An Exploration of the Impact of Gene Therapy on the Lives of People With Haemophilia and Their Families
Conditions: Hemophilia
Sponsor: Haemnet

 
Exigency Study Protocol v3.0 13Nov2020 
 
 
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An exploration of the impact of gene therapy on 
the lives of people with haemophilia  
and their families 
 
 
Principal investigators: Simon Fletcher 
Co-Investigators: 
Dr Kate Khair, Luke Pembroke  
Study Sponsor:  
Haemnet (Registered Charity No 1152241) 
Study Coordinator: 
Mike Holland, Haemnet 
Version date: 
 
13th November 2020 
Version number: 
 Version 3 
 
 
CONFIDENTIAL 
Information and data included in this document contain privileged or confidential 
information, which is the property of the sponsor. No person is authorised to make it 
public without written permission of the sponsor. These restrictions on disclosure will 
apply equally to all future information supplied to you, which is indicated as privileged or 
confidential. This material may be disclosed to and used by your staff and associates as 
may be necessary to conduct the clinical study. 
 
 
 

 
Exigency Study Protocol v3.0 13Nov2020 
 
 
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List of Abbreviations 
 
Abbreviation 
Definition 
AAV 
Adeno-associated viruses 
PIC 
Participant identification centres 
PWH 
People with haemophilia 
QoL 
Quality of life 
 
 
 
 
 
 

 
Exigency Study Protocol v3.0 13Nov2020 
 
 
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Study Synopsis 
Title 
Exigency: an exploration of the impact of gene therapy on the lives of 
people with haemophilia and their families 
Short Title 
Exigency 
Study Aim 
This study programme aims to examine the real-world experience and 
impact of gene therapy in a diverse community of people and families 
affected by haemophilia who have been or will be exposed to gene 
therapy. 
Primary 
Objective 
To explore the expectations that patients, and families in the UK have 
of gene therapy and its position in contemporary and future 
haemophilia management 
Secondary 
Objectives 
To understand the lived experience of people who have undergone 
gene therapy 
To understand the as yet “unseen” impact of gene therapy on the 
extended family 
To understand the impact of ineligibility for gene therapy trials 
To understand the impact of withdrawal from gene therapy on 
individuals and their ongoing attitude to their haemophilia care 
To understand why some patients and families opt not to participate 
in gene therapy trials as a treatment option 
Design 
Non-interventional qualitative study 
Number of 
Centres 
Seven PIC sites for Phases 1 and 2:   
 
Oxford University Hospitals NHS Foundation Trust 
 
Royal Free London NHS Foundation Trust 
 
Guy’s and St Thomas’ NHS Foundation Trust 
 
University Hospital Southampton NHS Foundation Trust 
 
Hammersmith Hospital, London – Imperial College Healthcare 
NHS Trust 
 
Royal London Hospital – Barts Health NHS Trust 
 
Addenbrooke’s Hospital – Cambridge University Hospitals 
NHS Foundation Trust 
Further recruitment will be undertaken via social media. 
Duration 
24 months total; data collection over 14-18 months 
Number of 
Subjects 
105, to include 65 people with haemophilia, and 40 family members  
Inclusion Criteria 
People with haemophilia A or B who consented to and have 
undergone gene therapy in the early dose-finding studies and a 
member of their family 
People with haemophilia A or B who consented to a gene therapy trial 
following the results of the early studies and a member of their family 
People with haemophilia A or B who consented to a gene therapy trial 
but who withdrew, were withdrawn from, or were ineligible for the 

 
Exigency Study Protocol v3.0 13Nov2020 
 
 
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study, and a member of their family 
People with haemophilia A or B who are definitely not interested in or 
unaware of gene therapy and a member of their family 
People with haemophilia A or B who are interested in but have not 
been offered gene therapy 
Those who have given written consent to be in the study 
All participants will be 16 years. 
Exclusion 
Criteria 
Participants will be excluded if they do not speak English (for the 
interviews) or do not consent to be in the study. 
Statistical 
Analysis 
This is a qualitative study using established qualitative research 
methodologies (grounded theory). Statistical evaluation is not 
appropriate. 
Operational Procedures 
Ethical Approval 
NHS ethical approval will be sought from the HRA 
Data Analysis 
To be conducted by Haemnet 
Write-up and 
Publication 
Lead researcher and research team 
 
 

 
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Exigency 
An exploration of the impact of gene therapy on the lives of people 
with haemophilia and their families 
Index 
1 
Background ............................................................................................................. 6 
1.1 
Disease introduction .................................................................................................... 6 
1.2 
Rationale for the study ................................................................................................. 7 
2 
Aim and Objectives .................................................................................................. 8 
2.1 
Aim ............................................................................................................................... 8 
2.2 
Primary objective ......................................................................................................... 8 
2.3 
Secondary objectives .................................................................................................... 8 
3 
Study Design ............................................................................................................ 8 
3.1 
General design .............................................................................................................. 8 
3.2 
Primary endpoints ........................................................................................................ 9 
3.3 
Secondary endpoints .................................................................................................... 9 
3.4 
Data gathering .............................................................................................................. 9 
3.5 
Statistical analysis and sample size calculation ............................................................ 9 
4 
Study Group .......................................................................................................... 10 
4.1 
Inclusion criteria ......................................................................................................... 10 
4.2 
Exclusion criteria ........................................................................................................ 10 
5 
Recruitment, Screening and Study Procedures ........................................................ 11 
5.1 
Study visits (inclusion) ................................................................................................ 11 
5.2 
Study sequence .......................................................................................................... 12 
5.3 
Study duration ............................................................................................................ 13 
6 
Data Analysis ......................................................................................................... 13 
7 
Ethics ..................................................................................................................... 14 
7.1 
Informed consent ....................................................................................................... 14 
7.2 
Anonymity/confidentiality ......................................................................................... 14 
7.3 
Ethical approval .......................................................................................................... 14 
7.4 
Reward for participants .............................................................................................. 14 
8 
Data Protection ..................................................................................................... 14 
9 
Finance and Funding .............................................................................................. 15 
9.1 
Study sponsor ............................................................................................................. 15 
10 
Dissemination ........................................................................................................ 15 
11 
Study Personnel ..................................................................................................... 16 
11.1 
Study Lead Investigators ............................................................................................ 16 
11.2 
Study Co-Investigator ................................................................................................. 16 
11.3 
About Haemnet .......................................................................................................... 16 
12 
References ............................................................................................................. 18 
Appendix 1:  Interview Guide ................................................. Error! Bookmark not defined. 
Appendix 2:  Haemnet Lone Worker Policy ..................................................................... 20 
 
 

 
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1 
Background 
1.1 
Disease introduction 
Haemophilia A and B are rare congenital disorders caused by an inherited genetic defect of 
the X chromosome that results in a deficiency in factor VIII or IX production in haemophilia A 
and B respectively. Factor VIII and IX play pivotal roles in the coagulation cascade, facilitating 
the formation of a blood clot to help stop bleeding. Haemophilia results in impaired clot 
formation and can lead to uncontrolled and often spontaneous bleeding. It affects 
approximately one in every 5,000 males [Srivastava et al, 2013]. Different types of severity 
are recognised:  
 
“severe” (factor activity is less than 1%) 
 
“moderate” (factor activity is 1-5%) 
 
“mild” (factor activity is 6-25%). 
In its severe form, haemophilia results in recurrent joint and muscle bleeds that predispose 
to arthropathy, muscle contracture and disability. Treatment of affected individuals in the 
UK involves prophylactic replacement of the missing factor, which decreases spontaneous 
bleeding events and resultant joint damage [Richards et al, 2010]. Although replacement 
therapy has improved life expectancy and quality, limitations include high costs and the 
frequency of infusions. Prophylaxis requires frequent intravenous infusions, which can be as 
often as daily but are usually 2–3 times per week. 
Recent years have witnessed the development and introduction of gene therapy for the 
treatment of haemophilia. Most gene therapies now undergoing clinical trials rely on a viral 
vector to achieve transduction of liver cells so that they produce the replacement gene. The 
majority of vectors are derived from adeno-associated viruses (AAV). Initial infusions of an 
AAV vector expressing a human factor IX transgene resulted in therapeutic but low factor IX 
plasma levels and clinical improvement for up to seven years in 10 men with severe 
haemophilia B [Nathwani et al, 2011; Nathwani et al, 2014]. However, following the 
introduction of gene for the Padua variant of the factor IX gene, near normal levels of factor 
expression have been seen in more recent cohorts [Perin et al, 2018]. Infusion of an AAV5 
vector encoding a B-domain-deleted human factor VIII gene was associated with the 
sustained normalisation of factor VIII activity level over a period of one year in six of seven 
participants who received a high dose, with stabilisation of haemostasis and a profound 
reduction in factor VIII use in all seven participants [Rangarajan et al, 2017]. 
With many more gene therapy trials in development, and with the possibility of licensure in 
the near future [Brown and Green, 2018], gene therapy may soon be introduced as a 
standard of care treatment [Pierce et al, 2019]. 
However, challenges remain. AAVs naturally cause infection in humans, provoking an 
immune response that generates antibodies; individuals with AAV antibodies are ineligible 
for some gene therapies. UK haemophilia centres have estimated the prevalence of 
antibodies to two AAV subtypes (5 and 8) among 100 adults with haemophilia [Standford et 
al, 2019]. The overall prevalence of antibodies or inhibitors was 30% for AAV5 and 40% for 
AAV8, suggesting a substantial proportion of people may be screened out of first-line gene 
therapy but may be eligible for newer gene therapy studies where AAV5 positivity is not an 
exclusion criterion. 

 
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Furthermore, gene therapy is unlikely to be available to those under the age of 18 years for 
quite some time. 
1.2 
Rationale for the study 
In potentially offering a “cure” for haemophilia, it is of little surprise that optimistic views 
have been expressed about gene therapy on haemophilia-specific social media websites and 
forums. Expectations within the community are high, with many patients voicing optimism 
for a treatment that is likely to have a significant impact on all areas of an individual’s life, 
including mobility and pain, and to result in freedom from infusions (although patients will 
inevitably be required to comply with regular safety monitoring). 
Quality of life (QoL) measurement tools have been integrated into all current gene therapy 
studies to assess the benefits of the treatment to the patients. Existing QoL tools have many 
limitations and may not offer adequate insight into outcomes that are relevant to those who 
undergo gene therapy [Iorio et al, 2018]. A number of the individuals involved in these 
studies have anecdotally expressed a degree of psychological distress as a result of a 
perceived change of identity [personal communication within the UK haemophilia nurse 
community]. This phenomenon has been seen in other treatment areas but has not yet been 
described in haemophilia care, as no group involved in gene therapy studies has sought to 
undertake any in-depth qualitative research into the impact of this treatment in this group. 
Gene therapy represents a substantial shift in the entire life experience of living with 
haemophilia for the patient and his family. As such, there is a need to look beyond the 
quantitative data collected in clinical trials and to assess the real impact of gene therapy on 
the everyday lives of patients and their families. This data is best captured using qualitative 
research techniques. 
Patients are rarely homogeneous in how they react. For some patients and families, gene 
therapy is likely to hold little interest, while for others (perhaps those with blood-borne 
infection or anti-factor inhibitors, or those with non-severe haemophilia) it may not 
currently be a realistic treatment option. Furthermore, it seems to be that around one third 
of the population with haemophilia will not be eligible for gene therapy. Being screened for 
a potentially life-changing therapy only to find it is not available is likely to result in 
significant disappointment, for which health care professionals will need to offer support. It 
may affect current treatment-taking behaviours and is also likely to have an impact on the 
lives of close family members (carers/adult children/adult siblings). 
 
 

 
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2 
Aim and Objectives 
2.1 
Aim  
The Exigency study programme aims to examine the real-world experience and impact of 
gene therapy in a diverse community of people, and families affected by haemophilia who 
have been or will be exposed to gene therapy. 
2.2 
Primary objective 
 
To explore the expectations that patients, and families in the UK have of gene 
therapy and its position in contemporary and future haemophilia management.  
2.3 
Secondary objectives 
 
To understand the lived experience of people who have undergone gene therapy 
 
To understand the as yet “unseen” impact of gene therapy on the extended family 
 
To understand the impact of not being able to participate in gene therapy trials 
 
To understand the impact of withdrawal from gene therapy on individuals and their 
ongoing attitude to their haemophilia care 
 
To understand why some patients and families decide not to choose gene therapy as 
a treatment option 
3 
Study Design 
3.1 
General design 
This is a prospective observational multiple cohort qualitative research study to be 
conducted among diverse groups within the haemophilia community whose lives may have 
been impacted by gene therapy. 
The study is designed to allow English-speaking patients and their families to tell their own 
life stories through narrative accounts. The narratives represent a true sharing of 
experiences valued by the tellers, listeners and gatherers [Hardy et al, 2009], and therefore 
offer insight into how these patients and families cope with haemophilia. 
Most experienced practitioners familiar with haemophilia have preconceived ideas and 
theories that may potentially bias data capture. Grounded theory is a research methodology 
that allows identification and description of the broad spectrum of life with haemophilia 
from the perspectives of the patient and their families. This methodology enables rich data 
capture across a large age range and allows for deep consideration of data, allowing 
research questions to be re-shaped as evolving themes and new concepts emerge. 
The study will form part of a PhD by published works undertaken by the lead researcher and 
supervised by Dr Kate Khair. 
 
 

 
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3.2 
Primary endpoints 
 
To gather a deep and thorough understanding about the real impact of gene therapy 
on the everyday lives of people with haemophilia and their families. 
3.3 
Secondary endpoints 
 
To understand the motivation of people with haemophilia for taking part in gene 
therapy studies, both at an early stage and when the procedure is known to be safe 
and efficacious. 
 
To understand the expectations of gene therapy among people with haemophilia, 
and whether these have been met. 
 
To understand how gene therapy impacts the lives of people with haemophilia and 
their families with regard to levels of factor expression and the post-gene therapy 
monitoring regimen. 
 
To understand the impact on people with haemophilia of being told they are 
ineligible for gene therapy, and how this affects their subsequent approaches to 
treatment. 
 
To understand why some people with haemophilia are not interested in gene 
therapy, and whether it will be possible to overcome these barriers in the future. 
 
To understand the considerations that may influence uptake in the future among 
people with haemophilia who are interested in gene therapy but have not been 
offered a trial. 
 
To understand the concerns of people with haemophilia who are undecided as to 
whether to have gene therapy, and whether the burden of initial follow-up is a 
factor at the present time. 
3.4 
Data gathering 
Data gathering will be undertaken through a combination of focus groups and interview-
based assessment, in each case using grounded theory methodology. In some interviews, 
“dyads” comprising of a patient and a close family member will be interviewed to identify 
both patient and family/carer perspectives. In all cases, each participant will be interviewed 
once only. 
Focus group discussion will be guided by the lead researcher, with the patient co-researcher 
in attendance to help facilitate and take process field notes. The focus groups will take a 
grounded theory approach to explore a variety of issues relating to gene therapy and its 
impact upon the participants’ everyday experience of living with haemophilia, and to 
generate and test ideas where appropriate. 
In-depth qualitative interviews can be conducted with both members of the dyad together 
though the interviews can be conducted separately at the request of the participants. This is 
a standard qualitative research methodology that allows for open discussion. Initial subject 
interviews will follow a guide developed by the research team (see Appendix 1). Each 
interview will be conducted by the lead researcher. 
3.5 
Statistical analysis and sample size calculation 
This is a qualitative study using established qualitative research methodologies. Statistical 
evaluation is not appropriate. 

 
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All focus groups and individual interviews will be recorded digitally so that the researcher 
can pay full attention to the subject, without the need to write down verbatim comments 
[Balen et al, 2000].  
Immediately following each interview, the researcher and patient co-researcher will record 
any thoughts, reflections or observations that arose during the interview. These will be 
analysed as part of the framework analysis described below [Ritchie et al, 2003]. 
After each of the focus groups and interviews, the sound files will be transcribed verbatim. 
The lead investigators will then analyse the transcripts using a grounded theory approach. 
The texts will be read and re-read, then coded into themes for further analysis using a 
transformational framework, identifying themes or concepts, summarising and synthesising 
the data, and using descriptive analysis to represent the views expressed [Spencer et al, 
2003]. A table of themes will then be produced, characterising recurring ideas and thoughts 
captured in the focus groups and interviews. These will form the basis for further analysis. 
Individual direct quotes may be used; this will be outlined in the information sheet(s) and 
consent. 
Inferential testing will be used to describe how outcomes differ between groups (e.g. 
patients vs. ). Correlation between groups may be achievable with explanatory factors (e.g. 
age, treatment regimen, bleeds, joint health, etc.). 
4 
Study Group 
The study population will comprise people over the age of 16, who fall into the categories 
outlined under Section 4.1 below. We hope to recruit up to 140 participants to the study in 
total, to include: 
 
Approximately 65 men with haemophilia 
 
Approximately 40 family members (spouse/partner/parent/carer or sibling of the 
person with haemophilia) to form patient/family member dyads 
 
4.1 
Inclusion criteria  
 
People with haemophilia A or B who consented to and have undergone gene 
therapy in the early dose-finding studies 
 
People with haemophilia A or B who consented to a gene therapy trial following the 
results of the early studies 
 
People with haemophilia A or B consented to a gene therapy trial but who withdrew, 
were withdrawn from, or were ineligible for the study 
 
People with haemophilia A or B who are definitely not interested in gene therapy 
 
People with haemophilia A or B who are interested in but have not been offered 
gene therapy 
 
Those who have given written consent to be in the study. 
4.2 
Exclusion criteria 
 
Non-English speakers 
 
Those who do not consent to be in the study. 

 
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5 
Recruitment, Screening and Study Procedures 
Once ethical approval has been received, people with haemophilia A or B who have 
undergone gene therapy and people with haemophilia A or B who withdrew from, were 
withdrawn from or who were ineligible for gene therapy will be recruited through Six PIC 
sites (i.e. sites that were responsible for either referring patients to dosing sites or were the 
primary dosing sites for the gene therapy). 
The PIC sites are: 
 
Royal Free London NHS Foundation Trust 
 
Guy’s and St Thomas’ NHS Foundation Trust 
 
University Hospital Southampton NHS Foundation Trust 
 
Hammersmith Hospital, London – Imperial College Healthcare NHS Trust 
 
Royal London Hospital – Barts Health NHS Trust 
 
Addenbrooke’s Hospital – Cambridge University Hospitals NHS Foundation Trust. 
Once identified, potential participants will be given information about the study by their 
clinical team and will be invited to participate. If they agree to participate, they will be 
contacted by the research team from the Oxford Haemophilia and Thrombosis Centre at  the 
Oxford University Hospitals NHS Foundation Trust (the lead site) to organise a mutually 
convenient time for their study interview, which could be undertaken at hospital, home or 
other mutually convenient site, either face-to-face or via video conference. 
The study will also be advertised on social media platforms to recruit those people with 
haemophilia A or B who have thought about gene therapy but are not interested, those who 
are interested in gene therapy but have not been offered gene therapy, and those who do 
not know about gene therapy, including parents of children where gene therapy is not yet a 
treatment option (see social media advertisement in Appendix 2). 
5.1 
Study visits (inclusion) 
For all participants there will be a single study visit at which all study data will be collected. 
This is summarised in the panel below. Each participant and/or dyad will participate once 
only either in a focus group or a face-to-face interview, either in person or via video 
conference. The Haemnet lone worker policy (Appendix 3) will be followed to ensure 
interviewer safety. 
The participant and dyad interviews can be carried out as a pair or individually, according to 
the preference of the interviewees. 
 
 

 
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5.2 
Study sequence 
Subject to patient availability, data-gathering activities will be conducted in two phases, as 
shown in the panel below.  
Two focus groups lasting one to two hours will each comprise eight to ten individuals from 
two subgroups: those who did not want to be part of gene therapy trials, and those not yet 
offered a gene therapy trial. Focus groups may be conducted either face-to-face or via video 
conference. 
Approximately 40 in-depth qualitative individual interviews, each lasting around two hours, 
will be conducted with patient/family member dyads from two subgroups: those who have 
undergone gene therapy, or those who were withdrawn or withdrew themselves after initial 
consent. In all cases, each participant/dyad will be interviewed once only, either face-to-face 
or via video conference. 
 

 
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5.3 
Study duration  
The study will last for 24 months. It is estimated that data collection will take around 14–18 
months. 
6 
Data Analysis  
The data generated in this study will be analysed using grounded theory. Grounded theory 
involves gathering rich data, using a variety of methods, including interviews, ethnography 
and textual analysis, to identify themes. Data are coded and the themes analysed, and finally 
theories are developed about the data that has emerged [Charmaz, 2014]. Grounded theory 
has been used extensively in research with children and families [Neill, 2007] and within 
haemophilia [Khair et al, 2019]. 
Audio-recorded interviews: 
 
Focus groups and interviews will be transcribed, verbatim, by a professional 
transcriptionist unknown to study participants. All data will be anonymised during 
the transcription process. 
 
The transcripts will be read and re-read by the research team. The transcribed data 
will be coded into themes for further analysis using a transformational framework, 
identifying themes or concepts, summarising and synthesising the data, and using 
descriptive framework analysis to represent the view expressed [Spencer et al, 
2003]. 
 
A table of themes will be produced, characterising recurring ideas and thoughts 
captured during the focus groups and interviews. These will form the basis for 
further analysis. 
 
Individual quotes may be used – these will be anonymised. Participants will be 
informed of this in the information sheet(s) and consent. 
Field notes: 
 
Immediately after the interviews and focus groups, the researcher and patient co-
researcher will record any thoughts, reflections or observations made during the 
interview or focus group. In particular, any thoughts or ideas about emerging 
themes will be recorded.  

 
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 
These notes will be analysed as part of the framework analysis [Ritchie et al, 2003]. 
7 
Ethics 
There is minimal risk to participants or researchers from this study. Participants will be 
invited to either one focus group or one interview to discuss their hopes, fears, expectations 
and the realities of gene therapy. 
In the event that any patient or family member becomes distressed by this, they will be 
referred (with consent) to the psychology services affiliated with the haemophilia centres 
from which they have been recruited.  
7.1 
Informed consent 
Study participants will be required to consent to be in the study; their consent can be 
withdrawn at any stage and will not have any impact upon their haemophilia care. Consent 
will be reaffirmed before the interviews take place.  
7.2 
Anonymity/confidentiality 
The use of focus groups and interviews raises issues of confidentiality, especially when direct 
quotes and/or the circumstances of quotes may be used in reports and publications. It is 
therefore imperative that individuals are anonymised. This will be achieved by the individual 
reports and quotes using study numbers which are known only to the research team. 
7.3 
Ethical approval 
The study will be registered with the research and development office at Oxford University 
Hospitals NHS Foundation Trust. It will also be registered on the National Institute for Health 
Research portfolio. 
Ethical approval for the focus groups and patient/family member dyad interviews will be 
sought from the Health Research Authority (HRA) using the standard IRAS application forms.  
Ethical approval is not necessary for the health care professional focus groups; however, an 
information sheet has been developed for their knowledge about the study and 
participation. 
7.4 
Reward for participants 
Participants who agree to attend focus groups will receive a £100 gift voucher for their 
participation, along with reimbursement of travel costs.  
Participants who agree to be interviewed for the study will be given a £50 gift voucher for 
their participation, up to a maximum of £100 per household, along with reimbursement of 
any travel costs. 
In both cases, details of these will be included in the participant information sheet(s).  
8 
Data Protection  
Participants in the Exigency study will be anonymised and will be known by study number 
only and managed in line with the EU General Data Protection Regulation (GDPR) (successor 
to the UK Data Protection Act 1998). 

 
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 
All audio recordings will be transcribed verbatim by a professional transcriptionist 
unknown to the study participants. The transcriptionist will have signed a 
confidentiality agreement. 
 
All data (paper records and audio recordings) will be kept in locked cupboards by 
Haemnet for the duration of the study.  
 
Recordings will be deleted by Haemnet once the study has been analysed. 
 
Paper records, including transcripts of interviews, will be kept for 10 years after the 
study, after which they will be shredded. 
 
Any data on computers will be password protected in line with NHS data protection 
procedures.  
Haemnet will act as sponsor to the study and will monitor data quality and undertake site 
audits as necessary. 
9 
Finance and Funding 
Funding for the study has been provided by uniQure  
All study funds will be managed by Haemnet. 
9.1 
Study sponsor 
The study is sponsored by and indemnified by Haemnet. 
10 
Dissemination 
Abstracts will be submitted to the 2021/2022 national and international haemophilia 
conferences, including the European Association for Haemophilia and Allied Disorders 
(EAHAD) Congress 2021, the Haemophilia Nurses Association (HNA) Conference 2021, and 
the Word Federation of Hemophilia Congress 2022. 
The study findings will also be submitted for publication in peer-reviewed journals serving 
medical/nursing/allied health professionals who work with people with haemophilia. 
The study results will be disseminated directly to study participants through a final summary 
report. Results will also be shared on social media and through the UK Haemophilia Society 
and European Haemophilia Consortium (EHC) websites, and through member newsletters. 
All investigators will contribute to study publications and will be named as co-authors. 
Authorship will be confirmed in line with journal publication guidance, such as International 
Committee of Medical Journal Editors (ICMJE) recommendations.  
 
 

 
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11 
Study Personnel 
11.1 Study Lead Investigators 
Simon Fletcher  
Lead Research Nurse at the Haemophilia and Thrombosis Centre at the Churchill Hospital, 
Oxford. Simon has been in post for six years and has extensive knowledge of clinical research 
and the care of people with haemophilia. He will oversee the study including ethical 
approval, study staff training, participant enrolment, study completion including evaluation 
of all outcome measures used, and ensure timely results presentation and publication. This 
work would contribute to his “PhD by publication” programme. simon.fletcher@ouh.nhs.uk 
Dr Kate Khair 
Director of Research at Haemnet; Visiting Professor of Health and Social Care, London South 
Bank University; Clinical Academic Careers Fellow, The Centre for Outcomes and Experience 
Research in Childhood Health, Illness and Disability, Great Ormond Street Hospital (GOSH) 
for Children, London. Formerly Nurse Consultant in Haemophilia at GOSH, Kate has 
extensive knowledge in qualitative research with children and young people with 
haemophilia. kate@haemnet.com 
11.2 Study Co-Investigator 
Luke Pembroke 
Project Manager and “Patient Researcher” at Haemnet. Luke has experience working within 
the medical education sector of the healthcare communications industry. Living with 
haemophilia himself, Luke is an active patient advocate, and has worked extensively with a 
network of patient groups within the UK, Europe and globally. luke@haement.com  
11.3 About Haemnet 
Haemnet is a registered charity (No 1152241) that supports health and social care 
professionals to ensure that excellent care becomes an everyday experience for people with 
bleeding disorders. The charity provides education, undertakes research and drives service 
innovation. Haemnet Ltd (Company No 12211003) is the trading arm of the charity. 
Haemnet will act as the study sponsor. Mike Holland is CEO of Haemnet and will oversee 
and manage all logistical aspects of the study. mike@haemnet.com  
Haemnet is currently engaged in a multi-methods study assessing the prevalence and impact 
of chronic pain in PWH, and a study looking at educating personal trainers to work with PWH. 
Previous research studies and publications have also included: 
 
Khair K, Pollard D, Harrison C, et al. HOw Patients view Extended half-life products: 
impressions from real world experience (The HOPE study). Haemophilia 2019; 25(5): 
814-820. doi: 10.1111/hae.13803. 
 
Khair K, Holland M. The Kids' immune thrombocytopenia Tool is not suitable for 
assessing quality of life in children with platelet function disorders. Haemophilia 
2018; 24(4): e259-e261. doi: 10.1111/hae.13528. 
 
Khair K, Klukowska A, Myrin Westesson L, et al. The burden of bleeds and other 
clinical determinants on caregivers of children with haemophilia (the BBC Study). 
Haemophilia 2019; 25(3): 416-423. doi: 10.1111/hae.13736. 

 
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 
von Mackensen S, Myrin Westesson L, Kavakli K, et al. The impact of psychosocial 
determinants on caregivers' burden of children with haemophilia (results of the BBC 
study). Haemophilia 2019; 25(3): 424-432. doi: 10.1111/hae.13684. 
 
Khair K, Holland M, Bladen M, et al; SO-FIT Study Group. Study of physical function 
in adolescents with haemophilia: The SO-FIT study. Haemophilia 2017; 23(6): 918-
925. doi: 10.1111/hae.13323. 
 
Khair K, Holland M, Pollard D. The experience of girls and young women with 
inherited bleeding disorders. Haemophilia 2013; 19(5): e276-81. doi: 
10.1111/hae.12155. 
 
Forrester C, Bielby H, Johns S, Efford J, Holland M, Khair K; United Kingdom 
Haemophilia Nurse's Association. Potential for development of haemophilia link 
nurse role within UK hospitals. Haemophilia 2013; 19(4): 578-82. doi: 
10.1111/hae.12144. 
 
Khair K, Holland M, Vidler V, Loran C, Harrington C. Why don't haemophilia nurses 
do research? Haemophilia 2012; 18(4): 540-3. doi: 10.1111/j.1365-
2516.2012.02749.x. 
 
Khair K, Holland M, Carrington S. Social networking for adolescents with severe 
haemophilia. Haemophilia 2012; 18(3): e290-6. doi: 10.1111/j.1365-
2516.2011.02689.x. 
Haemnet also runs an annual conference for haemophilia nurses, and two training courses 
aimed at members of the haemophilia multidisciplinary care team: “Contemporary Care of 
People with Bleeding Disorders” (a four-day residential training course) and the ASPIRE 
leadership development programme. 
 
 
 

 
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References 
 
Balen R, Holdroyd C, Mountain G, et al. Giving children a voice: methodological and practical 
implications of research involving children. Paediatric Nursing 2000; 12(10): 24-8. 
Brown K, Green G. The haemophilia drug market. Nat Rev Drug Discov 2018; 17(8): 541-42. 
Charmaz K. Constructing Grounded Theory. 2nd edition. Introducing Qualitative Methods 
series. 2014. London: SAGE Publications. 
Hardy S, Gregory S, Ramjeet J. An exploration of intent for narrative methods of inquiry. 
Nurse Researcher 2009; 16 (4) 7-19. 
Iorio A, Skinner MW, Clearfield E, et al; coreHEM panel. Core outcome set for gene therapy 
in haemophilia: Results of the coreHEM multistakeholder project. Haemophilia 2018; 24(4): 
e167-e172. doi: 10.1111/hae.13504. 
Khair K, Pollard D, Harrison C, Hook S, O’Driscoll M, Holland M. HOw Patients view Extended 
half-life products: impressions from real world experience (The HOPE study). Haemophilia 
2019; 25(5): 814-20. doi: 10.1111/hae.13803. 
Nathwani AC, Tuddenham EGD, Rangarajan S, et al. Adenovirus-associated virus vector-
mediated gene transfer in haemophilia B. N Engl J Med 2011; 365: 2357-65. 
Nathwani AC, Reiss UM, Tuddenham EGD, et al. Long-term safety and efficacy of factor IX 
gene therapy in haemophilia B. N Engl J Med 2014; 371: 1994-2004. 
Neill S. Grounded theory sampling: ‘whole’ family research. Journal of Research in Nursing 
2007; 12; 435-443. 
Perin GQ, Herzog RW, Markusic DM. Update of clinical gene therapy for haemophilia. Blood. 
2018; 33(7): 407-14. 
Pierce GF, Iorio A. Past, present and future of haemophilia gene therapy: From vectors and 
transgenes to known and unknown outcomes. Haemophilia. 2018; 24(Suppl. 6): 60-67. doi: 
10.1111/hae.13489. 
Pierce G, Coffin D; Members of the WFH Gene Therapy Round Table Program Committee 
and Organizing Committee. The 1st WFH Gene Therapy Round Table: Understanding the 
landscape and challenges of gene therapy for haemophilia around the world. Haemophilia 
2019; 25(2): 189-94. doi: 10.1111/hae.13673. 
Rangarajan S, Walsh L, Lester W, et al. AAV5–factor VIII gene transfer in severe haemophilia 
A. N Engl J Med 2017; 377: 2519-30. 
Richards M, Williams M, Chalmers E, et al. A United Kingdom Haemophilia Centre Doctors’ 
Organization guideline approved by the British Committee for Standards in Haematology: 
guideline on the use of prophylactic factor VIII concentrate in children and adults with 
severe haemophilia A. Br J Haematol 2010; 149(4): 498-507. 

 
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Ritchie J, Spencer L, O’Connor W. Carrying out qualitative analysis. In: Ritchie J, Lewis J (eds). 
Qualitative Research Practice: A Guide for Social Science Students and Researchers. 2003. 
London: SAGE Publications. 
Spencer L, Ritchie J, O’Connor. Analysis: practices, principles and processes. In: Ritchie J, 
Lewis J (eds). Qualitative Research Practice: A Guide for Social Science Students and 
Researchers. 2003. London: SAGE Publications. 
Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al; Treatment Guidelines Working Group 
on Behalf of the World Federation of Haemophilia. Guidelines for the management of 
haemophilia. Haemophilia 2013; 19(1): e1-47. 
Standford S, Pink R, Creagh D, et al. Adenovirus-associated antibodies in UK cohort of 
hemophilia patients: A seroprevalence study of the presence of adenovirus-associated virus 
vector-serotypes AAV5 and AAV8 neutralizing activity and antibodies in patients with 
hemophilia A. Res Pract Thromb Haemost 2019; 3: 161-67. doi: 10.1002/rth2.12177. 
 
 

 
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Appendix 1:  Social Media Advertisements  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Appendix 2: Haemnet Lone Worker Policy 
Haemnet staff will frequently work by themselves without close or direct supervision. 
Such work is usually home-office based. However, there may be occasions when 
Haemnet staff will need to work alone, visiting and interviewing service users, or 
running meetings with previously unknown colleagues, whether in or out of usual 
office hours. 
The Haemnet Lone Worker policy aims to ensure the health, safety and welfare of all 
staff who are required to work in such circumstances. The health and safety of lone 
workers depends on good risk assessment practices, effective communication, and 
shared responsibility. 
When working as a lone worker on Haemnet-related work, lone workers must: 
 
ensure that someone else knows the whereabouts of the lone workers and 
what they are doing; 
 
ensure they do not take unnecessary risks; 
 
care for their own health and safety and that of others who may be affected by 
their acts or omissions; 
 
seek and follow advice from their manager; 
 
follow all health and safety policies; 
 
comply with requests for information on whereabouts from managers; 
 
report any incidents including threats and potentially dangerous situations; 
 
ensure that the Team Administrator is aware of any changes to their contact 
details.