At present, cross-border trial access is a real grey area in Europe, making it difficult for sponsors to run trials, especially in rare diseases. Having clear-cut guidance in place would make it easier for sponsors to understand how they should go about enrolling patients who are from different countries to where the trial site is located. It does happen in some cases but there is no real understanding amongst the industry about how to best go about this due to legal, regulatory, and ethical considerations.
The EU-X-CT project, being jointly run by the European Forum for Good Clinical Practice (EFGCP) and the European Federation of Pharmaceutical Industries and Associations (EFPIA), aims to provide clarity to all parties involved in clinical trials.
The group has already run a public stakeholders' forum in April where those who had been impacted by this were able to share their experiences. There are documents available, however, for other sponsors, biotech companies, patients, contract research organisations (CROs) and patient groups to share their experiences if they were not at the meeting.
In the US patients can take part in trials in different states to improve recruitment, so, surprisingly, this is something which has not yet been properly established in Europe given the difficulties sponsors and biotechs encounter when recruiting in rare disease trials. The ability to do this has the potential to increase recruitment while maintaining reasonable trial costs for sponsors and biotechs.
Sarah Bly, director of Regulatory Science Strategy and Innovation at CRO Worldwide Clinical Trials is working on the EU-X-CT project. Bly and Matt Cooper, executive director and therapeutic strategy lead in oncology presented at Arena International’s Outsourcing in Clinical Trials (OCT) Europe 2024 conference, held in Barcelona about the scheme.
Following their presentation, Bly and Cooper spoke with the Clinical Trials Arena team about how the programme will help provide much-needed clarity in this space.
Abigail Beaney (AB): Tell me about the EU-X-CT project and how it will solve the problems of enrolling patients in different countries, something which is currently a bit of a grey area?
Sarah Bly (SB): Yes, it really is a grey area. What we have created is a group of volunteers who represent various stakeholder categories including sponsors, clinical research organisations, patient advocacy groups and academia. All these volunteers are coming together with a passion. This is especially helpful for rare diseases where you have a patient in Germany, for example, but the studies only open in France and Spain because the sponsor can't open a study in all member states.
It's really about the complexities because it's such a vital lifeline for this type of patient but how do you get that patient from Germany onto a clinical trial being run from Spain or France? It might sound simple but it's not. There is a lack of legislation, lack of guidance, especially in the EU, because there's so much centred around it. In the study start-up you have to consider; how do you get the patient from one location to another? What's the insurance requirements? What are the legal requirements? Because there's a lack of guidance out there, we need all these stakeholders to come together and give their experience. The EU-X-CT team has separated into three task forces detailing the regulatory, legal, ethical, financial, logistical and operational aspects to create guidance to make it a more streamlined process.
AB: Given the lack of legalisation, what are the current practices to get around this?
SB: The problem is there is a lack of current practices for cross-border clinical trial access and as a result, there's not much that anyone can go on. Some countries will put a little bit of a nod to it in guidance, but it's not detailed. One of the main questions we've asked is whether it is possible in a country. I believe we have not had a definite no from anyone yet, so it looks like it is a possibility across the board, but we still need to establish guidance to do that.
Matt Cooper (MC): I think it has become more prevalent due to modern technology. Patients can find out about studies that are taking place anywhere. Instead of a clinician finding a study for their patient, patients now are asking about these trials themselves and how they can get enrolled. As great as that is, there are just not enough resources to open sites in every country in the hope that a patient might suddenly pop up one day to be recruited.
AB: For small and medium biotechs, especially those that work in the rare disease space, is this also a cost saver by reducing the need for more sites?
SB: I think it depends on the study because there are other things you must factor in such as travel and accommodation for the patient. That is however likely less than setting up and running a site in every country.
MC: I would say probably the biggest cost saving would be in recruitment. In previous times, you would open a study and wait for patients to turn up with a monthly cost to the sponsor while you wait. If you can now identify patients from a bigger pool and bring patients from other countries into your trial, you can get your recruitment done in a more timely manner so that's probably more cost-saving than anything else. Yes, there'll be more costs per patient for travel and accommodation, but this isn't the same as having a trial open. On top of that, the trial can potentially be several years shorter because you don't have to wait for those patients.
AB: Could sponsors and biotechs set up just one site and enrol patients from across the continent? What are the risks with this and how is the legislation going to ensure this does not happen?
MC: You don't want to see a situation like that where the sponsor opens a site in a single country and then tries to fly everybody in from everywhere because it's not good for the patient.
SB: You have to ask questions about whether it is justifiable to ask patients to travel - are you putting the patient out by doing this? How is their condition? Can they travel? We can't just be thinking of this as a way of making the study easier and cheaper for the sponsor, it always must be the patient at the forefront, and how much this is going to affect them instead of opening from their country that they could easily travel to. You are going to have to justify your study design to regulators and why you're doing this.
That's why it's important to be thinking about this early on. It's the questions like – is this fit for our protocol design? Is it going to fit into our patient's lives or is it going to make it more difficult for them? It’s got to come straight back to the patient every time.
Check out other coverage from OCT Europe 2024 on Clinical Trials Arena:
OCT Europe: AI and RWD can avoid data replication in trials
OCT Europe: Mutual investment a better solution than patient centricity
OCT Europe: Data governance guidance provides much-needed clarity
