Psychometric evaluation of a patient-reported outcomes instrument for congenital thrombotic thrombocytopenic purpura.

BACKGROUND: Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare, life-threatening hereditary disorder that causes patients to experience significant morbidity and decreased health-related quality of life (HRQoL). A cTTP disease-specific patient-reported outcome (PRO) instrument that is reflective of patients' experiences with the disorder does not currently exist. The objective of this study was to evaluate and validate the psychometric properties of the Congenital Thrombotic Thrombocytopenic Purpura-Patient Experience Questionnaire (cTTP-PEQ), developed using a literature review, interviews with expert clinicians, and qualitative concept elicitation and cognitive debriefing interviews. METHODS: This prospective, observational study (NCT03519672) was conducted with patients diagnosed with cTTP currently receiving treatment. Patients were enrolled through investigator sites and direct-to-patient recruitment. Individuals completed electronic self-administered PRO measures, including the cTTP-PEQ, at baseline and Day 14 (+ up to 10 days). The cTTP-PEQ consisted of five multi-item domains (Pain/Bruising, Cognitive Impairment, Visual Impairment, Mood, Treatment Burden) and three single-item domains (Fatigue, Headache, Activity Limitation), and assessed symptoms and impact of cTTP in the previous 24 h, 7 days, and 2 weeks. Convergent and discriminant validity were evaluated using Spearman's rank correlation coefficients. Known-groups validity was assessed between patient groups separated by Patient Global Impression of Severity (PGI-S; normal vs. mild/moderate/severe). Internal reliability was assessed using Cronbach's alpha. Test-retest reliability was assessed using intraclass correlation coefficients (ICCs). RESULTS: Thirty-six patients participated in this study. Convergent validity was confirmed with high-to-moderate correlations (r ≥ 0.4) for 12/15 hypothesized relationships between pairs of domains and/or total scores. Discriminant validity was confirmed with low correlations (r < 0.3) observed for 5/7 hypothesized relationships. Known-groups validity was confirmed with significant differences (p ≤ 0.05) in mean cTTP-PEQ scores between the two PGI-S groups for most domains and items at both timepoints. Cronbach's alpha was 0.88 at baseline and 0.91 at Day 14, confirming internal consistency of the instrument. Test-retest reliability was also confirmed with a high ICC (0.96). CONCLUSION: This study validates the psychometric properties of the novel cTTP-PEQ for use in research and clinical practice to assess HRQoL among patients with cTTP. This instrument will be particularly useful when assessing cTTP disease burden and the impact of new treatments.

Exploring preferences of different modes of administration of hypomethylating agent treatments among patients with acute myeloid leukemia.

Introduction: About half of patients with Acute Myeloid Leukemia (AML) are not eligible for Standard Induction Chemotherapy (SIC). Hypomethylating Agents (HMAs) intravenously (IV) or subcutaneously (SC) in a clinical setting are typically offered as an alternative. However, injectable HMAs may be burdensome for patients given the frequent hospital visits and side effects. This study explored patient treatment preferences for different modes of administration (MOA) and the relative importance of treatment-related characteristics that influence treatment decisions. Methods: Semi-structured 1:1 interviews were conducted with 21 adult patients with AML in Germany, the United Kingdom, and Spain, who are not eligible for SIC, had experience with HMAs or were scheduled to be treated with HMAs. After discussing their experience of living with AML and its treatments, patients were presented with hypothetical treatment scenarios to explore their preferences, and a ranking exercise to assess the relative importance of treatment characteristics that influence their treatment-decisions for AML. Results: Most patients reported an overall preference for oral administration over parenteral routes (71%), mostly due to convenience. Those preferring IV or SC routes (24%) reasoned with faster speed of action and onsite monitoring. When presented with a hypothetical situation of a patient having to choose between two AML treatments that were identical except for their MOA, the majority preferred the oral route (76%). Regarding treatment characteristics that influence treatment decisions, patients most frequently reported efficacy (86%) and side effects (62%) as important, followed by mode of administration (29%), daily life impacts (24%) and location of treatment (hospital versus home) (14%). However, only efficacy and side effects were rated as number one deciding factors (67% and 19%, respectively). Patients most frequently rated dosing regimen (33%) as least important. Conclusion: The insights gained from this study may help support patients with AML who are receiving HMA treatment instead of SIC. A potential oral HMA with similar efficacy and tolerability profiles to injectable HMAs could influence treatment decisions. Furthermore, an oral HMA treatment might decrease the burden of parenteral therapies and improve patients' overall quality of life. However, the extent of influence MOA has on treatment decisions requires further investigation.

Physician treatment preferences for relapsed/refractory multiple myeloma: a discrete choice experiment.

Aim: This study aimed to assess physician preferences for later lines (third to fifth) of therapy in patients with relapsed/refractory multiple myeloma (RRMM) in the USA. Materials & methods: Factors relevant to physicians' treatment preferences for RRMM were identified from a literature search and refined in a qualitative phase. Preferences were quantitatively assessed using a discrete choice experiment. Physicians (n = 227) made choices regarding treatment scenarios for RRMM. Results: Efficacy had the highest mean relative importance, with overall survival valued as most important when making treatment decisions for patients with RRMM. Reduced incidences of keratopathy and thrombocytopenia had similar relative importance in later-line treatment. Conclusion: Greater understanding of physicians' criteria for clinical decision-making may help inform wider adoption of new treatments.

When deciding which treatment patients with relapsed or refractory multiple myeloma should receive, physicians have to weigh the benefits of each treatment against the risk of side effects. This study required physicians to complete a survey on aspects involved in their treatment decisions and identified those of highest importance. Physicians chose patient survival as the most important factor and minimization of side effects as less important considerations. Reducing patients' risk of developing corneal conditions or low platelet (a type of blood cell) count were of equal importance to doctors. Understanding physicians' treatment preferences and the reasons behind them will help identify gaps in education about new therapies as they become available.

Fatigue, quality of life and physical fitness following an exercise intervention in multiple myeloma survivors (MASCOT): an exploratory randomised Phase 2 trial utilising a modified Zelen design.

BACKGROUND: Exercise may improve fatigue in multiple myeloma survivors, but trial evidence is limited, and exercise may be perceived as risky in this older patient group with osteolytic bone destruction. METHODS: In this Phase 2 Zelen trial, multiple myeloma survivors who had completed treatment at least 6 weeks ago, or were on maintenance only, were enrolled in a cohort study and randomly assigned to usual care or a 6-month exercise programme of tailored aerobic and resistance training. Outcome assessors and usual care participants were masked. The primary outcome was the FACIT-F fatigue score with higher scores denoting less fatigue. RESULTS: During 2014-2016, 131 participants were randomised 3:1 to intervention (n = 89) or usual care (n = 42) to allow for patients declining allocation to the exercise arm. There was no difference between groups in fatigue at 3 months (between-group mean difference: 1.6 [95% CI: -1.1-4.3]) or 6 months (0.3 [95% CI: -2.6-3.1]). Muscle strength improved at 3 months (8.4 kg [95% CI: 0.5-16.3]) and 6 months (10.8 kg [95% CI: 1.2-20.5]). Using per-protocol analysis, cardiovascular fitness improved at 3 months (+1.2 ml/kg/min [95% CI: 0.3-3.7]). In participants with clinical fatigue (n = 17), there was a trend towards less fatigue with exercise over 6 months (6.3 [95% CI: -0.6-13.3]). There were no serious adverse events. CONCLUSIONS: Exercise appeared safe and improved muscle strength and cardiovascular fitness, but benefits in fatigue appeared limited to participants with clinical fatigue at baseline. Future studies should focus on patients with clinical fatigue. CLINICAL TRIAL REGISTRATION: The study was registered with ISRCTN (38480455) and is completed.