scholarly journals Explaining temporal trends in annualised relapse rates in placebo groups of randomised controlled trials in relapsing multiple sclerosis: systematic review and meta-regression

2013 ◽  
Vol 19 (12) ◽  
pp. 1580-1586 ◽  
Author(s):  
Simon M Steinvorth ◽  
Christian Röver ◽  
Simon Schneider ◽  
Richard Nicholas ◽  
Sebastian Straube ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Randomised Controlled Trials ◽  
Controlled Trials ◽  
Eligibility Criteria ◽  
Patient Age ◽  
Meta Regression ◽  
Randomised Controlled ◽  
Relapsing Multiple Sclerosis ◽  
Relapse Rates ◽  
Over Time

Background: Recent studies have shown a decrease in annualised relapse rates (ARRs) in placebo groups of randomised controlled trials (RCTs) in relapsing multiple sclerosis (RMS). Methods: We conducted a systematic literature search of RCTs in RMS. Data on eligibility criteria and baseline characteristics were extracted and tested for significant trends over time. A meta-regression was conducted to estimate their contribution to the decrease of trial ARRs over time. Results: We identified 56 studies. Patient age at baseline ( p < 0.001), mean duration of multiple sclerosis (MS) at baseline ( p = 0.048), size of treatment groups ( p = 0.003), Oxford Quality Scale scores ( p = 0.021), and the number of eligibility criteria ( p<0.001) increased significantly, whereas pre-trial ARR ( p = 0.001), the time span over which pre-trial ARR was calculated ( p < 0.001), and the duration of placebo-controlled follow-up ( p = 0.006) decreased significantly over time. In meta-regression of trial placebo ARR, the temporal trend was found to be insignificant, with major factors explaining the variation: pre-trial ARR, the number of years used to calculate pre-trial ARR and study duration. Conclusion: The observed decline in trial ARRs may result from decreasing pre-trial ARRs and a shorter time period over which pre-trial ARRs were calculated. Increasing patient age and duration of illness may also contribute.

scholarly journals Effects of statins in patients with chronic kidney disease: meta-analysis and meta-regression of randomised controlled trials

BMJ ◽  
2008 ◽  
Vol 336 (7645) ◽  
pp. 645-651 ◽  
Author(s):  
Giovanni F M Strippoli ◽  
Sankar D Navaneethan ◽  
David W Johnson ◽  
Vlado Perkovic ◽  
Fabio Pellegrini ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Meta Regression ◽  
Randomised Controlled

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 Total extraperitoneal endoscopic hernioplasty (TEP) versus Lichtenstein hernioplasty: a systematic review by updated traditional and cumulative meta-analysis of randomised-controlled trials

Hernia ◽  
2019 ◽  
Vol 23 (6) ◽  
pp. 1093-1103 ◽  
Author(s):  
P. Gavriilidis ◽  
R. J. Davies ◽  
J. Wheeler ◽  
N. de’Angelis ◽  
S. Di Saverio
Keyword(s):  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Current Evidence ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Vascular Injuries ◽  
Lichtenstein Hernioplasty ◽  
Randomised Controlled ◽  
Haematoma Formation ◽  
Over Time

Abstract Background–purpose Totally extraperitoneal (TEP) endoscopic hernioplasty and Lichtenstein hernioplasty are the most commonly used approaches for inguinal hernia repair. However, current evidence on which is the preferred approach is inconclusive. This updated meta-analysis was conducted to track the accumulation of evidence over time. Methods Studies were identified by a systematic literature search of the EMBASE, PubMed, Cochrane Library, and Google Scholar databases. Fixed- and random-effects models were used to cumulatively assess the accumulation of evidence over time. Results The TEP cohort showed significantly higher rates of recurrences and vascular injuries compared to the Lichtenstein cohort; [Peto Odds ratio (OR) = 1.58 (1.22, 2.04), p = 0.005], [Peto OR = 2.49 (1.05, 5.88), p = 0.04], respectively. In contrast, haematoma formation rate, time to return to usual activities, and local paraesthesia were significantly lower in the TEP cohort compared to the Lichtenstein cohort; [Peto OR = 0.26 (0.16, 0.41), p ≤ 0.001], [mean difference = − 6.32 (− 8.17, − 4.48), p ≤ 0.001], [Peto OR = 0.26 (0.17, 0.40), p ≤ 0.001], respectively. Conclusions This study, which is based on randomised-controlled trials (RCTs) of high quality, showed significantly higher rates of recurrences and vascular injuries in the TEP cohort than in the Lichtenstein cohort. In contrast, rate of postoperative haematoma formation, local paraesthesia, and time to return to usual activities were significantly lower in the TEP cohort than in the Lichtenstein cohort. Future multicentre RCTs with strict adherence to the standards recommended in the Consolidated Standards of Reporting Trials guidelines will shed further light on the topic.

scholarly journals Data-sharing recommendations in biomedical journals and randomised controlled trials: an audit of journals following the ICMJE recommendations

BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e038887
Author(s):  
Maximilian Siebert ◽  
Jeanne Fabiola Gaba ◽  
Laura Caquelin ◽  
Henri Gouraud ◽  
Alain Dupuy ◽  
...  
Keyword(s):  
Medical Journal ◽  
Data Sharing ◽  
Randomised Controlled Trials ◽  
Primary Outcome ◽  
Controlled Trials ◽  
Cross Sectional Survey ◽  
Eligibility Criteria ◽  
Cross Sectional ◽  
Data Set ◽  
Randomised Controlled

ObjectiveTo explore the implementation of the International Committee of Medical Journal Editors (ICMJE) data-sharing policy which came into force on 1 July 2018 by ICMJE-member journals and by ICMJE-affiliated journals declaring they follow the ICMJE recommendations.DesignA cross-sectional survey of data-sharing policies in 2018 on journal websites and in data-sharing statements in randomised controlled trials (RCTs).SettingICMJE website; PubMed/Medline.Eligibility criteriaICMJE-member journals and 489 ICMJE-affiliated journals that published an RCT in 2018, had an accessible online website and were not considered as predatory journals according to Beall’s list. One hundred RCTs for member journals and 100 RCTs for affiliated journals with a data-sharing policy, submitted after 1 July 2018.Main outcome measuresThe primary outcome for the policies was the existence of a data-sharing policy (explicit data-sharing policy, no data-sharing policy, policy merely referring to ICMJE recommendations) as reported on the journal website, especially in the instructions for authors. For RCTs, our primary outcome was the intention to share individual participant data set out in the data-sharing statement.ResultsEight (out of 14; 57%) member journals had an explicit data-sharing policy on their website (three were more stringent than the ICMJE requirements, one was less demanding and four were compliant), five (35%) additional journals stated that they followed the ICMJE requirements, and one (8%) had no policy online. In RCTs published in these journals, there were data-sharing statements in 98 out of 100, with expressed intention to share individual patient data reaching 77 out of 100 (77%; 95% CI 67% to 85%). One hundred and forty-five (out of 489) ICMJE-affiliated journals (30%; 26% to 34%) had an explicit data-sharing policy on their website (11 were more stringent than the ICMJE requirements, 85 were less demanding and 49 were compliant) and 276 (56%; 52% to 61%) merely referred to the ICMJE requirements. In RCTs published in affiliated journals with an explicit data-sharing policy, data-sharing statements were rare (25%), and expressed intentions to share data were found in 22% (15% to 32%).ConclusionThe implementation of ICMJE data-sharing requirements in online journal policies was suboptimal for ICMJE-member journals and poor for ICMJE-affiliated journals. The implementation of the policy was good in member journals and of concern for affiliated journals. We suggest the conduct of continuous audits of medical journal data-sharing policies in the future.RegistrationThe protocol was registered before the start of the research on the Open Science Framework (https://osf.io/n6whd/).

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 Incidence and prognostic factors of knee extension deficits following anterior cruciate ligament reconstruction: A systematic review and meta-analysis of randomised controlled trials

2020 ◽  
Author(s):  
Nalan Ektas ◽  
Corey Scholes ◽  
Meredith Harrison-Brown ◽  
Maha Jegatheesan ◽  
Ashwin Rajesh ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Randomised Controlled Trials ◽  
Acl Injury ◽  
Knee Extension ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Extension Deficit ◽  
Eligibility Criteria ◽  
Randomised Controlled

ABSTRACTBackground and aimsKnee extension deficits complicate recovery from ACL injury and reconstruction, however the incidence of knee extension loss is not well defined. The aim of this review was to identify the incidence of loss of extension (LOE) following ACL rupture and reconstruction, explore the definitions of knee extension deficits reported and identify prognostic factors affecting LOE incidence.Methods and analysisA systematic search was conducted in Medline, Cochrane Library and PEDro for studies in publication up to September 2019, with no restrictions on publication year. References were screened and assessed for inclusion using predetermined eligibility criteria. Randomised controlled trials (RCTs) that quantified knee angle, loss of extension or incidence of extension deficit were included for quality assessment and data extraction. Statistical summaries were generated and meta-analyses performed in two parts to examine: (i) the probability of a datapoint being zero incidence compared to a non-zero incidence, and (ii) the relationship between the predictors and non-zero LOE incidence.ResultsA sample of 8594 papers were retrieved using the search criteria, with 48 studies meeting eligibility criteria. Pooled results from 4065 participants were included for analysis, with 3965 participants who had undergone ACLR. The proportion of included studies judged at an overall low risk of bias was small (6%). The analysis revealed median LOE incidence of 15.9% (IQR 1.4 - 46.5) at a median follow up from treatment of 4.9 months (IQR 1.9 - 24). Median LOE incidence was 23 % (IQR 8.4 - 50.0) for the subset of studies reporting up to 12 months of follow up. The observed group and study were the most important predictors for whether a datapoint reported an incidence of extension deficit. Time to follow up (P < 0.001) and graft type (P = 0.02) were found to have a significant influence on non-zero LOE incidence (%).ConclusionsThis review examined the definitions for the measurement and interpretation of postoperative knee extension, and established the trajectory of knee extension deficit after ACL injury and reconstruction. While factors associated with loss of extension were identified, the trajectory of knee extension deficits were difficult to infer due to discrepancies in measurement techniques and patient variation. Clinicians should expect up to 1 in 3 patients to present postoperatively with loss of extension of at least 3 degrees, which may partially resolve over time. Future work should focus on the development of a standardised framework for postoperative measurement and reporting of LOE.

scholarly journals Exclusion of enrolled participants in randomised controlled trials: what to do with ineligible participants?

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e039546
Author(s):  
Andrea M Rehman ◽  
Rashida Ferrand ◽  
Elizabeth Allen ◽  
Victoria Simms ◽  
Grace McHugh ◽  
...  
Keyword(s):  
Lung Function ◽  
Randomised Controlled Trials ◽  
Statistical Power ◽  
Human Error ◽  
Trial Steering Committee ◽  
Controlled Trials ◽  
Primary Analysis ◽  
Intervention Effect ◽  
Eligibility Criteria ◽  
Randomised Controlled

ObjectivePost-randomisation exclusions in randomised controlled trials are common and may include participants identified as not meeting trial eligibility criteria after randomisation. We report how a decision might be reached and reported on, to include or exclude these participants. We illustrate using a motivating scenario from the BREATHE trial (Trial registration ClinicalTrials.gov, NCT02426112) evaluating azithromycin for the treatment of chronic lung disease in people aged 6–19 years with HIV in Zimbabwe and Malawi.Key pointsIncluding all enrolled and randomised participants in the primary analysis of a trial ensures an unbiased estimate of the intervention effect using intention-to-treat principles, and minimises the effects of confounding through balanced allocation to trial arm. Ineligible participants are sometimes enrolled, due to measurement or human error. Of 347 participants enrolled into the BREATHE trial, 11 (3.2%) were subsequently found to be ineligible based on lung function criteria. We assumed no safety risk of azithromycin treatment; their inclusion in the trial and subsequent analysis of the intervention effect therefore mirrors clinical practice. Senior trial investigators considered diurnal variations in the measurement of lung function, advantages of retaining a higher sample size and advice from the Data Safety and Monitoring Board and Trial Steering Committee, and decided to include these participants in primary analysis. We planned and reported analyses including and excluding these participants, and in our case the interpretation of treatment effect was consistent.ConclusionThe decision, by senior investigators, on whether to exclude enrolled participants, should reflect issues of safety, treatment efficacy, statistical power and measurement error. As long as decisions are made prior to finalising the statistical analysis plan for the trial, the risk of exclusions creating bias should be minimal. The decision taken should be transparently reported and a sensitivity analysis can present the opposite decision.

scholarly journals Mindfulness-based interventions for mental well-being among people with multiple sclerosis: a systematic review and meta-analysis of randomised controlled trials

2019 ◽  
Vol 90 (9) ◽  
pp. 1051-1058 ◽  
Author(s):  
Robert Simpson ◽  
Sharon Simpson ◽  
Nitish Ramparsad ◽  
Margaret Lawrence ◽  
Jo Booth ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Treatment Options ◽  
Well Being ◽  
Controlled Trials ◽  
Medical Subject Headings ◽  
Randomised Controlled ◽  
Mental Well Being

ObjectiveImpairment of mental well-being (anxiety, depression, stress) is common among people with multiple sclerosis (PwMS). Treatment options are limited, particularly for anxiety. The aim of this study was to update our previous systematic review (2014) and evaluate via meta-analysis the efficacy of mindfulness-based interventions (MBIs) for improving mental well-being in PwMS.MethodsSystematic searches for eligible randomised controlled trials (RCTs) were carried out in seven major databases (November 2017, July 2018), using medical subject headings and key words. Studies were screened, data extracted, quality appraised and analysed by two independent reviewers, using predefined criteria. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Mental well-being was the primary outcome. Random effects model meta-analysis was performed, with effect size reported as standardised mean difference (SMD).ResultsTwelve RCTs including 744 PwMS were eligible for inclusion in the systematic review, eight had data extractable for meta-analysis; n=635. Ethnicity, socioeconomic status, comorbidity and disability were inconsistently reported. MBIs varied from manualised to tailored versions, lasting 6–9 weeks, delivered individually and via groups, both in person and online. Overall SMD for mental well-being (eight studies) was 0.40 (0.28–0.53), p<0.01, I2=28%; against active comparators only (three studies) SMD was 0.17 (0.01–0.32), p<0.05, I2 =0%. Only three adverse events were reported.ConclusionsMBIs are effective at improving mental well-being in PwMS. More research is needed regarding optimal delivery method, cost-effectiveness and comparative-effectiveness.PROSPERO registration numberCRD42018093171.

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