention to how parents of children with undiagnosed disabling conditions use multiple means to gain insight into their children’s conditions and to find community.^{5, 22, 23, 24, 25} The UDN helps facilitate this sense of community through its Participant Engagement and Empowerment Resource (https://undiagnosed.hms.harvard.edu/resources/peer/) and the UDN Foundation.²⁶ The sense of partnership with the UDN that many participants expressed provides valuable opportunities for the UDN to build upon these infrastructures. One potential strategy based on our data would be to develop a standardized procedure for asking parents if they would like to connect with families whose children are found to share a diagnosis or variant of concern. This procedure could enable more families to have the affirming experience P0028 described. Beyond the UDN, these findings suggest that altruism and fostering a sense of community might be valuable facilitators for the participation of disability communities in genomics research. In clinical care contexts, similar opportunities for parents to meet other parents of children with genetic conditions are supported through the 2008 Prenatally and Postnatally Diagnosed Conditions Awareness Act.²⁷

The results describing disability-conscious approaches and disability-related logistical barriers to research suggest that researchers should design procedures that are sensitive to the ways in which rare disease status and disability status can compound each other. Universal Design, for example, is a framework intended to minimize the need for individualized disability accommodations by considering accessibility from the beginning of a design process.^{28, 29} The UDN’s disability-conscious approaches praised by some participants in our study (e.g., maintaining eye contact with a child, even if they have difficulties with communication) reflect procedures rooted in Universal Design that demonstrate some UDN team members’ individualized understandings of their participants’ disabilities. Similarly, building flexibility into travel requirements and scheduling by offering remote evaluations is one way that Universal Design would benefit many participants in our study, given that approximately 85% reported their children have difficulty coping with change (Table 2). Similar proposals have been made in other research contexts.^{8, 9, 15, 30} Future research might specifically explore how to institutionalize these kinds of practices, emphasizing approaches that are participant-centered and compatible with achieving study aims.

Individuals in this study face considerable barriers to research participation because of their children’s dual statuses as having rare diseases and disabilities, even while many of them see the barriers as minimally burdensome. This finding underscores Sabatello et al.’s research suggesting that promoting disability inclusion in genomics research requires understanding how disability status interacts with other forms of marginalization.^{31, 32}

Additionally, this study draws attention to the importance of integrating the perspectives of caregivers of individuals with disabilities in the research process, given their critical role in facilitating their loved one’s autonomy.^{33, 34} Previous studies exploring the role of caregivers in trials for brain-computer interfaces and cancer, for example, illustrate that caregivers play critical roles facilitating their loved ones’ research participation and often take on considerable burdens to do so.^{35, 36, 37, 38} Although some in our study have certain social advantages, such as robust social networks to help manage caregiving with other responsibilities, they still describe making sacrifices to facilitate their children’s research participation. Hiring paid caregivers to share care responsibilities while gathering extensive medical documentation or paying for travel expenses are two examples. The UDN and other studies should examine how to minimize these barriers as a means of making study participation easier for families and to help make research accessible to those who are unable to make those investments.^{39, 40} Minimizing these participation barriers in research can be particularly challenging given that they are indicative of broader structural barriers to community integration for those with disabilities. Nonetheless, these considerations are important for promoting the inclusion of people with disabilities in research because personal care and travel present additional financial cost to families caring for disabled individuals.

This study has several limitations. First, our sample is mostly comprised of privately insured, White, and highly educated mothers who had the resources to participate in the UDN and our study while caring for children with complex disabilities, and who had agreed to be recontacted for future studies. They also might be more likely to have had generally positive experiences with the UDN, and to value altruism as a benefit of research. Other studies including similar groups of UDN participants point to greater heterogeneity in individuals’ experiences.¹⁰ In addition, our study was limited to those who could complete interviews in English. Further, several individuals in the study reported having professional backgrounds in healthcare or disability services and therefore may have views more in line with disability rights than other UDN participants. Finally, four participants did not complete the demographic survey, which was administered after interviews were conducted. These factors may limit the generalizability of our results to other undiagnosed and/or disabled children and their parents.

Nonetheless, this study establishes preliminary findings on how living with disabilities resulting from rare/undiagnosed diseases can influence research participation. Follow-up studies should further interrogate these findings with a larger and more heterogeneous group of research participants, including adult patients. Future research should assess how the perspectives of researchers align with those of our participants.

Members of the Undiagnosed Diseases Network

Aaron Quinlan

Abdul Elkadri

Alan H. Beggs

Albert R. La Spada

Alden Huang

Aleksandra Foksinska

Alex Paul

Alistair Ward

Alyson Krokosky

Alyssa A. Tran

Andrea Gropman

Andres Vargas

Andrew B. Crouse

Andrew Stergachis

Anna Hurst

Anna Raper

Anne Slavotinek

Arian Nouraee

Arjun Tarakad

Ashley Andrews

Ashley McMinn

Ayuko Iverson

Barbara N. Pusey Swerdzewski

Ben Afzali

Ben Solomon

Beth A. Martin

Brandon M Wilk

Breanna Mitchell

Brendan C. Lanpher

Brendan H. Lee

Brent L. Fogel

Brett Bordini

Brett H. Graham

Bruce Gelb

Bruce R Korf

Camilo Toro

Cara Skraban

Carlos A. Bacino

Carlos Prada

Carson A. Smith

Cathy Shyr

Cecilia Esteves

Changrui Xiao

Charlotte Cunningham-Rundles

Chloe M. Reuter

Christine M. Eng

Christopher Mayhew

Chun-Hung Chan

Colleen E. Wahl

Corrine K. Welt

Cynthia J. Tifft

D Isum Ward

Dana Kiley

Dana Sayer

Daniel J. Rader

Daniel Wegner

Danny E. Miller

Daryl A. Scott

Dave Viskochil

David A. Sweetser

David Chiang

David R. Adams

Deborah Barbouth

Deepak A. Rao

Devin Oglesbee

Devon Bonner

Donald Basel

Donna Novacic

Dustin Baldridge

Elaine Seto

Elisabeth Rosenthal

Elizabeth A Worthey

Elizabeth A. Burke

Elizabeth Blue

Elizabeth C. Chao

Elizabeth Wohler

Ellen F. Macnamara

Elsa Balton

Emily Glanton

Emily Shelkowitz

Eneida Mendonca

Eric Allenspach

Eric Gamazon

Eric Gayle

Eric Klee

Eric Vilain

Erica Davis

Erin A. Wishart

Erin Conboy

Erin E. Baldwin

Euan A. Ashley

F. Sessions Cole

Filippo Pinto e Vairo

Frances High

Francesco Vetrini

Francisco Bustos

Fuki M. Hisama

Gabor Marth

Gail P. Jarvik

Ganesh Mochida

George Carvalho

Gerard T. Berry

Ghayda Mirzaa

Giorgio Sirugo

Gonench Kilich

Guney Bademci

Hector Rodrigo Mendez

Heidi Wood

Herman Taylor

Holly K. Tabor

Hongzheng Dai

Hsiao-Tuan Chao

Hugo J. Bellen

Ian Glass

Ian R. Lanza

Ingrid A. Holm

Isaac S. Kohane

Ivan Chinn

J. Carl Pallais

Jacinda B. Sampson

James P. Orengo

James Verbsky

Jared Sninsky

Jason Hom

Jason Schend

Jennefer N. Kohler

Jennifer Morgan

Jennifer Schymick

Jennifer Tousseau

Jennifer Wambach

Jiayu Fu

Jill A. Rosenfeld

Jimann Shin

Joanna Jen

Joanna M. Gonzalez

John A. Phillips III

John Carey

John E. Gorzynski

Joie Davis

Jonathan A. Bernstein

Jose Abdenur

Joseph Loscalzo

Joy D. Cogan

Julian A. Martínez-Agosto

Julie Hoover-Fong

Julie McCarrier

Kahlen Darr

Kai Lee Yap

Kaitlin Callaway

Kathleen A. Leppig

Kathleen A. Sisco

Kathleen Page

Kathleen Sullivan

Katrina Dipple

Kayla M. Treat

Kelly Regan-Fendt

Kelly Schoch

Kevin S. Smith

Khurram Liaqat

Kim Worley

Kimberly Ezell

Kimberly LeBlanc

Kumarie Latchman

Lakshitha Perera

Lance H. Rodan

Laura Keehan

Lauren Blieden

Lauren C. Briere

Lauren Jeffries

Laurens Wiel

Layal F. Abi Farraj

Leoyklang Petcharet

LéShon Peart

Lili Mantcheva

Lilianna Solnica-Krezel

Lindsay C. Burrage

Lindsay Mulvihill

Lisa Bastarache

Lisa Schimmenti

Lorenzo Botto

Lorraine Potocki

Louise Bier

Lynette Rives

Lynne A. Wolfe

Mafalda Barbosa

Maija-Rikka Steenari

Manish J. Butte

Manisha Balwani

Margaret Delgado

María José Ortuño Romero

María Paula Silva

Maria T. Acosta

Marie Morimoto

Mariya Shadrina

Mark Wener

Marla Sabaii

Martha Horike-Pyne

Martin G. Martin

Martin Rodriguez

Mary Koziura

Matt Velinder

Matthew Might

Matthew Robinson

Matthew T. Wheeler

May Christine V. Malicdan

Megan Bell

Meghan C. Halley

Melissa Walker

Mia Levanto

Michael Bamshad

Michael F. Wangler

Michael Muriello

Michael T. Zimmermann

Miranda Leitheiser

Mohamad Mikati

Mohamad Saifeddine

Monika Weisz Hubshman

Monkol Lek

Monte Westerfield

Mustafa Tekin

Naghmeh Dorrani

Nara Sobreira

Neil H. Parker

Neil Hanchard

Nicholas Borja

Nicola Longo

Nicole M. Walley

Orpa Jean-Marie

P Dane Witmer

Page C. Goddard

Paolo Moretti

Patricia Dickson

Patrick McMullen

Paul Auwaerter

Paul Berger

Paul G. Fisher

Pengfei Liu

Peter Byers

Pinar Bayrak-Toydemir

Pongtawat Lertwilaiwittaya

Precilla D’Souza

Queenie Tan

Rachel A. Ungar

Rachel Evard

Rachel Li

Rakale C. Quarells

Ramakrishnan Rajagopalan

Raquel L. Alvarez

Reaford Blackburn

Rebecca C. Spillmann

Rebecca Ganetzky

Rebecca Overbury

Rebekah Barrick

Richard A. Lewis

Richard Chang

Rizwan Hamid

Rong Mao

Ronit Marom

Rosario I. Corona

Runjun Kumar

Russell Butterfield

Sanaz Attaripour

Sandesh Nagamani

Saskia Shuman

Seema R. Lalani

Seth Perlman

Shamika Ketkar

Shilpa N. Kobren

Shinya Yamamoto

Shruti Marwaha

Sirisak Chanprasert

Stanley F. Nelson

Stephan Zuchner

Stephanie Bivona

Stephanie M. Ware

Stephen B Montgomery

Stephen C. Pak

Steven Boyden

Suha Bachir

Susan Shin

Tahseen Mozaffar

Tanner D Jensen

Taylor Beagle

Taylor Maurer

Teneasha Washington

Teodoro Jerves Serrano

Terra R. Coakley

Thomas Cassini

Thomas J. Nicholas

Timothy Schedl

Tina Truong

Tiphanie P. Vogel

Vaidehi Jobanputra

Valerie V. Maduro

Vandana Shashi

Virginia Sybert

Wendy Chung

Wendy Introne

Wendy Raskind

Willa Thorson

William A. Gahl

William E. Byrd

William J. Craigen

Winston Timp

Yan Huang

Yigit Karasozen

Yongen Chang

Yong-Hui Jiang

Yuka Manabe

Ziyuan Guo

Data and Code Availability Statement

Data is available on request from the corresponding author. Data are not publicly available because of privacy or ethical restrictions.