![enter image description here][1] #### Participants were asked about the particularities of phase 1 trials in cancer specifically, and what makes them special. **Gatekeepers: safeguarding the patients** - #### Phase 1 trials safeguard the patients by gatekeeping the drugs and treatments that have unacceptable toxicity or limited efficacy. *“(Phase 1 trials are) the infrastructure within which to learn. It's not just about recruiting the patients and collecting the data. It is the understanding of drug action that can allow you then to make sensible decisions about taking the drug forward into later phase trials.”* *“(...) saying, look, I think we should drop this drug now because either from an unacceptable toxicity which cannot be overcome by any other strategy, or because of lack of efficacy and being brave enough to say, just pull the plug on this drug at this point now, or I don't think this one's going to go forward in (a) competitive environment.”* **Enabling Future Therapies: moving the health service forward** - #### Phase 1 trials enable promising future treatments to go forward into later phase trials by being the first step of testing in human patients. *"If there are good new drugs coming through, and we have seen a huge number of really powerful and cheap practice changing drugs come through in the last 10 to 20 years, what you want is as fast as possible, that we get access for patients within the health service. And there are lots of factors that play into when those regulatory processes go through. And having active clinical trials and clinical research is a really important starting point for a country to keep its health service moving forward."* *"Almost all of the patients we talk to get the fact that if they don't benefit, somebody else might."* **Human centred** - *"We ask the patients with terminal cancer if they're prepared to take an experimental drug, where we don't know the dose and we don't necessarily know the side effects."* #### Patients are usually terminal and have exhausted standard treatment options. Phase 1 trials are very intensive and challenging for patients, especially since they may already have had a long cancer journey at this point. Being part of a trial means more hospital visits, procedures and commitments. Trialists need to be open to patients to gain informed consent, explain that they are not offering benefits and make sure the patients understand the implications correctly and that the trial is right for them. *"I used to invite the administrative staff into the clinic, basically, so they could see (that) this isn't just a paper or electronic exercise. So I think that you (need to) appreciate seeing the patient facing side of things."* *"(There is) this balance between not destroying hope, while not encouraging unrealistic expectations, being able to transition them so that you're providing both the supportive care that they are going to need, if and when they leave the clinical trial."* *"I think it's a special and different relationship with the patients. And the level of gratitude of patients is really humbling."* **Small Scale** - #### The smaller scale of Phase 1 trials creates a unique dynamic, not found in later phase trials. Oncologists get to know the patients better, which is important on a human level, but also gives the opportunity to develop pattern recognition to spot subtle unexpected side effects or toxicity. Trialist also get to have an important impact on the development of new drugs and treatments at an early stage. *"But we tend to see the early phase trial patients more frequently. So we tend to be a smaller team looking after the early phase trial patients so others see if they're agreeable, I find myself getting to know these patients better."* *"So there is a more intimate relationship with the development of a drug and the ability to shape how that drug is developed. The proximity to the action, and the sense that you're dealing with something that is genuinely novel, you're giving a chemical to people with cancer in the last few months of their lives, a chemical that looks like it's okay in mice that hasn't been given to people before. It is actually fairly mind blowing when you stand back and think about it."* *"Pattern recognition is important, because the way we set up these studies, rather than everybody doing them, you have them concentrated in a small number of investigators and a 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."* *"If each centre only sees one or two patients, you lose the opportunity for pattern recognition."* **Limited window of opportunity/urgency** - #### There is a limited window of opportunity for patients to take part in Phase 1 trials, so it is important for patients to be aware of their options at the right moment. *"And one of the challenges we have when patients are running out of treatment options is whether their attending clinician says to them, we've run out of treatment options. And things are likely to get more difficult. Do you want to think about a trial? Or whether the treating physician simply says, well, we'll give you a break off treatment at the moment and see you in three months time? And if you do the latter, then the window for an early clinical trial may well have closed or be much more limited?"* **Reputation/Trust** - #### A centre is only as good as it’s last trial. Sponsors rely on the reputation of centres to form relationships and trust them with their trials. *"It's a competitive business internationally to attract early phase trials to your centre, because we want opportunities for our patients (...) And there is a reputation that has to be acquired and maintained. And you know, they say football is only good as your last game, we're only as good as our last trial. If we foul it up, that sponsor is unlikely to come and approach us anytime soon afterwards. So I think there is a reputation that comes from building up a critical mass of early phase trials in your centre, that you can convince people who have invested an awful lot of money to develop this novel compound to trust you with its development in the critical phase and early phase trials."* *"It's about maintaining that relationship. And that comes down to whether you recruit the way (you said) you were going to do it, and whether you provided the data in a timely manner. Did you follow the protocol? Were there any concerns and serious protocol deviations?"* *"(Something that is) emphasized in terms of building up a trials department and having commercial relationships with pharma is punctuality and robustness of communication. (...) And the more robustly you deliver their trial, with good assessments and good documentation, then the more likely they are to come to you with another trial."* 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/jdrq9/?direct%26mode=render%26action=download%26public_file=False&initialWidth=560&childId=mfrIframe&parentTitle=OSF+%7C+THE+IMPORTANCE+copie.jpg&parentUrl=https://osf.io/jdrq9/&format=2400x2400.jpeg