Patient-reported outcome measures for systemic lupus erythematosus clinical trials: a review of content validity, face validity and psychometric performance.

BACKGROUND: Despite overall progress in treatment of autoimmune diseases, patients with systemic lupus erythematosus (SLE) experience many inflammatory symptoms representing an unmet medical need. This study aimed to create a conceptual model of the humanistic and economic burden of SLE, and review the patient-reported outcomes (PROs) used to measure such concepts in SLE clinical trials. METHODS: A conceptual model for SLE was developed from structured review of published articles from 2007 to August 2013 identified from literature databases (MEDLINE, EMBASE, PsycINFO, EconLit) plus other sources (PROLabels, FDA/EMA websites, Clinicaltrials.gov). PROs targeting key symptoms/impacts were identified from the literature. They were reviewed in the context of available guidance and assessed for face and content validity and psychometric properties to determine appropriateness for use in SLE trials. RESULTS: The conceptual model identified fatigue, pain, cognition, daily activities, emotional well-being, physical/social functioning and work productivity as key SLE concepts. Of the 68 articles reviewed, 38 reported PRO data. From these and the other sources, 15 PROs were selected for review, including SLE-specific health-related quality of life (HRQoL) measures (n = 5), work productivity (n = 1), and generic measures of fatigue (n = 3), pain (n = 2), depression (n = 2) and HRQoL (n = 2). The Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue), Brief Pain Inventory (BPI-SF) and LupusQoL demonstrated the strongest face validity, conceptual coverage and psychometric properties measuring key concepts in the conceptual model. All PROs reviewed, except for three Lupus-specific measures, lacked qualitative SLE patient involvement during development. The Hospital Anxiety and Depression Scale (HADS), Short Form [36 item] Health Survey version 2 (SF-36v2), EuroQoL 5-dimensions (EQ-5D-3L and EQ-5D-5L) and Work Productivity and Activity Impairment Questionnaire: Lupus (WPAI:Lupus) showed suitability for SLE economic models. CONCLUSIONS: Based on the identification of key symptoms and impacts of SLE using a scientifically sound conceptual model, we conclude that SLE is a condition associated with high unmet need and considerable burden to patients. This review highlights the availability and need for disease-specific and generic patient-reported measures of relevant domains of disease signs and symptoms, HRQoL and work productivity, providing useful insight for SLE clinical trial design.

Dressing-related trauma: clinical sequelae and resource utilization in a UK setting.

BACKGROUND: Dressings are the mainstay of wound care management; however, adherence of the dressing to the wound or periwound skin is common and can lead to dressing-related pain and trauma. Dressing-related trauma is recognized as a clinical and economic burden to patients and health care providers. This study was conducted to garner expert opinion on clinical sequelae and resource use associated with dressing-related trauma in a UK setting. METHODS: THIS WAS AN EXPLORATORY STUDY WITH TWO PHASES: qualitative pilot interviews with six wound care specialists to explore dressing-related trauma concepts, sequelae, and resource utilization; and online quantitative research with 30 wound care specialists to validate and quantify the concepts, sequelae, and resource utilization explored in the first phase of the study. Data were collected on mean health care professional time, material costs, pharmaceutical costs, and inpatient management per sequela occurrence until resolution. Data were analyzed to give total costs per sequela and concept occurrence. RESULTS: The results demonstrate that dressing-related trauma is a clinically relevant concept. The main types of dressing-related trauma concepts included skin reactions, adherence to the wound, skin stripping, maceration, drying, and plugging of the wound. These were the foundation for a number of clinical sequelae, including wound enlargement, increased exudate, bleeding, infection, pain, itching/excoriation, edema, dermatitis, inflammation, and anxiety. Mean total costs range from £56 to £175 for the complete onward management of each occurrence of the six main concepts. CONCLUSION: These results provide insight into the hidden costs of dressing-related trauma in a UK setting. This research successfully conceptualized dressing-related trauma, identified associated clinical sequelae, and quantified resource utilization associated with a typical occurrence of each trauma concept. Further research is warranted into dressing-related trauma and the associated costs.