Development and content validation of two new patient-reported outcome measures for endometriosis: the Endometriosis Symptom Diary (ESD) and Endometriosis Impact Scale (EIS)

Abstract

Background: Endometriosis is a common, chronic, impactful condition in women of reproductive age. In the absence of established sensitive and specific biomarkers, disease severity is determined by patient-reported symptoms and impacts. This article details the development of two new patient-reported outcome (PRO) measures designed to assess efficacy endpoints in clinical studies: The Endometriosis Symptom Diary (ESD) and the Endometriosis Impact Scale (EIS). Methods: The ESD and EIS were developed according to best practice and scientific standards (including the Food and Drug Administration (FDA) PRO Guidance) and with extensive input from women with surgically-confirmed endometriosis. Research included: a review of published qualitative literature; concept elicitation interviews in the US, Germany and France (n = 45) to explore the experiences of women with endometriosis and to inform ESD and EIS development; and cognitive interviews in the US and Germany (n = 31) to assess relevance and understanding of the ESD and EIS and usability of administration using an electronic handheld device. The FDA and the European Medicines Agency (EMA) as well as PRO and clinical experts were consulted throughout the process. Results: Pelvic pain was identified as the most frequent, severe and bothersome symptom for women with endometriosis. Pain was reported to be greatest during menstruation (dysmenorrhea) and during or after sexual intercourse (dyspareunia). Pain resulted in significant impairments in physical activities, work/study, social/leisure activities, household activities and sexual functioning. All women highlighted the emotional impact of endometriosis. Descriptions of pain and associated impacts were largely consistent across participants from the US and Europe, with the most notable differences being the words used to describe the location of pain (e.g., 'pelvis' vs. 'abdomen'). Testing during cognitive interviews indicated that the ESD and EIS were well understood and consistently interpreted. Furthermore, all participants found the ePRO devices easy to use and no issues regarding visual presentation, selection of responses or navigation were identified. Conclusions: Evidence from extensive qualitative research supports the content validity of the ESD and EIS as patient-reported measures of the disease-defining symptoms of endometriosis and the associated impact on women's lives. Future research will seek to establish the measurement properties of the measures.

Patients’ and clinicians’ perspectives on item importance, scoring, and clinically meaningful differences for the Endometriosis Symptom Diary (ESD) and Endometriosis Impact Scale (EIS)

“…Patients frequently described the relationship between EAPP and physical limitations and the relationship between EAPP and impact on emotional well-being. These findings, and those reported elsewhere [ 14 , 15 , 19 , 20 , 38 , 39 ], highlight that patients’ emotional well-being is directly influenced by pain severity and not just secondary to other aspects of endometriosis, such as avoidance of sexual intercourse and any associated feelings of guilt. Therefore, the impact of endometriosis on emotional well-being can be considered a proximal impact of EAPP.…”

“…The findings from this study supplement prior validation studies of the ESD and EIS [ 14 , 19 , 20 ] as fit-for-purpose measures of endometriosis symptoms and related impacts in clinical trials.…”

“…A systematic review of EAPP assessment has suggested that a visual analogue scale (VAS) or a numeric rating scale (NRS) adapted for endometriosis may optimize the assessment of EAPP in clinical research and practice and identified a potential gap in availability of measures developed on the basis of patient input [ 13 ]. Over the past few years several PRO measures have been developed for use to assess key clinical trial endpoints in the evaluation of endometriosis treatments addressing this gap, including the Endometriosis Symptom Diary [ 14 ] and the Endometriosis Pain Daily Diary (EPDD) [ 15 ]; both measures assessing similar concepts but with notable differences as described previously [ 14 ]. In conjunction measures have also been developed to assess the impact of endometriosis pain including the Endometriosis Daily Pain Impact Diary [ 16 ] and the Endometriosis Impact Scale (EIS) [ 14 ].…”

“…The measures of interest in this study, the ESD and EIS, were developed in accordance with scientific standards including FDA Guidance for Industry [ 17 ] and the European Medicines Agency (EMA) reflection paper [ 18 ]. The content of the ESD and EIS was developed based on a review of published literature, concept elicitation interviews with patients in the US, Germany, and France (n = 45), cognitive interviews with patients in the US and Germany (n = 31), and consultations with PRO and clinical experts throughout the development [ 14 ].…”

“…The ESD is a daily electronic diary which assesses the experience of endometriosis symptoms over the past 24 h mostly reported on a 0–10 NRS. The EIS is a weekly electronic diary comprising items assessing the impact of endometriosis symptoms on patients’ daily lives over the past 7 days using a 5-point VRS [ 14 , 19 ]. The psychometric properties of the ESD and the EIS were further investigated in accordance with scientific standards in the Validation study for Endometriosis PRO (VALEPRO), a prospective, non-interventional study conducted in the US and Germany which supported the ESD and EIS scores as reliable, valid, and sensitive to change for investigating endpoints in endometriosis clinical studies [ 19 , 20 ].…”