Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials

Sterne, Jonathan A C; Sutton, Alex J.; Ioannidis, John P. A.; Terrin, Norma; Jones, David R.; Lau, Joseph; Carpenter, James; Rücker, Gerta; Harbord, Roger; Schmid, Christopher H.; Tetzlaff, Jennifer; Deeks, Jonathan J; Peters, Jaime; Macaskill, Petra; Schwarzer, Guido; Duval, Sue; Altman, Douglas G.; Moher, David; Higgins, Julian P T

doi:10.1136/bmj.d4002

Cited by 5,526 publications

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“…For subgroup analysis, we tested for interaction using a χ 2 significance test 21. We planned to examine publication bias using funnel plots for outcomes for which data from 10 or more studies were available 22. Data were analysed with STATA software (version 14.2, TX, USA).…”

Section: Methodsmentioning

confidence: 99%

Corticosteroids for treatment of sore throat: systematic review and meta-analysis of randomised trials

Sadeghirad

Siemieniuk

Brignardello‐Petersen

et al. 2017

BMJ

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Objective To estimate the benefits and harms of using corticosteroids as an adjunct treatment for sore throat. Design Systematic review and meta-analysis of randomised control trials. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries up to May 2017, reference lists of eligible trials, related reviews. Study selection Randomised controlled trials of the addition of corticosteroids to standard clinical care for patients aged 5 or older in emergency department and primary care settings with clinical signs of acute tonsillitis, pharyngitis, or the clinical syndrome of sore throat. Trials were included irrespective of language or publication status. Review methods Reviewers identified studies, extracted data, and assessed the quality of the evidence, independently and in duplicate. A parallel guideline committee (BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including the selection of outcomes important to patients. Random effects model was used for meta-analyses. Quality of evidence was assessed with the GRADE approach. Results 10 eligible trials enrolled 1426 individuals. Patients who received single low dose corticosteroids (the most common intervention was oral dexamethasone with a maximum dose of 10 mg) were twice as likely to experience pain relief after 24 hours (relative risk 2.2, 95% confidence interval 1.2 to 4.3; risk difference 12.4%; moderate quality evidence) and 1.5 times more likely to have no pain at 48 hours (1.5, 1.3 to 1.8; risk difference 18.3%; high quality). The mean time to onset of pain relief in patients treated with corticosteroids was 4.8 hours earlier (95% confidence interval −1.9 to −7.8; moderate quality) and the mean time to complete resolution of pain was 11.1 hours earlier (−0.4 to −21.8; low quality) than in those treated with placebo. The absolute pain reduction at 24 hours (visual analogue scale 0-10) was greater in patients treated with corticosteroids (mean difference 1.3, 95% confidence interval 0.7 to 1.9; moderate quality). Nine of the 10 trials sought information regarding adverse events. Six studies reported no adverse effects, and three studies reported few adverse events, which were mostly complications related to disease, with a similar incidence in both groups. Conclusion Single low dose corticosteroids can provide pain relief in patients with sore throat, with no increase in serious adverse effects. Included trials did not assess the potential risks of larger cumulative doses in patients with recurrent episodes of acute sore throat. Systematic review registration PROSPERO CRD42017067808.

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Section: Methodsmentioning

confidence: 99%

Corticosteroids for treatment of sore throat: systematic review and meta-analysis of randomised trials

Sadeghirad

Siemieniuk

Brignardello‐Petersen

et al. 2017

BMJ

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“…Potential publication bias was examined for the primary end point by constructing a “funnel plot” in which the SE of the log RR was plotted against the RR. The asymmetry of the plot was estimated both visually and by a linear regression approach 9. The influence of each study and potential publication bias were addressed by testing whether deleting each study in turn would have changed significantly the pooled results of the meta‐analysis for the primary end point.…”

Section: Methodsmentioning

confidence: 99%

Cerebrovascular Events After No‐Touch Off‐Pump Coronary Artery Bypass Grafting, Conventional Side‐Clamp Off‐Pump Coronary Artery Bypass, and Proximal Anastomotic Devices: A Meta‐Analysis

Pawliszak

Kowalewski

Raffa

et al. 2016

JAHA

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BackgroundOff‐pump coronary artery bypass (OPCAB) has been shown to reduce the risk of neurologic complications as compared to coronary artery bypass grafting performed with cardiopulmonary bypass. Side‐clamping of the aorta while constructing proximal anastomoses, however, still carries substantial risk of cerebral embolization. We aimed to perform a comprehensive meta‐analysis of studies assessing 2 clampless techniques: aortic “no‐touch” and proximal anastomosis devices (PAD) for OPCAB.Methods and ResultsPubMed, CINAHL, CENTRAL, and Google Scholar databases were screened for randomized controlled trials and observational studies comparing “no‐touch” and/or PAD with side‐clamp OPCAB and reporting short‐term (≤30 days) outcomes: cerebrovascular accident and all‐cause mortality. A total of 18 studies (3 randomized controlled trials) enrolling 25 163 patients were included. Aortic “no‐touch” was associated with statistically lower risk of cerebrovascular accident as compared to side‐clamp OPCAB: risk ratio 95% CI: 0.41 (0.27–0.61); P<0.01; I2=0%. Event rates were 0.36% and 1.28% for “no‐touch” and side‐clamp OPCAB, respectively. No difference was seen between PAD and side‐clamp OPCAB: 0.71 (0.33–1.55); P=0.39; I2=39%. A trend towards increased 30‐day all‐cause mortality with PAD and no difference with “no‐touch” were observed when compared to side‐clamp OPCAB. In a subset analysis, “no‐touch” consistently reduced the risk of cerebrovascular accident regardless of patients’ baseline risk characteristics. A benefit with PAD was observed in low‐risk patients.ConclusionsAortic “no‐touch” technique was associated with nearly 60% lower risk of postoperative cerebrovascular events as compared to conventional side‐clamp OPCAB with effect consistent across patients at different risk.

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“…70 We did not quantify publication biases or selective outcome reporting biases because of the questionable statistical validity of the available tests. 71 We defined a high level of evidence on the basis of consistent findings from low risk-of-bias RCTs. We downgraded strength of evidence to moderate if at least one of the four strength-of-evidence criteria was not met and to low if two or more criteria were not met.…”

Section: Methodsmentioning

confidence: 99%

Preventive Pharmacologic Treatments for Episodic Migraine in Adults

et al. 2013

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ELIGIBILITY CRITERIA: English-language randomized controlled trials (RCTs) of preventive drugs compared to placebo or active treatments examining rates of ≥50 % reduction in monthly migraine frequency or improvement in quality of life. STUDY APPRAISAL AND SYNTHESIS METHODS:We assessed risk of bias and strength of evidence and conducted random effects meta-analyses of absolute risk differences and Bayesian network meta-analysis. RESULTS: Of 5,244 retrieved references, 215 publications of RCTs provided mostly low-strength evidence because of the risk of bias and imprecision. RCTs examined 59 drugs from 14 drug classes. All approved drugs, including topiramate (9 RCTs), divalproex (3 RCTs), timolol (3 RCTs), and propranolol (4 RCTs); offlabel beta blockers metoprolol (4 RCTs), atenolol (1 RCT), nadolol (1 RCT), and acebutolol (1 RCT); angiotensin-converting enzyme inhibitors captopril (1 RCT) and lisinopril (1 RCT); and angiotensin II receptor blocker candesartan (1 RCT), outperformed placebo in reducing monthly migraine frequency by ≥50 % in 200-400 patients per 1,000 treated. Adverse effects leading to treatment discontinuation (68 RCTs) were greater with topiramate, off-label antiepileptics, and antidepressants than with placebo. Limited direct evidence as well as frequentist and exploratory network Bayesian meta-analysis showed no statistically significant differences in benefits between approved drugs. Off-label angiotensin-inhibiting drugs and beta-blockers were most effective and tolerable for episodic migraine prevention. LIMITATIONS:We did not quantify reporting bias or contact principal investigators regarding unpublished trials. CONCLUSIONS: Approved drugs prevented episodic migraine frequency by ≥50 % with no statistically significant difference between them. Exploratory network meta-analysis suggested that off-label angiotensin-inhibiting drugs and beta-blockers had favorable benefit-to-harm ratios. Evidence is lacking for longterm effects of drug treatments (i.e., trials of more than 3 months duration), especially for quality of life.KEY WORDS: migraine; evidence based medicine; adverse drug effects.

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Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials

Cited by 5,526 publications

References 44 publications

Corticosteroids for treatment of sore throat: systematic review and meta-analysis of randomised trials

Corticosteroids for treatment of sore throat: systematic review and meta-analysis of randomised trials

Cerebrovascular Events After No‐Touch Off‐Pump Coronary Artery Bypass Grafting, Conventional Side‐Clamp Off‐Pump Coronary Artery Bypass, and Proximal Anastomotic Devices: A Meta‐Analysis

Preventive Pharmacologic Treatments for Episodic Migraine in Adults

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