Patient-centred research agenda for females with bleeding disorders

For the past 10 years, Hemophilia Federation of America (HFA), a nonprofit patient advocacy organization committed to assisting, educating and advocating for people with bleeding disorders (BD) in the USA, has been a leading voice in bringing the challenges of females (including individuals assigned female at birth, intersex and non-binary individuals) with symptoms or diagnoses of BD to the forefront. HFA is committed to ensuring that females are supported and cared for in their journey of managing symptoms and/or a diagnosis of a BD. The stories and experiences gathered by HFA from the females in the BD community formed the basis for initiating this work. HFA believes that females with symptoms or diagnoses of BD deserve better access to care and treatments grounded in the best evidence generated through research that is conducted with them and for them. To be able to address these challenges, HFA received several Eugene Washington Engagement Awards from the Patient-Centered Outcomes Research Institute (PCORI). Through these awards, HFA was able to build capacity among females to engage in research and bring together researchers, thought leaders, advocates and female patients to design a research agenda (RA). These projects successfully captured the voices of female patients and other stakeholders in the BD community to learn about their opportunities and experiences with patient-centred outcomes research and comparative effectiveness research. Themes emerged from the experiences of these two groups, most notably the lack of opportunity and participation for females in research, which leaves many females without access to appropriate care and treatment options. To bring the concerns of females into the research space, a bridging of the gaps among researchers and patients was necessary. HFA formed a community-based research network (CBRN), composed of patients, clinician-researchers, thought leaders and advocates from the BD community, which outlined a RA for females with symptoms or a diagnosis of BD. There was great intentionality in the process followed for developing this RA. Patient-participants of the CBRN were graduates of a prior HFA program that taught them about BD basics, women's health and wellness, research and clinical trials, and engagement while socially distancing, using an online private social networking site. Participants of this program also engaged in live presentations and discussions with clinician-researchers. After completing this program, HFA adapted a workbook available through PCORI's resources and tailored it to the BD community, which was used in conjunction with PCORI's Research Fundamentals training package to educate the CBRN patient-participants further on patient-centred outcomes research. Clinician-researchers and the other participants of the CBRN were also encouraged to review this learning package and discuss it with patient-participants. The females that participated in these trainings and meetings to develop the RA came from diverse ages, backgrounds, locations, races and patient experiences. Delivering the learning and social networking activities alongside the series of meetings was deliberate as the intent was to remove many of the barriers that sometimes hinder engagement among patients, clinicians, and other partners. HFA also wanted to model engagement and ensure that these skills and their relevance came across. As a result, training, equal compensation, and sharing leadership were hallmark pieces of this work. Through a series of five meetings with the CBRN, research topics, questions, and challenges regarding females with BD symptoms or diagnoses were discussed. During these meetings, each of the four female patient-participants were offered the opportunity to share with the team their diagnosis and/or treatment stories. The stories were shared with the intent of grounding participants in the importance of the conversations, to ensure partners understood the value of listening to each other, and to connect struggles of females with BD to familiar faces with whom relationships were already established. The intent behind this approach was to create a shared language, remove the power differential that often exists and create a community of engaged individuals focused on addressing the needs of females. HFA collated all the information generated through this series of discussions and developed a document outlining research areas, topics, and sample questions. This document may be the first of its kind in this community and the information contained in the document, being outlined jointly by patients and clinician-researchers, has the potential to be a launching pad for multiple research projects that could positively impact the delivery of clinical care for women with BD on a global scale. The RA, outlined in Table 1, is designed as a reference for research organizations to inform projects, with the aim of ensuring projects are directly useful to community members, supply research that informs policy and practice, and increase the capacity of stakeholders to conduct and use research. To that end, the CBRN identified research topics for females as areas of focus for work for the next three to five years. In addition, the CBRN outlined a few example research questions within these areas. The research topics and questions created by the CBRN were then further refined, added to, and vetted through three additional meetings held throughout 2022 by a Steering Committee (SC) composed of additional researchers, females with BD, and other BD stakeholders. The RA document was then shared more broadly among the colleagues/contacts of the SC to garner further input, refinement, and approval. It is important to note that the language of the RA was intended to be accessible to all individuals who participated in its development, and it is expected that modifications will need to be made when putting these research suggestions into practice. The agenda was informed by the lived experience of the females who participated and the expertise of the clinician-researchers as well as other partners. This is a collection of the ideas and experiences that the participants brought forth and is meant to identify topics of relevance to them, not to be a comprehensive literature review or prioritization process. After gaining the approval of the SC and their network of colleagues, HFA sought further validation by the wider BD community of the content of the RA. Thus, a convening was held in October 2022 to disseminate and seek approval of the RA, utilizing a hybrid (in-person and online) meeting approach. With a few minor edits, the Research Agenda for Females with Bleeding Disorders was unanimously approved (see Supporting information for the full approved document). Organizations involved in the final convening included representatives from Centers for Disease Control and Prevention (CDC), National Bleeding Disorder Foundation (formerly NHF), American Thrombosis and Hemostasis Network (ATHN), Health Resources and Services Administration (HRSA), Foundation for Women & Girls with Bleeding Disorders (FWGBD), PCORI, Hemophilia of Georgia, Cottrill's Specialty Pharmacy, Takeda, Genentech, Pfizer and Sanofi. The opportunity for further review and comment on the RA added to the credibility, scope, and value of the RA. During this meeting, HFA shared and explained the agenda and the work that went into it to an interested group of partners which also enabled real time discussions, feedback, and endorsements from key stakeholders in the community. The convening culminated in much interest in the adoption of research projects for females that came from this document by researchers, clinicians and patients in attendance, and the stakeholder organizations that were present committed to more collaborative efforts going forward. Clinical trial endpoints Burden of disorder Social health disparities Non-severe prophylaxis Aging with BD Family of males with BD Life experiences Addressing meaning of “normal” menstrual bleeding Mental health Classification of disorders Support available Universal screening tool Assessing knowledge of parents, patients, and providers Quality of life, including social aspects Fatigue score for females with reported heavy menstrual bleeding School policy assessment Pregnancy Childbirth complications Self-management as a caregiver Hormonal therapy Prophylactic treatment BD symptoms over time Menopause and haemostasis/factor levels Bone health Mental health While much energy, excitement and interest were created for the RA, it was clear that the BD stakeholder community needs to come together to make this work translate into reality and turn these ideas into funded projects. A common theme that was brought to light by the professional stakeholders was limited funding to move projects forward. Further conversation, planning and collaboration is needed to bring these projects to the forefront, and HFA is committed to making this happen and needs partners to make it a reality. Who will join us? R.F.S. has received honoraria for advisory boards from Genentech/Roche, Sanofi/Sobi, LFB/Hema Biologics, Pfizer, Octapharma, Guardian Therapeutics, HEMAb, Takeda, Bayer. R.F.S. has investigator-initiated grant support from Genentech, Takeda, and Octapharma. R.F.S. is the PI of the Wilate prophylaxis and Adynovate PUPs studies. M.C.B. has served as a paid consultant for Genentech. K.M.H. has received research funding from the American Thrombosis + Hemostasis Network/Hemostasis and Thrombosis Research Society. S.J. works for Paragon Healthcare. S.J. is a public speaker and contracts with Medexus Pharmaceuticals at times. Whitney Armijo, Janet Chupka, DeBran Tarver and Mabel Crescioni selected working group members from a group of applications and planned and led working group sessions with all authors. Mabel Crescioni wrote the body of the letter to the editor (with edits from all other authors). Whitney Armijo gathered input on top-priority research areas from females with BD. Robert F. Sidonio, Jr., Megan C. Brown, Kristina M. Haley, Patricia Huguelet, Karen Bowe-Hause, Julie Conde, Stormy Johnson, Aamina Iftikhar, and Candace Lerman made up the Community-based Research Network (CBRN) and contributed and refined ideas for research topics and example questions. Additional thanks are given to the Steering Committee (SC) members, who further reviewed, refined, and added to the research topics and example questions. These members included Kendall Fitzpatrick, Meera B. Chitlur, MD, Skye Peltier, MPH, PA-C, Michelle M. Rice, Jill McCary, Amy Moon, Christina Taylor, Patricia Huguelet, Robert F. Sidonio, Aamina Iftikhar, and Julia Conde. This work was funded through Patient-Centered Outcomes Research Institute (PCORI) Eugene Washington Engagement Award #EASCS-23237. The statements in this document are solely the responsibility of the authors and do not necessarily represent the views of PCORI, its Board of Governors or Methodology Committee. This document describes engagement projects that do not involve personal identifying information or interventions. All patients involved in the creation of this document consented to sharing their experiences, ideas, and priorities. Patients were able to discontinue participation at any time. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.