Work stream 3+ (variation to contract): a randomised controlled trial of Home-MCT

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. (Figure not reproduced here; see the original article.)

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. (Figure not reproduced here; see the original article.)

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