First, we present the findings of both studies according to the three main themes that were identified by Phelp’s et al [1] as influencing recruitment and retention to surgical trials – making sense, weighing up and trust. Given the significant amount of evidence that already exists around these themes [1, 4, 9-13], we present our findings using summary tables to highlight the key issues that were identified during ACTIVE and PRESTO. We then provide a descriptive account of ‘eligibility criteria’ and ‘patient pathways’; two themes that were identified as influencing recruitment and retention during ACTIVE and PRESTO which are not featured in Phelps’ et al’s review. [1]
Making sense
Randomisation
For patients to agree to participate in an RCT, they first need to ‘make sense’ of randomisation and the influence it has on their treatment and involvement in their care (table 3). Randomisation was a new concept for the majority of patients, which when described using trial jargon made the concept difficult to understand. In the most part, patients recalled randomisation, however, many had undergone significant trauma and so were heavily medicated when approached to take part in the study. As a result, patients were concerned that they lacked capacity at the time of recruitment and felt this restricted their ability to understand what was being proposed and make informed decisions. However, trial recruiters described various methods that were used during PRESTO to ensure capacity, for example, patients were asked to reiterate study aims before providing their consent.
Communication
How the trial is communicated to patients is also a critical factor influencing a patient’s decision to take part in a RCT. In both studies, the perceived quality of information sheets, information about treatment and recovery and when patients are approached to take part were pivotal to ensuring effective communication and influenced whether patients chose to take part (table 3).
Equipoise
Patients and trial recruiters provided various examples of situations where equipoise had been either deliberately, or unintentionally undermined (table 4).
Weighing Up
Patients’ decisions to participate in RCTs are underpinned by being in equipoise and their understanding of randomisation. However, these decisions also require patients to trade off various perceived benefits of participation, such as altruism against treatment preferences, personal circumstances and the perceived risks of randomisation (table 5).
Trust
If patients are to take part in a surgical trial, they need to feel confident and have trust in their surgeon and research team. When discussing how to optimise recruitment, it was considered crucial by the trial team to think about who is involved in recruitment consultations (table 6). Whilst there was agreement that recruitment consultations should involve senior clinicians and the research team, the practicalities of involving both teams in large numbers of recruitment consultations was acknowledged, with some sites opting for the research team and clinicians to approach patients independently to fit around conflicting work schedules and time constraints.
Ensuring clinical teams are engaged throughout research studies was also considered important by both trial recruiters and patients not only for ensuring the trust of patients but to maximise recruitment, particularly in studies of rare conditions where there is pressure to recruit every eligible patient.
Patient pathways
Patients are often admitted via complex referral pathways and as a result, may come into contact with clinicians from a range of specialties, depending on the specific injury (Emergency Department (ED), neurosurgery, orthopaedics) or from referring hospitals prior to being approached to take part in orthopaedic surgical trials. In PRESTO, the different ways that patients with thoracolumbar fractures could be referred to sites was a particular issue, with one site receiving referrals from up to 15 hospitals. The reduced awareness of on-going research studies, issues with equipoise and different treatment preferences of staff that are not involved in recruitment can mean that patients have multiple conversations about the treatment they are ‘likely’ to receive before official recruitment consultations and may lead to distrust in research and trial processes and/or patient’s being ‘biased’ towards specific treatments. The time between transfer of patients from local hospitals to Major Trauma Centres or hubs can mean that by the time patients are approached to take part in a research study they may no longer meet the eligibility criteria for the specific trial, for example they have already started to heal and in some cases receive non-operative treatment such as braces for stabilisation.
“We generally want to see them within a week of them sustaining the injury and a few times it has not been possible to arrange transport from the local hospital up to our centre, and that has caused patients to miss the reasonable timeframe that we would like to follow these patients, for example if they reach five to six weeks following the injury by the time to come to the clinic, then it is a moot point to then discuss surgical or operative options. Because conservatively they have reached that point in their treatment, where the fracture could have reasonable been expected to heal and we wouldn’t be doing justice to either the patient or the trial to then discuss the two separate options for them.” (PRESTO staff interview 06)
Communication between patients and specialties or clinicians that were not involved in trial recruitment was thought to have caused some patients across both studies to develop treatment preferences and view randomisation as unacceptable. Insufficient buy-in from clinical colleagues was seen by PRESTO recruiters to exacerbate this issue. Whilst attempts were made during PRESTO to increase engagement of neurosurgeons through multiple departmental presentations the difficulties of asking for a culture change ‘ahead of evidence’ was acknowledged particularly given the issues with surgical equipoise, the comparatively low levels of research activity in neurosurgical departments and the fact that neurosurgeons routinely provide the perceived less resource intensive option of conservative management.
“The neurosurgery team here are not the most helpful. (Laughter) I don't know whether that's because we haven't communicated the study very well or whether that's just their mentality to research. We have decided that we will do a presentation to them again to make sure that it's not a fault on our side. You'll probably hear (name of staff) talk about this as well, but we did notice a couple of the patients that we were screening were being reviewed or presented in A&E and then neurosurgery registrars would be going down to review them on the request of A&E doctors. Then they would discharge them from there, so they weren't getting admitted, which meant that those patients who have been told that they don't need to be managed with an- they essentially just get discharged with a brace. A couple of those patients we, potentially, could have included in PRESTO, but because we missed them due to- I guess the registrars were completely unaware of the trial.” (PRESTO staff interview, 10)
There were particular concerns amongst recruiters in both trials that treatment conversations between patients and EDs lead to patients being ‘biased’ towards a specific treatment. In addition to undermining equipoise, one patient described how receiving a call to return to hospital to discuss the possibility of surgery and participate in a trial after being discharged with either no or conservative treatment caused anxiety and provided a poor standard of care. Engaging ED doctors ahead of a full trial was considered a particular challenge given the pressure on ED to treat patients quickly to avoid affecting performance targets and the fact that patients are often admitted ‘out of hours’ which was perceived to increase the likelihood of patients being seen by doctors with a lower awareness of research studies based in other departments. High staff turnover, particularly of surgical registrars meant that Junior Doctors were also considered to be prone to inadvertently influencing patient expectations and be unaware of ongoing research protocols.
“Unfortunately these fractures come in late at night or early in the morning and they’re already seen by a junior member of the team. The junior staff change over so frequently, they’re not aware of the trial, and they just go by…..meaning for stable fractures don’t fix, for unstable fractures, fix, because that’s what you’ve been taught traditionally. Once they’ve told them in A&E that they don’t need an operation, because this trial is all about stable fractures, then it is quite difficult to convince the patients otherwise.” (PRESTO staff interview)
Variation in current practice and strong treatment preferences meant that the influence of ‘local logistics’, having strict eligibility criteria and carefully considering how to approach sites in future trials was considered crucial. Presenting a future trial, planned protocol and eligibility criteria at key clinical meetings was also suggested as a means to secure buy-in from the clinical community. Importance was placed on having centralised centres for recruitment with it considered unfeasible for referring hospitals to be involved in recruitment, engaging staff from other specialties at recruiting sites was considered important. Despite this, there were doubts as to the feasibility and implications on time and resources of involving multiple specialties in recruitment to a future trial a number of suggestions were proposed and are displayed in table 7.
Eligibility criteria
Difficulties operationalising eligibility criteria were reported across both trials and were largely due to clinical teams interpreting clinical criteria differently. For example, in PRESTO, there was a lack of consensus as to what constitutes a stable thoracolumbar fracture, whilst in ACTIVE there was disagreement as to the definition of an open fracture. Other factors which were perceived to affect the number of eligible patients during PRESTO included: difficulties obtaining consent and completing study documentation for patients for whom English is not their first language; mental health; frailty; patients living in a different area to the treating hospital and so wanting to be followed up locally and patients at high risk of infection or of encountering wound problems and wound breakdown. It was however suggested that staff may be ‘hiding behind personal biases’ rather than excluding patients for ‘objective reasons.’ Despite having screened approximately 80% of the predicted numbers of patients overall in the PRESTO study, surgeons reported that the target population was smaller than anticipated - the majority of patients were either considered ‘very stable’ or ‘very unstable’ therefore far fewer patients met the eligibility criteria than was predicted.
“I guess, perhaps, that will be much more useful to look at, at the end, when we see the trends really clearly and you can say, “Well, okay, this was a huge number of people we excluded for this reason. Was that actually justified, in terms of the science that we have out there at the moment, to say, “This group of patients should have been managed as they were, and excluded”?” (PRESTO, staff interview)