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A study protocol for the use of individual participant data from randomised controlled trials

Importance: Socioeconomic factors are associated with the prevalence of depression, but their associations with prognosis are unknown. Understanding this association would aid in the clinical management of depression.Objective: To determine whether employment status, financial strain, housing status, and educational attainment inform prognosis for adults treated for depression in primary care, independent of treatment and after accounting for clinical prognostic factors.Data Sources: The Embase, International Pharmaceutical Abstracts, MEDLINE, PsycINFO, and Cochrane (CENTRAL) databases were searched from database inception to October 8, 2021.Study Selection: Inclusion criteria were as follows: randomized clinical trials that used the Revised Clinical Interview Schedule (CIS-R; the most common comprehensive screening and diagnostic measure of depressive and anxiety symptoms in primary care randomized clinical trials), measured socioeconomic factors at baseline, and sampled patients with unipolar depression who sought treatment for depression from general physicians/practitioners or who scored 12 or more points on the CIS-R. Exclusion criteria included patients with depression secondary to a personality or psychotic disorder or neurologic condition, studies of bipolar or psychotic depression, studies that included children or adolescents, and feasibility studies. Studies were independently assessed against inclusion and exclusion criteria by 2 reviewers.Data Extraction and Synthesis: Data were extracted and cleaned by data managers for each included study, further cleaned by multiple reviewers, and cross-checked by study chief investigators. Risk of bias and quality were assessed using the Quality in Prognosis Studies (QUIPS) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tools, respectively. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses-Individual Participant Data (PRISMA-IPD) reporting guidelines.Main Outcomes and Measures: Depressive symptoms at 3 to 4 months after baseline.Results: This systematic review and individual patient data meta-analysis identified 9 eligible studies that provided individual patient data for 4864 patients (mean [SD] age, 42.5 (14.0) years; 3279 women [67.4%]). The 2-stage random-effects meta-analysis end point depressive symptom scale scores were 28% (95% CI, 20%-36%) higher for unemployed patients than for employed patients and 18% (95% CI, 6%-30%) lower for patients who were homeowners than for patients living with family or friends, in hostels, or homeless, which were equivalent to 4.2 points (95% CI, 3.6-6.2 points) and 2.9 points (95% CI, 1.1-4.9 points) on the Beck Depression Inventory II, respectively. Financial strain and educational attainment were associated with prognosis independent of treatment, but unlike employment and housing status, there was little evidence of associations after adjusting for clinical prognostic factors.Conclusions and Relevance: Results of this systematic review and meta-analysis revealed that unemployment was associated with a poor prognosis whereas home ownership was associated with improved prognosis. These differences were clinically important and independent of the type of treatment received. Interventions that address employment or housing difficulties could improve outcomes for patients with depression.

Background\ud Irritable bowel syndrome (IBS) is a common, chronic disorder that leads to decreased health-related quality of life and work productivity. A previous version of this review was not able to draw firm conclusions about the effectiveness of homeopathic treatment for IBS and recommended that further high quality RCTs were conducted to explore the clinical and cost effectiveness of homeopathic treatment for IBS. Two types of homeopathic treatment were evaluated in this systematic review: 1. Clinical homeopathy where a specific remedy is prescribed for a specific condition; 2. Individualised homeopathic treatment, where a homeopathic remedy based on a person’s individual symptoms is prescribed after a detailed consultation.\ud \ud Objectives\ud To assess the effectiveness and safety of homeopathic treatment for IBS.\ud \ud Search methods\ud For this update we searched MEDLINE, CENTRAL, Embase, Cumulative Index to Nursing and AlliedHealth Literature (CINAHL), Allied and Complementary Medicine Database (AMED), the Cochrane IBD Group Specialised Register and trials registers from inception to 31 August 2018.\ud \ud Selection criteria\ud Randomised controlled trials (RCTs), cohort and case-control studies that compared homeopathic treatment with placebo, other control treatments, or usual care, in adults with IBS were considered for inclusion.\ud \ud Data collection and analysis\ud Two authors independently assessed the risk of bias and extracted data. The primary outcome was global improvement in IBS as measured by an IBS symptom severity score. Secondary outcomes included quality of life, abdominal pain, stool frequency, stool consistency, and adverse events. The overall certainty of the evidence supporting the primary and secondary outcomes was assessed using the GRADE criteria. We used the Cochrane risk of bias tool to assess risk of bias. We calculated the mean difference (MD) and 95% confidence interval (CI) for continuous outcomes and the risk ratio (RR) and 95% CI for dichotomous outcomes.\ud \ud Main results\ud Four RCTs (307 participants) were included. Two studies compared clinical homeopathy (homeopathic remedy, asafoetida or asafoetida plus nux vomica) to placebo for IBS with constipation (IBS-C). One study compared individualised homeopathic treatment (consultation plus remedy) to usual care for the treatment of IBS in female patients. One study was a three armed RCT comparing individualised homeopathic treatment to supportive listening or usual care. The risk of bias in three studies (the two studies assessing clinical homeopathy and the study comparing individualised homeopathic treatment to usual care) was unclear on most criteria and high for selective reporting in one of the clinical homeopathy studies. The three armed study comparing individualised homeopathic treatment to usual care and supportive listening was at low risk of bias in four of the domains and high risk of bias in two (performance bias and detection bias).\ud \ud A meta-analysis of the studies assessing clinical homeopathy, (171 participants with IBS-C) was conducted. At short-term follow-up of two weeks, global improvement in symptoms was experienced by 73% (46/63) of asafoetida participants compared to 45% (30/66) of placebo participants (RR 1.61, 95% CI 1.18 to 2.18; 2 studies, very low certainty evidence). In the other clinical homeopathy study at two weeks, 68% (13/19) of those in the asafoetida plus nux vomica arm and 52% (12/23) of those in the placebo arm experienced a global improvement in symptoms (RR 1.31, 95% CI 0.80 to 2.15; very low certainty evidence). In the study comparing individualised homeopathic treatment to usual care (N = 20), the mean global improvement score (feeling unwell) at 12 weeks was 1.44 + 4.55 (n = 9) in the individualised homeopathic treatment arm compared to 1.41 + 1.97 (n=11) in the usual care arm (MD 0.03; 95% CI -3.16 to 3.22; very low certainty evidence).\ud \ud In the study comparing individualised homeopathic treatment to usual care, the mean IBS symptom severity score at 6 months was 210.44 + 112.4 (n = 16) in the individualised homeopathic treatment arm compared to 237.3 + 110.22 (n = 60) in the usual care arm (MD -26.86, 95% CI -88.59 to 34.87; low certainty evidence). The mean quality of life score (EQ-5D) at 6 months in homeopathy participants was 69.07 (SD 17.35) compared to 63.41 (SD 23.31) in usual care participants (MD 5.66, 95% CI -4.69 to 16.01; low certainty evidence).\ud \ud For In the study comparing individualised homeopathic treatment to supportive listening, the mean IBS symptom severity score at 6 months was 210.44 + 112.4 (n = 16) in the individualised homeopathic treatment arm compared to 262 + 120.72 (n = 18) in the supportive listening arm (MD -51.56, 95% CI -129.94 to 26.82; very low certainty evidence). The mean quality of life score at 6 months in homeopathy participants was 69.07 (SD 17.35) compared to 63.09 (SD 24.38) in supportive listening participants (MD 5.98, 95% CI -8.13 to 20.09; very low certainty evidence).\ud \ud None of the included studies reported on abdominal pain, stool frequency, stool consistency, or adverse events.\ud \ud Authors’ conclusions\ud The results for the outcomes assessed in this review are uncertain. Thus no firm conclusions regarding the effectiveness and safety of homeopathy for the treatment of IBS can be drawn. Further high quality, adequately powered RCTs are required to assess the efficacy and safety of clinical and individualised homeopathy for IBS compared to placebo or usual care.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the effectiveness of telephone interventions, delivered by healthcare professionals, when compared to usual care or non-telephone-based support interventions for educating and psychosocially supporting informal carers of people with acute and chronic diagnosed illnesses, on these carers' quality of life, psychosocial and physical well-being. We aim, additionally, to evaluate the cost-effectiveness of telephone interventions.

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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-patient and out-patient settings in any country. PARTICIPANTS: Adult patients aged 18 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% 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. This article is protected by copyright. All rights reserved.

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 groupTrial registration Current Controlled Trials ISRCTN91947481.

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.