How clinicians and persons with hemophilia may approach shared decision-making

KEYWORDS:

• Hemophilia
• hemophilia A
• hemophilia B
• treatment
• shared decision-making

1. Introduction

Hemophilia A (HA) and B (HB) are rare X-linked inherited bleeding disorders associated with high morbidity related to bleeding. For several decades prophylaxis with regular intravenous infusions of clotting factor concentrate (CFC) has been the only option to prevent bleeding for persons with hemophilia (PwH) and offered primarily for severe hemophilia. Treatment related decision-making focuses on if and when to start prophylaxis, the type of clotting factor, and dose and frequency to achieve a target goal. Several non-factor replacement prophylaxis strategies, including first generation bi-specific antibody therapies and re-balancing therapies, with less burdensome routes of administration and less frequent dosing are now available, and others are in late-stage clinical development. The first gene therapies for HB and HA were approved by the US Food and Drug Administration (FDA) in November 2022 and June 2023 respectively. Successful gene therapy has the potential to eliminate the need for ongoing factor replacement or other hemostatic treatments, but there remain unknowns related to variability and duration of effect and possible adverse effects, making the decision to receive gene therapy or not a complex one. In addition, monitoring following gene therapy infusion is more intense than that required for other prophylaxis treatments. Therefore, patient preferences and treatment goals will impact treatment decision-making.

2. Shared decision-making

Shared decision-making (SDM) for hemophilia is a communication process between PwH/caregivers and their health care team, aimed at empowering PwH to understand the available treatment options, potential benefits, harms, and side effects, and choose the best option in the context of their values and preferences. SDM is particularly important when there is more than one possible treatment option and when no treatment option has a clear advantage as is the current situation for many PwH, particularly those in high income countries, with access to many different types of treatment.

Treatment related medical decisions in hemophilia are based on several considerations, including the type and severity of hemophilia, the age of the PwH, available treatment options and patient preferences. With the evolving treatment landscape for hemophilia, PwH may switch therapies several times throughout their life. In young children, the first decision for parents is related to the type of treatment and timing of prophylaxis initiation [1,2]. This decision becomes more complex if a young child develops an inhibitor, which neutralizes the effect of the CFC, and necessitates decisions related to bleed treatment and inhibitor eradication. As PwH age and new products become available to them, they may consider adjusting their treatment regimen. There are several new classes of treatments approved for use, and others in late-stage clinical trials. They work on different pathways and carry different risk and efficacy profiles. This new complexity makes informed treatment decisions more important, particularly for gene therapy which carries many unknowns and is a treatment that cannot be reversed. It must be recognized that for PwH in low- and middle-income countries where there is insufficient, limited or no access to treatments, treatment decisions may focus on when and how to treat a bleed if treatment is available [3].

The hemophilia community has recognized the importance of SDM as the treatment landscape has evolved to include more options with varying risks, benefits, and modalities [4]. Patients who engage in decision-making are more likely to engage in their care and follow the treatment plan [5]. To meet these needs, investigators and community-based organizations have been conducting research and developing educational resources and SDM tools. A multidisciplinary panel of experts in hemophilia identified the importance of patient involvement, patient education, defining patient priorities, and utilizing decision-making tools to guide treatment decisions [6]. Clinical practice guidelines also include recommendations for SDM [7,8], and other organizations have created SDM tools to provide guidance and structure to shared decisions between healthcare teams and patients [9].

SDM tools facilitate the SDM process by providing a systematic and structured approach to goal setting and decision-making. The tools are designed to help people make informed and deliberate treatment choices. These tools provide information on the options and outcomes that are relevant to the patient’s health status and clarify personal values. The development of SDM tools follows a rigorous methodology based on defined standards that includes a review of the literature for scientific evidence; an iterative process of developing and testing of the tool with key stakeholders [5]. Interviews conducted with 25 men with hemophilia indicated that most (88%) believed a SDM tool would be useful when discussing gene therapy with the medical team [10].

For hemophilia most of the decision-making is related to treatment, although there are also decisions about surgery, pain management, laboratory testing, etc. Investigators have identified key information to include in hemophilia SDM tools: mechanism of action, eligibility, safety, efficacy, comparisons across treatments, practicalities of administration and follow-up [10–14]. PwH value tangible material to take home for further discussion [10]. Clinicians value a checklist of information. Tools must be designed so they can be tailored to individual needs and accompanied by training on how to use them and multimodal education that provides information on the options to be discussed.

Guided by initial discussions at the World Federation of Hemophilia (WFH) Gene Therapy Round Tables and recognition of the importance of SDM for the current hemophilia treatment era, a multidisciplinary working group was established to create the WFH SDM tool [9]. The working group is composed of PwH, clinicians and researchers with expertise in hemophilia, methodologists, educational experts and staff of the National Bleeding Disorder Foundation (NBDF) and WFH. The goal of the tool is to support PwH in informed and goal-oriented decisions in collaboration with their treatment team and other key stakeholders. It provides users with the tools and knowledge (videos and written educational content) needed to be part of that discussion. It is evidence-based, informed by published research, and is a living tool with updates projected every six months. The online tool provides a stepwise process to aid a PwH with their decision-making when multiple treatment options are available. The SDM tool does not provide treatment recommendations, but rather provides the resources necessary to make an informed decision. The tool includes questions and statements for reflections that help a PwH identify how hemophilia is currently impacting their life and, if they are considering a treatment change, what might impact their decision-making. The educational component includes short videos and in-depth fact sheets on each of the treatment classes: CFC therapy, bi-specific antibody therapy, re-balancing therapy, and gene therapy. An interactive comparison table allows users to easily compare attributes of each of the treatment classes. The information is organized in a ‘Personalized SDM Tool Summary’ that can be used for further review and discussion along with suggested questions to ask the healthcare team.

Although health care professionals in today’s era most often take a patient-centered approach to SDM, most are not trained in SDM. Therefore, the tool includes a ‘Step-by-Step Guide for the Healthcare Team.’

The WFH SDM Tools was launched 1 August 2023 and is now available in English, Spanish and French; with German, Dutch and Japanese in development. A global training program is ongoing and the SDM tool will be evaluated with a pilot study to assess the feasibility, usability, and effectiveness from both a patient and health care professional point of view.

3. Expert opinion

Hemophilia is a chronic condition that requires ongoing management, and treatment decisions may need to be adjusted over time based on individual circumstances and availability of treatments. With several new products coming to the market, the treatment landscape and medical decision-making are more complex. A SDM tool for hemophilia treatments can facilitate this process by providing PwH and healthcare providers with accurate and up-to-date information about the available treatment options, potential benefits and risks of each treatment, as well as the expected outcomes. Use of SDM tools may positively impact implementation and outcomes of new therapies.

In order to effectively implement SDM, clinicians must understand the patient’s baseline knowledge, health literacy, and cultural and language preferences as basic elements for effective communication tailored to an individual’s preferences. Clinicians must establish who else will be involved in decision-making and ask about the preferred learning methods and adapt the education to these preferences. Clinicians should expect multi-visit discussions depending on the complexity of the decision and clarify with the patients that the decision may be to remain on the current treatment, modify the current treatment, change to a new treatment, or continue education and follow-up discussions.

There are several aspects of communication about new treatment options which are important. Intentional communication is critical, because how you say something makes a difference in how information is received and used. This includes using a consistent, unbiased, clear, and accurate lexicon, providing transparency about available treatment options, and setting realistic expectations based on known risks and benefits. Risk data can be particularly confusing, and experts recommend using natural frequencies (ie 1 in 100) to convey absolute and relative risks.

In assessing patient goals and preferences, clinicians should remember the ‘platinum rule,’ to treat the patient how they want to be treated and not infer preferences based on our own preferences.

Implementation could be hampered since it is an online tool and limited access to computer or mobile devices may be a barrier in resource limited areas. In addition, language and cultural differences may limit usability until the tool is adapted for more languages and cultures. The WFH plans to address these implementation barriers over time.

Regarding implementation in clinical practice, the authors believe that it is feasible to implement the WFH SDM tool in clinical practice with a systematic approach. Hemophilia Treatment Centers (HTCs) may prepare to implement SDM through a stepwise process which includes key elements of defining the HTC’s approach, providing knowledge and role-based education, and identifying barriers and possible solutions to implementation (Table 1).

Table 1. Key elements for hemophilia treatment center preparedness for implementation of SDM.

Define your HTC’s approach to SDM. How are patients identified? Who will be included in the discussions? Physicians, advanced practice providers, nurses, social workers, genetic counselors, and psychologists may participate in these discussions. When and how will discussions occur? How much time should be scheduled? Virtual vs. in-person visits? How will the discussions be documented? Is there a process where peers can be connected to discuss treatment options? How can the local community-based organizations support education and SDM Identify barriers to SDM Insufficient personnel for SDM Insufficient time Lack of infrastructure appropriate for effective communication Lack of available treatments Lack of educational resources and SDM tools in first language Complete healthcare provider education. Identify which team members should be trained and what training they need. Education should be targeted based on role and baseline knowledge. Utilize available educational materials from hemophilia organizations (WFH, NBDF, ISTH, etc), community based patient organizations, and the medical literature for clinicians to learn about hemophilia treatments and SDM.* Update training on a regular basis

*Resources for hemophilia education: Gene and Innovative Therapies Education | National Hemophilia Foundation; https://genetherapy.isth.org/; https://elearning.wfh.org/resource/science-gene-therapy-hemophilia/.

https://Partnersprn.org; Clinical Advances in Gene Therapy for Hemophilia (medscape.org); Development of a haemophilia A gene therapy shared decision-making tool for clinicians - PubMed (nih.gov); The Hemophilia Gene Therapy Patient Journey: Questions and Answers for Shared Decision-Making - PubMed (nih.gov) https://www.dovepress.com/the-hemophilia-gene-therapy-patient-journey-questions-and-answers-for–peer-reviewed-fulltext-article-PPA; https://sdm.wfh.org/. Resources for SDM education: Foundation for Informed Medical Decision Making Decision-Making Resources for Patients | Patients & Visitors | DHMC and Clinics (dartmouth-hitchcock.org); Massachusetts General Hospital Health Decision Sciences Center www.mghdecisionsciences.org; Mayo Clinic Statin Choice Decision Aid; https://statindecisionaid.mayoclinic.org/; The Ottawa Hospital Patient Decision Aidshttps://decisionaid.ohri.ca/.

For the WFH SDM tool, clinicians may invite PwH to participate in the SDM process and engage with the WFH SDM Tool; review the personalized summary report to facilitate an informed discussion of the patient’s life goals and preferences and discuss the treatment options they are interested in; present the treatment options that are available and that the PwH is eligible for and interested in; and facilitate deliberation and decision-making. The clinician may ask if there are any barriers to deciding or if they need more information or time to decide. Once a PwH has made an informed choice, the clinician should support implementation. When a PwH asks the clinician to decide on the treatment plan, the clinician should still ask the PwH about their understanding and potential concerns about the treatment prior to implementation. When a decision is not urgent and the PwH needs more information or time to consider risks/benefits or discuss with others, the clinician should support continued reflection and deliberation. Finally, with any change in treatment, especially transformative changes, such as gene therapy, clinicians need to monitor physical outcomes and mental health and provide support as needed.

Potential barriers to SDM may be lack of time for SDM in the clinic or lack of clinician expertise. In order to address these barriers, HTCs may partner with other HTCs who already have experience with SDM and/or new therapies so that they can learn best practices for implementation. In regard to time and personnel, HTCs may evaluate their clinic efficiency to determine if any time-consuming processes or duplicate provider efforts could be streamlined to increase provider time for SDM. HTCs should also identify a private space for discussions; conference rooms could be used if exam rooms are limited or information sessions may be provided in groups settings. In resource limited areas, HTCs may contact the WFH for humanitarian aid and potentially participate in the Twinning Program to increase access to effective treatments.

Future research in this field may lead to better understanding of how to optimally implement SDM tools, how to adapt the tools to different treatments, patient populations and clinical settings, and the impact of SDM on patient engagement and outcomes.

In summary, SDM is more important than ever for PwH and there are available education and training resources for PwH and healthcare providers to use. There are opportunities for evaluation and optimization of the tools such that they have global implementation. Overall, we expect that in five years, the use of validated SDM tools will be widely incorporated into clinical practice, and PwH will be more informed and engaged in decision-making such that they are active participants in treatment decision-making and have improved clinical outcomes and overall well-being.

Declaration of interest

CD Thornburg has received institutional research funding from NovoNordisk, and has served as an advisor for CSL Behring, Genentech, Pfizer, Regeneron, Sanofi, and Spark Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.