Development and Content Validation of Novel Patient-Reported Outcome Measures to Assess Disease Severity and Change in Patients with Erythropoietic Protoporphyria: The EPP Impact Questionnaire (EPIQ)

Abstract

Susan D Mathias,1 Laurie Burke,2 Hilary H Colwell,1 George Mensing,3 Will Savage,3 Hetanshi Naik4 1Health Outcomes Solutions, Palm Beach Gardens, FL, USA; 2LORA Group, Normal, IL, USA; 3Disc Medicine, Watertown, MA, USA; 4Department of Genetics, Stanford University School of Medicine, Palo Alto, CA, USACorrespondence: Hetanshi Naik, Department of Genetics, Stanford University School of Medicine, Palo Alto, CA, USA, Email [email protected]: Erythropoietic protoporphyria (EPP), a rare inherited disorder, presents in early childhood with severe, painful phototoxicity, with significant impacts on health-related quality of life (HRQoL). Previous studies have not captured all concepts important to patients. Therefore, this study sought to develop a novel, comprehensive, and content valid patient-reported outcome (PRO) measure to assess the efficacy of new therapies.Patients and Methods: Qualitative interviews were conducted with EPP participants and clinical experts to obtain views on concepts relevant to patients. Results informed the development of novel PROs, which were debriefed during subsequent combined concept elicitation and cognitive debriefing interviews.Results: Twenty-three interviews were conducted with 17 adults and 6 adolescents with EPP. Concept elicitation revealed that participants experienced many symptoms with significant variability. The most common were burning, pain, swelling, and tingling. Tingling was the most common prodromal symptom, while burning was the most bothersome, and pain was the worst full reaction symptom. Participants reported being negatively impacted in their ability to do daily activities, and social and emotional functioning. Many reported impacted ability to work and be productive at their job. Participants reviewed and completed the newly developed PRO measures assessing full reactions and ability to do activities, as well as items to assess severity and change in severity of prodromal symptoms, full reactions, and EPP overall. All measures were found to be comprehensive, clear, and relevant.Conclusion: PRO measures are needed to assess important aspects of HRQoL and evaluate therapeutic response. These PRO measures are unique in assessing overall severity and change in EPP.Plain Language Summary: Erythropoietic protoporphyria (EPP) is a rare but severe condition; people with it experience painful reactions on their skin after exposure to sun and in some cases, artificial light. Measuring how EPP affects individual’s lives is critical to properly understanding the disorder. However, current questionnaires do not capture all the issues important to individuals with EPP. Therefore, we conducted interviews with individuals with EPP and doctors who are experts in EPP to create and evaluate a questionnaire that addresses these gaps. The interviews showed that people with EPP experience many symptoms with lots of variability, and that EPP impacts their ability to work and be productive at their job. This information was used to create a questionnaire that measures individual’s full EPP reactions and ability to do activities (EPP Impact Questionnaire), and how bad early warning symptoms, full reactions, and EPP overall are, as well as how they change (Patient Global Impression of Severity and Change). The questionnaire was found to be clear and relevant. This is important in being able to measure how patients feel and function and whether treatments work for people with EPP.Keywords: erythropoietic protoporphyria, porphyria, patient-reported outcome development, qualitative interviews, rare disease

Keywords

• erythropoietic protoporphyria
• porphyria
• patient-reported outcome development
• qualitative interviews
• rare disease