Development and Validation of the FSIQ-RMS: A New Patient-Reported Questionnaire to Assess Symptoms and Impacts of Fatigue in Relapsing Multiple Sclerosis.

OBJECTIVES: A new patient-reported outcome (PRO) instrument to measure fatigue symptoms and impacts in relapsing multiple sclerosis (RMS) was developed in a qualitative stage, followed by psychometric validation and migration from paper to an electronic format. METHODS: Adult patients with relapsing-remitting multiple sclerosis (RRMS) were interviewed to elicit fatigue-related symptoms and impacts. A draft questionnaire was debriefed in cognitive interviews with further RRMS patients, and revised. Content confirmation interviews were conducted with patients with progressive-relapsing multiple sclerosis (PRMS) and relapsing secondary-progressive multiple sclerosis (RSPMS). Psychometric analyses used data from adult patients with different RMS subtypes and matched non-RMS controls in a multicenter, observational study. After item reduction, the final instrument was migrated to a smartphone (eDiary) and usability was confirmed in interviews with additional adult RMS patients. RESULTS: The qualitative stage included 37 RRMS, 5 PRMS, and 5 RSPMS patients. Saturation of concepts was reached during concept elicitation. Cognitive interviews confirmed that participants understood the instructions, items, and response options of the instrument-named FSIQ-RMS-as intended. Psychometric validation included 164 RMS and 74 control patients. Internal consistency and test-retest reliability were demonstrated. The symptoms domain discriminated along the RMS symptom-severity continuum and between patients and controls. Patients were able to attribute fatigue-related symptoms to RMS. Usability and conceptual equivalence of the eDiary were confirmed (n = 10 participants). CONCLUSIONS: With 7 symptom items and 13 impact items (in 3 impacts subdomains: physical, cognitive and emotional, and coping) after item reduction, the FSIQ-RMS is a comprehensive, valid, and reliable measure of fatigue-related symptoms and impacts in RMS patients.

The CDI-DaySyms: Content Development of a New Patient-Reported Outcome Questionnaire for Symptoms of Clostridium difficile Infection.

OBJECTIVES: To develop a patient-reported outcome (PRO) questionnaire for symptoms of Clostridium difficile infection (CDI) following the US Food and Drug Administration PRO guidelines. METHODS: Patients' experiences of CDI symptoms were elicited in open-ended discussions with patients and nurses at five US sites (stage 1). A draft PRO measure was developed after demonstration of concept saturation. Two rounds of cognitive interviews were conducted with patients at three US sites (stage 2), with revision of the draft measure after each round. All patients were 18 years or older, with confirmed CDI. The study was conducted with input from a panel of five CDI experts in Europe and North America. RESULTS: Stage 1 included interviews with 18 patients and supplementary interviews with 6 nurses; 16 additional patients were interviewed in stage 2. Patients were representative of the general CDI population and were diverse in age, sex, and disease severity. Concept saturation was reached in stage 1. Items were organized in a draft conceptual framework with five hypothesized domains: diarrhea, abdominal discomfort, tiredness, lightheadedness, and other symptoms. Stage 2 demonstrated initial content validity of the 13-item draft daily diary (CDI-DaySyms). Participants reported that the questions were clear, relevant, and comprehensive. They were able to use the instructions to complete the diary correctly and considered the 24-hour recall period appropriate. CONCLUSIONS: The CDI-DaySyms captures symptoms relevant to patients undergoing CDI, demonstrating initial content validity. Final content and psychometric validity are being evaluated in a substudy comprising patients from two ongoing international clinical trials (ClinicalTrials.gov identifiers NCT01987895 and NCT01983683).

Development of the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT®) questionnaire: a new patient-reported outcome instrument for PAH.

BACKGROUND: Regulators and clinical experts increasingly recognize the importance of incorporating patient-reported outcomes (PROs) in clinical studies of therapies for pulmonary arterial hypertension (PAH). No PAH-specific instruments have been developed to date in accordance with the 2009 FDA guidance for the development of PROs as endpoints in clinical trials. A qualitative research study was conducted to develop a new instrument assessing PAH symptoms and their impacts following the FDA PRO guidance. METHODS: A cross-sectional study was conducted at 5 centers in the US in symptomatic PAH patients aged 18-80 years. Concept elicitation was based on 5 focus group discussions, after which saturation of emergent concepts was reached. A PRO instrument for PAH symptoms and their impacts was drafted. To assess the appropriateness of items, instructions, response options, and recall periods, 2 rounds of one-on-one cognitive interviews were conducted, with instrument revisions following each round. Additional interviews tested the usability of an electronic version (ePRO). PRO development considered input from an international Steering Committee, and translatability and lexibility assessments. RESULTS: Focus groups comprised 25 patients (5 per group); 20 additional patients participated in cognitive interviews (10 per round); and 10 participated in usability interviews. Participants had a mean ± SD age of 53.1 ± 15.8 years, were predominantly female (93 %), and were diverse in race/ethnicity, WHO functional class (FC I/II: 56 %, III/IV: 44 %), and PAH etiology (idiopathic: 56 %, familial: 2 %, associated: 42 %). The draft PRO instrument (PAH-SYMPACT®) was found to be clear, comprehensive, and relevant to PAH patients in cognitive interviews. Items were organized in a draft conceptual framework with 16 symptom items in 4 domains (respiratory symptoms, tiredness, cardiovascular symptoms, other symptoms) and 25 impact items in 5 domains (physical activities, daily activities, social impact, cognition, emotional impact). The recall period is the past 24 h for symptoms, and the past 7 days for impacts. CONCLUSIONS: The PAH-SYMPACT® was shown to capture symptoms and their impacts relevant to PAH patients, demonstrating content saturation, concept validity, and ePRO usability. Final content and psychometric validation of the instrument will be based on the results of an ongoing Phase IIIb clinical trial in PAH patients.

Quality of life and healthcare resource use associated with angiographic vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: In this analysis of data from a large clinical trial in aneurysmal subarachnoid hemorrhage, the impact of angiographic vasospasm (aVSP) on specific patient outcomes and inpatient healthcare resource use was assessed. METHODS: This was a post hoc analysis of exploratory end points collected for 409 patients with aneurysmal subarachnoid hemorrhage in the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial. Central reviewers graded severity of aVSP as none, mild, moderate, or severe based on comparison of catheter angiograms obtained at baseline and 7 to 11 days after aneurysmal subarachnoid hemorrhage. Assessments of cognitive status (Mini-Mental State Examination) and patient-relevant outcomes (EuroQol total score and visual analog scale and Functional Status Examination) were administered at Week 12. The relationship between severity of aVSP and these end points as well as inpatient healthcare resource use (intensive care, general ward, and total hospital lengths of stay) was assessed using univariate and multivariate analyses. RESULTS: Cognitive status and all patient-relevant outcome measures varied significantly (P<0.0001) with severity of aVSP (mean for severe aVSP versus no aVSP, respectively: Mini-Mental State Examination, 18.0 versus 27.6; EuroQol total, 0.38 versus 0.74; EuroQol visual analog scale, 50.9 versus 75.5; Functional Status Examination, 20.5 versus 11.7). A significant inverse relationship with severity of aVSP was observed for total hospital days (P=0.008) and days in the intensive care unit (P<0.0001). On average, patients with severe aVSP stayed in the hospital 5 days longer than those with no aVSP. CONCLUSIONS: Severe aVSP is associated with poor cognition, worse patient-relevant outcomes, and greater inpatient healthcare resource use. Future studies assessing new aVSP treatments should include outcome measures that evaluate quality of recovery among survivors.