Documenting the Journey of Patients with Eosinophilic Esophagitis and the Impact of the Disease on Patients and their Caregivers: A Cross-sectional, Qualitative Research Study

This was a cross-sectional, qualitative research study involving one-on-one, semi-structured interviews of patients with EoE and their caregivers in the USA. Caregivers were interviewed about their children with EoE (children aged 6–11 years and adolescents aged 12–17 years). In addition, caregivers were interviewed to determine the impact of an EoE diagnosis on their own HRQoL. Adolescents (aged 12–17 years) and adults (aged ≥ 18 years) with EoE were also interviewed separately. All interviews were completed by telephone. Caregivers and their adolescent children were interviewed independently of each other to ensure that both their perspectives were represented; however, a caregiver could attend the child’s interview session if preferred. Only one caregiver per patient participated in the study. This qualitative study was designed to obtain patient and caregiver perspectives on the humanistic burden of EoE, and, as such, was not powered to allow direct comparisons between groups. Furthermore, EoE is a rare condition [1], and thus responses were elicited directly from identified patients.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol and research materials were approved by an institutional review board (IRB; Ethical & Independent Review Services, Independence, MO, USA); study number 16102-01 (approved September 2, 2016). Once the central IRB review/approval was received (Ethical & Independent Review Services, Independence, MO, USA), Evidera designed, managed, collected, analyzed, and reported the study.

Participants were recruited by US-based patient advocacy organizations (the American Partnership for Eosinophilic Disorders (APFED) and the Campaign Urging Research for Eosinophilic Disease (CURED)) using their patient registries. Participants were recruited in the following planned cohorts: children with EoE (aged 6–11 years) and their caregivers; adolescents with EoE (aged 12–17 years) and their caregivers; and adults with EoE (aged ≥ 18 years). Patients and their caregivers were contacted by email, through promotional materials, and through social media advertisements. A purposive sampling strategy was used, with efforts made to recruit participants with diverse demographic characteristics (e.g., age and race/ethnicity), including at least 25% female participants and at least 40% male participants in each patient cohort; and to include participants from diverse backgrounds in terms of age, race, and ethnicity.

To be eligible, participants had to: have a caregiver report or self-report of a clinician-confirmed diagnosis of EoE; be able to read and speak English; be willing to participate in an audio-recorded telephone interview; and provide written informed consent (adults and caregivers) or assent (children and adolescents). Caregivers of children and adolescents with EoE also had to be aged 18 years or older, be the primary guardian, and have resided with the child for at least 6 months prior to participating in this study. Participants were excluded if they had any cognitive, visual, or hearing impairment that would interfere with participation in the study. Furthermore, only one caregiver of each child with EoE could participate in the study. Children with any clinically relevant and/or serious chronic medical conditions, which, in the opinion of the investigators, may have confounded the reporting of signs and symptoms of EoE, were excluded from this study. This included: malignancy; history of organ transplantation; congenital abnormalities; Ehler–Danlos Syndrome; vasculitis; Lupus; hypereosinophilic syndrome; other eosinophilic disorders (e.g., eosinophilic gastroenteritis); and other gastrointestinal diseases (e.g., Crohn’s disease). Concomitant gastroesophageal reflux disease (GERD), asthma, allergic rhinitis, or food allergies were not exclusionary.

Potential participants were screened by a trained qualitative researcher during a telephone call, and eligibility criteria collected using a recruitment and screening script. Eligibility data were then reviewed and confirmed by the investigation team. Participant contact information was sent via a secure, password-protected electronic document with permission from each individual and/or caregiver. Each participant received a US$100 gift certificate for their participation in the study. If a caregiver participated alone (e.g., for the cohort aged 6–11 years), only the caregiver received $100. In instances where caregivers and adolescents participated, both received $100.

Participants were asked to complete a questionnaire before the telephone interview to help facilitate discussions. A trained staff member then conducted qualitative telephone interviews according to the study protocol using (1) the completed pre-interview questionnaire, and (2) a semi-structured qualitative interview guide. Following the interview, participants were asked to complete a sociodemographic survey. Repeat interviews were not conducted. The pre-interview questionnaire and qualitative interview guide were developed based on a targeted literature review with input from two physicians with clinical and research expertise in EoE. The questionnaire and interview guide were not previously validated or pilot-tested, but were designed specifically for this study. The research team was led by two qualified outcomes research scientists [R.M.P. (PhD, MHA; female) and G.H. (MA; female), Evidera] and supported by research associates [including A.B. (BS; female), Evidera] and other qualified qualitative researchers from Evidera. An outcomes research scientist [L.T. (MBA; female)] and a clinician [J.W. (MD; male)] from the sponsor (Shire, a member of the Takeda group of companies) helped develop and refine the study methods. Participants were aware of the interviewer’s credentials and the purpose of the study, but did not speak with the interviewer until taking part in the study. A total of five staff members performed the interviews. This study utilized standardized recruitment and screening scripts, standardized qualitative interview guides, and standardized surveys/questionnaires for each cohort in the study in order to reduce any potential interviewer bias. All interviewers were trained on how to use the interview guide and followed the same guide.

The pre-interview questionnaire and other appropriate documents (e.g., the consent and assent forms, where applicable) were sent to participants via post for completion ahead of the interviews, and comprised questions about the patient’s journey leading to a diagnosis of EoE, their management of the disease, and their current experiences with EoE. It included questions about the patient’s medical history, signs and symptoms [pre-diagnosis and post-diagnosis (3 months before interview)], use of pharmacological treatments and dietary modifications, and the physical and psychosocial impact of the disease (pre- and post-diagnosis). Participants were also asked about episodic experiences, steps taken to modify their lifestyle to avoid symptoms, and whether specific triggers had been identified (e.g., allergy or food intolerance). Different versions of the pre-interview questionnaire were used for caregivers, adults, and adolescents.

Participants were provided with a brief introduction to the interview process, informed that the session would be audio-recorded, and given the opportunity to ask questions before the interview.

The interview sessions captured data on symptom experience, procedure history, diagnosis, clinical milestones, and other personal impact. Each interview lasted approximately 90 min, during which interviewers collected information as notes on the data collection form. A semi-structured qualitative interview guide was used in conjunction with results from the pre-interview questionnaire. It included open-ended questions about the participant’s experiences with EoE symptoms, the pathway to diagnosis of EoE (including medical milestones), the impact of EoE on HRQoL for both the patient and caregiver (including social activity, daily activity, physical well-being, emotional well-being, and relationships), and experience with treatments. Different versions of the qualitative interview guide were used for caregivers, adults, and adolescents.

Two different versions of the sociodemographic survey were used: one for caregivers and one for adults with EoE. Sociodemographic data for children and adolescents were collected using a caregiver version of the sociodemographic survey. The caregiver survey collected information about the caregiver and their child or adolescent with EoE, including age, sex, relationship to patient, and level of schooling. The adult survey included questions about age, sex, race, ethnicity, living situation, employment status, and educational background.

Qualitative data collected from interviewer notes and audio files were analyzed using a content analysis approach with thematic analysis in which qualitative data are organized by topic [18, 19]. Emerging concepts were tracked by interviewers in a concept tracking table. Quantitative data were summarized by cohort using descriptive statistics, including frequencies or means and standard deviations, in Microsoft Excel.

Overall, 65 individuals responded to the advertisement; of these, 25 were not screened due to difficulties with contacting them or the study recruitment quotas being reached. Of the 40 participants who were screened, two were not US residents and were thus not eligible for inclusion in this study (Supplementary Fig. S1 in the ESM). Thirty-eight participants were enrolled from 22 September to 28 November 2016 and completed the qualitative interviews (flow diagram presented in Supplementary Fig. S1 in the ESM). This included caregivers of children with EoE aged 6–11 years (n = 4; 75.0% of the children were male), adolescents with EoE aged 12–17 years (n = 7; 42.9% male) and their caregivers (n = 7), and adults with EoE aged ≥ 18 years (n = 20; 40.0% male). All 11 caregivers (for children, n = 4; and for adolescents, n = 7) were female and married (Table 1), and all were White (not Hispanic or Latino). The mean [standard deviation (SD)] age at first signs and symptoms for children, adolescents, and adults with EoE was 0.6 (1.0), 3.8 (4.0), and 17.2 (12.7) years, respectively. The mean (SD) age at diagnosis for these groups was 4.9 (3.9), 8.1 (4.1), and 27.3 (11.3) years, respectively (Table 1).

Signs and symptoms before diagnosis varied by cohort (Fig. 1). Pre-diagnosis signs and symptoms for children and adolescents were based on caregiver report. For children with EoE (n = 4; caregiver report), the most commonly reported signs and symptoms pre-diagnosis were: abdominal pain (100.0%); avoiding or refusing food; chest pain; regurgitation/reflux/GERD; and vomiting (each reported by 75.0% of caregivers). These findings were similar for adolescents with EoE (n = 7; caregiver report), with the most common signs and symptoms before diagnosis being: abdominal pain (100.0%); avoiding or refusing food; regurgitation/reflux/GERD; and vomiting (each reported by 57.1% of caregivers). In contrast, adults (n = 20; self-report) with EoE experienced a broader range of signs and symptoms before diagnosis, but the most common were: difficulty or discomfort swallowing solid foods and purees (90.0%); chest pain; feeling an obstruction in the throat (globus sensation); and odynophagia (each reported by 75.0% of adults). Furthermore, only adults with EoE reported globus sensation (75.0%); and food impaction/obstruction (60.0%).

Caregivers and adults with EoE were also asked about the physical and psychosocial impact of EoE before diagnosis (Table 2). Caregivers (n = 11) most commonly reported feeling fatigued/tired (72.7%); difficulties with completing daily activities at home, work, or school (63.6%); difficulties with participating in hobbies or leisure activities (72.7%); and spending more time to care for their child with EoE versus their other children (90.9%). Caregivers also commonly reported feeling frustrated/irritated/moody (81.8%); concerned/worried/anxious (100.0%); and out of control/helpless (81.8%). Caregivers reported that their children (n = 4) most commonly reported fatigue/tiredness (50.0%); difficulties participating in social activities with others (75.0%); feeling frustrated/irritated/moody (75.0%); and feeling like their life was centered or revolved around EoE (75.0%). Caregivers reported that their adolescent children (n = 7) most commonly experienced a reduced appetite/ability to eat (85.7%); fatigue/tiredness (71.4%); and weakness/reduced energy levels (71.4%). Caregivers also indicated that their adolescent children most commonly reported difficulties participating in activities for fun and enjoyment (85.7%); difficulties with participating in social activities with others (57.1%); and an impact on their relationships with family, friends, or other children (71.4%). Furthermore, all adolescents reported feeling frustrated/anxious/moody (100.0%); feeling concerned/worried/anxious as a result of having EoE was also common (71.4%). Similarly, adults with EoE (n = 20) most commonly reported fatigue/tiredness (70.0%); reduced appetite/reduced ability to eat (75.0%); and weakness/reduced energy level (70.0%). Adults also most commonly reported difficulties participating in social activities with others (75.0%); and impact on relationships with family, friends, or other children (65.0%). Adults, like caregivers and adolescents with EoE, reported feeling concerned/worried/anxious (90.0%), but also reported feeling embarrassed by their condition (75.0%).

EoE was reported to have an impact on adult patients’ and caregivers’ work productivity. Caregivers of children and adolescents with EoE and adults with EoE reported that they had to stop working [caregivers, 45.5% (5/11); adults, 20.0% (4/20)], or had to reduce the number of hours they worked owing to EoE [caregivers, 27.3% (3/11); adults, 15.0% (3/20)]. Two adults with EoE also had to work extra hours or more than one job to cover the costs of living with EoE (Supplementary Table S1 in the ESM).

For most participants, a formal diagnosis of EoE was obtained after consultation with a range of healthcare providers. This usually included a gastroenterologist or pediatric gastroenterologist, an allergist/immunologist, and a primary healthcare provider (Fig. 2a). Participants reported that they had undergone a range of procedures prior to receiving a diagnosis of EoE; all participants (children, adolescents, and adults) had undergone an upper endoscopy with biopsy (Fig. 2b). For children, adolescents, and adults with EoE, there was a mean (range) delay of 4.3 (0.9–9.7) years, 4.3 (1.0–6.9) years, and 11.1 (0.0–34.0) years, respectively, in time from onset of first signs and symptoms of EoE to diagnosis. The burden of reaching a formal diagnosis of EoE was described as “a great deal” or “a very great deal” for 75.0% of children (3/4), 71.4% of adolescents (5/7), and 70.0% of adults (14/20) with EoE (Fig. 2c). Qualitative feedback was similar across cohorts, including reports of being incorrectly diagnosed, feeling frustrated with healthcare professionals because they could not provide a diagnosis, stress related to obtaining a diagnosis, difficulty in pinpointing the reason for signs and symptoms, and having to attend multiple doctor visits to obtain a diagnosis (data not shown).

Signs and symptoms of EoE persisted for all cohorts even after diagnosis (Fig. 3a, b), the caregiver and self-report for adolescents were comparable (Fig. 3b), and EoE continued to have a physical and psychosocial impact on all patient cohorts after diagnosis (Table 3). Patients and caregivers also reported worries about the cost of EoE, in terms of expensive dietary supplements or dietary modifications and travel expenses that were not covered by their health insurance policies. Patients and caregivers highlighted the cost of their monthly or yearly deductibles on their insurance policies; some participants also reported worries about their lack of insurance coverage (data not shown).

In the 3 months before interview, the most common triggers for children with EoE (n = 4) were food triggers (100.0%) and environmental allergens (50.0%). Similarly, common triggers for adolescents (caregiver report) with EoE (n = 7), were: food triggers (100.0%) and environmental allergens (42.9%); stress was also reported (42.9%). Adolescents (self-report) additionally identified infection as a common trigger (57.1%). For adults with EoE (n = 20), food triggers (80.0%) and stress (50.0%) were reported as their most common triggers (Supplementary Table S2 in the ESM). Triggers could be avoided by the majority of patients [children, 100.0% (4/4); adolescents, 71.4% (5/7) according to caregivers and adolescents themselves; adults, 60.0% (12/20)], although most patients also had times when EoE triggers could not be avoided [children, 75.0% (3/4); adolescents, 71.4% (5/7) according to caregivers and adolescents themselves; adults, 75.0% (15/20)] (Supplementary Table S2 in the ESM).

The majority of participants (all cohorts) were receiving medication for the treatment of EoE [children, 100.0% (4/4); adolescents, 100.0% (7/7); adults, 70.0% (14/20)]. For all cohorts, the most common medications used were proton pump inhibitors and orally administered topical corticosteroids (e.g., administered as a slurry) (Supplementary Table S3 in the ESM). Rates of dietary elimination therapy were similarly high [children, 50.0% (2/4); adolescents, 71.4% (5/7); adults, 80.0% (16/20)]. The most common was an empiric 6-food elimination diet (soy, egg, dairy products, wheat, nuts, and seafood) (Supplementary Table S4 in the ESM). Some participants were on a combination of pharmacologic therapy and dietary modification [children, 50.0% (2/4); adolescents, 71.4% (5/7)]; and adults, 55.0% (11/20)].