Research Studies

Dr. Jill Johnsen is scientist and physician at the Washington Center for Bleeding Disorders in Seattle, WA.  She is an Associate Member at the Bloodworks Research Institute and also an Associate Professor of Medicine in the Division of Hematology at the University of Washington. Her research focuses on the study of hereditary and acquired modifiers of blood traits, with particular emphasis on the genetics and biology of variation in blood group and coagulation factors such as factor VIII, factor IX, and von Willebrand Factor.  Dr. Johnsen is honored by this award and grateful for this support that will further the development of a test to enable patients and providers to determine factor levels much more quickly without needing to send blood to a lab.

Introduction:

Photovoice is a qualitative research method that has been used for communities to share pictures as a tool for discussion that is often used at a grassroots advocacy level. Photovoice can show both strengths about a topic or concerns. Photovoice can create empowerment by sharing perspectives and can also create a foundation to advocate for awareness and change.

Long-term Goal:

To create more awareness surrounding bleeding disorders during the month of March, which is bleeding disorders awareness month.

Objectives:

1. To apply Photovoice methodology to the use of social media among the hemophilia population in the Cincinnati, Ohio geographical area.
2. To engage people with hemophilia and their families in sharing their stories related to their bleeding disorder by sharing photographic images on social media during bleeding disorders awareness month.

Methods:

People that follow the Tri-State Bleeding Disorder Foundation on social media as well as members of a closed social media group that consist of parents of children who are patients at Cincinnati Children’s Hospital were asked to participate in the pilot Photovoice project. Participants were asked to share pictures on their own social media pages and to use hashtags to link the photos to the Tri-State Bleeding Disorder Foundation’s page. The project was promoted by sharing an infographic that explained Photovoice and the details of the project. Several community stakeholders were identified as people active on social media and they were personally asked to participate so that examples of the project could be shared with others. There were weekly themes and a weekly contest for pictures that best exemplified that week’s theme with the winners winning a small gift card.

Summary:

This innovative pilot project applied the methodology of Photovoice to social media to generate awareness and advocacy during bleeding disorders awareness month. The theme of this Photovoice project was “Living with Hemophilia”. Weekly themes consisted of: living with a new diagnosis, living with treatment, living and learning about a bleeding disorder, and living with health and being physically active.

Conclusion:

Utilizing Photovoice and applying this methodology to social media as a pilot project with the bleeding disorder population is an innovative idea. This grass roots level movement is a modern way for people to share their story of living with a bleeding disorder. To date, the use of this methodology with the bleeding disorder population has not been documented in the literature. Participants in this project reported satisfaction with being a part of the project. The project’s authors reported that it was a positive and creative way to create more awareness on a personal level about bleeding disorders and they plan to repeat the project in the future. 

Objective:

To determine the medical and educational needs reported by persons with Type 3 and other severe types of Von Willebrand Disease (VWD) who attended the second USA National Type 3/Severe VWD Conference held in Florida in June 2018.

Little research has been done concerning medical issues and education in Type 3/Severe VWD.  As patient identification increases, it is vital that education, support and resources are available for these patients.

Methods:

A survey of 48 questions was developed and administered to 74 vetted patient attendees. Responses for any individual question varied between 62-66.  The survey was administered through an Audience Response System (ARS) utilizing handheld clickers. The responses were compiled and immediately visually available to the respondents via a projector screen.

The multiple-choice questions were used to identify basic demographics, medical and psychosocial concerns, and educational needs.

Summary:

In this self-reported ARS survey, basic demographic data was obtained. This sample of VWD patients reported a need for more education on several issues related to their medical and psychosocial issues including depression/mental health issues, lab results and product choices. In addition, subjects reported significant needs for care, treatment and education in the fields of orthopedic services and genetic counseling.

Respondents' answers expressed a lack of orthopedic care despite a need for it. Only 8 (13%) patients reported having an orthopedic surgeon attend his/her bleeding disorder clinic. Forty-two (67%) did not know of any orthopedic resources. However, 18 (28%) reported that he/she had already had at least one joint surgery/procedure due to VWD and 5 (*%) plan to have surgery in the future. Eight (12%) had had joint replacements. 

Only 25 (40%) of respondents knew that they had undergone genetic testing related to their bleeding disorder, 30 (48%) have not had genetic testing, 8 (13%) were unsure.  When asked, “Were your parents diagnosed with a bleeding disorder before your birth?” of the 63 who answered, 51 (81%) stated “no, neither parent”. When asked if a parent was diagnosed with a bleeding disorder after the respondent’s birth, 24 (38%) responded “yes” to one or both parents. Twelve (19%) respondents have had their diagnosis change since first being identified with a bleeding disorder.

Conclusion:

Orthopedic care, genetic testing and education are vital services wanted by Type 3/Severe VWD patients. The community should further evaluate these needs and take action to respond. These results may also empower persons with Type 3/Severe VWD to seek support from professional and social members of their community. 
 
 
 

Objective:

Hemophilia may negatively impact a patient’s health utility and quality of life (QoL). Health state utility values (HSUVs) and QoL are important inputs to the evaluation of novel treatment being developed in hemophilia, including gene therapies. This systematic literature review identified and evaluated HSUVs and QoL for people with hemophilia (PWH) type A and/or type B, as well as utility decrements relevant to the experience of PWH, by treatment and health state.

Methods:

Building on a review undertaken in 2014 (Grosse et al. 2015), we conducted a systematic literature review to March 2019 through a search of electronic medical databases, including MEDLINE®, Web of Science, Cochrane Library databases and the School of Health and Related Research Health Utilities Database (SCHARRHUD). Major clinical, patient, and pharmacoeconomic conferences in 2016-2019 were also queried. Studies were independently double screened by independent reviewers, after which data extraction was performed.  The information extracted included study design, description of treatment and health state, respondent details, instrument and tariff, HSUV and QoL estimates, quality of study, and appropriateness for use in economic evaluations of novel treatment.

Summary:

Of 1,511 titles and abstracts screened, 20 studies and 12 conference abstracts were included. The studies identified applied a mix of direct and indirect health utility elicitation techniques. Two studies applied direct time trade-off (TTO) methodology and the remaining 30 studies adopted indirect valuation methodologies. HSUVs were found to decrease with increasing disease severity. For example, in Hoxer et al. (2018), mean (standard deviation) HSUV were 0.80 (0.21), 0.73 (0.22) and 0.67 (0.25) in people with mild, moderate, and severe hemophilia, respectively.

Utility values were also found to vary by severity of musculoskeletal damage, frequency of bleed episodes, inhibitors, hemophilia subtype, treatment regimen, treatment adherence and other disease-related complications. Interestingly, HSUVs derived from valuations from the general public were found to be valued lower than those derived from PWH for similar health states. For example, in Carlsson et al. (2017), general population participants consistently rated significantly lower HSUVs for hemophilia disease states compared to PWH (range: 0.54-0.60 vs. 0.67-0.73).

Several hemophilia-specific QoL instruments were used alongside HSUV evaluations. These QoL findings further contribute to improving the understanding of the impact of hemophilia on PWH.

Conclusions:

This systematic review shows significant impact of hemophilia on health utilities and QoL among PWH. The substantial humanistic burden experienced by PWH highlights unmet needs remaining in hemophilia. Our review findings also suggest potential disease state adaptation among PWH, which warrants further research using robust patient preference studies.
 

Dr. Esther Cooke received her Ph.D. from the Leeds Institute of Cardiovascular and Metabolic Medicine at the University of Leeds, U.K., where she studied the role of fibrinogen phosphorylation in thrombosis. Dr. Cooke is currently a postdoctoral fellow in the laboratory of Dr. Annette von Drygalski, at the University of California San Diego, and in collaboration with the laboratory of Dr. Laurent Mosnier at the Scripps Research Institute. Dr. Cook's JGP Fellowship project will focus on pathological mechanisms associated with joint bleeding, re-bleeding, and the development of hemophilic arthropathy. Dr. Cooke will perform comprehensive gene expression analyses to explore key molecular markers and pathways that drive soft tissue inflammation and vascular changes in joints after bleeding. In this way, she hopes to identify new therapeutic targets and develop novel treatment strategies to down-regulate these processes, thereby reducing re-bleeding tendency and slowing the progression of hemophilic arthropathy.

Objective:

Demonstrate the success of collaborative efforts between the specialized multidisciplinary Infusion Pharmacy Provider (IPP), the prescriber, patient and payer, in achieving improved outcomes.

Methods:

A Case Study including chart review, cost analysis, and interviews with patient and prescriber.

Summary:

Patient is a 23-year-old male with severe hemophilia A and an inhibitor, followed by a Hemophilia Treatment Center (HTC). Patient developed a high titer inhibitor with a Bethesda Titre of 1000 BU/ml as a child. Several complex treatment plans including: Immune Tolerance Therapy (ITT) utilizing plasma derived and recombinant factor products, immunosuppressive therapy, and prophylaxis with bypassing agents failed. Complications with implanted ports resulted in hospitalizations and replacement of approximately twenty ports. Numerous hospitalizations for uncontrolled bleeding episodes and pain management contributed to a disruptive childhood/adolescence and suboptimal quality of life for the patient and family.

Patient was unable to attend school regularly, develop socially, or participate in normal age-appropriate activities. Repeated uncontrollable bleeding episodes led to the development of target joints and hemarthrosis. The complex nature of the patient’s treatment regimen, his psychosocial issues, bleed history, and cost of therapy resulted in frequent communication and collaboration between all stakeholders to maximize therapy outcomes.

Inhibitors presents a significant management challenge.2 Emicizumab (Hemlibra®) was approved for the treatment of hemophilia A with inhibitors in November 2017. Well in advance of the transition, the IPP and prescriber discussed the benefits with the patient. Although understandably reluctant due to his history of failed therapies, the patient agreed to try Emicizumab. Initial doses were administered at the IPP’s Alternate Infusion Suite (AIS) under clinical observation, per prescriber’s request. The patient and caregiver received extensive education regarding potential adverse events, self- administration, and bleed treatment regimen during these visits.

Conclusion:

The coordination of care, communication, and goal alignment by all stakeholders resulted in positive outcomes for this patient. Following eighteen months of therapy with Emicizumab, the patient reports improved over-all quality of life as evidenced by his ability to maintain employment, attend college, and engage in social events/ activities. Twenty-two hospitalizations in the twelve months prior to changing therapies decreased to one in the eighteen months after transitioning. His bleeding events decreased from six to eight bleeds per month to one bleed in the past eighteen months and this bleed was attributed to a missed dose. Education on the importance of adhering to prescribed dosing schedule was reinforced by both the IPP and HTC. His port has been removed. Along with his significant increase in quality of life, the dramatic decrease in overall cost of care will be highlighted.

Objective:

The formation of inhibitors to clotting factors is a serious complication in hemophilia A. Immune tolerance induction (ITI) therapy remains the primary method for eradicating inhibitors. This multicenter retrospective data collection project evaluated patient- and treatment-related factors associated with outcomes following primary or rescue ITI with an antihemophilic factor (Human) concentrate in patients with hemophilia A and high titer inhibitors.

Methods:

Medical records of nine inhibitor patients treated with antihemophilic factor (human) for primary or rescue ITI therapy between January 1, 2012 and July 31, 2017 were evaluated in four US hemophilia treatment centers. Data were de-identified and analyzed descriptively. Outcome measures were defined per the International Immune Tolerance Induction Study: successful (eradication of FVIII inhibitor and normal FVIII recovery), partial success (near normal FVIII recovery), and failure.

Results:

A total of nine patients between the ages of 10 months and 39 years at time of ITI were evaluated. Six out of nine patients (66.7%) had successful ITI; three with complete success (ages 27, 32, 32 years) and three with partial success (ages 5, 5, 21 years). Three patients failed ITI (ages 1.5, 10.5, 39 years) (Table 1.) Six of the patients had a combined previous ten attempts at ITI with other products (plasma derived and/or recombinant). Of these six rescue patients, ITI with antihemophilic factor (human) was successful in one and partially successful in three.

Conclusions:

While retrospective data has limitations, real-world evidence demonstrates that ITI with antihemophilic factor (human) concentrate can be successful or partially successful in diverse populations of moderately complex patients with hemophilia A and high titer inhibitor.