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

Symptomatic benefit of momelotinib in patients with myelofibrosis: Results from the SIMPLIFY phase III studies

Momelotinib; Myelofibrosis; Patient-reported outcomesMomelotinib; Mielofibrosi; Resultats informats pel pacientMomelotinib; Mielofibrosis; Resultados informados por el pacienteBackground Myelofibrosis (MF)-associated constitutional symptoms can severely impact health-related quality of life. Clinical trials in MF traditionally measure symptom response to treatment as a landmark endpoint of total symptom score (TSS) reduction ≥50% from baseline. However, this dichotomous assessment provides a limited view of clinically relevant symptomatic changes. Herein we evaluated longitudinal change from baseline in TSS over the continuous 24-week period and individual symptom scores to obtain a more comprehensive understanding of symptom benefits experienced by patients with MF receiving therapy. Methods Longitudinal symptom change was evaluated using mixed-effect model repeated measure (MMRM) methodology with individual item-level analyses to complement the interpretation of the landmark symptom results in the completed phase III SIMPLIFY studies of momelotinib in MF. MMRM compared mean change in TSS from baseline with Week 24 using data from all patient visits. Generalized estimating equations were used to estimate item-level odds ratios using multiple predictive imputations for missing data. Results Momelotinib and ruxolitinib groups reported similar overall symptom improvements, with a TSS difference of <1.5 points between groups for each post-baseline visit in SIMPLIFY-1. In SIMPLIFY-2, the improvement in TSS observed in momelotinib-treated patients was consistent with that observed in SIMPLIFY-1, whereas progressive TSS deterioration was observed with control. Item-level scores were heterogeneous in both studies. A similar and greater proportion of momelotinib-treated patients were categorized as “improved” or “stable” compared with control in SIMPLIFY-1 and SIMPLIFY-2, respectively. Odds ratios for between-group comparison ranged from 0.75 to 1.21 in SIMPLIFY-1, demonstrating similarity in likelihood of symptom improvement. In SIMPLIFY-2, the likelihood of symptom improvement in each item was higher in the momelotinib arm. Conclusions These findings suggest that momelotinib provides clinically relevant symptom benefits in the JAK inhibitor-naïve and JAK inhibitor-exposed settings.SIMPLIFY-1 and SIMPLIFY-2 were sponsored by Gilead Sciences. This analysis was sponsored by Sierra Oncology, a GSK company

Exploring content and psychometric validity of newly developed assessment tools for itch and skin pain in atopic dermatitis.

BackgroundAtopic dermatitis (AD) is a common skin disorder characterized by chronic inflammation, altered skin barrier function, and inflammatory cell skin infiltration that decreases health-related quality of life (HRQoL). The study objective was to understand the patient perspective of AD burden and determine suitable patient-reported outcome (PRO) measures.MethodsThis mixed methods study involved the collection of qualitative and quantitative information from adults (≥ 18 years old) and adolescents (12 - 17 years old) with clinician-confirmed AD regarding their experiences of AD symptoms and its impact on HRQoL. The first part of the study included three stages: in-person concept elicitation (CE) interviews, a 2-week daily electronic diary (eDiary) study, and in-person cognitive debriefing (CD) interviews. An Itch numeric rating scale (NRS) (v1.0) and a Skin Pain NRS (v1.0) evaluation during CD interviews required participants to think about their 'worst' itch and 'worst' skin pain in the past 24 h. Other PRO measures allowed for psychometric testing. The second part of the study involved telephone-depth interviews (TDIs) and qualitative feedback from participants who had not participated in the CD interviews. Qualitative data were thematically analyzed. Psychometric evaluation of NRS measures was performed using eDiary data.ResultsIn the CE interviews, itch and/or itching and skin pain were the most prevalent symptoms consistently discussed by participants. Both NRS measures demonstrated strong psychometric reliability and were applicable across ages with suitable concurrent validity. During the CD interviews, some participants focused their answers on their 'average' itch/itching in the past 24 h, rather than their 'worst' itch. Some participants answered the Skin Pain NRS thinking about general pain or other types of pain, rather than skin pain specifically. Consequently, modifications to both measures addressed these issues and re-tested as paper-and-pen versions in subsequent TDIs. Itch NRS (v2.0) modifications helped participants focus on their worst itching. Most participants preferred Skin Pain NRS v2.0b, which included skin pain descriptors.ConclusionsItching and skin pain are the most important and relevant AD symptoms. The Itch NRS (v2.0) and Skin Pain NRS (v2.0b) appear to be appropriate endpoints for the assessment of itching and skin pain severity for clinical trials with adults and adolescents with AD

Psychometric validation of the Dysphagia Symptom Questionnaire in patients with eosinophilic esophagitis treated with budesonide oral suspension

Abstract Background Eosinophilic esophagitis (EoE) is characterized by high levels of eosinophils in the esophageal mucosa. Patients with the disease present with a range of symptoms, including dysphagia (difficulty swallowing). The aim of this analysis was to assess the psychometric properties of the Dysphagia Symptom Questionnaire (DSQ), a patient-reported outcome (PRO) measure of dysphagia associated with EoE. Psychometric properties of the DSQ were assessed using data collected from a 12-week, phase 2, multicenter, randomized, double-blind, placebo-controlled trial of budesonide oral suspension in adolescents and adults (11–40 years old) with EoE. Results The study population comprised 93 patients with EoE; 94.6% of whom were white, 68.8% were male and the mean age (standard deviation) was 21.6 (7.7) years. Patients had been diagnosed with EoE for a mean of 37.6 months before study initiation. The DSQ was feasible to implement with few item-level data missing at baseline. Item discrimination was high, with floor and ceiling effects below the predefined threshold (≤9%). Higher DSQ scores corresponded with presence and increased severity of dysphagia, indicative of strong item discrimination among patients at baseline (threshold >50%). The DSQ was able to detect changes in symptoms over time and produced similar outcomes to those from physician- and other patient-rated measures, supportive of construct validity. The DSQ had strong test–retest reliability (intraclass correlation coefficient, r = 0.82); and was also responsive to disease-level changes, with higher DSQ scores corresponding to increased esophageal eosinophilic burden. Lastly, the percentage changes in the minimal clinically important difference and clinically important difference in DSQ score were estimated at −27.4% and −55.4%, respectively. Conclusions These analyses support the DSQ as a valid and reliable measure of dysphagia in patients with EoE. Changes in DSQ scores suggest a level of agreement between clinician, patient and histologic response. The DSQ should therefore be considered a viable PRO measure of dysphagia for use in future therapeutic studies of EoE

Psychometric evaluation of the PROMIS® Depression Item Bank: an illustration of classical test theory methods

Background: Psychometric theory offers a range of tests that can be used as supportive evidence of both validity and reliability of instruments aimed at measuring patient-reported outcomes (PRO). The aim of this paper is to illustrate psychometric tests within the Classical Test Theory (CTT) framework, comprising indices that are frequently applied to assess item- and scale-level psychometric properties of PRO instruments. Methods: Using data on the PROMIS Depression Item Bank, typical CTT indices for the assessment of psychometric properties are illustrated, including content validity, item-level data exploration, reliability, and construct validity, particularly confirmatory factor analysis, to test the unidimensionality assumption underlying the item bank. Analyses are carried out on an original item set of 51 depression items, the final (official) PROMIS Depression Item Bank consisting of 28 items, and an 8-item short form. Results: The analyses reported provide an informative illustration on how item- and scale-level reliability and validity statistics can be used to assess the psychometric quality of a PRO instrument. The results illustrate how the reported statistics can be used for item selection from an item pool (here: 51 items). Both the (final) 28-item bank and the 8-item short form show good psychometric properties supporting the high quality of individual items and the unidimensionality assumption of the item bank. Conclusions: It is our hope that our illustration of CTT methods, in conjunction with two companion papers illustrating modern test theory methods, will help researchers to confidently apply a range of statistical tests to evaluate item- and scale-level psychometric performance of PRO instruments

Deep vein thrombosis: validation of a patient-reported leg symptom index

<p>Abstract</p> <p>Introduction</p> <p>Deep vein thrombosis (DVT) is a serious health problem that affects more than 2 million people annually in the United States. Many of these patients develop asymptomatic DVT, but months to years later may experience symptomatic post-thrombotic syndrome (PTS). It is not known how many cases of PTS can be traced to "asymptomatic" DVT because venography is no longer routinely done and ultrasonography (US) may miss some asymptomatic clots. As a result, a clinical tool in addition to US to detect symptom emergence or exacerbation in patients after DVT would be of value.</p> <p>Methods</p> <p>Seventy-seven patients hospitalized with an acute DVT interviewed by telephone at 3–7 days, 30–40 days, and 12-months following discharge were included in this report. All were treated with a standard anticoagulation "Clinical Pathway Protocol" between April 1999 and January 2000. Using a 14-item Deep Vein Thrombosis Leg Symptom Index (DVT-LSI), patients were queried regarding leg pain, swelling, skin discoloration, cosmetic appearance, activity tolerance, emotional distress, and leg-related sleep problems.</p> <p>Results</p> <p>The DVT-LSI for each leg was reliable at all assessments, with instrument reliability (alpha coefficients) greater than 0.70 at all time points (range 0.71–0.87). DVT-LSI scores, and the percentage of patients exhibiting symptoms, were higher in the DVT-affected leg at all time points. Among patients with unilateral disease, symptom severity ratings were significantly worse for patients in the affected leg compared to the normal leg at all time points, with the exception of those with a right-leg DVT at 12 months. Patients with bilateral thrombi did not have different scores on one leg compared to the other.</p> <p>Conclusion</p> <p>The DVT-LSI is useful in assessing symptomatic clinical outcomes in patients after diagnosis of DVT, and may represent a surrogate marker for DVT otherwise presumed to be asymptomatic.</p