Resource intensive nature of trials including adults with impaired capacity
Trial set up was frequently reported to be prolonged for trials involving adults lacking capacity due to additional delays associated with preparing alternative forms of documents and for gaining ethical approvals. In addition to standard participant information sheets (PIS) and consent forms, trials including adults lacking capacity had to create versions of the PIS for consultees and legal representatives, and an alternative consent form or consultee declaration form. Some trials used the same version for both personal and nominated/professional consultees and legal representatives, whilst others developed separate versions. Some trials also created accessible information for participants with cognitive impairments (e.g brief summary, pictorial or easy read versions, video format). The development and document control aspects of multiple documents required additional resources, particularly to ensure that effective public involvement was undertaken, and where versions translated into other languages were also being used.
“[A trial] where maybe you need only two information sheets, it is quicker. But for this, I think last time we probably submitted about ten or twelve different information sheets, and you want to consult with different people, you want more time to consult with not just a lay group, you probably want to consult with [care home] residents and with staff and with relatives. So, there's a lot of work to do to do it properly I think which we’d probably skimp on because we just don’t have the time.” [ID 06, TM]
However, it was the additional delays around ethical approval, particularly where there were sites in Scotland as well as England and Wales, that was reported to have the greatest impact. Again, this was adversely affected by a lack of expertise in conducing these trials.
“We have tried to maintain the same protocol across both nations because I thought at the outset that that might be easier. With hindsight it probably wasn’t but the advice wasn’t there when we set off, so we had to just do what we felt would work. Essentially, we've got a different IRAS number for the capacity elements of the study in Scotland and not the rest of it, and we almost have two complete document sets now.” [ID 17, TM]
The dual ethical approval processes meant that applications were reviewed sequentially - in England and Wales and then Scotland where only one NHS REC reviews research involving adults who lack capacity – which impacted on opening sites and potentially having to re-submit documents where one REC required changes but not the other.
“So that in itself was quite tricky because for a while we had ethical approval in one country, but we didn’t have it in the other and then if we had any amendments they had to go separately and then we had to wait.” [ID 20, STM]
Differences included terminology and who could act as an alternative decision-maker, as well as processes of establishing if a participant lacked capacity to consent. For example, in Scotland certificates of incapacity are issued under the AWI [25], and so protocols and context-specific site training needed to take account of these differences. Some trials reported having very high numbers of different consent and information documents. Where trials involved emergency situations, it became even more complex, with accompanying additional uncertainties over timescales.
“Scotland have slightly different guidelines again, so we’ve had to kind of model pathways that are as universal as possible but representing the differences. But obviously, there is the worry that they may disagree with our process, in which case you’ve then got to go back and potentially start that process again, you know, in terms of protocol and so on.” [ID 22, STM]
It also led to knock on delays such as database development which was already complex due to the array of forms required, multiple addresses (participant, consultee) to be stored, and potential changes to data collection (self-report, proxy completed) over time.
The additional resources needed to recruit adults with cognitive impairments was also highlighted by participants. This included the additional time needed to provide information about the trial to the person with the cognitive impairment, and to check their understanding which in turn might lead to the need for an assessment of their capacity to consent.
“It’s knowing that sometimes you have to take time with patients to be able to absorb the information. So, it’s not always a straightforward you can go and complete a consent form with someone. It might be that you go back and forth a few times to allow them to retain the information that they need about the trial. I mean it’s expected but sometimes, you know, we are under pressure to recruit a lot of the time.” [ID 16, research team lead]
Assessing whether a participant had capacity to consent to the trial required additional time and also necessitated having trained and experienced personnel to appropriately conduct assessments. This was viewed as particularly challenging in populations where capacity fluctuated and for interventional trials which required complex information to be understood. Only a few participants reported having a specific process to follow in a trial. Some described the use of cognitive tests such as Montreal Cognitive Assessment (MoCA) or Mini-Mental State Examination (MMSE) to inform their capacity assessment when the test was already being used in the trial, or applying the principles of the MCA to conduct an assessment. Although some reported the challenges of assessing capacity.
“So, I found it very difficult, if not impossible, for me, as a researcher, to be able to assess their capacity. I mean I’ve never done any kind of formal mini mental state exams or anything like that. Any kind of formal capacity assessment other than following the principles of the Act… so I go by those principles rather a kind of battery of tests which I know that other people have done.” [ID 02, care home researcher]
Others described using the judgement of colleagues who may have been more experienced in assessing capacity or with this population, or the person’s usual care team who may have been more familiar with the person, which all took additional time. As the assessment was often recorded on study-specific forms in addition to the person’s clinical care records, additional trial documents were needed.
Having assessed a potential participant as lacking capacity to consent, recruiting staff then needed to identify and approach someone to act as a personal consultee or legal professional. This was considered to be the most resource-intensive part of recruiting adults lacking capacity. In non-emergency trials recruiting in secondary care settings this was generally more straight-forward, although it may still have required multiple attempts to contact a family member. However, it was especially time-consuming in settings where family members may not be available or are not in close contact such as in care homes, or where there was little way of contacting families such as remote recruitment in primary care. Even once a family member had been identified, there were issues around non-responses that led to uncertainties about whether the family member had received the information, was not willing to act as consultee or legal representative, or if this should be interpreted as a passive form of declining participation on the person’s behalf. This led to potential participants being left in a ‘state of limbo’.
“I may have gone out [to the potential participant’s home] and realised that that person may need a personal consultee, but there wasn’t anyone that they lived with, a spouse or anyone, or a family member in the home. So, I would then often leave the personal consultee information and I would write my name and number on it and sometimes I would get contacted, other times I wouldn’t. But then you don’t know whether that information’s been seen, or acted on, or whatever.” [ID 08, researcher in older people]
If no family member or close friend could be identified, an additional process was needed to identify and approach someone in a professional capacity to act as a consultee or legal representative. This could be a member of the person’s usual care team, e.g the doctor responsible for their care or a member of care home staff, provided they were not involved in the trial.
“We kind of go down the route of trying to identify a [care home resident’s] family member or friend to start with, and in most cases, there would be somebody that we can send information to initially. We would send information out to them, give them a couple of weeks to contact us or to send back their agreement form, and then we’d send out a chase, and then if we hadn’t heard anything another seven days after that, then we’d go down the route of identifying a nominated consultee.” [ID 06, TM]
In some care homes, a suitable member of the care team would be identified once a consultee or legal representative was needed, in others it was a pre-delegated and one member of the care team would take on this role for all residents if needed. Not all care homes or staff were comfortable with this process however, and some required additional explanation and reassurance or did not wish to use this approach in their care home. In secondary care settings, some research nurses reported having prospectively created a pool of colleagues to act as potential consultees or legal representatives which facilitated the process. This sometimes took the form of a log that was maintained by the research nurse and was considered particularly useful in time-sensitive trials such as those involving trauma. It was viewed by some as a way for clinical staff to get involved in supporting research without the requirements of GCP training. It was reported that some felt reassured that it was an interim arrangement as consent would later be sought from the patient or their family, although there was no guidance or support for this role in any of the trials.
“They know that it's only a finite consent that they're giving because the next step will be either the participant themselves if they agree [when] gaining capacity, or the relative. And the professional consultee only stands if the patient dies.” [ID 13, research nurse]
Participants also acknowledged the additional time required for collecting data and completing outcome measures both with participants with cognitive impairment and when proxy reported.
“Obviously a lot of them are having to sit down and fill out measures with staff, it's not just handing out, you know, if you were doing a trial in an adult population, or something, you just give them a load of questionnaires to fill out themselves and it just doesn't work like that for studies where you've got to get staff to do proxy measures, or you’re getting self-report from people with dementia, you're having to sit down with them to do that.” [ID 15, CI]
These resource implications and the need to meet expected or metric-driven recruitment rates sometimes resulted in participants feeling under pressure to recruit more quickly or to find alternatives to including participants with impaired capacity.
“Oh, you’ve only recruited such and such an amount? Like what’s the delay can you not just move it on? I think with this population things take longer, and recruitment takes longer, there’s more people involved, there’s extra things to be sensitive, mindful about. Yeah, wouldn’t it be easier if we could just talk to their parents or talk to their support workers and get their answers, but just because something’s easy doesn’t mean it should be that way.” [ID 03, learning disabilities researcher]
Having adequate support and resources was seen as a key facilitator, and some participants described how their experiences had led them to build in additional resources when developing funding applications, beyond those usually available through R&D departments or clinical research networks.
“We funded a half–time research nurse at every site because of the difficulties in working with these patients and their families, and the sorts of visits that were needed, going out to their homes. It was quite intensive so that was funded on the grant.” [ID 20, STM]
However, the competitiveness of funding applications that need to be seen as offering value for money alongside other trials with populations which are more straightforward to recruit was a significant challenge. Participants also reported the challenges of having caps for particular funding schemes, e.g the tiers in NIHR Research for Social Care (RfSC) and Research for Patient Benefit (RfPB) programmes, which did not take account of these additional resource requirements. This was particularly the case where the research was conducted in non-NHS settings such as care homes and so did not have equitable access to research delivery infrastructure.
The challenges of pressure to conduct more inclusive trials, with limited funding and resources available to adequately support inclusion, was also highlighted as a barrier to both conducting trials involving adults lacking capacity and other under-served populations in general.
“Sometimes you have to bear in mind you need to get the numbers, but you also need to think about inclusivity with that …. I don't think resources is the reason not to do it, but it’s got to be a consideration. You know, you can't ask for the world and not fund it.” [ID 12, qualitative researcher]
The role of funders and grant reviewers in encouraging inclusive research was welcomed, however the responsibility to conduct more inclusive trials was viewed as being shared between funders, RECs and research teams.
“Applications where you force people to think about how [they] have they addressed inclusivity and then also being willing to provide funds to support those extra [requirements], because it does take time and the cost in some cases is huge. I think making researchers think about it earlier, but funders also being prepared to allocate resources to support that I think is key.” [ID 25, STM]
Effective communication processes
Participants described the role of effective communication in successfully conducting trials involving adults lacking capacity. This included communication between members of trial teams when designing and co-ordinating trials, but also the importance of two-way communication between the trial team and those delivering the trial at research sites to ensure that key messages about the barriers being encountered and strategies to overcome them were being fed back. It also included communication between clinical staff and research staff at sites to more closely integrate research and clinical care and to ensure that potential participants and their consultees and legal representatives were being identified and communicated with.
“We’ve got quite close links with the Trauma Coordinators, they’d be like I’ve already spoken to [the patient’s] next of kin, and she’s happy, here’s her number, and what have you. It’s about communicating as a whole team and to discuss it with colleagues and trial offices about the problems and things that were working well and things that weren’t.” [ID 18, research nurse]
Communicating with potential participants with cognitive impairment was viewed by research nurses and others involved in recruitment as requiring confidence and experience, as well as having accessible information to facilitate information provision. This included the use of summary information sheets as well as alternative formats which could be used to scaffold information about the trial and enable to person to express their informed views about participation where possible.
“We did actually have an aphasia friendly information leaflet for those who didn’t have capacity [to consent] but had some capacity to understand the study. It was a large font, so it was fourteen point, one and a half times spacing, the layout was in boxes with images, so that was all broken down.” [ID 19, TM]
Other strategies to overcome communication difficulties included approaching the person when family members were present who could support the person to understand the information and make a decision about participation where possible, or the involvement of interpreters where language was considered to be a barrier. Where research nurses considered a communication disorder to play a role in capacity and decision-making, particularly for people who had experienced a stroke, some reported seeking the involvement of a speech and language therapist (SLT) or tagging their discussion about the trial onto the end of a routine SLT session where possible.
Effective communication was also viewed as an important part of engaging with family members who were approached to act as a consultee or legal representative and was considered to be particularly challenging when the approach was made remotely e.g via post, or when usual care teams had to be relied upon to send out information about the trial due to data protection requirements.
“You don’t want to harass the relative. So, unless the relative contacts us, we can’t contact them. So, unless the relative says, I would like some more information about this, we can’t give them more information even though we’ve written to them. I naively said, ‘Well why can’t we ring them up a few days later, and check they’ve got the letter and ask them what they thought about it?’, but you can’t do that.” [ID 11, CI]
The challenges of family members making a decision about participation on the person’s behalf was also seen as a barrier, primarily around how families can be orientated to base their decision on the person’s wishes and feelings rather than their own views, and how they might access those wishes in the absence of explicit discussions about research participation.
“I think it's hard to try and say what that person would want if you haven’t specifically had that conversation with them previously about whether they'd want to be involved in research or even what types of research. It's difficult when you're asking someone to consent on behalf of someone else, they are always going to have their own views, and it's difficult with the best will in the world, to make a decision based purely on what someone else would want and not what you would want.” [ID 01, research governance lead]
Building a rapport with family members and using a person-centred approach to discuss what mattered most to the person was viewed as a useful approach to supporting the family member to make a decision based on the person’s wishes and feelings.
Issues around communication were also raised when there were changes in a person’s capacity status during a trial and consent was revisited. This including the use of a ‘deferred consent’ model where the person was enrolled without prior consent (or through brief verbal consent) during an emergency and then consent to remain in the trial was sought from them once they had recovered or their family approached if not [43]. In these situations, they had received the intervention at the point they were approached, and so they were informed about their participation and were asked to provide consent for data collection to continue. Participants recognised the sensitive and potentially challenging nature of these discussions, and the need to tailor the timing and approach to the context and the person’s ongoing health needs. Research nurses highlighted the importance of maintaining a relationship with the person and their family and the care team throughout their time in a study, including regular bedside conversations when completing visits to the ward for data collection. This also provided opportunities for ongoing assessment for any changes in capacity. Participants reported rarely encountering anyone who declined to continue in a trial, with high levels of acceptability towards the consent approach used, although there were instances of people being discharged or transferred or dying before consent could be sought.
“At the time we get to them all the work has been done, so it’s just asking consent to keep the data and I’m always surprised at how accepting people are. It’s very rare that we have somebody that is really unhappy about what has happened, once you sit down and explain to them. And many patients are really happy that they’ve been able to contribute to improve treatment for somebody like them in the future.” [ID 16, research team lead]
Good communication with RECs was also seen as facilitative, and research teams described how building a relationship with particular RECs meant that there was a shared understanding about the ethical issues involved and how trials could best be designed to overcome these. However, this supportive communication with RECs was not experienced by all researchers, with some expressing frustration with the process and the inability to discuss these complex applications in detail or in advance of submitting an application.
“One of the panels didn't seem to get it at all, and it was like really difficult to try and explain. The other problem is that when panel's running behind they might not allow enough time and so when [the researchers] got into the room, they've got like five minutes and so they didn't get a chance to answer, be asked or answer any of the questions or explain anything, so it was all very rushed, and not having a chance to actually talk through the study and have a conversation about it.” [ID 15, CI]
“What would have been useful, and I don’t know whether it is accessible, is contacting REC beforehand to kind of talk through that proposal because, obviously, if we had had that conversation and they’d gone, well, you need to make these changes. Well, that could have just pretty much saved us probably two and a half, three months. That’s a massive amount of time.” [ID 22, STM]
Use of adaptive strategies including COVID-19 related adaptations
The importance of designing in flexibility in a trial, and adapting processes in response to challenges encountered, was seen as key to the successful delivery of trials with this population, including in response to the pandemic. Participants expressed how COVID-19 had presented particular challenges which highlighted the need for adaptive strategies in response to the high numbers of acutely and critically ill patients, the introduction of Urgent Public Health studies with a pause in almost all non-COVID trials, and universal infection control measures. Challenges also included the involvement of research-naïve and redeployed staff who required rapid general research and trial-specific training that was sufficiently comprehensive but minimally burdensome. However, the greatest impact was the stopping of all hospital visitors which included family members who would act as consultees and legal representatives. Participants reported a change in many trials towards enabling remote forms of consultation with families through email, phone calls and video calling which facilitated the recruitment of people who lacked capacity to consent. This included COVID-19 trials as well as amendments to non-COVID trials in other settings such as care homes and the community. COVID-19 was seen by some as a driver in enabling long-awaited advancements in trial conduct.
“I think there was question about whether that [the use of professionals as nominated consultees] could happen, but since COVID that has now come in as being acceptable and they’ve had a substantial amendment on the trial to allow for professional consultee to be enough.” [ID 13, research nurse]
Research nurses talked about the value of sustaining this flexible approach and embedding it in more trials in the future that recruit adults lacking capacity.
“It would be better to have a few more [studies allowing] consent that we could do over the phone with relatives. Because it’s something that we’ve found to be quite helpful to have with some of the COVID trials and they’ve adapted some of the non-COVID trials as well. But many of our trials don’t have that at all.” [ID 16, research team lead]
However, others reported that the challenges of communicating about the trial with these populations and those who care for them may not be easily addressed through these adaptions which limit personal interaction and the building of relationships.
“In the original study, we were going into the [care] home. We were going to meet people face to face and now we’re trying to do that remotely via Zoom, so it’s sort of turned into a different animal. In a way that also brings subtle changes to the way you engage with people. Very, very different.” [ID 11, CI]
Research nurses described the challenges of communicating about a trial with patients with COVID-19 who often had impaired capacity due to hypoxia or other conditions. This was intensified by the requirement for research staff to use PPE and reduce physical contact which limited non-verbal communication, and patients requiring respiratory support such as CPAP (Continuous Positive Airway Pressure) hoods which made it difficult for them to hear above the noise and meant that patients who usually wore glasses may not have been able to read information about the trial. Even research nurses who were familiar with impaired and fluctuating capacity in a range of conditions described the more complex nature of assessing hypoxia-related capacity impairment. Other COVID-19 related challenges included the infection control risk from contaminated paper consent forms which necessitated alternative approaches such as photographing or quarantining completed forms, or the use of witnessed verbal consent or e-consent with people with capacity as well as consultees/legal representatives for those who lacked capacity. However, the use of digital tools such as email and video conferencing raised additional concerns about the exclusion of those without access to such technology.
Outside of secondary care, challenges included care homes closing to all non-essential visitors which included research staff, and ‘lockdown’ restrictions which prevented research visits in primary care. For trials that remained open, this necessitated a rapid change in contact methods with potential participants, their families, and sites such as care homes, which could also be affected by limited digital access and poor connectivity issues. It also presented new challenges such as having to undertake virtual assessments of capacity which were unfamiliar to researchers.
However, research nurses reported a positive impact from COVID-19 where the high-profile and urgent search for effective treatments for this novel disease meant that there was a high awareness about research in the general public. This facilitated discussions about trial participation with both patients and their families when contacted. COVID-19 adaptations also removed geographical location as a barrier to participation in some instances and led to greater embracing of digital technologies for some groups. This was seen in a study involving people with learning disabilities which originally recruited through local advocacy groups but switched to online recruitment and data collection.
“So originally, because it was meant to be face-to-face around [local area], when they went on-line it was actually an opportunity because they were recruiting people from all over. There’s people who weren’t involved in any of the advocacy groups prior to the pandemic, but then they’d been looking for like social lifelines and they are now [participating].” [ID 03, learning disabilities researcher]