Reporting of eligibility criteria of randomised trials: cohort study comparing trial protocols with subsequent articles

ObjectiveTo investigate to what extent evidence from previous similar trials or systematic reviews was considered before conducting new trials.DesignCohort study of contemporary protocols for trials with ethical approval.MethodsAll protocols for randomised trials approved by the five ethical committees in Denmark between January 2012 and March 2013 were screened for eligibility. Included protocols were read in full to determine whether a systematic search had been conducted and references were checked to evaluate whether trial rationale and design could be challenged for not adequately considering previous evidence. To investigate whether protocols cited relevant trials, we used simple search strategies that could easily be conducted by researchers without experience with literature searches.ResultsSixty-seven protocols were included. Only two (3%) of the protocols explicitly stated to have conducted a literature search and only one (1%) provided information that allowed the search to be replicated. Eleven (16%) of the protocols described trials where we found the information insufficient to judge if the trial was ethically justified, either due to a comparator that was not supported by the presented evidence (six protocols), because they did not present a rationale for conducting the trial (two protocols), or for both reasons (three protocols). For eight (12%) of the protocols, our search identified trials that could have been relevant to cite as justification.ConclusionsWhile most protocols seem to adequately consider existing evidence, a substantial minority of trials might lack a sufficient evidence base. Very few trials seemed to have been based on a literature search which makes it impossible to know whether all relevant previous trials had been considered. Rules for ethical approval should include requirements for systematic literature searches to ensure that research participants are not exposed to sub-optimal treatments or unnecessary harms as well as to reduce research waste.

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P1-541 Reporting of eligibility criteria of randomised trials: empirical study comparing trial protocols to subsequent articles

Journal of Epidemiology & Community Health ◽

10.1136/jech.2011.142976h.28 ◽

2011 ◽

Vol 65 (Suppl 1) ◽

pp. A216-A216

Author(s):

A. Bluemle ◽

J. Meerpohl ◽

G. Ruecker ◽

G. Antes ◽

M. Schumacher ◽

...

Keyword(s):

Empirical Study ◽

Randomised Trials ◽

Eligibility Criteria ◽

Trial Protocols

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Conflicts of Interest at Medical Journals: The Influence of Industry-Supported Randomised Trials on Journal Impact Factors and Revenue – Cohort Study

PLoS Medicine ◽

10.1371/journal.pmed.1000354 ◽

2010 ◽

Vol 7 (10) ◽

pp. e1000354 ◽

Cited By ~ 69

Author(s):

Andreas Lundh ◽

Marija Barbateskovic ◽

Asbjørn Hróbjartsson ◽

Peter C. Gøtzsche

Keyword(s):

Cohort Study ◽

Conflicts Of Interest ◽

Impact Factors ◽

Randomised Trials ◽

Medical Journals ◽

Journal Impact

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Statin use in the secondary prevention of coronary heart disease in primary care: cohort study and comparison of inclusion and outcome with patients in randomised trials

BMJ ◽

10.1136/bmj.38398.408032.8f ◽

2005 ◽

Vol 330 (7495) ◽

pp. 821 ◽

Cited By ~ 51

Author(s):

Li Wei ◽

Shah Ebrahim ◽

Christopher Bartlett ◽

Peter D Davey ◽

Frank M Sullivan ◽

...

Keyword(s):

Primary Care ◽

Coronary Heart Disease ◽

Cohort Study ◽

Heart Disease ◽

Secondary Prevention ◽

Randomised Trials ◽

Statin Use

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Programme frequency, type, time and duration do not explain the effects of balance exercise in older adults: a systematic review with a meta-regression analysis

British Journal of Sports Medicine ◽

10.1136/bjsports-2016-096874 ◽

2018 ◽

Vol 53 (16) ◽

pp. 996-1002 ◽

Cited By ~ 5

Author(s):

Melanie K Farlie ◽

Lauren Robins ◽

Romi Haas ◽

Jennifer L Keating ◽

Elizabeth Molloy ◽

...

Keyword(s):

Systematic Review ◽

Older Adults ◽

Systematic Reviews ◽

Centre Of Mass ◽

Randomised Trials ◽

Eligibility Criteria ◽

Exercise Interventions ◽

Balance Exercise ◽

Control Centre ◽

Meta Analyses

ObjectiveThe objective of this systematic review was to examine the effects of different balance exercise interventions compared with non-balance exercise controls on balance task performance in older adults.DesignSystematic review.Data sourcesMedline, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Scopus and Cochrane Database of Systematic Reviews were searched until July 2017.Eligibility criteria for selecting studiesSystematic reviews and meta-analyses of randomised trials of balance exercise interventions for older adults were identified for extraction of eligible randomised trials. Eligibility criteria for inclusion of randomised trials in meta-analyses were comparison of a balance exercise intervention with a control group that did not perform balance exercises, report of at least one end-intervention balance outcome measurement that was consistent with the five subgroups of balance exercise identified, and full-text article available in English.ResultsNinety-five trials were included in meta-analyses and 80 in meta-regressions. For four balance exercise types (control centre of mass, multidimensional, mobility and reaching), significant effects for balance exercise interventions were found in meta-analyses (standardised mean difference (SMD) 0.31–0.50), however with considerable heterogeneity in observed effects (I2: 50.4%–80.6%). Risk of bias assessments (Physiotherapy Evidence Database score and funnel plots) did not explain heterogeneity. One significant relationship identified in the meta-regressions of SMD and balance exercise frequency, time and duration explained 2.1% of variance for the control centre of mass subgroup.ConclusionLimitations to this study included the variability in design of balance interventions, incomplete reporting of data and statistical heterogeneity. The design of balance exercise programmes provides inadequate explanation of the observed benefits of these interventions.

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Efficacy, immunogenicity and safety of a recombinant tetravalent dengue vaccine (CYD-TDV) in children aged 2–17 years: systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2017-019368 ◽

2019 ◽

Vol 9 (3) ◽

pp. e019368 ◽

Cited By ~ 3

Author(s):

Bruno Rodrigues Rosa ◽

Antonio José Ledo Alves da Cunha ◽

Roberto de Andrade Medronho

Keyword(s):

Systematic Review ◽

Incomplete Data ◽

Meta Analysis ◽

Randomised Trials ◽

Dengue Vaccine ◽

Eligibility Criteria ◽

Registration Number ◽

Randomised Controlled

BackgroundRandomised controlled trials have evaluated the recombinant tetravalent dengue vaccine (CYD-TDV). However, individual results may have little power to identify differences among the populations studied.ObjectiveTo evaluate efficacy, immunogenicity and safety of CYD-TDV in the prevention of dengue in children aged 2–17 years.DesignSystematic review and meta-analysis.Data sourcesMEDLINE (from 1950 to 5 December 2018), EMBASE (from 1947 to 5 December 2018) and Cochrane (from 1993 to 5 December 2018).Eligibility criteria of studiesRandomised trials comparing efficacy, immunogenicity and safety of CYD-TDV with placebo or other vaccines for preventing dengue cases in children aged 2–17 years.Outcome measuresEfficacy, immunogenicity and safety of CYD-TDV.Study appraisal and methodsCalculations were made of relative risk (RR) and mean difference (MD) for dichotomous and continuous outcomes, respectively. All estimates were calculated considering a 95% CI estimate. A p<0.05 was considered statistically significant.ResultsNine studies involving 34 248 participants were included. The overall efficacy of CYD-TDV was 60% (RR 0.40 (0.30 to 0.54)). Serotype-specific efficacy of the vaccine was 51% for dengue virus type-1 (DENV-1) (RR 0.49 (0.39 to 0.63)); 34% for DENV-2 (RR 0.66 (0.50 to 0.86)); 75% for DENV-3 (RR 0.25 (0.18 to 0.35)) and 77% for DENV-4 (RR 0.23 (0.15 to 0.34)). Overall immunogenicity (MD) of CYD-TDV was 225.13 (190.34 to 259.93). Serotype-specific immunogenicity was: DENV-1: 176.59 (123.36 to 229.83); DENV-2: 294.21 (181.98 to 406.45); DENV-3: 258.78 (146.72 to 370.84) and DENV-4: 189.35 (141.11 to 237.59). The most common adverse events were headache and pain at the injection site.LimitationsThe main limitation of this study was unclear or incomplete data.Conclusions and implications of key findingsCYD-TDV is considered safe and able to partially protect children and adolescents against four serotypes of DENV for a 1-year period. Despite this, research should prioritise improvements in vaccine efficacy, thus proving higher long-term protection against all virus serotypes.PROSPERO registration numberCRD42016043628.

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Observational cohort study of first-line bevacizumab combined with chemotherapy in metastatic colorectal cancer (HGCSG0802): Comparison of infusional FU/oxaliplatin(OX)+BV and oral FU/OX+BV.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.527 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 527-527 ◽

Cited By ~ 1

Author(s):

Kazuteru Hatanaka ◽

Satoshi Yuki ◽

Hiroshi Nakatsumi ◽

Hiraku Fukushima ◽

Hirohito Naruse ◽

...

Keyword(s):

Colorectal Cancer ◽

Cohort Study ◽

Adverse Events ◽

Metastatic Colorectal Cancer ◽

Observational Cohort Study ◽

Rank Test ◽

First Line ◽

Eligibility Criteria ◽

Significant Difference ◽

Observational Cohort

527 Background: A few reports have shown no difference between the efficacy of infusional FU and that of oral FU (Capecitabine/S-1) for colorectal cancer, and some studies have reported the non-inferiority between infusional FU/Oxaliplatin (OX) and oral FU/OX for metastatic colorectal cancer (mCRC). We performed a sub-group comparison between infusional FU/OX (mFOLFOX6 + BV: iFU) and oral FU/OX (CapeOX/SOX + BV: oFU) from the HGCSG0802 observational cohort study with investigated Japanese patients (pts) treated with first line BV for mCRC. Methods: The objective of HGCSG0802 was to evaluate progression-free survival (PFS), overall survival (OS), time to treatment-failure (TTF), response rate (RR), safety and so on. The key eligibility criteria of HGCSG0802 were with evaluable lesions, older than 20 years, ECOG PS 0-2, and this analysis used the cohort treated with OX-based regimens.In this analysis, pts characteristics, RR and safety were compared using Fisher’s exact test. PFS and TTF were compared using log-rank test. Results: Of 108 pts (the full analysis set), 95 pts were evaluable for treated with OX-based regimens. Forty-eight pts (50.5%) were treated with iFU and 47 pts (49.5%) were treated with oFU (CapeOX + BV 42 pts/SOX + BV 5 pts). The pts characteristics between those were generally balanced except for PS 0-1 (72.9% in iFU/93.6% in oFU; p=0.012) and synchronous liver metastases (mets) (93.8% in iFU/78.8% in oFU; p=0.040). Adverse events ≥grade 3 were balanced except for leucopenia (25.0% in iFU versus 2.1% in oFU; p=0.002) and neutropenia (43.5% in iFU and 10.9% in oFU; p=0.001). Hand-foot skin reaction was not different between two cohorts. RR was 62.5% in iFU versus 71.1% in oFU (p=0.835). The median PFS was 8.3 months in iFU versus 8.2 months in oFU (p=0.835). Conclusions: The HGCSG0802 could be a database to investigate first line BV for mCRC in clinical practice. As a result of this analysis, in Japanese daily practice, efficacy was no significant difference between infusional FU/OX and oral FU/OX, and the profiles of adverse events varied from each regimens.

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Incidence and Risk Factors for Progression to Diabetes Mellitus: A Retrospective Cohort Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph19010123 ◽

2021 ◽

Vol 19 (1) ◽

pp. 123

Author(s):

Min Kyung Hyun ◽

Jong Hern Park ◽

Kyoung Hoon Kim ◽

Soon-Ki Ahn ◽

Seon Mi Ji

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Cohort Study ◽

National Health ◽

Health Screening ◽

Eligibility Criteria ◽

The Republic ◽

High Risk Drinking ◽

Cox Proportional Hazard Regression

(1) Objective: This study examined the incidence and risk factors contributing to the progression to diabetes mellitus (DM) in a seven-year follow-up study of non-diabetic National Health Examinees. (2) Methods: For this retrospective observational cohort study, we used two national representative databases: the National Health Screening (HEALS) database 2009 and the National Health Insurance Service (NHIS) database 2009–2015. The eligible subjects without DM with blood sugar levels of <126 mg/dL were selected using the HEALS database. The subsequent follow-up and clinical outcomes were evaluated using the NHIS database. Cox proportional hazard regression was applied to examine the effects of the covariates on progression to diabetes. (3) Results: Among those who took part in the national health screening in 2009, 4,205,006 subjects who met the eligibility criteria were selected. Of these, 587,015 were diagnosed with DM during the follow-up by 2015. The incidence of progression from non-diabetes to DM was 14.0%, whereas that from impaired fasting glucose (IFG) to DM was 21.9%. Compared to the normal group, the newly diagnosed DM group was more likely to comprise older, female, currently smoking, and high-risk drinking participants and participants with IFG, hypertension, dyslipidemia, and metabolic syndrome. (4) Conclusions: This epidemiological study in the Republic of Korea found risk factors similar to those of other studies, but the incidence of progression to DM was 22.8 per 1000 person-years, which is higher than that previously reported. Hence, more care is needed to prevent DM.

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Mesenchymal stromal cells for COVID-19: A living systematic review protocol

10.1101/2020.04.13.20064162 ◽

2020 ◽

Cited By ~ 1

Author(s):

Gabriel Rada ◽

Javiera Corbalán ◽

Patricio Rojas ◽

Keyword(s):

Systematic Review ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Direct Evidence ◽

Meta Analysis ◽

Grey Literature ◽

Cochrane Central Register ◽

Randomised Trials ◽

Eligibility Criteria ◽

The Impact

ABSTRACTObjectiveTo determine the impact of mesenchymal stromal cells outcomes important to patients with COVID-19.DesignThis is the protocol of a living systematic review.Data sourcesWe will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralised repository in L·OVE (Living OVerview of Evidence). L·OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L·OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal.Eligibility criteria for selecting studies and methodsWe adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question.We will include randomised trials evaluating the effect of mesenchymal stromal cells versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating other coronavirus infections, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case we find no direct evidence from randomised trials, or if the direct evidence provides low- or very low-certainty for critical outcomes.Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will pool the results using meta-analysis and will apply the GRADE system to assess the certainty of the evidence for each outcome.A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it every time the conclusions change or whenever there are substantial updates.Ethics and disseminationNo ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.PROSPERO RegistrationSubmitted to PROSPERO (awaiting ID allocation).

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Lopinavir/ritonavir for the treatment of COVID-19: A living systematic review protocol

10.1101/2020.04.11.20062109 ◽

2020 ◽

Cited By ~ 1

Author(s):

Francisca Verdugo-Paiva ◽

Ariel Izcovich ◽

Martín Ragusa ◽

Gabriel Rada

Keyword(s):

Systematic Review ◽

Direct Evidence ◽

Grey Literature ◽

Cochrane Central Register ◽

Randomised Trials ◽

Eligibility Criteria ◽

Web Based ◽

Central Register ◽

Review Protocol ◽

Meta Analyses

ABSTRACTObjectiveTo assess the efficacy and safety of lopinavir/ritonavir for the treatment of patients with COVID-19.DesignThis is the protocol of a living systematic review.Data sourcesWe will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralised repository in L·OVE (Living OVerview of Evidence). L·OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L·OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal.Eligibility criteria for selecting studies and methodsWe adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question.We will include randomised trials evaluating the effect of lopinavir/ritonavir— as monotherapy or in combination with other drugs — versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating lopinavir/ritonavir in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case no direct evidence from randomised trials is found, or if the direct evidence provides low- or very low-certainty for critical outcomes.Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use GRADE to assess the certainty of the evidence for each outcome.A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it if the conclusions change or there are substantial updates.Ethics and disseminationNo ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.PROSPERO RegistrationSubmitted to PROSPERO (awaiting ID allocation).

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