Development of the Pediatric Quality of Life Inventory™ Eosinophilic Esophagitis Module items: qualitative methods

Eosinophilic esophagitis (EoE) is a chronic esophageal inflammatory condition with a prevalence that continues to increase [1]. Food allergies are a common cause of EoE, and therefore food restriction is a common treatment [1]. Although patients experience significant disease- and treatment-related sequelae, there is no validated EoE-specific health-related quality of life (HRQOL) instrument to document the impact of EoE on the daily lives of affected pediatric patients. Additionally, current clinical practice in EoE pays little attention to patient HRQOL, instead focusing primarily on histologic and symptomatic improvement outcomes [1].

In order to partly address this significant gap in the empirical literature, we recently utilized the Pediatric Quality of Life Inventory™ (PedsQL™) 4.0 Generic Core Scales to investigate the generic HRQOL of patients with eosinophilic gastrointestinal (GI) disease (EGID, including EoE) in comparison with several other pediatric chronic conditions and healthy controls [2]. Not only did patients with EGID and their parents report significantly lower generic HRQOL than healthy controls, but they reported generic HRQOL lower than pediatric patients with inflammatory bowel disease, epilepsy, type 1 diabetes, sickle cell disease, post-renal transplantation, cystic fibrosis, and obesity [2].

Although the PedsQL™ 4.0 Generic Core Scales assess generic issues common across healthy and ill pediatric populations [3], a disease-specific HRQOL instrument is essential to understanding the particular health issues most germane to pediatric EoE patients from their perspective. In addition, an EoE disease-specific HRQOL instrument would be expected to be more sensitive to detecting change in health status over time within a population of EoE children than a generic scale. To better understand differences in health status within the population of pediatric EoE patients and to enhance the ability to measure the impact of disease-modifying therapies, we previously conducted individual focus interviews of pediatric patients with EoE and parents and solicited medical expert review in the development of the conceptual model and the initial items for a new multidimensional disease-specific HRQOL instrument targeted to pediatric EoE [4]. In the current study, we further utilize qualitative methods, specifically cognitive interviewing techniques, to support content validity and to finalize the items for a quantitative analysis subsequent to field testing.

The FDA patient-reported outcome (PRO) guidance for industry defines content validity as evidence demonstrating that an instrument measures “the concept of interest, including evidence that the items and domains of an instrument are appropriate and comprehensive relative to its intended measurement concept, population, and use” [5]. Furthermore, the FDA has emphasized the critical value of patient input in supporting content validity, noting that “documentation of patient input in item generation as well as evaluation of patient understanding through cognitive interviewing can contribute to evidence of content validity” [5]. Qualitative methods, in particular focus groups/individual interviews and cognitive interviewing techniques, have emerged as the standard methodology for supporting the content validity for new or existing PRO instruments [6‐10] and have served as the foundation for previous PedsQL™ Disease-Specific Modules [11‐18]. These qualitative methods are consistent with recent FDA guidelines on PRO measures, and as such help establish the content validity of newly developed disease-specific HRQOL items [5]. These iterative steps include: a comprehensive review of the literature, expert opinion, and the patient perspective derived from focus groups/individual interviews (used to develop the conceptual model for relevant disease-specific domains), item generation guided by the conceptual model, and the iterative process of revising the items and item content based on patient cognitive interviewing techniques [6‐10]. Previously, Flood and colleagues contributed significantly to EoE PRO development by utilizing expert opinion and cognitive interviews to generate a pediatric EoE symptom metric (the Symptom Questionnaire for Eosinophilic Esophagitis) for use by patients aged 8 – 17 and caregivers of patients aged 2 – 7 [19]. However, this measure was limited by age range and methods of item generation.

Given the lack of an empirically-validated multidimensional pediatric EoE disease-specific HRQOL instrument in the extant literature for patient self-report for ages 5–18 years and parent proxy-report for ages 2–18 years, the objective of the present study was to address this gap in the empirical literature and to describe the qualitative methods, specifically cognitive interviewing techniques, utilized in the further item development and content validation phase for generating the final items for the new PedsQL™ Eosinophilic Esophagitis Module for pediatric patients with EoE.

All research for this study was performed in compliance with both the Declaration of Helsinki (http://​www.​wma.​net/​e/​policy/​b3.​htm) and Cincinnati Children’s Hospital Medical Center (CCHMC) ethical guidelines for clinical research, in addition to being approved by the CCHMC Institutional Review Board. Parental permission (informed consent) was obtained from all caregivers and assent from children aged 8 – 17. Informed consent was obtained from patients aged 18.

The validated PedsQL™ module development guidelines, the consolidated criteria for reporting qualitative research (COREQ), and the FDA guidelines on PRO development were used to develop the methodology for item development and content validity [5, 16, 17, 20]. Development of the initial items for the PedsQL™ EoE Module began in 2008.

The PedsQL™ EoE Module is the first and only content-validated pediatric patient self-report for ages 5–18 years and parent proxy-report for ages 2–18 years multidimensional HRQOL measurement instrument specific to EoE, and consequently addresses an important gap in the current empirical literature for this pediatric chronic disease.

Pediatric patients and their parents felt that the EoE-specific domains of symptoms, treatment, worry, communication, food and eating, and feelings better expressed the salient HRQOL concerns of families than the PedsQL™ 4.0 Generic Core Scales alone. The domains of food and worry were frequently identified by patients and families as key components of EoE-specific HRQOL. The use of separate cohorts for the focus interviews and cognitive interviewing phases allowed further elucidation of pediatric patient self-reported and parent proxy-reported opinions and concerns, resulting in content saturation. The cognitive interviews were particularly helpful in clarifying the directions and modifying the items to allow for reading ease by using patient-centered vocabulary. Utilizing the cognitive debriefing methodology in the current study, the semi-structured question format allowed patients and families the opportunity to explain in their own words the impact of EoE on their family and to achieve content saturation prior to finalizing the items.

Although being an important stride forward in the field of pediatric EoE, this study is limited by a few concerns, in particular when applying these results to non-Caucasians and those with co-morbidities. To address these potential limitations, we will next test the PedsQL™ EoE Module items in a large national multisite field test of patients and parents with a wide variety of demographics and comorbidities. Finally, we will then utilize quantitative methods to evaluate the reliability, validity, and responsiveness of the PedsQL™ EoE Module, allowing assessment of the potential performance of the PedsQL™ EoE Module in clinical trials.

It is of critical importance to include patient self-reported and parent proxy-reported outcomes when evaluating pediatric EoE treatments. Our work both demonstrates and emphasizes the significant impact of EoE on overall health and well-being, rather than just a focus on specific gastrointestinal symptoms, and is an important consideration for future pediatric clinical trials of new medications for pediatric EoE. The PedsQL™ EoE Module will not only address critical gaps in the literature and clinical practice, but also will provide pediatric patients and their families a voice to express the impact of EoE on their daily lives.