Content validity and psychometric evaluation of the Functional Assessment of Chronic Illness Therapy-Fatigue scale in patients with chronic lymphocytic leukemia.

PURPOSE: Fatigue is a prominent symptom in individuals with chronic lymphocytic leukemia (CLL). This work evaluates the content validity and psychometric properties of the Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-Fatigue) in patients with CLL to determine if it is fit for purpose in CLL research. METHODS: The FACIT-Fatigue yields a 13-item total score from a five-item symptom subscale and an eight-item impact subscale. To evaluate content validity, cognitive debriefing interviews were conducted with 40 patients with CLL in the first-line or relapsed or refractory setting. Psychometric properties, including structural validity, internal consistency, construct and known-groups validity, were investigated using data from a phase 3 trial in relapsed or refractory CLL (NCT02970318). RESULTS: Interviewed patients considered the FACIT-Fatigue items relevant to their CLL experience, understood the terminology and agreed with response options. Confirmatory factor analysis confirmed the presence of symptom and impact subscales, but also supported unidimensionality of the FACIT-Fatigue. The FACIT-Fatigue total, symptom and impact subscales demonstrated good internal consistency (Cronbach's coefficient α > 0.85 and McDonald's omega ω > 0.90), and strong correlations with relevant EORTC QLQ-C30 scales (all Spearman's r ≥ 0.5). Known-groups validity was shown by significant differences between groups defined by baseline performance status, hemoglobin level and constitutional symptoms (all p < .0001). Cluster analysis supported FACIT-Fatigue score thresholds of 30 and 34 to define a severe fatigue population. CONCLUSIONS: Content validity and psychometric evaluation in patients with CLL demonstrated that the FACIT-Fatigue has good psychometric properties and is fit for purpose in CLL.

Validity and performance of the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) among advanced urothelial cancer patients.

PURPOSE: The recent increase in emerging novel therapies in the bladder cancer therapeutic area has increased the need for fit-for-purpose patient-reported outcome (PRO) measures for these patients. This study evaluates the psychometric properties of the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) in 182 patients with advanced urothelial cancer (UC) and fills an important gap by demonstrating its validity for use in clinical trials. METHODS: Data were collected as part of a multicentre, open-label study of durvalumab in patients with inoperable or metastatic solid tumours. Psychometric properties evaluated include item and subscale characteristics (including correlation analysis), reliability (estimated using Cronbach's α), validity (by independent sample t test), responsiveness (using mixed models with repeated measures), and clinically meaningful changes using both anchor-based and distribution-based methods. RESULTS: One hundred and seventy-two patients completed the FACT-Bl questionnaire at baseline. Many individual items had floor or ceiling effects indicative of minimal symptoms and high functioning. The psychometric properties of the existing established scales were assessed and found to range from acceptable to very good. Internal consistency (most Cronbach's α coefficients range 0.66-0.85) and stability (test-retest reliability) generally exceeded standards for good reliability (most estimated intraclass correlations [ICCs] exceeded 0.70, although ICCs for some items [e.g. emotional well-being, ICC 0.58; social well-being, ICC 0.66] were lower than 0.70). Evidence for known-group validity of relevant FACT-Bl subscales and total score was demonstrated by significant differences between groups defined by baseline tumour burden and quality of life scores (difference of FACT-Bl total between low/high tumour burden groups 11.72 (p = 0.001); difference between low/high QoL scores groups 30.51 (p < 0.0001)). The FACT-Bl subscale and total scores were responsive to changes in bladder cancer symptom severity. Clinically meaningful changes in FACT-Bl scores were estimated. CONCLUSIONS: Results support the use of the FACT-Bl within this patient population in future clinical research.

Cost-effectiveness of a fixed-dose combination of solifenacin and oral controlled adsorption system formulation of tamsulosin in men with lower urinary tract symptoms associated with benign prostatic hyperplasia.

BACKGROUND: Storage symptoms, associated with benign prostatic hyperplasia (BPH), often co-exist with voiding symptoms in men with lower urinary tract symptoms (LUTS). Storage symptoms are likely to be most bothersome, and may not be adequately resolved by treatment with α-blocker or antimuscarinic monotherapy. A recent randomised controlled phase 3 trial (NEPTUNE) demonstrated that a fixed-dose combination (FDC) of solifenacin 6 mg plus an oral controlled absorption system (OCAS™) formulation of tamsulosin (TOCAS, 0.4 mg) improved storage symptoms, as well as quality of life, compared with TOCAS alone in men with moderate-to-severe storage symptoms and voiding symptoms. This analysis aimed to assess the cost-effectiveness of a FDC tablet of solifenacin 6 mg plus TOCAS relative to tolterodine plus tamsulosin given concomitantly, from the perspective of the UK National Health Service (NHS). METHODS: A Markov model was developed for men aged ≥45 years with LUTS/BPH who have moderate-to-severe storage symptoms and voiding symptoms. The model calculated cost-effectiveness over an analytical time horizon of 1 year and estimated total treatment costs, quality adjusted life years (QALYs) and incremental cost-effectiveness ratio. RESULTS: The FDC tablet of solifenacin 6 mg plus TOCAS was associated with lower total annual costs (£860 versus £959) and increased QALYs (0.839 versus 0.836), and was therefore dominant compared with tolterodine plus tamsulosin. Time horizon, discontinuation or withdrawal rates, drug cost and utility values were the main drivers of cost-effectiveness. The probability that the FDC tablet of solifenacin 6 mg plus TOCAS is cost-effective was 100% versus tolterodine plus tamsulosin, at a willingness-to-pay threshold of £20,000/QALY gained. CONCLUSIONS: The FDC tablet of solifenacin 6 mg plus TOCAS provides important clinical benefits and is a cost-effective treatment strategy in the UK NHS compared with tolterodine plus tamsulosin for men with both storage and voiding LUTS/BPH.