scholarly journals Protocol for a systematic scoping review of reasons given to justify the performance of randomised controlled trials

BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e027575 ◽  
Author(s):  
Brian Dewar ◽  
Mark Fedyk ◽  
Lucas Jurkovic ◽  
Stephanie Chevrier ◽  
Rosendo Rodriguez ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomised Controlled Trials ◽  
Data Extraction ◽  
Grey Literature ◽  
Medical Knowledge ◽  
Controlled Trials ◽  
Trial Methodology ◽  
Clinical Trial Methodology ◽  
Scoping Reviews ◽  
Randomised Controlled

IntroductionRandomised controlled trials (RCTs) are widely viewed to generate the most reliable medical knowledge. However, RCTs are not always scientifically necessary and therefore not always ethical. Unfortunately, it is not clear when an RCT is not necessary or how this should be established. This study seeks to systematically catalogue justifications offered throughout the medical and ethics literature for performing randomisation within clinical trials.Methods and analysisWe will systematically search electronic databases of the medical literature including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov; databases of philosophical literature including Philosopher’s Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE, National Reference Centre for Bioethics; the library catalogue at the University of Ottawa; bibliographies of retrieved papers; and the grey literature. We will also pursue suggestions from experts in the fields of medical ethics, philosophy and clinical trial methodology. Article screening, selection and data extraction will be performed by two independent reviewers based on prespecified inclusion/exclusion criteria. A third reviewer will be consulted to resolve any discrepancies. We will then extract the reasons given to justify randomisation using methodology established to extract data in a defensible, systematic manner. We will track the reasons given, their frequency of use and changes over time. Finally, using grounded theory, we will combine the reasons into broader themes. These themes will form the foundation of our subsequent analysis from qualitative and quantitative perspectives. This review will map existing arguments that clinicians, ethicists and philosophers use to ethically justify randomisation in clinical trials.Ethics and disseminationNo research ethics board approval is necessary because we are not examining patient-level data. This protocol complies with the reported guidance for conducting systematic scoping reviews. The findings of this paper will be disseminated via presentations and academic publication. In a subsequent phase of this research, we hope to engage with stakeholders and translate any recommendations derived from our findings into operational guidelines.

scholarly journals Analysis and reporting of adverse events in randomised controlled trials: a review

BMJ Open ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. e024537 ◽  
Author(s):  
Rachel Phillips ◽  
Lorna Hazell ◽  
Odile Sauzet ◽  
Victoria Cornelius
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Hypothesis Testing ◽  
Randomised Controlled Trials ◽  
Data Extraction ◽  
Safety Data ◽  
Multiple Hypothesis Testing ◽  
Controlled Trials ◽  
Reporting Practices ◽  
Randomised Controlled

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.

scholarly journals Comparative efficacy and safety of interventions for treating head lice: a protocol for systematic review and network meta-analysis

2021 ◽  
Vol 5 (1) ◽  
pp. e001129
Author(s):  
Bill Stevenson ◽  
Wubshet Tesfaye ◽  
Julia Christenson ◽  
Cynthia Mathew ◽  
Solomon Abrha ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Grey Literature ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Head Lice ◽  
Efficacy And Safety ◽  
Randomised Controlled ◽  
Meta Analyses

BackgroundHead lice infestation is a major public health problem around the globe. Its treatment is challenging due to product failures resulting from rapidly emerging resistance to existing treatments, incorrect treatment applications and misdiagnosis. Various head lice treatments with different mechanism of action have been developed and explored over the years, with limited report on systematic assessments of their efficacy and safety. This work aims to present a robust evidence summarising the interventions used in head lice.MethodThis is a systematic review and network meta-analysis which will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement for network meta-analyses. Selected databases, including PubMed, Embase, MEDLINE, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials will be systematically searched for randomised controlled trials exploring head lice treatments. Searches will be limited to trials published in English from database inception till 2021. Grey literature will be identified through Open Grey, AHRQ, Grey Literature Report, Grey Matters, ClinicalTrials.gov, WHO International Clinical Trials Registry and International Standard Randomised Controlled Trials Number registry. Additional studies will be sought from reference lists of included studies. Study screening, selection, data extraction and assessment of methodological quality will be undertaken by two independent reviewers, with disagreements resolved via a third reviewer. The primary outcome measure is the relative risk of cure at 7 and 14 days postinitial treatment. Secondary outcome measures may include adverse drug events, ovicidal activity, treatment compliance and acceptability, and reinfestation. Information from direct and indirect evidence will be used to generate the effect sizes (relative risk) to compare the efficacy and safety of individual head lice treatments against a common comparator (placebo and/or permethrin). Risk of bias assessment will be undertaken by two independent reviewers using the Cochrane Risk of Bias tool and the certainty of evidence assessed using the Grading of Recommendations, Assessment, Development and Evaluations guideline for network meta-analysis. All quantitative analyses will be conducted using STATA V.16.DiscussionThe evidence generated from this systematic review and meta-analysis is intended for use in evidence-driven treatment of head lice infestations and will be instrumental in informing health professionals, public health practitioners and policy-makers.PROSPERO registration numberCRD42017073375.

scholarly journals Rationalisations for women-only randomised controlled trials in conditions that affect both sexes: a scoping review protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e043370
Author(s):  
Ainsley Matthewson ◽  
Olena Bereznyakova ◽  
Brian Dewar ◽  
Alexandra Davis ◽  
Mark Fedyk ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Scoping Review ◽  
Randomised Controlled Trials ◽  
Standard Of Care ◽  
Standards Of Care ◽  
Controlled Trials ◽  
Theory Approach ◽  
Reference Centre ◽  
Cochrane Database ◽  
Randomised Controlled

IntroductionWomen have historically been under-represented in randomised controlled trials (RCTs), including many landmark RCTs that established standards of care. In light of this fact, some modern researchers are calling for replication of earlier landmark trials with women only. This approach is ethically concerning, in that it would require some enrolled women to be deprived of treatments that are currently considered standard of care.ObjectiveIn an attempt to better understand the justification of a women-only approach to designing clinical trials, this study looks to systematically categorise the number of women-only RCTs for conditions that affect both men and women and the reasons given within the medical and philosophical literatures to perform them.MethodologyThis scoping review of the literature will search, screen and select articles based on predetermined inclusion/exclusion criteria, after which a grounded theory approach will be used to synthesise the data. It is expected that there will be a variety of reasons given for why a women-only trial may be justified. Electronic databases that will be searched include MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov, Philosopher’s Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE and the National Reference Centre for Bioethics.SignificanceThe scope of this study is to determine published rationales used to justify women-only randomised trials, both in the case of new trials and in the repetition of landmark trials.Ethics and disseminationResearch ethics board approval is not required for this study as there is no participant involvement. Results will be published as a stand-alone manuscript and will inform a larger project related to the ethics of a women-only RCT of carotid intervention for women with symptomatic high-grade carotid stenosis.

scholarly journals Stability of ARDS subphenotypes over time in two randomised controlled trials

Thorax ◽  
2018 ◽  
Vol 73 (5) ◽  
pp. 439-445 ◽  
Author(s):  
Kevin Delucchi ◽  
Katie R Famous ◽  
Lorraine B Ware ◽  
Polly E Parsons ◽  
B Taylor Thompson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Outcomes ◽  
Randomised Controlled Trials ◽  
Latent Class ◽  
Lung Protective Ventilation ◽  
Controlled Trials ◽  
Transition Analysis ◽  
Class 1 ◽  
Randomised Controlled ◽  
Over Time

RationaleTwo distinct acute respiratory distress syndrome (ARDS) subphenotypes have been identified using data obtained at time of enrolment in clinical trials; it remains unknown if these subphenotypes are durable over time.ObjectiveTo determine the stability of ARDS subphenotypes over time.MethodsSecondary analysis of data from two randomised controlled trials in ARDS, the ARMA trial of lung protective ventilation (n=473; patients randomised to low tidal volumes only) and the ALVEOLI trial of low versus high positive end-expiratory pressure (n=549). Latent class analysis (LCA) and latent transition analysis (LTA) were applied to data from day 0 and day 3, independent of clinical outcomes.Measurements and main resultsIn ALVEOLI, LCA indicated strong evidence of two ARDS latent classes at days 0 and 3; in ARMA, evidence of two classes was stronger at day 0 than at day 3. The clinical and biological features of these two classes were similar to those in our prior work and were largely stable over time, though class 2 demonstrated evidence of progressive organ failures by day 3, compared with class 1. In both LCA and LTA models, the majority of patients (>94%) stayed in the same class from day 0 to day 3. Clinical outcomes were statistically significantly worse in class 2 than class 1 and were more strongly associated with day 3 class assignment.ConclusionsARDS subphenotypes are largely stable over the first 3 days of enrolment in two ARDS Network trials, suggesting that subphenotype identification may be feasible in the context of clinical trials.

scholarly journals Inequity in rehabilitation interventions after hip fracture: a systematic review

2019 ◽  
Vol 48 (4) ◽  
pp. 489-497 ◽  
Author(s):  
K J Sheehan ◽  
L Fitzgerald ◽  
S Hatherley ◽  
C Potter ◽  
S Ayis ◽  
...  
Keyword(s):  
Nursing Home ◽  
Cognitive Impairment ◽  
Hip Fracture ◽  
Randomised Controlled Trials ◽  
Care Pathway ◽  
Data Extraction ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Eligibility Criteria ◽  
Randomised Controlled

Abstract Objective to determine the extent to which equity factors contributed to eligibility criteria of trials of rehabilitation interventions after hip fracture. We define equity factors as those that stratify healthcare opportunities and outcomes. Design systematic search of MEDLINE, Embase, CINHAL, PEDro, Open Grey, BASE and ClinicalTrials.gov for randomised controlled trials of rehabilitation interventions after hip fracture published between 1 January 2008 and 30 May 2018. Trials not published in English, secondary prevention or new models of service delivery (e.g. orthogeriatric care pathway) were excluded. Duplicate screening for eligibility, risk of bias (Cochrane Risk of Bias Tool) and data extraction (Cochrane’s PROGRESS-Plus framework). Results twenty-three published, eight protocol, four registered ongoing randomised controlled trials (4,449 participants) were identified. A total of 69 equity factors contributed to eligibility criteria of the 35 trials. For more than 50% of trials, potential participants were excluded based on residency in a nursing home, cognitive impairment, mobility/functional impairment, minimum age and/or non-surgical candidacy. Where reported, this equated to the exclusion of 2,383 out of 8,736 (27.3%) potential participants based on equity factors. Residency in a nursing home and cognitive impairment were the main drivers of these exclusions. Conclusion the generalisability of trial results to the underlying population of frail older adults is limited. Yet, this is the evidence base underpinning current service design. Future trials should include participants with cognitive impairment and those admitted from nursing homes. For those excluded, an evidence-informed reasoning for the exclusion should be explicitly stated. PROSPERO CRD42018085930.

scholarly journals Interventions for oropharyngeal dysphagia in acute and critical care: a protocol for a systematic review and meta-analysis

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Sallyanne Duncan ◽  
Jennifer Mc Gaughey ◽  
Richard Fallis ◽  
Daniel F. McAuley ◽  
Margaret Walshe ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Critical Care ◽  
Acute Care ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Oropharyngeal Dysphagia ◽  
Length Of Hospital Stay ◽  
Controlled Trials ◽  
Randomised Controlled

Abstract Background Oropharyngeal dysphagia or swallowing difficulties are common in acute care and critical care, affecting 47% of hospitalised frail elderly, 50% of acute stroke patients and approximately 62% of critically ill patients who have been intubated and mechanically ventilated for prolonged periods. Complications of dysphagia include aspiration leading to chest infection and pneumonia, malnutrition, increased length of hospital stay and re-admission to hospital. To date, most dysphagia interventions in acute care have been tested with acute stroke populations. While intervention studies in critical care have been emerging since 2015, they are limited and so there is much to learn about the type, the delivery and the intensity of treatments in this setting to inform future clinical trials. The aim of this systematic review is to summarise the evidence regarding the relationship between dysphagia interventions and clinically important patient outcomes in acute and critical care settings. Methods We will search MEDLINE, EMBASE, CENTRAL, Web of Science, CINAHL and clinical trial registries from inception to the present. We will include studies conducted with adults in acute care settings such as acute hospital wards or units or intensive care units and critical care settings. Studies will be restricted to randomised controlled trials and quasi-randomised controlled trials comparing a new dysphagia intervention with usual care or another intervention. The main outcomes that will be collected include length of time taken to return to oral intake, change in incidence of aspiration and pneumonia, nutritional status, length of hospital stay and quality of life. Key intervention components such as delivery, intensity, acceptability, fidelity and adverse events associated with such interventions will be collected to inform future clinical trials. Two independent reviewers will assess articles for eligibility, data extraction and quality appraisal. A meta-analysis will be conducted as appropriate. Discussion No systematic review has attempted to summarise the evidence for oropharyngeal dysphagia interventions in acute and critical care. Results of the proposed systematic review will inform practice and the design of future clinical trials. Systematic review registration PROSPERO CRD 42018116849 (http://www.crd.york.ac.uk/PROSPERO/)

50 Tips for Clinical Trialists

2017 ◽  
Vol 19 (1) ◽  
pp. 59-69 ◽  
Author(s):  
Lisa A. Harvey ◽  
Joanne V. Glinsky ◽  
Robert D. Herbert
Keyword(s):  
Clinical Trials ◽  
Randomised Controlled Trials ◽  
Controlled Trials ◽  
Randomised Controlled

This paper presents ‘Tips’ for researchers of brain impairment who are interested in conducting randomised controlled trials. The paper is intended for researchers who are planning to undertake their first trial, but may also be of interest to more experienced trialists or clinicians who want to further their understandings of clinical trials. The Tips include suggestions for how to design, conduct, analyse and report clinical trials.

scholarly journals A systematic review of inequalities in the uptake of, adherence to and effectiveness of behavioural weight management interventions

2021 ◽  
Author(s):  
Jack Birch ◽  
Rebecca Jones ◽  
Julia Mueller ◽  
Matthew McDonald ◽  
Rebecca Richards ◽  
...  
Keyword(s):  
Systematic Review ◽  
Weight Management ◽  
Health Inequalities ◽  
Randomised Controlled Trials ◽  
Data Extraction ◽  
Meta Analysis ◽  
Original Research ◽  
Controlled Trials ◽  
Management Interventions ◽  
Randomised Controlled

Background: It has been suggested that interventions focusing on individual behaviour change, such as behavioural weight management interventions, may exacerbate health inequalities. These intervention-generated inequalities may occur at different stages, including intervention uptake, adherence and effectiveness. We conducted a systematic review to synthesise evidence on how different measures of inequality moderate the uptake of, adherence to and effectiveness of behavioural weight management interventions in adults. Methods: We updated a previous systematic literature review from the US Preventive Services Taskforce to identify trials of behavioural weight management interventions in adults that could be conducted in or recruited from primary care. Medline, Cochrane database (CENTRAL) and PsycINFO were searched. Only randomised controlled trials and cluster-randomised controlled trials were included. Two investigators independently screened articles for eligibility and conducted risk of bias assessment. We curated publication families for eligible trials. The PROGRESS-Plus acronym (place of residence, race/ethnicity, occupation, gender, religion, education, socioeconomic status, social capital, plus other discriminating factors) was used to consider a comprehensive range of health inequalities. Data on trial uptake, intervention adherence, weight change, and PROGRESS-Plus related-data were extracted. Results: Data extraction in currently underway. A total of 108 studies are included in the review. Data will be synthesised narratively and through the use of Harvest Plots. A Harvest plot for each PROGRESS-Plus criterion will be presented, showing whether each trial found a negative, positive or no health inequality gradient. We will also identify potential sources of unpublished original research data on these factors which can be synthesised through a future individual participant data meta- analysis. Conclusions and implications: The review findings will contribute towards the consideration of intervention-generated inequalities by researchers, policy makers and healthcare and public health practitioners. Authors of trials included in the completed systematic review may be invited to collaborate on a future IPD meta-analysis. PROSPERO registration number: CRD42020173242

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