The adaptive designs CONSORT extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design

Dimairo, Munyaradzi; Pallmann, Philip; Wason, James; Todd, Susan; Jaki, Thomas; Julious, Steven A.; Mander, Adrian P.; Weir, Christopher J.; König, Franz; Walton, Marc K.; Nicholl, Jon; Coates, Elizabeth; Biggs, Katie; Hamasaki, Toshimitsu; Proschan, Michael A.; Scott, John; Ando, Yuki; Hind, Daniel; Altman, Douglas G.

doi:10.1186/s13063-020-04334-x

Cited by 27 publications

(48 citation statements)

References 257 publications

(386 reference statements)

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“…However, the trial was assessed as at high risk of bias and had methodological limitations ( S2 Table , S3 Table ). First, the trial is described as an adaptive trial, but the reporting of the trial does not comply with the Consolidated Standards of Reporting Trials (CONSORT) extension on adaptive designs [ 71 ]. For example, according to the CONSORT extension, trialists should report: “Elements of decision-making rules describing whether, how, and when the proposed trial adaptations will be used during the trial.…”

Section: Discussionmentioning

confidence: 99%

“…It involves pre-specifying a set of actions guiding how decisions about implementing the trial adaptations are made given interim observed data (decision rules). It also involves pre-specifying limits or parameters to trigger trial adaptations (decision boundaries)” [ 71 ]. However, in the protocol and the statistical analysis plan of the RECOVERY trial, it is stated that the data monitoring committee will request data at a frequency relevant to the emerging data, and no other information is provided.…”

Section: Discussionmentioning

confidence: 99%

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Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

et al. 2020

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Background Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused extensive burden to individuals, families, countries, and the world. Effective treatments of COVID-19 are urgently needed. Methods and findings This is the first edition of a living systematic review of randomized clinical trials comparing the effects of all treatment interventions for participants in all age groups with COVID-19. We planned to conduct aggregate data meta-analyses, trial sequential analyses, network meta-analysis, and individual patient data meta-analyses. Our systematic review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Cochrane guidelines, and our 8-step procedure for better validation of clinical significance of meta-analysis results. We performed both fixed-effect and random-effects meta-analyses. Primary outcomes were all-cause mortality and serious adverse events. Secondary outcomes were admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and nonserious adverse events. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. We searched relevant databases and websites for published and unpublished trials until August 7, 2020. Two reviewers independently extracted data and assessed trial methodology. We included 33 randomized clinical trials enrolling a total of 13,312 participants. All trials were at overall high risk of bias. We identified one trial randomizing 6,425 participants to dexamethasone versus standard care. This trial showed evidence of a beneficial effect of dexamethasone on all-cause mortality (rate ratio 0.83; 95% confidence interval [CI] 0.75–0.93; p < 0.001; low certainty) and on mechanical ventilation (risk ratio [RR] 0.77; 95% CI 0.62–0.95; p = 0.021; low certainty). It was possible to perform meta-analysis of 10 comparisons. Meta-analysis showed no evidence of a difference between remdesivir versus placebo on all-cause mortality (RR 0.74; 95% CI 0.40–1.37; p = 0.34, I 2 = 58%; 2 trials; very low certainty) or nonserious adverse events (RR 0.94; 95% CI 0.80–1.11; p = 0.48, I 2 = 29%; 2 trials; low certainty). Meta-analysis showed evidence of a beneficial effect of remdesivir versus placebo on serious adverse events (RR 0.77; 95% CI 0.63–0.94; p = 0.009, I 2 = 0%; 2 trials; very low certainty) mainly driven by respiratory failure in one trial. Meta-analyses and trial sequential analyses showed that we could exclude the possibility that hydroxychloroquine versus standard care reduced the risk of all-cause mortality (RR 1.07; 95% CI 0.97–1.19; p = 0.17; I 2 = 0%; 7 trials; low certainty) and ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

et al. 2020

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“…We used the adaptive designs Consolidated Standards of Reporting Trials Extension ( CONSORT Extension ) (ACE) statement for reporting this trial. 18 , 19 …”

Section: Methodsmentioning

confidence: 99%

Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19

et al. 2021

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IMPORTANCEData on the efficacy of hydroxychloroquine or lopinavir-ritonavir for the treatment of high-risk outpatients with COVID-19 in developing countries are needed. OBJECTIVE To determine whether hydroxychloroquine or lopinavir-ritonavir reduces hospitalization among high-risk patients with early symptomatic COVID-19 in an outpatient setting. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial was conducted in Brazil.Recently symptomatic adults diagnosed with respiratory symptoms from SARS-CoV-2 infection were enrolled between June 2 and September 30, 2020. The planned sample size was 1476 patients, with interim analyses planned after 500 patients were enrolled. The trial was stopped after the interim analysis for futility with a sample size of 685 patients. Statistical analysis was performed in December 2020.INTERVENTIONS Patients were randomly assigned to hydroxychloroquine (800 mg loading dose, then 400 mg daily for 9 days), lopinavir-ritonavir (loading dose of 800 mg and 200 mg, respectively, every 12 hours followed by 400 mg and 100 mg, respectively, every 12 hours for the next 9 days), or placebo. MAIN OUTCOMES AND MEASURESThe primary outcomes were COVID-19-associated hospitalization and death assessed at 90 days after randomization. COVID-19-associated hospitalization was analyzed with a Cox proportional hazards model. The trial included the following secondary outcomes: all-cause hospitalization, viral clearance, symptom resolution, and adverse events. RESULTSOf 685 participants, 632 (92.3%) self-identified as mixed-race, 377 (55.0%) were women, and the median (range) age was 53 (18-94) years. A total of 214 participants were randomized to hydroxychloroquine; 244, lopinavir-ritonavir; and 227, placebo. At first interim analysis, the data safety monitoring board recommended stopping enrollment of both hydroxychloroquine and lopinavir-ritonavir groups because of futility. The proportion of patients hospitalized for COVID-19 was 3.7% (8 participants) in the hydroxychloroquine group, 5.7% (14 participants) in the lopinavirritonavir group, and 4.8% (11 participants) in the placebo group. We found no significant differences between interventions for COVID-19-associated hospitalization (hydroxychloroquine: hazard ratio [HR], 0.76 [95% CI, 0.30-1.88]; lopinavir-ritonavir: HR, 1.16 [95% CI, 0.53-2.56] as well as for the secondary outcome of viral clearance through day 14 (hydroxychloroquine: odds ratio [OR], 0.91 (continued)

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“…The whole procedure of managing participants followed the CONSORT 2010 flow diagram. The contents reported throughout the paper were addressed according to each item demonstrated in both the CONSORT 2010 statement and Adaptive designs CONSORT Extension (ACE) statement [ 23 , 24 ].…”

Section: Resultsmentioning

confidence: 99%

Discovery of Urinary Biomarkers of Seaweed Intake Using Untargeted LC–MS Metabolomics in a Three-Way Cross-Over Human Study

Dragsted

Tullin

et al. 2020

Metabolites

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Seaweeds are a marine source rich in potentially bioactive components, and therefore have attracted attention since the middle of the twentieth century. Accurate and objective assessment of the intake of seaweeds to study their health effects is hampered by a lack of validated intake biomarkers. In this three-armed, randomized, cross-over study, an untargeted metabolomics approach was applied for discovering novel intake biomarkers. Twenty healthy participants (9 men and 11 women) were provided each of three test meals in a randomized order: 5 g of Laminaria digitate (LD), 5 g of Undaria pinnatifida (UP), or a control meal with energy-adjusted pea protein. Four urine samples and a 24 h pooled urine were collected along with blood samples at seven time-points. All samples were profiled by LC-ESI-QTOF-MS and the data were analyzed by univariate analysis and excretion kinetics to select putative intake biomarkers. In total, four intake biomarkers were selected from urine samples. They were identified as hydroxyl-dihydrocoumarin at Level III, loliolid glucuronide at level I, and isololiolid glucuronide at level II, while the last one remains unknown. Further identification and validation of these biomarkers by a cross-sectional study is essential to assess their specificity and robustness.

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The adaptive designs CONSORT extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design

Cited by 27 publications

References 257 publications

Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19

Discovery of Urinary Biomarkers of Seaweed Intake Using Untargeted LC–MS Metabolomics in a Three-Way Cross-Over Human Study

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