2.2.1 PROMIS item banks

Nine Dutch PROMIS item banks were selected by nine members of the PROMIS in Hemophilia Care’ workgroup (IK, MT, LV, MP, SG, MHC, LH, KF, MH), including physicians, physical therapists, and psychologists. Seven item banks were assessed as CAT: V1.2, physical function; V1.1, pain interference; V1.0, depression; V1.0, anxiety; V2.0, ability to participate in social roles and activities (participation); V2.0, satisfaction with social roles and activities (satisfaction with participation); and V1.0, fatigue.15 For two items banks no CAT was available; these were assessed as short form with 8 questions: V1.0, self-efficacy for managing medications and treatment (self-efficacy medications); and V1.0, self-efficacy for managing symptoms (self-efficacy symptoms). All item banks use a 5-point Likert scale. The CATs automatically stopped when the standard error (SE) was ≤2.2 (95% reliability) and/or a maximum of 12 items was administered. PROMIS total scores are calculated by transforming the item scores into T scores, based on US population data, with a mean of 50 and a standard deviation (SD) of 10. For all item banks, higher scores represent more presence of the construct (eg, more pain interference or better physical function). The scores of the short forms were calculated in the PROMIS Assessment Center Scoring Service. All item banks cover a 7-day recall period, except from the physical function and participation, which do not use a recall period, and the self-efficacy item banks, which ask the current level of confidence.

2.2.2 Legacy instruments from HiN-6

The HAL is a validated instrument for assessment of self-reported limitations in activities and participation in patients with hemophilia. It contains 42 items, distributed over seven domains (lying down/sitting/kneeling/standing, functions of the legs, functions of the arms, use of transportation, self-care, household tasks, and leisure activities and sports). Patients score the items on a 6-point Likert scale (impossible, always, mostly, sometimes, rarely, never), with a not applicable (N/A) scoring option for some items. Domain scores, component scores, and sum scores are converted to a normalized domain score ranging from 0 (worst possible functional abilities) to 100 (best possible functional abilities). Domain and component scores were calculated only if a minimum of 50% of items of a domain or component were scored on the 6-point Likert scale. The HAL uses a recall period of 1 month.24, 25 The internal consistency of the HAL was high (Cronbach’s α, 0.97-0.98).24, 26

The RAND-36 measures health-related quality of life across 8 domains (‘physical functioning, role limitations due to physical health problems, bodily pain, general health, energy/fatigue, social functioning, role limitations due to emotional health problems, and emotional well-being), and construct validity has been studied in patients with hemophilia.27 In six of eight domains, patients score the items on a 3- to 6-point Likert scale, and in two of eight domains, patients score yes or no. Scores range from 0 to 100, with higher scores indicating better health status. The recall period varies from at this moment to the last four weeks.28, 29 The internal consistency of the RAND-36 was high (Cronbach’s α, 0.78-0.95).30

The HEP-test-Q is a validated questionnaire for the assessment of subjective physical performance in patients with hemophilia. The HEP-test-Q consists of 25 items pertaining to four domains (mobility, strength & coordination, endurance, and body perception). The response options are a 5-point Likert scale (never to always). Subscales and the total score were transformed to a scale ranging from 0 to 100, with high scores indicating better physical performance. The HEP-test-Q used a recall period of 4 weeks, except for two items assessing physical activity: at this moment and compared to the last year.31 The internal consistency of the HEP-test-Q was high (Cronbach’s α, 0.96).31

The VERITAS-Pro is a validated questionnaire for the assessment of prophylactic treatment adherence in patients with hemophilia. The 24-item questionnaire consists of six subscales (time, dose, plan, remember, skip, communicate). The response options were a 5-point Likert scale (always to never). The score ranges from 100 to 0, with an optimum score of 0. The VERITAS-Pro has a recall period of 3 months.32 The VERITAS-Pro was available only for patients on prophylactic treatment. The internal consistency of the VERITAS-Pro was high (Cronbach’s α, 0.92).32

The PAM-13 measures patient knowledge, skills, and confidence for self-management. All 13 items have five possible responses, with scores ranging from 1 (disagree strongly) to 4 (agree strongly) or 0 (not applicable). The PAM-13 has a calibrated scale range from 38.6 to 53.0 (on a theoretical 0-100 point scale, with 100 as the optimum score). The PAM-13 does not specify a recall period.33, 34 In the general population, internal consistency of the PAM-13 was high (Cronbach’s α, 0.88).34

2.2.3 Patient characteristics

Patient characteristics analyzed included age at HiN-6 participation, type of hemophilia (A or B), severity of the disease (mild [factor VIII/IX activity, 0.06-0.40 IU/mL], moderate [factor VIII/IX activity, 0.01-0.05 IU/mL] or severe [factor VIII/IX activity, <0.01 IU/mL]), clotting factor regimens (prophylaxis yes/no), inhibitor status (current/former/never) and comorbidities (HIV yes/no, hepatitis C current/past/unknown, and other comorbidities).