IMPORTANCE Self-guided internet-based cognitive behavioral therapy (iCBT) has the potential to increase access and availability of evidence-based therapy and reduce the cost of depression treatment.OBJECTIVES To estimate the effect of self-guided iCBT in treating adults with depressive symptoms compared with controls and evaluate the moderating effects of treatment outcome and response.DATA SOURCES A total of 13 384 abstracts were retrieved through a systematic literature search in PubMed, Embase, PsycINFO, and Cochrane Library from database inception to January 1, 2016.STUDY SELECTION Randomized clinical trials in which self-guided iCBT was compared with a control (usual care, waiting list, or attention control) in individuals with symptoms of depression. DATA EXTRACTION AND SYNTHESISPrimary authors provided individual participant data from 3876 participants from 13 of 16 eligible studies. Missing data were handled using multiple imputations. Mixed-effects models with participants nested within studies were used to examine treatment outcomes and moderators. MAIN OUTCOMES AND MEASURESOutcomes included the Beck Depression Inventory, Center for Epidemiological Studies-Depression Scale, and 9-item Patient Health Questionnaire scores. Scales were standardized across the pool of the included studies. RESULTSOf the 3876 study participants, the mean (SD) age was 42.0 (11.7) years, 2531 (66.0%) of 3832 were female, 1368 (53.1%) of 2574 completed secondary education, and 2262 (71.9%) of 3146 were employed. Self-guided iCBT was significantly more effective than controls on depressive symptoms severity (β = −0.21; Hedges g = 0.27) and treatment response (β = 0.53; odds ratio, 1.95; 95% CI, 1.52-2.50; number needed to treat, 8). Adherence to treatment was associated with lower depressive symptoms (β = −0.19; P = .001) and greater response to treatment (β = 0.90; P < .001). None of the examined participant and study-level variables moderated treatment outcomes.CONCLUSIONS AND RELEVANCE Self-guided iCBT is effective in treating depressive symptoms. The use of meta-analyses of individual participant data provides substantial evidence for clinical and policy decision making because self-guided iCBT can be considered as an evidence-based first-step approach in treating symptoms of depression. Several limitations of the iCBT should be addressed before it can be disseminated into routine care. M any studies [1][2][3][4] have found that depressive symptoms can be effectively treated with psychotherapy, pharmacotherapy, or both. Nevertheless, many people with depressive symptoms do not seek help, and even well-resourced health care systems find it difficult to marshal enough qualified therapists to offer psychological interventions. Access barriers to psychotherapy include limited availability of trained clinicians, high cost of treatment, and fear of stigmatization.5-8 As a consequence, a significant number of individuals with depressive symptoms remain untreated.9,10Self-guided internet-based cognitive behavioral therapy (iCBT) wi...

ObjectiveTo ascertain contemporary approaches to the collection, reporting and analysis of adverse events (AEs) in randomised controlled trials (RCTs) with a primary efficacy outcome.DesignA review of clinical trials of drug interventions from four high impact medical journals.Data sourcesElectronic contents table of the BMJ, the Journal of the American Medical Association (JAMA), the Lancet and the New England Journal of Medicine (NEJM) were searched for reports of original RCTs published between September 2015 and September 2016.MethodsA prepiloted checklist was used and single data extraction was performed by three reviewers with independent check of a randomly sampled subset to verify quality. We extracted data on collection methods, assessment of severity and causality, reporting criteria, analysis methods and presentation of AE data.ResultsWe identified 184 eligible reports (BMJ n=3; JAMA n=38, Lancet n=62 and NEJM n=81). Sixty-two per cent reported some form of spontaneous AE collection but only 29% included details of specific prompts used to ascertain AE data. Numbers that withdrew from the trial were well reported (80%), however only 35% of these reported whether withdrawals were due to AEs. Results presented and analysis performed was predominantly on ‘patients with at least one event’ with 84% of studies ignoring repeated events. Despite a lack of power to undertake formal hypothesis testing, 47% performed such tests for binary outcomes.ConclusionsThis review highlighted that the collection, reporting and analysis of AE data in clinical trials is inconsistent and RCTs as a source of safety data are underused. Areas to improve include reducing information loss when analysing at patient level and inappropriate practice of underpowered multiple hypothesis testing. Implementation of standard reporting practices could enable a more accurate synthesis of safety data and development of guidance for statistical methodology to assess causality of AEs could facilitate better statistical practice.

BackgroundDepression and anxiety are major causes of absence from work and underperformance in the workplace. Cognitive behavioural therapy (CBT) can be effective in treating such problems and online versions offer many practical advantages. The aim of the study was to investigate the effectiveness of a computerized CBT intervention (MoodGYM) in a workplace context.MethodThe study was a phase III two-arm, parallel randomized controlled trial whose main outcome was total score on the Work and Social Adjustment Scale (WSAS). Depression, anxiety, psychological functioning, costs and acceptability of the online process were also measured. Most data were collected online for 637 participants at baseline, 359 at 6 weeks marking the end of the intervention and 251 participants at 12 weeks post-baseline.ResultsIn both experimental and control groups depression scores improved over 6 weeks but attrition was high. There was no evidence for a difference in the average treatment effect of MoodGYM on the WSAS, nor for a difference in any of the secondary outcomes.ConclusionsThis study found no evidence that MoodGYM was superior to informational websites in terms of psychological outcomes or service use, although improvement to subthreshold levels of depression was seen in nearly half the patients in both groups.

BackgroundLittle is known about potential harmful effects as a consequence of self-guided internet-based cognitive behaviour therapy (iCBT), such as symptom deterioration rates. Thus, safety concerns remain and hamper the implementation of self-guided iCBT into clinical practice. We aimed to conduct an individual participant data (IPD) meta-analysis to determine the prevalence of clinically significant deterioration (symptom worsening) in adults with depressive symptoms who received self-guided iCBT compared with control conditions. Several socio-demographic, clinical and study-level variables were tested as potential moderators of deterioration.MethodsRandomised controlled trials that reported results of self-guided iCBT compared with control conditions in adults with symptoms of depression were selected. Mixed effects models with participants nested within studies were used to examine possible clinically significant deterioration rates.ResultsThirteen out of 16 eligible trials were included in the present IPD meta-analysis. Of the 3805 participants analysed, 7.2% showed clinically significant deterioration (5.8% and 9.1% of participants in the intervention and control groups, respectively). Participants in self-guided iCBT were less likely to deteriorate (OR 0.62, p < 0.001) compared with control conditions. None of the examined participant- and study-level moderators were significantly associated with deterioration rates.ConclusionsSelf-guided iCBT has a lower rate of negative outcomes on symptoms than control conditions and could be a first step treatment approach for adult depression as well as an alternative to watchful waiting in general practice.

Cognitive decline in aging is a pressing issue associated with significant healthcare costs and deterioration in quality of life. Previously, we reported the successful use of a novel brain-computer interface (BCI) training system in improving symptoms of attention deficit hyperactivity disorder. Here, we examine the feasibility of the BCI system with a new game that incorporates memory training in improving memory and attention in a pilot sample of healthy elderly. This study investigates the safety, usability and acceptability of our BCI system to elderly, and obtains an efficacy estimate to warrant a phase III trial. Thirty-one healthy elderly were randomized into intervention (n = 15) and waitlist control arms (n = 16). Intervention consisted of an 8-week training comprising 24 half-hour sessions. A usability and acceptability questionnaire was administered at the end of training. Safety was investigated by querying users about adverse events after every session. Efficacy of the system was measured by the change of total score from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after training. Feedback on the usability and acceptability questionnaire was positive. No adverse events were reported for all participants across all sessions. Though the median difference in the RBANS change scores between arms was not statistically significant, an effect size of 0.6SD was obtained, which reflects potential clinical utility according to Simon’s randomized phase II trial design. Pooled data from both arms also showed that the median change in total scores pre and post-training was statistically significant (Mdn = 4.0; p<0.001). Specifically, there were significant improvements in immediate memory (p = 0.038), visuospatial/constructional (p = 0.014), attention (p = 0.039), and delayed memory (p<0.001) scores. Our BCI-based system shows promise in improving memory and attention in healthy elderly, and appears to be safe, user-friendly and acceptable to senior users. Given the efficacy signal, a phase III trial is warranted.Trial RegistrationClinicalTrials.gov NCT01661894