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Background: Patient-reported outcome (PRO) instruments provide robust and effective means of evaluating patients' treatment experience; however, none adequately cover experience using self-injection devices with enhanced features, such as an electromechanical autoinjector (e-Device). The aim of this study was to develop a PRO instrument that accurately assesses patient experience of using an e-Device and to evaluate its psychometric properties., Methods: A mixed-methods approach was taken; two parallel, targeted literature reviews were conducted to identify relevant concepts and existing self-injection PRO instruments that could be adapted. Patient feedback obtained from two focus groups was used to inform initial instrument development. The pilot instrument was then administered in a multicenter, open-label, phase 3 clinical study in which patients self-injected certolizumab pegol using an e-Device, to gather evidence of its psychometric qualities. Exit interviews were conducted with a sub-sample of patients enrolled in the study to confirm the appropriateness and clarity of the items included and cognitively debrief the instrument. Confirmatory factor analysis (CFA) was conducted on all items, and each domain's internal consistency was measured using Cronbach's ɑ., Results: The literature searches identified several e-Device-specific concepts related to device features, device function, side effects/reactions/pain, confidence, and interference/convenience in daily life. Seven existing PRO instruments were identified. The Self-Injection Assessment Questionnaire (SIAQ), containing pre- and post-injection questionnaire modules, was selected as most suitable and adapted using feedback from 19 patients in the two focus groups to form the pilot Assessment of Self-Injection (ASI) questionnaire. CFA resulted in some changes to the grouping of items in the post-injection module domains following psychometric evaluation of the ASI. Internal consistency was satisfactory for all pre- and post-injection domains (ɑ > 0.8). Cognitive debriefing results from 12 patient exit interviews confirmed the ASI's appropriateness and clarity., Conclusions: The ASI was developed iteratively with patient input and was evaluated in its intended clinical context of use. Psychometric analyses indicated promising cross-sectional results; the ASI was well understood and considered relevant by patients self-injecting using the e-Device, suggesting that it could be used in real-world settings to aid with clinical decision making., Trial Registration: NCT03357471.

Objectives: The aim was to document, from the perspective of the empirical literature, the primary symptoms of functional dyspepsia (FD), evaluate the extent to which existing questionnaires target those symptoms, and, finally, identify any missing evidence that would impact the questionnaires' use in regulated clinical trials to assess treatment efficacy claims intended for product labeling., Methods: A literature review was conducted to identify the primary symptoms of FD and existing symptom-based FD patient-reported outcome (PRO) instruments. Following a database search, abstracts were screened and articles were retrieved for review. The primary symptoms of FD were organized into a conceptual model and the PRO instruments were evaluated for conceptual coverage as well as compared against evidentiary requirements presented in the FDA's PRO Guidance for Industry., Results: Fifty-six articles and 16 instruments assessing FD symptoms were reviewed. Concepts listed in the Rome III criteria for FD (n = 7), those assessed by existing FD instruments (n = 34), and symptoms reported by patients in published qualitative research (n = 6) were summarized in the FD conceptual model. Except for vomiting, all of the identified symptoms from the published qualitative research reports were also specified in the Rome III criteria. Only three of the 16 instruments, the Dyspepsia Symptom Severity Index (DSSI), Nepean Dyspepsia Index (NDI), and Short-Form Nepean Dyspepsia Index (SF-NDI), measure all seven FD symptoms defined by the Rome III criteria. Among these three, each utilizes a 2-week recall period and 5-point Likert-type scale, and had evidence of patient involvement in development. Despite their coverage, when these instruments were evaluated in light of regulatory expectations, several issues jeopardized their potential qualification for substantiation of a labeling claim., Conclusions: No existing PRO instruments that measured all seven symptoms adhered to the regulatory principles necessary to support product labeling. As such, the development of a new FD symptom PRO instrument is supported., Competing Interests: Compliance with Ethical Standards The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE) and were fully responsible for all aspects of manuscript development. Fiona Taylor participated in planning and executing the study, analyzing and interpreting the data, and drafting the manuscript; Catherine Foley and Farrah Pompilus participated in planning and executing the study, collecting, analyzing and interpreting the data, and drafting the manuscript; Ramon Iovin participated in collecting, analyzing, and interpreting the data and drafting the manuscript; Alan L. Shields participated in planning and executing the study, interpreting the data, and drafting the manuscript; David S. Reasner provided input on the study design and drafting of the manuscript; Robyn T. Carson, Linda S. Deal, Debra G. Silberg, and Jason Lundy provided input on the study design and manuscript. FT, CF, and ALS are employees of Adelphi Values, which received payment from the sponsors to conduct the research; RI and FP were employees of Adelphi Values at the time this research was conducted. DSR is a member of Albemarle Scientific Consulting and an employee of Ironwood Pharmaceuticals, and owns stock and stock options in Ironwood. RTC is an employee of Allergan and owns stock and stock options in Allergan. At the time of the research, LSD and DGS were employees of Shire, and have shareholdings in Shire and other pharmaceutical companies through stocks and mutual funds. JJL was an employee of the Critical Path Institute at the time this research was conducted. Any views expressed in this publication represent the personal opinions of the authors, not those of their respective employer. The authors’ respective organizations were given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.