Director of the HRB Clinical Research Facility at University College Cork, Prof Joe Eustace, speaks with Pat Kelly about the recent International Clinical Trials Day and the overall state of play in clinical research in Ireland.
Celebrated on or around 20 May each year, International Clinical Trials Day commemorates the occasion when James Lind commenced his famous clinical trial on scurvy on 20 May 1747. Lind’s efforts are recognised as laying the foundations for modern clinical research and the occasion provides an opportunity for clinical research specialists, research organisations, and the public to acknowledge and discuss the achievements that clinical research has made possible, and to talk about various topics around clinical trials.
This year, a high-profile one-day conference was held on 12 May, hosted by the Health Research Board (HRB) national clinical trials office (NCTO). The event highlighted some of the most impressive Irish clinical research initiatives and researchers, and launched the calendar of International Trials Day events in the subsequent weeks to showcase Ireland’s research talent.
Prof Joe Eustace, Director of the HRB Clinical Research Facility at University College Cork (UCC) and Director of the NCTO, who delivered a talk at the event, spoke with the Medical Independent (MI) about the importance of highlighting the quality of Irish research in this way, as well as the contentious issue of funding.
“The meeting largely focussed on the processes that underpin research, rather than presentations of different pieces of research,” he commented. “The NCTO’s role in helping to facilitate and develop the infrastructure, resources and capacity for doing multi-centre clinical trials was also discussed. A lot of what was talked about related to that capacity. It was a very successful event – we had representatives from the funders, including the HRB and Enterprise Ireland, as well as regulators, such as the Health Products Regulatory Authority and the ethics committee [national office for research ethics committees], industry, and all the academic entities that participate in all of that.”
The afternoon featured a panel event that comprised members from all of these stakeholders, but one of the standout aspects of the event for Prof Eustace was a palpable sense of common purpose among the stakeholders. “It’s great to see, over time, an increasing degree of cohesion and alignment that was completely lacking 10 years ago,” he said. “When I first took over the role as Director of the Clinical Research Facility in Cork, the situation was very different. In that interim, there has been a very large investment in clinical research facilities and in grants supporting clinical trials, and a variety of these enabling processes by the HRB, as well as the HSE. Historically, the HSE would not have had much insight into research – it would have left it all to the universities. This in itself causes a lot of problems, because you can’t run a modern medical or health research process without the strong involvement of the hospital and governance [structures].
“All of that has changed,” he continued. “There is now a research and development office in HSE corporate and they were represented at the meeting. Just seeing all of those various stakeholders coming together and discussing some of the issues and the challenges – that kind of cohesion and alignment is one of the key standouts for me.”
Prof Eustace emphasised that his main area of interest is in patient-focussed research and he remarked on the development and advances in this field in Ireland over the past decade. “It has progressed a lot – if you look back many years, research would have been quite informal, with very few resources, and it would have been done in a very ad-hoc fashion,” he told MI. “That’s no longer feasible, certainly with all the regulations and requirements that are out there to govern it all appropriately, as well as data protection regulations ensuring the privacy and wellbeing of patients – all of those elements,” he said.
“In modern practice, you really can’t successfully do this research unless you have dedicated resources, so we have seen the development of dedicated facilities in most of the major university teaching hospitals, and similarly in the shape of formal grants that fund, at a reasonable level, clinical trials or feasibility [studies] for clinical trials.”
“So it has developed a lot, and I think the acid test for this was Covid,” Prof Eustace explained. “There was a need to participate in some of the international trials, trying to identify treatments, in which Ireland participated. We were able to leverage those resources to speed-up multi-centre trials in Ireland affiliated with international European trials. That demonstrates the flexibility of the system, and that would have been much harder to do several years ago. That emphasises the importance of clinical trials.”
Prof Eustace continued: “For example, at the start of the pandemic two years ago, there was a lot of talk about and promotion of hydroxychloroquine, with no evidence. So some people were taking it and as a result, the people who needed that medication for conditions like lupus were running out of it, or it was unavailable.”
Prof Eustace was also asked about the importance of research being translational, so that practising clinicians can relate it to their day-to-day efforts. “Absolutely – that’s the essential nature of a clinical trial,” he said. “You can do all the observational work and come up with hypotheses, but it’s really only when you do a proper clinical trial with two agents, one placebo and one blinded, that you can actually assess the attributable benefits or risks of the intervention and whether it actually does anything or not. Even if there are interventions with a lot of suggestions to support them, it sometimes turns out that they are not effective, so guiding implementation based on results becomes the critical feature.
“Sometimes we will see delays in moving from clinical trials to clinical practice. The harder the evidence base, the stronger the evidence-base, and [therefore] the more readily you can make the case for that implementation in clinical practice.”
Another area where Ireland has seen great progress is in improved patient recruitment for these trials. “Ireland is very fortunate, in that we have a very altruistic population,” said Prof Eustace. “For recruitment onto clinical trials in Ireland, more often than not, most people you approach – unless there is a reason they can’t do it, such as having to make multiple visits to a site – most people, if they are able to, they will do it. We are very fortunate in Ireland to have a population that’s very supportive of research, and is knowledgeable, and puts stock in it, so there is great confidence in science,” he continued. “One of the key pieces of International Trials Day was that we had patient involvement in the organising committee, as well as representatives in the meeting itself. One of the things that has become very important in research, as in clinical practice itself, is not that we are doing research on and for patients, but that we actually have patients fully integrated in all stages of that research and that tremendously enriches the research and makes it more effective… there is an awful lot to be had from listening to that patient voice.”
Having worked in the US, Prof Eustace noted how much easier it is to enroll patients onto clinical trials in Ireland in comparison “and it is a critical thing to try to protect that”.
It has long been known that Irish medical practitioners are held in high regard worldwide and are known for their exemplary levels of training, expertise and professionalism when they work abroad in different facilities. Prof Eustace was also asked if Irish clinical researchers are held in similarly high regard among the international medical community. “Ireland has a very strong reputation [in this area] for the quality of its work and we see this in a lot of the clinical trials that we support,” he said.
“We get a lot of companies returning to Ireland for future trials because of the quality of the work and that comes down to having the appropriate systems and dedicated staff. You simply can’t maintain that kind of quality if you don’t have the right people with enough time to do it properly.”
“Ireland is well regarded from a research viewpoint,” said Prof Eustace.
There are some complexities and areas for improvement, such as certain processes that are not as efficient as they could be and the lack of an electronic patient record, but “the thing that counter-balances that is the quality of the work and that is our main selling point for research,” said Prof Eustace.
Despite all of these advantages and advances, the actual volume of clinical trials and other patient-focussed research in Ireland is still relatively low, Prof Eustace pointed out. “If you compare us to countries like Denmark, for example, we only do about one-fifth of the number of clinical trials they do, and we have a similar population,” he explained. “Some of that relates to absolute levels of funding. The HRB and other organisations can only give out the funding that they get from Government so historically, those levels are substantially lower than in many other European countries, and that’s almost certainly still the case.
“When you look across the different areas, there is obviously a lot of research historically into cancer and heart disease, for example, but if you look at the emerging areas, such as dementia – there is a condition with a huge societal impact,” he continued. “The HRB has funded a set of schematic networks, and one of the most recently-funded ones is in that area of dementia clinical trials, so hopefully that will help to increase and promote that research. But in absolute terms, it is still at a modest level. If you look to the UK, there is a key message of having a certain percentage of patients being involved in clinical trials, or that a certain percentage of them are at least approached about participating in a trial.
“Here, it would be more of the exception to have a patient take part in a clinical trial… I suggest that a high proportion of people with a diagnosis would be very happy to contribute in an attempt to find a successful treatment. Even if their participation wasn’t going to be meaningful for them, it could be meaningful for their children and other generations to come. But our ability to meet the potential capacity is really quite limited because of the absolute level of funding; we talked about dementia, but you could almost apply that across the board with any specialty… we have a huge opportunity to allow more patients to contribute to and benefit from research and that would also benefit the whole health system, because it’s a huge quality-enabler.”
Funding and time
Funding would be a big component in rectifying this situation, said Prof Eustace, and more funding from the Government to the HRB would allow it to build and promote more research. However, there are other elements in the scenario that are particular to Ireland, he added. “There is a limited role for clinicians, who obviously play a major role in driving the research and getting protected time. If we could get the time with the dedicated staff – such as research nurses and data managers to support the trial work – but the person leading the trial is still a full-time clinician with very busy clinical services. That becomes a limitation, and if you wanted to scale-up the amount of research, the ability to build on that is clearly limited. That’s one of the things that limits the absolute amount of research we can take on in this country.”
If funding and clinicians’ time were addressed, that would significantly increase Ireland’s ability to conduct more high-quality, patient-focused research, but Ireland also needs to continue to produce high-quality research and clinical staff in tandem. Prof Eustace was asked what he might say to a young person starting out on a medical career to entice them to take up a role dedicated to clinical research.
“Doing clinical research is still very much a trade,” he told MI. “You have got to work with people who are good at doing research. You can learn a certain amount from studying or training in statistics, but to actually become a successful researcher, it’s also really important to identify an appropriate mentor, as well as finding somewhere where you can take part in a research project and spend time learning how to actually do that properly and to a high standard, with good quality.
“One of the problems we see in clinical practice at the moment, because it is so busy and we have so little time, is that it would have been the case that all clinicians in training had to do a substantial amount of research, so they would know how to do that. Because of time constraints, that has become less the case over time, but unless you know how to do research – and not only the research that you do – your ability to interpret research and the ‘next big thing’ that’s coming over the horizon and interpreting the papers on what may be a new and effective therapy [are hampered]; without these, you can’t effectively be at the cutting-edge unless you are involved and know how to be at that cutting-edge yourself.
“That’s the real learning about doing research – it’s not only that it empowers you to do your own work, it also enables you to see what’s relevant for your patients and pick the right new interventions for research where the evidence-base isn’t strong enough. This has huge benefits, not only to the patients you enroll in trials, but it is a huge quality-enabler for the health system generally and if you look at it on an individual clinician’s level, it keeps you constantly reassessing your practice against the international standards.”