Reliability and Validity of the FACT-AN In Patients with Low or Int-1-Risk Myelodysplastic Syndromes with Deletion 5q.

Assessment of health-related quality of life (HRQoL) is important for the comprehensive evaluation of treatment effectiveness from the patient's perspective. The Functional Assessment of Cancer Therapy-Anemia (FACT-An) was developed to measure HRQoL and fatigue in cancer patients with anemia. There is little evidence on the reliability and validity of the FACT-An in patients with low or intermediate-1 (Int-1) risk myelodysplastic syndromes (MDS) with deletion (del) 5q cytogenetic abnormality.

To evaluate the reliability, validity and responsiveness of the FACT-An based on a secondary analysis of data from a phase 3 randomized placebo controlled clinical trial (MDS-004) in patients with low or Int-1-risk MDS with del5q.

This is a secondary analysis of clinical and HRQoL data from a randomized phase 3 clinical trial (Fenaux, 2009) comparing lenalidomide treatment with placebo in patients with MDS with del5q. Patient-reported HRQoL was assessed using the FACT-An questionnaire (Yellen, 1997; Cella, 2002). FACT-A consists of the FACT-General plus additional items that assess the impact of fatigue (FACT-F subscale) and other anemia-related symptoms (FACT-An subscale). The FACT-An was administered at baseline, and weeks 12, 24, 36, and 48. Preference-based HRQoL was measured by the EQ-5D at baseline. Internal consistency reliability (coefficient alpha) was assessed, and construct validity was evaluated using correlations between the baseline FACT scales and the EQ-5D index score. Known groups validity was assessed by analyzing FACT-An scores by hemoglobin (Hb) groups (<8; 8-<10; >=10gd/L) using analysis of variance models. T-tests were used to compare changes in FACT-An scores between Hb responders (>= 1 g/dL improvement) to non-responders at 12 weeks relative to baseline.

Overall, 205 patients participated in the clinical trial; 188 were included in the psychometric analyses (median age 68 y, range 36–86 y). Internal consistency reliability was 0.93 for FACT-An total, 0.94 for the FACT-An Treatment Outcome Index (TOI), 0.93 for the FACT-F TOI, 0.92 for the FACT-An subscale, and 0.91 for FACT-F subscale scores, and ranged from 0.72 to 0.83 for FACT-G scores. At baseline, FACT-An scores were correlated 0.65 to 0.72 with the EQ-5D index score. Mean FACT-An total (p=0.007), FACT-An TOI (p=0.005), FACT-F TOI (p=0.003), FACT-An subscale (p=0.001), FACT-F subscale (p=0.0004) score varied significantly by Hb group, with greater impairment associated with lower Hb levels. Hb responders reported significantly increased FACT-An total (7.5, p=0.0003), FACT-An TOI (8.5, p=0.0001), FACT-F TOI (6.5, p=0.0004), FACT-An subscale (5.5, p<0.0001), and FACT-F subscale (4.2, p=0.0002) scores.

The FACT-An has good reliability and validity in patients with low or Int-1 risk MDS with del5q and is a relevant measure of HRQoL outcomes for clinical trials in patients with this disorder. FACT-An scores were responsive to changes in Hb, demonstrating the ability to detect patient-reported longitudinal changes in HRQoL associated with changes in underlying disease status.

Brandenburg:Celgene: Employment, Equity Ownership. Revicki:Celgene: Consultancy, Research Funding.