Identifying thresholds for meaningful improvements in NTDT-PRO scores to support conclusions about treatment benefit in clinical studies of patients with non-transfusion-dependent beta-thalassaemia: analysis of pooled data from a phase 2, double-blind, placebo-controlled, randomised trial
Issued Date
2024-11-14
Resource Type
eISSN
20446055
Scopus ID
2-s2.0-85209828892
Pubmed ID
39542473
Journal Title
BMJ open
Volume
14
Issue
11
Rights Holder(s)
SCOPUS
Bibliographic Citation
BMJ open Vol.14 No.11 (2024) , e085234
Suggested Citation
Taher A.T., Musallam K.M., Viprakasit V., Kattamis A., Lord-Bessen J., Yucel A., Guo S., Pelligra C.G., Shields A.L., Shetty J.K., Glassberg M.B., Bueno L.M., Cappellini M.D. Identifying thresholds for meaningful improvements in NTDT-PRO scores to support conclusions about treatment benefit in clinical studies of patients with non-transfusion-dependent beta-thalassaemia: analysis of pooled data from a phase 2, double-blind, placebo-controlled, randomised trial. BMJ open Vol.14 No.11 (2024) , e085234. doi:10.1136/bmjopen-2024-085234 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/102202
Title
Identifying thresholds for meaningful improvements in NTDT-PRO scores to support conclusions about treatment benefit in clinical studies of patients with non-transfusion-dependent beta-thalassaemia: analysis of pooled data from a phase 2, double-blind, placebo-controlled, randomised trial
Corresponding Author(s)
Other Contributor(s)
Abstract
OBJECTIVES: To estimate thresholds for defining meaningful within-patient improvement from baseline to weeks 13-24 and interpreting meaningfulness of between-group difference for the non-transfusion-dependent beta-thalassaemia patient-reported outcome (NTDT-PRO) tiredness/weakness (T/W) and shortness of breath (SoB) scores. A secondary objective was to determine the symptom severity threshold for the NTDT-PRO T/W domain to identify patients with symptomatic T/W. DESIGN: Pooled blinded data from the phase 2, double-blind, placebo-controlled, randomised BEYOND trial in NTDT (NCT03342404) were used. Anchor-based analyses supplemented with distribution-based analyses and empirical cumulative distribution function (eCDF) curves were applied. Distribution-based analyses and receiver operating characteristic curves were used to estimate between-group difference and symptomatic thresholds, respectively. SETTING: Greece, Italy, Lebanon, Thailand, the UK and the USA. PARTICIPANTS: Adults (N=145; mean age 39.9 years) with NTDT who were transfusion-free ≥8 weeks before randomisation. MEASURES: Score changes from baseline to weeks 13-24 in PROs used as anchors (correlation coefficient ≥0.3): NTDT-PRO T/W and SoB scores, Patient Global Impression of Severity, Functional Assessment of Chronic Illness Therapy-Fatigue (Fatigue Subscale, item HI12 and item An2) and Short Form Health Survey version 2. RESULTS: The eCDF curves support the use of estimates from the improvement by one level group for all anchors to determine the threshold(s) for meaningful within-patient improvement. Mean (median) changes from these groups and estimates from distribution-based analyses suggest that a ≥1-point reduction in the NTDT-PRO T/W or SoB domains represents a clinically meaningful improvement. Meaningful between-group difference threshold ranges were 0.53-1.10 for the T/W domain and 0.65-1.15 for the SoB domain. The optimal symptomatic threshold for the T/W domain (by maximum Youden's index) was ≥3 points. CONCLUSIONS: The thresholds proposed may support the use of NTDT-PRO in assessing and interpreting treatment effects in clinical studies and identifying patients with NTDT in need of symptom relief.