“I’d go on a hike with my kids… that would make me feel so happy.” Recognising what people with haemophilia B identify as meaningful when considering personal goals and the potential for gene therapy

Haemnet is a research and communications agency embedded in the bleeding disorders community. Through Haemnet’s research database, we identified males from the UK, aged over 16 years, with severe or moderate haemophilia B, currently treated with prophylaxis, and invited potential participants to take part in an audio recorded, four-hour face-to-face workshop. Those who were unable to attend the workshop participated in individual two-hour online qualitative research interviews, which were audio recorded.

An ‘Open Space’ methodology was used to stimulate discussion among the participants ^[24]. Recognising the subject matter as an area where discordance may exist between health care professionals’ (HCPs’) perceptions of patient understanding and preference and patients’ actual lived experience, it was important to create a space for active listening ^[25]. The Open Space methodology invites participants to contribute, listens to their responses and perspectives, and notes their experiences and views, rather than holding an actively led discussion. In the context of the workshop, this allowed participants to raise topics they classified as important, rather than pursuing preconceived assumptions about PwHB’s priorities. As such, it also enabled the identification of areas where there is tangible energy for deeper understanding of the issues that directly affect PwHB.

A broad outline guide was used to help prompt the discussion, focusing on:

Experience of living with haemophilia B and its treatment

Ethical approval was not required based on the UK Health Research Authority decision tool ^[26]. However, written consent to use direct quotes was given by all participants on the understanding that no personal details would be shared. Participants were free to withdraw at any stage. All data collected were anonymised and managed in line with the UK Data Protection Act 1998.

Each participant was assigned an individual study number. Audio recordings were transcribed verbatim. The transcripts were thematically analysed and coded in NVivo using an inductive approach to explore themes, review emergent codes, reflect, refine and identify final themes. To ensure that codes and/or themes emerged from the workshop and interviews, and not pre-existing researcher experience or literature, no pre-defined code trees were created ^[27,28]. Field notes and observations made during the workshop and interviews were used to provide further context for the analysis.

Participants were advised that the research was funded by an unnamed pharmaceutical company. They received an honorarium for their time and all travel costs were reimbursed.

Partnership with patients is increasingly recognised as enabling health research to address questions of impact ^[29], and has been noted specifically with regards to haemophilia as a way of ensuring research outcomes are meaningful and relevant to those who live with it ^[30]. The value of patient authorship is increasingly recognised in medical publishing ^[31]. To bring the value of such approaches into this study, we actively involved a person who lives with severe haemophilia in its development, analysis, and write-up.

Of 61 PwHB in Haemnet’s research database, 36 were identified as adults (over 16 years) with a confirmed diagnosis of severe or moderate haemophilia B treated with prophylaxis, and therefore eligible to participate in the study. The recruitment process is outlined in Figure 1.

Figure 1.

Recruitment flow diagram

The participants were aged 21 to 64 (median 34 years) and represented a wide geographical area within the UK. All had severe haemophilia B and were diagnosed in childhood. They reflected a broad mix of awareness, knowledge, and engagement with haemophilia: some were involved in scientific teaching and/or haemophilia advocacy with a high level of knowledge due to personal histories, however others were relatively unfamiliar with scientific, medical or advocacy influences, terminologies, and developments.

All participants considered themselves ‘well treated’, having received prophylaxis for many years; all those under 40 had been treated prophylactically from early childhood whilst older participants received prophylaxis later in childhood/adolescence. One participant was treated with standard half-life factor, five with extended half-life factor and three were participating in clinical trials of investigational medical products. All were able to self-infuse and treated themselves at home using tailored prophylaxis based on individual pharmacokinetics and physical activity.

During the analysis, emergent codes were refined into three overarching themes (Table 1; Figure 2):

Living with haemophilia

Figure 2.

Core themes identified in workshops and interviews: living with haemophilia, goals, and gene therapy

These are discussed in depth here with supporting quotes, anonymised to participant number [e.g. P01].

On a superficial level, the goals of the PwHB who participated in this research can be viewed as little different from those of peers who are not affected by haemophilia. They reflect a desire to have strong secure relationships with family and friends, to enjoy success in education, to find a good job, to engage in sport and other physical activities, and to travel and see the world. Some of the goals expressed could be seen as modest in nature, but they should not be underestimated. In the context of living with haemophilia B, they should be considered for their potential impact on QoL rather than the material difficulty of achieving them. From many of the goals expressed – walking the dog or going on a hike with children – it is evident that seemingly small changes in personal circumstances could significantly amplify positive outcomes in an individual’s sense of wellbeing.

The study participants’ goals should be considered through the lens of their lived experience as PwHB, including the inherent limitations they have learned to live with and accommodate as a matter of course into daily life. This is a phenomenon that could be attributed to living with a ‘haemophilia mind’ ^[33,34]. All participants, irrespective of their circumstances, expressed a strong desire not to be held back by haemophilia B. However, despite ‘normality’ being a core motivation underpinning and influencing their goals, their actions and decisions are determined by their haemophilia, which presents a need for constant ‘risk assessment’ and a psychological burden. This common ambition to strive for ‘normality’, not be treated differently, and ‘prove people wrong’ presents a paradox, in that the ‘normality’ PwHB perceive represents a life far from normal ^[35,36]. This is supported by the work of O’Hara et al who identified the ‘disability paradox’, which showed that PwH report good or excellent QoL while the general population characterise the daily struggles of living with haemophilia much less favourably ^[37]. Our research in this study further enhances the understanding of the burdens that affect PwHB whilst recognising that the perception of those burdens differs between people with and without haemophilia.

Despite some goals being identified as ‘achievable’, they reflect significant levels of drive and determination. The participant group included a number of highly motivated, goal-orientated individuals, and some of the goals they considered ‘achievable’ would perhaps not be so for all PwHB. The group as a whole shared a view that they had not been held back by their haemophilia, expressing a desire to ‘just get on with things’ or an attitude that ‘it is what it is’. However, they also had aspirations that were not recognised as goals due to their belief that the likelihood of them being achievable was low. In this sense, participants normalised the limitations they live with ^[38] rather than normalising their goals.

The ‘social model’ of disability ^[39] encourages us to question the ways in which PwH’s goals are rendered intrinsically unachievable through their haemophilia, rather than the broader social lack of reasonable adjustments that might allow PwH to participate; i.e., that social and environmental factors also impact the limitations imposed by haemophilia. This is clearly seen in the experience of participant P08, for example, who felt unable to achieve travel goals due to incidents of feeling stigmatised for carrying needles. This limitation has little to do with the clinical characteristics of haemophilia itself; it is the result of a social response to disability and difference. Similarly, participants’ sense that they are unable to participate in sports speaks to lack of opportunities and funding for parasports, rather than a straightforward limitation of haemophilia. The social model of disability has been used to understand lived experience in various chronic conditions ^[40,41], but has had little application in haemophilia. There are opportunities for future research to better understand how PwH’s goals are circumscribed not only by bleeding or joint damage, but by socio-environmental factors.

The psychological impact of being told to avoid or moderate activities to minimise risk meant participants often adapted their goals to what they believed to be achievable, rather than allowing themselves to consider activities they had been repeatedly told they could not do. These limitations are often rooted deeply in the haemophilia mind ^[30,31]. The research team noted that even well-treated participants with relatively good joint health precluded themselves from certain activities or engaged in them at a lower level (e.g., non-contact sport alternatives, watching activities they would like to take part in). As such, they can be understood to present acceptance, as ‘normal’, of a lower QoL than they would hope to achieve without haemophilia B ^[12,34].

Similarly, we noted a reluctance to celebrate what were perceived as more mundane forms of activity. For example, one participant felt his career in education, albeit successful, was imposed by the limitations of his haemophilia. He had harboured ambitions to join the police; while teaching is not as physically demanding, hours spent standing at the front of a classroom is an achievement that previous generations of PwHB may have only dreamed of.

Although not set out as an objective or explicitly sought by this research, this sense of loss within the haemophilia mind can be interpreted as one of the most significant impacts of current standards of treatment. This was not directly acknowledged by participants but evidenced in comments such as:

“My greatest regret in life is when my kids were young I couldn’t kick a football with them and I still can’t.”

‘Unachievable goals’ were defined as those that participants had been unable to achieve as a result of their current situation, and that they considered unachievable in the future. Underlying the desire to live a ‘normal’ life was the recognition that living with haemophilia B has limitations, in particular the nature of the jobs they felt able to aspire to do (and in some cases were allowed to do), their ability to engage in sport and other physical activities, and, to some extent, their ability to travel.

Participants saw some goals as unachievable due to the effectiveness and limitations of treatment, including associated physical impacts, and the self-limiting behaviour described above. Those with complex treatment histories experienced mobility limitations due to joint disease and living with pain, though comments about joint damage, pain and mobility were not entirely absent among those who had benefitted from access to prophylactic treatment from a young age. All participants expressed common frustrations with treatment, including the need for frequent infusions ^[12], impacts on joint health and mobility ^[42], the stigma associated with infusing factor products ^[43], and limited access to physiotherapy and dental care. These represent known frustrations and unmet needs.

While not a primary objective of this research, the themes identified as frustrations represent a broad range of treatment-related goals which influence how PwHB perceive their ability to achieve other goals in their lives. These are inter-related and include:

Reducing bleeds and their disruption to health status and activities of daily living

Future goals remain for all participants in this research, including improved QoL for forthcoming generations of PwHB. Their achievement may be facilitated as future treatments evolve, and the theme of travel in particular illustrated how treatment advances could influence the ambitions of PwHB. Alongside this, the research team noted participants’ shared sense of what ‘should be’ achievable for PwHB. Novel treatments offering enhanced factor half-lives clearly provide greater protection against joint and muscle bleeds ^[10]. Treatments such as gene therapy for haemophilia B offer the potential for a ‘once and done’ approach with a prolonged durability of FIX expression equivalent to mild haemophilia or into the ‘normal’ range ^[16]. In offering a functional ‘cure’ for a period of time, it has the potential to offer relief from the less obvious burdens associated with treatment (such as the need for intravenous therapy and constant ‘risk management’) and a step towards the ‘haemophilia free mind’ that has been posited as a new aim of future therapies ^[30,31]. However, participants’ concerns about their identity as PwH indicate a need to offer psychological support to PwHB both pre-gene therapy and when adjusting to life post-gene therapy ^[44]. Challenges remain in addressing the more intangible limitations imposed by pre-existing joint damage and chronic pain, and it is essential that efforts around patient education for gene therapy continue to keep pace as these treatments enter the market. Future research, following access to innovative therapies for PwHB, will reveal how, or if, these treatments reduce previously imposed lifestyle limitations including career choices, sports participation and impact on overall QoL.

It is important to recognise that the goals of PwHB can be influenced by seemingly small changes to lifestyle factors that result in a significantly amplified positive influence on an individual’s lived experience – for example, the ability to be more spontaneous in everyday decision-making.

In many respects, the goals of PwHB are aligned to those of people without haemophilia: desires to form strong personal relationships, have equitable access to education and employment, and to feel confident when engaging in sports, physical activity and travel. Innovations in treatment will, undoubtedly, impact these findings. Equity for PwHB can be achieved by enhancing access to appropriate treatments, including education and guidance to enable informed treatment decisions, and the removal of the inherent limitations that have traditionally influenced their ambitions and life choices.

While significant therapeutic advances have been made in recent years, gene therapy for haemophilia B is not yet widely available despite being authorised in the UK ^[45]. Future studies of the impact of gene therapy for PwHB should investigate the impact on psychological health and wellbeing, alongside long-term physical outcomes, to promote and enhance lived experience and goal achievement.