![Diagram][1] > *“We mustn't forget that this is still very much experimental medicine.”* #### These are themes we identified referring to changes, currently happening or predicted to happen, that would change the dynamic of trials and the way they are handled. **Patient involvement in trials** - #### Patients are more willing to take an active role in looking for trials, and trialists understand the need to involve patients and patient representatives at all stages of a trial and its design to better understand their needs. *"So I think there is now that approach, and we get patients hunting for trials. There's an informed patient population out there."* *"You'll assume, as a clinician, that a patient wants to reduce number of visits or you know, wants to have tablets, instead of intravenous, or all of the ER make all these assumptions, and you won't necessarily be right. They may find that coming to the hospital is actually very reassuring and they don't want to reduce the frequency of visits. Or they may actually hate taking tablets and feel like they're rattling all day, if they're having to take 20 tablets a day and prefer to come once every three weeks to have a drip. So, so we can't assume that we know anything about the treatment pathway without checking the patients."* *"Patients aren't as involved at the minute as they will be in the future. And I think public and patient involvement is becoming a much more important aspect of research. Having patient input to research decisions, even at an early stage is advantageous even from practical perspectives of the big additional commitment to going on to a phase one trial in terms of hospital visits and extra tests and extra blood tests and biopsies, etc. And, you know, patient representatives from an early stage can let you know what they think might be acceptable and what might not be acceptable, which can help in research and clinical trial planning from an early stage."* **Changing Population** - #### The target population for First in Human Trials is changing, and including less terminal patients who haven't exhausted their treatment options. This prompts a reconsideration of the side effects and long term effects. *"Increasingly, early phase trials are open patients who haven't exhausted their standard treatment options. So then you've got a different dynamic, where you need to identify with the people looking after the patient, their primary team, a window of where it is reasonable to look at an experimental treatment, on the basis that they their condition won't deteriorate, even if that treatment isn't effective, and that you won't have exhausted any of your future treatments. So in breast cancer, we get patients who have reached the end of endocrine therapy, but who don't have a pressing need to start chemotherapy. That's an amazing opportunity, in that situation, to look at something that is more novel. So that there has been a move away from these patients being pre-terminal."* **Growing size of studies and competition** - #### The growing size of Phase one trials disrupts their dynamic and brings a perceived dilution of the unique research opportunities afforded by their [small scale][2]. *"(there is a) changing nature of early phase trials. Because we are of a generation that remembers doing phase one trials where there was (...) 20 to 30 patients, but now you've got drugs been licensed on the basis of a phase one study where there's 1000 patients (...) And with that has come perhaps the dilution of the balance between risk benefit and the anticipated benefit for patients as well, the perception has changed. And yeah, we mustn't forget that this is still very much experimental medicine."* *"Pattern recognition is important, because the way we set up these studies, rather than everybody doing them, you have them concentrated in small number of investigators and small number of centres, so that they see the multiple patients getting treated with the same trial. So they have the opportunity of seeing that unusual, unexpected pattern recognition toxicity that would be diluted if a study of not very large patient sample size was diluted across too many centres."* *"Traditional phase one trialists would say that two or three centres is optimal. And if it's a tumor specific or site specific trial, you'd say, not a huge number of centres, because it's not (just) wanting ownership of the patients. If each centre only sees one or two patients, you lose the opportunity for that pattern recognition."* *"If you look at every possible combination of immunotherapy that could be done, there aren't enough for patients and early phase trials in the world to do it. It is increasingly competitive. But it has to be done in a rational and sensible way."* **Digital Data & Knowledge Management** - #### Digital Data collection tools offers new opportunities for monitoring patients and their quality of life more accurately. #### Available and long-term access to Data streamlines the research process and allows comparison to similar datasets. *"We’ve been coming through patient reported outcome measures, where you capitalize on digital technology to get patients fill in apps and tell you how they’re feeling and, you know, day by day and collect more real time data."* *"Patients are going to want to do more remotely going forward, I think there will be much more electronic inputting. And I hope that we'll move away completely from paper data entry. (We will) need to be much more aware of how to do electronic data entry. I'm hoping there'll be a lot more access to source data so that we won't have to start from scratch with everybody."* *"In our most recent trial, we've built in doing a test of brain function, a series of really short computer games, at the end of treatment, the basic tests kind of how well you can concentrate and memorize things and, and kind of plan your way through a maze and things like that. And on its own as a static measurement (...) it might answer a little bit of science, but not loads. But having got that we can then potentially go back and get people to repeat it in five years time. And we've got that baseline on all the children."* *"We have this huge potential to be much more efficient in the way we collect data, because the NHS collects a huge quantities of data routinely. And all that data is potentially linkable, collectible and analyzable. And you can use that to return information on trials and make progress. And that's a massive potential to make things much more efficient."* **What's next?** - We reflected on the future population that would take part in phase 1 trials, and the impact early detection and prevention strategies would have on the cancer population. How will the target population for First in Human Trials change in the Future (different tumour types / age groups / disease stage), and what impact will it have on trials? How will Trials have to adapt? For example, if a younger, less terminal population is taking part in Phase 1 trials, how will side effects and long term effects be considered? Will quality of life be measured differently? COVID-19 has put clinical trials in the public eye and given a very concrete example to show the value of trials. In the future, how can the value of trials be more clearly communicated to promote public awareness? Trialists will need an increasingly broad knowledge base. How can early career researchers get this experience, and gain more exposure to different types of cancer and treatments. Phase One Trials currently benefit from the positive dynamics of working in a "niche" subject, with a small scale. What are the positives and what are ways to keep them in the future in a growing field? You can view the full enhanced report here: https://osf.io/azg8e/ You can download the full enhanced report here: https://osf.io/azg8e/download [1]: https://mfr.de-1.osf.io/export?url=https://osf.io/du6pk/?direct%26mode=render%26action=download%26public_file=False&initialWidth=560&childId=mfrIframe&parentTitle=OSF+%7C+changingdynamics.jpg&parentUrl=https://osf.io/du6pk/&format=2400x2400.jpeg [2]: https://osf.io/9cs7w/