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

Purpose

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

Data Sharing Statement

The datasets generated and/or analyzed during the current study are not publicly available due to privacy concerns but are available from the corresponding author on reasonable request.

Ethics Approval and Consent to Participate

This study was approved by an IRB and all participants consented.

Consent for Publication

All participants consented to publication with consent to participate in this study.

Acknowledgments

We are indebted to the individuals with EPP who participated in study and would like to thank the United Porphyrias Association for assisting with recruitment.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. SDM, HHC, LB, and HN were primarily responsible for the design, content, and interpretation of the study.

Disclosure

GM and WS are employed by and have a financial interest in Disc Medicine. SDM is an employee of Health Outcomes Solutions (HOS), and HHC is a consultant to HOS, which received funding from Disc Medicine for the conduct of this study, and LB is a consultant for Disc Medicine. In addition to funding from Disc Medicine related to this work, LB has past and ongoing research support and contracts from various non-profit organizations and for-profit companies that are unrelated to this work. HN consults for Alnylam Pharmaceuticals, Recordati Rare Diseases, and Mitsubishi Tanabe. The authors report no other conflicts of interest in this work.

Additional information

Funding

Support was provided by Disc Medicine.