Faculty Opinions recommendation of Efficacy and safety of combined intraventricular fibrinolysis with lumbar drainage for prevention of permanent shunt dependency after intracerebral hemorrhage with severe ventricular involvement: A randomized trial and individual patient data meta-analysis.

Introduction: Observational evidence from single center studies indicates that lower admission hemoglobin (Hb) levels are associated with poor outcome after spontaneous intracerebral hemorrhage (ICH). We combined data from three multicenter studies to test the hypothesis that Hb levels inversely correlate with functional outcome in ICH. Methods: We conducted a meta-analysis of individual patient data from the clinical trials ATACH-II and FAST and the multi-ethnic study ERICH. We included participants with available Hb and outcome data. We used multivariable logistic regression to test for association between admission Hb levels and 3-month dichotomized (0-3 versus 4-6) modified Rankin Scale (mRS), adjusting for the variables contained in the ICH score. We pooled study-specific estimates using inverse-variance weighted, fixed effects meta-analysis. Results: A total of 4106 ICH patients were included in the analysis. Each additional g/dL of admission Hb was associated with a 12% (OR 0.88, 95%CI 0.85-0.91; p<0.001) and 8% (OR 0.92, 95%CI 0.88-0.96; p<0.001) reduction in the odds of poor outcome in unadjusted and adjusted analyses, respectively (Table 1). Dose-response analyses indicated a linear relationship between Hb levels and poor outcome across the entire evaluated range (Figure 1, test-for-trend p<0.001). In metanalysis, there were not significant associations between Hb and ICH volume or expansion (both p>0.05). Conclusion: Lower hemoglobin levels are associated with poor outcome in ICH. Further studies of the underlying biological mechanisms are warranted. If replicated, this pathway could become an appealing target to be tested in clinical trials.

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Extending the I-squared statistic to describe treatment effect heterogeneity in cluster, multi-centre randomized trials and individual patient data meta-analysis

Statistical Methods in Medical Research ◽

10.1177/0962280220948550 ◽

2020 ◽

pp. 096228022094855

Author(s):

Karla Hemming ◽

James P Hughes ◽

Joanne E McKenzie ◽

Andrew B Forbes

Keyword(s):

Randomized Trial ◽

Treatment Effect ◽

Treatment Effects ◽

Randomized Trials ◽

Individual Patient Data ◽

Meta Analysis ◽

Cluster Randomized Trial ◽

Patient Data ◽

Treatment Effect Heterogeneity ◽

Effect Heterogeneity

Treatment effect heterogeneity is commonly investigated in meta-analyses to identify if treatment effects vary across studies. When conducting an aggregate level data meta-analysis it is common to describe the magnitude of any treatment effect heterogeneity using the I-squared statistic, which is an intuitive and easily understood concept. The effect of a treatment might also vary across clusters in a cluster randomized trial, or across centres in multi-centre randomized trial, and it can be of interest to explore this at the analysis stage. In cross-over trials and other randomized designs, in which clusters or centres are exposed to both treatment and control conditions, this treatment effect heterogeneity can be identified. Here we derive and evaluate a comparable I-squared measure to describe the magnitude of heterogeneity in treatment effects across clusters or centres in randomized trials. We further show how this methodology can be used to estimate treatment effect heterogeneity in an individual patient data meta-analysis.

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Tenecteplase versus alteplase in stroke thrombolysis: An individual patient data meta-analysis of randomized controlled trials

International Journal of Stroke ◽

10.1177/1747493016641112 ◽

2016 ◽

Vol 11 (5) ◽

pp. 534-543 ◽

Cited By ~ 24

Author(s):

Xuya Huang ◽

Rachael MacIsaac ◽

John LP Thompson ◽

Bruce Levin ◽

Richard Buchsbaum ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Individual Patient Data ◽

Meta Analysis ◽

Patient Data ◽

Controlled Trials ◽

Modified Rankin Scale ◽

Neurological Improvement ◽

Randomized Controlled ◽

Symptomatic Intracerebral Hemorrhage ◽

Stroke Thrombolysis

Background Tenecteplase, a modified plasminogen activator with higher fibrin specificity and longer half-life, may have advantages over alteplase in acute ischemic stroke thrombolysis. Aims We undertook an individual patient data meta-analysis of randomized controlled trials that compared alteplase with tenecteplase in acute stroke. Methods Eligible studies were identified by a MEDLINE search, and individual patient data were acquired. We compared clinical outcomes including modified Rankin Scale at three months, early neurological improvement at 24 h, intracerebral hemorrhage, symptomatic intracerebral hemorrhage, and mortality at three months between all dose tiers of tenecteplase and alteplase. Results Three relevant studies (Haley et al., Parsons et al., and ATTEST) included 291 patients and investigated three doses of tenecteplase (0.1, 0.25, 0.4 mg/kg). There were no differences between any dose of tenecteplase and alteplase for either efficacy or safety end points. Tenecteplase 0.25 mg/kg had the greatest odds to achieve early neurological improvement (OR [95%CI] 3.3 [1.5, 7.2], p = 0.093), excellent functional outcome (modified Rankin Scale 0–1) at three months (OR [95%CI] 1.9 [0.8, 4.4], p = 0.28), with reduced odds of intracerebral hemorrhage (OR [95%CI] 0.6 [0.2, 1.8], P = 0.43) compared with alteplase. Only 19 patients were treated with tenecteplase 0.4 mg/kg, which showed increased odds of symptomatic intracerebral hemorrhage compared with alteplase (OR [95% CI] 6.2 [0.7, 56.3]). Conclusions While no significant differences between tenecteplase and alteplase were found, point estimates suggest potentially greater efficacy of 0.25 and 0.1 mg/kg doses with no difference in symptomatic intracerebral hemorrhage, and potentially higher symptomatic intracerebral hemorrhage risk with the 0.4 mg/kg dose. Further investigation of 0.25 mg/kg tenecteplase is warranted.

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Metformin in Pregnancy Study (MiPS): protocol for a systematic review with individual patient data meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-036981 ◽

2020 ◽

Vol 10 (5) ◽

pp. e036981

Author(s):

Aya Mousa ◽

Tone Løvvik ◽

Ijäs Hilkka ◽

Sven M Carlsen ◽

Laure Morin-Papunen ◽

...

Keyword(s):

Individual Patient Data ◽

Data Extraction ◽

Meta Analysis ◽

A Priori ◽

Patient Data ◽

Sensitivity Analyses ◽

Efficacy And Safety ◽

Adverse Pregnancy ◽

The Impact ◽

In Pregnancy

IntroductionGestational diabetes mellitus (GDM) is a common disorder of pregnancy and contributes to adverse pregnancy outcomes. Metformin is often used for the prevention and management of GDM; however, its use in pregnancy continues to be debated. The Metformin in Pregnancy Study aims to use individual patient data (IPD) meta-analysis to clarify the efficacy and safety of metformin use in pregnancy and to identify relevant knowledge gaps.Methods and analysisMEDLINE, EMBASE and all Evidence-Based Medicine will be systematically searched for randomised controlled trials (RCT) testing the efficacy of metformin compared with placebo, usual care or other interventions in pregnant women. Two independent reviewers will assess eligibility using prespecified criteria and will conduct data extraction and quality appraisal of eligible studies. Authors of included trials will be contacted and asked to contribute IPD. Primary outcomes include maternal glycaemic parameters and GDM, as well as neonatal hypoglycaemia, anthropometry and gestational age at delivery. Other adverse maternal, birth and neonatal outcomes will be assessed as secondary outcomes. IPD from these RCTs will be harmonised and a two-step meta-analytic approach will be used to determine the efficacy and safety of metformin in pregnancy, with a priori adjustment for covariates and subgroups to examine effect moderators of treatment outcomes. Sensitivity analyses will assess heterogeneity, risk of bias and the impact of trials which have not provided IPD.Ethics and disseminationAll IPD will be deidentified and studies contributing IPD will have ethical approval from their respective local ethics committees. This study will provide robust evidence regarding the efficacy and safety of metformin use in pregnancy, and may identify subgroups of patients who may benefit most from this treatment modality. Findings will be published in peer-reviewed journals and disseminated at scientific meetings, providing much needed evidence to inform clinical and public health actions in this area.

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