Improving the Effectiveness of Psychological Interventions for Depression and Anxiety in Cardiac Rehabilitation: The PATHWAY Research Programme Including 4 RCTs

Article history

The research reported in this issue of the journal was funded by PGfAR as award number RP-PG-1211-20011. The contractual start date was in September 2014. The draft manuscript began editorial review in February 2022 and was accepted for publication in January 2024. As the funder, the PGfAR programme agreed the research questions and study designs in advance with the investigators. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The PGfAR editors and production house have tried to ensure the accuracy of the authors’ manuscript and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this article.

Copyright statement

Copyright © 2024 Wells et al. This work was produced by Wells et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This is an Open Access publication distributed under the terms of the Creative Commons Attribution CC BY 4.0 licence, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. See: https://creativecommons.org/licenses/by/4.0/. For attribution the title, original author(s), the publication source – NIHR Journals Library, and the DOI of the publication must be cited.

2024 Wells et al.

Background

Aims and objectives of PATHWAY

The primary aim of PATHWAY was to improve access to more effective psychological interventions for a range of heart disease patients attending CR services. We aimed to integrate two metacognitive interventions: a group intervention and a home-based intervention. The project set out to achieve the following objectives:

1. Conduct a pilot randomised controlled trial (RCT) of a group MCT (Group-MCT) for patients with depression and/or anxiety.

2. Establish evidence for the effectiveness and cost-effectiveness of Group-MCT in a full- scale RCT.

3. Produce a rigorous, well-specified Group-MCT package.

4. Develop a home-based metacognitive intervention (Home-MCT) for patients with depression and/or anxiety.

5. Establish the feasibility and acceptability of integrating Home-MCT into the CR pathway.

6. Establish provisional evidence of the effectiveness and cost-effectiveness of Home-MCT.

7. Develop a protocol and manual to inform a full-scale RCT of Home-MCT.

To meet these objectives, we developed a series of work streams (WSs) with integrated qualitative and health economic evaluations. Figure 1 shows the research pathway diagram and Table 1 gives an overview of the original programme objectives, WSs and outputs.

FIGURE 1.

Research pathway diagram.

Work stream 1 was a pilot trial of Group-MCT for patients with depression and/or anxiety. We undertook an initial small-scale pilot trial to establish the acceptability to CR patients and therapists (CR staff trained to deliver the manualised MCT treatment) of adding MCT to usual CR. The pilot also evaluated the feasibility of conducting a full-scale RCT of the intervention.

Work stream 2 was a full-scale RCT to evaluate the effectiveness and cost-effectiveness of Group-MCT plus usual CR compared with usual CR alone. Progression to WS2 depended on the findings of WS1 with regard to the acceptability and feasibility of delivering MCT and implementing a full-scale RCT.

Work stream 3 was to develop a home-based MCT intervention (Home-MCT) and then evaluate the acceptability and feasibility of integrating Home-MCT into the CR pathway in a feasibility trial.

We were able to fully meet the programme objectives:

• WS1 demonstrated that a trial of Group-MCT added to usual CR was feasible and acceptable and confirmed our original sample size estimate.

• The WS2 and WS3 trials recruited to target and had excellent retention.

• Group-MCT + CR was found to be more effective than CR alone at 4- and 12-month follow-up.

• Home-MCT + CR was found to be feasible and acceptable and was extended to a full-scale trial under a variation to contract (VTC) to utilise a study underspend.

• The full-scale trial of Home-MCT demonstrated that the treatment was associated with significantly improved psychological outcomes when added to usual CR.

• We co-designed the Home-MCT intervention with patients and clinicians.

• We completed a cost-effectiveness analysis of group- and home-based MCT.

Work stream 1 overview

Anxiety and depression are common among CR patients. However, existing psychological interventions used in CR produce only modest reductions in emotional distress. An alternative therapy currently not used in CR, MCT, has shown promising results in improving anxiety and depression in mental health settings and in patients with physical illnesses. WS1 aimed to evaluate the acceptability and feasibility of delivering Group-MCT to CR patients experiencing anxiety and depression.

Work stream 1 was a multicentre pilot feasibility study with 4- and 12-month follow-up comparing Group-MCT plus usual CR (intervention) with usual CR alone (control). The study was designed as an internal pilot of the full-scale RCT (WS2). Prespecified criteria for progression to a full RCT were (1) a mean recruitment rate of 8.7 per month, with a rate of 10 per month being desirable; (2) ≥ 65% of participants in the MCT arm attending at least four of the six Group-MCT sessions; and (3) 75% retention at 4-month follow-up. Additionally, the pooling of data collected under the pilot with those collected under the full RCT in the final analysis depended on no substantial changes being made to the trial procedures (e.g. patient eligibility criteria, follow-up schedule) or the trial instruments (e.g. outcome measures) as a result of the pilot. Both study progression and the pooling of data sets required the agreement of the TSC and NIHR as the funding body. The study was approved by the National Research Ethics Service of the NHS (reference 15/NW/0163) and registered with a clinical trial database (ISRCTN reference ISRCTN74643496).

Collaboration with our patient and public involvement (PPI) advisory group took place throughout the study, with PPI members involved at every stage. WS1 recruited 52 CR patients who had elevated anxiety and depression scores on the HADS. Patients were recruited from three NHS trusts in north-west England: University Hospital of South Manchester NHS Foundation Trust, Central Manchester University Hospitals NHS Foundation Trust and East Cheshire NHS Foundation Trust.

The results of the pilot study provided evidence that Group-MCT was acceptable and feasible to deliver within CR. With the agreement of the TSC and NIHR, we progressed directly to a full-scale randomised trial of adding Group-MCT to CR (WS2). The pilot study found that no substantial changes to the trial procedures or instruments were required; therefore, agreement was also given to merge the pilot and main trial data in the RCT analysis. The re-estimation of the full trial sample size based on the pilot data and available resources resulted in a decision to increase the total recruitment target to 332, providing 90% power to detect the desired 0.4 effect size.

Aims and objectives

1. Confirm procedures for recruitment, randomisation, intervention delivery and data collection prior to a full-scale trial.

2. Collect data on recruitment and retention rates, and variability and clustering, in outcome measures, to confirm the sample size calculation and timeline for the full-scale trial.

3. Obtain preliminary economic data to inform economic modelling in the full-scale trial.

4. Include outcome data in analysis of the full-scale trial if no changes are required to the key features of the trial following the pilot.

5. Interview Group-MCT patients, including those who declined to participate or dropped out, to assess their (1) emotional experience since the index event, (2) interaction of emotional state with clinical care, (3) reactions and expectations on being offered the intervention and (4) for those engaged, their perceptions of the intervention.

6. Interview control patients to assess their (1) emotional experience since the index event and (2) interaction of emotional state with clinical care.

Methods

Work stream 1 was delivered in accordance with the grant proposal and employed a randomised pilot feasibility study with 4- and 12-month follow-up comparing Group-MCT plus usual CR (intervention) with usual CR alone (control). The study was designed as an internal pilot of the full-scale RCT (WS2).

Fifty-two CR patients with elevated anxiety and/or depression were recruited to a single-blind randomised feasibility trial between July 2015 and February 2016 from three NHS trusts in north-west England (University Hospital of South Manchester NHS Foundation Trust, Central Manchester University Hospitals NHS Foundation Trust and East Cheshire NHS Foundation Trust). The target sample size was originally 50 patients (25 per arm), determined as sufficient to evaluate recruitment and retention rates for a full-scale trial as well as rates of completion of the intervention. This sample was also adequate for estimating variability in outcome measures for which samples of 40 are generally considered sufficient. However, parallel recruitment across sites meant that 52 patients had consented by the end of the recruitment period and were included in the sample.

After giving informed consent, patients were randomly allocated to a trial condition in a 1 : 1 ratio using a minimisation algorithm that incorporated a random component in order to maximise balance between the arms in sex distribution, HADS anxiety and depression scores, and hospital site. Randomisation was conducted via a telephone link to the Manchester University Clinical Trial Unit (Manchester CTU).

The acceptability and feasibility of adding Group-MCT to CR was evaluated with respect to recruitment rates; attrition by the primary end point of 4 months; number of MCT and CR sessions attended; completion of follow-up questionnaires; and ability of the outcome measures to discriminate between patients. The study was also used to re-estimate the required sample size for a full-scale trial. We also examined the extent to which non-specialists in mental health (i.e. CR health providers) adhered to the Group-MCT protocol. For details of the data collection method, see the protocol. 17

Analysis

We assessed the feasibility and acceptability of adding Group-MCT to usual CR.

Feasibility outcomes included:

1. Completion of follow-up questionnaires (proportions of missing values, both overall and within-trial arms)

2. Ability of the outcome measures to discriminate between patients (range of scores, floor or ceiling effects)

3. Re-estimation of the required sample size based on the findings of this study (number of recruited patients required to detect an effect size of 0.4 on HADS total score at 80% power, controlling for baseline scores and allowing for attrition and clustering of patients within therapy groups)

4. Therapist adherence to study protocol

Acceptability outcomes included:

1. Study recruitment rate (number agreeing to participate out of those approached, and number recruited per month)

2. Withdrawal or drop-out by the primary end point of 4 months (attrition rate)

3. Numbers of MCT and CR sessions attended

4. Therapist adherence to study protocol

Results

Conclusion

The results suggested that a full-scale trial of Group-MCT within CR was feasible and acceptable to deliver.

Qualitative evaluations

Study participants (intervention and control) were interviewed in semi-structured qualitative interviews to explore the potential enablers of/barriers to recruitment/retention at several levels: patient (e.g. attitudes to emotional needs and support), intervention (e.g. comprehensibility) and service (e.g. practices or staff communications that contradict or support the intervention).

Some parts of these sections have been reproduced with permission from McPhillips et al. 14 and McPhillips et al. 15 These are Open Access articles distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/licenses/by/4.0/. The text below includes minor additions and formatting changes to the original text.

Ethics approval was obtained from NRES Committee Northwest REC (reference 15/NW/0163). All participants provided written informed consent prior to being interviewed. Qualitative interviews were audio-recorded, transcribed verbatim and pseudonymised. Analysis varied depending on the research question.

Analysis of the data to determine CR patients’ emotional distress and psychological needs followed a constant comparative approach that occurred in parallel with interviews to develop a thematic framework. The framework was further developed with subsequent interview transcripts. 14 The analysis was evaluated based on its ‘catalytic’ and ‘theoretical’ validity, whereby findings had practical implications and connected with broader theory. The analysis was inductive in that they presented features of patients’ accounts based on emerging data/transcripts rather than on the significance for a priori theories. Theoretical frameworks were drawn on after the analysis was complete to consider the implications of the findings. 14,36

Analysis of qualitative interviews also aimed to understand patient distress from the perspectives of CBT and MCT and comprised three stages: inductive analysis followed by a constant comparative approach, and, finally, reviewing transcripts combining deductive and inductive elements. 15 The exploration of patients’ experience of MCT used thematic analysis. Using a systematic approach, codes were produced by grouping similar concepts together to identify key themes.

Psychological experiences and psychological needs of cardiac rehabilitation patients

We conducted a qualitative study using semi-structured interviews of 46 CR patients who had elevated symptoms of anxiety and/or depression. 14 The study aims included:

1. Understanding how distressed cardiac patients describe their emotional needs

2. Understanding how CR patients described and understood their distress

3. Exploring patients’ thoughts about how well they thought their current CR and routine care addressed their psychological needs and their views on the role of formal psychological interventions

Patients often described their emotional experience since their cardiac event as negative, reporting how they felt low in mood and often engaged in worrying about and dwelling on a range of concerns, including ones that were unrelated to their health and predated their cardiac event. 14 We did not find differences in accounts between men and women or between patients from different centres.

While patients were found to worry about and dwell on a range of topics, which is in line with findings of previous studies,36,37 they also described how they believed that worrying was uncontrollable and harmful, and they worried about worry (a process known as metaworry). The concerns CR patients have about worry (i.e. metaworry) have not been described previously; however, they are central to the metacognitive model38–40 and clarify how CR patients’ distress might be better addressed.

Patients described how they wanted to ‘get back to normal’ and stop worrying. 14 They felt that they lacked a way to achieve this other than waiting for time to pass, and when they did seek support, they sought reassurance from staff and peers to check that they were responding ‘normally’. 14 However, the effects of reassurance were generally transient and, consistent with previous findings, appeared to have little benefit for patients with cardiac symptoms. 41,42 A new and potentially important finding was that, despite wanting reassurance, most patients were reluctant to talk about their worries in the context of CR unless they had been previously socialised into psychological interventions. 1 Furthermore, despite being troubled by worry, most were dismissive of stress management and guided relaxation techniques offered in the context of existing CR. These techniques seemed superficial and difficult to apply in real life and needed more practice than CR provided. Patients also noted that they associated CR primarily with exercise classes and physical rehabilitation, which is in line with previous research, which may be a barrier to using CR as a setting to support mental health. 43

Using MCT may overcome some of the barriers associated with current psychological approaches in CR, as summarised in Figure 2.

FIGURE 2.

Barriers faced in current CR psychological treatment and solutions provided by MCT: a visual summary of discussion in our qualitative study. 14

Work stream 2 overview

A full-scale, two-arm, single-blind RCT with a nested qualitative study was conducted to assess the clinical effectiveness and cost-effectiveness associated with the Group-MCT intervention plus usual CR (MCT + CR). CR services from five NHS trusts across north-west England (University Hospital of South Manchester, Central Manchester University Hospitals NHS Foundation Trust, East Cheshire NHS Trust, Stockport NHS Foundation Trust and Pennine Acute Hospitals NHS Trust) recruited 332 patients attending CR with symptoms of anxiety and/or depression. Participants were randomly assigned to receive MCT + CR or usual CR alone. Patients assigned to receive MCT + CR attended six additional weekly sessions of Group-MCT led by two CR staff members, with each session lasting 60–90 minutes. The primary outcome was level of anxiety/depression as measured by total HADS score at 4-month follow-up. Secondary outcomes included HADS score at 12 months plus scores on the Impact of Events Scale Revised (IES-R), Metacognitive Beliefs Questionnaire-30 (MCQ-30), EuroQol-5 Dimensions, five-level version (EQ-5D-5L) and Cognitive Attentional Syndrome Scale-1 Revised (CAS-1R) at 4- and 12-month follow-up. At 4 months, patients in the MCT + CR arm had significantly reduced total HADS scores compared with those in the CR-alone arm. At 12 months, the group difference was reduced but still statistically significant (p < 0.01). The results for most secondary outcomes also favoured the MCT + CR arm at both 4 and 12 months. The protocol of this trial and the principal results have been published. 17,19

A qualitative interview study found Group-MCT to be effective, positive and beneficial. Patients identified advantages of the group format linked to non-specific supportive factors, and they valued the techniques used in treatment and supported delivery of the intervention by non-mental health specialists. The full qualitative results have been published. 22

Work stream 2 aims

1. Evaluate the effectiveness of MCT + CR compared with usual CR alone in alleviating depression and/or anxiety in patients attending CR.

2. Evaluate the impact of Group-MCT on secondary outcomes including post-traumatic stress, metacognitive beliefs, health status, adherence to CR, health and social care utilisation and work resumption.

3. Assess the durability of treatment outcomes at 4- and 12-month follow-up.

4. Obtain patient qualitative data to help interpret evidence of effectiveness, including processes that might underpin or compromise effectiveness or explain heterogeneity in effectiveness.

5. Obtain practitioner qualitative data to evaluate practitioner experience of Group-MCT delivery and understanding of patients’ emotional needs and identify potential enablers of/barriers to the recruitment and retention of patients.

6. Obtain data from a stated preferences survey about participants’ relative preferences, utility and willingness to pay (WTP) for components of Group-MCT to inform future policy and commissioning decisions.

7. Establish the cost-effectiveness of Group-MCT.

Methods

We conducted a multicentre, two-arm, single-blind RCT with 4- and 12-month follow-up comparing Group-MCT plus usual CR (MCT + CR) with usual CR alone.

Participants were recruited from CR centres across five NHS trusts in north-west England (University Hospital of South Manchester, Central Manchester University Hospitals NHS Foundation Trust, East Cheshire NHS Trust, Stockport NHS Foundation Trust and Pennine Acute Hospitals NHS Trust). No changes were made to the study eligibility criteria following WS1; see WS1 for a full description. For details of patient recruitment and study eligibility, see the published trial protocol. 17 Patients were randomly allocated to the trial arms by Manchester Academic Health Science Centre Clinical Trials Co-ordination Unit using a computer in a 1 : 1 ratio using a minimisation algorithm to balance the trial arms with respect to hospital site, sex and HADS scores. Patients were informed of their trial arm allocation by a member of the research team. The trial chief investigator, trial statistician and research assistants collecting assessment data were masked to treatment allocation.

Analysis

Analysis was conducted in accordance with a prespecified analysis plan specifying the analytical models, primary and secondary outcomes, choice of covariates, sensitivity analyses and other key aspects of the analysis. Prior to data analysis or unmasking, the analysis plan was finalised and approved by the TSC.

The primary outcome was:

1. HADS total score at 4-month follow-up (after treatment).

The secondary outcomes included:

1. HADS total score at 12-month follow-up

2. Post-traumatic stress symptoms measured on the IES-R at 4- and 12-month follow-up

3. Metacognitive beliefs measured on the MCQ-30 total and uncontrollability and danger subscale at 4- and 12-month follow-up

4. Health status measured on the EQ-5D-5L at 4- and 12-month follow-up

5. Repetitive negative thinking and coping mechanisms measured on the CAS-1R at 4- and 12-month follow-up

6. Adverse events related or unrelated to the study

The primary analyses used intention-to-treat principles. A linear mixed-effects regression model was applied for continuous outcomes, incorporating all three time points (baseline, 4 months and 12 months). The prespecified covariates used were randomisation factors (hospital site, sex, baseline total HADS score), age and medication for depression or anxiety (never taken/currently taking/taken in the past). All other potential covariates were below predefined imbalance criteria for sensitivity testing [standardised mean difference (SMD) > 0.25 or category difference of > 10% between arms]. We applied hierarchical regression models with random effects at the levels of the patient and the CR (or MCT + CR) course attended. The covariance matrix for the model was chosen as either unstructured or first-order autoregressive depending on whichever gave the lower Bayesian information criteria score.

The effects associated with the intervention at 4- and 12-month follow-up were examined using the treatment-group-by-time-point interaction terms from the mixed-effects model analysis, where time point was a categorical variable to provide independent tests of effect at 4 and 12 months. No adjustments for multiple testing were applied, and an alpha value of 5% was used throughout. Sensitivity analysis was conducted using multiple imputation (MI) to assess the robustness of the results against missing values. There were very few missing values at baseline (one missing outcome value and a maximum of three missing values on any covariate); therefore, these were imputed by simple regression imputation using all available variables at baseline but excluding trial arm. MI was then used to impute missing outcome values at 4 and 12 months using the full set of variables and including the interaction term between trial arm and time point (for consistency with the analysis model). The chained-equations MI procedure was used and 20 MI data sets.

A mixed-effects logistic regression was conducted to assess the differences between the arms in engagement in economic activity (as a binary outcome) at 4- and 12-month follow-up. Covariates in the model were the same as for the continuous outcome measures.

All outcome measures demonstrated skewness and kurtosis below the threshold of 1.0 specified in the analysis plan and so sensitivity against non-normality was not assessed. The trial eligibility criteria allowed the inclusion of participants without clinically relevant anxiety provided they had at least mild depression, and vice versa; 23% and 40% of participants respectively fell into these categories at baseline, closely balanced between the arms. To determine how this might have impacted on analysis results for HADS anxiety and depression as separate outcomes we conducted sensitivity analyses excluding these individuals. Analyses were conducted using Stata version 14 (StataCorp LP, College Station, TX, USA).

Results

Participants: overview

Between July 2015 and January 2018, 3808 patients were referred to CR across all five sites. A total of 992 patients had a score of ≥ 8 on the HADS subscales; of these, 332 were consented to the trial following eligibility screening and initial contact. One hundred and sixty-three patients were randomly allocated to MCT + CR and 169 patients were randomly allocated to usual CR alone (see Figure 3). For further details, see Wells et al. 19

FIGURE 3.

Work stream 2 trial profile. Figure reproduced with permission from Wells et al. 19 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/licenses/by/4.0/. The figure includes minor additions and formatting changes to the original figure.

Effects associated with Group-MCT

Mean HADS total scores and 95% confidence intervals (CIs) for each trial arm at pre- and post-treatment assessment points are presented in Figure 4. The mean HADS total score under CR alone declined gradually over time in an almost linear fashion, compared with a large reduction over the first 4 months under MCT + CR followed by a plateauing of scores. On the primary outcome – HADS total at 4 months – the results significantly favoured MCT + CR [adjusted mean difference (AMD) −3.24, 95% CI −4.67 to −1.81, p < 0.001; SMD 0.52]. The between-group difference in HADS remained significant at 12 months, albeit at a lower level (AMD −2.19, 95% CI −3.72 to −0.66, p = 0.005; SMD 0.33). Mean HADS anxiety was significantly lower in patients in the MCT + CR arm at 4 months (AMD −1.67, 95% CI −2.54 to −0.81, p < 0.001; SMD 0.44) and 12 months (AMD −1.35, 95% CI −2.22 to −0.48, p = 0.002; SMD 0.34). MCT + CR patients achieved a lower HADS depression mean score at 4 months (AMD −1.58, 95% CI −2.37 to −0.79, p < 0.001; SMD 0.47) but not at 12 months (AMD −0.85, 95% CI −1.75 to 0.05, p = 0.065; SMD 0.23).

FIGURE 4.

Unadjusted mean total HADS scores at baseline and at 4- and 12-month follow-up. Note: bars are 95% CIs. Figure reproduced with permission from Wells et al. 19 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/licenses/by/4.0/. The figure includes minor additions and formatting changes to the original figure.

Most other outcomes also favoured the MCT intervention: adjusted mean IES-R scores were lower with MCT + CR at 4 months (AMD −4.92, 95% CI −9.04 to −0.81; p = 0.019) but not at 12 months (AMD −3.28, 95% CI −7.92 to 1.36; p = 0.166); MCQ-30 total scores were lower at both 4 and 12 months (AMD −8.57, 95% CI −11.95 to −5.18, p < 0.001; AMD −7.37, 95% CI −11.24 to −3.50, p < 0.001, respectively); MCQ-30 negative beliefs subscale scores were lower at both time points (AMD −3.15, 95% CI −4.16 to −2.14, p < 0.001; AMD −2.35, 95% CI −3.43 to −1.26, p < 0.001) and the CAS-1R was also lower with MCT + CR at both 4 and 12 months (AMD −126.25, 95% CI −165.83 to −86.67, p < 0.001; AMD −116.29, 95% CI −159.13 to −73.45, p < 0.001). EQ-5D-5L utility scores showed no statistically significant group difference at 4 months (AMD 0.03, 95% CI −0.02 to 0.09; p = 0.200) or 12 months (AMD 0.03, 95% CI −0.02 to 0.10; p = 0.201); the difference on the EQ-5D-VAS was not significant at either time point (4 months: AMD 4.62, 95% CI −0.10 to 9.34, p = 0.055; 12 months: AMD 0.66, 95% CI −4.12 to 5.45, p = 0.786). Sensitivity analysis using MI changed the statistical significance of one secondary outcome, the IES-R at 4 months, which ceased to be statistically significant (p > 0.05). There was no significant difference between the arms in engagement in economic activity at 4-month (odds ratio 0.94, 95% CI 0.26 to 3.47; p = 0.93) or 12-month follow-up (odds ratio 1.10, 95% CI 0.24 to 4.99; p = 0.90).

To aid in the interpretation of the clinical impact of findings, the Reliable Change Index (RCI)44 was computed for the primary outcome. The RCI represents the difference between two measurements made in a single individual that would be statistically significant at a p-value of < 0.05. It was computed for the HADS total score at the primary 4-month follow-up. Using the control sample, we calculated a Cronbach’s alpha of 0.91 at 4 months for the HADS to estimate reliability for the usual CR population. Based on this, a reduction of 6 points in an individual’s score was defined as statistically reliable improvement, while an increase in 6 points was defined as a reliable worsening of symptoms. Calculations of the HADS total score at 4-month follow-up showed that 21% of patients in the CR-alone arm reliably improved compared with 33% of patients in the MCT + CR arm. The proportion of patients exhibiting psychological deterioration was 15% in the CR-alone arm compared with 4% in the MCT + CR arm.

Qualitative evaluation: overview

From the intervention arm of the trial, 32 patients took part in qualitative interviews prior to starting Group-MCT but during CR [time point 1 (T1)]. Patients who attended four or more Group-MCT sessions were defined a priori as having completed a minimal dose of the intervention likely to produce benefit. Among intervention patients who consented to take part in qualitative interviews, 22 completed the intervention, with 20 completing time point 2 (T2) interviews. Ten did not complete the intervention but five completed T2 interviews; four of these patients attended two or more Group-MCT sessions and their interviews were included in the analysis, and one patient interviewed did not attend any Group-MCT sessions due to work commitments and therefore was excluded from the analysis.

Interviews were conducted at T1 and T2 and were conversational in nature. Topic guides with a mixture of open and closed questions with open-ended prompts were used to encourage patients to share experiences and probe specific points. T1 interviews are discussed in WS1. Data gathered in T1 interviews were used to inform T2 interviews, which explored patients’ emotional experiences since T1, their views and experiences of Group-MCT, and their engagement with techniques from the intervention. Interviews were tailored to the individual, drawing on specifics from T1 interviews. Interview guides were modified iteratively as the interviews and analysis proceeded so that developing ideas could be tested. The interviews lasted an average of 52 minutes (range 14–88 minutes). The interviews were audio-recorded, transcribed verbatim and pseudonymised. Full detailed results have been published. 22

Ten CR staff delivering MCT were interviewed about their experiences of training in and delivery of Group-MCT. Group-MCT was initially delivered by seven CR practitioners across three CR services participating in PATHWAY. Six of these practitioners were interviewed before training, with one practitioner declining to be interviewed at this point. However, all seven were interviewed during training and after they had delivered Group-MCT, as the practitioner who had originally declined later contacted the research team to take part. Two more CR services later joined the study. Two CR practitioners from one of these services and two clinical research nurses (CRNs) were trained in Group-MCT. The two CR practitioners provided written informed consent and were interviewed during training and after they had delivered Group-MCT. One CRN was interviewed during training only, as she left the study shortly afterwards, and the other CRN declined to take part in the study.

Qualitative studies received ethics approval from NRES Committee Northwest REC (reference 15/NW/0163). All participants provided written informed consent prior to being interviewed.

Qualitative data analysis

Inductive thematic analysis was used. Data in each transcript were coded to explore patients’ experiences and understanding of Group-MCT. Generated codes were discussed within the research team and discrepancies were resolved during discussion. Coded data were reviewed and collated into candidate themes. Candidate themes were discussed by the research team and on agreement semantic themes were identified.

Patients experience of Group-MCT

Two main themes were identified in patient experience of Group-MCT: general therapy factors and MCT-specific factors. The first theme concerned general therapy factors central to positive experiences of treatment, with subthemes of interaction with other CR patients and CR staff’s delivery of the intervention. Interaction with other CR patients was an important factor to most patients, providing reassurance, normalisation of feelings in a positive environment and facilitation of the intervention. Patients who were in small groups found that this negatively impacted their experience of Group-MCT, as small groups affected the delivery of the therapy. This highlighted the importance of having a minimum of three or four patients in a group to optimise patient experience. The delivery of the therapy by CR staff was generally received positively by patients as it enabled a positive and relaxing environment. For some patients, CR staff’s specific knowledge and experience of cardiology was important to their delivery of the therapy. However, a minority of patients criticised the staff’s delivery by because of a perceived lack of knowledge and the style of delivery. Patients’ perceptions of CR staff’s delivery were overall positive and demonstrated that CR staff, who were not mental health specialists, established and maintained a therapeutic alliance valued by patients.

The second theme related to MCT-specific factors, with subthemes of patients’ perceptions and understanding of the aims, experiences of individual techniques and perceptions of effectiveness of Group-MCT. Accounts of the aims of Group-MCT varied from those consistent with the model to those that were ‘off-model’. Patients who did not complete Group-MCT had negative perceptions of the aims of the therapy. Patients who correctly understood the aims of the therapy appeared to demonstrate a greater flexibility in their reaction to worry. All patients who completed the intervention were positive about the techniques introduced in MCT. Most patients were able to use these techniques in a manner consistent with the therapy model. However, in some cases techniques were used in a manner not consistent with the model. The results suggest that the techniques used in Group-MCT are largely understood and beneficial; however, therapists should be mindful of patients’ potential misinterpretation and inappropriate use of the techniques based on these narratives.

Practitioners experience of training and delivery of Group-MCT

Cost-effectiveness of group-metacognitive therapy

Stated preferences survey

Work stream 3 overview

BACPR suggests that CR should employ a menu-based approach to CR, allowing a choice of home-based programmes. 2 Although CR offers home-based CR programmes, this has not been applied to psychological support, which has predominantly been delivered and evaluated in face-to-face formats. 48

Home-based psychological support may increase access to psychological help, especially for CR patients who may not be able or willing to attend face-to-face treatment or may be returning to work. Current self-help psychological therapies for cardiac patients are focused on applying relaxation techniques and CBT7 and are limited in efficacy. 48–50 As current home-based psychological options have variable effects, there is room to develop more effective alternatives.

While MCT has demonstrated efficacy in face-to-face delivery, a self-help version of MCT has yet to be evaluated. We therefore set out to develop and evaluate the feasibility and acceptability of home-based MCT.

Work stream 3 aims

1. Develop a home-based metacognitive intervention (Home-MCT) for CR patients with depression and/or anxiety.

2. Establish the acceptability and feasibility of integrating Home-MCT into the CR pathway.

3. Establish provisional evidence of the effectiveness and cost-effectiveness of Home-MCT.

4. Obtain qualitative data to help refine the presentation and delivery or Home-MCT for a full-scale trial.

5. Obtain data from a stated preferences survey about participants’ relative preferences, utility and WTP for components of the intervention to inform the design of a full-scale trial.

6. Collect data on patient variables and outcome measures to inform the design of a full-scale trial.

Methods

The PATHWAY Home-MCT feasibility study is a multicentre RCT with 4- and 12-month follow-up comparing home-based MCT plus usual CR (intervention) with usual CR alone (control). The trial received full ethics approval from the Northwest – Greater Manchester West Research Ethics Committee (reference 16/NW/0786, IRAS ID 186990) and was registered with a clinical trials database (ClinicalTrials.gov, identifier number NCT03129282). Participants were recruited from two NHS CR services (Bolton NHS Foundation Trust and Aintree University Hospitals NHS Foundation Trust). For further details of the trial protocol, including participant assessment and recruitment, see Wells et al. 28

Analysis

With a view to the potential for the study to act as an internal pilot for a subsequent definitive trial (i.e. the data would be combined with subsequent data if the trial were extended and no changes were made to the methods), data analysis was restricted so that it was primarily descriptive, with no between-group analysis of outcome measures, thereby ensuring that masking to treatment allocation would be maintained if the trial were extended.

Acceptability of adding Home-MCT to usual CR was assessed by:

1. Recruitment into the study (number of patients agreeing to participate out of those approached, and number recruited per month)

2. Withdrawal or drop-out by the primary end point of 4 months and by 12-month follow-up (attrition rates)

3. Numbers of MCT modules completed (including time spent on each module)

4. Number of CR sessions attended

The feasibility of conducting a full trial was assessed by:

1. Completion of follow-up questionnaires (proportions of missing values)

2. Ability of the outcome measures to discriminate between patients (range of scores; floor or ceiling effects)

3. Re-estimation of the sample size for a definitive trial based on the findings of this study

Unlike the WS1 pilot, specific thresholds for progression to a full RCT were not defined for WS3, as our original protocol was not designed to continue to a full RCT within the research programme. However, we found ourselves in the position of being able to progress to a full-scale evaluation at no extra cost and did so following consultation with the TSC and NIHR under a ‘variation to contract’. The results of the full trial (WS3+) are reported later in this report.

Results (work stream 3)

Summary of findings of work stream 3

Overall, Home-MCT was found to be an acceptable and feasible addition to CR. No adverse events were reported in either trial arm. These results suggested that we could progress to a full-scale RCT to evaluate the efficacy of Home-MCT. The full trial would also provide a more definitive evaluation of the tendencies seen in the pilot for retainment in the trial and attendance at usual care to be somewhat lower among those offered Home-MCT. The success of the feasibility study supported a VTC to extend recruitment to a full-scale RCT.

Stated preference survey

Overview

The PATHWAY study was granted a VTC to undertake a full RCT of the effectiveness of Home-MCT. The results of the full home-based trial have been published. 34

Aims

We aimed to evaluate if the addition of Home-MCT to usual CR improved anxiety and depression outcomes in comparison with usual care alone.

Methods

A multicentre, two-arm, single-blind, RCT with 4-month follow-up comparing Home-MCT plus usual CR (Home MCT + CR) with usual CR alone was conducted between April 2017 and March 2020. Patients were recruited from CR services at five NHS hospital trusts (Aintree University Hospitals NHS Foundation Trust, Bolton NHS Foundation Trust, Manchester University NHS Foundation Trust, East Cheshire NHS Trust and Pennine Acute Hospitals NHS Trust) across north-west England. The study followed the published protocol. 28 Participant eligibility criteria were not changed from earlier WSs.

The trial was designed to detect a SMD between the trial arms of 0.4 in HADS total score at 4-month follow-up, with 90% power, where 0.4 is in the middle of the range of effect sizes reported for other forms of psychological interventions for depression. 53 We assumed a 0.5 correlation between HADS at baseline and 4-month follow-up and 20% attrition. This indicated a total recruitment target of 246 (123 per arm). The first 108 patients constituted a pilot study (WS3) for ascertaining the feasibility of recruitment and retention and for confirming the sample size for the main trial.

Analyses were conducted in accordance with a prespecified analysis plan approved by the TSC and used intention-to-treat principles. A linear mixed-effects regression model was applied including both time points (baseline and 4 months). Prespecified covariates in the model were the randomisation factors (hospital site, sex, baseline total HADS score), plus age and medication for depression or anxiety (never taken/currently taking/taken in the past).

The RCI,44 which represents the difference between two measurements made in a single individual that would be statistically significant at a p-value of < 0.05, was computed for the HADS total score at 4-month follow-up. Using the control sample, we calculated a Cronbach’s alpha of 0.91 at 4 months for the HADS in order to estimate reliability for the usual CR population. Based on this, a reduction of 7 points in an individual’s score was defined as a statistically reliable improvement, and an increase in 7 points was defined as a reliable worsening of symptoms.

The RCI can be a conservative calculation of recovery; as such, we repeated this process using a minimally clinically important difference (MCID) of a 2-point change in the HADS anxiety and depression subscale. 54 For the HADS total we used an MCID of 3 points, requiring at least one subscale to change by ≥ 2 points.

Results

Two hundred and forty patients were consented to the trial, of whom 118 (49.2%) were randomly allocated to Home-MCT plus CR and 122 (50.8%) were randomly allocated to CR alone. Due to the COVID-19 pandemic, recruitment ended before the intended sample size target had been reached (n = 246), which was approved by the TSC. As the study had a high rate of retention at 4-month follow-up, it was deemed that ending recruitment ahead of target would have minimal impact on the analyses.

Demographic and clinical data for participants at baseline are provided in Wells et al. 34

Attendance at usual CR was high in both trial arms. Patients in the CR-alone arm attended a median of 5 [interquartile range (IQR) 2–6] CR exercise sessions. Similarly, the MCT + CR patients attended a median of 5 (IQR 2–7) CR exercise session; there was no significant difference between the arms in CR exercise attendance (p = 0.951).

Attendance at CR educational sessions was lower [medians: CR 4 (IQR 1 to 6), MCT + CR 4 (IQR 0–6)] and did not differ between the arms (p = 0.657).

At 4-month follow-up, the adjusted group difference on the HADS total (primary outcome) significantly favoured the MCT + CR arm (AMD −2.64, 95% CI −4.49 to −0.78, p = 0.005; SMD 0.38, 95% CI 0.11 to 0.64). Figure 5 presents the mean HADS total scores and 95% CIs for each trial arm at each assessment point, for complete cases only. The CR-alone arm mean score demonstrated little change, in comparison with a notable reduction in the mean for the Home-MCT + CR arm.

FIGURE 5.

Mean HADS total scores and 95% CIs for each trial arm at each assessment point, for complete cases only. Reproduced with permission from Wells et al. 34 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/licenses/by/4.0/. The figure includes minor additions and formatting changes to the original figure.

Patients in the MCT + CR arm achieved a significantly lower mean HADS anxiety subscale score (AMD −1.18, 95% CI −2.26 to −0.10, p = 0.032; SMD 0.29), plus a lower HADS depression subscale mean score (AMD −1.46, 95% CI −2.48 to −0.45, p = 0.005; SMD 0.39). Most other secondary outcomes also favoured the MCT intervention. 34

The percentages of patients reaching the threshold for a reliable improvement on HADS total and clinical improvement based on the MCID are presented in Table 2.

Figure 6 outlines the patient flow through Home-MCT. Approximately 76% of participants in the Home-MCT arm entering treatment completed four or more Home-MCT modules, which is our criterion for a minimal clinically effective exposure.

FIGURE 6.

Home-MCT patient flow.

Conclusion

The addition of Home-MCT to CR was associated with significantly better symptoms of anxiety and depression than CR alone. The tendency seen in the pilot study for attendance at CR sessions to be lower for patients in the Home-MCT + CR arm was not borne out in the larger RCT, which found no impact of trial arm on CR attendance. However, attrition from the trial was greater under the MCT + CR condition. Sensitivity analyses indicated it highly unlikely that the results of the trial in favour of the MCT + CR condition could be accounted for by the group differences in attrition. The study demonstrated for the first time that a home-based intervention of MCT in addition to CR is associated with improvements in symptoms of anxiety and depression beyond the effects of CR alone. Home-based MCT might be offered as a psychological intervention option for CVD patients in addition to or as an alternative to group-based therapist-led MCT.

Cost-effectiveness of Home-MCT

The economic component of the Home-MCT trial originally aimed to establish provisional evidence for the cost-effectiveness of Home-MCT, utilising health status (EQ-5D-5L) and service use data collected prospectively collected from participants in the pilot trial. A request to NHS Digital was planned, with the aim of capturing comprehensive service use from participants using electronic records, which has the benefit of reducing participant burden and minimising missing data. A reduced economic patient questionnaire that captured primary, community and social care was administered to collect data that could not be accessed or linked using NHS Digital. However, the NHS Digital request could not go ahead as planned due to difficulties requesting the data, which included information and technology requirements as well as timeframe and budget constraints. Subsequently, the economic evaluation component was left with insufficient data on healthcare service use and could not robustly make conclusions about cost-effectiveness. Furthermore, there were no statistically significant differences in EQ-5D-5L values (utility) between the arms at follow-up, and mortality rates were similar, and so a difference in QALYs would not be expected. 34

Overview

This section provides an overview of PPI in PATHWAY, demonstrating how PPI was integrated throughout the study. A detailed overview of our PPI framework and how this compared with NIHR PPI standards has been published. 27

Involvement in grant development

Although the study idea was generated by members of the research team, prior to submitting the grant proposal, links were formed with local charity organisations such as the Ticker Club at Wythenshawe Hospital. In developing the grant application, 30 service users across two cardiac service groups were consulted on the preliminary research ideas, the acceptability and feasibility of the proposed research within services and plans for PPI.

Forming the advisory group

To ensure that our patient advisory group comprised a range of service users with varying experiences, we recruited from multiple patient networks, including Salford Citizen Scientist, the Ticker Club and Salford Heart Care, and asked that they had experience of one or more of the following:

1. Heart disease

2. Psychological distress (anxiety and/or depression)

3. Caring for someone with heart disease and/or psychological distress, including professional carers

Sixteen individuals expressed an interest in joining the group; 13 of these attended an initial meeting, and 10 went on to form our patient advisory group. Table 3 gives the demographic characteristics of our PPI members.

Over the next 5 years, three members left, the most common reason being ill-health. When consulted, the advisory group felt that this was to be expected due to the length of the study and the health of the membership and highlighted that that it would not be helpful to re-recruit to the group due to the complex nature and the duration of the project.

Structures and processes

Patient and public involvement meetings took place two or three times per year to provide feedback on and insight into various aspects of the trial. Initially meetings were face to face but during the COVID-19 pandemic these were changed to online meetings using Zoom (Zoom Video Communications, San Jose, CA, USA). Group members were provided with additional opportunities to contribute throughout the study by e-mail or telephone, allowing choice and flexibility of approach and opportunity.

The PPI lead developed and oversaw all aspects of involvement and worked in collaboration with the advisory group and research team to ensure a shared understanding and that everyone’s needs were met.

The advisory group included a chairperson to represent the group and to provide an additional point of contact for any concerns they wanted to raise. The chairperson attended the executive committee along with the PPI lead.

A PPI member independent of the research team and advisory group was also appointed as a member of the TSC.

All service users were reimbursed for their time and travel expenses, in line with INVOLVE guidelines.

Service user involvement throughout the study

Patient and public involvement was integrated throughout the lifecycle of the study and in all WSs, including the stated preference survey, with the degree of involvement and contribution altering throughout the research process. Figure 7 shows an overview of PPI throughout the study.

FIGURE 7.

Overview of PPI throughout the PATHWAY trial. Reproduced with permission from Capobianco et al. 27 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/licenses/by/4.0/. The figure includes minor additions and formatting changes to the original figure.

The advisory group’s insights ensured that the language in our patient-facing documents was appropriate and that any likely concerns or questions had been addressed. For example, the group said that an explanation was needed of what to expect from the home-based manual and what to do when it arrived. They also suggested we give a simpler explanation of how to complete the homework sections and emphasise that the modules should be worked through at the patient’s own pace.

Asking group members to pilot the psychological therapy (home-based manual) not only allowed us to modify the timing and content of phone calls, but also provided them with greater knowledge of the intervention and participant experience that they used to inform dissemination activities. For example, advisory group members noted that it would be interesting and engaging to try to incorporate some the techniques in the manual into dissemination workshops and presentations.

The group’s suggestion of a newsletter to provide updates on the study, remind participants of its importance and highlight the impact of returning questionnaires was an important factor in improving our rate of return on follow-up questionnaires.

The group’s input also informed the designs of the stated preference studies, including choosing and defining attribute and levels, and revising survey materials. For further details of PPI involvement in the stated preference survey, see Shields et al. 20 The PPI activities were used as a case study on a paper exploring PPI involvement in stated preference research.

Our PPI group also co-developed the dissemination and impact plan and dissemination materials prior to the COVID-19 pandemic. Our PPI group helped us to modify our dissemination and impact plan, which was reduced because of the pandemic. This included identifying key messages, audiences and channels for dissemination, and co-creating dissemination materials (i.e. videos and blogs about personal experiences). They also suggested that we ask members of the Ticker Club to evaluate our first patient-facing presentation and suggest other potential audiences for dissemination (see Appendix 5).

Our PPI group was involved in co-delivering the dissemination activities. For example, on 15 July 2021, we held an online dissemination event for patients, members of the public and clinicians. The dissemination event was developed in collaboration with our PPI group, and one of our PPI members was involved in discussing their experience along with a study participant, which provided a patient voice and highlighted the study’s importance and benefit.

Impact on the advisory group

The advisory group members each completed a questionnaire to assess the personal impact of their involvement (see Report Supplementary Material 1). Members agreed that taking part had given them an opportunity to use their skills and make a difference and meet people who had experienced similar things, given them more hope that people will be supported in the future, increased their understanding of how research works, and improved their understanding of coping with anxiety and depression and their own ability to cope with mental health needs. One advisory group member reported:

I think it’s great that psychological, the emotional side is now being sort of trying to be managed because it’s not been there … I didn’t know until we started getting the paperwork what it was [anxiety and depression] … and now I know why I didn’t want to go out of the house for 6 months. I never ever suffered with depression before, but I now know why.

PPI member 3

They concluded that it had been an enjoyable experience, it had increased their trust in research and researchers, and it had made them more likely to discuss research with friends and family. Comments included:

I have gained a better understanding of all the difficult decisions that researchers have to make … The opportunity for the future looks promising and will certainly help more participants to cope.

PPI member 5

It has been a fulfilling experience. Too often patients’ views are not taken into account. I felt that we were listened to at every stage of the research and our suggestions were treated with respect.

PPI member 7

Although no negative impacts of participation were reported, one member had been unaware that they were eligible for transport to the venue by taxi and undertook quite a challenging journey until the research team became aware of the situation.

INVOLVE standards and suggestions for future patient and public involvement

The advisory group’s regular evaluation of our PPI approach, including their review of our approach against the INVOLVE national standards (see Figure 8), highlighted various challenges in achieving the standards. Below we discuss the main challenges and solutions, and the advisory group’s suggestions for the future.

FIGURE 8.

Overview of PATHWAY trial implementing INVOLVE PPI standards.

Conclusion

Patient and public involvement had a positive impact throughout the lifecycle of our study and across the varying components. It also had a positive impact on the advisory group members who took part.

Our approach to PPI was felt to be effective by our advisory group and was aided by the process of ongoing evaluation and adjustment. Several key learning points have emerged that will inform our practice in the future.

Challenges and limitations

A number of challenges were faced throughout the grant, and below we summarise the main challenges and limitations.

The studies reported here did not include a comparison or control group involving the addition of an alternative psychological treatment to CR. We are therefore unable to attribute the improved outcomes in the MCT conditions to the effect of MCT solely, rather than to the provision of extra support and contact time this entailed. As previous trials in mental health have demonstrated that MCT can produce superior outcomes to other psychological treatments in anxiety and depression,13 we chose a more pragmatic research question here: can we improve outcomes when we add MCT to CR?

One of the main challenges faced in WS1 and WS2 was the delivery of MCT by CR staff who had no previous training in mental health treatment. During the feasibility study,14 it was not possible to assess the quality of therapy delivered because of limitations of obtaining consent for audio-recording the sessions. As a result, we were reliant on staff feedback on challenges they encountered during Group-MCT delivery. As the treatment was delivered by CR staff who are not mental health specialists, this may mean that Group-MCT was not delivered optimally. To understand the delivery of MCT further, we interviewed patients to assess their understanding and experience of Group-MCT. 22 Despite therapists receiving limited training in MCT, patients did understand the aims of MCT and its techniques and found the therapy beneficial. However, we were unable to gain a thorough understanding of why some patients did not complete Group-MCT, as only four patients who withdrew from Group-MCT were interviewed. This is an important consideration for any future roll-out of Group-MCT and could provide information to support the transferability of MCT across the CR context.

The study did not include a measure specific to quality of life, and further research should explore the relationship between anxiety and depression outcomes and broader quality of life in the CR population.

In the economic evaluation components, the key challenges and limitations concerned the availability of data. For WS3+ in particular, the inability to access service use data to support costing because of information and technology requirements, as well as time frame and budget constraints, prevented an economic evaluation. For WS2, the economic evaluation was also affected by the sample size and large amount of missing data.

In the stated preference survey,26 one of the limitations was sample recruitment as the sample size for the study was limited and lacked diversity. The sample that responded to the survey was homogeneous, with most respondents being male, over the age of 55 years and retired. This limited the ability to investigate which patient characteristics were tied to delivery preferences. Recruitment for the stated preference survey occurred during the COVID-19 pandemic, which may have influenced the response rate and the responses, which in turn limits generalisability. We discussed the results with our PPI group, who noted that patient preference indicated in the survey may have been affected by local and national lockdown restrictions, which might have strengthened preferences for home-based interventions.

Implications for practice

Improving psychological support within cardiac services is imperative, as elevated anxiety and depression in CVD patients is associated with increased mortality and morbidity, poorer quality of life, greater social problems and higher healthcare costs. The PATHWAY programme has demonstrated that adding Group-MCT to CR was associated with significantly improved anxiety and depression and a wider range of psychological gains that could be sustained over 12 months. Furthermore, a home-based version of MCT when added to CR was also related to improved outcomes when assessed over 4 months. The effect sizes of treatment compare favourably with those of previous studies of psychological interventions, and the treatments could potentially be delivered by CR staff with minimal additional training.

The implications for clinical practice can be summarised as follows:

1. Evidence of positive outcomes associated with a recent psychological treatment (MCT) when used in the context of CR

2. Greater integration of physical and mental health care in heart disease

3. Two formats of psychological treatment (group based and home based) that contribute towards a menu-based approach to CR that is sensitive to patient needs and improves access

4. A better understanding of the mental health needs of CR patients and their preferences for psychological intervention delivery in the NHS that will support service planning, evaluation and research

5. Manualised interventions that could potentially be incorporated in routine CR as a first-line approach for patients with anxiety/depression, with more complex specialist delivered mental health interventions offered to non-responders or those requiring additional help

The results of qualitative analysis coupled with trial outcomes on primary and secondary (psychological mechanism) variables are supportive of MCT as particularly well suited to CVD in comparison with other treatments. It may offer improvements over interventions that target reality-testing of thoughts and relaxation as it offers a good fit with patients’ needs and experiences. The results add to the growing body of studies suggesting that MCT, which targets metacognitions may be suited to alleviating anxiety and depression in patients with a range of physical health conditions. 22,23,31,32

If used in practice, the expectation would be that MCT should be adopted as an option in the National Audit of Cardiac Rehabilitation database so that its use can continue to be assessed. Further training and supervision in the delivery of MCT would be required.

Recommendations for future research

There are a wide range of recommendations for future research that stem from the current series of studies. The relative effects of MCT in comparison with other therapies or additional contact time remains a major question for future research to examine. Further important recommendations in order of priority are summarised as follows:

1. To help realise the clinical potential of MCT in CR, future research should examine its implementation in the NHS and examine the barriers to and enablers of its adoption and roll-out across CR services.

2. Evaluation of the longer-term (12-month) follow-up effects associated with home-based MCT is recommended and should be undertaken as a matter of priority.

3. Health-economic impacts of the inclusion of MCT in CR should be part of future large-scale evaluations. Further research should aim to reduce the uncertainty in the findings for Group-MCT related to cost-effectiveness, for example with larger sample sizes. Additional research exploring how cost-effectiveness differs according to the implementation of MCT within CR and how cost-effectiveness differs by setting would be useful for decision-makers in other settings. Finally, an economic evaluation to establish the cost-effectiveness of Home-MCT is needed.

4. Our stated preference studies demonstrated that there is likely to be heterogeneity across populations with respect to their preferences for the delivery of psychological therapy in CR. Further research with larger and more varied samples should assess how preferences differ by group.

5. We were able to interview only a small number of patients who did not complete treatment and future research is required to examine the reasons that patients drop out of therapy.

6. Given that MCT is based on a model of specific causal psychological mechanisms that are directly targeted in treatment, mechanism-focused research is clearly indicated. Such research can test mechanisms of anxiety and depression and mechanisms of recovery, helping to refine and strengthen interventions.

Conclusions

The data suggest that currently the psychological needs of patients in CR are not being met, as evidenced by the rates of anxiety and depression among this group, by the lack of standard provision of psychological therapy and by the results of our qualitative studies on patient needs and preferences for therapy. An analysis of psychological needs appeared to fit the objectives of MCT better than the objectives of cognitive–behavioural approaches. Moreover, CR patients did not particularly value current techniques such as relaxation methods used in CR.

We found that both Group-MCT and Home-MCT were feasible and acceptable treatments to deliver and evaluate within CR for the treatment of anxiety and depression. Both treatments were associated with significant reductions in overall depression and anxiety symptoms at 4 months when added to CR that exceeded the effects observed with usual CR alone. Group-MCT was also evaluated at 12 months, at which point anxiety and depression outcomes remained better than with usual CR alone. The long-term impact of Home-MCT remains to be evaluated. The economic evaluation suggests that Group-MCT may be a cost-effective treatment to deliver within CR. However, sample size, missing data and variability in the data led to considerable uncertainty about the cost-effectiveness.

The DCEs demonstrate that participants (including the general public and trial participants) would value making psychological treatment available. For face-to-face therapy there was a preference for individual treatment, while people appear to favour online/smartphone-assisted therapy for home-based therapy, but this was not significant and might have been impacted by the COVID-19 pandemic restrictions.

It is important to highlight the context of this research programme, namely that the chief investigator (AW) is the originator of MCT and the director of the Metacognitive Therapy Institute. He has received funding as chief investigator on the subsequent study ‘Implementing Group Metacognitive Therapy in Cardiac Rehabilitation Services (PATHWAY-Beacons; NIHR29567)’ and is chief investigator on the projects NIHR201495 and NIHR35997 and also co-chief investigator on NIHR203634. Steps were taken throughout the research programme to maintain objectivity; these have been highlighted in this report and included the masking of patient treatment allocation from Adrian Wells, the trial statistician and the research assistants, data being managed by a separate clinical trials unit, data analysis following a prespecified plan and project monitoring and support being provided by an independent TSC.

In conclusion, MCT appeared to be an acceptable addition to CR that fit well with patients’ underlying needs in addressing symptoms of depression and anxiety. MCT was associated with improved psychological outcomes, with the implication that it could contribute to effective treatment offered in CR services within the NHS.

Acknowledgements

We would first like to thank all of our patients who took part in the trial. Thank you for your time and dedication to the project, without which this study would not have been possible. We would also like to thank the PATHWAY research assistants, Dr Rebecca McPhillips, Ms Helen Morley, Dr Hannah Gaffney, Ms Rebecca Anderson, Dr Cintia Faija, Mr Avinash Atwal, Ms Zara Husain and Ms Bethany Cooper, and PATHWAY administrator Wendy Clarke, who contributed to patient recruitment and study organisation. We would like to thank Professor Bob Lewin for his contributions to the PATHWAY design. We would like to thank Dr Peter Salmon for his contribution to the qualitative aspects of the PATHWAY trial. We would like to thank Dr Stuart Wright for his contribution to the stated preference research. We would like to thank Dr Elizabeth Camacho for her contribution to the economic evaluation work. We would also like to thank Dr Kirsten McNicoll for assisting in grant preparation. We are most grateful for and thank the members of the Trial Steering Committee chaired by Professor Kate Jolly and including Professor Gill Lancaster, Professor Gerry Humphris and Mr Chris Houston. We would also like to thank our patient and public involvement group who advised throughout the entirety of the project: Christine Barker, Jerry Benjamin, Stephen Clegg, Jim Collins, Chris Cooper and Marie Holmes.

Contributions of authors

Adrian Wells (https://orcid.org/0000-0001-7713-1592). Professor of Clinical & Experimental Psychopathology. Conceived the study and obtained CLAHRC funding to develop the initial grant proposal and assemble the team; designed the study programme and obtained the funding; had overall responsibility for grant development and programme implementation; developed the MCT interventions, wrote the treatment manuals and clinically trained staff in delivering MCT; designed the study programme.

David Reeves (https://orcid.org/0000-0001-6377-6859). Professor of Biostatistics. Contributed to and oversaw the methodological and statistical design of the trials and contributed to study design, was responsible for the analysis of the feasibility trials and RCTs, and designed the study programme and obtained the study funding.

Peter Fisher (https://orcid.org/0000-0002-7388-720X). Reader in Clinical Psychology. Supported the qualitative methodology, analysis and dissemination and designed the study programme and obtained the study funding.

Linda Davies (https://orcid.org/0000-0001-8801-3559). Professor of Health Economics. Contributed to the health economics study design, conducted the health economic evaluation, and designed the study programme and obtained the study funding.

Gemma Shields (https://orcid.org/0000-0003-4869-7524). Lecturer in Health Economics. Conducted the health economic evaluation.

Patrick Joseph Doherty (https://orcid.org/0000-0002-1887-0237). Professor of Cardiovascular Health. Consulted on the structure of CR and supported study dissemination.

Anthony Heagerty (https://orcid.org/0000-0002-9043-2119). Professor of Medicine. Provided medical oversight and supported study dissemination.

Calvin Heal (https://orcid.org/0000-0002-6445-1551). Research Fellow. Was responsible for the analysis of the feasibility trials and RCTs.

Lindsey Brown (https://orcid.org/0009-0004-7332-1320). PPI Contributor. Provided PPI oversight and input.

Lora Capobianco (https://orcid.org/0000-0001-6877-8650). Senior Research Fellow. Contributed to the management of the study, data collection and report writing and co-ordinated PPI contributions to the studies.

Adrian Wells and Lora Capobianco compiled the first draft of this report with contributions from David Reeves, Calvin Heal, Peter Fisher, Gemma Shields, Lindsey Brown and Linda Davies.

All named authors reviewed and commented on drafts of the report. Investigators making specific contributions are listed in Acknowledgements.

Disclosure of interests

Full disclosure of interests: Completed ICMJE forms for all authors, including all related interests, are available in the toolkit on the NIHR Journals Library report publication page at https://doi.org/10.3310/TMJA2644.

Primary conflicts of interest: Adrian Wells is chief investigator of the current research funded by the National Institute for Health Research (NIHR) (RP-PG-1211-20011). Adrian Wells is the originator of metacognitive therapy and director of the Metacognitive Therapy Institute. Adrian Wells received funding as chief investigator for a subsequent study, ‘Implementing Group Metacognitive Therapy in Cardiac Rehabilitation Services’ (PATHWAY-Beacons; NIHR29567), and is chief investigator on projects NIHR201495 and NIHR35997 and co-chief investigator on project NIHR203634. David Reeves was a co-investigator and received funding from the NIHR Programme Grants for Applied Research (PGfAR) programme for a subsequent study ‘Implementing Group Metacognitive Therapy in Cardiac Rehabilitation Services’ (PATHWAY-Beacons; reference number 29567).

Linda Davies reports grants from NIHR (NIHR132269, NIHR200460, RP-PG-0218-20006, 17/80/09, 16/167/76, 17/31/05) and Trial Steering Committee/Data Monitoring Committee membership for various NIHR studies (16/111/91; 16/116/82). Linda Davies also reports membership of advisory boards for Public Health England and is a member of the NIHR Health Technology Assessment Clinical Evaluation and Trials Committee (2010–14). Linda Davies has been a member of a core group of methodological experts for the NIHR PGfAR programme (2011–15). Linda Davies also reports membership of the editorial board for BMC Psychiatry. Gemma Shields is co-investigator for other NIHR studies (NIHR134702, NIHR132690, NIHR201495, NIHR132622, NIHR203300, NIHR201482, NIHR203474, NIHR203507, NIHR132269, NIHR201093) unrelated to the MCT Pathway programme of work. Lora Capobianco is a co-chief investigator for the NIHR study NIHR203634 and a co-investigator for the following NIHR studies: NIHR29567, NIHR201495 and NIHR35997.

The NIHR PGfAR programme funded the work that this manuscript reports and a subsequent (ongoing) study to evaluate the implementation of group-metacognitive therapy within cardiac rehabilitation services.

Patient data statement

This work uses data provided by patients and collected by the NHS as part of their care and support. Using patient data is vital to improve health and care for everyone. There is huge potential to make better use of information from people’s patient records, to understand more about disease, develop new treatments, monitor safety, and plan NHS services. Patient data should be kept safe and secure, to protect everyone’s privacy, and it’s important that there are safeguards to make sure that it is stored and used responsibly. Everyone should be able to find out about how patient data are used. #datasaveslives You can find out more about the background to this citation here: https://understandingpatientdata.org.uk/data-citation.

Data-sharing statement

All data requests should be submitted to the corresponding author for consideration. Access to anonymised data may be granted following review.

Ethics statement

Work stream 1 (WS1) was approved by the National Research Ethics Service of the UK’s NHS (reference 15/NW/0163) and registered with a clinical trial database (ISRCTN74643496). Ethical approval was sought from NRES Committee North West REC reference (15/NW/0163) for associated qualitative work.

Work stream 2 (WS2) was obtained from the Preston Research Ethics Committee (REC Reference 15/NW/0163) along with site-specific approval. The trial is registered with the ISCRTN registry, No. ISRCTN74643496. Associated Qualitative work received ethical approval from NRES Committee Northwest REC reference (15/NW/0163) on 6 March 2015.

Work stream 3 (WS3) received full ethical approval from the Northwest – Greater Manchester West Research Ethics Committee (Reference 16/NW/0786, IRAS ID 186990) and was registered with a clinical trials database (NCT03129282) on 11 Nov 2016.

Work stream 3+ (WS3+) obtained ethical approval from the Northwest – Greater Manchester West Research Ethics Committee (REC Reference 16/NW/0786) on 03 January 2017, along with site-specific approval.

Information governance statement

Greater Manchester Mental Health NHS Foundation Trust is committed to handling all personal information in line with the UK Data Protection Act (2018) and the General Data Protection Regulation (EU GDPR) 2016/679. Under the Data Protection legislation, Greater Manchester Mental Health NHS Foundation Trust is the Data Controller, and you can find out more about how we handle personal data, including how to exercise your individual rights and the contact details for our Data Protection Officer here (https://www.gmmh.nhs.uk/gdpr-in-research)

Department of Health and Social Care disclaimer

This publication presents independent research commissioned by the National Institute for Health and Care Research (NIHR). The views and opinions expressed by the interviewees in this publication are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, MRC, NIHR Coordinating Centre, the PGfAR programme or the Department of Health and Social Care.

This monograph was published based on current knowledge at the time and date of publication. NIHR is committed to being inclusive and will continually monitor best practice and guidance in relation to terminology and language to ensure that we remain relevant to our stakeholders.

Publications

Disclaimers

This article presents independent research funded by the National Institute for Health and Care Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, CCF, PGfAR or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, the PGfAR programme or the Department of Health and Social Care.

Aims

To assess CR staff’s experience of learning and delivering MCT.

Methodology

Cardiac rehabilitation staff were interviewed at three time points: before Group-MCT training, in the middle of training, and after delivering Group-MCT. A topic guide was developed and used to guide the interviews.

Nine CR staff delivering MCT were interviewed regarding their experience of training and delivery of Group-MCT. Table 4 gives the CR staff characteristics.

Group-MCT was initially delivered by seven CR practitioners across three CR services participating in PATHWAY. Six of these practitioners were interviewed before training, with one practitioner declining to be interviewed at this point. However, all seven were interviewed during training and after they had delivered Group-MCT, as the practitioner who originally declined subsequently contacted the research team in order to take part. Two more CR services later joined the study. Two CR practitioners from one of these services and two CRNs were trained in Group-MCT. The two CR practitioners provided written informed consent and were interviewed during training and after they had delivered Group-MCT. One CRN was interviewed during training only, as she left the study shortly afterwards, and the other CRN declined to take part in the study. See Table 4 for an overview of the therapists included in interviews.

The study received ethics approval from NRES Committee North West REC (reference 15/NW/0163). All participants provided written informed consent prior to being interviewed. Qualitative interviews were audio-recorded, transcribed verbatim, pseudonymised and analysed using thematic analysis.

Extracts representative of participants’ responses are used to illustrate the main findings. Practitioners are identified by participant numbers, which are prefaced with ‘BT’ when extracts are taken from interviews conducted before Group-MCT training, with ‘DT’ when extracts are taken from interviews during training, and with ‘AD’ when extracts are taken from interviews after practitioners had delivered Group-MCT as part of the RCT. Ellipses indicate omitted talk and square brackets are used for explanatory comments.

Results

Aim

The within-trial economic evaluation compares the cost-effectiveness of MCT plus usual care with that of usual care from the perspective of health and social care in the UK.

Methodology

A protocol reporting the design of the economic evaluation has been published separately. 21

In brief, the measure of health benefit used was the QALY; this was estimated using the EQ-5D-5L, which was collected at baseline and at 4- and 12-month follow-up. The EQ-5D-5L has been validated in the population and recommended by NICE. 55,56 In line with current NICE recommendations, the crosswalk algorithm was used to estimate utility values from the EQ-5D-5L. 57

Data on health and social care use were collected using an economic patient questionnaire (capturing inpatient, outpatient, day case, accident, and emergency, primary, community and social care use). Unit costs of NHS and social care services were derived from national average unit cost data, and the price year was 2019.

Cardiac rehabilitation sessions (both education and exercise) were costed as £48 per participant per session. 46 In the primary analysis, MCT costs included staff time for preparation and delivery, and the costs associated with providing a manual and CD (compact disc). The cost of manual and CD was negligible (£3.55). Staff costs were estimated using the mean of a range of staff at band 6 and band 7, including community nurses, hospital-based physiotherapists and occupational therapists. 45 Two healthcare practitioners were costed to deliver sessions, with 2 hours assumed to cover preparation and delivery. A cost per participant was calculated using the average group size from the trial. This resulted in a mean cost per metacognitive therapy session per participant of £54, which was multiplied by the number of sessions attended.

Single imputation was used to impute missing baseline variables, with MI used to impute values missing at follow-up. The primary measure of interest is the ICER. Regression analysis was used to estimate net costs and net QALYs, and these estimates were bootstrapped to generate 10,000 net pairs of costs and QALYs to inform the probability of cost-effectiveness. Regression analyses adjusted for participant characteristics (covariates). Covariates for costs and QALYs included age, gender, hospital site, baseline HADs score, medication for depression or anxiety, body mass index, smoking status, alcohol units consumed per month and number of comorbidities. Net monetary benefit statistics were produced for each pair of simulated net costs and net benefits. The monetary value of simulated QALYs were varied from £0 to £30,000 to reflect a range of hypothetical WTPT. Key sensitivity analyses were used to test the impact of the study design on the results of the cost-effectiveness acceptability analysis.

Data manipulation and analysis were conducted in SPSS version 25 (IBM Corporation, Armonk, NY, USA) and Stata version 14. Details of the methods for the economic evaluation can be found in the protocol. 21

It was planned that a de novo economic model would be constructed with the aims of (1) exploring the cost-effectiveness of MCT over a longer time horizon and (2) exploring the cost-effectiveness of MCT in different populations/settings. However, during the model design, discussions highlighted that without additional evidence becoming available the economic model would not be useful and robust. In particular, high-quality data generalisable to the UK are needed to support the rates of relapse and remission of depression and/or anxiety symptoms and mortality rates specific to the CR population, as is evidence to support the long-term effectiveness of MCT for this population. The protocol noted that subgroup analysis would be conducted if participant numbers/completion allowed; however, owing to the existing limitations of sample size/missingness, these were not explored.

Results

Baseline participant demographics are reported in the trial publication by Wells et al. with no significant differences identified in any of the measured variables across groups. 19 Cost and QALY data were complete for 179 participants (54%; 91 control, 88 intervention). Three hundred and thirty-one participants had complete EQ-5D-5L data at baseline, 260 (78%) had complete data at 4-month follow-up and 245 (74%) had complete data at 12-month follow-up. A total of 262 (79%) participants at baseline, 203 (61%) participants at 4-month follow-up and 211 (64%) participants at 12-month follow-up had sufficient data from the service use questionnaire to estimate baseline costs. Table 5 reports the mean utility value at each assessment for participants with complete cost and QALY data. Table 6 reports a breakdown by cost category for these cases; wide 95% CIs indicate a high level of variation.

Table 7 reports the key results. In primary analyses and the majority of sensitivity analysis, MCT intervention is dominant (cost saving and health increasing). However, the CIs are wide and overlap zero, indicating a high level of variability/uncertainty in the estimates.

Figure 9 displays the uncertainty in the analysis as demonstrated as the net cost/QALY pairs are spread across each of the four quadrants. Figure 10 shows that at a commonly discussed threshold (£30,000 per QALY), the MCT intervention is around 70% likely to be cost-effective.

Discussion

Although the primary cost-effectiveness analysis and the majority of sensitivity analyses indicate that MCT intervention may be cost saving and health increasing, the wide CIs that overlap zero indicate a high level of variability and uncertainty in the estimates. In the primary analysis the probability of cost-effectiveness ranges from 59% at a threshold of £0 per QALY to 76% at a threshold of £30,000 per QALY. Even so, given the uncertainty in the estimates, it cannot be concluded that there is evidence to suggest that MCT is or is not cost-effective.

Regarding the sensitivity analysis, the results at 4-month follow-up are very similar to the primary analysis (12 months). The complete-case analysis does not affect conclusions and uncertainty remains. As would be expected, different assumptions around the cost of MCT affect the probability of cost-effectiveness (e.g. larger group size). Although the decrease in HADS score is significant, it is left to decision-makers to decide how much they would be prepared to pay for a reduction in this measure. In two of the sensitivity analyses, MCT was associated with a net cost increase (not significant). Both of these analyses restricted the participant sample. The first focused on those who met the HADS cut-off point for depression and/or anxiety at baseline, excluding those who no longer met the criteria. The second restricted the MCT arm to the participants assigned to intervention who attended one or more sessions of MCT. Although the ICERs estimated for these analyses were under commonly discussed thresholds, the level of uncertainty is vast, as demonstrated by the CIs and probability of cost-effectiveness. These highly explorative analyses again highlight the need to consider how the implementation of MCT in CR will have an impact on cost-effectiveness. For example, if there is a substantial wait time for therapy in reality, this will have a knock-on effect on the cost-effectiveness.

FIGURE 9.

Cost-effectiveness plane.

FIGURE 10.

Cost-effectiveness acceptability curve.

To the authors’ knowledge, as well as expanding the evidence base for psychological therapy in CR, this is the first economic of MCT (for any population group).

The economic evaluation shared the strengths and limitations of the trial. 19 Although the trial achieved a high rate of follow-up at the primary time horizon, there was a relatively large number of missing data for economic measures at the final follow-up. Overall, 54% of participants had complete cost and utility data at both baseline and follow-up. Larger numbers of missing data reduce the robustness of imputation. Data were imputed by category of cost and EQ-5D-5L domain to make best use of all available data and a complete-case analysis was conducted for comparison. However, given the number of missing data, the results should be interpreted with caution. The number of missing data is similar to that in other trials that have collected self-report data using a similar questionnaire in mental health populations. 58–61 The sample size and missing data limited the potential for subgroup analyses. Health and social care service use was self-reported. While this is a valid approach to data collection, especially in the UK where access to electronic data is associated with hurdles in terms of time and budget, it is open to recall bias and missing data. 62 Service use data are often variable and the sample size of the study and data completeness limits conclusions. Unit costs (especially related to cardiac inpatient admissions) can be substantial. Further research should investigate how the addition of psychological therapy impacts the categories of service use and the interactions between these categories, to more robustly determine how intervention may affect net costs across health and social care. The Recovering Quality of Life (ReQoL) measure is now available, which is a generic self-report measure for use with people experiencing mental health concerns. In comparison with the EQ-5D-5L, this has more focus on mental health and quality of life and also allows for the estimation of utilities for use in economic evaluation. Subsequently, in future research, the exploration of different measures is recommended, as the EQ-5D-5L cannot reflect all aspects of health for all diseases and all patients. The results may not be generalisable to other settings; cardiac services (including the type of CR offered) and populations vary by area. 2,5

Section C: hypothetical psychological therapy alternatives

The next section of questions asks you to compare possible descriptions of different psychological therapies and to choose which you prefer by ticking a box to indicate your choice. Following your choice, you can indicate whether you would take part in your choice or whether you would actually opt out of partaking in psychological therapy. There are 16 of these questions. There are no right or wrong answers. But if you are unsure or have problems answering these questions, please do feel free to contact the research team for help with the questionnaire. Contact details are provided on the instructions. Please try to answer all questions.

C1. Two potential psychological therapies are described below. Remember these would be received in addition to the standard CR package. The statements on the left describe different delivery of the therapy. The statements on the right describe the different options. Imagine that you are offered the choice between therapy A and B. Taking everything into account which therapy would you prefer? Choose which therapy you prefer by ticking the box under therapy A and therapy B. There are no right or wrong answers; it is your view that is important.

C2. Two potential psychological therapies are described below. Remember these would be received in addition to the standard CR package. The statements on the left describe different delivery of the therapy. The statements on the right describe the different options. Imagine that you are offered the choice between therapy A and B. Taking everything into account which therapy would you prefer? Choose which therapy you prefer by ticking the box under therapy A and therapy B. There are no right or wrong answers; it is your view that is important.