The REEACT-2 trial is, to our knowledge, the first head-to-head comparison of minimally supported versus telephone-facilitated cCBT in UK primary care. It answers an important question relating to the level of support required for cCBT in clinical practice in order to ensure uptake of the technology and its clinical effectiveness. The REEACT-2 trial results build on an earlier Health Technology Assessment programme-funded trial (REEACT) in which it was found that cCBT was not effective in the form that it was delivered in routine NHS care (i.e. with minimal professional support).12 The REEACT-2 trial specifically tests the hypothesis that increasing the level of professional support offered alongside cCBT leads to a greater level of engagement with the computer technology and in turn leads to improved outcomes. The need for the REEACT-2 trial was highlighted by the negative results of the REEACT trial and the emergence of indirect evidence from systematic reviews which showed that meta-analyses of professionally supported cCBT demonstrated larger effect sizes than minimally supported cCBT.9
Prior to the REEACT and REEACT-2 trials there had been no large-scale pragmatic trials of cCBT products in UK primary care and the REEACT trials were commissioned following an earlier technology appraisal in this area that identified the need for trials conducted independently of product developers.6 The cCBT technology evaluated in the REEACT-2 trial (MoodGYM) was recommended in depression guidelines issued by NICE at the time of design of the REEACT-2 trial, and MoodGYM remains a NICE-endorsed treatment at the time of publication of this trial.39
The REEACT-2 trial was unusual in comparison with earlier trial-based evaluations in that it included an extended follow-up to 12 months. Outcomes were measured across a broad range of domains, including psychological well-being and quality-of-life/health state utility. Important aspects of service utilisation were also recorded, and the trial included a concurrent economic evaluation.
The main findings of the REEACT-2 study will now be discussed in relation to (1) trial-based estimates of the clinical effectiveness of telephone facilitation of cCBT and (2) trial-based estimates of cost-effectiveness.
Trial-based estimates of the clinical effectiveness of telephone-facilitated computer-delivered cognitive behaviour therapy
The REEACT-2 trial found that when telephone facilitation was added to cCBT there were statistically significant benefits in the primary outcome of depression symptomatology and severity across the follow-up period, as measured by a commonly used tool for the identification of depression (PHQ-9). The benefit was most evident at 4 months and the magnitude of benefit was 1.9 points on the PHQ-9 scale, which equated to a small to moderate clinical effect size (Cohen’s d = 0.32).40 By 12 months the between-group difference was attenuated and was no longer statistically significant. The odds of no longer being depressed (defined as a PHQ-9 score of < 10) at 4 months were increased twofold in the facilitated cCBT group compared with minimally supported cCBT group (OR 2.05, 95% CI 1.23 to 3.42).
Turning to the range of secondary outcomes that were collected in the REEACT-2 trial, there was evidence of statistically significant effects on the overall (including all time points) mean depression scores and anxiety scores (as measured by the GAD-7; between-group difference 1.1, 95% CI 0.1 to 2.3; p = 0.037). For somatoform complaints there was some evidence of a benefit, but the difference was not statistically significant (PHQ-15 between-group difference 1.1, 95% CI 0.0 to 1.8; p = 0.051).
When engagement with cCBT was monitored in the trial with reference to computer records, it was found that there was enhanced uptake and use of programmes. Telephone facilitation, therefore, had the anticipated effect of increasing engagement with computer-based technology. Nevertheless, very few participants (only 19%) completed all five treatment sessions. As was found in the REEACT trial, the use of computer sessions was quite low in the minimally supported treatment arm (with only 45% completing the first session) than in the telephone-facilitated group (65%).
In summary, the main finding is therefore that, for the primary outcome of depression severity and symptomatology, there was a clinically and statistically significant additional benefit across a range of psychological outcomes when participants were offered a telephone-facilitated form of computerised therapy in addition to usual GP care. This benefit was also seen in a range of secondary outcomes. Telephone facilitation resulted in additional clinical improvements when compared with minimally supported cCBT. The comparator arm represented an intervention that replicated cCBT as it is currently offered in routine NHS services, and the additional technology of telephone facilitation was therefore effective in improving clinical outcomes.
Summary of trial-based estimates of cost-effectiveness
The within-trial results of the economic analysis suggest that telephone facilitation resulted in increased quality of life (QALYs) and reduced health-care costs (i.e. it was dominant). In a more conservative sensitivity analysis, the scenario changed and telephone-facilitated cCBT was no longer dominant. However, the additional benefit in terms of QALYs was incurred at an acceptable ratio to costs. In the cost-effectiveness analysis, an ICER of £6933 per additional QALY for telephone facilitation was observed. The addition of telephone facilitation was likely to be cost-effective at a £20,000 per QALY threshold.
Although the cost-effectiveness conclusions appear sensitive to the choice costs, the magnitude of the differences between the two groups was relatively minor for both cost and QALY estimates in both the scenarios. Hence, minor differences in the assumptions can lead to different cost-effectiveness interpretations of either dominance or cost-effectiveness, and some caution should be exercised when interpreting these results. However, under no scenario was telephone facilitation cost-ineffective (> £30,000 per QALY) or dominated by minimally supported cCBT.
Discussion of main findings
The clinical results of the REEACT-2 trial are consistent with some increase in benefit that has been observed in systematic reviews of computer-mediated cCBT.9 The addition of telephone facilitation based on a manualised support programme enhanced the effectiveness of cCBT. Minimally supported cCBT (such as is used in the NHS at present) was shown in the REEACT trial to be no more effective than usual GP care. In the REEACT-2 trial, a more intensive telephone facilitation was added to cCBT, and this resulted in statistically significant clinical benefit over and above usual GP care. This finding is important for those who deliver or commission psychological services in primary care. cCBT is a commonly advocated first-line low-intensity treatment option in UK primary care and the offer of this treatment without the provision of telephone facilitation is, on average, unlikely to be of benefit to patients. By adding a level of telephone facilitation that is structured and reinforces the content of CBT treatment sessions, engagement with the programme and clinical outcomes are, on average, improved. The magnitude of this benefit was small to moderate, and was broadly in line with other low-intensity psychological interventions for depression that are delivered in primary care. A systematic review and meta-analysis by Cuijpers et al.41 has demonstrated that the magnitude of effect of primary care-based psychological interventions is, on average, small to moderate (pooled effect size, Cohen’s d = 0.31, 95% CI 0.17 to 0.45) and the results of the REEACT-2 trial are broadly in line with this body of research.41 In comparison with other estimates of effect size obtained from developer-led trials, the magnitude of effect observed in REEACT-2 is smaller. It should be noted that REEACT-2 is a pragmatic trial, which recruited in primary care rather than specialist cCBT services and was conducted independently of product developers. We would therefore expect that the effect size would be smaller and more representative of the benefits expected under conditions of routine care.
To date there have been only limited cost-effectiveness data relating to psychological therapies generally and low-intensity therapies specifically.39 In relation to cCBT there are very few economic evaluations, and those that do exist (e.g. Kaltenthaler et al.6 and Proudfoot et al.7) have been conducted alongside developer-led trials framed in specialist services and with larger clinical effect sizes than were observed in the REEACT and REEACT-2 trials. The REEACT and REEACT-2 trials represent the largest economic evaluations of cCBT to date, and directly examine the cost-effectiveness of cCBT from the perspective of the UK NHS. The results of the REEACT-2 trial-based economic evaluation indicate that telephone-supported cCBT is either dominant (cost saving and more effective) or cost-effective within an acceptable threshold of willingness to pay. These economic data will be of interest to decision-makers and those charged with the commissioning of services.
An important feature of the REEACT-2 trial is that we evaluated a free-to-use cCBT package that can be accessed by UK NHS patients at no direct cost. There are a number of cCBT products and packages that could be used in the NHS and that could have been trialled within the REEACT-2 trial. The rationale for choosing MoodGYM was threefold. First, there was evidence of effect from developer-led trials,8 suggesting that MoodGYM had the potential to be effective in NHS services. Second, we have shown in the REEACT trial that MoodGYM is not inferior to commercially developed cCBT products.12 Third, the technology can be accessed at no direct cost to patients in the UK NHS and it had received cautious support in earlier technology appraisals.6 The results of the REEACT-2 trial are therefore of relevance to decision-makers as investment or commissioning of the use of cCBT will not require purchase of commercially developed products.
There were limitations to the REEACT-2 trial. The first limitation is that we did not obtain a standardised diagnosis of depression at the point of entry to the trial. Instead, we chose a more pragmatic method that judged the presence of symptomatic depression in a more pragmatic way, according to scores on a depression severity scale (the PHQ-9). We also noted that coexisting anxiety and somatoform complaints were common. Although this might be a more heterogeneous population than that seen in efficacy studies, it could be argued that the participants in the REEACT-2 trial were more representative of people with common mental disorders seen in primary care. The level of severity of depression observed with a PHQ-9 cut-off point of ≥ 10 is in line with moderate depression and previous research has shown that this cut-off point is sensitive and specific in identifying people with clinically significant depression. The second limitation is that the level of use of cCBT was quite low and was lower than that observed in developer-led trials. It might be argued that higher levels of uptake and use might have produced larger and more clinically significant effect sizes. However, we have noted that higher levels of uptake have generally been observed in developer-led trials or studies for which there was intensive one-to-one input from a psychological therapist with the therapist present at the time of delivery of the cCBT intervention.7 We would argue that the REEACT-2 trial represented an evaluation of a feasible model of cCBT and low-intensity support that might more readily be delivered at scale within NHS primary care psychological therapy services. The third limitation is the greater than planned level of loss to follow-up that was observed in the REEACT-2 trial. We observed that 27% of participants were lost to follow-up at 4 months and 26% of participants were lost to follow-up at 12 months. There was some evidence of differential attrition, with levels of attrition between 3% and 5% higher in the minimally supported cCBT group. The levels of loss to follow-up were, however, broadly in line with other primary care-based studies of psychological interventions (e.g. King et al.42).
Conclusion
Computerised CBT forms a core component of stepped psychological care in the UK primary care and other health systems. We have previously found in the REEACT trial that minimally supported cCBT is clinically ineffective and cost-ineffective and confers no additional benefit over usual GP care for depression. In the REEACT-2 trial, a level of telephone-delivered facilitation was added to cCBT and modest but statistically significant improvements were found in the primary outcome of the presence of depression and other psychological symptoms. Telephone-facilitated cCBT was also cost-effective.
Implications for health care
In this trial for primary care patients with moderate depression, telephone-facilitated cCBT was clinically effective compared with minimally supported cCBT. Current models of care might usefully be re-examined in the light of these findings with due consideration of the level of support that should be offered alongside cCBT.
Minimally supported cCBT (which is routinely offered in the NHS in many services) is ineffective and our research suggests that outcomes may improve only when there is sufficient staff in place to support this technology with guidance and facilitation by telephone. This can be offered by telephone according to structured delivery manuals, and allows support to be offered at low intensity and higher volume.
Telephone-facilitated cCBT is likely to be cost saving or cost-effective to the NHS.
Recommendations for research
The uptake and use of cCBT was not as high as expected. More research is needed to understand the reasons for lower uptake, and more development is needed for cCBT products to further evolve such that they are more acceptable to people with depression. This requires further research and innovation at the human–computer interface.
People with depression commonly have coexisting anxiety and somatoform complaints. Although some benefits were observed in these symptoms, the cCBT materials did not specifically address these problems. Further research and development is needed to ensure that cCBT products are able to address coexisting common mental disorders within a single-treatment programme.
cCBT is a form of self-help. It would be useful to know how cCBT compares to other forms of guided self-help because computer-delivered therapy is not acceptable to a significant portion of patients. Large-scale pragmatic trials of treatments such as bibliotherapy or telephone-based psychological interventions are therefore needed.
There is a need to examine comparative effectiveness and cost-effectiveness of facilitated cCBT and traditional face-to-face therapy in head-to-head trials.
All effectiveness studies should be framed in primary care and conducted by researchers other than product developers.
Studies should include measures of absenteeism/presenteeism and be powered to examine explanatory variables.
