Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis

Wetterslev, Jørn; Thorlund, Kristian; Brok, Jesper; Gluud, Christian

doi:10.1016/j.jclinepi.2007.03.013

Cited by 1,493 publications

(1,054 citation statements)

References 35 publications

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“…Indeed, traditional meta‐analytic methods may sometimes lead to false‐positive results, especially when pooled estimates are updated with the publication of new trials in cumulative meta‐analyses 14. The aim of this approach is to determine whether enough evidence has been obtained to reach a conclusion regarding the superiority of one treatment over another, or if a new RCT addressing the same comparison should be undertaken 15, 16. Briefly, in TSA, a cumulative meta‐analysis of RCTs is similar to several interim analyses of a single RCT, with the construction of specific trial sequential monitoring boundaries by using the Lan–DeMets α spending function approach 15, 16.…”

Section: Methodsmentioning

confidence: 99%

“…To this aim, we included published data from all RCTs and unpublished data from the 3‐arm CLOSE trial, allowing head‐to‐head comparison of all the abovementioned therapeutic strategies and calculation of the absolute risk of stroke and corresponding number needed to treat. Because traditional updated meta‐analyses may sometimes lead to false‐positive results due to repeated significance testing,14 we performed trial sequential analyses (TSA), a method similar to interim analyses of a single RCT, in order to determine whether enough evidence has been obtained to reach a conclusion 15, 16…”

Section: Introductionmentioning

confidence: 99%

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Closure, Anticoagulation, or Antiplatelet Therapy for Cryptogenic Stroke With Patent Foramen Ovale: Systematic Review of Randomized Trials, Sequential Meta‐Analysis, and New Insights From the CLOSE Study

Turc

Calvet

Guérin

et al. 2018

JAHA

119

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BackgroundWe conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) comparing patent foramen ovale (PFO) closure, anticoagulation, and antiplatelet therapy to prevent stroke recurrence in patients with PFO‐associated cryptogenic stroke.Methods and ResultsWe searched Medline, Cochrane Library, and EMBASE through March 2018. The primary outcome was stroke recurrence. Pooled incidences, hazard ratios, and risk ratios (RRs) were calculated in random‐effects meta‐analyses. PFO closure was associated with a lower risk of recurrent stroke compared with antithrombotic therapy (antiplatelet therapy or anticoagulation: 3560 patients from 6 RCTs; RR=0.36, 95% CI: 0.17–0.79; I2=59%). The effect of PFO closure on stroke recurrence was larger in patients with atrial septal aneurysm or large shunt (RR=0.27, 95% CI, 0.11–0.70; I2=42%) compared with patients without these anatomical features (RR=0.80, 95% CI, 0.43–1.47; I2=12%). Major complications occurred in 2.40% (95% CI, 1.03–4.25; I2=77%) of procedures. New‐onset atrial fibrillation was more frequent in patients randomized to PFO closure versus antithrombotic therapy (RR=4.33, 95% CI, 2.37–7.89; I2=14%). One RCT compared PFO closure versus anticoagulation (353 patients; hazard ratio=0.14, 95% CI, 0.00–1.45) and 2 RCTs compared PFO closure versus antiplatelet therapy (1137 patients; hazard ratio=0.18, 95% CI, 0.05–0.63; I2=12%). Three RCTs compared anticoagulation versus antiplatelet therapy, with none showing a significant difference.Conclusions PFO closure is superior to antithrombotic therapy to prevent stroke recurrence after cryptogenic stroke. The annual absolute risk reduction of stroke was low, but it has to be tempered by a substantial time at risk (at least 5 years) in young and middle‐aged patients. PFO closure was associated with an increased risk of atrial fibrillation.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Closure, Anticoagulation, or Antiplatelet Therapy for Cryptogenic Stroke With Patent Foramen Ovale: Systematic Review of Randomized Trials, Sequential Meta‐Analysis, and New Insights From the CLOSE Study

Turc

Calvet

Guérin

et al. 2018

JAHA

119

View full text Add to dashboard Cite

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“…TSA could reduce type I error because it combines estimation of required information size with adjusted threshold for statistical significance 13, 20, 21. TSA was performed for cardiovascular outcomes by anticipating a 20% relative risk reduction, an overall 5% risk of type I error, and a statistical test power of 80%.…”

Section: Methodsmentioning

confidence: 99%

Cardiovascular Safety, Long‐Term Noncardiovascular Safety, and Efficacy of Sodium–Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Systemic Review and Meta‐Analysis With Trial Sequential Analysis

Zhang

Zhu

Chen

et al. 2018

JAHA

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BackgroundThe cardiovascular and long‐term noncardiovascular safety and efficacy of SGLT2 (sodium–glucose cotransporter 2) inhibitors have not been well documented.Methods and ResultsFor cardiovascular outcomes, we performed a meta‐analysis with trial sequential analysis of randomized controlled trials and adjusted observational studies, each with a minimum of 26 weeks and 2000 patient‐years of follow‐up. For long‐term noncardiovascular safety and efficacy outcome analyses, we included only randomized controlled trials with at least 2 years and 1000 patient‐years of follow‐up. Five studies with 351 476 patients were included in cardiovascular outcomes analysis. Meta‐analyses showed that SGLT2 inhibitors significantly reduced the risks of major adverse cardiac events (hazard ratio [HR]: 0.80; 95% confidence interval [CI], 0.69–0.92; P=0.002), all‐cause mortality (HR: 0.67; 95% CI, 0.54–0.84; P<0.001), cardiovascular mortality (HR: 0.77; 95% CI, 0.60–0.98; P=0.03), nonfatal myocardial infarction (HR: 0.86; 95% CI, 0.76–0.98; P=0.02), hospitalization for heart failure (HR: 0.62; 95% CI, 0.55–0.69; P<0.001), and progression of albuminuria (HR: 0.68; 95% CI, 0.58–0.81; P<0.001). No significant difference in nonfatal stroke was found. Analyses limited to randomized controlled trials showed similar findings. Trial sequential analysis provided firm evidence of a 20% reduction in major adverse cardiac events, all‐cause mortality, and hospitalization for heart failure with SGLT2 inhibitors, but evidence remains inconclusive for cardiovascular mortality. Nine randomized controlled trials contributed to long‐term noncardiovascular and efficacy analyses. SGLT2 inhibitors reduced incidence of hypoglycemia and acute kidney injury but increased the risks of urinary tract and genital infections.Conclusions SGLT2 inhibitors showed remarkable cardiovascular‐ and renal‐protective effects and good long‐term noncardiovascular safety with sustained efficacy.

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“…The strengths of this clinical practice guideline include the application of current standards for trustworthy guidelines, including the GRADE methodology which support a systematic and transparent process,9 and use of TSA to assess the risk of random errors 13. The limitations include the reliance upon existing systematic reviews for some recommendations, including the risk of trial heterogeneity, indirectness, and bias.…”

Section: Discussionmentioning

confidence: 99%

“…We used trial sequential analysis (TSA) to assess the risk of random errors (spurious findings) due to repetitive testing and sparse data13. TSA was applied using an a priori 20% relative risk reduction, an alfa of 5%, beta of 90%, and a control event proportion according to the results from the included trials.…”

Section: Methodsmentioning

confidence: 99%

Scandinavian SSAI clinical practice guideline on choice of inotropic agent for patients with acute circulatory failure

Møller

Granholm

Junttila

et al. 2018

Acta Anaesthesiol Scand

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BackgroundAdult critically ill patients often suffer from acute circulatory failure and those with low cardiac output may be treated with inotropic agents. The aim of this Scandinavian Society of Anaesthesiology and Intensive Care Medicine guideline was to present patient‐important treatment recommendations on this topic.MethodsThis guideline was developed according to GRADE. We assessed the following subpopulations of patients with shock: (1) shock in general, (2) septic shock, (3) cardiogenic shock, (4) hypovolemic shock, (5) shock after cardiac surgery, and (6) other types of shock, including vasodilatory shock. We assessed patient‐important outcome measures, including mortality and serious adverse reactions.ResultsFor all patients, we suggest against the routine use of any inotropic agent, including dobutamine, as compared to placebo/no treatment (very low quality of evidence). For patients with shock in general, and in those with septic and other types of shock, we suggest using dobutamine rather than levosimendan or epinephrine (very low quality of evidence). For patients with cardiogenic shock and in those with shock after cardiac surgery, we suggest using dobutamine rather than milrinone (very low quality of evidence). For the other clinical questions, we refrained from giving any recommendations or suggestions.ConclusionsWe suggest against the routine use of any inotropic agent in adult patients with shock. If used, we suggest using dobutamine rather than other inotropic agents for the majority of patients, however, the quality of evidence was very low, implying high uncertainty on the balance between the benefits and harms of inotropic agents.

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Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis

Cited by 1,493 publications

References 35 publications

Closure, Anticoagulation, or Antiplatelet Therapy for Cryptogenic Stroke With Patent Foramen Ovale: Systematic Review of Randomized Trials, Sequential Meta‐Analysis, and New Insights From the CLOSE Study

Closure, Anticoagulation, or Antiplatelet Therapy for Cryptogenic Stroke With Patent Foramen Ovale: Systematic Review of Randomized Trials, Sequential Meta‐Analysis, and New Insights From the CLOSE Study

Cardiovascular Safety, Long‐Term Noncardiovascular Safety, and Efficacy of Sodium–Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Systemic Review and Meta‐Analysis With Trial Sequential Analysis

Scandinavian SSAI clinical practice guideline on choice of inotropic agent for patients with acute circulatory failure

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