• Adherence and a Potential Trade-Off Currently Faced in Optimizing Hemophilia Treatment

      Burke, Tom; Asghar, Sohaib; Misciattelli, Natalia; Kar, Sharmila; Morgan, George; Dhillon, Harpal; O'Hara, Jamie (American Society of Hematology, 2020-11-05)
      INTRODUCTION Severe hemophilia, i.e., <1% normal FVIII level (A) or FIX level (B), are congenital bleeding disorders characterized by uncontrolled bleeding. The clinical benefits of prophylactic FVIII/IX replacement therapy are well understood, but require adherence to a schedule of routine infusions. Optimal adherence is associated with better joint outcomes and lower rates of chronic pain. Nonetheless a lack of patient-reported data has to date limited our understanding of the patient burden associated with adherence to treatment, and the relationship between adherence and the ability to work, among people living with hemophilia in the US. Data from the Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) study reported a high proportion of adults with hemophilia B receiving routine infusions (at least one infusion per month), showing a negative impact on their ability to work, and people receiving routine infusions were more likely than people treated on-demand to report an inability to work in most situations. The ability of people living with hemophilia to participate in the labor force, without barriers to job choice or working hours, is a key outcome in the drive to achieve health equity. The objective of the analysis is to examine the relationship between adherence and the labor force participation of people with severe hemophilia in the US. METHODS This analysis draws data from a patient-reported study, the 'Cost of Severe Hemophilia Across the US: A Socioeconomic Survey' (CHESS US+). Conducted in 2019, the CHESS US+ study is a cross-sectional patient-centered study of adults with severe hemophilia in the US. A patient-completed questionnaire collected data on clinical, economic, and humanistic outcomes, for a 12-month retrospective period. This analysis examines labor force participation and employment status (full-time, part-time, unemployed, retired) and chronic pain categorized by 'none', low-level ('1-5'), and high-level ('6-10'). The analysis was stratified by adherence to treatment, self-reported on a 1-10 scale, from "not at all" to "fully", categorized into low (1-6), moderate (7-9) and full (10) adherence. Results are presented as mean (standard deviation) or N (%). RESULTS The analysis comprised 356 people with severe hemophilia A (73%) and B (27%) who participated in CHESS US+ study. In Table 1, the baseline characteristics of the study population are stratified by full adherence (N = 119), moderate adherence (N=134) and low adherence (N=103). Having no chronic pain was most prevalent in the full adherence group (37.7%), compared to moderate (8.3%) or low (13.9%) adherence cohorts. Chronic pain, both low- and high-levels were least prevalent among people with full adherence. Moreover, people with low adherence were disproportionately more likely to have high-levels of chronic pain relative to moderate adherence or full adherence (Table 1). Unemployment, however, was highest in full adherence (21.1%), and people with full adherence were also least likely to be in full-time employment (42%). The full-time employment rate decreased as adherence declined from full to moderate (Table 1), and was comparable in people with low adherence (57.3%) or moderate adherence (54.5%). CONCLUSIONS This analysis of CHESS US+ examined the complex relationship between labor market outcomes and adherence to treatment, among adults with severe hemophilia in the US. Adherence was associated with lower rates of chronic pain, representing the importance of achieving an optimal treatment strategy. Nonetheless, patients achieving optimal adherence were less likely to be in full-time employment, and more likely to be part-time or unemployed, comparatively. Together, these data characterize a trade-off in clinical outcomes versus workforce participation, and suggest that the goal of achieving health equity may currently still be unmet. Disclosures Burke: HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Asghar:HCD Economics: Current Employment. Misciattelli:Freeline: Current Employment, Current equity holder in publicly-traded company. Kar:Freeline: Current Employment, Current equity holder in publicly-traded company. Morgan:uniQure: Consultancy; HCD Economics: Current Employment. Dhillon:HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Other: All authors received editorial support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. . O'Hara:HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy.
    • Adherence and a Potential Trade-Off Currently Faced in Optimizing Hemophilia Treatment

      Burke, Tom; Asghar, Sohaib; Misciattelli, Natalia; Kar, Sharmila; Morgan, George; Dhillon, Harpal; O'Hara, Jamie (Elsevier, 2021-08-03)
      INTRODUCTION Severe hemophilia, i.e., <1% normal FVIII level (A) or FIX level (B), are congenital bleeding disorders characterized by uncontrolled bleeding. The clinical benefits of prophylactic FVIII/IX replacement therapy are well understood, but require adherence to a schedule of routine infusions. Optimal adherence is associated with better joint outcomes and lower rates of chronic pain. Nonetheless a lack of patient-reported data has to date limited our understanding of the patient burden associated with adherence to treatment, and the relationship between adherence and the ability to work, among people living with hemophilia in the US. Data from the Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) study reported a high proportion of adults with hemophilia B receiving routine infusions (at least one infusion per month), showing a negative impact on their ability to work, and people receiving routine infusions were more likely than people treated on-demand to report an inability to work in most situations. The ability of people living with hemophilia to participate in the labor force, without barriers to job choice or working hours, is a key outcome in the drive to achieve health equity. The objective of the analysis is to examine the relationship between adherence and the labor force participation of people with severe hemophilia in the US. METHODS This analysis draws data from a patient-reported study, the ‘Cost of Severe Hemophilia Across the US: A Socioeconomic Survey’ (CHESS US+). Conducted in 2019, the CHESS US+ study is a cross-sectional patient-centered study of adults with severe hemophilia in the US. A patient-completed questionnaire collected data on clinical, economic, and humanistic outcomes, for a 12-month retrospective period. This analysis examines labor force participation and employment status (full-time, part-time, unemployed, retired) and chronic pain categorized by ‘none’, low-level ('1-5'), and high-level ('6-10'). The analysis was stratified by adherence to treatment, self-reported on a 1-10 scale, from “not at all” to “fully”, categorized into low (1-6), moderate (7-9) and full (10) adherence. Results are presented as mean (standard deviation) or N (%). RESULTS The analysis comprised 356 people with severe hemophilia A (73%) and B (27%) who participated in CHESS US+ study. In Table 1, the baseline characteristics of the study population are stratified by full adherence (N = 119), moderate adherence (N=134) and low adherence (N=103). Having no chronic pain was most prevalent in the full adherence group (37.7%), compared to moderate (8.3%) or low (13.9%) adherence cohorts. Chronic pain, both low- and high-levels were least prevalent among people with full adherence. Moreover, people with low adherence were disproportionately more likely to have high-levels of chronic pain relative to moderate adherence or full adherence (Table 1). Unemployment, however, was highest in full adherence (21.1%), and people with full adherence were also least likely to be in full-time employment (42%). The full-time employment rate decreased as adherence declined from full to moderate (Table 1), and was comparable in people with low adherence (57.3%) or moderate adherence (54.5%). CONCLUSIONS This analysis of CHESS US+ examined the complex relationship between labor market outcomes and adherence to treatment, among adults with severe hemophilia in the US. Adherence was associated with lower rates of chronic pain, representing the importance of achieving an optimal treatment strategy. Nonetheless, patients achieving optimal adherence were less likely to be in full-time employment, and more likely to be part-time or unemployed, comparatively. Together, these data characterize a trade-off in clinical outcomes versus workforce participation, and suggest that the goal of achieving health equity may currently still be unmet. Disclosures Burke: HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Asghar: HCD Economics: Current Employment. Misciattelli: Freeline: Current Employment, Current equity holder in publicly-traded company. Kar: Freeline: Current Employment, Current equity holder in publicly-traded company. Morgan: uniQure: Consultancy; HCD Economics: Current Employment. Dhillon: HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Other: All authors received editorial support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. . O'Hara: HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy.
    • Adult lifetime cost of hemophilia B management in the US: Payer and societal perspectives from a decision analytic model.

      Li, Nanxin; Sawyer, Eileen K; Maruszczyk, Konrad; orcid: 0000-0002-0173-5020; Guzauskas, Greg; orcid: 0000-0002-9095-1672; Slomka, Marta T; Burke, Tom; Martin, Antony P; O'Hara, Jamie; Stevenson, Matt; Recht, Michael (2021-02-16)
      Hemophilia B (HB) is a rare congenital disorder characterized by bleeding-related complications which are managed by prophylactic or post-bleeding event ("on-demand") replacement of clotting factor IX (FIX). The standard of care for severe HB is life-long prophylaxis with standard half-life (SHL) or extended half-life (EHL) products given every 2-3 or 7-14 days, respectively. FIX treatment costs in the US have been investigated, but the lifetime costs of HB treatment have not been well characterized, particularly related to the impact of joint health deterioration and associated health resource utilization. We developed a decision-analytic model to explore outcomes, costs and underlying cost drivers associated with FIX treatment options over the lifetime of an adult with severe or moderately severe HB. With participation from clinicians, health technology assessment specialists and patient advocates, a Markov model was constructed to estimate bleeding events and costs associated with health states including 'bleed into joint', 'bleed not into joint', 'no bleed' and death. Sub-models of joint health were based on 0, 1, or ≥2 areas of chronic joint damage. US third-party payer and societal perspectives were considered with a lifetime horizon; sensitivity analyses tested the robustness of primary findings. Total adult lifetime costs per patient with severe and moderately severe HB were $21,086,607 for SHL FIX prophylaxis, $22,987,483 for EHL FIX prophylaxis, and $20,971,826 for on-demand FIX treatment. For FIX prophylaxis, the cost of FIX treatment account for >90% of the total HB treatment costs. This decision analytic model demonstrated significant economic burden associated with the current HB treatment paradigm.
    • An Insight into the Impact of Hemophilia a on Daily Life According to Disease Severity: A Preliminary Analysis of the CHESS II Study

      Noone, Declan; Nissen, Francis; Xu, Tao; Burke, Tom; Asghar, Sohaib; Dhillon, Harpal; Aizenas, Martynas; Meier, Oliver; O'Hara, Jamie; Khair, Kate (Elsevier, 2021-08-03)
      Introduction: Hemophilia A (HA) is a congenital bleeding disorder caused by a deficiency in clotting factor VIII (FVIII). There are currently limited data on the impact of HA on daily life. Here we examine the impact of HA on the daily life of adult persons with HA (PwHA) without current FVIII inhibitors according to disease severity. Methods: The Cost of Haemophilia in Europe: a Socioeconomic Survey II (CHESS II) is a retrospective, burden-of-illness study in adults with mild, moderate, and severe HA or hemophilia B (defined by endogenous FVIII/IX [IU/dL] relative to normal; mild, 5-<40%; moderate, 1-5%; severe, <1%); this analysis includes only PwHA. Male participants (aged ≥18 years) diagnosed with HA (without FVIII inhibitors) at least 12 months prior to clinical consultation were enrolled from Denmark, France, Germany, Italy, the Netherlands, Romania, Spain, and the UK. Data on clinical outcomes and healthcare resource utilization were captured via electronic case report forms disseminated to hemophilia specialists. PwHA completed a paper-based questionnaire utilizing 5-point Likert scales to assess the disease burden on their daily life. Overall, 12 months’ retrospective data were examined. Informed consent was obtained and the study was approved by the University of Chester ethical committee. Results: Of 258 PwHA completing questionnaires, 15.9% (n=41), 27.9% (n=72), and 56.2% (n=145) had mild, moderate, and severe HA, respectively. Of those with severe HA, 60.0% were currently receiving FVIII prophylaxis (standard of care for severe HA); in comparison, 4.9% and 6.9% of those with mild and moderate HA were receiving prophylaxis (Table 1). Treatment adaptation in anticipation of physical or social activity was reported by 19.5%, 23.6%, and 38.6% of those with mild, moderate, and severe HA, respectively. Over a third of participants with mild (36.6%) and moderate (44.4%) HA, and 64.8% of those with severe HA (58.6% with severe HA receiving on-demand treatment and 69.0% receiving prophylaxis) agreed or strongly agreed that HA had reduced their physical activity (Figure 1). Overall, 38.9% of those with moderate HA and 58.6% of those with severe HA (63.8% with severe HA receiving on-demand treatment and 55.2% receiving prophylaxis) agreed or strongly agreed that their HA had reduced their social activity; this was less pronounced in mild HA (9.8%). Additionally, 31.7%, 36.1%, and 64.1% of those with mild, moderate, and severe HA (62.1% with severe HA receiving on-demand treatment and 65.5% receiving prophylaxis) agreed or strongly agreed that their HA had caused them to miss opportunities. Correspondingly, frustration due to HA was felt by 19.5%, 34.7% and 57.9% (56.9% with severe HA receiving on-demand treatment and 58.6% receiving prophylaxis) of people, respectively. When asked whether they believed their daily life was compromised due to their hemophilia, 24.4%, 37.5%, and 63.4% of those with mild, moderate, and severe HA, respectively, agreed. Pain, as reported by the physician, was noted in 36.6% of people with mild HA (100% was reported as 'mild'); in people with moderate HA, pain was reported as 'mild', ‘moderate’, and ‘severe’ in 44.4%, 20.8%, and 1.4% of PwHA, respectively. In people with severe HA, pain was reported as ‘mild’, ‘moderate’, and ‘severe’ in 39.7%, 27.6%, and 8.6% for those receiving on-demand treatment, and 37.9%, 32.2%, and 8.0% for those receiving prophylaxis, respectively. Conclusions: In all disease severity groups, there was a notable group of PwHA that felt that they have had to reduce their physical and social activity, have had fewer opportunities and are frustrated due to their disease. While the impact on daily life is most pronounced in people with severe HA (including those receiving on-demand treatment and those receiving prophylaxis), it is also apparent in mild and moderate HA, indicating that there may be an unmet medical need in these groups. Disclosures Noone: Healthcare Decision Consultants: Membership on an entity's Board of Directors or advisory committees; Research Investigator PROBE: Research Funding; European Haemophilia Consortium: Membership on an entity's Board of Directors or advisory committees. Nissen: F. Hoffmann-La Roche Ltd: Current Employment; Actelion: Consultancy; Novartis: Research Funding; GSK: Research Funding. Xu: F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Burke: University of Chester: Current Employment; HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Asghar: HCD Economics: Current Employment. Dhillon: F. Hoffmann-La Roche Ltd: Other: All authors received editorial support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. ; HCD Economics: Current Employment. Aizenas: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Meier: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. O'Hara: HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy. Khair: Biomarin: Consultancy; HCD Economics: Consultancy; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medikhair: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Takeda: Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Haemnet: Membership on an entity's Board of Directors or advisory committees.
    • Bleeding Data across Baseline FIX Expression Levels in People with Hemophilia B: An Analysis Using the 'Factor Expression Study'

      Burke, Tom; Shaikh, Anum; Ali, Talaha; Li, Nanxin; Konkle, Barbara A; Noone, Declan; O'Mahony, Brian; Pipe, Steven W; O'Hara, Jamie (American Society of Hematology, 2021-11-05)
      Abstract Introduction Complications such as spontaneous and trauma-related bleeding events typically experienced by people with hemophilia B (PWHB) are associated with long-term joint damage and chronic pain, and burdensome treatment with intravenous factor IX administration. Gene therapy, designed to enable the endogenous production of the missing clotting factor, has potential for curative benefit in PWHB (Dolan et al, 2018). Due to its link to risk for bleeding episodes, factor expression level (FEL) is commonly used as an endpoint in hemophilia gene therapy trials. However, little data currently exist linking FEL to bleeding risk in PWHB, most notably within the mild range. As such, the aim of this analysis was to examine the relationship between annual bleed rate (ABR) data across baseline FEL in PWHB. Methods Data from adult non-inhibitor PWHB, across Europe and the United States (US) who received clotting factor on-demand (OD), were drawn from the 'Cost of HaEmophilia in adults: a Socioeconomic Survey' (CHESS) studies. The CHESS studies are retrospective, burden-of-illness studies in people with hemophilia A or B, capturing the economic and humanistic burden associated with living with hemophilia. Additional data were collected to supplement the existing CHESS studies, particularly in people with exogenous FEL in the mild and moderate range. ABR was defined as the physician-reported number of bleed events experienced by the patient in the 12 months to study capture. A generalized linear model (GLM) was used to analyze variation in ABR data across FEL, adjusting for covariates age, body mass index (BMI), and blood-borne viruses. Following this, a multivariable restricted cubic spline (RCS) GLM regression was performed to create, model, and test for the potential non-linear relationship between FEL and ABR. The RCS regression employed 3 knots, located at baseline FEL values of 1, 5, and 10, and controlled once again for age, BMI, and blood-borne viruses. Results A total of 407 adult non-inhibitor PWHB, receiving an OD therapy regimen and with information on ABR, were profiled. The GLM provided adequate fit for the modeling of bleed data; the average marginal effect at the mean was computed from the GLM regression outputs. After controlling for the effects of all other model covariates, the regression analysis showed a significant association between FEL and ABR; for every 1% increase in FEL, the average ABR decreased by 0.08 units (p&amp;lt;0.001). The results of the RCS regression found a significant non-linear relationship between FEL and ABR, ceteris paribus (p&amp;lt;0.001). Conclusions The results of this analysis found baseline FEL to be significantly associated with ABR in PWHB; as baseline FEL increased, ABR reduced. This highlights the clinical importance of new hemophilia gene therapies potentially increasing FEL to that of the mild or non-hemophilic range in terms of reducing patient burden through the better prevention of bleeding events in PWHB. Disclosures Ali: UniQure: Current Employment. Li: UniQure: Current Employment. Konkle: Pfizer, Sangamo, Sanofi, Sigilon, Spark, Takeda and Uniqure: Research Funding; BioMarin, Pfizer and Sigilon: Consultancy. O'Mahony: BioMarin Pharmaceutical Inc.: Consultancy; Freeline: Consultancy; Uniqure: Speakers Bureau. Pipe: Apcintex: Consultancy; ASC Therapeutics: Consultancy; Bayer: Consultancy; Biomarin: Consultancy, Other: Clinical trial investigator; Catalyst Biosciences: Consultancy; CSL Behring: Consultancy; HEMA Biologics: Consultancy; Freeline: Consultancy, Other: Clinical trial investigator; Novo Nordisk: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy, Other; Sangamo Therapeutics: Consultancy; Sanofi: Consultancy, Other; Takeda: Consultancy; Spark Therapeutics: Consultancy; uniQure: Consultancy, Other; Regeneron/ Intellia: Consultancy; Genventiv: Consultancy; Grifols: Consultancy; Octapharma: Consultancy; Shire: Consultancy.
    • Bleeding Data across Baseline FIX Expression Levels in People with Hemophilia B: An Analysis Using the 'Factor Expression Study'

      Burke, Tom; Shaikh, Anum; Ali, Talaha; Li, Nanxin; Konkle, Barbara A; Noone, Declan; O'Mahony, Brian; Pipe, Steven W; O'Hara, Jamie (Elsevier, 2021-12-24)
      Introduction Complications such as spontaneous and trauma-related bleeding events typically experienced by people with hemophilia B (PWHB) are associated with long-term joint damage and chronic pain, and burdensome treatment with intravenous factor IX administration. Gene therapy, designed to enable the endogenous production of the missing clotting factor, has potential for curative benefit in PWHB (Dolan et al, 2018). Due to its link to risk for bleeding episodes, factor expression level (FEL) is commonly used as an endpoint in hemophilia gene therapy trials. However, little data currently exist linking FEL to bleeding risk in PWHB, most notably within the mild range. As such, the aim of this analysis was to examine the relationship between annual bleed rate (ABR) data across baseline FEL in PWHB. Methods Data from adult non-inhibitor PWHB, across Europe and the United States (US) who received clotting factor on-demand (OD), were drawn from the 'Cost of HaEmophilia in adults: a Socioeconomic Survey' (CHESS) studies. The CHESS studies are retrospective, burden-of-illness studies in people with hemophilia A or B, capturing the economic and humanistic burden associated with living with hemophilia. Additional data were collected to supplement the existing CHESS studies, particularly in people with exogenous FEL in the mild and moderate range. ABR was defined as the physician-reported number of bleed events experienced by the patient in the 12 months to study capture. A generalized linear model (GLM) was used to analyze variation in ABR data across FEL, adjusting for covariates age, body mass index (BMI), and blood-borne viruses. Following this, a multivariable restricted cubic spline (RCS) GLM regression was performed to create, model, and test for the potential non-linear relationship between FEL and ABR. The RCS regression employed 3 knots, located at baseline FEL values of 1, 5, and 10, and controlled once again for age, BMI, and blood-borne viruses. Results A total of 407 adult non-inhibitor PWHB, receiving an OD therapy regimen and with information on ABR, were profiled. The GLM provided adequate fit for the modeling of bleed data; the average marginal effect at the mean was computed from the GLM regression outputs. After controlling for the effects of all other model covariates, the regression analysis showed a significant association between FEL and ABR; for every 1% increase in FEL, the average ABR decreased by 0.08 units (p<0.001). The results of the RCS regression found a significant non-linear relationship between FEL and ABR, ceteris paribus (p<0.001). Conclusions The results of this analysis found baseline FEL to be significantly associated with ABR in PWHB; as baseline FEL increased, ABR reduced. This highlights the clinical importance of new hemophilia gene therapies potentially increasing FEL to that of the mild or non-hemophilic range in terms of reducing patient burden through the better prevention of bleeding events in PWHB. Disclosures Ali:  UniQure: Current Employment. Li:  UniQure: Current Employment. Konkle:  Pfizer, Sangamo, Sanofi, Sigilon, Spark, Takeda and Uniqure: Research Funding; BioMarin, Pfizer and Sigilon: Consultancy. O'Mahony:  BioMarin Pharmaceutical Inc.: Consultancy; Freeline: Consultancy; Uniqure: Speakers Bureau. Pipe:  Apcintex: Consultancy; ASC Therapeutics: Consultancy; Bayer: Consultancy; Biomarin: Consultancy, Other: Clinical trial investigator; Catalyst Biosciences: Consultancy; CSL Behring: Consultancy; HEMA Biologics: Consultancy; Freeline: Consultancy, Other: Clinical trial investigator; Novo Nordisk: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy, Other; Sangamo Therapeutics: Consultancy; Sanofi: Consultancy, Other; Takeda: Consultancy; Spark Therapeutics: Consultancy; uniQure: Consultancy, Other; Regeneron/ Intellia: Consultancy; Genventiv: Consultancy; Grifols: Consultancy; Octapharma: Consultancy; Shire: Consultancy.
    • Clinical, humanistic, and economic burden of severe haemophilia B in adults receiving factor IX prophylaxis: findings from the CHESS II real-world burden of illness study in Europe.

      Burke, Tom; Asghar, Sohaib; orcid: 0000-0001-8276-0131; O'Hara, Jamie; Chuang, Margaret; Sawyer, Eileen K; Li, Nanxin; email: n.li@uniqure.com (2021-12-20)
      <h4>Background</h4>Real-world studies of the burden of severe haemophilia B in the context of recent therapeutic advances such as extended half-life (EHL) factor IX (FIX) products are limited. We analysed data from the recent CHESS II study to better understand the clinical, humanistic, and economic burden of severe haemophilia B in Europe. Data from male adults with severe haemophilia B receiving prophylaxis were analysed from the retrospective cross-sectional CHESS II study conducted in Germany, France, Italy, Spain and the United Kingdom. Inhibitors were exclusionary. Patients and physicians completed questionnaires on bleeding, joint status, quality of life, and haemophilia-related direct and indirect costs (2019-2020). All outcomes were summarised using descriptive statistics.<h4>Results</h4>A total of 75 CHESS II patients were eligible and included; 40 patients (53%) provided self-reported outcomes. Mean age was 36.2 years. Approximately half the patients were receiving EHL versus standard half-life (SHL) prophylaxis (44% vs 56%). Most patients reported mild or moderate chronic pain (76%) and had ≥ 2 bleeding events per year (70%), with a mean annualised bleed rate of 2.4. Mean annual total haemophilia-related direct medical cost per patient was €235,723, driven by FIX costs (€232,328 overall, n = 40; €186,528 for SHL, €290,620 for EHL). Mean annual indirect costs (€8,973) were driven by early retirement or work stoppage due to haemophilia. Mean quality of life (EQ-5D) score was 0.67.<h4>Conclusions</h4>These data document a substantial, persistent real-world burden of severe haemophilia B in Europe. Unmet needs persist for these patients, their caregivers, and society.
    • Clinical, humanistic, and economic burden of severe hemophilia B in the United States: Results from the CHESS US and CHESS US+ population surveys.

      Burke, Tom; Asghar, Sohaib; orcid: 0000-0001-8276-0131; O'Hara, Jamie; Sawyer, Eileen K; Li, Nanxin; email: n.li@uniqure.com (2021-03-20)
      Hemophilia B is a rare congenital bleeding disorder that has a significant negative impact on patients' functionality and health-related quality of life. The standard of care for severe hemophilia B in the United States is prophylactic factor IX replacement therapy, which incurs substantial costs for this lifelong condition. Accurate estimates of the burden of hemophilia B are important for population health management and policy decisions, but have only recently accounted for current management strategies. The 'Cost of Severe Hemophilia across the US: a Socioeconomic Survey' (CHESS US) is a cross-sectional database of medical record abstractions and physician-reported information, completed by hematologists and care providers. CHESS US+ is a complementary database of completed questionnaires from patients with hemophilia. Together, CHESS US and CHESS US+ provide contemporary, comprehensive information on the burden of severe hemophilia from the provider and patient perspectives. We used the CHESS US and CHESS US+ data to analyze the clinical, humanistic, and economic burden of hemophilia B for patients treated with factor IX prophylaxis between 2017 and 2019 in the US. We conducted analysis to assess clinical burden and direct medical costs from 44 patient records in CHESS US, and of direct non-medical costs, indirect costs, and humanistic burden (using the EQ-5D-5L) from 57 patients in CHESS US+. The mean annual bleed rate was 1.73 (standard deviation, 1.39); approximately 9% of patients experienced a bleed-related hospitalization during the 12-month study period. Nearly all patients (85%) reported chronic pain, and the mean EQ-5D-5L utility value was 0.76 (0.24). The mean annual direct medical cost was $614,886, driven by factor IX treatment (mean annual cost, $611,971). Subgroup analyses showed mean annual costs of $397,491 and $788,491 for standard and extended half-life factor IX treatment, respectively. The mean annual non-medical direct costs and indirect costs of hemophilia B were $2,371 and $6,931. This analysis of patient records and patient-reported outcomes from CHESS US and CHESS US+ provides updated information on the considerable clinical, humanistic, and economic burden of hemophilia B in the US. Substantial unmet needs remain to improve patient care with sustainable population health strategies.
    • Effect of Moderate and Severe Hemophilia a on Daily Life in Children and Their Caregivers: A CHESS Paediatrics Study Analysis

      Khair, Kate; Nissen, Francis; Silkey, Mariabeth; Burke, Tom; Shang, Aijing; Aizenas, Martynas; Meier, Oliver; O'Hara, Jamie; Noone, Declan (American Society of Hematology, 2020-11-05)
      Introduction: Hemophilia A (HA) is a congenital bleeding disorder, caused by a deficiency in clotting factor VIII (FVIII) and characterized by uncontrolled bleeding and progressive joint damage. This analysis assesses the impact of disease burden on the daily life of children with hemophilia A (CwHA) and their caregivers, addressing a deficit of current research on this topic. Methods: The Cost of Haemophilia in Europe: a Socioeconomic Survey in a Paediatric Population (CHESS Paediatrics) is a retrospective, burden-of-illness study in children with moderate and severe HA (defined by endogenous FVIII [IU/dL] relative to normal; moderate, 1-5%; severe, &amp;lt;1%) across France, Germany, Italy, Spain and the UK. CwHA were recruited and stratified by both age group (0-5 years:6-11 years:12-17 years=1:1:1) and disease severity (severe:moderate=approximately 2:1, prioritizing children with severe HA [CwSHA]). Data for this analysis were captured from physicians, children, and their caregivers. Physicians completed online case report forms for treated children, and the child and/or their caregivers completed a paper-based questionnaire utilizing 5-point Likert scales. For CwHA aged 0-7, the questionnaire was completed by the caregiver, while for CwHA aged 8-17, children and caregivers completed different sections. Hours of care provided by the caregiver and work lost by the caregiver were reported as median values due to non-normal data distribution. Informed consent was obtained for all participants. Upon review, the study was approved by the University of Chester ethical committee. Results: Data from child/caregiver questionnaires were available for 196 CwHA (moderate, 25.5%; severe, 74.5%); the majority of these children, as expected, were receiving prophylaxis (72.4%), and did not have FVIII inhibitors (89.8%; Table 1). There was a direct impact of disease burden on CwHA, particularly with regard to physical and social activities (Figure 1). Overall, it was agreed or strongly agreed by the child or caregiver that 48.0% and 57.5% of children with moderate HA (CwMHA) and CwSHA respectively, have reduced physical activity due to HA, and 46.0% and 57.5%, respectively, have reduced social activity due to HA. A total of 36.0% and 61.0% of CwMHA and CwSHA, respectively, had adapted their treatment in anticipation of physical or social activity (Table 1). Furthermore, 34.0% of CwMHA and 55.4% of CwSHA were frustrated due to their disease, and many (CwMHA, 36.0%; CwSHA, 50.7%) felt that they had missed opportunities (Figure 1). For 66.0% of CwMHA and 76.0% of CwSHA, it was reported that their daily life was compromised due to their HA. Caregivers provided a median (interquartile range [IQR]) of 19.0 (10.0-59.5) and 12.0 (5.0-20.0) hours a week of care for the hemophilia-related needs of their CwMHA (n=30) or CwSHA (n=105), respectively. Of those who responded, 17.4% (n=4/23) and 25.0% (n=20/80) of caregivers to CwMHA or CwSHA, respectively, stated they have lost work due to their caregiving duty. This was more than twice as common for caregivers in families with multiple CwHA (42.9%, n=9/21 responses) compared with those in families with one CwHA (18.5%, n=15/81 responses). Median (IQR) hours of work per week estimated to be lost were 20.0 (17.0-22.0) for caregivers of CwMHA (n=4) and 12.5 (4.50-20.0) for caregivers of CwSHA (n=20). Conclusions: In conclusion, both children and caregivers make sacrifices in their daily lives due to HA; many CwHA reported reduced physical and social activities, fewer opportunities and feelings of frustration due to their HA. Caregivers reported spending a significant number of hours caring for their child and some reported losing work due to their caring responsibilities. However, some outcomes may be limited by the small number of respondents and narrow response options, particularly those regarding the caregiver burden. Responses on the hours of work lost may be subject to selection bias, as caregivers who have lost work may be more likely to respond to this question. Additionally, as this question is targeted at caregivers in employment, it is unknown if some caregivers have left employment due to their caregiving responsibilities. According to this analysis, children/caregivers are frequently required to adapt the child's treatment before the child engages in activities. Overall, the burden of disease was similar in children with moderate and severe HA. Disclosures Khair: Takeda: Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Biomarin: Consultancy; HCD Economics: Consultancy; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medikhair: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Haemnet: Membership on an entity's Board of Directors or advisory committees. Nissen:GSK: Research Funding; Novartis: Research Funding; Actelion: Consultancy; F. Hoffmann-La Roche Ltd: Current Employment. Silkey:Aerotek AG: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Burke:HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Shang:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Aizenas:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Meier:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. O'Hara:HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy. Noone:Research Investigator PROBE: Research Funding; Healthcare Decision Consultants: Membership on an entity's Board of Directors or advisory committees; European Haemophilia Consortium: Membership on an entity's Board of Directors or advisory committees.
    • Effect of Moderate and Severe Hemophilia a on Daily Life in Children and Their Caregivers: A CHESS Paediatrics Study Analysis

      Khair, Kate; Nissen, Francis; Silkey, Mariabeth; Burke, Tom; Shang, Aijing; Aizenas, Martynas; Meier, Oliver; O'Hara, Jamie; Noone, Declan (American Society of Hematology, 2020-11-05)
      Introduction: Hemophilia A (HA) is a congenital bleeding disorder, caused by a deficiency in clotting factor VIII (FVIII) and characterized by uncontrolled bleeding and progressive joint damage. This analysis assesses the impact of disease burden on the daily life of children with hemophilia A (CwHA) and their caregivers, addressing a deficit of current research on this topic. Methods: The Cost of Haemophilia in Europe: a Socioeconomic Survey in a Paediatric Population (CHESS Paediatrics) is a retrospective, burden-of-illness study in children with moderate and severe HA (defined by endogenous FVIII [IU/dL] relative to normal; moderate, 1-5%; severe, &amp;lt;1%) across France, Germany, Italy, Spain and the UK. CwHA were recruited and stratified by both age group (0-5 years:6-11 years:12-17 years=1:1:1) and disease severity (severe:moderate=approximately 2:1, prioritizing children with severe HA [CwSHA]). Data for this analysis were captured from physicians, children, and their caregivers. Physicians completed online case report forms for treated children, and the child and/or their caregivers completed a paper-based questionnaire utilizing 5-point Likert scales. For CwHA aged 0-7, the questionnaire was completed by the caregiver, while for CwHA aged 8-17, children and caregivers completed different sections. Hours of care provided by the caregiver and work lost by the caregiver were reported as median values due to non-normal data distribution. Informed consent was obtained for all participants. Upon review, the study was approved by the University of Chester ethical committee. Results: Data from child/caregiver questionnaires were available for 196 CwHA (moderate, 25.5%; severe, 74.5%); the majority of these children, as expected, were receiving prophylaxis (72.4%), and did not have FVIII inhibitors (89.8%; Table 1). There was a direct impact of disease burden on CwHA, particularly with regard to physical and social activities (Figure 1). Overall, it was agreed or strongly agreed by the child or caregiver that 48.0% and 57.5% of children with moderate HA (CwMHA) and CwSHA respectively, have reduced physical activity due to HA, and 46.0% and 57.5%, respectively, have reduced social activity due to HA. A total of 36.0% and 61.0% of CwMHA and CwSHA, respectively, had adapted their treatment in anticipation of physical or social activity (Table 1). Furthermore, 34.0% of CwMHA and 55.4% of CwSHA were frustrated due to their disease, and many (CwMHA, 36.0%; CwSHA, 50.7%) felt that they had missed opportunities (Figure 1). For 66.0% of CwMHA and 76.0% of CwSHA, it was reported that their daily life was compromised due to their HA. Caregivers provided a median (interquartile range [IQR]) of 19.0 (10.0-59.5) and 12.0 (5.0-20.0) hours a week of care for the hemophilia-related needs of their CwMHA (n=30) or CwSHA (n=105), respectively. Of those who responded, 17.4% (n=4/23) and 25.0% (n=20/80) of caregivers to CwMHA or CwSHA, respectively, stated they have lost work due to their caregiving duty. This was more than twice as common for caregivers in families with multiple CwHA (42.9%, n=9/21 responses) compared with those in families with one CwHA (18.5%, n=15/81 responses). Median (IQR) hours of work per week estimated to be lost were 20.0 (17.0-22.0) for caregivers of CwMHA (n=4) and 12.5 (4.50-20.0) for caregivers of CwSHA (n=20). Conclusions: In conclusion, both children and caregivers make sacrifices in their daily lives due to HA; many CwHA reported reduced physical and social activities, fewer opportunities and feelings of frustration due to their HA. Caregivers reported spending a significant number of hours caring for their child and some reported losing work due to their caring responsibilities. However, some outcomes may be limited by the small number of respondents and narrow response options, particularly those regarding the caregiver burden. Responses on the hours of work lost may be subject to selection bias, as caregivers who have lost work may be more likely to respond to this question. Additionally, as this question is targeted at caregivers in employment, it is unknown if some caregivers have left employment due to their caregiving responsibilities. According to this analysis, children/caregivers are frequently required to adapt the child's treatment before the child engages in activities. Overall, the burden of disease was similar in children with moderate and severe HA. Disclosures Khair: Takeda: Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Biomarin: Consultancy; HCD Economics: Consultancy; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medikhair: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Haemnet: Membership on an entity's Board of Directors or advisory committees. Nissen:GSK: Research Funding; Novartis: Research Funding; Actelion: Consultancy; F. Hoffmann-La Roche Ltd: Current Employment. Silkey:Aerotek AG: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Burke:HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Shang:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Aizenas:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Meier:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. O'Hara:HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy. Noone:Research Investigator PROBE: Research Funding; Healthcare Decision Consultants: Membership on an entity's Board of Directors or advisory committees; European Haemophilia Consortium: Membership on an entity's Board of Directors or advisory committees.
    • Effect of Moderate and Severe Hemophilia a on Daily Life in Children and Their Caregivers: A CHESS Paediatrics Study Analysis

      Khair, Kate; Nissen, Francis; Silkey, Mariabeth; Burke, Tom; Shang, Aijing; Aizenas, Martynas; Meier, Oliver; O'Hara, Jamie; Noone, Declan (Elsevier, 2021-08-03)
      Introduction: Hemophilia A (HA) is a congenital bleeding disorder, caused by a deficiency in clotting factor VIII (FVIII) and characterized by uncontrolled bleeding and progressive joint damage. This analysis assesses the impact of disease burden on the daily life of children with hemophilia A (CwHA) and their caregivers, addressing a deficit of current research on this topic. Methods: The Cost of Haemophilia in Europe: a Socioeconomic Survey in a Paediatric Population (CHESS Paediatrics) is a retrospective, burden-of-illness study in children with moderate and severe HA (defined by endogenous FVIII [IU/dL] relative to normal; moderate, 1-5%; severe, <1%) across France, Germany, Italy, Spain and the UK. CwHA were recruited and stratified by both age group (0-5 years:6-11 years:12-17 years=1:1:1) and disease severity (severe:moderate=approximately 2:1, prioritizing children with severe HA [CwSHA]). Data for this analysis were captured from physicians, children, and their caregivers. Physicians completed online case report forms for treated children, and the child and/or their caregivers completed a paper-based questionnaire utilizing 5-point Likert scales. For CwHA aged 0-7, the questionnaire was completed by the caregiver, while for CwHA aged 8-17, children and caregivers completed different sections. Hours of care provided by the caregiver and work lost by the caregiver were reported as median values due to non-normal data distribution. Informed consent was obtained for all participants. Upon review, the study was approved by the University of Chester ethical committee. Results: Data from child/caregiver questionnaires were available for 196 CwHA (moderate, 25.5%; severe, 74.5%); the majority of these children, as expected, were receiving prophylaxis (72.4%), and did not have FVIII inhibitors (89.8%; Table 1). There was a direct impact of disease burden on CwHA, particularly with regard to physical and social activities (Figure 1). Overall, it was agreed or strongly agreed by the child or caregiver that 48.0% and 57.5% of children with moderate HA (CwMHA) and CwSHA respectively, have reduced physical activity due to HA, and 46.0% and 57.5%, respectively, have reduced social activity due to HA. A total of 36.0% and 61.0% of CwMHA and CwSHA, respectively, had adapted their treatment in anticipation of physical or social activity (Table 1). Furthermore, 34.0% of CwMHA and 55.4% of CwSHA were frustrated due to their disease, and many (CwMHA, 36.0%; CwSHA, 50.7%) felt that they had missed opportunities (Figure 1). For 66.0% of CwMHA and 76.0% of CwSHA, it was reported that their daily life was compromised due to their HA. Caregivers provided a median (interquartile range [IQR]) of 19.0 (10.0-59.5) and 12.0 (5.0-20.0) hours a week of care for the hemophilia-related needs of their CwMHA (n=30) or CwSHA (n=105), respectively. Of those who responded, 17.4% (n=4/23) and 25.0% (n=20/80) of caregivers to CwMHA or CwSHA, respectively, stated they have lost work due to their caregiving duty. This was more than twice as common for caregivers in families with multiple CwHA (42.9%, n=9/21 responses) compared with those in families with one CwHA (18.5%, n=15/81 responses). Median (IQR) hours of work per week estimated to be lost were 20.0 (17.0-22.0) for caregivers of CwMHA (n=4) and 12.5 (4.50-20.0) for caregivers of CwSHA (n=20). Conclusions: In conclusion, both children and caregivers make sacrifices in their daily lives due to HA; many CwHA reported reduced physical and social activities, fewer opportunities and feelings of frustration due to their HA. Caregivers reported spending a significant number of hours caring for their child and some reported losing work due to their caring responsibilities. However, some outcomes may be limited by the small number of respondents and narrow response options, particularly those regarding the caregiver burden. Responses on the hours of work lost may be subject to selection bias, as caregivers who have lost work may be more likely to respond to this question. Additionally, as this question is targeted at caregivers in employment, it is unknown if some caregivers have left employment due to their caregiving responsibilities. According to this analysis, children/caregivers are frequently required to adapt the child's treatment before the child engages in activities. Overall, the burden of disease was similar in children with moderate and severe HA. Disclosures Khair: Takeda: Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Biomarin: Consultancy; HCD Economics: Consultancy; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medikhair: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Haemnet: Membership on an entity's Board of Directors or advisory committees. Nissen: GSK: Research Funding; Novartis: Research Funding; Actelion: Consultancy; F. Hoffmann-La Roche Ltd: Current Employment. Silkey: Aerotek AG: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Burke: HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Shang: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Aizenas: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Meier: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. O'Hara: HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy. Noone: Research Investigator PROBE: Research Funding; Healthcare Decision Consultants: Membership on an entity's Board of Directors or advisory committees; European Haemophilia Consortium: Membership on an entity's Board of Directors or advisory committees.
    • Evidence of a disability paradox in patient-reported outcomes in haemophilia.

      O'Hara, Jamie; Martin, Antony P; Nugent, Diane; Witkop, Michelle; orcid: 0000-0003-0758-286X; Buckner, Tyler W; Skinner, Mark W; orcid: 0000-0002-0934-0680; O'Mahony, Brian; Mulhern, Brendan; Morgan, George; orcid: 0000-0003-2014-3415; Li, Nanxin; et al. (2021-02-17)
      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). 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. 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. 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. 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. [Abstract copyright: © 2021 The Authors. Haemophilia published by John Wiley & Sons Ltd.]
    • Evidence of a Hemophilia Employment Gap: Comparing Data from CHESS US+ and the 2019 Current Population Survey

      Asghar, Sohaib; Burke, Tom; Misciattelli, Natalia; Kar, Sharmila; Morgan, George; O'Hara, Jamie (Elsevier, 2021-08-03)
      INTRODUCTION Severe hemophilia A (<1% normal FVIII activity) and B (<1% normal FIX activity) are congenital bleeding disorders characterized by uncontrolled bleeding, either spontaneously or in response to trauma or surgery. Recent commentary has identified a number of patient-important and patient-relevant outcomes that have been understudied, namely the challenges faced by people living with hemophilia to participate in the labor force. The socio-economic impact of hemophilia is comparatively less well understood than clinical outcomes and therapy-related costs. Under-employment and under-utilization have long-term consequences to individuals' job prospects and psychosocial health, as well as an economic cost to the society. The objective of the analysis is to compare labor market participation, among people with severe hemophilia from the US and the general population. This analysis draws on household data derived from the 2019 Current Population Survey (CPS), and on patient-reported data from a patient-centric study conducted in 2019 of people with severe hemophilia, in the US: the ‘Cost of Severe Hemophilia Across the US: A Socioeconomic Survey’ (CHESS US+). METHODS A patient-centric framework informed the design of CHESS US+ a retrospective (12 months prior to study enrollment), cross-sectional dataset of adults with severe hemophilia in the US. Conducted in 2019, the study used a patient-completed questionnaire to collect data on patient-relevant clinical, economic, and humanistic outcomes. This analysis examines labor market participation (full-time, part-time, unemployed), and corresponding general population data derived from the 2019 Current Population Survey (CPS). Data on the general population were sourced from the 2019 CPS ‘Employment status of the civilian noninstitutional population’. Persons ‘not in the labor force’ in the 2019 CPS and retired persons in CHESS US+ were not included in the analysis. We present data on the civilian labor force, in CHESS US+ and in the 2019 CPS. Results are presented as mean (standard deviation) or N (%). RESULTS Of 356 patients profiled in the CHESS US+ study, 97 (27%) had severe hemophilia B and 257 (73%) had severe hemophilia A. Mean age and weight (kg) of the cohort was 34.99 (12.15) and 85.71 (22.81), respectively. The labor force participation rates of non-retired people with severe hemophilia in CHESS US+ (N = 340) and the general population (161,458) are described in Table 1. Examining aggregate data on employment status observed a higher proportion of people with severe hemophilia in part-time employment (24.4% vs. 15.7%). Differences in the labor force participation of people living with severe hemophilia compared to the general population were most pronounced in the full-time employment rate and the unemployment rate. Compared to 80.7% of the general population (Table 1), only 53.5% of people with severe hemophilia in CHESS US+ had a full-time job. Moreover, the unemployment rate (Table 1) in the 2019 CPS compared with the rate observed in CHESS US+ (3.7% vs. 22.1%) provides a stark contrast in the employment experiences of people living with severe hemophilia relative to the general population. CONCLUSIONS This analysis of CHESS US+ illustrates the impact of severe hemophilia on labor force participation. People with severe hemophilia were more likely than the general population to be unemployed, or in part-time employment. A notable contrast was observed in the rate of full-time employment and unemployment, among the general population compared to people living with severe hemophilia. These data illustrate the need to quantify the impact of hemophilia using a holistic approach that considers the cost of involuntary illness-related part-time and unemployment. Disclosures Asghar: HCD Economics: Current Employment. Burke: HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy; University of Chester: Current Employment. Misciattelli: Freeline: Current Employment, Current equity holder in publicly-traded company. Kar: Freeline: Current Employment, Current equity holder in publicly-traded company. Morgan: HCD Economics: Current Employment; uniQure: Consultancy. O'Hara: F. Hoffmann-La Roche Ltd: Consultancy; HCD Economics: Current Employment, Current equity holder in private company.
    • Examination and Validation of a Patient-Centric Joint Metric: “Problem Joint”; Empirical Evidence from the CHESS US Dataset

      Burke, Tom; Rodriguez Santana, Idaira; Chowdary, Pratima; Curtis, Randall; Khair, Kate; Laffan, Michael; McLaughlin, Paul; Noone, Declan; O'Mahony, Brian; Pasi, John; et al. (Elsevier, 2021-08-03)
      Introduction Severe hemophilia (FVIII/FIX level <1%) is characterized by spontaneous hemarthrosis leading to progressive joint deterioration and chronic pain in the affected individual. Unless these recurrent hemarthroses can be prevented, e.g. with the use of prophylactic factor replacement therapy, these patients will develop chronic synovitis, pain, and eventually destruction of the joint. Current metrics such as ’Target joint’ and other clinical measures of joint morbidity are prevalent and widely accepted. Measures focused solely on bleeding activity, such as the ’Target joint’ metric, are arguably becoming less sensitive as current treatment strategies look to significantly reduce or eradicate joint bleeds, though they maintain clinically relevant and complementary to delivery of comprehensive hemophilia care. Key opinion leaders in the haemophilia field have debated the need for a more patient relevant measure of haemophilia-related joint morbidity. ‘Problem Joint’ (PJ), which is defined as having chronic joint pain and/or limited range of movement due to compromised joint integrity (chronic synovitis and/or haemophilic arthropathy), with or without persistent bleeding was derived through consensus. The objectives of this working group are to examine the usefulness and validity of the PJ metric. Initial research presented here was used to test the sensitivity of PJ as a patient relevant metric with respect to key outcomes for US haemophilia patients. Methods Data on PJs, as well as demographic, clinical and socio-economic variables was captured within the ‘Cost of Haemophilia Across Europe: A Socioeconomic Survey’ datasets (CHESS: I, II, Paediatric, and US studies). These data contain a total of 992 paediatric (age 1-17) and 2,437 adults (age 18+) with haemophilia from eight European countries and the US. Statistical analysis explored the association of PJ count and location with respect to two key outcomes: quality of life, as measured by an EQ-5D score, and overall work impairment, measured by the Work Productivity and Activity Impairment Questionnaire (WPAI). Those with current inhibitors were excluded from the analysis, and the US cohort comprised the focus of this initial research into the topic. Results The US cohort contained information on 345 people with haemophilia (PwH) and captured adults only, with a mean age of 35 years. Approximately, 43% of PwH had one or more PJs. Lower body PJs were more prevalent than upper body: 40% had one or more lower body PJs vs. 27% upper body. The majority of PJs were located in the ankles, knees and elbows. The relationship between EQ-5D and number of PJs showed a negative trend (see Figure 1): the average EQ-5D score was: 0.81 for those with zero PJs (N=197); 0.79 for those with one PJ (N=24); 0.70 for two PJs (N=29); 0.68 for three PJs (N=24) and 0.49 for those patients with four of more PJs (N=59). Similarly, an increase in number of PJs meant greater work productivity impairment versus no PJs recorded: 30.08% (N=102) vs. 19.51% (N=137), respectively. Discussion Results from the US cohort found that an increase in the number of PJs was associated with an increasing humanistic burden in PwH. The proposed Problem Joint definition takes a holistic viewpoint and provides a patient relevant perspective. Further work is planned to evaluate the appropriateness of the measure, and test the sensitivity in European and pediatric cohorts. Disclosures Burke: HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Rodriguez Santana: HCD Economics: Current Employment. Chowdary: Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sobi: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Shire (Baxalta): Membership on an entity's Board of Directors or advisory committees; Spark: Membership on an entity's Board of Directors or advisory committees; BioMarin: Honoraria; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Chugai: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Freeline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Curtis: Bayer: Consultancy; Novo Nordisk: Consultancy; Patient Reported Outcomes, Burdens and Experiences: Consultancy; USC Hemophilia Utilization Group Study (HUGS): Consultancy. Khair: Haemnet: Membership on an entity's Board of Directors or advisory committees; Biomarin: Consultancy; HCD Economics: Consultancy; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medikhair: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Takeda: Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau. Laffan: Shire: Consultancy; LFB: Consultancy; Roche: Consultancy; Sobi: Consultancy; Pfizer: Consultancy; CSL: Consultancy; Pfizer: Speakers Bureau; Bayer: Speakers Bureau; Roche-Chugai: Speakers Bureau; Takeda: Speakers Bureau; Leo-Pharma: Speakers Bureau; Octapharma: Consultancy. McLaughlin: BioMarin: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Roche/Chugai: Speakers Bureau; Takeda: Speakers Bureau. Noone: European Haemophilia Consortium: Membership on an entity's Board of Directors or advisory committees; Research Investigator PROBE: Research Funding; Healthcare Decision Consultants: Membership on an entity's Board of Directors or advisory committees. O'Mahony: Biomarin: Honoraria, Membership on an entity's Board of Directors or advisory committees; Freeline: Honoraria; UniQure: Honoraria. Pasi: BioMarin: Consultancy, Honoraria, Other: Grants, personal fees, and nonfinancial support; honoraria as member of scientific advisory boards and symposia; uniQure: Other: Grants and nonfinancial support , Research Funding; ApcinteX: Consultancy, Other: Personal fees ; Octapharma: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia , Speakers Bureau; Novo Nordisk: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia ; Catalyst Biosciences: Consultancy, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Biotest: Consultancy, Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Alnylam (Sanofi): Other: Personal fees and nonfinancial support ; Takeda: Consultancy, Honoraria, Other: Personal fees; honoraria as member of scientific advisory boards and symposia ; Sanofi: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia, Research Funding; Sigilon: Research Funding; Tremeau: Research Funding; Sobi: Consultancy, Honoraria, Other; Roche: Honoraria, Other; Pfizer: Other. Skinner: Genentech: Consultancy, Honoraria; Spark Therapeutics: Other, Speakers Bureau; Pfizer: Other, Speakers Bureau; Takeda: Honoraria, Research Funding; uniQure: Research Funding; Biomarin: Consultancy, Research Funding; CSL Behring: Research Funding; Freeline Therapeutics: Research Funding; Novo Nordisk: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding, Speakers Bureau; Sobi: Research Funding; Bayer: Consultancy, Research Funding. O'Hara: HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy.
    • Patient preferences and priorities for haemophilia gene therapy in the US: A discrete choice experiment

      Witkop, Michelle; Morgan, George; orcid: 0000-0003-2014-3415; email: george.morgan@hcdeconomics.com; O'Hara, Jamie; Recht, Michael; Buckner, Tyler W.; Nugent, Diane; Curtis, Randall; orcid: 0000-0002-6859-6432; O'Mahony, Brian; orcid: 0000-0001-9780-6972; Skinner, Mark W.; orcid: 0000-0002-0934-0680; Mulhern, Brendan; et al. (2021-07-26)
      Abstract: 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.
    • Patient preferences and priorities for haemophilia gene therapy in the US: A discrete choice experiment

      Witkop, Michelle; Morgan, George; orcid: 0000-0003-2014-3415; O'Hara, Jamie; Recht, Michael; Buckner, Tyler W.; Nugent, Diane; Curtis, Randall; orcid: 0000-0002-6859-6432; O'Mahony, Brian; orcid: 0000-0001-9780-6972; Skinner, Mark W.; orcid: 0000-0002-0934-0680; Mulhern, Brendan; et al. (Wiley, 2021-07-26)
    • Patient preferences and priorities for haemophilia gene therapy in the US: A discrete choice experiment

      Witkop, Michelle; Morgan, George; orcid: 0000-0003-2014-3415; O'Hara, Jamie; Recht, Michael; Buckner, Tyler W.; Nugent, Diane; Curtis, Randall; orcid: 0000-0002-6859-6432; O'Mahony, Brian; orcid: 0000-0001-9780-6972; Skinner, Mark W.; orcid: 0000-0002-0934-0680; Mulhern, Brendan; et al. (Wiley, 2021-07-26)
    • Patient‐relevant health outcomes for hemophilia care: Development of an international standard outcomes set

      Balen, Erna C.; orcid: 0000-0002-3678-6581; O'Mahony, Brian; Cnossen, Marjon H.; Dolan, Gerard; Blanchette, Victor S.; Fischer, Kathelijn; Gue, Deborah; O'Hara, Jamie; Iorio, Alfonso; orcid: 0000-0002-3331-8766; Jackson, Shannon; et al. (Wiley, 2021-03-06)
    • Patient‐relevant health outcomes for hemophilia care: Development of an international standard outcomes set

      van Balen, Erna C.; orcid: 0000-0002-3678-6581; O'Mahony, Brian; Cnossen, Marjon H.; Dolan, Gerard; Blanchette, Victor S.; Fischer, Kathelijn; Gue, Deborah; O'Hara, Jamie; Iorio, Alfonso; orcid: 0000-0002-3331-8766; Jackson, Shannon; et al. (2021-03-06)
      Abstract: Background: Patient‐relevant health outcomes for persons with hemophilia should be identified and prioritized to optimize and individualize care for persons with hemophilia. Therefore, an international group of persons with hemophilia and multidisciplinary health care providers set out to identify a globally applicable standard set of health outcomes relevant to all individuals with hemophilia. Methods: A systematic literature search was performed to identify possible health outcomes and risk adjustment variables. Persons with hemophilia and multidisciplinary health care providers were involved in an iterative nominal consensus process to select the most important health outcomes and risk adjustment variables for persons with hemophilia. Recommendations were made for outcome measurement instruments. Results: Persons with hemophilia were defined as all men and women with an X‐linked inherited bleeding disorder caused by a deficiency of coagulation factor VIII or IX with plasma activity levels <40 IU/dL. We recommend collecting the following 10 health outcomes at least annually, if applicable: (i) cure, (ii) impact of disease on life expectancy, (iii) ability to engage in normal daily activities, (iv) severe bleeding episodes, (v) number of days lost from school or work, (vi) chronic pain, (vii) disease and treatment complications, (viii) sustainability of physical functioning, (ix) social functioning, and (x) mental health. Validated clinical as well as patient‐reported outcome measurement instruments were endorsed. Demographic factors, baseline clinical factors, and treatment factors were identified as risk‐adjustment variables. Conclusion: A consensus‐based international set of health outcomes relevant to all persons with hemophilia, and corresponding measurement instruments, was identified for use in clinical care to facilitate harmonized longitudinal monitoring and comparison of outcomes.
    • Patient‐relevant health outcomes for hemophilia care: Development of an international standard outcomes set

      Balen, Erna C.; orcid: 0000-0002-3678-6581; O'Mahony, Brian; Cnossen, Marjon H.; Dolan, Gerard; Blanchette, Victor S.; Fischer, Kathelijn; Gue, Deborah; O'Hara, Jamie; Iorio, Alfonso; orcid: 0000-0002-3331-8766; Jackson, Shannon; et al. (Wiley, 2021-03-06)