Alpha-Stim-D trial study design and participants

The Alpha-Stim-D trial was a large multi-centre double-blind randomised controlled trial evaluating the clinical and cost effectiveness of the Alpha-Stim AID cranial electrical stimulation (CES) device for patients with depressive symptoms in primary care. The design and methods are outlined in more detail in a published trial protocol paper [22] and trial findings [23].

Recruitment and retention strategies

Ethical approval was granted in February 2020 from the East Midlands—Leicester South Research Ethics Committee (REC Reference: 20/EM/0061). A month prior to the first UK COVID-19 lockdown, GP surgeries reported that there would need to be a minimum 6-month recruitment delay because they were under extreme pressures. Subsequently, the monthly recruitment rate had to increase from 10–12 participants to 13–14 participants to meet the recruitment target on time.

A diagram of participant flow to the Alpha-Stim-D trial is shown in Fig. 1.

Fig. 1

Alpha-Stim D trial participant flow

A total of 4921 invites were sent between September 2020 and November 2022 (27 months) and 555 (11.3%) responded. Of these, 61 (11.0%) were not eligible and 183 (33.0%) declined to participate or were not able to be contacted. A further 75 (13.5%) were excluded during completion of the baseline assessment. In total, 236 participants (42.5%) were recruited to the trial, slightly exceeding the recruitment target of 230. An additional six participants were recruited because their baseline assessments had been pre-booked before the recruitment target had been met. We also maintained a high retention rate of 84% at 16-week follow-up; this was almost 10% above an anticipated follow-up rate of 75%. This led to a larger pool for analysis (199) than was required in the sample size calculation.

Figure 2 illustrates the modified recruitment process to facilitate recruitment because of COVID-19 restrictions.

Fig. 2

Modified recruitment process

Table 1 provides a breakdown of target versus actual participant recruitment throughout the trial. Although the trial recruited to time and target, the initial recruitment plan was adapted to the evolving situation of the COVID-19 pandemic. Following the initial 6-month delay to recruitment, the first modification was made to introduce remote recruitment approaches (strategy 1).

Table 1 Revised target versus actual monthly recruitment figuresStrategy 1: remote recruitment processes (September 2020–January 2022)

Following the government imposing a national lockdown in March 2020 due to COVID-19 pandemic, a substantial amendment was submitted to the Health Research Authority (HRA) Research Ethics Committee (REC). Changes made to the recruitment approach consisted of offering assessments remotely—over the telephone or via Microsoft Teams to minimise face-to-face contact and overcome COVID-19 restrictions. The added benefit of remote completion of assessments was that it provided greater flexibility for participants and study researchers and reduced logistical barriers. Initial training on the use of the device was anticipated to be at the GP surgery by a healthcare professional. To overcome this, an instructional training video was developed in collaboration with a Patient and Public Involvement and Engagement (PPI/E) representative, which provided instructions on the use of the device and offered tips whilst showing participants how to log device usage. This enabled devices to be directly posted to participant’s homes and for participants to be able to view the instructional video on YouTube (https://youtu.be/5eti64s0hys). The research team arranged for devices to be sent directly to participants home by the distributers along with pre-paid envelopes so that they could return the devices with no additional cost incurred to them.

Table 1 shows that, in the first few months of recruiting using opportunistic methods at primary care consultations, recruitment rates were under target with 37 fewer participants than required recruited by month 4, which is not uncommon in RCTs [24]. Recruitment figures then increased steadily and 90 participants had been recruited by month 9. Eleven months into the trial (end of July 2021), with only 6 months left to recruit, 118 participants (just over 50%) had been recruited, indicating a need for further efforts to improve recruitment. Strategy 2 was then introduced.

Strategy 2: utilising multiple referral approaches (May 2021–November 2022)

During the initial set-up stage of the trial, GPs suggested that an opportunistic approach whereby potential participants were approached about the study, based on clinical knowledge during consultation, would be most feasible. This approach was perceived to be straightforward and require minimal input from GPs, as they only had to obtain verbal consent to being contacted from participants and share contact details with the study researchers.

As shown in Table 1, 6 months into the trial study researchers recognised there was a need for additional methodological changes to be implemented to increase referral rates, particularly as fewer face-to-face mental health consultations were taking place. Therefore, systematic recruitment as a referral approach was introduced. This referral approach consisted of a search being conducted by GP surgeries of patients’ primary care medical records to identify potentially eligible participants. A letter of invitation, participant information sheet and a pre-paid envelope were then sent from the GP surgery. Interested patients were asked to complete an expression of interest form and return this to the research team.

Figure 3 shows the number of postal invitations sent out by GP surgeries; there was an increase between May 2021 and July 2021 and again from September 2021 which peaked during November 2021 (1600 postal invites were sent in November). This increase in referrals translated into the largest number of participants being recruited in November and December 2021 (26 and 37 participants respectively) as shown in Table 1. This highlights the effectiveness of the postal invitation referral approach in comparison to the opportunistic approach that was primarily relied upon prior to May 2021.

Fig. 3

Number of postal invitations sent out

We believe that in addition to the recruitment methodological changes utilised due to COVID-19 pandemic, the following additional strategies (3 and 4) contributed to successful recruitment and retention of clinicians and participants.

Strategy 3: collaborative working from study inception to dissemination (November 2019–January 2023)

An integral aspect that led to successful recruitment of the Alpha-Stim-D trial was collaborative working, which involved GP surgeries, Clinical Research Networks (CRNs) and Patient and Public Involvement and Engagement (PPI/E) representatives.

GP surgeries

The study team recognised the importance of setting up initial meetings with staff at GP surgeries to introduce the trial. Due to the COVID-19 pandemic, all meetings with recruiting sites took place over Microsoft Teams. Study researchers highlighted the benefits of taking part in the research and clarified the trial processes. GP surgeries were also informed that in line with recommended NHS service support for research they would receive £94.92 for each participant recruited; this was to reimburse primary care staff for their contribution and time. Where possible, a member of the GP practice team was designated as the main point of contact who would liaise with the lead researcher with referrals and any queries. Trial processes were kept simple and clear for primary care staff to keep their workload to a minimum.

We regularly updated GP surgeries in terms of recruitment figures and sought feedback on any recruitment challenges experienced. We sent out newsletters to all participating sites updating them on recruitment progress and commending top recruiting sites. Between November 2021 and January 2022, a total of 74 participants were recruited enabling us to meet our recruitment target 14 days ahead of time.

Clinical Research Network (CRN) support

The study was adopted onto the NIHR research portfolio and, as such, was eligible for CRN support. However, between April 2020 and August 2020, CRN support was restricted to COVID-19 studies only. This meant that CRNs could not support the trial in terms of releasing their staff to support the trial with the promotion or recruitment of participants. The CRN in the East Midlands commenced promoting and supporting the trial in August 2020. In January 2021, the CRN in the Thames Valley and South Midlands region also commenced promoting the study to GPs in their region. The study lead researcher arranged monthly meetings with the CRN leads, updates were provided, and CRN leads chased up GP surgeries if required. CRN researchers were provided with a half-day training on trial processes and the assessments. This enabled some CRN researchers to provide additional support to the study team by conducting participant assessments.

Working in collaboration with PPI/E representatives

PPI/E input was at all stages, from proposal to dissemination. During set up, three PPI/E representatives were recruited as permanent members of the study team. The PPI/E representatives provided input on all patient-facing documents. We collaborated with PPI/E representatives on the development of the instructional YouTube video and study researchers continued to hold regular remote meetings with PPI/E representatives. This enabled researchers to update PPI/E representatives and to share ideas and help overcome any recruitment barriers. This was also highlighted by our PPI/E representatives to be beneficial for their mental health, particularly during the pandemic. Our PPI/E representatives played a pivotal role in the dissemination of findings and interpretation of results, as well as sharing their experiences of being involved in the trial through national conferences and online video testimonials.

Leadership, peer support and provision of training

The study was guided by strong leadership, which included regularly monitoring recruitment rates, engaging with researchers and GP surgery staff and evaluating the timing and application of recruitment strategies, such as opening additional referral sites. This was critical to achieving recruitment and retention goals. Although all study researchers were required to work remotely, they provided regular support to one another. Prior to any researcher completing assessments, the lead researcher provided training. Throughout the trial, the lead researcher arranged weekly meetings with trial researchers to discuss participant recruitment and trial progress.

Strategy 4: role of study researchers in communicating with participants and collecting data (September 2020–January 2022)

The study researchers comprised one full-time lead researcher, two part-time research assistants and a research nurse from the Clinical Research Network (CRN) who offered 1 day a week on the trial. Following referral by the primary care team, the research team made initial contact with participants to introduce the study, determine eligibility, consent participants and conducted baseline and follow-up assessments. We believe the following aspects may have contributed to improved recruitment and retention rates.

Introducing the study to participants

The initial communication from the study team with interested participants was in the form of a verbal conversation over the telephone. Study researchers informed participants about the study rationale, potential benefits and costs involved in taking part in the trial and what their participation would involve. Potential participants were offered the opportunity to ask questions and express any initial concerns, facilitating rapport building with the study researchers. The decision to communicate with participants verbally prior to emailing a copy of the Participation Information Sheet (PIS) was to reduce the likelihood that participants might be overwhelmed by a long-written document.

Communication skills of the researchers

All researchers were approachable, trustworthy and had good knowledge of the trial. They individualised their communication style to the needs and values of the participants. For example, completion of follow-up assessments with a study researcher was offered over the phone or via video-calling based on participant preference. Study researchers dedicated additional time to speak to the participants and listen to their experiences. A qualitative study embedded within the Alpha-Stim D trial was conducted to explore participant experience of using the Alpha-Stim AID device. The findings have been published [25].

Following completion of all follow-up assessments, participants were emailed Amazon gift vouchers, which they were able to use online, as a token of appreciation. Upon completion of the trial and data analysis, all participants were emailed a summary of the findings. This was in the form of a lay person two-page summary of the key study findings and its implications. The summary was produced in collaboration with PPI/E representatives to ensure that it was appropriate and understandable.

In addition, study researchers also communicated to GPs any risk issues that were highlighted at baseline or follow-up assessments. This ensured that participants were followed up by their clinicians and risk managed.

Continuity and flexibility of study researchers

Outcome measures were intended to be simple and concise requiring minimal time commitment from participants. These were completed with the researcher over the phone or via Microsoft Teams depending on patient preference. Where possible, the same researcher conducted the baseline and follow-up assessments to ensure continuity and consistency. All participants were contacted via text message a week prior to their follow-up assessments to arrange a time for this. If participants did not respond, two reminder texts were sent out followed by a phone call if no response was received.

Researchers were flexible, offering assessments outside of their working hours to accommodate participants’ lifestyles where possible. This included assessments in the evenings and occasional weekend working. This both facilitated recruitment and retention rates.

Figure 4 illustrates a timeline of recruitment, the onset of strategies and milestones.

Fig. 4

A summary of the strategies utilised to improve recruitment figures and perceived impacts are presented in Table 2.

Table 2 Strategies utilised to boost recruitment rates