Understanding treatment burden in hemophilia: development and validation of the Hemophilia Treatment Experience Measure (Hemo-TEM)

Abstract

Background To capture the broad range of treatment burden issues experienced by adolescent and adult people with hemophilia (PWH), the Hemophilia Treatment Experience Measure (Hemo-TEM) was developed. We describe the development of this new hemophilia-specific patient-reported outcome (PRO) measure including concept elicitation, cognitive debriefing, and psychometric validation. Results Concept elicitation interviews were conducted with 5 clinical experts and 30 adult PWH in the United States (US). The qualitative analysis of these interviews and a review of the literature informed the PRO measure development. The project team reviewed concept endorsement rates and generated a 27-item preliminary version of the Hemo-TEM. Cognitive debriefing interviews were conducted to ensure participant understanding and item relevance in samples of (adolescent (n = 20) and adult (n = 14)) PWH in the US. The refined, validation-ready version of the Hemo-TEM included 30 items. Lastly, data from 3 clinical trials comprised the 4 analysis sets used for the psychometric validation with a sample size of N = 88. Item reduction dropped 4 items resulting in a final 26-item measure. Factor analysis generated 5 domains in the Hemo-TEM [injection difficulties (3 items), physical impact (6 items), treatment bother (7 items), interference with daily life (4 items), and emotional impact (6 items)] and a total score. All scores were reliable [internally consistent (0.84–0.88)]. For convergent validity, with the exception of one domain, all hypothesized associations were met. Preliminary sensitivity to change effect sizes were between − 0.30 and − 0.70. Meaningful change thresholds ranged from 6 points (physical impact and emotional impact) to 10 points (treatment bother) with 8 points for the Hemo-TEM total score. Conclusions Findings from the concept elicitation, cognitive debriefing, and psychometric validation phases provide evidence that the Hemo-TEM is a well-designed, valid, and reliable measure of the burden of hemophilia treatment, including treatment impact on adolescent and adult PWH.

Concizumab prophylaxis in persons with hemophilia A or B with inhibitors: patient-reported outcome results from the phase 3 explorer7 study

“…Treatment administration has a substantial physical and emotional impact on patients [ 10 , 30 ]. Key aspects of the treatment burden include injection difficulties, such as venous access issues, interference with daily life due to frequent injections, and the time required for treatment preparation and administration [ 10 ]. Issues contributing to treatment burden may include both the route and mode of administration.…”

“…Patient-reported outcomes (PROs) are an important way of evaluating a patient’s health status, with information reported directly by the patient [ [1] , [2] , [3] ]. PROs can provide insights on patients’ health-related quality of life (HRQoL) [ 2 , 4 , 5 ], activity and physical functioning [ [6] , [7] , [8] ], or treatment-related adherence, satisfaction, or burden [ [9] , [10] , [11] , [12] ]. For persons with hemophilia, both the burden of disease as well as the burden of treatment can impact overall HRQoL, particularly in terms of pain and physical functioning [ [13] , [14] , [15] , [16] ].…”

“…Among persons with hemophilia who develop neutralizing antibodies (inhibitors) against factor replacement products, HRQoL may be further reduced due to more frequent bleeding episodes and the associated limitations in everyday activities [ 14 , 17 , 18 ]. Persons with hemophilia complicated by inhibitors and their caregivers also have a substantial treatment burden [ 3 , 10 , 11 ]. Prophylaxis with bypassing agents has been used in the past with inconsistent results, especially for persons with hemophilia B (HB) with inhibitors (HBwI) [ 3 , 19 ].…”

“… Change from baseline to week 24 PROMIS Numeric Rating Scale v1.0 Pain Intensity 1a Generic measure of average pain intensity experienced in the past 7 days from 0 (no pain) to 10 (worst imaginable pain); higher scores indicate higher pain intensity. Change from baseline to week 24 Hemo-TEM [ 10 ] Hemophilia-specific tool to assess the burden of hemophilia treatment; 26 items are evaluated in 5 domains: injection difficulties, physical impact, treatment bother, interference with daily life, and emotional impact; scores range from 0 to 100; higher scores indicate a higher treatment burden. Change in “total score” from baseline to week 24 H-PPQ a Assesses patient’s hemophilia treatment preference using questions related to preference, including the reasons for, and strength of, their preference.…”

Efanesoctocog alfa: the renaissance of Factor VIII replacement therapy

“…Haematologists, especially when dealing with previously untreated patients (PUPs), based treatment choices on the inhibitor risk associated with the available products. Conflicting study reports on inhibitor development risk for recombinant and plasma-derived FVIII products [6][7][8] , observations of young adults discontinuing prophylaxis, treatment burden with venous access challenges, painful injections, and the time required for intravenous infusion 9 FVIII is produced by vascular endothelial cells and hepatic sinusoidal cells 10 . Most of the produced FVIII circulates bound to its chaperone protein, the large multimeric VWF 11 which is synthesised by endothelial cells and megakaryocytes.…”