Pain attitudes and pain outcomes among people with bleeding disorders: Results from community voices in research.

INTRODUCTION: Among people with bleeding disorders (PwBD), pain is a major problem and pain treatments are often ineffective. Understanding of psychological factors involved in pain processing is limited. Maladaptive pain attitudes are associated with worse pain outcomes and adaptive pain attitudes are associated with better outcomes in high pain conditions, but relationships between pain attitudes and pain outcomes are so far unexplored among PwBD. AIM: To investigate relationships between pain attitudes and pain outcomes among PwBD. METHODS: Pain attitudes were measured with the Survey of Pain Attitudes, containing two adaptive scales (Control and Emotion) and five maladaptive scales (Disability, Harm, Medication, Solicitude, Medical Cure). Adults with bleeding disorders, who had pain, and were enrolled in Community Voices in Research were eligible. Participants (n = 72) completed an online survey. Cross sectional associations between pain attitudes and pain outcomes (pain and prescribed pain medication use) were investigated using logistic regression. RESULTS: After adjustment for covariates, greater Control attitudes were associated with lower odds of more severe pain, and greater Disability, Harm, and Medication attitudes were all associated with higher odds of more severe pain and with higher odds of any prescribed pain medication use and opioid pain medication use. CONCLUSIONS: We presented compelling evidence of relationships between pain attitudes and pain outcomes in PwBD, though corroboration is needed from other populations. Our findings suggest that modification of pain attitudes presents a possible avenue for interventions to improve pain outcomes and increase patient satisfaction with pain management.

Cross-cultural assessment of the influence of the COVID-19 pandemic on the perceived mental health and medical experiences of persons with inherited bleeding disorders and their parents/guardians.

BACKGROUND: Objectives were to 1) assess COVID-19-associated medical and psychological challenges facing persons with inherited bleeding disorders (PIBD) and their parents/guardians (PG) in Germany, the US, and the UK; 2) describe similarities and differences among these countries; 3) identify needs and opportunities for intervention by patient advocacy organizations (PAGs). RESEARCH DESIGN & METHODS: A cross-sectional, international survey was conducted in three countries using validated psychometric instruments and investigator-developed items. RESULTS: Five hundred and four surveys were included. Significant differences between countries were found including experiences with medical care, specific thoughts, and concerns about COVID-19, anxiety, and other mental health measures, as well as resources used to cope with stress. Age, education, income, race, IBD diagnosis, PIBD vs. BD group, and gender had moderating effects on resources used. Communication with friends/relatives and use of PAG and HTCs as resources for information/coping decreased in all countries during the pandemic. CONCLUSIONS: There were similarities and differences between respondents across the country in the perceived impact of the pandemic, mental health scores, and strategies used to cope with stress.  Recommendations: strategies to increase PAG access for PIBD and their PG during pandemics and natural disasters, ongoing assessment and adaptation to provide supportive resources to specific patient subgroups.

Persons with inherited bleeding disorders (PIBD) and their parents faced many challenges during the COVID-19 pandemic. An online survey was conducted within three countries: Germany, the United States, and the United Kingdom to explore these challenges and address how patient advocacy organizations can better meet their needs. Areas explored included experiences with medical care, concerns, and thoughts expressed during the pandemic, and coping resources used before and during the pandemic. In addition, mental health issues were explored addressing anxiety, COVID-related fears, depression, and resilience. Differences were found regarding experiences with medical care, specific thoughts, and concerns about COVID-19, anxiety, and other mental health measures, as well as resources used to cope with stress. These results provide an opportunity for advocacy organizations for PIBD to develop appropriate assessment, adaptation, and education resources to help patients during pandemics and/or natural disasters in the future.

The National Hemophilia Foundation State of the Science Research Summit initiative: executive summary.

INTRODUCTION: The National Hemophilia Foundation State of the Science Research Summit initiative sought to unify research efforts in the US inherited bleeding disorders (BDs) community around key topics of importance to people living with inherited BDs, the lived experience experts. AREAS COVERED: This community-led and -informed project focused on six broad areas - hemophilia A or B; von Willebrand Disease (VWD), platelet dysfunctions and other mucocutaneous inherited BDs; ultra-rare inherited BDs; the unique challenges of people with the potential to menstruate with inherited BDs; diversity, equity and inclusion, health services research, and implementation science; and facilitating research in the inherited BD community through designing an optimizied research infrastructure, enabling resources and funding, and furthering workforce capabilities required to execute the research priorities. EXPERT OPINION: The work summarized here, and in the accompanying supplement manuscripts , has implications not only for the US population but for people globally who have inherited BDs. The information is equally relevant to people living with hemophilia, VWD, the spectrum of inherited platelet disorders, ultra-rare factor deficiencies, and all other inherited BDs as it is to the health care providers and researchers focused on the care and treatment of inherited BDs in the US and globally.

Building the blueprint: Formulating a community-generated national plan for future research in inherited bleeding disorders.

INTRODUCTION: Decades of inherited bleeding disorders (BD) research transformed severe haemophilia from a childhood killer to a disorder managed across a full lifespan for many in economically developed countries. Health equity, a life unimpaired by disease complications, however, remains unimaginable for most people with an inherited BD (PWIBD). AIM: The National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network (ATHN) undertook the development of a community-driven United States (US) National Blueprint for Inherited Bleeding Disorders Research to transform the experience of all PWIBD and those who care for them. METHODS: Extensive community consultations were conducted to identify the issues most important to PWIBD and those who love and care for them. Expert multidisciplinary teams distilled these key areas of need into prioritised research questions, and identified the resources and infrastructure required to pursue them. A summit was held to gather feedback and inform the detailed blueprint. RESULTS: Community-prioritised research areas fell into three broad categories: issues common across inherited BDs, those specific to individual disorders, and issues of infrastructure and capacity. NHF State of the Science Research Summit discussions of the research questions derived from the community priorities by six working groups provided important input for the drafting of the research blueprint for the coming decades. CONCLUSION: The inherited BD community came together to develop the US National Blueprint for Inherited Bleeding Disorders Research dedicated to transforming the lives of all PWIBD including innovating solutions for the rarest disorders and under-represented populations.

Big picture initiatives in bleeding disorders.

INTRODUCTION: The inherited bleeding disorders (IBD) community has witnessed significant therapeutic advances recently, yet important gaps persist, particularly for those with rare disorders and historically underserved populations. AIMS: -To create a national research blueprint agenda, led by the National Hemophilia Foundation (NHF), enhancing patient-centric principles, accelerate research progress and address important gaps in care. -To review critical gaps that remain to be addressed in women with IBDs, who face specific bleeding challenges. METHODS: The NHF research blueprint research agenda was defined by input from across the community, including caregivers and patients who are considered subject matter experts of their IBD, research leaders, allied health professionals and specialists, and representatives of the biopharmaceutical industry. In addition, two medical experts in the field of IBDs performed a comprehensive review to address the knowledge gaps in women with IBDs. RESULTS: Two foundational principles of the NHF blueprint are: (1) it must deliver on key issues that significantly impact the lives of those affected by IBDs, and (2) the priorities defined are relevant and actionable aimed to achieve health equity among all those affected by IBDs. A multidisciplinary approach is necessary for an optimal management of puberty, transition to adulthood and pregnancy. Even if strict guidelines are followed, recent studies show that women with IBDs are still facing a high burden. CONCLUSION: NHF blueprint will be issued in 2022. A specific research agenda is needed in women with IBDs to further improve their management and quality of life.

Quality of life in a large multinational haemophilia B cohort (The B-Natural study) - Unmet needs remain.

INTRODUCTION: The B-Natural study is a multicentre, multinational, observational study of haemophilia B (HB) designed to increase understanding of clinical manifestations, treatment and quality of life (QoL). AIM: To characterise and compare QoL in HB across disease severity groups and individuals with inhibitors to identify gaps in treatment. METHODS: A total of 224 individuals from 107 families were enrolled from a total of 24 centres in North America (n = 16), Europe (n = 7) and Asia (n = 1). Of these, 68 (30.4%) subjects had severe (<1 IU/dL), median age 15.6 years, 114 (50.9%) moderate (1-5 IU/dL), age 13.3 years, and 42 (18.8%) mild (>5-< 40 IU/dL), age 12.1 years, disease. Twenty-nine participants had inhibitors or a history of inhibitors. Three versions of the EQ-5D instrument were used as a measure of QoL: proxy (ages 4-7), youth (ages 8-15) and self (age 16+). Each instrument included a visual analogue scale ranging from 100 (best health) to 0 (worst health) to assess current day's health (EQ VAS). Range-of-motion (ROM) for elbows, knees and ankles was assessed using a four-point scale, from which a composite score was calculated. RESULTS: In all severity groups, a proportion of subjects showed less than optimal QoL. The majority of the mild and moderate severe participants reported a normal EQ-5D health profile (79% and 72%, respectively), whereas about half (47%) of the severe participants and only 13% of the inhibitor participants reported this profile. CONCLUSION: The B-Natural study reveals impacted QoL in all disease severities of HB including those with inhibitors. Unmet needs remain and include nonsevere HB.

Physical therapy within US HTCs: A multicentre survey of utilization, practice patterns and pain management approaches.

INTRODUCTION: Practice patterns and utilization of physical therapists (PTs) affiliated with Hemophilia Treatment Centers (HTCs) in the United States (US) are not well known. AIMS: Describe utilization, role responsibilities and practice patterns of US HTC PTs. Identify practice patterns specifically focusing on assessment and treatment of pain. Recognize gaps in utilization and role responsibilities of PTs as part of the multidisciplinary team and suggest guidelines for PT involvement within the HTC. METHODS: Respondents were a subset of a convenience sample of healthcare providers who responded to a non-validated survey developed by a multi-disciplinary panel of haemophilia experts. RESULTS: A 33.0% response-rate (n = 59) representing all regions of US HTCs was achieved. Those working ≥10 hours per week were more likely to provide nutrition education (P = .026) and surgical options education (P < .001). Those who billed insurance for their services during comprehensive visits were more likely to provide education regarding surgical options (P = .046). The majority of PTs (95.0%) evaluated pain regardless of time spent in clinic and felt comfortable treating pain. Fifty-eight percent used a formal pain measurement tool and more likely to use a formal pain measurement tool if billing insurance (P = .004). Top five non-pharmacologic treatments recommended for pain management included splints/braces (84.8%), aquatic therapy (74.6%), orthotics (71.2%), surgical options (47.5%) and yoga (32.2%). CONCLUSIONS: This study demonstrated PT utilization across HTC centres varies widely. Gaps in care may be addressed through salary support, funded education, greater regional/national collaboration of PTs specializing in bleeding disorders and advocacy for insurance coverage for appropriate services.

Understanding the Pain Management Landscape Within the US Bleeding Disorder Community: A Multi-Center Survey.

OBJECTIVES: Pain is a known complication in persons with hemophilia (PWH) as a result of muscle and joint bleeding. Little is known regarding national Hemophilia Treatment Center (HTC) practice patterns related to pain management. The aim of this study was to: 1) Describe pain management practice patterns of HTC providers, 2) Identify gaps and areas of alignment with the CDC pain guidelines, and 3) Address educational opportunities for pain management. This survey is the first extensive description of multidisciplinary practice patterns of pain management for PWH. METHODS: This descriptive study involved physicians, nurse practitioners, nurses, physical therapists, and social workers from federally funded Hemophilia Treatment Centers (HTC) eligible to complete an online survey exploring pain management practice patterns within the CDC pain guidelines. RESULTS: Results of this survey shed light on areas of strength and cohesiveness between HTC providers, including the following: dedication to effective pain management, utilization of non-pharmacological pain options, trial of non-opioid medications first before opioids, maintaining follow-up with patients after opioid prescription initiation, recognizing and utilizing clinically important findings before prescribing opioids, and counseling their patients regarding potential risk factors. CONCLUSIONS: There remain opportunities to incorporate into clinical practice consistent use of tools such as formal screening questionnaires, opioid use agreements, written measurable goals, ongoing prescription monitoring, and written plans for discontinuation of opioid therapy. These results provide opportunities for improvement in education of HTC team members thus optimizing pain management in persons with bleeding disorders.

Patient preferences and priorities for haemophilia gene therapy in the US: A discrete choice experiment.

INTRODUCTION: Gene therapy has shown promise in clinical trials for patients with haemophilia, but patient preference studies have focused on factor replacement treatments. AIM: We conducted a discrete choice experiment (DCE) to investigate the relative importance and differential preferences patients provide for gene therapy attributes. METHODS: We surveyed male adults with haemophilia in the United States recruited from patient panels including the National Hemophilia Foundation Community Voices in Research platform using an online survey over 4 months in 2020/21. Participants indicated preferences for gene therapy attributes including dosing frequency/durability, effect on annual bleeding, uncertainty related to side effects, impact on daily activities, impact on mental health, and post-treatment requirements. The relative importance of each attribute was analysed overall and for subgroups based on haemophilia type and severity. RESULTS: A total of 183 males with haemophilia A (n = 120) or B (n = 63) were included. Half (47%) had severe haemophilia; most (75%) were White. Overall, participants gave effect on bleeding rate the greatest relative importance (31%), followed by dose frequency/durability (26%), uncertainty regarding safety issues (17%), and impact on daily activities (11%). Dose frequency/durability had the greatest importance for those with haemophilia B (35%). CONCLUSION: People with haemophilia prioritised reduced bleeding and treatment burden; the former was more important in haemophilia A and the latter in haemophilia B, followed by safety and impact on daily life in this DCE of gene therapy attributes. These findings and differences can inform clinical and health policy decisions to improve health equity for people with haemophilia.

Evidence of a disability paradox in patient-reported outcomes in haemophilia.

INTRODUCTION: People with inherited and long-term conditions such as haemophilia have been shown to adapt to their levels of disability, often reporting better quality of life (QoL) than expected from the general population (the disability paradox). AIM: To investigate the disability paradox in people with haemophilia in the United States by examining preference differences in health state valuations versus the general population. METHODS: We conducted a discrete choice experiment including duration to capture valuations of health states based on patient-reported preferences. Participants indicated their preferences for hypothetical health states using the EQ-5D-5L, where each participant completed 15 of the 120 choice tasks. Response inconsistencies were evaluated with dominated and repeated scenarios. Conditional-logit regressions with random sampling of the general population responses were used to match the sample of patients with haemophilia. We compared model estimates and derived preferences associated with EQ-5D-5L health states. RESULTS: After removing respondents with response inconsistencies, 1327/2138 (62%) participants remained (177/283 haemophilia; 1150/1900 general population). Patients with haemophilia indicated higher preference value for 99% of EQ-5D-5L health states compared to the general population (when matched on age and gender). The mean health state valuation difference of 0.17 indicated a meaningful difference compared to a minimal clinically important difference threshold of 0.07. Results were consistent by haemophilia type and severity. CONCLUSION: Our findings indicated the presence of a disability paradox among patients with haemophilia, who reported higher health states than the general population, suggesting the impact of haemophilia may be underestimated if general population value sets are used.

Identified unmet needs and proposed solutions in mild-to-moderate haemophilia: A summary of opinions from a roundtable of haemophilia experts.

INTRODUCTION: The experiences of patients with mild-to-moderate haemophilia differ from those of patients with severe haemophilia or those without a bleeding disorder and include a challenging diagnosis and variability in bleeding symptoms and treatment needs. In addition, there is a significant lack of data on mild-to-moderate haemophilia, and many unmet needs remain to be identified and addressed in this group of patients. METHODS: Challenges for these patients, including women with haemophilia, were identified during a roundtable meeting attended by a group of US-based experts including healthcare professionals (e.g., physicians, nurses, and physical therapists) and patients who live with a bleeding disorder. RESULTS: Identified unmet needs included a lack of proper education on the management of their disorder and prompt treatment of bleeds, absenteeism from school and work, and challenges with personal relationships. Initiatives to assist with alleviating these unmet needs were proposed and include suggestions for healthcare professionals, haemophilia treatment centres (HTCs) and national and local organizations within the bleeding disorders community. These included HTC and community engagement programmes for patients with mild-to-moderate haemophilia, revised transition guidelines for these patients as they approach adulthood and revised diagnostic classification of mild and moderate haemophilia. Challenges unique to women with haemophilia and ways to address these issues were also discussed. CONCLUSION: This paper summarizes the challenges, initiatives and suggestions that were identified by the haemophilia experts during the roundtable meeting.

Impact of haemophilia on patients with mild-to-moderate disease: Results from the P-FiQ and B-HERO-S studies.

INTRODUCTION: Epidemiologic studies suggest that joint bleeding occurs in patients with mild-to-moderate haemophilia, including women and girls. However, most previous studies on the impacts of haemophilia focus on men with severe disease. AIM: To identify unmet needs in men and women with mild-to-moderate haemophilia. METHODS: The Pain, Functional Impairment, and Quality of Life (P-FiQ) study assessed the impact of pain on functional impairment and health-related quality of life in men with haemophilia A or B of any severity. The Bridging Hemophilia B Experiences, Results and Opportunities Into Solutions (B-HERO-S) study evaluated the psychosocial needs of adults and children with haemophilia B of any severity, including women and girls. Both studies employed patient-reported outcome measures. RESULTS: In the P-FiQ study, 16% (62/381) of participants had mild and 13% (50/381) had moderate haemophilia. In the B-HERO-S study, 29% (86/299) of adult participants were female, 25% (74/299) had mild haemophilia, and 63% (189/299) had moderate haemophilia. In addition, 63% (46/74) of patients with mild and 86% (162/189) of patients with moderate haemophilia routinely infused factor products to prevent bleeding. Patients reported difficulty gaining access to factor products (54%; 142/263) and a haemophilia treatment centre (17%; 44/263). During the P-FiQ study, 78% (48/62) of patients with mild and 87% (44/50) with moderate haemophilia described problems with pain on the Brief Pain Inventory. Patients also reported issues with anxiety, depression and relationships. CONCLUSIONS: Mild-to-moderate haemophilia has physical and psychosocial impacts on patients. We offer some solutions to help alleviate these impacts and resolve unmet needs.

Natural history study of factor IX deficiency with focus on treatment and complications (B-Natural).

INTRODUCTION: Haemophilia B (HB) is less well studied than haemophilia A (HA); despite similarities between the two inherited bleeding disorders, important differences remain that require further research. AIM: B-Natural is a multi-centre, prospective, observational study of HB, designed to increase understanding of clinical manifestations, treatment, quality-of-life (QoL), inhibitor development, immune tolerance induction (ITI) outcome, renal function and create a biorepository for future investigations. METHODS: Participants include sibling pairs/groups without a current/history of inhibitors and singletons or siblings with a current/history of inhibitors followed for six months. Demographics, medical, social history and treatment were recorded. A physical examination including joint range of motion (ROM) was performed; QoL was assessed. Samples were collected for F9 gene mutation, HLA typing, non-inhibitory antibodies and renal function testing. RESULTS: Twenty-four centres enrolled 224 individuals from 107 families including 29 with current/history of inhibitors. Of these, 68, 30.4%, had severe (<1% FIX level of normal); 114, 50.9%, moderate (1%-5%); and 42, 18.8%, mild (>5-<40%) disease. At enrolment, 53.1% had 50 + exposure days to exogenous FIX. Comparison of joint scores showed significant (P < .05) differences between those with severe (with/without inhibitors), and those with moderate/mild disease. The majority with severe disease, 80.0% with current/history of inhibitors and 64.3% of those without, were treated with prophylaxis. CONCLUSION: B-Natural provides data supporting an increased understanding of HB and its impact throughout life. The need for optimal disease control to normalize physical and psychosocial outcomes is underscored, and further analyses will contribute to an increased understanding of critical issues in HB.

Awareness, Care and Treatment In Obesity maNagement to inform Haemophilia Obesity Patient Empowerment (ACTION-TO-HOPE): Results of a survey of US haemophilia treatment centre professionals.

BACKGROUND: Despite the high prevalence of overweight and obesity in the United States, few studies have assessed the impact of obesity on haemophilia-specific outcomes or experiences/perceptions of healthcare providers (HCPs) treating haemophilia. AIM: The Awareness, Care and Treatment In Obesity maNagement to inform Haemophilia Obesity Patient Empowerment (ACTION-TO-HOPE) study was designed to identify HCP insights on the unique challenges of patients with haemophilia and obesity/overweight (PwHO) and the barriers to chronic weight management. METHODS: An online survey collected data from haemophilia treatment centre-based HCPs. Respondents included 10 adults and 29 paediatric haematologists, 27 nurses/nurse practitioners/physician assistants, 22 physical therapists and 17 social workers. RESULTS: Almost all HCPs rated obesity of moderate/high concern and reported that weight significantly affects future health and has an impact on life expectancy, yet fewer than 60% reported discussing the impact of weight on health with their patients. HCPs reported that few PwHO tried to lose weight; not many were 'successful'. HCPs perceived a desire to feel better physically and joint pain as top motivating factors. HCPs believe that PwHO would have less joint bleeding and pain and greater mobility if they lost weight. HCPs viewed lack of exercise and food preferences/habits as the biggest barriers to initiating/maintaining weight loss and therefore recommended increasing exercise and healthier eating to their patients. However, physical activity in this patient population is limited and requires advice and support. CONCLUSIONS: Most HCPs appreciated the impact of obesity on joint bleeding, pain, and function and quality of life. Reduced food intake and increased activity are the most commonly recommended weight-loss strategies but the least likely to be successful. HCPs desire additional education/materials to understand weight management for PwHO.

Interrelationship between depression, anxiety, pain, and treatment adherence in hemophilia: results from a US cross-sectional survey.

PURPOSE: Depression, anxiety, pain, and treatment adherence have reciprocal effects not characterized extensively in hemophilia. This study explored the relationships between depression, anxiety, chronic pain, and treatment adherence in adults with hemophilia. PATIENTS AND METHODS: Adults with self-reported hemophilia A or B completed the cross-sectional IMPACT QoL II survey. Depression (9-item Patient Health Questionnaire [PHQ-9]), anxiety (7-item Generalized Anxiety Disorder scale [GAD-7]), chronic pain (Faces Pain Scale-Revised [FPS-R]), social support (Duke UNC Functional Social Support questionnaire), level of pain control, clotting factor treatment adherence (VERITAS-Pro or -PRN), and previous depression/anxiety were analyzed. RESULTS: Among 200 participants (male, 77.3%; female, 22.8%), 54% had PHQ-9 and 52% had GAD-7 scores indicating moderate to severe depression or anxiety without diagnosis of either disorder. Participants with PHQ-9 scores ≥10 (moderate to severe depression) were more likely to have lower treatment adherence than those with PHQ-9 scores <10 (P<0.05). Participants with PHQ-9 or GAD-7 scores ≥10 were more likely to report uncontrolled pain and less social support versus PHQ-9 or GAD-7 scores <10 (χ2 P<0.05). Significant correlations were found between PHQ-9 and GAD-7 (P<0.0001), PHQ-9 and FPS-R (P=0.0004), PHQ-9 and VERITAS (P=0.01), GAD-7 and FPS-R (P=0.02), and GAD-7 and VERITAS (P=0.001). CONCLUSION: Depression and anxiety are underdiagnosed in hemophilia. Depression is associated with anxiety, pain, and lower treatment adherence. While treatment providers play an important role in diagnosis, social workers may play a pivotal role in depression and anxiety screening. This study highlights the importance of regular screening and treatment for these disorders.

Correlations between patient-reported outcomes and self-reported characteristics in adults with hemophilia B and caregivers of children with hemophilia B: analysis of the B-HERO-S study.

PURPOSE: Pain, anxiety, depression, and other aspects of health-related quality of life (HRQoL) are important issues for people with hemophilia and caregivers of children with hemophilia. Patient-reported outcome (PRO) instruments may be used to assess aspects of HRQoL; however, the use of PROs in clinical management of patients with hemophilia is limited and inconsistent. The Bridging Hemophilia B Experiences, Results and Opportunities Into Solutions (B-HERO-S) study evaluated the impact of hemophilia B on HRQoL and other psychosocial aspects in affected adults and caregivers of children with hemophilia B. This post hoc analysis assessed correlations between PRO scores and psychosocial questions commonly asked in comprehensive care settings among B-HERO-S respondents. PATIENTS AND METHODS: B-HERO-S consisted of two online surveys, one administered to adults with hemophilia B (n=299) and one administered to caregivers of children with hemophilia B (n=150). The adult survey included EQ-5D-5L with visual analog scale, BPI, HAL, and PHQ-9. The caregiver survey included PHQ-9 and GAD-7. Questions related to demographics, hemophilia treatment, and psychosocial questions asked in comprehensive care visits were also included in the surveys. A post hoc analysis was performed to assess correlations between responses to selected psychosocial questions with PRO scores. RESULTS: For adults with hemophilia B, greater pain severity and pain interference scores were associated with work-related problems, functional limitations, and relationship, psychological, and treatment issues. Significant correlations were also noted between some of these psychosocial outcomes and depressive symptoms. For caregivers, greater depression and anxiety were associated with employment issues, their child's functional, relationship, and psychological issues, having had difficulty or concerns with treatment/factor availability or affordability, and having less frequent HTC visits. CONCLUSION: High correlations were observed between PRO scores measuring pain, depression, and anxiety and questions commonly used in the comprehensive care setting to assess the psychosocial impact of hemophilia.

Reliability and validity of patient-reported outcome instruments in US adults with hemophilia B and caregivers in the B-HERO-S study.

OBJECTIVE: To assess the reliability and validity of six patient-reported outcomes (PRO) instruments for evaluating health-related quality of life in adults with mild-severe hemophilia B and caregivers of children with hemophilia B, including affected women/girls. METHODS: Adults with hemophilia B and caregivers completed separate online surveys containing several PRO instruments, which were administered to adult participants only (EQ-5D-5L, Brief Pain Inventory v2 Short Form, Hemophilia Activities List, and International Physical Activities Questionnaire), both adults and caregivers (Patient Health Questionnaire [PHQ-9]), or caregivers only (Generalized Anxiety Disorder 7-Item [GAD-7] scale). Construct validity and item-total correlation were assessed using Pearson product-moment correlation, internal consistency was assessed using Cronbach's alpha coefficient, and known-group validity was assessed by comparisons to self-reported characteristics based on the Kruskal-Wallis test. RESULTS: Patient-reported outcomes instruments generally showed satisfactory reliability for adults (n = 299) and caregivers (n = 150). In adults, PRO instruments generally showed high construct validity. Most PRO instruments showed expected significant differences among known groups for adults and caregivers. PHQ-9 and GAD-7 did not show significant differences among caregiver age groups. CONCLUSIONS: Patient-reported outcomes instruments administered in B-HERO-S demonstrated reliability and validity in the broader population of adults with hemophilia B and caregivers when including all severities and genders.