Research Studies

Objective:

Patient-centered medical home (PCMH), a team-based model of practice involving patients, families, providers and care team members, focuses on high quality, efficient, and patient-centered care. The purpose of this project was to implement appropriate elements of the PCMH model in the care delivered by the Intermountain Hemophilia and Thrombosis Center (IHTC).

Methods:

The IHTC, as a medical home neighbor, participated in a 3 1⁄2 year (5/2011- 11/2014) Children’s Health Improvement Collaborative Medical Home Demonstration (MHD) that involved 3 specialty and 9 primary care practices in Utah. IHTC focused on both MHD- wide and practice-specific quality improvement (QI) goals. Our QI team included the IHTC core multidisciplinary team and a parent partner and medical home coordinator (MHC) who were funded by the MHD. The MHD led four sequential, 8-12 month projects: “Improving Collaboration Among Pediatric Generalists and Specialists,” “Implementing Care and Self- Care Plans for Children with Chronic Conditions,” “Improving Healthcare Transitions for Children with Special Health Care Needs,” and “Sustainability.” Practice-specific projects targeted goals established via a needs assessment and parent partner input. Plan-Do-Study- Act (PDSA) cycles were facilitated by the MHC and a practice coach from the MHD. Continuing education and peer support were provided via learning sessions, webinars, and ongoing mentorship.

Summary:

IHTC met all MHD-wide and practice-specific goals. Selected MHD-wide improvements included: completion of the patient history prior to new consultation (improved from ~15% to 95%); patient self-care plans (0% to 97%); and youth with an up-to-date transition tool (0% to 100%). To address “sustainability,” IHTC will continue using QI, implementing the PCMH model, and will maintain the MHC as a member of the care team. Practice-specific strategies resulted in improved efficiency and family-centered approach to the annual comprehensive clinic visit (31⁄2 hour visit decreased to 2 hours with reduced redundancy), reduced no-show/cancellations (~33% to 10%), established means for continuous individual patient/family feedback, and a formalized IHTC-specific emergency preparedness plan (currently in progress).

Conclusions:

Via participation in the MHD, the IHTC learned that QI is both realistic and rewarding. Essential components for ongoing improvement include: specific, defined and measurable goals; a QI leader; parent/consumer input; and participation by all clinical team members. The PCMH model provides a framework for meaningful change for patients, families, and clinical practice.

Acknowledgments: 

Funded in part by a CHIPRA Quality Demonstrations grant: CFDA 93.767 from the U.S. Department of Health and Human Services, Centers for Medicare & Medicaid Services.

Introduction and Objective:

Prospective clinical trials have demonstrated the efficacy of prophylaxis in reducing bleeding episodes in hemophilia A and B patients and those with inhibitors. However, data, predominantly from observational studies, have suggested more equivocal effects on health-related quality of life (HRQoL) [Buchbinder 2013]. The present review examined the impact of prophylaxis on HRQoL as measured during prospective trials.

Methods:

We conducted a systematic literature review of prospective studies evaluating the efficacy of prophylaxis in hemophilia using factor VIII, factor IX, or bypassing agents. Applying the inclusion criteria, we selected studies which evaluated HRQoL via validated instruments and summarized key data.

Results:

A total of 12 studies (hemophilia A [n=7]; hemophilia B [n=2]; inhibitors [n=3]) met all inclusion criteria and were reviewed. Of these studies, the investigational products were Advate (n=2), Kogenate (n=2), NovoEight (n=2), Eloctate (n=1), Rixubis (n=1), Aprolix (n=1), Feiba (n=2), and NovoSeven (n=1). HRQoL was assessed using one or a combination of the following instruments: SF-36 (n=3), EQ-5D (n=5), Haemo-QoL (n=2), Haem-A-QoL (n=3), Haemo-QOL-A (n=2) and general pain VAS (n=1). Seven of the 12 studies reported significant improvement in ≥1 HRQoL measure following prophylaxis. Advate, Rixubis and Feiba prophylaxis (among good responders with ≥ 50% bleed reduction) demonstrated statistically significant and clinically meaningful improvement in the physical component and certain domain(s) scores of the SF-36 (Valentino 2012; Windyga 2013; Gringeri 2013). Additionally, prophylaxis with Feiba showed clinically meaningful and/or statistically significant improvements in HRQoL (EQ-5D, Haemo-A-QoL), general health status (EQ-VAS) and general pain scores (VAS) (Antunes 2014; Stasyshyn 2014). Although, a previous Kogenate study indicated non-significant change in HRQoL measures (Collins 2003), recently published results from the SPINART trial demonstrated statistically significant and clinically meaningful improvement in several domains of the Haemo-QoL-A (Hong 2014). Prophylaxis with Eloctate and Alprolix resulted in non-significant change in the HRQoL measures used in their respective trials (Wyrwich 2013). Statistical and clinical significance were not reported for prophylaxis treatment with NovoEight (Santagostino 2014). Prophylaxis with NovoSeven showed a non-significant trend towards improvement in all dimensions of the EQ-5D but statistical improvement in general health status (EQ-VAS) (Hoots 2008).

Conclusion:

Results from Advate, Kogenate, Rixubis and Feiba trials offer robust evidence of clinically and statistically significant improvement in HRQoL in hemophilia patients treated with prophylaxis.

Introduction and Objective:

Limited information exists in the recent literature capturing real- world utilization and cost of bypassing agents among hemophiliac patients with inhibitors in the US. The present study compared the cost of on-demand and prophylaxis treatment between aPCC and rFVIIa among inhibitor patients with severe hemophilia.

Methods:

A retrospective analysis of two large US specialty pharmacy databases was conducted using dispensing data over a 28-month period (Jan. 2012 to April 2014). Subjects were included if they had a diagnosis of hemophilia A or B (ICD-9 code 286.0 or 286.1) that was classified as severe and ≥12 months of consecutive prescription claims for only bypassing agents. For patients who switched between bypassing agents or between on- demand (OD) and prophylaxis (P) during the observation period, observations of ≥6 months with consistent prescriptions were selected and analyzed independently. Bypassing agent utilization was annualized and normalized by patient weight (kg). Cost was calculated using 2013 Redbook® US wholesale acquisition costs (aPCC=$1.81/U and rFVIIa=$1.77/μg) and compared by product and regimen using non-parametric statistics.

Results:

A total of 78 subjects with 84 observations met the inclusion criteria. Median age was 20 years old (range 2-64) and median time between the first and last prescription filled was 20.5 months. Approximately 34.5% of the subjects were on aPCC (44.8% [OD] and 55.2% [P]) and 40.5% were on rFVIIa (85.3% [OD] and 14.7% [P]). The remaining subjects (25%) were on various combinations of aPCC and rFVIIa. Median annualized utilization for aPCC and rFVIIa was 7,183U/kg (2,186U/kg [OD] and 9,612U/kg [P]) and 13,838μg/kg (9,493μg/kg [OD] and 27,245μg/kg [P]), respectively. Median annualized cost/kg was significantly lower (p=0.0071) among patients treated on-demand with aPCC ($3,956/kg) compared to rFVIIa ($16,801/kg). Similarly, median annualized cost/kg was also significantly lower (p=0.0093) among patients treated prophylactically with aPCC ($17,399/kg) compared to rFVIIa ($48,223/kg). Overall, median annualized cost/kg for on-demand and prophylaxis treatments was 76.5% and 63.9% lower, respectively, with aPCC compared to rFVIIa. Furthermore, there was no significant difference (p=0.6438) in median annualized cost/kg between aPCC prophylaxis and rFVIIa on-demand.

Conclusion:

Overall, these data suggest that the annualized treatment cost with aPCC is significantly lower compared to that of rFVIIa for both on-demand and prophylaxis regimens. For each patient treated on-demand or prophylactically with rFVIIa, approximately 3-4 patients could be treated with aPCC at comparable cost. Additionally, the median rFVIIa on- demand patient could be prescribed aPCC prophylactically to reduce bleeding episodes without significant cost implications.

Objective:

To assess treatment of young adult (YA) patients with hemophilia (PWH) and issues around access to and use of factor and comprehensive care.

Methods:

Analysis of US respondents aged 18-30 years in the international HERO study conducted in 2010-2011.

Summary:

Of 189 adult PWH HERO respondents in the United States, 66 were aged 18-30 years. More YA-PWH were on prophylaxis (50%) than on-demand alone (24%) or with occasional short-term prophylaxis (24%). Only 27% used treatment medication exactly as prescribed, with 27% a little less, and 21% varying (sometimes more/less). Twenty-six percent reported issues with access to factor in the prior 5 years due to availability or affordability, with 82% citing financial issues. YA-PWH reported a median of 2 bleeds in the prior month and median (IQR) annual bleed rate of 9.5 (12-22) bleeds. Similar to older adults, 80% of YA-PWH reported that a single joint suffers more bleeds than others; the most common joints reported were the ankle (77%), elbow (26%), and knee (21%). YA-PWH rated perceived disease control (1-10 scale, 10=most control) as median (IQR) 8 (7-9). HTC visit frequency was median (mean) 1 (1.66) per year. Similar to older adults (aged >40 years), 21% of YA-PWH reported difficulty in visiting the HTC. Accessibility was the most common reason (79%)—distance to travel (57%) or time to travel (29%); time constraints were more commonly reported by YA-PWH (57%), including being unable to get time off work (50%). When identifying health care professionals (HCPs) involved in management of their hemophilia, YA-PWH named hematologists (83%), nurses (67%), social workers (48%), counselors/psychologists (30%), and physical therapists (26%). The majority were satisfied with care provided by HCPs. YA-PWH reported being very/somewhat knowledgeable about hemophilia (91%). When looking to the future (pessimistic=1 to optimistic=7), YA-PWH were generally optimistic, with median (IQR) 5 (5-7).

Conclusions:

YA-PWH in the United States are more likely to be on prophylaxis than older adults, but less likely to use medication exactly as prescribed. Additional research is warranted to better understand why prescribed regimens are not followed. Despite 50% prophylaxis use, bleeding occurred ~1-2 times/month and YA-PWH reported high perceived disease control. During this period of transition to independence, it is important to note one quarter reported issues around access to treatment and one fifth reported difficulty in visiting the HTC. YA-PWH were satisfied with care, but infrequently reported social workers and physical therapists as part of management.

Objectives:

The objective of this study was to compare the rate of prophylaxis between severe hemophilia B and severe hemophilia A patients.

Methods:

A retrospective cross sectional study was conducted using a large US specialty pharmacy dispensing database and 16 months of data (January 2013 to April 2014). Patients with ICD-9 diagnosis codes 286.0 (hemophilia A) or 286.1 (hemophilia B), who filled a prescription for any FVIII or FIX product were included. Prophylaxis patients were defined by having at least one prophylaxis dispensing record, while on-demand patients were defined by those without any prophylaxis dispensing record during the study period. Descriptive statistics were used to report patient characteristics and the percent of prophylaxis and on-demand patients by hemophilia A and B. Logistic regression was used to compare the rate of prophylaxis between severe hemophilia A and severe hemophilia B, while controlling for age.

Results:

A total of 1565 hemophilia A patients and 376 hemophilia B patients were included in the analysis. A higher percentage of hemophilia A patients had severe hemophilia than hemophilia B patients (63.1% vs. 45.0%, P<0.0001). The mean age for severe hemophilia patients was 24.6 and 22.8 years, respectively (P=0.04). Overall, more severe hemophilia A patients were on prophylaxis compared to severe hemophilia B patients (80.3% vs 73.4%, P=0.04)). When controlling for age, severe hemophilia A patients were significantly more likely to be on prophylaxis compared to severe hemophilia B patients (OR=1.63, P=0.02).

Conclusion:

Severe hemophilia B patients were less likely to be prescribed prophylaxis compared to severe hemophilia A patients. Efforts should be made so the benefits of prophylaxis are extended to more hemophilia B patients.

Objective:

Joint status was assessed in the 3-year SPINART study, which compared routine prophylaxis versus on-demand treatment in adults with severe hemophilia A. We report joint outcomes at year 3 obtained using magnetic resonance imaging (MRI).

Methods:

The open-label, randomized, controlled, parallel-group, multinational SPINART study enrolled males aged 12–50 years with severe hemophilia A who had ≥150 exposure days with any factor VIII (FVIII) product, no inhibitors, no prophylaxis for >12 consecutive months in the past 5 years, and 6–24 documented bleeding events or treatments in the previous 6 months. Patients were treated with Bayer’s sucrose-formulated recombinant FVIII (rFVIII-FS), either on demand or as prophylaxis (25 IU/kg 3 times weekly, with dose escalation by 5 IU/kg permitted once per year). MRI was performed at baseline and year 3 to evaluate the structure of 6 index joints. Each MRI was read by 3 radiologists blinded to treatment assignment who independently completed the extended MRI (eMRI) scale; higher eMRI scores indicate greater joint structure damage. The score for each joint was based on the readers’ median change score for each of the 45 eMRI scale items when comparing MRIs from different timepoints. Total patient score was derived; change from baseline in total patient score was prespecified as the first in a hierarchy of 2 secondary endpoints. Between- group comparison was made using constrained longitudinal data analysis. Data are presented for the intent-to-treat population.

Summary:

Of 84 patients enrolled (42 per treatment group), MRI data were available for 38 on-demand and 41 prophylaxis patients. Least squares (LS) mean change from baseline to year 3 on the eMRI scale total score was 0.96 for on demand and 0.79 for prophylaxis (LS mean difference, –0.17; 95% CI, –0.92 to 0.59; P=0.66). LS mean change from baseline to year 3 for on demand and prophylaxis was 0.06 and 0.01 for the eMRI soft-tissue domain (LS mean difference, –0.04; 95% CI, –0.18 to 0.10; P=0.53) and 0.90 and 0.78 for the eMRI osteochondral domain (LS mean difference, –0.12; 95% CI, –0.82 to 0.58; P=0.74).

Conclusions:

In adults with severe hemophilia A, progression of structural joint damage was not significantly different between patients using rFVIII prophylactically or on demand over a 3-year follow-up period, although less progression was seen with prophylaxis.

Dr. Tammuella Chrisentery-Singleton is an Assistant Professor of Clinical Pediatrics at Tulane University and is board certified in pediatric hematology/oncology. She will receive training under the mentorship of Cindy Leissinger, MD, Chief, Section of Hematology & Medical Oncology at Tulane University School of Medicine and Director of the Louisiana Center for Bleeding and Clotting Disorders. Chrisentery-Singleton graduated with honors from Xavier University, received her MD from Louisiana State University and then completed her pediatric residency at the University of Miami. Following residency, she completed pediatric hematology/oncology fellowship training at Johns Hopkins University, where she worked with Dr. Jim Cassella and developed a serious interest in disorders of coagulation, particularly hemophilia. After her fellowship training, she was recruited to join the pediatric hematology/oncology faculty at LSU and Children's Hospital of New Orleans. In 2010, Chrisentery-Singleton accepted a position at Tulane University because of her desire to receive more training and spend more time in the specialized coagulation medicine program. As an NHF-Baxter Clinical Fellow, she will receive dedicated training in bleeding and clotting disorders for both children and adult patients, along with mentoring in clinical research related to bleeding disorders. She will also continue her work on several ongoing clinical trials, and pursue her project in developing models to better determine pharmacokinetic parameters with a minimal number of needle sticks in pediatric patients with hemophilia. Her goals are to steadily improve her knowledge and skills in caring for patients with coagulation disorders, and continue building her academic career in coagulation medicine.

Dr. Jonathan Roberts is currently a pediatric hematology and oncology fellow with the Medical College of Wisconsin and the Children's Hospital of Wisconsin. His fellowship mentor will be Joan Gill, MD, Professor of Pediatrics at the Medical College of Wisconsin and Director of the Comprehensive Center for Bleeding Disorders (CCBD) at the BloodCenter of Wisconsin. Roberts graduated with honors from Greenville College, Illinois, and received his MD from Southern Illinois University School of Medicine. He did his residency in Pediatrics at the University of Illinois at Peoria and Children's Hospital of Illinois, where he also distinguished himself, receiving awards of excellence for critical care and research. During his pediatric residency, Roberts worked with Dr. Michael Tarantino to initiate a clinical research trial to assess the role of FXIII on intraventricular hemorrhage in premature, low birth weight infants. As a NHF-Baxter Clinical Fellow, Roberts will receive focused training and gain clinical experience through the hemostasis clinics at CCBD and further develop his research skills in a project to develop a new ELISA-based assay for assigning VWF phenotype. Roberts has plans to pursue a Master's Degree in Clinical and Translational Science. His goal is to become an expert physician/scientist with a long-term career focus on hemophilia, and other bleeding and clotting disorders.