“I Can’t Take off My Shirt or Do My Own Hair”—A Qualitative Investigation of the Symptoms and Impact Experience of Children and Adolescents with Fibrodysplasia Ossificans Progressiva (FOP)

Our participant sample was recruited through a collaboration with the International Fibrodysplasia Ossificans Progressiva Association (IFOPA; www.​ifopa.​org); participants were recruited in the US, UK, and Canada. The sample comprised 17 children and adolescents with FOP and their parents. Participants were included if they provided assent and informed consent signed by a parent or legal guardian, were male or female aged 4–17 years at time of consent, had a parent-reported diagnosis of FOP, and had parent-reported FOP disease activity within 1 year of the screening call. We defined FOP disease activity as self- or parent-reported pain, swelling, stiffness, warmth, redness, or other signs and symptoms associated with FOP flare-up, or worsening of joint function, or radiographic progress of HO [(increase in size or number of HO lesions) with/without being associated with flare-up episodes]. Participants were excluded if they did not speak English fluently or if they were currently participating in a clinical trial for FOP. The target recruitment was 20 child/parent dyads to achieve conceptual saturation, i.e., the point at which no new information emerges from additional interviews [13, 14]. Two clinicians who regularly treat children and adolescents with FOP were also interviewed.

Sixty-minute interviews were conducted virtually using Microsoft Teams by experienced qualitative researchers who received specific training for the current project. A semi-structured interview guide was used to elicit the child/adolescent and parent experience of FOP, including symptoms and impacts on daily life. For children aged 4–7 years, the child participated in a short interview with the parent present, and most of the interview was conducted with the parent alone; for children aged 8–11 years, the child participated in an interview alone and the parent participated in an interview alone; and for adolescents aged 12–17 years, the adolescent interviewed alone, without parents present. These age groupings were based on recommendations from the ISPOR task force report on good practices for patient-reported outcomes assessments in children and adolescents [15]. During the interview, open-ended questions were asked first, followed by specific probes as needed to gather more details. Examples of questions included: “Can you tell me what it is like for you to have FOP?” “What is it like when you have a flare-up?” “Are there things you can’t do because of FOP? Can you tell me about them?”

Two clinicians with expertise in FOP were interviewed separately in the fall of 2020. Each interview lasted approximately 1 h. Clinicians were asked to describe symptoms and impacts associated with flare-ups.

Interviews were recorded, professional transcribed, and anonymized.

All transcripts were coded in ATLAS.ti software [16], using a data-driven approach and open inductive coding [13, 14, 17, 18]. As this is applied qualitative research, it was focused on a specific issue (symptoms and impacts of FOP) and did not follow a particular theoretical orientation [19]. Researchers developed the initial coding template after reviewing a subset of transcripts. This coding template was applied to two identical transcripts by two independent researchers. Any discrepancies or inconsistencies between the two researchers were resolved through discussion. The coding template was revised throughout the coding process to reflect the evolving understanding of the researchers of symptoms and the impact experience. This coding template laid the basis for developing a conceptual model. A conceptual model is a visual representation of aspects of patients’ experiences, including their symptoms and their associated impacts on daily functioning. The model was developed using standard analytical techniques [13, 17].

The adequacy of the sample size was assessed by saturation analysis performed on each group of five interviews to determine how much new information about the patient experience of flare-ups was obtained in each group. Saturation analysis was conducted at the code level with child/adolescent and parent data combined on flare-related symptoms and impacts. We chose to conduct saturation only on flare-related symptoms and impacts because this is a discrete context.

Interviews were conducted with 2 clinicians, 11 parent/child dyads, and 6 adolescents (demographic data other than age were missing for n = 1 parent/child dyad). Six children were in the youngest age group (age range 5–7 years), five were in the middle age group (age range 9–11 years), and six were in the oldest age group (age range 15–17 years). Most participants were non-Hispanic and white (children/adolescents n = 10/16; parents n = 10/16). Half of the children/adolescents (n = 7/16) and almost all parents were female (15/16). Most children/adolescents were diagnosed before the age of 2 years and were experiencing symptoms at the time of diagnosis (n = 11/16). See Table 1 for the overview of participant characteristics.

Clinicians interviewed reported that pain and swelling are among the most common symptoms that patients with FOP report; secondary symptoms include loss of movement, redness, tenderness, and stiffness. Clinicians also report that when assessing patients, they focus on restriction in movement and pain.

Patients and parents reported various symptoms and impacts of FOP, which were reported in relation to a flare-up or FOP more generally. All concepts emerged in the first 13 interviews, with no new flare-related concepts emerging in interviews 14–17. Thus, conceptual saturation was achieved for flare-related symptoms and impacts.

Children, adolescents, and parents reported various symptoms and functional impacts of FOP, and these were spontaneously reported in relation to a flare-up or FOP more generally. The conceptual model of symptoms and functional impacts can be found below in Fig. 1.

Symptoms of FOP reported by children/adolescents, parents, and clinicians were pain, swelling, redness, and stiffness. When describing their FOP symptoms, one adolescent stated:

“It feels really big. I think it feels bigger than it is, and just very uncomfortable because of the swelling mostly.” (15 years old)

While these symptoms were distinct, children/adolescents and their parents often reported experiencing multiple symptoms at the same time, such as this adolescent complaining of pain, redness, and swelling (which are all related to inflammation):

“Pain—a lot of pain. And then it turns red. Usually the area’s red or hot, and it starts swelling.” (17 years old)

Additional symptoms reported by both children/adolescents and parents included feeling sick, having flu-like symptoms, or being tired. Parents alone reported the most variation in symptoms related to flares for their child, including the child feeling tired, tingling, or itchy, having a veiny pattern on the skin, and having strong-smelling urine. Two other symptoms, twitching in eyes and migraine, were also reported by parents but were specific to a flare location (back and neck) and not general symptoms.

“We had migraines, and then we had a twitching issue that was happening, and they felt that that was happening because there’s no place for the inflammation to go, so it was going to his brain and causing the migraines and causing an issue with his eyes.” (Parent of a 9-year-old)

In the supplementary materials, Online Appendix A provides a list of illustrative quotes from children/adolescents and parents to provide further insight regarding the child/adolescent and parent experience of symptoms.

Additionally, children/adolescents and parents reported that the duration of flare-ups varies significantly. Some participants reported that they come in cycles, while others complained of difficulty determining the end of a flare-up. When a flare-up ends, patients report that they feel back to normal, the pain subsides, swelling goes down, and redness goes away. Similarly, the frequency of flare-ups varies, with children/adolescents and parents reporting pretty often, once or twice a year, every week or every month, continuous, and once every 4 to 5 months. The size of flare-ups and severity of pain also vary; patients and parents report that the larger flare-ups are the ones that hurt more. Some flare-ups result in new bone growth, while others do not. This information is consistent with what was reported in Pignolo et al. (2015), which reports on the results of a global survey of the natural history of flare-ups in FOP [20].

Functional impacts of flares and FOP in general were also described by children/adolescents and parents, including accommodations, mobility, activities of daily living (ADLs), daily activities, and social activities. Impacts were attributed to the difficulties children and adolescents faced living with a disease that prohibited common activities. Children/adolescents and parents alike described the challenges in daily life, saying:

“Sometimes getting dressed, it’s kind of hard to do it on my own.” (16 years old)

“I do also have to help her with her toiletry like in the restroom to make sure her hygiene is good, because she cannot reach behind her back or reach down.” (Parent of a 5-year-old)

“There’s been times when he has felt left out because he couldn’t—he wasn’t allowed to do things for safety reasons, like bounce houses at birthday parties and those kinds of things.” (Parent of a 5-year-old)

Impact concepts described only by parents included school, mental health, and medical impacts. For example, one parent said:

“Again, he's had a really good year, but previously there have been times where he's missed a lot of school due to pain, and that was really difficult for him, too, just socially—anything at school that he had to do differently, like not participating in gym or doing it differently or special equipment in the classroom, stuff like that.” (Parent of an 11-year-old).

Other impacts reported included a limitation in mobility, difficulty focusing on anything else, and problems with sleep, moodiness, and appetite being affected. One adolescent commented:

“Well, it’s like when I sleep, it’s a lot of pain, and I’m awfully—mostly uncomfortable a lot of the time. Sleeping, I end up turning a lot.” (17 years old)

Some of these concepts were further broken down into sub-concepts; supplementary details and illustrative quotes can be found in Appendix B in the supplementary materials.