Ireland offers a centre for MedTech and healthcare innovation; why can’t it be a leader in clinical trials as well? Here, Cois Coiribe connects with Prof Fidelma Dunne, Professor in Medicine at the College of Medicine, Nursing and Health Sciences, University of Galway and Interim Director of the Institute for Clinical Trials. She offers insight into the state of healthcare and clinical trials, and she explores advancements in diabetes medicine and management. Read more below to get a glimpse into Prof Dunne’s vision for Ireland.
Fidelma Dunne (FD): I am a Professor in Medicine at the College of Medicine, Nursing and Health Sciences, University of Galway, and am currently the Interim Director of the Institute for Clinical Trials. I’m a Galwegian; I went to medical school in Galway, and then on to the UK for postgraduate training. I returned to Galway in 2003 and have worked here in the HSE and the University ever since. It was great to come back to my alma mater because I really wanted to give something back. Recently, I’ve taken up this role as Interim Director of the Institute for Clinical Trials, and I feel truly challenged and delighted. My specialty is diabetes and endocrinology, and this has been a fantastic area to work in. There has been an explosion of treatments in the last number of years for diabetes. I have a particular interest in diabetes and pregnancy. I learned that treating the mother with diabetes and her infant in utero can have huge implications for the future health of both of them, and this translates into better health of families.
FD: The Institute was set up in May 2023. In Ireland, we are good at completing clinical trials; the quality of the trial evidence we produce is excellent, but the number of trials is small. We are behind comparable European countries in the number of trials we complete. Despite a rich ecosystem in the West of the country, particularly in the MedTech space, we are not delivering the expected number of trials. This is due to a number of blocks nationally in the setup of clinical trials. The objective of the Institute is to try to solve these problems by working with key stakeholders.
Within the Institute, we have five pillars of critical activities. The first is building relationships, with industry, MedTech, and other academic institutions in Ireland and abroad with the US and Europe. We need to face outwards and develop bigger collaborations to ensure higher involvement in clinical trials and higher impact.
The second pillar is showing we can deliver trials in an efficient and predictable way. The current problem is the 12 to 18 months delay in setting up a trial before it starts enrolling participants. We are addressing this through a Hypercare process we have established in Pillar 2. In this process we work with sponsor companies in their preparation for submissions to the national regulatory body (HPRA) and national research ethics committee (NREC). We also guide through contract negotiations. We hope Hypercare will streamline these processes and reduce delays allowing trials to quickly move to patient enrolment. This approach aims to make the setup of trials more efficient and reproducible.
Pillar 3 focuses on methodology. Currently, everything is centralised – ordinarily you have to come to a hospital site or Clinical Research Facility (CRF) to participate in a trial. The institute will work with the HRB Methodology Research Network to help design innovative trials incorporating AI. We also need to use routinely collected data better. Take, for example, diabetes clinics in all hospital, community, and primary care sites, there is a lot of data collected. We could use this data to answer important questions pragmatically without completing an expensive clinical trial.
Pillar 4 is about education – training and building capacity. Trials need doctors, nurses, research associates, biostatisticians, economists. Without such a skilled workforce, trials could not happen, and Pillar 4 is focused on the education and training of the workforce and building capacity.
Lastly, Pillar 5 focuses on policy and guidelines. A great trial will only have benefits for patients if it informs policy and guidelines, and we have expertise in navigating these areas in Pillar 5.
FD: The Institute cannot stand alone and be successful; we have to look at the ecosystem of the University. This is where the Institute for Health Discovery and Innovation (IHDI) is important. Through it, we will have a pipeline of emerging innovations that will need to be tested in humans. Working with the IHDI we will be aware of what is in development and know that a number of new discoveries will come to the Institute for Trials in a few years. We need to make sure these proposed innovations will be acceptable and deliverable to patients. For example, in diabetes, a new sugar-monitoring device must be practical for patients to use; otherwise, it will not be adopted. Engaging clinicians and patients early helps refine both innovation and product design, increasing their chances of reaching clinical trials.
The other groups that are going to influence our Institute activities are CÚRAM and BioInnovate, and the expertise that exists within these groups. We must focus on MedTech over the coming decade. We have had interesting input nationally from Lord James O’Shaughnessy from the UK House of Lords. He did an exercise in the UK examining the roadblocks to clinical trials there and shared his knowledge with us nationally. He said that, as an outsider looking into Ireland, our unique selling point is the MedTech space. We need to use this incredible ecosystem around us, and we have the building blocks to make this very strong.
FD: Yes, we have been doing clinical trials, but not enough of them. In Denmark, which is comparable to Ireland in size, population, and economy, they are doing six to 10 times the number of trials we are doing. They have realised the very strong link between clinical trials and the health of the nation and the economic advantages and this has driven the clinical trials space. For every euro that goes into clinical trials, the economy gains €4. In July 2023, Minister Donnelly set up the National Clinical Trials Oversight Group (INCTOG) to examine both problems and solutions and create an implementation plan in the clinical trials space. I represent the Institute on this group, and I look forward to a successful outcome from it.
FD: COVID-19 taught us that when we need a solution, everybody can roll in together and conduct a trial. It showed us that the development of a new vaccine doesn’t have to take 10 years. It taught us about the process and benefits of platform trials and collaborations.
We know that platform trials involve enrolling a large population into a single trial that then has multiple treatment arms. For example, during COVID-19, many treatments were investigated and dismissed quickly if benefit was not seen, allowing the platform trial to focus on more promising options. This approach streamlines testing multiple treatments within one trial.
I think COVID-19 did smarten us up, but I’d like for us to continue to learn from what it taught us. Unfortunately, research and clinical trials are not always prioritised, but really, they need to be top of the agenda.
Within the Institute we have clusters of activities. One research cluster, the CORRIB Core Lab, focuses on imaging for cardiovascular disease. There is also the global INTERSTROKE study, which Prof Martin O’Donnell and colleagues have worked on. There are useful, practical outcomes from INTERSTROKE in relation to lifestyle choices. Another cluster focuses on cancer therapies and innovative new cellular options. Finally, across diabetes, colleagues are examining the use of stem cells for diabetes complications and healthcare delivery options for young adults with type 1 diabetes. In my own research, I completed the EMERGE trial last year looking at the use of a tablet called metformin to treat gestational diabetes (GDM), and this will likely impact national and global policy and guidelines going forward.
I would like to see the Institute as a centre for ideas, design, delivery, and dissemination of trials with global impact. We have both the people and the skillset to focus on new ideas and new trial designs.
When you talk to sponsor companies, they say that Ireland excels in the quality of data collected in clinical trials and that the retention of patients in Irish trials is very high. These are two really important selling points we should promote for hosting a trial in Ireland. By streamlining the setup processes and ensuring reproducibility of timelines together with the high quality of trial data and strong retention rates, Ireland is in a very good position for conducting clinical trials.
FD: We are in a unique position because we are an island nation, with a homogeneous population. This can be an advantage for clinical trials. Where we are disadvantaged is that we have a large rural population where current access to clinical trials is difficult. Currently, we conduct clinical trials in level 4 hospitals, like Galway University Hospital. People in a level 4 hospital are not truly representative of the entire disease population. To do a trial in diabetes, ideally you should have people from the level 4 hospital but also from primary care, and from the community care hubs. With the new Regional Health Authorities, we can in time explore conducting clinical trials in a broader spectrum of sites. This is especially important for AI-related trials and technology-based trials.
I don’t see the ethical question as a challenge at all. It is important to ask patients if they would be willing to be involved in a trial. I don’t think there is any ethical dilemma in conducting a well-designed clinical trial, but you do need to take the time with patients to explain all that is involved, the benefits and risks. In fact, I would say that in modern healthcare, clinical trials should be a usual standard of care. So, if you have breast cancer, I should be able to say: this is your care, the available tests, the standard treatments, and the clinical trials that are going on. I think Trial A would be suitable for you. It’s an ethical concern to me that inefficiency is preventing trials coming to Ireland and patients with conditions that might be helped by a new trial medicine cannot access it in a timely manner. For example, for rare diseases or advanced cancers with no standard treatments left, clinical trials may be the only option. With limited time, I believe it’s ethically wrong to create unnecessary barriers preventing access to these trials.
Absolutely. I sometimes think if I never did any research, I’d be doing the same thing I did 20 years ago. What’s the point in that? If you can do it, you have a duty to do it. If you don’t, you’re not fulfilling what your profession encourages you to do, which is advancing healthcare and patient care by exploring new options.
In type 2 diabetes – diabetes that is not dependent on insulin (90% of diabetes) – two new medications have transformed healthcare. GLP-1 analogues are the drugs you hear about for weight loss. They were originally designed for patients with diabetes. They have really improved the care of patients with Type 2 diabetes in respect of glucose control, weight loss, protection of kidneys, and lowering cardiovascular risk which is high in people with type 2 diabetes. It is a similar story for another class of drugs, the SGLT2 inhibitors. They also have improved outcomes for those with type 2 diabetes. In type 1 diabetes, the revolution is in continuous glucose monitoring (CGM) and insulin pump therapy. Nowadays, you can wear a device that tells you what your sugar level is continuously. We also have smarter insulins and insulin pen devices, and the icing on the cake is pump therapy, which delivers insulin according to your sugar level. In pregnancy, small changes in glucose can lead to significantly improved outcomes. For example, sugar control targets are stricter for pregnant women than for those who are not pregnant, improving outcomes for both mother and baby. However, tightening sugar control increases the risk of hypoglycaemia, which must also be managed. For pregnant women with type 1 diabetes, continuous glucose monitoring and hybrid closed-loop pump systems are now the standard of care. In Galway we participated in the international trials in this area.
Of course, communicating the value of hybrid closed-loop systems to the Department of Health is challenging, due to their cost and staff intensity, as they require extensive training, frequent data review, and communication.
In the EMERGE trial in pregnancy, we looked at a tablet called metformin in women with gestational diabetes. We found it to be effective. Women were 25% less likely to require insulin, they gained less weight and preferred it as a treatment option. Babies were lighter at birth and less likely to be obese at birth. There were no new unexpected issues seen for mothers or their babies exposed to metformin. If you look at the impact of that trial globally, a huge amount of gestational diabetes occurs in emerging countries where insulin is unavailable or unaffordable. Metformin which is cheap may be the only option for treatment. Gestational diabetes increases the chances of obesity and diabetes for both mother and infant, so treating it effectively is essential.
FD: In five years’ time, I would like to be able to say: the Institute of Clinical Trials has been instrumental in sorting out the barriers to trials in Ireland, and our trial set up times are efficient and reproducible; that we have attracted increased income to conduct trials from funders and industry because we can show effectiveness; that we are the go-to place in Ireland to conduct early feasibility and first-in-human studies in the MedTech space; that we are working effectively with the IHDI and have a pipeline of innovations coming to our Institute; that we use AI and big data during trial design to see if trials can be more efficient and cheaper; that we are delivering trials with impact and recruiting participants from a variety of health care settings.
I think it is important to conduct trials in diseases impacting health in Ireland, e.g. cancers, cardiovascular disease, obesity, chronic diseases like diabetes. Trials in these areas may focus on MedTech, new medicines and innovative processes for delivering healthcare.
