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Introduction
Hemophilia is an inherited bleeding disorder characterized by recurrent hemorrhaging, particularly within the synovial joints, leading to progressive arthropathy, chronic pain, reduced mobility, and long-term functional limitations. These musculoskeletal complications significantly affect the patient’s ability to perform daily activities and participate fully in social and occupational roles, making functional assessment a central component of modern care. Consequently, reliable patient-reported outcome measures (PROMs) that capture self-perceived functional ability are increasingly important for monitoring treatment outcomes and guiding rehabilitation strategies [1, 2].
The Haemophilia Activities List (HAL) was developed as a disease-specific PROM to evaluate functional abilities in adults with hemophilia based on the conceptual framework of the International Classification of Functioning, Disability and Health (ICF) [3–6]. The initial validation study demonstrated strong internal consistency and good construct validity through correlations with established functional and disability measures, supporting the HAL as a reliable tool for assessing functional limitations [6]. Since its introduction, the HAL has been translated and validated in multiple countries, each demonstrating consistent psychometric properties and confirming the applicability of the instrument across diverse linguistic and cultural settings [2, 4, 7]. Despite these advances, cross-cultural validation remains an essential step before implementation in new populations is possible. Previous studies emphasized that linguistic translation alone is insufficient and must be accompanied by an evaluation of cultural equivalence and psychometric performance to ensure a meaningful interpretation of the results [2, 4].
Despite the growing international adoption of the HAL, a validated Korean version is currently unavailable. Cultural differences in daily activity patterns, environmental contexts, and healthcare delivery may influence individuals’ perceptions and reports of functional limitations. The absence of a validated Korean HAL limits the systematic assessment of patient-reported functional outcomes and hinders direct comparison with international data.
This study aimed to translate, culturally adapt, and evaluate the reliability and construct validity of the Korean version of the HAL for use in adult patients with hemophilia in Korea.
Materials and methods
Study design and participants
This cross-cultural adaptation and psychometric validation study evaluated the reliability and validity of a Korean version of the HAL in adult patients with hemophilia. The methodological framework was based on previously published HAL validation studies followed by structured procedures designed to ensure linguistic accuracy, cultural equivalence, and reliable measurements across populations. This study comprised three sequential phases. First, the original English version of the HAL was translated into Korean and culturally adapted using standardized forward–backward translation procedures. Second, the translated questionnaire was administered to adult patients with hemophilia to assess its internal consistency and construct validity. Third, the questionnaire was readministered to a subgroup of participants after a predefined interval to evaluate the test–retest reliability. The overall design was cross-sectional to evaluate construct validity and internal consistency, with an additional longitudinal component to assess test–retest reliability. The reliability and validity testing procedures were aligned with those used in international validation studies of hemophilia-specific functional outcomes.
Adult patients with hemophilia were recruited from specialized hemophilia clinics affiliated with tertiary care institutions and the Korea Hemophilia Foundation Seoul Clinic. Participants were consecutively recruited from outpatient clinics at the participating institutions, representing the routine clinical population of adult patients with hemophilia in Korea. Eligible participants were male patients aged ≥ 18 years with a confirmed diagnosis of hemophilia A or B. Participants were required to have adequate literacy in Korean to complete self-administered questionnaires independently. Patients with severe cognitive impairment or other medical conditions that could interfere with their comprehension of the questionnaire items were excluded. In addition, patients experiencing acute bleeding episodes at the time of recruitment were temporarily excluded to minimize the influence of transient functional impairment unrelated to the baseline functional status. Baseline demographic and clinical information was collected from medical records and patient interviews. These included age, hemophilia type, disease severity, and clinical characteristics related to joint status.
A total of 87 participants completed the baseline questionnaire and were included in the analysis of internal consistency and construct validity. A subset of 30 participants voluntarily completed the HAL questionnaire again after a 2-week interval to assess test–retest reliability.
Translation and cultural adaptation of the Korean HAL
The translation and cultural adaptation of the HAL were conducted according to structured multistep procedures previously applied in cross-cultural HAL validation studies [8]. These procedures were designed to achieve semantic, conceptual, and cultural equivalence between the original and translated versions. Permission to translate and use the HAL was obtained from Dr. Fisher before the translation process.
The process began with the forward translation of the original English HAL into Korean by bilingual translators fluent in both languages. Two independent forward translations were performed to ensure alternative wording and reduce translational bias. The translated versions were then reviewed and synthesized into a single preliminary version through consensus discussions between the translators and investigators.
Back-translation was subsequently performed by independent bilingual translators who were blinded to the original version. The back-translated versions were compared with the original English questionnaire to identify discrepancies in meaning and interpretation. Differences were discussed and resolved through iterative revisions of the translated version.
An expert review panel, comprising clinicians experienced in hemophilia management and researchers familiar with patient-reported outcome measures, evaluated the translated questionnaire for clarity, cultural appropriateness, and conceptual equivalence. The functional activities described in the HAL were carefully reviewed to ensure their relevance in the Korean sociocultural context. This expert review process has been emphasized as a critical component in previous HAL cross-cultural validation studies.
Pilot testing of the preliminary Korean version of the HAL was conducted in a small group of adult patients with hemophilia. Participants were asked to complete the questionnaire and provide feedback on their comprehension and the questionnaire’s clarity. Based on this feedback, minor revisions were made to improve readability and usability. The final Korean version of the HAL was used in the psychometric validation phase. The Korean version of the HAL questionnaire is provided in Supplementary File 1.
Instrument: HAL
The HAL is a disease-specific, self-administered questionnaire designed to evaluate the functional abilities of adults with hemophilia. It consists of multiple items covering domains related to daily activities and participation, including upper- and lower-extremity functions, self-care, mobility, and leisure activities. This instrument was originally developed based on the ICF framework to capture patient-perceived functional limitations. Each item was scored using a Likert-type response scale that reflects the level of difficulty experienced while performing specific activities. Domain and total scores are calculated according to standardized scoring procedures, with higher scores indicating better functional abilities. The HAL has demonstrated strong internal consistency and construct validity in multiple international validation studies [6, 9].
Instrument: EuroQol five‑dimension five‑level questionnaire
The EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L) is a widely used, generic health-related quality of life instrument that evaluates five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression [10]. The Korean version of the EQ-5D-5L has previously been validated and demonstrated acceptable reliability and validity for measuring general health status [11]. The EQ-5D-5L index scores were calculated using a Korean value set developed for the South Korean population. In the present study, the EQ-5D-5L was used as a generic comparator to assess the construct validity of the Korean HAL. Previous studies have adopted similar approaches to evaluate the relationship between disease-specific functional instruments and general health status. The EQ-5D-5L was used with permission from the EuroQol Research Foundation.
Instrument: Routine Assessment of Patient Index Data 3
The Routine Assessment of Patient Index Data 3 (RAPID3) questionnaire is a functional assessment tool derived from multidimensional health assessment questionnaires and includes components that evaluate physical function, pain, and global health status [12]. The Korean version has been validated as a functional outcome measure of musculoskeletal conditions. In this study, the RAPID3 questionnaire was used as a functional comparator to evaluate the convergent validity of the Korean HAL, as both instruments measure patientperceived functional status.
Assessment of validity
The construct validity of the Korean HAL was evaluated by examining the correlations between HAL scores and other established measures of functional status and healthrelated quality of life. Convergent validity was assessed by calculating the correlation coefficients between the overall HAL and domain scores and the EQ-5D-5L [10, 11] and RAPID3 [12] outcomes, which have been previously validated and widely used in hemophilia and musculoskeletal disease research [13, 14].
Assessment of reliability
The internal consistency reliability was assessed using Cronbach’s alpha coefficients for the overall HAL scores and individual domains. A Cronbach’s alpha value of ≥ 0.70 was considered acceptable. Test–retest reliability was evaluated in a subset of participants who completed the Korean HAL twice during a clinically stable period. Intraclass correlation coefficients (ICCs) were calculated using a two-way random-effects model with absolute agreement. An ICC value ≥ 0.75 was considered indicative of good reliability.
Statistical analyses
Descriptive statistical methods were used to summarize participant characteristics and questionnaire scores. Continuous variables are expressed as means with standard deviations or medians with interquartile ranges, as appropriate, while categorical variables are presented as frequencies and percentages. The internal consistency of the Korean version of the HAL was assessed using Cronbach’s alpha. Test–retest reliability was evaluated using ICCs based on a two-way random-effects model with absolute agreement. Convergent validity was examined using Spearman’s rank correlation coefficients between the overall HAL and domain scores, and EQ-5D-5L and RAPID3 scores. All statistical analyses were performed using SAS software (version 9.4; SAS Institute Inc., Cary, NC, USA). All tests were two-sided, and a p-value < 0.05 indicated statistical significance.
Reporting guidelines
This study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cross-sectional studies [15].
Ethics statement
This study was approved by the Institutional Review Boards of the participating institutions, including Keimyung University Dongsan Medical Center (IRB No. 2013–07–033) and Kyungpook National University Chilgok Hospital (IRB No. 2016–01–021). Written informed consent was obtained from all participants.
Results
Participant characteristics
A total of 100 eligible patients were invited to participate in the study, of whom 87 (87%) completed the questionnaires and were included in the final analysis. The mean age of the participants was 37 years (range: 18–62 years). Among the study population, 68 and 19 patients were diagnosed with hemophilia A and B, respectively. Most participants had severe hemophilia (79 patients), seven had moderate hemophilia, and one had mild hemophilia. Among patients with hemophilia A, 63 had severe disease, four had moderate disease, and one had mild disease. Among the patients with hemophilia B, 16 had severe disease, and three had moderate disease.
All participants completed the Korean version of the HAL at baseline and provided valid responses for the analysis of internal consistency and construct validity. A subgroup of 30 participants completed repeated HAL assessments after a 2-week interval to evaluate test–retest reliability. No major linguistic or cultural issues were identified during translation or pilot testing of the Korean version of the HAL. The translated items were well understood by the participants, and no substantial modifications were required. No conceptual discrepancies were observed between the original and Korean versions.
Internal consistency reliability
The internal consistency of the Korean version of the HAL was high across all domains. The Cronbach’s alpha coefficients ranged from 0.78 to 0.95. The overall HAL scores showed excellent internal consistency with a Cronbach’s alpha value of 0.97. These findings indicate that the Korean HAL items are strongly interrelated and consistently measure functional abilities. The internal consistency results for the total score and each domain are presented in Table 1.
Test–retest reliability
The test–retest analysis demonstrated high temporal stability of the Korean HAL. The ICC for the overall HAL score was 0.95, and the ICCs for the individual domains ranged from 0.80 to 0.95, indicating good to excellent test–retest reliability across the domains. All correlations were statistically significant (p < 0.01), confirming the stability of the Korean HAL in repeated measurements. The test–retest reliability results for the total score and each domain are presented in Table 2.
Construct validity
Significant correlations with both the EQ-5D-5L and RAPID3 scores supported the construct validity of the Korean HAL.
The overall HAL score demonstrated a strong positive correlation with the EQ-5D-5L overall score (r = 0.78, p < 0.01) and moderate to strong correlations with the EQ-5D-5L subdomains, particularly mobility (r = 0.74, p < 0.01), self-care (r = 0.62, p < 0.01), and usual activities (r = 0.79, p < 0.01).
The overall HAL score also showed a strong negative correlation with the RAPID3 physical function score (r = −0.82, p < 0.01). The negative correlation observed between the HAL and RAPID3 scores reflects the opposing scoring systems of the two instruments: higher HAL scores indicate better functional ability, whereas lower RAPID3 scores indicate better physical function. Similar correlation patterns were observed across individual HAL domains, supporting the construct validity of the Korean HAL. The construct validity results for the overall score and each domain are presented in Table 3. Scatter plots illustrating these correlations are shown in Supplementary Figs. 1 and 2.
Discussion
The present study demonstrated that the Korean version of the HAL has excellent reliability and validity in adult patients with hemophilia. The internal consistency was high, with a Cronbach’s alpha coefficient of 0.97 for the total score and domain-specific values ranging from 0.78 to 0.95. Test–retest reliability also demonstrated excellent temporal stability, with an ICC of 0.95 over a 2-week interval, confirming the reproducibility of the Korean HAL under stable clinical conditions. Construct validity was supported by significant correlations between HAL scores and established comparator instruments. Strong correlations with both the EQ-5D-5L and RAPID3 scores indicate that the Korean HAL appropriately reflects general health-related quality of life and functional status. Overall, these findings support the suitability of the Korean HAL as a functional outcome measure in adults with hemophilia and provide a basis for comparison with previously reported international validation studies. The psychometric properties of the Korean HAL observed in this study were consistent with those reported in previous international validation studies.
The internal consistency (Cronbach’s alpha, 0.97) and test–retest reliability (ICC, 0.95) observed in this study were comparable to those reported in the original HAL validation and subsequent reliability studies, which demonstrated strong internal coherence and temporal stability across the functional domains [6, 16]. Cross-cultural validation studies conducted in multiple countries have also reported comparable psychometric performance of translated HAL versions, supporting the robustness of the instrument across different linguistic and cultural settings [2, 4, 7]. These findings indicate that the Korean version preserved the conceptual framework and measurement properties of the original instrument. Overall, the similarity in reliability and validity outcomes across multiple populations supports the generalizability of the Korean HAL and its applicability in both clinical practice and research settings.
The construct validity of the Korean version of the HAL was supported by significant correlations with established comparator instruments, including the EQ-5D-5L and RAPID3 instruments. Strong correlations with these measures indicate that the Korean HAL appropriately reflects patient-perceived functional ability and captures clinically meaningful functional limitations, consistent with previous validation studies of functional outcome measures in hemophilia [7, 14]. The correlations observed with the EQ-5D-5L are particularly meaningful because this instrument is widely used as a generic measure of health-related quality of life across diverse clinical populations, including Korean cohorts [11]. The significant relationship between the HAL and EQ-5D-5L outcomes suggests that functional limitations assessed using the HAL are closely associated with broader aspects of daily functioning and overall health status. Similarly, the strong correlations observed between the HAL and RAPID3 scores further support the functional validity of the Korean HAL. As the RAPID3 evaluates patientreported physical function, the observed alignment indicates that the Korean HAL effectively captures functional domains relevant to patient-perceived physical ability. More importantly, the magnitude of the correlation, rather than its direction, is a key indicator of construct validity. The strong absolute correlations observed in this study support the validity of the Korean HAL as a functional outcome measure, consistent with previous studies demonstrating moderate-to-strong associations between the HAL and other functional instruments [6, 16].
These findings indicate that the Korean version of the HAL demonstrates appropriate relationships with both general and functional health measures, supporting its validity as a comprehensive patient-reported outcome measure capable of assessing functional limitations in adult patients with hemophilia [6, 13]. The consistent construct validity demonstrated in this study highlights the potential clinical applicability of the Korean HAL for routine patient assessment and long-term functional monitoring.
The clinical landscape of hemophilia care has changed substantially in recent years with the widespread adoption of prophylactic treatment strategies and novel therapies, including non-factor replacement agents such as emicizumab [17, 18]. These advances have contributed to improved bleeding control and better preservation of joint function and musculoskeletal health, particularly in younger patients receiving early prophylactic interventions. Consequently, musculoskeletal phenotypes and activity limitations in contemporary hemophilia populations may differ from those observed in historical cohorts used in early validation studies [13]. Although the HAL remains a valuable patient-reported outcome measure for functional assessment, continued evaluation of its responsiveness and sensitivity is warranted in patients with mild functional limitations and evolving treatment patterns.
The availability of a validated Korean version of the HAL has important clinical and research implications. In clinical practice and research settings, the Korean HAL can facilitate systematic assessment of patient-reported functional status, complementing traditional clinical indicators such as bleeding frequency and joint status, and enabling standardized outcome evaluation and meaningful comparison with international data [2, 4, 7]. Establishing a validated Korean version may also facilitate future investigations evaluating functional outcomes in patients receiving contemporary treatment approaches and support the longitudinal assessment of evolving musculoskeletal health in Korean patients with hemophilia.
Although the present study demonstrated strong reliability and validity of the Korean version of the HAL, several aspects require further investigation. An important direction for future research is the evaluation of responsiveness, which is defined as the ability of an instrument to detect clinically meaningful changes in functional status over time. Responsiveness testing is particularly relevant in patients with hemophilia undergoing long-term treatment, where functional ability may change gradually owing to disease progression or therapeutic intervention. Previous studies have emphasized the importance of longitudinal evaluations in confirming sensitivity to clinical changes [16].
Multicenter studies involving diverse patient populations would further strengthen the generalizability of the Korean HAL scale across different clinical settings and support its integration into national registries and collaborative research networks. Continued evaluation of responsiveness, feasibility, and long-term clinical applicability will enhance the utility of the Korean HAL as a standardized outcome measure in hemophilia care [13].
This study had several limitations that should be considered when interpreting the findings. First, it was conducted in a single national setting, which may limit the generalizability of the results to hemophilic populations in different cultural or healthcare environments. Although translation and cultural adaptation procedures have been systematically performed, functional perceptions and activity patterns may vary across different populations. Therefore, additional multicenter studies involving broader patient populations would be valuable to confirm the general applicability of the Korean version of the HAL.
Second, this study primarily evaluated cross-sectional reliability and construct validity and did not include an assessment of responsiveness, which is defined as the ability of an instrument to detect clinically meaningful changes in functional status over time. Responsiveness is particularly important in patients with hemophilia undergoing long-term treatment, where functional ability may change gradually due to disease progression or therapeutic intervention. Future longitudinal studies are warranted to determine whether the Korean HAL is sensitive to functional changes associated with clinical interventions and long-term musculoskeletal outcomes. In addition, the study population was recruited during an earlier treatment era preceding the widespread use of current prophylactic regimens and non-factor therapies, such as emicizumab, and therefore may not fully reflect the functional characteristics of contemporary hemophilia populations. Therefore, additional studies involving contemporary treatment cohorts are warranted.
Third, although the sample size was adequate for psychometric validation, the number of participants available for test–retest reliability analysis was limited (n = 30). Increasing the number of participants in repeated measurement studies and evaluating floor and ceiling effects may further strengthen the precision and interpretability of the reliability estimates.
Despite these limitations, this study demonstrated the consistent reliability and validity of the Korean HAL, supporting its use as a standardized functional assessment tool for adult populations with hemophilia.
In conclusion, the Korean version of the HAL demonstrated excellent reliability and good construct validity in adult patients with hemophilia. These findings support its use as a culturally appropriate patient-reported outcome measure for the standardized functional assessment and long-term monitoring of adult populations with hemophilia.
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