Center for Clinical Trials and Evidence Synthesis

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Center for Clinical Trials and Evidence Synthesis

Baltimore, United States

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Yesufu-Udechuku A.,University College London | Harrison B.,National Collaborating Center for Mental Health | Mayo-Wilson E.,Center for Clinical Trials and Evidence Synthesis | Young N.,University of Cardiff | And 3 more authors.
British Journal of Psychiatry | Year: 2015

Background: Informal caregiving is an integral part of the care of people with severe mental illness, but the support needs of those providing such care are not often met. Aims: To determine whether interventions provided to people caring for those with severe mental illness improve the experience of caring and reduce caregiver burden. Method: We conducted a systematic review and meta-analyses of randomised controlled trials (RCTs) of interventions delivered by health and social care services to informal carers (i.e. family or friends who provide support to someone with severe mental illness). Results: Twenty-one RCTs with 1589 carers were included in the review. There was evidence suggesting that the carers' experience of care was improved at the end of the intervention by psychoeducation (standardised mean difference -1.03, 95% CI -1.69 to -0.36) and support groups (SMD = -1.16, 95% CI -1.96 to -0.36). Psychoeducation had a benefit on psychological distress more than 6 months later (SMD = -1.79, 95% CI -3.01 to -0.56) but not immediately post-intervention. Support interventions had a beneficial effect on psychological distress at the end of the intervention (SMD = -0.99, 95% CI -1.48 to -0.49) as did problem-solving bibliotherapy (SMD = -1.57, 95% CI -1.79 to -1.35); these effects were maintained at follow-up. The quality of the evidence was mainly low and very low. Evidence for combining these interventions and for self-help and self-management was inconclusive. Conclusions: Carer-focused interventions appear to improve the experience of caring and quality of life and reduce psychological distress of those caring for people with severe mental illness, and these benefits may be gained in first-episode psychosis. Interventions for carers should be considered as part of integrated services for people with severe mental health problems. © 2015, Royal College of Psychiatrists. All rights reserved.


Li T.,Center for Clinical Trials and Evidence Synthesis | Lindsley K.,Center for Clinical Trials and Evidence Synthesis | Friedman D.S.,Wilmer Eye Institute | Wormald R.,London School of Hygiene and Tropical Medicine | Dickersin K.,Center for Clinical Trials and Evidence Synthesis
Ophthalmology | Year: 2016

Primary open-angle glaucoma (POAG) is a highly prevalent condition worldwide and the most common cause of irreversible sight loss. The objective is to assess the comparative effectiveness of first-line medical treatments in patients with POAG or ocular hypertension through a systematic review and network meta-analysis, and to provide relative rankings of these treatments. Clinical Relevance Treatment for POAG currently relies completely on lowering the intraocular pressure (IOP). Although topical drops, lasers, and surgeries can be considered in the initial treatment of glaucoma, most patients elect to start treatment with eye drops. Methods We included randomized controlled trials (RCTs) that compared a single active topical medication with no treatment/placebo or another single topical medication. We searched CENTRAL, MEDLINE, EMBASE, and the Food and Drug Administration's website. Two individuals independently assessed trial eligibility, abstracted data, and assessed the risk of bias. We performed Bayesian network meta-analyses. Results We included 114 RCTs with data from 20 275 participants. The overall risk of bias of the included trials is mixed. The mean reductions (95% credible intervals) in IOP in millimeters of mercury at 3 months ordered from the most to least effective drugs were as follows: bimatoprost 5.61 (4.94; 6.29), latanoprost 4.85 (4.24; 5.46), travoprost 4.83 (4.12; 5.54), levobunolol 4.51 (3.85; 5.24), tafluprost 4.37 (2.94; 5.83), timolol 3.70 (3.16; 4.24), brimonidine 3.59 (2.89; 4.29), carteolol 3.44 (2.42; 4.46), levobetaxolol 2.56 (1.52; 3.62), apraclonidine 2.52 (0.94; 4.11), dorzolamide 2.49 (1.85; 3.13), brinzolamide 2.42 (1.62; 3.23), betaxolol 2.24 (1.59; 2.88), and unoprostone 1.91 (1.15; 2.67). Conclusions All active first-line drugs are effective compared with placebo in reducing IOP at 3 months. Bimatoprost, latanoprost, and travoprost are among the most efficacious drugs, although the within-class differences were small and may not be clinically meaningful. All factors, including adverse effects, patient preferences, and cost, should be considered in selecting a drug for a given patient. © 2016 American Academy of Ophthalmology.


PubMed | Center for Clinical Trials and Evidence Synthesis, Wilmer Eye Institute and London School of Hygiene and Tropical Medicine
Type: Journal Article | Journal: Ophthalmology | Year: 2015

Primary open-angle glaucoma (POAG) is a highly prevalent condition worldwide and the most common cause of irreversible sight loss. The objective is to assess the comparative effectiveness of first-line medical treatments in patients with POAG or ocular hypertension through a systematic review and network meta-analysis, and to provide relative rankings of these treatments.Treatment for POAG currently relies completely on lowering the intraocular pressure (IOP). Although topical drops, lasers, and surgeries can be considered in the initial treatment of glaucoma, most patients elect to start treatment with eye drops.We included randomized controlled trials (RCTs) that compared a single active topical medication with no treatment/placebo or another single topical medication. We searched CENTRAL, MEDLINE, EMBASE, and the Food and Drug Administrations website. Two individuals independently assessed trial eligibility, abstracted data, and assessed the risk of bias. We performed Bayesian network meta-analyses.We included 114 RCTs with data from 20 275 participants. The overall risk of bias of the included trials is mixed. The mean reductions (95% credible intervals) in IOP in millimeters of mercury at 3 months ordered from the most to least effective drugs were as follows: bimatoprost 5.61 (4.94; 6.29), latanoprost 4.85 (4.24; 5.46), travoprost 4.83 (4.12; 5.54), levobunolol 4.51 (3.85; 5.24), tafluprost 4.37 (2.94; 5.83), timolol 3.70 (3.16; 4.24), brimonidine 3.59 (2.89; 4.29), carteolol 3.44 (2.42; 4.46), levobetaxolol 2.56 (1.52; 3.62), apraclonidine 2.52 (0.94; 4.11), dorzolamide 2.49 (1.85; 3.13), brinzolamide 2.42 (1.62; 3.23), betaxolol 2.24 (1.59; 2.88), and unoprostone 1.91 (1.15; 2.67).All active first-line drugs are effective compared with placebo in reducing IOP at 3 months. Bimatoprost, latanoprost, and travoprost are among the most efficacious drugs, although the within-class differences were small and may not be clinically meaningful. All factors, including adverse effects, patient preferences, and cost, should be considered in selecting a drug for a given patient.


PubMed | Psychiatry and Behavioral science, University of Maryland, Baltimore, Johns Hopkins University, Center for Public Health and Human Rights and 5 more.
Type: | Journal: Systematic reviews | Year: 2015

Systematic reviews should provide trustworthy guidance to decision-makers, but their credibility is challenged by the selective reporting of trial results and outcomes. Some trials are not published, and even among clinical trials that are published partially (e.g., as conference abstracts), many are never published in full. Although there are many potential sources of published and unpublished data for systematic reviews, there are no established methods for choosing among multiple reports or data sources about the same trial.We will conduct systematic reviews of the effectiveness and safety of two interventions following the Institute of Medicine (IOM) guidelines: (1) gabapentin for neuropathic pain and (2) quetiapine for bipolar depression. For the review of gabapentin, we will include adult participants with neuropathic pain who do not require ventilator support. For the review of quetiapine, we will include adult participants with acute bipolar depression (excluding mixed or rapid cycling episodes). We will compare these drugs (used alone or in combination with other interventions) with placebo or with the same intervention alone; direct comparisons with other medications will be excluded. For each review, we will conduct highly sensitive electronic searches, and the results of the searches will be assessed by two independent reviewers. Outcomes, study characteristics, and risk of bias ratings will be extracted from multiple reports by two individuals working independently, stored in a publicly available database (Systematic Review Data Repository) and analyzed using commonly available statistical software. In each review, we will conduct a series of meta-analyses using data from different sources to determine how the results are affected by the inclusion of data from multiple published sources (e.g., journal articles and conference abstracts) as well as unpublished aggregate data (e.g., clinical study reports) and individual participant data (IPD). We will identify patient-centered outcomes in each report and identify differences in the reporting of these outcomes across sources.CRD42015014037 , CRD42015014038.


Rouse B.,Center for Clinical Trials and Evidence Synthesis | Cipriani A.,University of Oxford | Shi Q.,International Vaccine Access Center | Coleman A.L.,University of California at Los Angeles | And 2 more authors.
Annals of Internal Medicine | Year: 2016

Background: Network meta-analysis compares multiple treatment options for the same condition and may be useful for developing clinical practice guidelines. Purpose: To compare treatment recommendations for first-line medical therapy for primary open angle-glaucoma (POAG) from major updates of American Academy of Ophthalmology (AAO) guidelines with the evidence available at the time, using network meta-analysis. Data Sources: MEDLINE, Embase, and the Cochrane Library were searched on 11 March 2014 for randomized, controlled trials (RCTs) of glaucoma monotherapies compared with placebo, vehicle, or no treatment or other monotherapies. The AAO Web site was searched in August 2014 to identify AAO POAG guidelines. Study Selection: Eligible RCTs were selected by 2 independent reviewers, and guidelines were selected by 1 person. Data Extraction: One person abstracted recommendations from guidelines and a second person verified. Two people independently abstracted data from included RCTs. Data Synthesis: Guidelines were grouped together on the basis of literature search dates, and RCTs that existed at 1991, 1995, 1999, 2004, and 2009 were analyzed. The outcome of interest was intraocular pressure (IOP) at 3 months. Only the latest guideline made a specific recommendation: prostaglandins. Network meta-analyses showed that all treatments were superior to placebo in decreasing IOP at 3 months. The mean reductions (95% credible intervals [CrIs]) for the highest-ranking class compared with placebo were as follows: 1991: β-blockers, 4.01 (CrI, 0.48 to 7.43); 1995: α2-adrenergic agonists, 5.64 (CrI, 1.73 to 9.50); 1999: prostaglandins, 5.43 (CrI, 3.38 to 7.38); 2004: prostaglandins, 4.75 (CrI, 3.11 to 6.44); 2009: prostaglandins, 4.58 (CrI, 2.94 to 6.24). Limitation: When comparisons are informed by a small number of studies, the treatment effects and rankings may not be stable. Conclusion: For timely recommendations when multiple treatment options are available, guidelines developers should consider network meta-analysis. © 2016 American College of Physicians.


Oud M.,Trimbos Institute | Mayo-Wilson E.,Center for Clinical Trials and Evidence Synthesis | Braidwood R.,University College London | Schulte P.,Treatment Center for Bipolar Disorders | And 5 more authors.
British Journal of Psychiatry | Year: 2016

Background Psychological interventions may be beneficial in bipolar disorder. Aims To evaluate the efficacy of psychological interventions for adults with bipolar disorder. Method A systematic review of randomised controlled trials was conducted. Outcomes were meta-analysed using RevMan and confidence assessed using the GRADE method. Results We included 55 trials with 6010 participants. Moderate-quality evidence associated individual psychological interventions with reduced relapses at post-treatment (risk ratio (RR) = 0.66, 95% CI 0.48-0.92) and follow-up (RR = 0.74, 95% CI 0.63-0.87), and collaborative care with a reduction in hospital admissions (RR =0.68, 95% CI 0.49-0.94). Low-quality evidence associated group interventions with fewer depression relapses at posttreatment and follow-up, and family psychoeducation with reduced symptoms of depression and mania. Conclusions There is evidence that psychological interventions are effective for people with bipolar disorder. Much of the evidence was of low or very low quality thereby limiting our conclusions. Further research should identify the most effective (and cost-effective) interventions for each phase of this disorder. © The Royal College of Psychiatrists 2016.


PubMed | Karolinska Institutet, RAND Corporation. and Center for Clinical Trials and Evidence Synthesis
Type: Journal Article | Journal: Journal of consulting and clinical psychology | Year: 2016

Prospective registration increases the validity of randomized controlled trials (RCTs). In the United States, registration is a legal requirement for drugs and devices regulated by the Food and Drug Administration (FDA), and many biomedical journals refuse to publish trials that are not registered. Trials in clinical psychology have not been subject to these requirements; it is unknown to what extent they are registered.We searched the 25 highest-impact clinical psychology journals that published at least 1 RCT of a health-related psychological intervention in 2013. For included trials, we evaluated their registration status (prospective, retrospective, not registered) and the completeness of their outcome definitions.We identified 163 articles that reported 165 RCTs; 73 (44%) RCTs were registered, of which only 25 (15%) were registered prospectively. Of registered RCTs, only 42 (58%) indicated their registration status in the publication. Only 2 (1% of all trials) were registered prospectively and defined their primary outcomes completely. For the primary outcome(s), 72 (99%) of all registrations defined the domain, 67 (92%) the time frame, and 48 (66%) the specific measurements. Only 19 (26%) and 5 (7%) defined the specific metric and method of aggregation, respectively, for all primary outcomes.Very few reports of RCTs published in clinical psychology journals were registered prospectively and completely. Clinical psychology journals could improve transparency and reproducibility, as well as reduce bias, by requiring complete prospective trial registration for publication and by including trial registration numbers in all reports of RCTs. (PsycINFO Database Record


Mayo-Wilson E.,Center for Clinical Trials and Evidence Synthesis | Imdad A.,SUNY Upstate Medical University | Junior J.,Harvard University | Dean S.,Albert Einstein Medical Center | And 2 more authors.
BMJ Open | Year: 2014

Objective: Zinc deficiency is widespread, and preventive supplementation may have benefits in young children. Effects for children over 5 years of age, and effects when coadministered with other micronutrients are uncertain. These are obstacles to scale-up. This review seeks to determine if preventive supplementation reduces mortality and morbidity for children aged 6 months to 12 years. Design: Systematic review conducted with the Cochrane Developmental, Psychosocial and Learning Problems Group. Two reviewers independently assessed studies. Meta-analyses were performed for mortality, illness and side effects. Data sources: We searched multiple databases, including CENTRAL and MEDLINE in January 2013. Authors were contacted for missing information. Eligibility criteria for selecting studies: Randomised trials of preventive zinc supplementation. Hospitalised children and children with chronic diseases were excluded. Results: 80 randomised trials with 205 401 participants were included. There was a small but non-significant effect on all-cause mortality (risk ratio (RR) 0.95 (95% CI 0.86 to 1.05)). Supplementation may reduce incidence of all-cause diarrhoea (RR 0.87 (0.85 to 0.89)), but there was evidence of reporting bias. There was no evidence of an effect of incidence or prevalence of respiratory infections or malaria. There was moderate quality evidence of a very small effect on linear growth (standardised mean difference 0.09 (0.06 to 0.13)) and an increase in vomiting (RR 1.29 (1.14 to 1.46)). There was no evidence of an effect on iron status. Comparing zinc with and without iron cosupplementation and direct comparisons of zinc plus iron versus zinc administered alone favoured cointervention for some outcomes and zinc alone for other outcomes. Effects may be larger for children over 1 year of age, but most differences were not significant. Conclusions: Benefits of preventive zinc supplementation may outweigh any potentially adverse effects in areas where risk of zinc deficiency is high. Further research should determine optimal intervention characteristics and delivery strategies.


Li T.,Center for Clinical Trials and Evidence Synthesis | Yu T.,Center for Clinical Trials and Evidence Synthesis | Hawkins B.S.,Center for Clinical Trials and Evidence Synthesis | Dickersin K.,Center for Clinical Trials and Evidence Synthesis
PLoS ONE | Year: 2015

Randomized crossover trials are clinical experiments in which participants are assigned randomly to a sequence of treatments and each participant serves as his/her own control in estimating treatment effect. We need a better understanding of the validity of their results to enable recommendations as to which crossover trials can be included in meta-analysis and for development of reporting guidelines. Objective To evaluate the characteristics of the design, analysis, and reporting of crossover trials for inclusion in a meta-analysis of treatment for primary open-angle glaucoma and to provide empirical evidence to inform the development of tools to assess the validity of the results from crossover trials and reporting guidelines. Methods We searched MEDLINE, EMBASE, and Cochrane's CENTRAL register for randomized crossover trials for a systematic review and network meta-analysis we are conducting. Two individuals independently screened the search results for eligibility and abstracted data from each included report. Results We identified 83 crossover trials eligible for inclusion. Issues affecting the risk of bias in crossover trials, such as carryover, period effects and missing data, were often ignored. Some trials failed to accommodate the within-individual differences in the analysis. For a large proportion of the trials, the authors tabulated the results as if they arose from a parallel design. Precision estimates properly accounting for the paired nature of the design were often unavailable from the study reports; consequently, to include trial findings in a metaanalysis would require further manipulation and assumptions. Conclusions The high proportion of poorly reported analyses and results has the potential to affect whether crossover data should or can be included in a meta-analysis. There is pressing need for reporting guidelines for crossover trials. Copyright: © 2015 Li et al.


PubMed | Center for Clinical Trials and Evidence Synthesis and University of Ioannina
Type: Journal Article | Journal: Internal and emergency medicine | Year: 2016

Network meta-analysis is a technique for comparing multiple treatments simultaneously in a single analysis by combining direct and indirect evidence within a network of randomized controlled trials. Network meta-analysis may assist assessing the comparative effectiveness of different treatments regularly used in clinical practice and, therefore, has become attractive among clinicians. However, if proper caution is not taken in conducting and interpreting network meta-analysis, inferences might be biased. The aim of this paper is to illustrate the process of network meta-analysis with the aid of a working example on first-line medical treatment for primary open-angle glaucoma. We discuss the key assumption of network meta-analysis, as well as the unique considerations for developing appropriate research questions, conducting the literature search, abstracting data, performing qualitative and quantitative synthesis, presenting results, drawing conclusions, and reporting the findings in a network meta-analysis.

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