Support systems29 December 2020
For years, the patient-centric promise of the decentralised trial was little more than a utopian dream. But, with a global pandemic keeping people in their homes, 2020 brought the model crashing into capricious reality. Mae Losasso speaks to Jennifer Goldsack, executive director of the Digital Medicine Society (DiMe), Gareth Powell, business development offi cer at the UK’s National Institute for Health Research (NIHR), and Olivia Barnes, senior research nurse at Sherbourne Medical Centre, UK, to assess how these trial designs can best approach the delicate issues of community, sociability and psychological well-being.
“In normal times, I’d invite you to the surgery,” Olivia Barnes explains over the phone. “I’d show you around, I’d give you a cup of tea and a chocolate biscuit. You know, I’d see you.” Barnes is a senior research nurse at Sherbourne Medical Centre, UK. Through more than 20 years in clinical research, she’s traced a range of slow, specific evolutions in dealing with patients: the gradual implementation of social media platforms, say, or text messages. But, in 2020, those minor adjustments have become tectonic shifts. “Mostly, everything was done here by myself and the principal investigator,” she says. “Everything to do with the study, all the investigations, all the visits. Since Covid has happened, we’ve started to go postal or we’ve got patients to do more things at home.”
Sherbourne Medical Centre is a primary care clinic – “a family doctor”, as Barnes stresses – and the shifts she describes – to the use of take-home questionnaires, e-consent forms, and remote monitoring devices – are just the tip of the Covid-19 iceberg. As Gareth Powell, business development officer at the UK’s National Institute for Health Research (NIHR), puts it, the pandemic has been “a colossal catalyst for change”.
Back in 2019, he explains, “virtual, decentralised or remote clinical trials were seen as a potential magic bullet for overcoming the challenges to patient-centricity”, but regulators were resistant to implementing the new measures necessary to get them off the ground. Covid-19 changed that. “We’re seeing an accelerated uptake of these remote ways of working, both by necessity but also because there’s been a real driving force behind this uptake before.”
The heart of the trial
Thanks to the pandemic, Powell’s magic bullet has penetrated the heart of clinical trials around the world. As Jennifer Goldsack, executive director of the Digital Medicine Society (DiMe), explains, “There were [already] a lot of pressing challenges that decentralised approaches lent themselves to and I think that Covid has shown that there’s no reason to hold back.” For Goldsack, as for Powell, patient-centricity is the driving force. “Decentralised clinical trials are about building clinical trials out from around the patient,” she says, “rather than building them out from around the clinic.”
With such an approach comes a cascade of benefits, not only to the patient but to the trial sponsor. In the past, the necessity for in-person visits to physical trial sites meant that the pool of participants remained shallow. Effectively, recruitment was only open to those who lived within a short distance of the testing site and who could spare the time to visit. “One in five trials shut down,” Goldsack notes, “because they can’t enrol. They [can’t] question whether their drug works or not, because they just can’t get enough patients.” As she points out, it is a lot to ask someone to “schlep” through traffic to an inconveniently located clinic and pay $15/h parking for the privilege.
“One in five trials shut down, because they can’t enrol. They [can’t] question whether their drug works or not, because they just can’t get enough patients.”
“You might not be able to afford that,” she continues, “your care partner has had to take a day off work, and then you come in and you’re flustered. That’s the only snapshot [the clinician] might get of a patient’s wellbeing and their health for a month, or for a quarter. That’s what we’re making decisions about drugs on. But what if we could passively monitor patients 24/7? What if we could understand the days that are so hard that they don’t get out of bed? What if we understood the good days, when they’re able to walk up the stairs or leave the house and go to the grocery store?”
It’s hard to argue with Goldsack, but one question manifests: in all this digitising, virtualising and decentralising, what will happen to the myriad social interactions that accompany the traditional clinical trial? Goldsack is quick to respond: “I think we ascribe too much to this idea of people wanting to go running back to a new clinical trial and develop a new relationship with the trial coordinator. I just don’t see that.” But this social question reaches beyond the remit of the clinical trial, revealing the double-edged role that the Covid-19 crisis plays in this shift. On the one hand, the event of a global pandemic has exposed not only the necessity, but the feasibility of decentralised modes. They’ve played their part in keeping the global trial ecosystem from collapsing – even after three out of every four studies worldwide were stopped or delayed. Yet, medical advancements aside, the past eight months have also brought to light our irrepressible and irreplaceable need for real human engagement.
In the realm of the clinical trial, this adds up to more than just the desire to socialise; it becomes a legitimate health concern. Powell recalls a patient who saw his clinician on an annual basis and formed a very strong relationship with them. “They knew each other very well,” he says, “and he relished that opportunity to meet with his clinician.” But when the patient was informed that, due to the partial success of the treatment, these visits could be reduced, it was “a huge blow, both to the management of his condition and to the social network”.
The placebo effect
The in-person, human element of the clinical trial might be said to amount to something of a placebo. The placebo has been a mainstay of the traditional clinical trial since the mid-nineteenth century. The term first appeared in Robert Hooper’s 1811 Medical Dictionary and was defined as “an epithet given to any medicine [used] more to please than benefit the patient”. And it is this notion of the placebo – not as a dummy, but as a medicine or procedure prescribed for a patient’s psychological well-being – that corresponds with the social aspects of the traditional clinical trial. Powell picks up on this in relation to one particular demographic, noting that older populations suffer quite severely from loneliness, a major factor that can lead to “reductions in longevity and quality of life”.
Accounting for these groups is a crucial consideration in the design of clinical trials. Yet their importance also serves as a reminder of the restricted demographics of most studies. And if the use of decentralised modes might have a negative effect on one group’s sense of community, it also promises, by the same token, to help forge others. “It’s usually the older generation […] who are appropriate for clinical trials,” Powell admits, “but there are others who have chronic conditions who are much younger and who currently don’t have the same opportunities to participate: the working age demographic.” For these groups, the decentralised approach not only makes trial participation possible, but provides forms of community through social media platforms – and there is evidence to suggest that these platforms are engendering inter-patient communities on an unprecedented scale.
“With social media you’ve got very active patient groups being formed who speak to each other on a fairly regular basis,” Powell explains. The impact of such a broad and immediate support network may not, however, always be to the benefit of trial findings. “I have heard accounts where [patients] have participated in a clinical trial and say, ‘I’ve started this medication, I’m six weeks in and this is the effect it’s starting to have’, while others are saying, ‘well, I’ve not had that effect. I wonder if I’m on the placebo’.” Through these interactions, patients “start unblinding the trials among themselves […] inadvertently pulling apart that system, the RCT model, which is still enshrined as the way forward.” One variation of the placebo, it seems, is displacing another.
So, for every positive effect there is a negative one – and back again. “It’s a balancing act,” Powell offers, “weighing the burden of the condition against the burden of the trial.” In fact, Barnes, Powell and Goldsack all intone the same phrase: “there is no one-size-fits-all”. Goldsack sums this up with what she calls her cafeteria analogy. “You may pick virtual visits, you may pick a variety of different digital technologies, you may pick using a local lab to get biological testing done, you might pick a visiting nurse to go to the home.” Crucially, however, “each one should be different and thoughtful, and appropriate to the patient population you’re trying to serve, appropriate to the drug or device under investigation, [and] appropriate to the protocol”.
There were problems and challenges before decentralisation, and there will be problems and challenges to come. It might sound woolly, but it is a more honest account of the developing landscape. “I don’t think we serve our patients well, or the field well, if we take a black and white view to this,” Goldsack stresses. The best we can do is to be mindful, thoughtful and careful: listening to patients, building out from their needs and their feedback, and putting frameworks and measures in place to ensure the maintenance of human interaction where possible. And from conversations with Goldsack, Powell and Barnes, it’s clear that strenuous work is going on behind the scenes to address these concerns from the earliest design stages.Perhaps the most convincing, and immediately workable, solution comes from Barnes, who proposes a hybrid model in which the trial might only conduct the first and last screening visits at the secondary care site. “Let the patient come here for their other visits,” she says, “to their GP. I think that hybrid model would work much better. It’s not really decentralisation – or, I suppose it is in another guise.” There are impressive innovations coming out of secondary care research centres, and extraordinary work is being done to develop technologies that make these models possible. But there is something in Barnes’ clear-sighted and practical approach: bringing people back to their family doctors, building a sense of community back into the heart of the decentralised model – and maybe giving them a cup of tea and a chocolate biscuit too.