Consistent with Medical Research Council (MRC) guidance [55] a two-phase study was planned, including a mixed-method feasibility study, followed by a pilot cluster randomised controlled trial (RCT) and nested qualitative interview study.
Pre-pilot feasibility study
Although the focus of this paper is to report the design of the pilot trial, a brief summary of the feasibility study is provided here. The feasibility study (completed March 2015 prior to commencing the pilot trial) employed a mixed-method design to develop and assess an EPC intervention and to undertake preliminary testing of its implementation. Observations of usual care, a before and after observational study, and qualitative interviews with staff and service users were undertaken. The EPC intervention was developed working with four nurses from three NHS CCRP services (stages 2–5; see Fig. 1) from South West England. Nine eligible patients (i.e. individuals with ‘new onset’ depression) were recruited, and both staff and patients were invited to comment on the feasibility and acceptability of implementing and/or experiencing EPC. Additional CR process data was recorded, including participant attendance at, and adherence with the CCRP with embedded EPC. The findings from this feasibility study were used to refine and develop the EPC intervention and the pilot trial methods. Specifically, qualitative and observational data, considered along with findings arising from discussions with lay representatives, identified the need to reduce the intensity of the BA component of the EPC delivered by CR nurses operating within the context of routine care. The EPC intervention to be delivered in the pilot study will thus retain the nurse acting as a mental health care coordinator, using clearly defined clinical decision-making points and applying evidence-based referral pathways, with the BA component delivered as a participant-led BA intervention, actively supported by the CR nurse.
Pilot cluster randomised controlled trial
An external pilot cluster RCT [56, 57] will be undertaken, including the piloting of economic data collection, and a qualitative interview study. A Consolidated Standards of Reporting Trials (CONSORT) diagram describing the flow of participants through the study is presented in Fig. 2.
Trial interventions
Usual care (control) intervention
Usual care is defined here as the standard CR rehabilitation commencing at the point of assessment undertaken by a CR specialist nurse from a locality-based CCRP (stages 2–3). Of patients invited to attend CCRP, around 41 % attend structured sessions within 2–10 weeks (stage 4) [27]. Treatment as usual in CCRPs typically includes intensive rehabilitation for 1–2 sessions per week for approximately 8 weeks. Sessions generally last around 2 hours and include structured exercise, education (e.g. managing lifestyle and cardiac risk) and some psychological input (e.g. relaxation, stress management) in order to meet the core standards of care described by BACPR [26]. On exiting CCRP, a final assessment (stage 5) and discharge arrangements will be made to community services (stage 6).
There is debate as to what constitutes standard psychological care within CR [27], and a core objective is to clarify this definition. National audit data found that psychological expertise within locality-based CCRPs is uncommon (< 10 %). In the feasibility study, some patients with depressive symptoms were referred to a clinical psychologist. However, no systematic approach was routinely adopted to identify patients as being suitable for referral. The decision was pragmatic, being based on a combination of reviewing depression scores obtained in standard CCRP assessments, discussions with patients, and clinical judgment regarding who might benefit from referral. Informal discussions with mental health specialists and CR staff suggest that there is considerable variation in local CCRP protocols across the UK.
Enhanced psychological care (treatment) intervention
Based on our feasibility findings, we propose to embed EPC within existing CR care pathways, with referrals to existing community mental health services as appropriate. CR nurses from operationally distinct ‘clusters’ – locality-based CCRPs (see Fig. 1, stages 2–5) will be trained to deliver EPC based on a nurse training manual developed and refined during the feasibility study. The CR nurse will implement mental health care coordination [29, 30], including an embedded participant-led BA programme [38, 40–42, 53, 54]. Pre-existing participant and nurse training materials used by the co-applicant (DAR), in previous research, were adapted during the feasibility phase following an iterative process of qualitative data collection with trainers, CR nurses and patients, combined with lay and clinical advisors’ feedback.
To deliver mental health care coordination, CR nurses will apply clinical decision-making rules based on current best practice [29, 30], matching the intensity of treatment with participant preferences for mental health care. All patients referred to a locality-based CCRP and who agree to undertake an initial assessment (stages 2–3), will be routinely screened for depressive symptoms using the Patient Health Questionnaire (PHQ-9) [58, 59]. This tool assesses the nine Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) depression criteria, with individuals scoring 10 or more (out of a possible score of 27) during their initial CR assessment deemed eligible for inclusion.
On identifying an eligible individual, the nurse will explain what evidence-based treatment options are available. This includes BA self-help materials supported by the nurse, GP referral, referral to local IAPT services, and/or referral to specific cardiac patient psychological support services where available. Nurses will coordinate care by monitoring symptoms of depression and anxiety, assessing risk to self or others and agreeing a plan of care with participants that may include BA and/or referral to GP, IAPT or other therapeutic agencies as described above.
As part of this care coordination protocol, all participants will be offered nurse-supported self-help using a participant BA manual. The self-help BA manual consists of a structured programme aimed at enabling participants to re-engage with sources of positive reinforcement from their environment and to develop future strategies for managing their depressive symptoms. The manual adopts a functional analytical approach, aiming to help the participant develop an understanding of behaviours that might interfere with meaningful, goal-oriented behaviours (e.g. negative avoidant behaviours). The manual also explains how to self-monitor mood, and then to identify patterns of behaviour associated with their depression. Participants are encouraged to develop alternative behaviours which are goal- orientated, targeting routine, pleasurable, and necessary activities, and activity scheduling of these identified behaviours.
Although our pilot intervention involves a participant-led self-help BA manual, the CR nurses will actively support participants. The CR nurses will attend a 2-day training course delivered by experienced mental health practitioners, during which they will receive training on the key techniques of mental health care coordination, managing safety and risks, and BA. This training will allow nurses to actively support participants during care coordination and as they work through the BA manual alongside their CR programme. Nurses will also be provided with a session-by-session guide, detailing the types of care coordination tasks which might be relevant for participants as they move through their 6–8 week structured programme (Additional file 1). This guide is flexible to accommodate participant preferences for care. Nurses who are delivering EPC to study participants will also receive bi-weekly clinical supervision by an experienced mental health practitioner.
For those participants who complete CCRP (stage 5), structured details of the care received will be sent to their GP. All participants, including those receiving BA and whose depressive symptoms do not respond, will be given an opportunity to review their management options with the nurse. Here, treatment response is defined as achieving a minimally important clinical difference (MICD) for the PHQ-9 equivalent to a 5-point reduction in score [60]. It is important to note, however, that some people who achieve such a MICD may remain above the PHQ-9 diagnostic threshold (≥ 10). As part of their care coordination, these individuals will be referred for continuing mental health management.
Randomisation and allocation concealment
An external pilot cluster RCT [56, 57] will be undertaken, seeking to recruit and randomise eight CCRPs (clusters) to a treatment or a control arm in a 5:3 ratio. The randomisation ratio was informed by data emerging from our feasibility study, including the need to ensure that sufficient nurses and patients have EPC exposure to support the aims of the qualitative process evaluation. Randomisation will be conducted using the stratifying variables of CR team setting (hospital-based, community-based, or mixed hospital and community), and monthly throughput of new patients assessed for CR at stages 2–3, facilitating division into small and large teams. Team setting has been selected as a stratifying variable because our feasibility study suggested that teams working in hospital and community settings may encounter different resource issues that could affect the delivery of EPC. Throughput of new patients into CR services has been selected as a stratifying variable, as this is an indicator of team workload, and will ensure that sufficient participants are recruited into each trial arm.
Randomisation will be carried out by a statistician, independent from the researchers recruiting CR teams, using computer-generated random numbers. A cluster randomised design, as opposed to individual participant randomisation, is essential to avoid contamination between trial arms (i.e. intervention participants coming into direct contact with controls and sharing aspects of their treatment). Our EPC intervention involves training CR nurses to apply mental health care coordination with embedded participant-led BA. Once trained, it would be very difficult operationally for the nurse to apply structured care coordination to only a subset of eligible participants (as would be required with individual randomisation).
Settings and study population
CCRP recruitment procedures
Eight locality-based CCRPs in South West England will be recruited and randomised. Teams who took part in the feasibility study will be excluded. A two-stage approach to local CCRP recruitment will be employed. We will write to the lead CR nurse in each of the 20 operationally distinct CCRPs in South West England providing detailed information about the study and inviting their participation. In each of the geographical areas the recruitment letter will be co-signed by the trial chief investigator and the local co-applicant. Each team indicating an interest in participation will receive a briefing visit, where the trial design and methods will be explained by the researcher, and the staff will be given an opportunity to ask questions about what might be involved, before being asked to provide written consent to participate in the study.
Nurses in teams allocated to the CCRP with EPC intervention arm will receive EPC and self-harm risk management training (total of two full days) before they start to recruit patients. EPC-trained nurses will be supervised regularly by experienced specialist clinicians/BA practitioners.
Participant eligibility criteria
A pragmatic approach will be adopted, whereby adult patients (aged 18 years or over) referred for CR based on local clinical referral protocols will be screened (stages 2–3) for eligibility. The majority will be individuals previously admitted with an ACS (unstable angina, non-ST-elevation MI or ST-elevation MI) or following a coronary revascularization procedure (percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG)), with or without heart failure [61]. Patients with a new episode of depressive symptoms identified through nurse screening at the start of CCRP using the PHQ-9 [58, 62] (score 10 or more) are potentially eligible for inclusion. Patient exclusion criteria include: individuals reporting having been actively treated for depression (psychological or drug therapy) within the previous 6 months, or where there is evidence of alcohol or drug dependency, being acutely suicidal, or having poorly controlled bipolar disorder or psychosis/psychotic symptoms based on a clinical review (seeking external confirmation from the GP or other clinicians as required). No language exclusion will be applied; we anticipate that the majority of patients will have sufficiently good English language skills to engage with EPC. However, consistent with routine practice in delivering psychological therapy, NHS translation resources will be employed to assist participants where required.
Patient participant recruitment procedure
The CR nurse will apply a structured checklist to ascertain participant eligibility based on our inclusion/exclusion criteria. Eligible participants will be invited to take part in the trial by the CR nurse, and given brief study information to take away and review. The nurse will also ask permission to pass the individual’s contact details on to the study researcher. The researcher will then contact the patient within 7 days to discuss study participation and provide them with a detailed Participant Information Sheet. The researcher will arrange to visit the potential participant to obtain written consent and baseline assessment before the participant commences CCRP (stage 4). Potential participants will be reminded of their right to refuse participation, or to withdraw from the study at any time without it affecting their clinical care.
Sample size
Using UK national audit data (2010–2011), 55,452 patients (for MI, PCI, CABG) undertook phase 3 CR from 280 teams: an average of 200 patients per team per year. Assuming 17 % have depressive symptoms [27], this equates to 35 eligible patients per team each year. The participant consent rate will be established through piloting as no relevant UK data, applicable to cluster trials, are available. Two RCTs (individual randomisation) from the US, exploring psychological/drug therapy in cardiac rehabilitation settings, observed highly variable consent rates of 85 % (150/177 – Vanguard CODIACS study) [51] and 37 % (2481/6854 – ENRICHD study) [49]. Based on the patient throughput and rates of depressive symptoms observed in our feasibility study, and an assumed participation rate of 50 %, we aim to recruit 64 patients through the eight teams in 6 months. This sample size is sufficient to estimate a follow-up percentage as low as 50 % with margin of error ±12.8 % based on the width of the 95 % confidence interval (CI), and as high as 90 % with a margin of error of ±9.3 % based on the lower bound of the 95 % CI. We do not plan to use estimates from the pilot of the intra-cluster (intra-CR team) correlation coefficients (ICCs) for key outcomes to plan the sample size for the definitive trial as the pilot sample is small and estimates will be imprecise. Using national audit data (2010–2011; 6272 patients; 119 CR teams), we estimate the ICC for depression to be 0.047 (95 % CI: 0.034 to 0.062). This ICC estimate and CI will be used to inform the sample size calculations for the definitive trial.
Data collection
Participants in both arms will complete baseline measures prior to commencing CCRP, and then two face-to-face follow-up interviews with a researcher at 5 and 8 months post randomisation (Fig. 2). Blinding of patients, practitioners or researchers extracting data on study outcomes is not possible in this cluster design, but the final analysis will be carried out by a statistician who is blind to treatment allocation. Data will be collected on process measures, patient-reported outcomes, and resource use and costs.
Process measures
Process data relating to participant throughput and intervention fidelity will be collected.
To ascertain study eligibility and recruitment we will ask CR nurses to report the numbers of patients: attending an initial CCRP nurse assessment, the proportion identified with depressive symptoms during this assessment, the prevalence of ‘new onset’ (as opposed to existing) depression and the number of patients who were eligible for study participation. Of eligible patients, we will describe: the number offered study entry; the number who later agreed to be contacted by a researcher; and who subsequently consented to take part and underwent a baseline interview with a researcher. We will also capture data on participant socio-demographic characteristics (age, sex, ethnicity/preferred language) and clinical condition resulting in a CR referral to document how well we have engaged with service users from diverse backgrounds, such as non-English speakers.
Intervention fidelity will be established through a structured notes review documenting the numbers of participants recruited who do not attend CCRP and the proportion with documentary evidence of care coordination in their notes. For participants engaging with the EPC intervention, we will assess adherence by recording the number of BA sessions offered and the number of sessions attended, the number of participants with documentary evidence of care coordination on exiting CCRP, and the type of psychological referrals made (if appropriate).
Participant-reported outcomes measures
Measures are selected on the basis of evidence of their validity in this population, and to ensure coverage of key areas from a clinical and patient perspective (with input from our lay and clinical advisors).
Baseline assessment only
This assessment includes some measures that will not be repeated at follow-up. The revised clinical interview schedule (CIS-R) [63, 64] will be administered to ascertain a clinical diagnosis of depression. This score will not determine study eligibility, but will allow its comparison to the other patient-reported measures of depression symptom severity ascertained using the Beck Depression Inventory (BDI-II) (described below). Some short questions to ascertain, and account for, participant treatment preferences [65] will be included. We will extract data from clinical records (GP, CCRP) relating to known cardiac risk factors (body mass index (BMI), blood pressure, glycosylated haemoglobin (HbA1c), lipids, smoking status) as recorded at the participant’s latest clinical assessment prior to recruitment.
Baseline and follow-up measures
Although we will request that NHS providers inform us of any participant deaths, we will also tag their NHS records to ensure we capture any cardiac- and non-cardiac-related deaths between baseline and the 8-month follow-up. At the last follow-up we will also request that the date and last recorded known cardiac risk factors in CCRP records are extracted. At the same time we will contact the participant’s GP to request that they extract the same data from primary care records, and that they summarise the incidence of any new cardiac events, i.e. death and/or hospital admissions for ACS or revascularisation procedures (CABG or PCI), or mental health events (e.g. self-harm, suicidality) arising since study enrolment. In addition to being outcomes, these data will be part of the safety monitoring of serious adverse events (SAEs) and adverse events (AEs).
The baseline and follow-up interviews will include self-reported cardiac- and non-cardiac- related morbidity and smoking status, antidepressant medication use [66], and resource use. Depressive symptoms will be measured using the BDI-II [67, 68], a 21-item self-report instrument measuring symptom severity with an emphasis on affective and cognitive symptoms. Higher scores represent greater depression severity (range 0–63), and minimal (0–13), mild (14–19), moderate (20–28) and severe (29–63) symptom severity ranges have been specified. The Beck Anxiety Inventory [69, 70] will be applied as anxiety is commonly comorbid with depression. This 21-item, self-report measure asks patients to report anxiety symptoms over the last week from 0 (none: it did not bother me at all), 1 (mildly: it did not bother me much), 2 (moderately: it was very unpleasant, but I could stand it), and 3 (severely: I could barely stand it). Item scores are summed with total scores of 8–15, 26–25, and 26–63 taken as cut-off points defining categories for mild, moderate, or severe anxiety respectively. Health-related quality of life will be assessed using both generic and disease-specific measures. The 5-item EuroQoL (EQ-5D) [71] is a standardised generic measure of health-related quality of life, which is suitable for use in people with a wide range of health conditions, and is recommended by NICE for economic evaluations alongside clinical trials. We will also administer the HeartQoL [72, 73], a tool comprising 14 items, with 10-item physical and 4-item emotional subscales, which are scored from 0 (poor health-related quality of life) to 3 (better). To assess when and how participants become activated over the course of their EPC, we will administer the 9-item Behavioral Activation for Depression Scale – Short Form (BADS-SF) [74] at baseline, and the 5-month and 8-month follow-up assessments. The BADS-SF is a 9-item tool, where each item is rated from 0 (not at all) to 6 (completely). The total score ranges from 0 to 54, with high scores representing greater activation. Finally, participant experiences of care will be assessed at the 5-month follow-up only, using the 8-item, self-reported Client Satisfaction Questionnaire (CSQ-8) [75] and an adapted version of the NHS Friends and Family Test (FFT). The CSQ items use a 4-point Likert scale (1 to 4) response set, with the total scores ranging from a possible 8 to 32; and higher values indicating greater satisfaction. The FFT consists of a single item with a 5-point rating scale (‘Extremely likely’ to ‘Extremely unlikely’) and two free-text items (‘What was good about your experience?’ and ‘What would have made your experience better?’).
Economic evaluation
The analytical perspective of NICE’s decision-making is a societal costing perspective. The pilot study will test methods of resource and service use data collection enabling estimation of the costs to the NHS, costs to social care and PSS, and relevant costs to patients and their carers/families (including NHS and privately funded mental health care). Wherever feasible, these will distinguish use of services for (1) depression or anxiety; (2) for other mental health problems; (3) for other health reasons or social needs. A preliminary assessment of the cost of providing EPC within CR will be undertaken. Service use data will be collected from routine/administrative sources (e.g. hospital records, GP records, community mental health team records, social care records) and participant self-report using the Service and Resource Use Questionnaire (SRUQ). The SRUQ will be adapted from the Client Services Receipt Inventory [76], with input from our lay advisors. The completeness, validity and reliability of participant-reported versus routine administrative data will be compared in relation to the types/amounts of health care/service used over the follow-up periods planned for a definitive trial.
Statistical analysis plan
Trial data will estimate CR team recruitment and patient study completion rates. As this is a pilot study we will not report definitive estimates of effectiveness and costs; our primary aim is to document the adequacy of trial procedures, intervention acceptability and outcome measures. All pilot study data will be collected [77] and reported according to the CONSORT extension for cluster randomised trials [78]. Recruitment, intervention and control uptake, outcome completion rates, and drop out will be reported (with 95 % CIs). We will compare the recruitment rate and participant characteristics at baseline between the trial arms to assess whether there is evidence of selection bias resulting from (cluster) randomising teams before participant recruitment [79]. Patient outcome data (including resource use) will be analysed descriptively (e.g. means, standard deviations (SDs)) for each arm at each follow-up and we will report outcome effect sizes (i.e. between-group mean differences and 95 % CIs) based on an intention-to-treat analysis. We will explore the impact of patient preferences documented at baseline in the analysis. We will also conduct an exploratory sensitivity analysis reporting between-group outcomes in the sub-groups of patients who do, or do not attend, cardiac rehabilitation programmes.