Sally Brabyn

Computerised cognitive behaviour therapy (cCBT) as treatment for depression in primary care (REEACT trial): large scale pragmatic randomised controlled trial.

Study question How effective is supported computerised cognitive behaviour therapy (cCBT) as an adjunct to usual primary care for adults with depression? Methods This was a pragmatic, multicentre, three arm, parallel randomised controlled trial with simple randomisation. Treatment allocation was not blinded. Participants were adults with symptoms of depression (score ≥10 on nine item patient health questionnaire, PHQ-9) who were randomised to receive a commercially produced cCBT programme (“Beating the Blues”) or a free to use cCBT programme (MoodGYM) in addition to usual GP care. Participants were supported and encouraged to complete the programme via weekly telephone calls. Control participants were offered usual GP care, with no constraints on the range of treatments that could be accessed. The primary outcome was severity of depression assessed with the PHQ-9 at four months. Secondary outcomes included health related quality of life (measured by SF-36) and psychological wellbeing (measured by CORE-OM) at four, 12, and 24 months and depression at 12 and 24 months. Study answer and limitations Participants offered commercial or free to use cCBT experienced no additional improvement in depression compared with usual GP care at four months (odds ratio 1.19 (95% confidence interval 0.75 to 1.88) for Beating the Blues v usual GP care; 0.98 (0.62 to 1.56) for MoodGYM v usual GP care). There was no evidence of an overall difference between either programme compared with usual GP care (0.99 (0.57 to 1.70) and 0.68 (0.42 to 1.10), respectively) at any time point. Commercially provided cCBT conferred no additional benefit over free to use cCBT or usual GP care at any follow-up point. Uptake and use of cCBT was low, despite regular telephone support. Nearly a quarter of participants (24%) had dropped out by four months. The study did not have enough power to detect small differences so these cannot be ruled out. Findings cannot be generalised to cCBT offered with a much higher level of guidance and support. What this study adds Supported cCBT does not substantially improve depression outcomes compared with usual GP care alone. In this study, neither a commercially available nor free to use computerised CBT intervention was superior to usual GP care. Funding, competing interests, data sharing Commissioned and funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (project No 06/43/05). The authors have no competing interests. Requests for patient level data will be considered by the REEACT trial management group Trial registration Current Controlled Trials ISRCTN91947481.

A randomised controlled trial of computerised cognitive behaviour therapy for the treatment of depression in primary care: the Randomised Evaluation of the Effectiveness and Acceptability of Computerised Therapy (REEACT) trial

BACKGROUND Computerised cognitive behaviour therapy (cCBT) has been developed as an efficient form of therapy delivery with the potential to enhance access to psychological care. Independent research is needed which examines both the clinical effectiveness and cost-effectiveness of cCBT over the short and longer term. OBJECTIVES To compare the clinical effectiveness and cost-effectiveness of cCBT as an adjunct to usual general practitioner (GP) care against usual GP care alone, for a free-to-use cCBT program (MoodGYM; National Institute for Mental Health Research, Australian National University, Canberra, Australia) and a commercial pay-to-use cCBT program (Beating the Blues(®); Ultrasis, London, UK) for adults with depression, and to determine the acceptability of cCBT and the experiences of users. DESIGN A pragmatic, multicentre, three-armed, parallel, randomised controlled trial (RCT) with concurrent economic and qualitative evaluations. Simple randomisation was used. Participants and researchers were not blind to treatment allocation. SETTING Primary care in England. PARTICIPANTS Adults with depression who scored ≥ 10 on the Patient Health Questionnaire-9 (PHQ-9). INTERVENTIONS Participants who were randomised to either of the two intervention groups received cCBT (Beating the Blues or MoodGYM) in addition to usual GP care. Participants who were randomised to the control group were offered usual GP care. MAIN OUTCOME MEASURES The primary outcome was depression at 4 months (PHQ-9). Secondary outcomes were depression at 12 and 24 months; measures of mental health and health-related quality of life at 4, 12 and 24 months; treatment preference; and the acceptability of cCBT and experiences of users. RESULTS Clinical effectiveness: 210 patients were randomised to Beating the Blues, 242 patients were randomised to MoodGYM and 239 patients were randomised to usual GP care (total 691). There was no difference in the primary outcome (depression measured at 4 months) either between Beating the Blues and usual GP care [odds ratio (OR) 1.19, 95% confidence interval (CI) 0.75 to 1.88] or between MoodGYM and usual GP care (OR 0.98, 95% CI 0.62 to 1.56). There was no overall difference across all time points for either intervention compared with usual GP care in a mixed model (Beating the Blues versus usual GP care, p = 0.96; and MoodGYM versus usual GP care, p = 0.11). However, a small but statistically significant difference between MoodGYM and usual GP care at 12 months was found (OR 0.56, 95% CI 0.34 to 0.93). Free-to-use cCBT (MoodGYM) was not inferior to pay-to-use cCBT (Beating the Blues) (OR 0.91, 90% CI 0.62 to 1.34; p = 0.69). There were no consistent benefits of either intervention when secondary outcomes were examined. There were no serious adverse events thought likely to be related to the trial intervention. Despite the provision of regular technical telephone support, there was low uptake of the cCBT programs. Cost-effectiveness: cost-effectiveness analyses suggest that neither Beating the Blues nor MoodGYM appeared cost-effective compared with usual GP care alone. Qualitative evaluation: participants were often demotivated to access the computer programs, by reason of depression. Some expressed the view that a greater level of therapeutic input would be needed to promote engagement. CONCLUSIONS The benefits that have previously been observed in developer-led trials were not found in this large pragmatic RCT. The benefits of cCBT when added to routine primary care were minimal, and uptake of this mode of therapy was relatively low. There remains a clinical and economic need for effective low-intensity psychological treatments for depression with improved patient engagement. TRIAL REGISTRATION This trial is registered as ISRCTN91947481. FUNDING This project was funded by the National Institute for Health Research Health Technology Assessment programme.

Acupuncture for irritable bowel syndrome: primary care based pragmatic randomised controlled trial.

BackgroundAcupuncture is used by patients as a treatment for irritable bowel syndrome (IBS) but the evidence on effectiveness is limited. The purpose of the study was to evaluate the effectiveness of acupuncture for irritable bowel syndrome in primary care when provided as an adjunct to usual care.MethodsDesign: A two-arm pragmatic randomised controlled trial.Setting: Primary care in the United Kingdom.Patients: 233 patients had irritable bowel syndrome with average duration of 13 years and score of at least 100 on the IBS Symptom Severity Score (SSS).Interventions: 116 patients were offered 10 weekly individualised acupuncture sessions plus usual care, 117 patients continued with usual care alone.Measurements: Primary outcome was the IBS SSS at three months, with outcome data collected every three months to 12 months.ResultsThere was a statistically significant difference between groups at three months favouring acupuncture with a reduction in IBS Symptom Severity Score of −27.43 (95% CI: –48.66 to −6.21, p = 0.012). The number needed to treat for successful treatment (≥50 point reduction in the IBS SSS) was six (95% CI: 3 to 17), based on 49% success in the acupuncture group vs. 31% in the control group, a difference between groups of 18% (95% CI: 6% to 31%). This benefit largely persisted at 6, 9 and 12 months.ConclusionsAcupuncture for irritable bowel syndrome provided an additional benefit over usual care alone. The magnitude of the effect was sustained over the longer term. Acupuncture should be considered as a treatment option to be offered in primary care alongside other evidenced based treatments.Trial RegistrationCurrent Controlled Trials ISRCTN08827905

Bias in recruitment to cluster randomized trials: a review of recent publications

OBJECTIVES To assess recruitment bias and the techniques employed to counter this problem in a recent selection of published cluster randomized trials. DESIGN Review of 24 cluster trials published in 2008 in four leading medical journals. DATA EXTRACTION Studies were assessed by four reviewers to identify if an alternative design could have been employed using individual randomization. Data were also extracted on the randomization procedure and the likelihood of this introducing bias to the selection of participants into the study. RESULTS Of the 24 trials, eight could have used individual randomization as an alternative to cluster allocation. Seven studies could have recruited participants prior to cluster randomization but did not. In eight studies where recruitment bias was possible, more than half (five) demonstrated some evidence of differential recruitment rates. CONCLUSIONS Many cluster trials published in leading medical journals are not clear in their justification for the design. We also found significant proportions of cluster trials used suboptimal designs that increase their risk of introducing selection bias. Better design of cluster trials is possible and should be adopted.

Varenicline for smoking cessation and reduction in people with severe mental illnesses : systematic review and meta-analysis

AIMS To determine the effectiveness and safety of varenicline in treating tobacco dependence in patients with severe mental illness. DESIGN A systematic review and meta-analysis of randomised controlled trials that compared varenicline with a placebo or an alternative intervention for smoking cessation or reduction. SETTING Both in- and out-patient settings in any country. PARTICIPANTS Adult patients aged 18 years and over with any type of severe mental illness. The systematic review included eight studies comprising 398 participants. MEASURES Primary outcome measures were (1) smoking cessation, (2) smoking reduction measured by changes in the number of cigarettes smoked per day and (3) number of psychiatric adverse events, which were collected at the end of treatment. FINDINGS The random-effect pooled estimates from the five studies that reported smoking-related outcomes found that varenicline is statistically superior to placebo in smoking cessation [risk ratios 4.33; 95% confidence interval (CI) = 1.96-9.56], and smoking reduction was higher in varenicline groups (mean reduced daily cigarettes was 6.39; 95% CI = 2.22-10.56). There is no significant difference regarding neuropsychiatric and other adverse events. CONCLUSIONS Varenicline appears to be significantly more effective than placebo in assisting with smoking cessation and reduction in people with severe mental illness. There appears to be no clear evidence that varenicline was associated with an increased risk of neuropsychiatric or other adverse events compared with placebo.

Cost-effectiveness of acupuncture for irritable bowel syndrome: findings from an economic evaluation conducted alongside a pragmatic randomised controlled trial in primary care

BackgroundThere is insufficient evidence to determine whether acupuncture is a cost-effective treatment for irritable bowel syndrome. The objective of this study is to assess the cost-effectiveness of acupuncture as an adjunct to usual care versus usual care alone for the treatment of Irritable Bowel Syndrome (IBS).MethodsCost-utility analysis conducted alongside a pragmatic, multicentre, randomised controlled trial. 233 patients with irritable bowel syndrome were randomly allocated to either acupuncture plus usual care, or usual care alone. Cost-effectiveness outcomes are expressed in terms of incremental cost per quality adjusted life year (QALY) at one year after randomisation. Costs were estimated from the UK National Health Service perspective for a time horizon of one year. Cost-utility ratios were estimated based on complete case analysis for the base case analysis, where only patients with available EQ-5D and cost data were included. Sensitivity analyses comprised a multiple imputation approach for missing data and a subgroup analysis for the more severe cases of IBS.ResultsThe base case analysis showed acupuncture to be marginally more effective than usual care (gain of 0.0035 QALYs, 95% CI: -0.00395 to 0.0465) and more expensive (incremental cost of £218 per patient (95% CI: 55.87 to 492.87) resulting in an incremental cost-effectiveness ratio of approximately £62,500. Sensitivity analysis using multiple imputation for missing data resulted in acupuncture appearing less effective and more costly than usual care, so usual care is dominant. Subgroup analysis selecting the most severe cases of IBS (Symptom Severity Score of over 300) suggested that acupuncture may be a cost-effective treatment option for this group, with a cost-per-QALY of £6,500.ConclusionsAcupuncture as an adjunct to usual care is not a cost-effective option for the whole IBS population; however it may be cost-effective for those with more severe irritable bowel syndrome.Trial registrationCurrent Controlled Trials ISRCTN08827905

The completeness of intervention descriptions in randomised trials of supervised exercise training in peripheral arterial disease

Research supports the use of supervised exercise training as a primary therapy for improving the functional status of people with peripheral arterial disease (PAD). Several reviews have focused on reporting the outcomes of exercise interventions, but none have critically examined the quality of intervention reporting. Adequate reporting of the exercise protocols used in randomised controlled trials (RCTs) is central to interpreting study findings and translating effective interventions into practice. The purpose of this review was to evaluate the completeness of intervention descriptions in RCTs of supervised exercise training in people with PAD. A systematic search strategy was used to identify relevant trials published until June 2015. Intervention description completeness in the main trial publication was assessed using the Template for Intervention Description and Replication checklist. Missing intervention details were then sought from additional published material and by emailing authors. Fifty-eight trials were included, reporting on 76 interventions. Within publications, none of the interventions were sufficiently described for all of the items required for replication; this increased to 24 (32%) after contacting authors. Although programme duration, and session frequency and duration were well-reported in publications, complete descriptions of the equipment used, intervention provider, and number of participants per session were missing for three quarters or more of interventions (missing for 75%, 93% and 80% of interventions, respectively). Furthermore, 20%, 24% and 26% of interventions were not sufficiently described for the mode of exercise, intensity of exercise, and tailoring/progression, respectively. Information on intervention adherence/fidelity was also frequently missing: attendance rates were adequately described for 29 (38%) interventions, whereas sufficient detail about the intensity of exercise performed was presented for only 8 (11%) interventions. Important intervention details are commonly missing for supervised exercise programmes in the PAD trial literature. This has implications for the interpretation of outcome data, the investigation of dose-response effects, and the replication of protocols in future studies and clinical practice. Researchers should be mindful of intervention reporting guidelines when attempting to publish information about supervised exercise programmes, regardless of the population being studied.

Telephone-supported computerised cognitive-behavioural therapy: REEACT-2 large-scale pragmatic randomised controlled trial.

BackgroundComputerised cognitive-behavioural therapy (cCBT) for depression has the potential to be efficient therapy but engagement is poor in primary care trials.AimsWe tested the benefits of adding telephone support to cCBT.MethodWe compared telephone-facilitated cCBT (MoodGYM) (n = 187) to minimally supported cCBT (MoodGYM) (n = 182) in a pragmatic randomised trial (trial registration: ISRCTN55310481). Outcomes were depression severity (Patient Health Questionnaire (PHQ)-9), anxiety (Generalized Anxiety Disorder Questionnaire (GAD)-7) and somatoform complaints (PHQ-15) at 4 and 12 months.ResultsUse of cCBT increased by a factor of between 1.5 and 2 with telephone facilitation. At 4 months PHQ-9 scores were 1.9 points lower (95% CI 0.5-3.3) for telephone-supported cCBT. At 12 months, the results were no longer statistically significant (0.9 PHQ-9 points, 95% CI -0.5 to 2.3). There was improvement in anxiety scores and for somatic complaints.ConclusionsTelephone facilitation of cCBT improves engagement and expedites depression improvement. The effect was small to moderate and comparable with other low-intensity psychological interventions.

The use of unequal randomisation in clinical trials — An update

OBJECTIVE To update a 2005 review of the reasons researchers have given for the use of unequal randomisation in randomised controlled trials (RCTs). MAIN MEASURES Intervention being tested; type of study; number of participants; randomisation ratio; sample size calculation and reason given for using unequal randomisation. METHODS Review of trials using unequal randomisation. DATABASES AND SOURCES Cochrane library, Medline and CINAHL. RESULTS A total of 86 trials were identified. Of these 82 trials (95%) recruited patients in favour of the experimental group. Various reasons for the use of unequal randomisation were given including: gaining treatment experience; identification of adverse events; ethical; logistic and enhancing recruitment. No trial reported explicitly used it for cost-effectiveness. Most of the papers (i.e. 47, 55%) did not state why they had used unequal randomisation and only 38 trials (44%) appeared to have taken the unequal randomisation into account in their sample size calculation. CONCLUSION Most studies did not mention the rationale for unequal allocation, and a significant proportion did not appear to account for it in the sample size calculations. Unlike the previous review economic considerations were not stated as a rationale for its use. A number of trials used it to enhance recruitment, although this has not been tested.

The 2 2 cluster randomized controlled factorial trial design is mainly used for efficiency and to explore intervention interactions: a systematic review

OBJECTIVES To describe the health care settings, purposes, and study reporting quality of the 2 × 2 cluster randomized controlled factorial trial design. STUDY DESIGN AND SETTING This study is a systematic review. We searched Medline, Embase, Cochrane Library, and Web of Knowledge for articles published up to May 2012. Cluster randomized controlled 2 × 2 factorial trials in health, evaluating at least one complex intervention, were included. Two authors independently reviewed and extracted data from the studies. RESULTS Twenty-nine studies covering a wide range of clinical areas and health care settings were included. The cluster design was mostly used to minimize contamination. The factorial design was mostly used to assess the effects of two interventions in the same study and to explore interactions between interventions. However, although most studies explored the presence or absence of intervention interactions, they were often either not sufficiently powered to detect any interactions or did not provide information on whether the study was sufficiently powered to detect any interactions. There was a considerable variability in the reporting of a number of study characteristics and methodological aspects. Study quality was also variable within and across studies. CONCLUSION The design has been used in a wide range of health care settings and clinical areas to minimize contamination, assess the effects of two interventions in the same study, and explore intervention interactions. There is need for improvement on and guidelines for the reporting of factorial trials.