Perceptions and Recommendations Regarding Haemophilia B Gene Therapy: A Multistakeholder View From Patients, Caregivers and Healthcare Professionals

ABSTRACT

Background

Gene therapy for Haemophilia B has received FDA approval, offering patients a transformative therapeutic option. However, effective communication about the benefits, risks, long‐term efficacy and follow‐up of gene therapy remains essential for informed decision‐making. This study aimed to explore the diverse expectations, concerns and perspectives of patients with Haemophilia B, their caregivers and healthcare professionals (HCPs) regarding gene therapy and to identify strategies for improving communication.

Methods

A prospective qualitative study was conducted using semi‐structured interviews with male patients aged ≥12 years with moderate or severe Haemophilia B (factor level ≤ 2%), their caregivers and HCPs (physicians, nurses, social workers, advanced practice providers and pharmacists). Interviews were audio‐recorded, transcribed and analysed thematically.

Results

Thirty participants were interviewed, including 15 patients (mean age, 21.1 years), caregivers and 15 HCPs across the United States. Patients and caregivers emphasised five themes: (1) current challenges; (2) hope and optimism; (3) concerns and skepticism; (4) the complex emotional challenges of decision‐making and (5) preferences for transparent, patient‐friendly communication. HCPs identified four complementary themes: (1) variable patient knowledge; (2) the need for transparency in discussing ‘curative’ language; (3) factors influencing treatment decisions (trust, prior experiences and financial concerns) and (4) strategies to improve communication (clear language, visuals and testimonials).

Conclusion

Stakeholders view gene therapy as both promising and uncertain. Targeted educational interventions, transparent communication and patient‐centred decision discussions are essential to fill knowledge gaps and support informed consent in this transformative era of treatment for Haemophilia B.

1. Introduction

Haemophilia B is an X‐linked recessive disorder characterised by a deficiency in clotting Factor IX, which leads to abnormal bleeding in joints and muscles [1]. Advances in replacement therapy and the use of extended half‐life products, non‐factor products and rebalancing agents have improved outcomes for persons with Haemophilia B [2, 3, 4, 5, 6, 7, 8, 9]. Recently, two gene therapy products have been evaluated in the United States: etranacogene dezaparvovec (approved by the FDA in November 2022) and fidanacogene elaparvovec (approved by the FDA in April 2024 but later withdrawn by the manufacturer) [10, 11, 12, 13].

In clinical trials, gene therapy has demonstrated promising efficacy and safety [10, 11, 14, 15, 16, 17, 18, 19], but its successful integration into practice requires addressing barriers such as limited health literacy, misinformation and challenges in informed consent. Multiple national and international organisations, including the American Society of Gene + Cell Therapy, the World Federation of Haemophilia and the National Bleeding Disorders Foundation, have developed engaging educational tools to demystify gene therapy, such as visual aids, educational video series, expert‐level webinars on topics such as Factor VIII expression, workshops with knowledge assessment and a comprehensive glossary to simplify complex terms [20, 21, 22]. However, much of the content targets healthcare professionals (HCPs), is primarily in English and may not meet the diverse needs of patient populations.

Prior studies suggest that although people with haemophilia view gene therapy as potentially transformative, they harbour concerns about its safety, cost, durability and long‐term risks. A US‐based qualitative study of 21 patients with Haemophilia A or B found that the anticipated benefits of gene therapy included bleeding prevention and improved quality of life, whereas concerns centred on treatment failure and the financial burden, highlighting the need for clear safety and efficacy information [23].

A multicentre discrete‐choice experiment conducted with 183 patients in the United Kingdom, North America and Australia showed bleeding rate reduction to be the top priority (for 31% of participants), followed by reduced dosing frequency and durability (for 26%). Safety concerns also weighed heavily (for 17% in the short term, 11% in the long term) [24]. In Belgium, a qualitative study with 20 patients found generally positive attitudes: 40% (n = 8) were ‘very willing’ and 35% (n = 7) were ‘willing’ to try gene therapy, although discussions emphasised concerns regarding bleeding rates, factor levels, long‐term risks, daily life impact and discontinuation of prophylaxis [25]. The UK Exigency program further explored experience, knowledge, barriers to gene therapy, concerns and expectations among patients in and outside clinical trials, providers and caregivers. Patients and caregivers expressed overall enthusiasm for the life‐changing potential of gene therapy, but there was significant variation in their knowledge and understanding. Patients in trials reported real benefits but also unexpected challenges, whereas those outside trials and their caregivers often felt excluded and underinformed, and they highlighted the need for better education, equitable access and long‐term psychosocial support [26].

Although gene therapy is seen as a promising option for people with haemophilia, little is known about preferred communication methods among patients, caregivers and HCPs or how education can be optimised to support decisions. Key knowledge gaps remain around vector delivery, immune responses and transgene expression. Low health literacy, difficulty in understanding technical language and misinformation further emphasise the need for accessible, accurate education that enables informed decision‐making and realistic expectations [27].

This study aimed to explore knowledge, beliefs and communication preferences regarding gene therapy among patients with Haemophilia B, caregivers and HCPs, with the goal of informing patient‐centred educational strategies. The insights derived from this study can guide the development of educational programs that are comprehensive, accessible and tailored to patients’ individual preferences and needs.

2. Methods

2.1. Study Design

A prospective qualitative study using semi‐structured interviews was conducted to explore knowledge, attitude and beliefs about gene therapy among individuals with Haemophilia B, caregivers and HCPs, with findings reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines (Supporting Information S1) [28]. Institutional review board approval was obtained from St. Jude Children's Research Hospital, Memphis, Tennessee.

2.2. Participants and Recruitment Process

Eligible patients were ≥12 years of age, with moderate or severe Haemophilia B (with Factor IX levels of ≤2% or <1%, respectively). Caregivers were invited to participate. Eligible HCPs included physicians, nurses, advanced practice providers, pharmacists and social workers actively providing haemophilia care. Recruitment was conducted using convenience sampling. Patients were informed through flyers distributed via patient coalitions and treatment centres. HCPs were recruited through the Haemophilia and Thrombosis Research Society email list, as well as through professional and informal networks, to ensure broad reach across US haemophilia treatment centres. Interested participants contacted the study team directly, after which a team member obtained informed consent and scheduled an interview.

2.3. Interview Guides

Interview guides were developed through a literature review and consultation with experts in haemophilia and qualitative research. Drafts were piloted and refined twice through interviews with two or three patients with Haemophilia B and HCPs. The final guides were organised around thematic domains with open‐ended questions.

2.3.1. Patient and Caregiver Guide

Interviews began with demographics (age, distance from treatment centres, education, occupation and internet/smartphone access). Key domains included (1) experiences living with haemophilia, including physical, emotional and psychological aspects; (2) knowledge of gene therapy, focusing on principles and potential applications; (3) beliefs and attitudes towards gene therapy, capturing the emotional context of decision making and (4) communication preferences, including desired clarity, level of detail and preferred formats [24, 29, 30, 31, 32].

2.3.2. Healthcare Provider Guide

Initial data collected included age, role in care and years of haemophilia experience. Domains paralleled those of patients/caregivers but were adapted to capture HCP perspectives. These include (1) experiences, challenges and successes in caring for patients with Haemophilia B; (2) perceptions of patient knowledge and educational gaps concerning gene therapy; (3) insights into patient beliefs and attitudes towards gene therapy; (4) approaches to communication and patient support regarding new treatments and (5) perspectives on patient preferences for receiving gene therapy information.

2.4. Data Collection

A team of four trained qualitative interviewers conducted all sessions, each lasting 45–60 min. Interviews were conducted by phone or via the HIPAA‐compliant platform iTracks to ensure confidentiality. All sessions were audio recorded, transcribed verbatim by a certified transcription service and verified for accuracy.

2.5. Data Analysis

A three‐member coding team conducted thematic analysis using NVivo14, a qualitative research software [33, 34]. To identify similarities and emerging trends for each interview question, transcripts were carefully reviewed by trained coders. The team followed a rigorous, iterative process that included memoing, that is, recording reflections and insights during code development, which informed the creation of a preliminary codebook.

To assess its reliability, the codebook was systematically applied to a subset of transcripts by the same coders. This pilot phase ensured consistent application of codes, strengthening the reliability of the analysis. Based on these results, the codebook was revised to improve its clarity and validity. The finalised codes were then applied to all transcripts, with at least two coders independently analysing each one. Inter‐coder reliability was assessed using Cohen's kappa, with a threshold of >0.7 confirming acceptable consistency [35].

Discrepancies were addressed through team discussions, in which coders discussed differences and reached a consensus with the help of an independent third person to ensure fair decisions. This systematic approach ensured consistency, strengthened credibility and enabled the team to identify recurring themes and develop meaningful concepts grounded in the qualitative data.

3. Results

3.1. Participant Demographics

Thirty participants with diverse demographics completed the interviews (Table 1). They included 15 male patients with moderate/severe Haemophilia B (mean age, 21.1 years; median, 17 years; range, 12–53 years), their caregivers and 15 HCPs (three physicians, two advanced practice providers, three nurses, three social workers, two pharmacists and two school educators) from across the United States. HCPs reported a median of 15 years of haemophilia care experience (range, 1–27 years).

TABLE 1.

Participant demographic information.

		N (%)
Patients and caregivers (n = 15)
Age (years)	12–18	8 (53%)
	>18	5 (33%)
	Not answered	2 (13%)
Average distance from haemophilia treatment centre (miles)		Mean: 61 (range: 20–200)
Occupation	Student	8 (53%)
	Teacher	2 (13%)
	Engineer	1 (7%)
	Salesperson	1 (7%)
	Homemaker	1 (7%)
	Patient advocate	1 (7%)
	Information technology	1 (7%)
Healthcare professionals (n = 15)
Years of experience		Mean: 11.6 (range: 1–40)
Role	Physician	3 (20%)
	Advanced practice provider/physician assistant	2 (13%)
	Nurse	3 (20%)
	Pharmacist	2 (13%)
	Social worker	3 (20%)
	School educator a	2 (13%)

^a Included because of involvement in patient care and education.

3.2. Thematic Analysis

3.2.1. Overview of Thematic Analysis

Thematic analysis revealed multiple themes and subthemes (Figure 1). Interviews of patients and caregivers identified five themes, and HPC interviews identified four themes with multiple subthemes.

FIGURE 1.

Themes and subthemes identified by stakeholders (patients, caregivers and healthcare professionals).

3.2.2. Patient and Caregiver Perspectives

Analysis of the interviews revealed five central themes, with related subthemes, that captured participants’ attitudes towards and beliefs about gene therapy (Table 2). The first theme, current challenges with haemophilia, highlighted the burden of managing existing treatment regimens, which demand frequent infusions, frequent, unpredictable bleeds and activity limitations. Caregivers emphasised the constant need to be vigilant with every bleed was stressful and emotionally taxing. Second theme, hope and optimism about gene therapy reflected cautious optimism that gene therapy could reduce their treatment burden and stabilise factor levels, with many participants viewing it as a potential opportunity to improve quality of life while acknowledging remaining uncertainties. Third theme, concerns and skepticism captured hesitation among some participants with key subthemes including the financial implications leading to unequal access, questions surrounding the safety and durability of the treatment, and potential unknown long‐term side effects, which tempered enthusiasm for some families. The fourth theme, emotional impact of a difficult decision underscored how the severity of Haemophilia B strongly influenced decision‐making processes for caregivers and patients who faced the complex task of managing a chronic ailment while simultaneously weighing the possibility of investing in a potentially curative option. This mindset was mixed with emotional considerations and anxiety about making the wrong decision with the fear of disappointment should the treatment yield unfavourable outcomes. Fifth theme, communication preference and recommendations emphasised the importance of clear, empathetic and thorough communication regarding gene therapy. Participants provided recommendations on enhancing the dissemination of information to patients and their families. Their suggestions included developing patient‐centred educational materials that simplify complex concepts into clear and concise language, devoid of technical language to elucidate the principles and aims of gene therapy. It was recommended to use diagrams or videos to clarify intricate ideas visually. Subthemes included multimodal education material tailored to patients, preference for visuals (videos/diagrams) and live presentations to explain complex concepts, transparent discussions about risks and benefit, direct discussions with clinicians and peers who experienced gene therapy, multidisciplinary individualised consultation that includes discussions with physicians, nurse practitioners, nurses, social workers to understand all aspects of changes patient may go through, frequent updates on the availability of new data, using testimonials and patient stories, support groups and community meetings and addressing financial concerns with all stakeholders.

TABLE 2.

Patients’ and caregivers’ themes, subthemes and impactful quotes.

Theme 1: Current challenges with haemophilia

‘It's hard to understand kind of the, the hidden illness that haemophilia is, so there, you know, there's bullying, the typical grade school stuff that you deal with and, and kind of work through. And then, you know, with the physical limitations comes the mental challenges. You know, not being able to participate in certain sports or playing one day but not the next and, and different challenges like that.’ (PT_SJ11) ‘We tried public school. No accommodations that, you know, for just everything for him; so we homeschool him. He got bullied a lot, picked on a lot; and so now I've been homeschooling him for years. So, I mean, it affects our daily life always. Since birth to now.’ (PTMother_SJ10) ‘… I had to make sure that he got to get his medicine because I didn't want him to fall down. He was rough and climbed the fence and, run out there with the other kids and scar his knee up.’ (PTMOTHER_SJ01) ‘… I bump into something… a normal everyday thing will ruin my life for a week or two. Meaning I have swelling in my knee, so I can't play golf, I can't walk the dog, I can't exercise…’ (PT_SJ06)

Theme 2: Hope and optimism

‘Basically, like she [his mother] said, it was like, like she said earlier that I'm quite forgetful, and I feel like doing it, like doing, taking the medicine, not as often. It [gene therapy] would give me more relief and I would seem like to feel more excited, and it would become a more significant part of my day and I feel more excited too.’ (PTMOTHER_SJ01) ‘… the idea that his factor level could potentially be stable somewhere between 30% or 40% would be fantastic…and, heck, over 5% would be great. I'd even go for that.’ (PTFATHER_SJ02)

Theme 3: Concerns and skepticism

Subtheme A: Cost and concerns about accessibility

‘It's just something like the cost of it. You know, it a little concerning. Like to think, man, that's a lot for something to not be, you know, 100% guaranteed.’ (PT_SJ15) ‘And then of course the whole insurance side of things, I mean, this was the highest per‐dollar amount drug ever approved by the FDA. So, if I'm going to go through the whole thing of being that 1% of patients out there that tilts the healthcare dollars spent in our nation, I want to make sure it's going to work for me and ultimately save money. But I just don't know right now.’ (PT_SJ11)

Subtheme B: Durability of efficacy

‘So, this is kind of where, like, with gene therapy, I kind of feel like my son isn't of age yet for this to be something that would benefit him. I know that it's just a one‐time infusion, you know that, and that it would essentially cure him. But it's not a lifelong cure that only lasts for a while. And that it's really expensive and this is, and its still kind of like new out there. So I'm assuming that by the time that my son's ready to, you know, look into this himself, when he's old enough that he, he will be the one who will make the decision on whether that's an option for him or something that he would want to do.’ (PTMOTHER_SJ10) ‘I don't … know how long it [gene therapy] lasts, so I don't know [whether it is a good option]. You may be good for a year but then it comes back, and it causes a lot of damage while it was done. So, … I don't know [if gene therapy would be beneficial].’ (PTMOTHER_SJ09)

Subtheme C: Unknown long‐term side effects

‘You know, like I said, it's extremely promising, you know, and I'm in, I'm in support of the new technologies and the new discoveries that help improve the quality of life for patients. However, in general, I feel like haemophilia is in a place that currently is saturated with products that work […] so I don't necessarily see the, the sentiment [there] and the, the, I guess what would make it too enticing to take the risk for gene therapy? The, you know, it would be different if we were even a few years ago, before extended half‐life products, before you know, these non‐factor products […] that really, really do and are effective at controlling bleeds. Before they came out, we were in a little bit different of a spot as a community as a whole. I see the reason why it [gene therapy] exists, and I see the need for it. However, I don't believe that I am in a place that I would willingly sign up to, to have it at this point. I don't know how it will effect or work in the long term, it so new.’ (PT_SJ12) ‘No, I'm not so for gene therapy. To me, the pros don't outweigh the cons because, you know, what it can do to your liver. You can only do it one time, you know, if it doesn't work, and in the middle of all of it, it never says that it can just totally get rid of your haemophilia and might move you from severe to moderate or moderate to mild. And you still may have to do, …, your infusions with a factor …. in the long run. To me, when I look at it and look at my son, it's like, I would just rather keep doing factor than to put him at risk.’ (PTMOTHER_SJ10)

Theme 4: Emotional impact of difficult decision

Subtheme A: Anxiety about making the wrong decision

‘[…] and part of it, maybe because, you know, we were on the same med for 10 years, and then we've been on the same meds since 2016. So we were very familiar, or very familiar with both. Um, and I don't know if it's across the haemophilia community, but once we try something and it works, don't monkey with it, you know <laugh>. So, so change, change in something that is set and we understand, and it works. Something that we're not sure is gonna work—is sometimes stressful.’ (PTMOTHER_SJ03) ‘As long as it [gene therapy] don't make him sicker, long as it keep him … on the healthy side, we all for it, but then again, I don't want nothing to start breaking his body down that he just really become … dependent, well, he's dependent on it now, but get to a place that he can't do without it. He have to go bedridden or he can't function no way unless he falling out or in a distress at all times. As long as it don't do that, I am game for it.’ (PT_SJ01_MOTHER) ‘You can only do it one time. If I take that risk, I want it all. I want to be done with haemophilia.’ (PT_SJ06)

Subtheme B: Emotional rollercoaster of dealing with chronic illness

‘So I would say once a month I bump into something, hit my shin, kind of a normal everyday thing for a normal individual that will ruin my life for a week or two. Meaning I have swelling in my knee so I can't play golf, I can't walk the dog, I can't exercise. And that's kind of the challenge of my life is the little simple things where if there was a pill to take that was reasonable, I would have those injuries that I could pop a pill for a couple days, stop the bleeding, and I would feel more normal. So not to get too much detail, but that's kind of how it affects me physically.’ (PT_SJ11) ‘I guess when I was younger was a little difficult being in school and the only kid in school that suddenly shows up in a wheelchair for one day and then he's walking the next and, you know, bunch of, you know, a bunch of mean kids saying all kinds of stuff, you know, when I was younger, but, you know, as I got older it's like I was actually in decent enough shape that I was able to actually have some pretty physical jobs for a while and just never let it bother me. So I just kind of moved on, moved through it.’ (PT_SJ05)

Theme 5: Communication preferences and recommendations

Subtheme A: Multimodal education tailored to patients

‘The best mode of communication, I would say, is by like, um, brochures and pamphlets. Like, maybe if I went to the doctor's office it used …I used to didn't notice brochures and pamphlets and I wouldn't read them. But now if I saw one, I would definitely read it.’ (PTMother_SJ04) ‘Videos are always more engaging, and they can help complement any pamphlet. So, I definitely think multiple modes of mediums or whatever to, to explain a very complex idea of gene therapy.’ (PT_SJ11) ‘The presentations where there somebody is actually there that knows about the, the products or the gene therapy or whatever and explains it, that's the most useful.’ (PT_SJ10) ‘Do presentations, give your opinions on it, and then have experts, that are studying that stuff and have them talk about [it].’ (PT_SJ07) ‘Most of the ways that I like to learn is through visuals. So, I would really like doing videos.’ (PT_SJ03) ‘[…] a group setting with likeminded individuals; have an education piece like a slideshow with pamphlets or a quick video with some animation.’ (PT_ST15) ‘[…] pamphlets or in like a group setting with likeminded individuals. You know, like have an education piece like whether it be a slideshow with pamphlets or you know a quick video like you said with some animation.’ (PT_SJ15)

Subtheme B: Transparent discussion about risks and benefits

‘I would certainly wanna ask about the side effects and, um, whether the doctor could treat him or not.’ (PT_SJ04) ‘I think the most important thing would be, like, the side effects of the medication […] yeah, basically the side effects, because [son with haemophilia is] really anxious about things like that, cause he's had obviously a bad time with having an allergy to the factor IX. So when he used to take something new, it makes him really anxious because he's scared of, like, repeating that process, you know?’ (PTMOTHER_SJ08) ‘I mean, just being open and transparent with everything that's found, but I think again, a lot of it's going to come down to just the length of the study. Being able to see the lifespan of a person who's had the therapy to see how it benefits them and side effects that may come about.’ (PT_SJ14) ‘… provide a phone number for somebody to call to get information, make sure that a live human answers the phone… and can get them started on that path towards getting them the information, even if they're not the guy to talk to. “Yes, ma'am. We'll, we'll talk to Dr. Such‐and‐such, and we'll have the team reach out to you immediately” and keep that… timeline moving. Don't let moss grow on it.’ (PT_SJ05)

Subtheme C: Individualised consultation with detailed post‐care plan

‘Our doctor, for our new [port], he was explaining to us and instead of just like explaining it, he actually wrote out all the steps it would take for this, how this medication works and everything. So I like he talked to me and then he wrote it down and I we did at the same time and I stopped and asked questions and that helped me understand how that medication worked instead of just like him just like talking to me, you know what I mean?’ (PTMOTHER_SJ08) ‘I think we have to meet one‐on‐one with our patient. I personally think that we need a team of providers that are, that are specific to gene therapy, whether that's a, an MD or an APP, but in conjunction with an RN and it that, that are the team for us. You need people that have expertise and knowledge and know how to, to manage [gene therapy follow‐up] but also have a consistent relationship with the patient and have had time to build up that trust relationship. And so that you have communication with the patient and you have a really good understanding of what the, the education they've received, what their understanding is of a knowledge base is, and that you can, that they trust the, that healthcare team to report and to, to ask questions.’ (PT_SJ11)

Subtheme D: Frequent updates on availability of new data

‘[to reassure him about engaging in gene therapy, the healthcare team should provide] anything about the testing that's been happened prior. How many people have gone through the study already? What's the success rate of the therapy?’ (PT_SJ06) ‘They should keep giving us information about the different test trials and the data from those trials to reassure [us about any uncertainties].’ (PTMOTHER_SJ07)

Subtheme E: Use of testimonials and patient stories

‘I think at one point we should have somebody that was in, like, a trial with gene therapy and talk about. Talk about it ‘cause, like, when you’re, when you go to, like, the meetings and everything you talk about, you know, oh, you know, this medication helps me or if I have a bleed, I do this or so forth and so forth. You know, especially when you have, like, my son has an inhibitor and it‘s very, very few people have that. So, when I talk to another parent that has a child that has that, you know, it’s nice to talk to that parent and get their information. Or […] if they have like a son that‘s younger, then I tell them our experiences, you know, and it helps them.’ (PTMOTHER_SJ08) ‘[…] some patients don’t necessarily feel they have a good rapport with a doctor, et cetera. You know, and, and I‘ve, and I’ve thrown this out to the people in my study in particular, to talk to somebody who‘s been through it, you know; it, it, it’s one thing to come from a doctor, but it‘s another thing to have information come from somebody who’s actually experienced the trial and experienced the changes in their life. To me, that would be one of the, one of the big ways to help convey, you know, the, the, the positive aspects of the gene therapy stuff.' (PT_SJ05)

Subtheme F: Support groups and community meetings

[The best way to learn is] ‘Through our coalition or our chapters, because we have a lot of families. I mean, we've made a lot of friends, and everybody comes together to learn and we're all really there for the same reason. And so, you know, teaching us through what through those meetings.’ (PT_SJ10)

Subtheme G: Address financial concerns with all stakeholders

‘Well, first off, probably the cost [would be the biggest factor in a decision to get gene therapy]. Would I be able to afford it? Does the insurance cover it?’ (PT_SJ14) ‘I don't know how long it lasts; you may be good for a year or two, but then it comes back. Which insurance company will pay for that? Doctors and nurses should get together with these pharma companies and insurance companies.’

3.2.3. Healthcare Professional Perspectives

HCPs viewed themselves not only as providers of treatment but also as stewards of trust and interpreters of complex science, emphasising that successful integration of gene therapy depended less on clinical efficacy alone and more on transparent, empathetic communication that acknowledged past experiences, addressed misconceptions and set realistic expectations (Table 3). The first theme, perceptions of patient knowledge and misinformation, reflected HCPs’ observations of patients with variable baseline knowledge, including misconceptions about DNA integration and long‐term effects, uncertainty about eligibility criteria, widespread misinformation about gene therapy and a lack of easy‐to‐understand information. The second theme, transparency and trust in communication, underscored the importance of avoiding the term ‘curative’ and safeguarding trust, particularly in research and consent contexts, with subthemes including honesty in discussing the concept of ‘cure’, respect for haemophilia identity and careful consideration of the style and frequency of discussions. The third theme, decision‐influencing factors, highlighted how prior experiences with the healthcare system, perceived industry influence and financial burden shaped receptivity to gene therapy, with subthemes including potential cost, impact on quality of life, fear of side effects and uncertainty of outcomes. The fourth theme, communication strategies to support decision‐making, emphasised the use of plain language, consistent messaging, visual tools and credible sources tailored to patient literacy and preferences, with subthemes including the use of visuals to explain concepts, clear communication without technical language and reliance on trusted sources to overcome medical distrust.

TABLE 3.

Healthcare professionals’ themes, subthemes and impactful quotes.

Theme 1: Perception of knowledge in patients and caregivers

Subtheme A: Uncertainty about eligibility criteria

‘[…] another misconception that patients have is that everybody with haemophilia is potentially eligible for gene therapy trials. Or, or for gene therapies. And, […] I think I forget the percentages, but a good number of patients have neutralising antibodies, so they, so they would by default not be eligible for it. So, I think that's another thing that, that patients need to understand.’ (PROV_SJ01) ‘We don't have a lot of […] kids that I can think of that are that age that would be eligible [for gene therapy]. So, it's kind of more of just preparing families that this is something that is coming but your child isn't eligible yet; sometimes people don't know that.’ PROV_SJ13

Subtheme B: Misinformation about gene therapy

‘I've seen in the haemophilia community when, like we talked about earlier, the, uh, human plasma‐derived factor products that caused so many problems when the newer products and later‐generation products that were not plasma‐derived, a lot of our parents still didn't trust it. And they were afraid to infuse their child for fear it would cause more harm, um, than help. And it was very difficult to get some of our parents over that hurdle because they remembered what their father or their brother went through. Um, so when they had their child with haemophilia, that's the culture they came from, and it was several parents. I had one that was still just adamant that, um, she did not want to keep infusing her child to prevent bleeds. She wanted to wait until he had a bleed ‘cause she did not wanna have to use it if possible, because in her mind it still had, uh, something in it that caused a AIDS or hepatitis B, and no amount of education that we gave her each visit, including the home health nurse that would come to help her infuse her child, that reinforced, you know, look, “this is product has not got any human blood in it”; she still was adamant about not doing prophylaxis for her child. I can see gene therapy having the same problem.’ (PROV_SJ07) ‘[…] you are also up against, I mean, you've seen this in our, in the culture, that there's information everywhere and some of it's good. Some of it's not, and people can be influenced, you know, that's a big part of our whole practice that is—I think we need to get a better understanding, you know, of the influence of social media on decision making and information. It's a part of our world now, and it could be good and it could be bad.’ (PROV_SJ05)

Subtheme C: Lack of easy‐to‐understand information

‘I think [family's understanding on gene therapy] depends on each unique family's access to information. And what I mean by that is we have some families from my experience who do not have enough organisation and stability in their life to be able to connect to other families who have haemophilia. They don't have the ability go and attend, like, the annual haemophilia conferences, even when they're two hours away, they can't make it happen. Um, and they maybe don't, they just don't have a lot of connection with, with the community. And so they're kind of left with what they see on the media, um, what they see in movies, uh, what they, I happen to read that they can process. […] I just think that we have, it just depends on the family's access to information, so some families will have tremendous misconceptions just because they don't have access [to information].’ (PROV_SJ04) ‘I think the biggest concern for parents [is] “are you going to change their DNA?” … when you use non‐integrating products, they do not by definition integrate with … the whole DNA. But … there's a small percentage that actually do integrate. … And that is acceptable, but … that part needs to be highlighted, not everyone gonna know DNA and gene and what it means.’ (PROV_SJ01)

Theme 2: Transparency in communication

Subtheme A: Being honest about word ‘curative’

‘I think probably the biggest misunderstanding is that they think it's, they think they're cured. Um, so making sure to address that, you know, these patients are still technically have mild haemophilia. You still need to correct clotting factor levels if having, you know, potentially if having surgery, um, and things like that, making sure that they understand that not every patient responds the same way, there's a, you know, kind of a, a spectrum there. And then again, emphasising that we're, you know, while we think this is going to be a long‐lasting solution or we it's designed to be that there's, you know, that's still to be determined through studies and, you know, ongoing surveillance.’ (PROV_SJ09) ‘Our current understanding and experience is that, depending on how the individual responds, [gene therapy] may be a treatment but not a cure. And they may need to continue to receive some factor throughout their life. […] I think that's news to them. Okay. Because in industry, industry doesn't use the word “cure,” or they haven't in any talks I've been in, involved in, but the perception from the patient is that this gene therapies may cure my haemophilia.’ (PROV_SJ11)

Subtheme B: Respecting haemophilia identity

‘Based on my long exposure to patients with haemophilia, there is a basic underlying fear and distrust of medical treatments based on past experience. It's understandable. Many of these men live through the terrible HIV times and the terrible hep C times. So many of them are cautious in terms of expanding their mindset about new therapies. I've heard many of them say “It's very interesting, but I kind of always feel the other shoe is gonna drop.” Many of them say if it ain't broke, don't fix it. In other words, factor has kept them out of the hospital, has helped them delay or decrease, mitigate their joint involvement. So, some of them are, especially the older men, are pretty satisfied staying with what they have. The younger patients, um, who have not experienced those dark times, especially of HIV, I think are more open to alternative therapies.’ (PROV_SJ12) ‘I've seen that in the haemophilia community when, […], the, uh, human plasma‐derived factor products that caused so many problems when the newer products and later‐generation products that were not plasma derived, a lot of our parents still didn't trust it. And they were afraid to infuse their child for fear it would cause more harm, um, than help. And it was very difficult to get some of our parents over that hurdle because they remembered what their father or their brother went through; so when they had their child with haemophilia, that's the culture they came from.’ (PROV_SJ07)

Subtheme C: Style and frequency of discussion

‘Most of the people that wanna know about it know very little about gene therapy. Um, so I have to kind of explain from the beginning, you know, exactly how, you know, what a viral vector is, how it's administered the body and what the risks are there, or the potential risk, theoretical risk, um, how it's, you know, intended to be a one‐time infusion. But, you know, we're not sure exactly what the long‐term stability is. So we have to talk about that a lot. Um, some patients, you know, have done a little bit of research and so they are a little more savvy to it. And so we can talk kind of a little more technical, like they wanna know ‘Will my insurance cover this?’ And so we can kind of dig into what might be required for insurance coverage. But I would say in general, most patients, you kinda have to start at ground zero and build up and it takes usually multiple conversations to kind of, for some of it to click.’ (PROV_SJ09) ‘Maybe bringing it up at every visit, um, you know, making that part of, like, our checklist of what we do each visit. So that way, um, hopefully they're more informed by the time it comes up, you know, to actually join one of these studies or, um, receive gene therapy. So maybe just, um, introducing the topic at every visit. Um, okay. So that way they're a little bit more informed.’ (PROV_SJ03) ‘As most of those patients between, you know, late thirties and forties, they still have some joint damage gene. Therapy's not gonna cure that joint damage. So their, I guess their perception of what gene therapy can do for them, including this side effects of gene therapy, has more to do with their quality of life. But in a different way, I don't have to stick so much. I don't have to do this as much, but it's not gonna take away their joint damage. So it's two different separate con conversations. I think you have to have at certain age groups.’ (PROV_SJ06)

Theme 3: Decision‐influencing factors

Subtheme A: Potential cost

‘[…] parents are actually pretty interested in the cost, okay, of their treatment, and even if they are not bearing the, the burden of the, of the cost of the therapy, they really wanna know about how much it, they still wanna know how much the product costs them, costs whoever is paying for it. And again, talking to parents or, or talking to participants, a lot of times when I ask them, like, “What do you think about gene therapy?” A good number of them were, “Well, it's gonna cost millions of dollars upfront and I don't see my payer pay for it.”’ (PROV_SJ01) ‘Well, they want to know how it works or if it does work, uh, they want to know how expensive it is. I think that's a big question in their minds. Um, they, they want to know, um, since it is going to be a costly procedure, is the cost justified by long‐term positive results?’ (PROV_SJ12)

Subtheme B: Impact on quality of life

‘If you're approaching a parent about gene therapy, one of the things you can say to that parent is hopefully, hopefully you're gonna prevent a lot of joint damage. That's why we had factor, you know, way long time ago, even before Pete treated, we're hoping to prevent and the longevity of life, um, as factors and improved and got better. Our goal was then prophylaxis to prevent joint damage in children and in young adults.’ PROV_SJ06 ‘I think it's very interesting and I think it's beneficial for our kids. I've only been a part of two factor VIII studies on gene therapy, so I have not, no personal experience with the factor IX, but I do think that it could be life‐changing for our patients. I'm excited about it. Just by minimising their bleeding risk, preserving joint health, preventing all the infusions that they have to get for their prophylaxis and bleeding.’ (PROV_SJ13)

Subtheme C: Fear of side effects

‘[It is a] 50–50 chance, uh, that they would agree to do [gene therapy], um, versus if there is documentation [of results of gene therapy versus] standard of care, uh, what do they know for sure in the gene therapy area that is working with the least amount of side effects, would be a potential for them to agree, uh, to take a risk, but at all in all, when it comes to children and pediatrics, I think the parents always are gonna err on the side of caution about making those kinds of decisions.’ (PROV_SJ07) ‘The most important thing [in families’ decision‐making]? Yeah, I think they, they generally want to make sure that it's not going to harm them; so, so the, the vector is not gonna cause problems down the line in terms of their liver or other organs.’ (PROV_SJ10)

Subtheme D: Uncertainty of outcomes

‘Yeah, I, I don't know if I would say that they're misconceptions [about gene therapy]. It's just lack of understanding, lack of, of, you know, full understanding; and, you know, that goes along with any new treatment that comes along you know, with number one, does it work?’ (PROV_SJ10) ‘I think there's so, um, in the haemophilia community that there's just not a lot of information yet because of no, uh, long‐term research, you know, to see is it going to work? Is it gonna be harmful if we try this? I mean, there's a certain amount of risk even in doing an infusion, but it, it's much more of a risk when you're talking about gene therapy, I think in the parent's mind and also in [the patient's] mind. So you want those assurances that if this is going to be a, uh, possible option, that it is safe for my child.’ (PROV_SJ07) ‘I think families are just very skeptical of new things and they want to see, um, a, a good majority of them, or at least maybe half of them want to maybe want to feel it out. And, um, you know, it's a close it to some degree, it's a close‐knit community. So these families know each other, they hear stuff from each other. Again, they hear from drug reps, which is not, is not a good source of information, but, you know, I think once they see that patients are going through some of these patients, some of these families, once they see that, um, other families have opted to go through with the therapy, um, I think that more and more will come to, uh, to accept it, maybe.’ (PROV_SJ08)

Theme 4: Communication strategies

Subtheme A: Visuals to explain concepts

‘I think it'd be helpful if we had just a basic teaching education, like something written through a pamphlet or something that they can look through that gives ′em a basic understanding of what gene therapy is and what outcomes we're hoping for. And go ahead and give that to them prior to even the discussion of gene therapy so they can kind of get the ball rolling as far as doing some independent research or getting their thoughts together.’ (PROV_SJ13) ‘I think like maybe a handout with things broken down at layman's terms, um, and giving it to [families] and kind of discussing what gene therapy is first, would be, um, a better option than just kind of saying, ‘Hey, there's this new and upcoming treatment, you know.’′ (PROV_SJ03)

Subtheme B: Clear communication without technical language

‘[…] when I was at [previous HTC], we had yearly family get‐togethers, and it was a, it was really nice. The families got together, but it was, the providers were there. And I, I get a chance to meet with the families outside of the medical situation and give information, and you can kind of talk to them outside of the hospital and you could give them new information that we know and, and, you know, then, then it's a group and, um, know they, they talk amongst the, each other and you, don't. It's tricky because, you know, there's pharmaceuticals that often will sponsor these things. And, but if you've got too much pharmaceutical support, then there's always said, like, what, you know, why are they talking about it? Yeah. So, but I think having that relationships also, um, well, what I've found is really helpful and some people just wanted for me, you know?’ (PROV_SJ05) ‘Maybe you should be interfacing with them [patient advocacy groups] and you have to be careful, because when you approach them, then there's a little bit of, like, mistrust. Like, why, why are you pushing this on us? You know, is pharma, what are you getting out of this? This is a pharmaceutical thing. Are they getting money? It's millions of dollars for, for this. So, you know, I think there's that aspect. Uh, again, you know, it's a deep‐rooted culture that it's historical.’ (PROV_SJ05)

Subtheme C: Trusted sources to overcome medical distrust

‘So the track record for gene therapy is gonna be very dependent on what the outcomes are for the research studies, uh, and the documentation that says this is a safe thing to do that the provider can give to the parent to show them, you know, this is definitely something that is, could be a reality for you that, you know, you have parents want proof and ‘cause that's the life of their child. And I think that's the important thing is, you know, the trust between, uh, the parent and the provider, um, that's going to do the gene therapy and then showing proof of a track record that it has worked and it's worked efficiently and without any problems, that would be the ideal situation where they would probably say yes, I'm willing to try this.’ (PROV_SJ07) ‘But I think the team members, uh, like our nurse and myself, are very important because of the trust level that we have with our patients. Yeah. I mean, for example, some of our patients who lived through HIV and Hep C have known me since they were little boys. you know, and now they're young men, they're graduating college, they've gotten married, they're having kids of their own. So I've sort of, you know, become like a grandma in a way, you know? Yeah. And so, and I, they know that they can't get the specific scientific information from me that they have to talk to their doctor, but if, if I encourage them to learn more, there's a lot of trust there. And, and they, they would, they would never believe that I'm trying to do something that might harm them. Yeah. So, so I think, I think it's the medical person, the haematologist that needs to give the medical information, but I think the other team members, like the nurse and the social worker can draw upon the trust the patients have in us over time to open their minds to this idea.’ (PROV_SJ12)

4. Discussion

This study has highlighted the complex interplay of knowledge, communication and individual circumstances that define the evolving landscape of gene therapy for Haemophilia B. The findings offer insights into the perspectives of patients living with Haemophilia B, caregivers and HCPs. We have provided insights into how hope, uncertainty about eligibility and durability, concerns about cost and decision‐making challenges emerged, influencing the attitudes of patients and caretakers to this transformative therapy. The perspectives shared by stakeholders revealed key strategies for conveying complex concepts in a patient‐tailored and understandable manner.

Patients and caregivers expressed a range of feelings that intertwined optimism with apprehension regarding gene therapy. Many expressed hopes for a long‐term solution that could significantly alleviate the burden associated with regular treatment and the distress of frequent bleeding episodes. However, this optimism was tempered by concerns about the safety and affordability of treatment and the durability of its effect. Such apprehensions resonate with the existing literature on the adoption of innovative therapies, wherein uncertainties about long‐term efficacy and potential adverse effects pose considerable challenges to acceptance [25, 36, 37, 38]. In addition, the study captured the emotional weight of decision‐making in the complex realm of chronic disease management, wherein the promise of a transformative therapy also stirs new anxieties over the risks of treatment failure and its potential repercussions on quality of life. These intrinsic and extrinsic factors pertaining to gene therapy and patient decision factors can potentially explain the less‐than‐expected uptake of commercial gene therapy [39]. Therefore, our findings suggest that, compared to traditional treatment choices, gene therapy decisions require more structured decisional support, particularly given the one‐time nature of such an intervention.

A central theme across interviews was the demand for communication that is clear, jargon‐free and delivered with empathy. Patients and caregivers consistently valued visual aids, explainer videos and testimonials from individuals who had undergone gene therapy. These preferences echo findings from the Exigency program and from other studies documenting barriers to comprehension and trust in gene therapy [16, 17, 19, 20, 21]. Importantly, both patients and caregivers emphasised the necessity for structured post‐treatment support, including well‐defined follow‐up plans, to reinforce confidence and adherence. These insights align with calls for educational frameworks that not only deliver accessible information but also minimise decisional regret through shared decision‐making models [31, 32]. Patient‐centred communication that caters to diverse levels of health literacy and emotional readiness, in addition to consents written at appropriate literacy levels, improves comprehension of consent processes among patients with low health literacy [30].

A particularly novel insight obtained from this study was the perceived difference in communication styles among provider types. Patients and caregivers often felt more comfortable discussing uncertainties with nurses, case managers and social workers, who were viewed as empathetic and conversational. In contrast, physicians and advanced practice providers tended to emphasise technical and clinical details, which, although essential, sometimes left patients hesitant to raise concerns. HCPs themselves acknowledged these disparities, recognising that trust and openness often developed more readily with non‐physician providers. This hierarchy of communication styles, not well documented in prior gene therapy research, reinforces the importance of multidisciplinary care in which distinct provider roles complement one another [26, 27]. These findings resonate with the broader literature on patient‐centred communication, which has identified relational style, rather than professional designation, as the driver of patient comfort and engagement [28, 29].

Trust emerged as a cross‐cutting determinant of decision‐making. Patients’ willingness to consider gene therapy was shaped by prior experiences with the healthcare system, perceptions of industry influence and the transparency of providers. HCPs underscored the risks of misusing terms such as ‘curative’, emphasising that unmet expectations could undermine long‐term trust and erode confidence in the healthcare system [13, 14, 15, 19, 26, 27, 28, 29]. Conversely, participants highlighted the fact that communication grounded in honesty and empathy fostered stronger therapeutic relationships and greater patient empowerment.

The implications of this study are both striking and actionable. First, there is an urgent need to develop patient‐centred educational resources that prioritise clarity and accessibility. Current consent procedures often fall short, with patients struggling to retain critical details about risks and post‐treatment requirements [17]. Language and tone are central – previous work has shown how framing can influence perceptions and decision‐making in gene therapy discussions [19, 20, 21]. Educational resources must, therefore, provide balanced, evidence‐based analyses, dispel misconceptions and integrate real‐world patient narratives. Community support and hearing from other patients who have undertaken the gene therapy journey may be additional useful tools.

Second, HCPs should establish structured frameworks for repeated, open discussions, allowing patients to voice their concerns freely. These discussions should take a multidisciplinary approach, actively involving physicians, nurses and social workers and enabling patients to benefit from their complementary strengths [20, 21]. Incorporating validated literacy assessment tools and multimedia resources such as diagrams, videos and participatory learning strategies can further enhance comprehension [30].

Finally, embedding shared decision‐making frameworks into clinical practice is critical. These approaches have been shown to improve patient satisfaction, strengthen trust and minimise decisional regret in gene therapy decision‐making [31, 32]. Equally important is ensuring robust post‐treatment support, including clear follow‐up plans and guidance on managing bleeding events, to sustain patient confidence and adherence.

5. Conclusions

This study underscores the fact that decisions about gene therapy for Haemophilia B extend well beyond clinical considerations. Patients and families balance hope for durable benefit against persistent concerns about safety, durability and financial burden, illustrating the dual medical and psychosocial dimensions of choice. Our findings advance the literature by revealing that patients often turn to nurses, social workers and case managers as their most trusted source, underscoring the central role of multidisciplinary teams in communication and consent. A limitation of the study is the small and convenient sampling of participants with a higher proportion of participants in adolescent age group.

The rollout of gene therapy demands communication and consent tools that are iterative, interactive and tailored to diverse levels of health literacy. Tools and discussions must not only convey data with clarity but also acknowledge and address the emotional, social and economic weight of irreversible treatment decisions. Policy reforms that reduce financial barriers and embed structured follow‐up are essential complements to these educational strategies. Integration of robust communication frameworks with system‐level supports, the haemophilia community can ensure that the promise of gene therapy is realised in a manner that is ethically sound, equitable and genuinely patient centred.

Author Contributions

N.B. and U.M.R. conceived the study. N.B. designed the study and wrote the manuscript. T.B., H.K. and J.R.H. collected and analysed the qualitative data. T.A., G.F. and L.F. assisted in study design and performed regulatory tasks. All authors critically revised the intellectual content of the manuscript and approved the final version for submission.

Funding

This study was supported by Pfizer Grant Number 71064837 and support from American Lebanese Syrian Associated Charities.

Ethics Statement

This study was reviewed and approved by Institutional Ethics committee at St. Jude Children's Research Hospital (Approval Number #21‐0769). All procedures were conducted in accordance with the ethical standards of the institutional review board/Institutional ethics committee as per the guidelines outline in the Declaration of Helsinki.

Consent

Informed consent was obtained from all participants or their legal guardians prior to the study participation.

Conflicts of Interest

Nidhi Bhatt serves on Octapharma advisory board and has received honoraria. All other authors have no competing interests to disclose.

Supporting information

Supporting File 1: hae70314‐sup‐0001‐SuppMat.docx

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request. Data are not publicly available due to privacy and ethical restrictions related to patient confidentiality.