Psychometric evaluation of the NTDT-PRO questionnaire for assessing symptoms in patients with non-transfusion-dependent beta-thalassaemia

Abstract

ObjectivesThe non-transfusion-dependent beta-thalassaemia-patient-reported outcome (NTDT-PRO) questionnaire was developed for assessing anaemia-related tiredness/weakness (T/W) and shortness of breath (SoB) among patients with NTDT. Psychometric properties were evaluated using blinded data from the BEYOND trial (NCT03342404).DesignAnalysis of a phase 2, double-blind, randomised, placebo-controlled trial.SettingUSA, Greece, Italy, Lebanon, Thailand and the UK.ParticipantsAdults (≥18 years) (N=145) with NTDT who had not received a red blood cell transfusion within 8 weeks prior to randomisation, with mean baseline haemoglobin level ≤100 g/L.MeasuresNTDT-PRO daily scores from baseline until week 24, and scores at select time points for the 36-Item Short Form Health Survey version 2 (SF-36v2), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) and Patient Global Impression of Severity (PGI-S).ResultsCronbach’s alpha at weeks 13–24 was 0.95 and 0.84 for the T/W and SoB domains, respectively, indicating acceptable internal consistency reliability. Among participants self-reporting no change in thalassaemia symptoms via the PGI-S between baseline and week 1, intraclass correlation coefficients were 0.94 and 0.92 for the T/W and SoB domains, respectively, indicating excellent test–retest reliability. In a known-groups validity analysis, least-squares mean T/W and SoB scores at weeks 13–24 were worse in participants with worse scores for the FACIT-F Fatigue Subscale (FS), SF-36v2 vitality or PGI-S. Indicating responsiveness, changes in T/W and SoB domain scores were moderately correlated with changes in haemoglobin levels, and strongly correlated with changes in SF-36v2 vitality, FACIT-F FS, select FACIT-F items and the PGI-S. Improvements in least-squares mean T/W and SoB scores were higher in participants with greater improvements in scores on other PROs measuring similar constructs.ConclusionsThe NTDT-PRO demonstrated adequate psychometric properties to assess anaemia-related symptoms in adults with NTDT and can be used to evaluate treatment efficacy in clinical trials.

Nutrition in Thalassemia: A Systematic Review of Deficiency, Relations to Morbidity, and Supplementation Recommendations

“…Guidelines on the clinical management of transfusion (2014) and non-transfusion-dependent Thal (2017) have been published by the Thalassemia International Federation (TIF). 84,85 While recognizing the risk of nutrient deficiency, TIF does not recommend routine supplementation of any individual micronutrient other than zinc in transfusion-dependent patients identified as zinc deficient (2014). Rather, a diverse, high calcium, high vegetable, and low simple carbohydrate diet is recommended to maximize skeletal development and delay the onset of impaired glucose tolerance.…”

Analysis of Hematological Indices and Splenectomy Rates in 2,130 Patients with Hemoglobin H Diseases or β-Thalassemia

“…Per the Thalassemia International Federation [14,15], to qualify for a splenectomy, a patient's age should exceed 5 years and demonstrate advanced anemia, which can lead to stunted growth such as the inability to receive blood transfusion or iron chelation therapy. Further, the patients demonstrate hypersplenism which can lead to leukopenia, worsening anemia or thrombocytopenia, and clinical problems, such as recurrent bacterial infections or bleeding.…”

Untreated Anemia in Nontransfusion-dependent β-thalassemia: Time to Sound the Alarm

“…In such individuals, transfusions have been commonly reserved for situations of acute stress or an anticipated drop in the hemoglobin level such as during infection, pregnancy, or surgery. Some physicians may prefer to introduce more regular transfusions for NTDT patients, especially to promote growth during childhood or to manage specific morbidities in older patients 7 . When such practices were reviewed in retrospective observational studies, it was well‐established that patients with NTDT who received regular transfusion therapy by reducing ineffective erythropoiesis and improving tissue oxygenation had improved growth, lower prevalence of several morbidities (thromboembolic disease, pulmonary hypertension, leg ulcers, extramedullary hematopoiesis), and improved survival compared to those who did not 8–10 .…”

“…Some physicians may prefer to introduce more regular transfusions for NTDT patients, especially to promote growth during childhood or to manage specific morbidities in older patients. 7 When such practices were reviewed in retrospective observational studies, it was well-established that patients with NTDT who received regular transfusion therapy by reducing ineffective erythropoiesis and improving tissue oxygenation had improved growth, lower prevalence of several morbidities (thromboembolic disease, pulmonary hypertension, leg ulcers, extramedullary hematopoiesis), and improved survival compared to those who did not. [8][9][10] This was already an indication that anemia in this patient population should not be left untreated and several subsequent studies further support this conclusion.…”