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Objective: Acute intermittent porphyria is a rare metabolic disorder that affects heme synthesis. Patients with acute intermittent porphyria may experience acute debilitating neurovisceral attacks that require frequent hospitalizations and negatively impact quality of life. Although clinical aspects of acute intermittent porphyria attacks have been documented, the experience of patients is not well known, particularly for those more severely affected patients who experience frequent attacks. The aim of the present study was to qualitatively characterize the experience of patients with acute intermittent porphyria who have frequent attacks, as well as the impact of the disease on daily living., Methods: Patients with acute intermittent porphyria who experience frequent attacks were recruited and took part in 2-h qualitative one-on-one interviews with a semi-structured guide. Interviews were anonymized, transcribed, and coded. The inductive coding approach targeted textual data related to acute intermittent porphyria attack symptoms, chronic symptoms, and the impact of the disease. Saturation analysis was conducted to assess whether the research elicited an adequate account of patients' experiences., Results: In total, 19 patients with acute intermittent porphyria were interviewed (mean age 40 years; 79% female). Eighteen patients (95%) experienced both attack and chronic symptoms. Patients described attacks as the onset of unmanageable symptoms that generally lasted 3-5 days requiring hospitalization and/or treatment. Pain, nausea, and vomiting were considered key attack symptoms; pain, nausea, fatigue, and aspects of neuropathy (e.g., tingling and numbness) were considered key chronic symptoms., Conclusions: In this study population of acute intermittent porphyria with frequent attacks, most patients had symptoms during and between attacks. In these patients, acute intermittent porphyria appears to have acute exacerbations as well as chronic day-to-day manifestations, and is not just intermittent as its name implies. As a result, patients reported limitations in their ability to function across multiple domains of their lives on a regular basis and not just during acute attacks.

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.

Background: Chronic low back pain (CLBP) is the most common chronic pain condition and is associated with clinical, economic, social, and public health impacts. The effect of CLBP on patients' health-related quality of life (HRQoL) is significant. The symptoms and impacts most often associated with CLBP include pain and disability; patients most affected are often crippled by the condition. CLBP also affects patients' mental, physical, and psychosocial well-being. A variety of self-report measures have been developed for the assessment of CLBP, such as the Roland Morris Disability Questionnaire (RMDQ); however, existing measures may not meet current regulatory expectation for the development, documentation, and use of patient-reported outcomes (PRO) questionnaires (U.S. Department of Health and Human Services, Food and Drug Administration, 2009)., Objectives: This report describes the qualitative development of the Chronic Low Back Pain Impact Questionnaire (CLBP-IQ), created for use in clinical trials., Methods: A total of 22 CLBP patients recruited by clinicians participated in concept elicitation interviews to identify target measurement concepts. An instrument development team generated the instructions, items, and response options guided by patient input. Cognitive debriefing interviews were conducted with 21 patients recruited by the same clinicians who recruited for concept elicitation interviews. During cognitive interviews, a draft instrument composed of 28 items was presented to individuals with CLBP to evaluate its readability and comprehensiveness. All research activities were conducted in the US., Results: During concept elicitation interviews, participants reported a variety of physical, emotional, and social impacts associated with CLBP. Participants also reported CLBP impacts on sleep, energy, daily activities, work, household activities, leisure activities, cognition, self-care, and sex life. Impacts deemed simple, important, and relevant to CLBP patients became targets of measurement for the CLBP-IQ. During cognitive debriefing, seventeen items were interpreted as intended by at least 90 % of participants, and no items were interpreted incorrectly by more than five patients (24 %). Additionally, seventeen items were experienced by at least 90 % of participants, and no single item was experienced by less than 67 % of participants (n = 14)., Conclusions: The CLBP-IQ was developed in accordance with current US Food and Drug Administration guidance on instrument development. Results from both concept elicitation and cognitive debriefing interviews support the content validity of the CLBP-IQ in patients with CLBP. Future development should proceed with psychometric evaluation.