Quality of life as a motivation for participation.

Participants reported multiple reasons for enrolling in a phase I clinical trial, many of which reflected their hopes of preserving or improving quality of life. Hope for therapeutic benefit was the most typical factor, particularly among younger patients – even though they acknowledged that physicians had been transparent about the lack of guaranteed improvement. This is illustrated by the following quotes from a patient (P) and their informal caregiver (IC):

“(P) I hope – expectations are something else – I hope it works, yes.

(IC) While they haven’t... given her any reason for hope, that’s not it. That has been made clear, it’s an experiment. So, it doesn’t cure, but it can of course prolong and keep (her) in good condition.

(P) So nothing about recovery or so, I know that’s not possible.” (Patient & informal caregiver)

Many participants saw trial participation as their last available option for treatment – a choice that could stabilize their condition and provide structured follow-up, reducing fears of being left without support and maintaining quality of life in the face of uncertainty. Some also cited non-personal motivations, such as altruism and contributing to science: “Many say, you help science, and potentially other people.” (Phase I study coordinator) Others framed their decision relationally, seeking to extend life for loved ones or reach important milestones. Healthcare providers largely echoed these motivations, noting that patients who sign up often have a strong wish for continued treatment. However, some providers pointed out that patients may feel pressured to participate when suggested by their oncologist.

Experienced quality of life and well-being.

Patients overwhelmingly described their quality of life and well-being during the trial as positive, specifically due to symptom improvement and to the psychological boost and hope provided by having this, as they often perceived it, ‘final chance’. This is illustrated particularly well by the following quote where a patient notes that participation grants perspective that otherwise would not have been there: “[…] the study gives hope, of course […]. If you have nothing left, I think that’s more difficult.” (Patient)

Patients often expressed great gratitude for being afforded the opportunity to participate in the trial. They also noted feeling secure due to the 24/7 availability of phase I staff, signifying stronger monitoring than during standard oncological treatment: “You feel safer. They emphasize that too. When they say, ‘you can reach me tonight if necessary’, it gives a kind of comfort. That’s important too.” (Patient)

Nevertheless, challenges were also reported. Besides the potential side effects, which varied greatly across treatments, uncertainty regarding treatment effectiveness and long-term outcomes was a source of distress for some, with some patients describing a sense of being ‘guinea pigs’: “I am a guinea pig. I’m not really a patient here, if you know what I mean – they’re observing what the drug does to me in a strictly scientific way.” (Patient)

Additionally, the time demands of the trial, including frequent hospital visits and extensive testing, were perceived as burdensome by all types of interviewed participants, although less so by the patients than the other interviewees.

Staff efforts to support quality of life.

Phase I staff expressed routinely verbally inquiring about quality of life, which patients echoed, who generally indicated feeling heard. Phase I staff noted that they would refer patients to psychologists or dieticians, although only reactively upon noticing a clear need, rather than proactively. However, informal caregivers and non-trial healthcare providers were less positive, highlighting a gap in psychosocial support. Notably, while phase I staff indicated that they understood quality of life to be highly subjective based on each patient and what they deemed to be important for their own lives, this was not reflected by the perception of informal caregivers and non-trial providers, who indicated that inquiring into patients’ quality of life remains surface-level and that how the patient is ‘really’ doing is often not addressed:

“It’s never about quality of life. It’s always about objective things [medical results].” (GP)

“What the patient reports, often those are questionnaires or an interview with a psychologist, but that’s more in phase II or phase III studies. What the patient thinks is less considered in phase I.” (Oncologist)

While phase I staff indicated that patients sometimes complete quality of life questionnaires, this was inconsistent across studies. When such questionnaires were administered, staff members admitted that the results were typically not available to them, only being collected for study purposes and not being acted upon. While personal goals and wishes of patients were not always explicitly discussed (e.g., preferences for timing of treatments), phase I staff did report making efforts to balance patients’ personal preferences with trial protocol requirements, although this also highlights the concessions that patients may have to make to remain with the boundaries of the study protocols:

“That’s not always in our hands, we’re somewhat bound to the protocols that must be followed. But of course, the patient’s wish is always the most important. We certainly take that into account. If they report something like, look, that really wouldn’t work, then we try to adjust.” (Phase I study coordinator)

Patient attitudes towards palliative care.

Patients mostly held negative attitudes and resistance towards the concept of palliative care, associating it with terminal care. Many did not consider themselves as ‘palliative’ – nor terminal – and perceived conversations about palliative care as premature or unnecessary, as illustrated by the following quotes:

“I’ve never been in that mindset of ‘it won’t be long – I have two months to live.’ I’ve never been there. It’s also never been said to me. If they told me tomorrow, ‘sorry, you have two months left.’ Only then would I consider myself truly palliative and prepare my mind for death. But I’m not occupied with that yet. That’s not the case now, not yet.” (Patient)

“(And has the word palliative care ever come up? Has the doctor or a nurse ever mentioned it?) No. But I think they also know not to bring it up with me.” (Patient)

Most patients interviewed appeared unaware of the broader scope of palliative care and benefits it could offer; those who were aware, attributed their knowledge to doing their own research, rather than being informed by healthcare providers.

Communication about palliative care with patients.

While phase I staff acknowledged the importance of – and their responsibility in – discussing palliative care, there was no systematic integration of palliative care conversations within the phase I trial setting. Conversations about palliative care were rarely held in the context of the phase I trial setting, either remaining unaddressed or being postponed until patients’ condition worsened significantly, in which case staff would refer to palliative care specialists who would thus only be involved reactively in their care trajectories. They also noted that the study population has a particularly very strong will to live, indicating to them that discussing palliative care is likely not welcomed. Some phase I staff felt that the context of a phase I trial did not easily allow for a focus on palliative care:

“Yes, I think, time-wise. We have to discuss a lot of practical things, a lot about the study. Hm, and it also falls somewhere within that… but it’s also about balancing giving hope while we are focused on the side effects, right? Yes, sometimes that just falls by the wayside, I must say.” (Phase I physician)

Taking into account this difficult context, phase I staff often indicated that the task of bringing up palliative care may be more suited for the referring oncologist, as patients typically do not remain sufficiently long in the trial to build up a strong connection:

“In phase I, [palliative care] is not immediately actively started, I think, or only rarely. Because those patients are usually referred by the treating oncologist, since you’re somewhat the interim oncologist. They’ve usually been in a palliative trajectory for quite some time. So I’m not with the patient... That might be something I pay too little attention to. But with the idea that, yes, that might already have been started by the treating oncologist.” (Phase I physician)

However, referring oncologists noted that referral to a phase I trial was a barrier for them to start such conversations, as it seemed too much of a mixed message to the patient to them. Importantly, some healthcare providers, whether phase I staff or referring oncologists, expressed that they did bring up palliative care with their patients, but attributed this to a personal conviction of its benefits rather than a systematic approach. When palliative care was addressed, many healthcare providers avoided using the term ‘palliative’, instead opting for more neutral language such as comfort care. However, some providers, mainly palliative care specialists, expressed the importance of using the term ‘palliative’ as to avoid the patient not understanding the severity of the situation, while offering an explanation to the patient of what the term precisely entails.

Communication about palliative care between healthcare providers.

Information exchange about palliative care between healthcare providers was inconsistent. While the referring oncologist is asked to provide a large amount of information to the phase I unit upon their referral, details on palliative care status, needs, or conversations are neither asked, nor systematically shared. While some oncologists chose to provide this information organically, this was limited and based on personal conviction rather than standardized practice. As such, phase I staff also often were unaware of whether palliative care conversations had been held with the patients prior to their enrollment in the trial trajectory, or even whether palliative care support at home had been set up:

“(Are you aware of whether, when people come here, [palliative care] has already been discussed?) I don’t always know that. Usually or often it is, but not always, or they haven’t remembered it. But I don’t know in advance, systematically, what they already know about it and what they don’t.” (Phase I physician)

During the phase I trial, communication between the phase I unit and referring oncologists or GPs was notably limited. Although a system of notification letters is used by the phase I staff to keep the referring oncologist or GP up to date, the latter groups lamented the lack of useful information shared through these letters, often focusing on highly specific medical details and not including any information on palliative care. Referring oncologists noted that they often ‘lose’ a patient once they start participation in a phase I trial, even though they feel they might play a role in further follow-up, including palliative care. GPs specifically felt that a lack of communication resulted in them not being able to take up palliative care conversations with the patient, which they deemed to be a core task given their often longstanding relationship with the patient. Instead, they typically only see the patient once they are already dismissed from the trial, often much later than they had preferred to still play a meaningful role in their care. Patients indicated that once they started the oncological trajectory, their oncologist became their primary point of contact, leading them to less frequently visit the GP.

Perceived benefits of integration.

Patients typically indicated having no need for palliative care – at least at the stage where they were at. Informal caregivers were generally more open to the idea of standardized integration of palliative care in the phase I trajectories, noting that they themselves also had information and psychosocial support needs resulting from the patient’s illness. They also expressed that some patients may not be sufficiently assertive to demand forms of palliative care if it is not actively offered to them. Healthcare providers identified several potential benefits of integrating palliative care into phase I trials, mainly centered around providing less aggressive care and broad forms of advance care planning. Normalization of palliative care could make them more accessible to patients and families – but also offering a clear framework for discussing palliative care to support healthcare providers who may be uncertain about how to broach the subject. Specifically, improved visibility of palliative care was noted as an important benefit, as many patients still remain unaware of the scope of palliative care and what it can offer them:

“Yes, exactly, that we, yes, that visibility, that people know it exists and where they can possibly turn to and where it’s located. I think that can indeed be improved.” (Phase I physician)

A standardized approach could prevent difficult conversations from being delayed until crisis moments, with improved expectation management being highlighted as an advantage, especially with the only small chances of effectiveness in mind:

“We still offer a trial option, so there’s still hope, but actually, that’s only a small hope. And what if it goes wrong? Then we’re suddenly back at the point where there are no options. So that can be anticipated.” (Oncologist)

Enhanced interdisciplinary communication was also viewed as a benefit, with a more integrated palliative care approach potentially ensuring that referring oncologists, GPs, and phase I teams remained aligned. GPs specifically felt that they had a more active role to play, yet were not given the opportunity to do so, as illustrated by the following quote:

“I’ve experienced too often that patients die during the study. And where I then felt, darn, I would have wanted to be involved, to tell the patient: don’t you see that what you’re doing is pointless? Patients still die while receiving treatment.” (GP)

Barriers to potential integration.

Both patients and healthcare providers felt that bringing up palliative care while still receiving treatment could be perceived as giving conflicting messages, undermining patients’ hope for therapeutic benefit that in turn influences their wellbeing. This conflict was at the heart of almost all interviews conducted:

“I know that we are supposed to do advance care planning earlier, on paper, but just imagine sitting in front of a patient to whom you are still offering a treatment option, and at the same time, you have to say, ‘we should also start thinking about your end of life.’ That patient wouldn’t understand what you’re doing, because essentially, you’re giving two contradictory messages.” (Oncologist)

Furthermore, phase I staff noted that integrating palliative care is complicated by the uncertain prognosis of phase I trial participants, many of whom are still in relatively good condition while in the trial, once again undermining the context necessary to start palliative care conversations. Conflicts were also intrinsic to the phase I staff, as illustrated by the following quote of a phase I physician who admits that despite the realization that trials have a small chance of success, the balance between this fact and their therapeutic role is a challenging one:

“I think we’re too focused, that we let it appear as if it’s curative, too much still. I notice a tension among our doctors as well – that’s what we struggle with as a team.” (Phase I nurse)

The current lack of communication and continuity in treatment between these providers also presents a barrier to this integration. Finally, healthcare providers noted hindrances by resource constraints (e.g., limited time and insufficient staff) and by the current healthcare system not financially incentivizing palliative care.

Strategies for potential integration.

Healthcare providers proposed several specific strategies to facilitate the integration of palliative care into phase I trials. These mainly included different suggestions for when palliative care conversations could be systematically offered to patients within the trial context. Some suggested scheduling a standardized palliative care conversation at trial initiation with a palliative care specialist, although many participants pointed out that the early stages of the trial are overloaded with information and that, for example, a month after initiation would be better suited. Others felt that it had to be offered at the end of the trial, at a minimum:

“I think that upon ending phase I studies, regardless of whether it’s a decision by the patient or exclusion due to medical study-related results, a conversation about palliative care and end-of-life decisions should be offered.” (Palliative care specialist)

Crucially, healthcare providers agreed that trajectories of patients, specifically with palliative care in mind, are too diverse in terms of prognosis and condition to strictly adhere to a structured approach – patients may not be open to such conversations. However, providers agreed that while palliative care should not be pushed onto the patients, it should nevertheless be more systematically brought up to note its potential benefits, with this currently being a missed opportunity due to patients not receiving the information they may, at some point, need:

“I think you mainly have to offer [palliative care], that everyone should offer it a bit, and I think it’s not bad if it’s also offered somewhat in phase I, I think those people are very much in survival mode, and if that doesn’t work, then they fall off, and then, well, if they don’t know that safety net of palliative care exists, that’s very unfortunate.” (Oncologist)

Other suggestions focused on practical tools. The development of a protocol outlining when and how palliative care should be introduced was suggested as a means to ensure consistency across providers, as expressed succinctly by the following GP:

“Protocoling isn’t just about rules. Through a protocol, you develop reflexes.” (GP)

Providing patients with accessible information about palliative care resources and incorporating quality-of-life monitoring tools, such as through standardized checklists and through utilizing the questionnaires that patients already have to complete for study purposes, were also recommended. Finally, electronic medical records were suggested as the most feasible way to improve information exchange between oncologists, GPs, and phase I staff, in language that is understandable for every healthcare provider and related to palliative care discussions.