Maeve Jones-O'Connor UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland
Dr. Amanda McCann UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland
Avril Kennan DEBRA Ireland, Clanwilliam Terrace, Grand Canal Quay, Dublin 2, Ireland



There has been much investigation of attitudes towards clinical research (CR) in the general population [1-11]. This research mainly concerns attitudes towards clinical trials in a general sense, i.e. in a non-disease specific way. In the context of rare diseases, the general research is of limited relevance.

The aim of this study was to examine attitudes towards CR and factors involved in clinical trial (CT) participation in epidermolysis bullosa (EB) researchers and patients.

This was a two phase, mixed methods study. Semi-structured interviews were used to gather the views of EB clinical researchers (n=11). The results were thematically analysed and inductive analysis was performed. An online survey of patients and carers (n=43) gathered the patient perspective, in relation to factors influencing the decision on whether to participate in clinical trials and perceptions of clinical research.

The main themes that emerged from the interviews with researchers were:

  1. many and varied challenges face EB clinical research
  2. there is a degree of polarisation of opinion and experience and
  3. community development and collaboration are necessary for progress.

There is much variation in attitudes, with some reporting negative experiences of research and low levels of motivation and others, the opposite. Findings of the patient survey highlighted patients’ and families’ motivation to find a cure and relief of local symptoms, but also that there are barriers to participation in the form of fear of risks to health, additional pain and travel issues. Both branches of the study confirmed the importance of a trusting, cooperative relationship between members of the community.

There are many, varied attitudes towards clinical research in the EB community which are both positive and negative. The cohort of researchers interviewed have high levels of motivation, despite many challenges and frequently, negative experiences. Reports of patients’ attitudes as perceived by researchers were mixed and polarised. Data from the patient cohort is suggestive of motivated but risk-averse attitudes. Coordinated efforts by the EB community as a whole are necessary for the progression of research. More investigation is needed to explore the nuances of this topic in relation to subsets of EB and its community. 





In an era of rapidly evolving technologies, medical advances are not keeping pace. This is due to a variety of factors, including increased regulation and decreased funding. Another pervasive factor also requires attention – lack of patient engagement with, and participation in, clinical trials. Low rates of patient participation are a well-recognised barrier to clinical trials and, thus, to the advancement of medical research [3, 10, 12, 13].
Much research has investigated this consistently poor engagement in research and the attitudes that lead to it in the general population. A range of non-disease specific attitudes and barriers to engagement have been unearthed by others. Typical examples of these include: a lack of trust of medicine; poor awareness of clinical research, and lack of motivation [1, 3, 10, 12-14]. Most of these attitudes may be generally attributed to a weak relationship, and poor quality of communication, between those involved in medical science and the general population [3-7]

In a disease-specific context, information from the general population provides only some of the answers for poor levels of participation. In rare diseases, in particular, attitudes towards research in their communities have not been thoroughly analysed.

Epidermolysis bullosa (EB) is an example of one such rare disease. Inherited EB is a group of rare genetic skin diseases, characterised by extreme skin and tissue fragility and recurrent blistering [15]. There are over 30 different genotypes and phenotypes of the condition. The major subtypes of EB are simplex (EBS), junctional (JEB) and dystrophic (DEB); these are differentiated on the basis of the mutated proteins and the level at which cleavage takes place in the skin [16]. EB has a reported incidence in the USA of 19 per million live births,15 with EBS being the most common type, followed by DEB and JEB.

'There is no cure'

There is no cure for EB. Medical treatment primarily involves meticulous wound care and dressing, nutritional support and symptomatic relief of pain and itch. Clinical research (CR) into EB is currently active in a variety of potential treatment domains, including protein, cell, gene and drug therapies.

It is well known that EB patients and families want more and better treatments. Despite this, CR and clinical trials (CTs) are not always well enrolled or successfully completed. The reasoning for this poor engagement is anecdotal and not well established. This study aimed to begin analysing this phenomenon, by undertaking preliminary investigations into attitudes and perceptions towards CR, within the global EB community.


This research was conducted during the period of May-August, 2014, under the auspices of DEBRA Ireland, on behalf of DEBRA International. DEBRA is a patient organisation that focuses on patient care and research. There are numerous national DEBRA organisations around the world and they come together under the umbrella of DEBRA International.

The aim of the study was to gather information from both clinical researchers involved in EB and people living with EB about their experiences of clinical research and their attitudes towards clinical trials.
As well as this, factors involved in patients’ and their families’ decisions to take part in clinical trials were to be investigated. DEBRA has a central position as a trusted advocate in this community, which facilitated the engagement of participants in the study.

An explanatory mixed-methods approach was adopted. As a  first step, the views of researchers were explored through interviews. The themes emerging from this qualitative phase were then used to guide the design of a survey to explore the views of patients in a quantitative manner.


Twenty-four senior investigators with experience in EB clinical research were contacted
in May and June of 2014. These investigators were either known to be involved in past or active clinical trials and/or were listed as investigators on the main clinical trial registries. Thirteen responded and eleven of these were interviewed. The interviews took place over the phone or via Skype®. Ten open-ended questions were used to guide each conversation in a semi-structured manner. These questions were made available to each participant beforehand.

Confidentiality was assured at the beginning of each interview. Consent to record the interview and for opinions to be published on an anonymous basis was requested. Each person was encouraged to raise any additional topics or points of information during the course of the conversation. Interviewees were asked questions on a range of topics, including their experiences of recruiting patients, the particular issues for EB patients participating in CR and the role DEBRA might play in supporting recruitment. Interviewees were asked to consider the topics from their perspective as both a researcher and a patient advocate. An opportunity was given at the end of each interview for any additional comments the interviewee may have had.

Notes were hand written during the interview, with key words and phrases being highlighted. During this process, care was taken to reflect the views of the participants accurately. These notes were de-identified and served as the main material for analysis. They were then reviewed on the principles of thematic analysis [18]. Patterns in the interviews were highlighted, and emergent themes were cross- checked between interviews. A single investigator completed the review, coding and description of overarching themes; this approach was necessitated due to time and resource constraints. Thus, methodical rigor via triangulation was not available, though there was much discussion between authors, after the analytical framework was drafted.
The themes that emerged were used to define a focus of questioning for the second, quantitative phase of the study.


The survey was designed on the basis of the outcomes of the interviews, the experiential knowledge of DEBRA representatives and the literature relating to general populations. It was targeted towards patients themselves and their parents/carers. It was an online survey, disseminated internationally through digital media. The survey was made available in English, so a good proficiency in this language was required. Requests were made to some DEBRA representatives internationally for assistance in spreading awareness of the survey.
It was noted that the fact that they survey was disseminated through DEBRA channels, and that the participants were self-selecting, might introduce selection bias. That is, those participating were likely to have a prior interest in the topic and to be positively disposed towards DEBRA.
The preamble to the survey contained information about the purpose of the study, what the results would be used for and assured participants of confidentiality. Moving from the introduction to the body of questions implied consent for results to be used in analysis.

The survey was hosted on SurveyMonkey Inc
(www. It was publicly available
from June to August. Respondents were asked nine questions in total; three of these provided the background of the respondent; one asked about their previous experience with clinical trials; two asked about where they would source information; two asked to rank the relative weight of factors in their decision-making process. Questions took a variety of formats, including open questions and fixed response questions, some of which incorporated 5-point Likert scales. There was a total of 43 respondents to the survey.
The full text of the survey is presented in Table 1.

Table 1 - Detail of survey questions and answers

At close of the project, data was downloaded from the hosting website and responses were analysed. The results of the survey were then considered on their own merit and in consideration of the themes emerging from the researcher interviews.



Three major themes emerged from analysis of the content of the interviews with EB clinical researchers. These represent attitudes and ideas that are held across the spectrum of those interviewed. However, in a small community such as EB, the outliers that may not be represented by broad themes are proportionally very important. As such, this analysis does not purport to be exhaustive.

Theme 1: EB clinical research is more challenging than expected by those involved
Many positive enabling factors exist for EB clinical research. These include:

  • A good, communicative relationship between EB patients and their clinicians
  • A patient and family cohort who are quite medically literate and willing to engage
  • A motivated network of researchers.

However, on balance, the experience of CR is seen to be more challenging than straightforward. Pervasive negative factors and challenges exist, such as:

  • Many subtypes of EB, which complicates study design
  • Limited current evidence on the natural history of EB
  • Patients are small in number and geographically scattered
  • High burden of disease on the patient
  • Lack of up-to-date and quality registries
  • Issues with coordination between different clinics, in some cases
  • In addition to these challenges, there was some mention of particular challenges with regulatory bodies and other groups, such as insurance companies. These references were noted, but not explored in detail.

Theme 2: Heterogeneity of opinion of patients towards research
The researchers reported a diversity in the attitudes to clinical research among patients. One one hand, most reported engaging with patients who were consistently interested and keen to be involved. On the other hand, many had also encountered patients who would not - or often, could not - take on the extra burden of being engaged in research.

All researchers acknowledged that face-to-face communication, such as taking extra time with patients in clinic to explain more about research or a particular trial opportunity, might help to positively change attitudes to CR. Other opportunities to spread information about research, such as speaking at conferences, were also viewed as having a positive effect, although most also expressed an opinion that this was not frequently feasible. This type of sentiment was suggestive of a sense of frustration within the EB research community as well. Researchers appear to be aware that flexible, creative methods may help overcome some challenges, but these are seen as unrealistic due to resource constraints. Overall, clinicians were aware that they would have to adapt and be flexible when undertaking EB clinical research.

Theme 3: The central role of community and collaboration
The idea of there being an EB "community", "world" or "network" was a strong theme across the interviews. It is generally considered to consist of patients and their families at the centre, with DEBRA, clinicians and researchers beside them.

It appears to be agreed opinion that patients and their advocates must be involved in clinical research efforts on an equal standing to the researchers, if clinical research is to be successful. Researchers’ efforts tended to be more fruitful when they collaborated with DEBRA, for example. However, there is a wide variation in how much the community aspect of EB is utilised in this regard. Whether this is due to not knowing how to collaborate, or some members of the community being unwilling to do so, is unclear.

Researchers’ efforts tended to be more fruitful when they collaborated with DEBRA

Most people directly mentioned community in their final comments. This was most frequently expressed in the context of a desire for more unity and collaboration, particularly within the medical community, and between the medical community and patient. The next most frequently mentioned sentiment was in praise of ongoing community building efforts.


Of the total number of survey respondents (43), 39.53% were people with EB and 48.8% were parents of children with EB (it was not specified how many of their children were affected). Mild and moderate EB were the most common severities of EB cited (44.2% and 41.9%, respectively). The geographical locations of respondents spanned five continents.

Only 9.3% of respondents reported having taken part in a clinical trial. The majority of people (76.7%) expressed a willingness to participate in a clinical trial; 34.88% of these reported to be "very eager" to take part and 41.86% reported they would "consider taking part with reservations". Only 1 respondent (2.32%) chose the explicitly negative option of "I would never take part in an EB clinical trial"; however, with a small sample as this, such responses should not be deemed insignificant.

In responding to Question 5, on where respondents would go for information on EB clinical trials, DEBRA was the most commonly quoted source of information for EB clinical trials (26 mentions of 63 total), followed by search engines (“internet” or “Google”; 16 of 63). Medical personnel (dermatologists, nurses or clinics) were mentioned as a source 9 times in total. Other responses included "social media" (5), other organisations (2) and don’t know/not sure (5).

In total, 37 of the 43 respondents completed Questions 6 to 8. Responses to the following three questions: “To what extent would the following factors POSITIVELY/NEGATIVELY influence your decision to take part in an EB clinical trial?” and “To what extent would you trust information from the following people/groups, in considering whether to participate in an EB clinical trial?” are presented in Tables 2,3 and 4.

Table 2 - Responses to Q.6, “To what extent would the following factors POSITIVELY influence your decision to take part in an EB clinical trial?

Question 6 asked about factors that would positively influence a decision to participate in a CT. The vast majority (75%; n=193) of scale points chosen across all options were either “very strong” or “strong” influence. 94.5% listed symptom relief as either a “very strong” or “strong” influence, compared with 89.1% for the possibility of finding a cure. Access to the trial intervention after completion of the study was the next most influential factor, with 78.3% of responses showing it was either “very strong” or “strong” influence.

Table 3 - Responses to Q.7, “To what extent would the following factors NEGATIVELY influence your decision to take part in an EB clinical trial?”

Question 7 asked about factors that may negatively influence the decision to participate in EB clinical trials. The single most utilised scale point in this set of answers was “moderate influence”, with 26.7% of all responses. When the number of responses to “very strong” and “strong” influence are combined, the leading negative influences from this series were: the possibility of a major risk to health (89.19% of responses either “very strong” or “strong”) and the need for painful procedures during the trial (64.86%). It is interesting to note that most people ranked travel concerns as a “moderate" influence. Overall, the distribution of points chosen was more balanced across the scale as compared to Question 6.

Question 8 asked about the trustworthiness of sources within the EB community. Responses to this question also showed a tendency towards the positive scale points, i.e. "would definitely/likely trust". These results are reported in Table 4. The results also show that social media networks are more likely to be considered trustworthy than not.
Responses to Question 9 were given in a free text manner. 18.6% of survey respondents wrote an answer. Two answers expressed an opinion as to the direction research should be moving, asking for a focus on oral and gastrointestinal issues. Three respondents expressed surprise at the fact that it may be hard to enroll trials adequately; they and another expressed a desire for more information. Another suggested having a new method of registering interest for trials. The final respondent expressed a desire to find a cure for EB.



Prior to this study, the evidence relating to the attitudes and opinions of researchers and patients towards CR in EB was primarily anecdotal. Being a small community with a strong network, such evidence should not be discounted. However, this study aimed to add to understanding of the attitudes to EB clinical research by objective investigation.

The anecdotal evidence indicated that patient engagement and participation in EB clinical research is a particular issue; as such, it was chosen as a central theme for this research. The qualitative portion of this research acted as an exploratory phase, from which additional themes emerged. The semi-structured approach taken allowed these new themes to emerge, as well as allowing specific questions to be answered. Much information and insight into attitudes to CR was garnered in this way.

It would be inappropriate to try and label researchers’ attitudes to CR as wholly “positive” or “negative” in the context of EB. The general attitude is both broadly positive and negative – positive in the sense that there is a great sense of motivation amongst researchers, and negative in the sense that they experience it to be a very challenging area of research - indeed, of medicine in general.

The vast majority of researchers believe in the importance of community and collaboration between researchers, patients and their advocates

The three themes that emerged on analysis of the interviews with researchers are reflective of the more common attitudes to research within the medical community as a whole. However, one theme itself must be remembered in any attempt to categorise the attitudes towards EB CR - the prevalence of heterogeneity, in terms of experience and of opinion. Some researchers reported excellent and relatively straightforward experiences; others, the opposite. This must be kept in mind for actions taken in future.

Despite this, it would be legitimate to suggest that the vast majority of researchers believe in the importance of community and collaboration between researchers, patients and their advocates, in this area of medical research. During the course of the interviews, this idea was either shared explicitly or seen as an implicit part of any efforts. However, the context in which these people were being interviewed must be taken into account – this research was done under the auspices of DEBRA, a leading coordinator of the EB community, so this may have created a kind of selection bias in the people who chose to cooperate with this study.

The quantitative portion of the study investigated patients’ and their families’ attitudes towards CR, with a particular focus on the factors that influence their participation. As such, the results of the survey provide good data on what factors are involved in a decision to participate. Motivation levels and perceptions are also probed in this question set, but in an indirect way.

The overwhelmingly positive tendency in responses to Question 6, on factors that positively influence participating in clinical trials (Table 2), was interesting to note. This consistent trend to list factors as “Very strong” or “Strong” influences suggests that patients are open to the idea of many types of research, from curative to localised symptom management This is indicative of a general open-minded, positive attitude towards CR. As well, the advancement of medical knowledge into EB was consistently rated as a very positively influencing factor. This demonstrates a strong altruistic motivation to participate. Understandably however, factors with the potential to positively influence the patient’s own health are of foremost consideration.

'the advancement of medical knowledge into EB was consistently rated as a very positively influencing factor'

As mentioned previously, Question 7 asked about negative factors involved in decision making. Here, answers lacked the trend towards positive scale points seen for Question 6, with more of a central tendency. Thus, on a relative scale, the degree of in uence exerted by positive factors outweighs the in uence of negative factors (Tables 3,4). This suggests that positive factors play a more decisive, stronger role in decision making than negative factors. The one strong exception to this was the possibility of a major risk to health which was rated as having a strongly negative in uence on the decision to participate in a clinical trial. In this case, only 3 respondents suggested that it would not be a "very strong" or "strong" negative in uence. This risk aversion is not surprising - the decision making process can be seen to be akin to a risk/bene t analysis. The higher the possible risk, the higher the possible gain must be to overcome that barrier.

The survey data on perceived trustworthiness of different information sources provided some interesting, but not entirely surprising, insights. Primary doctors were considered only slightly more trustworthy than family members as an information source on clinical trials. This is perhaps indicative of the fact that primary care specialists are rarely expert in a complex condition like EB. DEBRA was viewed as a highly trustworthy source of information; this should be viewed cautiously, in consideration of the fact that all respondants were recruited through engagement with the charity. One of the most interesting findings here is the general positive attitude towards information received from social media networks, with almost half the respondents reporting that they would likely trust EB social networks. The role of social media in clinical trials is a new and growing phenomenon that needs further attention. It holds the possibility of being of massively beneficial or hugely detrimental to CR; vested interests need to be actively aware of what is happening on social media, in order to reduce the likelihood of the latter occurring. Other social networks, such as other families with EB, also play an important role in the dissemination of information. Again, this is not surprising in a small and close community. However, such dissemination can be troublesome if the information itself is not accurate.

'half the respondents report that they would likely trust EB social networks'

One conclusion that can be drawn from the combined results of the interviews and survey is that patient attitudes are very variable. Reports from interviews suggest that there are two main cohorts of patients. One is highly motivated and positively predisposed; they will consistently find and engage with research, be that by general support or active participation. The other cohort consistently do not want to paticipate and cannot be convinced, in large part, due to the daily burden of the disease. The survey results do not contradict this. It is positive to note that there is a well engaged and informed cohort; similarly, it is disappointing to note that there is a well-populated cohort that seem to be struggling with the daily pressures of living with EB. Here is where advocacy groups can play a very important role. Those who are struggling need critical support in their day to day lives; those who want to engage with research need to be supported in their own way as well.

It is likely that most who participated in the survey are interested in CR; as such, the other segment of the patient population, mentioned above, are unlikely to be well represented in these results. It is important that this cohort is engaged with in exploring these topics, to get a complete picture of what opinions to CR are and what drives participation.


It should be made clear that this study does not aim to be comprehensive. The  ndings are to
be used by DEBRA and others as a basis for further research, and as a starting point from which solutions to problems can be found. Themes which were not possible to exlore in-depth in this study, such as the researchers' experiences of engaging with regulators and the implications of cross-border collaboration, are areas in need of further investigation.
There are limitations to this piece of research, the vast majority of which were anticipated before the project commenced. Chief among these was the limited timeframe available for data collection and the small sample sizes.


Clinical research into epidermolysis bullosa is a known to be a challenging endeavour. We aimed to investigate the attitudes towards clinical research within the community, by engaging medical researchers, and patients and families. Attitudes within the community are not homogenous, but among those who are positively predisposed, motivation levels are high and consistent. Patient participation poses a particular challenge for the progress of clinical trials. The barriers to this are well recognised by all, but they are not insurmountable. Engagement with clinical research is seen in the light of perceived risks and benefits. Efforts should be made to educate people as to what the actual risks and bene ts are, as well as minimising risk and maximising bene ts for patients and families, where possible.




DEBRA Ireland provided funding for this project. The authors would also like to express their sincere gratitude to all patients, families, advocates and medical personnel who supported this project.



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