Dataset Information

The effect of blinding on estimates of mortality in randomised clinical trials of intensive care interventions: protocol for a systematic review and meta-analysis.

ABSTRACT:

Introduction

Evidence exists that unblinded randomised clinical trials (RCTs) overestimate intervention effects compared with blinded RCTs. It has been suggested that this is less pronounced for objective (ie, not subject to interpretation) outcome measures, including mortality. This may not apply in the intensive care unit (ICU), as most deaths are preceded by decisions to withhold or withdraw treatments. Lack of blinding of physicians in RCTs of ICU interventions may potentially influence the decision towards a higher threshold for discontinuing treatment in patients who receive the investigational treatment and/or a lower threshold for discontinuing treatment in patients who receive the comparator (control). This may have important implications for patients, caregivers, researchers and society. Accordingly, we aim to assess whether lack of blinding affects mortality effect estimates in RCTs of ICU interventions.

Methods and analysis

We will conduct a systematic review with meta-analyses and assess the effect of blinding versus no blinding on mortality effect estimates in RCTs of interventions used in adult ICU patients.We will systematically search the Cochrane Library for systematic reviews reporting mortality effect estimates of any intervention used in adult ICU patients which includes at least one RCT with 'low risk of bias' in the bias domains 'blinding of participants and personnel' and/or 'blinding of outcome assessment' and one RCT with 'unclear' or 'high risk of bias' in the same bias domain(s). For each intervention, we will compare summary mortality effect estimates in blinded versus unblinded trials.

Ethics and dissemination

This research does not require ethical approval as we will use summary data from trials already approved by relevant ethical institutions. We will report the results in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and submit the final paper to an international peer-reviewed journal.

Trial registration number

PROSPERO, registration number: CRD42017056212.

SUBMITTER: Anthon CT

PROVIDER: S-EPMC5541632 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Publications

The effect of blinding on estimates of mortality in randomised clinical trials of intensive care interventions: protocol for a systematic review and meta-analysis.

Anthon Carl Thomas CT Granholm Anders A Perner Anders A Laake Jon Henrik JH Møller Morten Hylander MH

BMJ open 20170711 7

<h4>Introduction</h4>Evidence exists that unblinded randomised clinical trials (RCTs) overestimate intervention effects compared with blinded RCTs. It has been suggested that this is less pronounced for objective (ie, not subject to interpretation) outcome measures, including mortality. This may not apply in the intensive care unit (ICU), as most deaths are preceded by decisions to withhold or withdraw treatments. Lack of blinding of physicians in RCTs of ICU interventions may potentially influe ...[more]

PMID: 28701412

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Project description:ObjectivesTo study the impact of blinding on estimated treatment effects, and their variation between trials; differentiating between blinding of patients, healthcare providers, and observers; detection bias and performance bias; and types of outcome (the MetaBLIND study).DesignMeta-epidemiological study.Data sourceCochrane Database of Systematic Reviews (2013-14).Eligibility criteria for selecting studiesMeta-analyses with both blinded and non-blinded trials on any topic.Review methodsBlinding status was retrieved from trial publications and authors, and results retrieved automatically from the Cochrane Database of Systematic Reviews. Bayesian hierarchical models estimated the average ratio of odds ratios (ROR), and estimated the increases in heterogeneity between trials, for non-blinded trials (or of unclear status) versus blinded trials. Secondary analyses adjusted for adequacy of concealment of allocation, attrition, and trial size, and explored the association between outcome subjectivity (high, moderate, low) and average bias. An ROR lower than 1 indicated exaggerated effect estimates in trials without blinding.ResultsThe study included 142 meta-analyses (1153 trials). The ROR for lack of blinding of patients was 0.91 (95% credible interval 0.61 to 1.34) in 18 meta-analyses with patient reported outcomes, and 0.98 (0.69 to 1.39) in 14 meta-analyses with outcomes reported by blinded observers. The ROR for lack of blinding of healthcare providers was 1.01 (0.84 to 1.19) in 29 meta-analyses with healthcare provider decision outcomes (eg, readmissions), and 0.97 (0.64 to 1.45) in 13 meta-analyses with outcomes reported by blinded patients or observers. The ROR for lack of blinding of observers was 1.01 (0.86 to 1.18) in 46 meta-analyses with subjective observer reported outcomes, with no clear impact of degree of subjectivity. Information was insufficient to determine whether lack of blinding was associated with increased heterogeneity between trials. The ROR for trials not reported as double blind versus those that were double blind was 1.02 (0.90 to 1.13) in 74 meta-analyses.ConclusionNo evidence was found for an average difference in estimated treatment effect between trials with and without blinded patients, healthcare providers, or outcome assessors. These results could reflect that blinding is less important than often believed or meta-epidemiological study limitations, such as residual confounding or imprecision. At this stage, replication of this study is suggested and blinding should remain a methodological safeguard in trials.

Project description:INTRODUCTION:There is rising awareness that we need multidisciplinary approaches integrating psychological treatments for schizophrenia, but a comprehensive evidence based on their relative efficacy is lacking. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs) to rank psychological treatments for schizophrenia according to their efficacy, acceptability and tolerability. METHODS AND ANALYSIS:We will include all RCTs comparing a psychological treatment aimed at positive symptoms of schizophrenia with another psychological intervention or with a no treatment condition (waiting-list and treatment as usual). We will include studies on adult patients with schizophrenia, excluding specific subpopulations (eg, first-episode patients or patients with psychiatric comorbidities). Primary outcome will be the change in positive symptoms on a published rating scale. Secondary outcomes will be acceptability (dropout), change in overall and negative symptoms of schizophrenia, response, relapse, adherence, depression, quality of life, functioning and adverse events. Published and unpublished studies will be sought through database searches, trial registries and websites. Study selection and data extraction will be conducted by at least two independent reviewers. We will conduct random-effects NMA to synthesise all evidences for each outcome and obtain a comprehensive ranking of all treatments. NMA will be conducted in Stata and R within a frequentist framework. The risk of bias in studies will be evaluated using the Cochrane Risk of Bias tool and the credibility of the evidence will be evaluated using an adaptation of the Grading of Recommendations Assessment, Development and Evaluation framework to NMA, recommended by the Cochrane guidance. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings. ETHICS AND DISSEMINATION:No ethical issues are foreseen. Results from this study will be published in peer-reviewed journals and presented at relevant conferences. PROSPERO REGISTRATION NUMBER:CRD42017067795.

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Project description:IntroductionTherapeutic recommendations for hidradenitis suppurativa (HS) have recently shifted towards non-invasive pharmacological options. Recent evidence has shown promising efficacy for specific treatments. However, data regarding the comparative efficacy of these treatments in patients with HS are still limited. Therefore, we plan to conduct a systematic review and network meta-analysis (NMA) to summarise the benefits and harms of different pharmacological interventions for treating people living with HS.Methods and analysisWe will search electronic databases, including Medline, Embase, PubMed, Web of Science, Scopus, CINAHL and Cochrane Library beginning from their inception dates with no language restrictions. A grey literature search will be performed to supplement the electronic databases. Both randomised trials and non-randomised studies using validated measurement tools that investigated the benefits and harms of pharmacological interventions among people living with HS will be included. The predefined primary outcomes will include treatment responses that reflect the patient's perspective and all-cause discontinuation. Screening, selection, extraction, assessment of the risk of bias and analysis of the strength of the evidence will be performed independently by a pair of reviewers. A two-step approach of traditional pairwise and NMA will be performed. Based on a random-effects model, standardised weighted mean differences and ORs with corresponding 95% CIs will be pooled as effect estimates for the continuous and categorical endpoints, respectively. Statistical and methodological heterogeneities will be assessed. Preplanned subgroup analyses and univariate meta-regression will be conducted to quantify the potential sources of heterogeneity. Evidence-based synthesis will be based on the magnitudes of effect size, evidence certainty and the surface under the cumulative ranking curve values.Ethics and disseminationEthical approval is not required because this study is based on existing published data. These findings will be disseminated through scientific meetings and publications in peer-reviewed journals.Prospero registration numberCRD42022302795.

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Dataset Information

The effect of blinding on estimates of mortality in randomised clinical trials of intensive care interventions: protocol for a systematic review and meta-analysis.

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Publications

The effect of blinding on estimates of mortality in randomised clinical trials of intensive care interventions: protocol for a systematic review and meta-analysis.

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