Dataset Information

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

ABSTRACT: INTRODUCTION:Gestational 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 ANALYSIS:MEDLINE, 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 DISSEMINATION:All 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.

SUBMITTER: Mousa A

PROVIDER: S-EPMC7247411 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Mousa Aya A Løvvik Tone T Hilkka Ijäs I Carlsen Sven M SM Morin-Papunen Laure L Tertti Kristiina K Rönnemaa Tapani T Syngelaki Argyro A Nicolaides Kypros K Shehata Hassan H Burden Christy C Norman Jane E JE Rowan Janet J Dodd Jodie M JM Hague William W Vanky Eszter E Teede Helena J HJ

BMJ open 20200521 5

<h4>Introduction</h4>Gestational 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.<h4>Methods and analysis</h4>MEDLINE, EMBASE an ...[more]

PMID: 32444434

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Project description:BackgroundPlacenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality in developed nations. Women who have experienced these complications are at an elevated risk of recurrence in subsequent pregnancies. However, despite decades of research no effective strategies to prevent recurrence have been identified, until recently. We completed a pooled summary-based meta-analysis that strongly suggests that low-molecular-weight heparin reduces the risk of recurrent placenta-mediated complications. The proposed individual patient data meta-analysis builds on this successful collaboration. The project is called AFFIRM, An individual patient data meta-analysis oF low-molecular-weight heparin For prevention of placenta-medIated pRegnancy coMplications.Methods/designWe conducted a systematic review to identify randomized controlled trials with a low-molecular-weight heparin intervention for the prevention of recurrent placenta-mediated pregnancy complications. Investigators and statisticians representing eight trials met to discuss the outcomes and analysis plan for an individual patient data meta-analysis. An additional trial has since been added for a total of nine eligible trials. The primary analyses from the original trials will be replicated for quality assurance prior to recoding the data from each trial and combining it into a common dataset for analysis. Using the anonymized combined data we will conduct logistic regression and subgroup analyses aimed at identifying which women with previous pregnancy complications benefit most from treatment with low-molecular-weight heparin during pregnancy.DiscussionThe goal of the proposed individual patient data meta-analysis is a thorough estimation of treatment effects in patients with prior individual placenta-mediated pregnancy complications and exploration of which complications are specifically prevented by low-molecular-weight heparin.Systematic review registrationPROSPERO (International Prospective Registry of Systematic Reviews) 23 December 2013, CRD42013006249.

Project description:IntroductionHypothalamic hamartomas (HHs) are deep-seated congenital lesions that typically lead to pharmacoresistant epilepsy and a catastrophic encephalopathic syndrome characterised by severe neuropsychological impairment and decline in quality of life. A variety of surgical approaches and technologies are available for the treatment of HH-related pharmacoresistant epilepsy. There remains, however, a paucity of literature directly comparing their relative efficacy and safety. This protocol aims to facilitate a systematic review and meta-analysis that will characterise and compare the probability of seizure freedom and relevant postoperative complications across different surgical techniques performed for the treatment of HH-related pharmacoresistant epilepsy.Methods and analysisThis protocol was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Individual Participant Data guidelines. Three major databases, PubMed, Embase and Scopus, will be systematically searched from database inception and without language restrictions for relevant articles using our predefined search strategy. Title-abstract and full text screening using inclusion and exclusion criteria created a priori will be performed by two independent reviewers to identify eligible articles. Conflicts will be resolved via discussion with a third team member. Following data extraction of both study-level and individual patient data (IPD), a study-level and IPD meta-analysis will be performed. Study-level analysis will focus on assessing the degree of heterogeneity in the data and quantifying overall seizure outcomes for each surgical technique. The IPD analysis will use multivariable regression to determine perioperative predictors of seizure freedom and complications that can guide patient and technique selection.Ethics and disseminationThis work will not require ethics approval as it will be solely based on previously published and available data. The results of this review will be shared via conference presentation and submission to peer-reviewed neurosurgical journals.Prospero registrationCRD42022378876.

Project description:BackgroundCompared to subgroup analyses in a single study or in a traditional meta-analysis, an individual patient data meta-analysis (IPDMA) offers important potential advantages. We studied how many IPDMAs report on surgical interventions, how many of those surgical IPDMAs perform subgroup analyses, and whether these subgroup analyses have changed decision-making in clinical practice.MethodsSurgical IPDMAs were identified using a comprehensive literature search. The last search was conducted on 24 April 2012. For each IPDMA included, we obtained information using a standardized data extraction form, and the quality of reporting was assessed. We also checked whether results were implemented in clinical guidelines.ResultsOf all 583 identified IPDMAs, 22 (4%) reported on a surgical intervention. Eighteen (82%) of these IPDMAs presented subgroup analyses. Subgroups were mainly based on patient and disease characteristics. The median number of reported subgroup analyses was 3.5 (IQR 1.25-6.5). Statistical methods for subgroup analyses were mentioned in 11 (61%) surgical IPDMAs.Eleven (61%) of the 18 IPDMAs performing subgroup analyses reported a significant overall effect estimate, whereas six (33%) reported a non-significant one. Of the IPDMAs that reported non-significant overall results, three IPDMAs (50%) reported significant results in one or more subgroup analyses. Results remained significant in one or more subgroups in eight of the IPDMAs (73%) that reported a significant overall result.Eight (44%) of the 18 significant subgroups appeared to be implemented in clinical guidelines. The quality of reporting among surgical IPDMAs varied from low to high quality.ConclusionMany of the surgical IPDMAs performed subgroup analyses, but overall treatment effects were more often emphasized than subgroup effects. Although, most surgical IPDMAs included in the present study have only recently been published, about half of the significant subgroups were already implemented in treatment guidelines.

Project description:IntroductionPregnant women are more vulnerable to malaria leading to adverse impact on both mothers and fetuses. However, knowledge on the efficacy and safety of antimalarials in pregnancy is limited by the paucity of randomised control trials and the lack of standardised protocols in this special subpopulation. Pooling individual patient data (IPD) for meta-analysis could address in part these limitations to summarise accurately the currently available evidence on treatment efficacy and risk factors for treatment failure.Methods and analysisTo assess the treatment efficacy of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy, seven databases (Medline, Embase, Global Health, Cochrane Library, Scopus, Web of Science and Literatura Latino Americana em Ciências da Saúde) and two clinical trial registries (International Clinical Trials Registry Platform and ClinicalTrial.gov) were searched. Both interventional and observational cohort studies following up for at least 28 days will be included. IPD of the identified eligible published or unpublished studies will be sought by inviting principal investigators. Raw IPD will be shared through the web-based secure platform developed by the WorldWide Antimalarial Resistance Network using the established methodology. The primary objective is to compare the risk of PCR-corrected treatment failure among different treatments and to find the risk factors. One-stage IPD meta-analysis by Cox model with shared frailty will be conducted. A risk of bias assessment will be conducted to address the impact of unshared potential data and of the quality of individual studies. Potential limitations include difficulty in acquiring the IPD and heterogeneity of the study designs due to the lack of standard.Ethics and disseminationThis IPD meta-analysis consists of secondary analyses of existing anonymous data and meets the criteria for waiver of ethics review by the Oxford Tropical Research Ethics Committee. The results of this IPD meta-analysis will be disseminated through open-access publications at peer-reviewed journals. The study results will lead to a better understanding of malaria treatment in pregnancy, which can be used for clinical decision-making and conducting further studies.Prospero registration numberCRD42018104013.

Project description:BACKGROUND: Preterm infants requiring assisted ventilation are at significant risk of both pulmonary and cerebral injury. Inhaled Nitric Oxide, an effective therapy for pulmonary hypertension and hypoxic respiratory failure in the full term infant, has also been studied in preterm infants. The most recent Cochrane review of preterm infants includes 11 studies and 3,370 participants. The results show a statistically significant reduction in the combined outcome of death or chronic lung disease (CLD) in two studies with routine use of iNO in intubated preterm infants. However, uncertainty remains as a larger study (Kinsella 2006) showed no significant benefit for iNO for this combined outcome. Also, trials that included very ill infants do not demonstrate significant benefit. One trial of iNO treatment at a later postnatal age reported a decrease in the incidence of CLD. The aim of this individual patient meta-analysis is to confirm or refute these potentially conflicting results and to determine the extent to which patient or treatment characteristics may explain the results and/or may predict benefit from inhaled Nitric Oxide in preterm infants. METHODS/DESIGN: The Meta-Analysis of Preterm Patients on inhaled Nitric Oxide (MAPPiNO) Collaboration will perform an individual patient data meta-analysis to answer these important clinical questions. Studies will be included if preterm infants receiving assisted ventilation are randomized to receive inhaled Nitric Oxide or to a control group. The individual patient data provided by the Collaborators will be analyzed on an intention-to-treat basis where possible. Binary outcomes will be analyzed using log-binomial regression models and continuous outcomes will be analyzed using linear fixed effects models. Adjustments for trial differences will be made by including the trial variable in the model specification. DISCUSSION: Thirteen (13) trials, with a total of 3567 infants are eligible for inclusion in the MAPPiNO systematic review. To date 11 trials (n = 3298, 92% of available patients) have agreed to participate. Funding was successfully granted from Ikaria Inc as an unrestricted grant. A collaborative group was formed in 2006 with data collection commencing in 2007. It is anticipated that data analysis will commence in late 2009 with results being publicly available in 2010.

Project description:BackgroundMeta-analyses (MA) based on individual patient data (IPD) are regarded as the gold standard for meta-analyses and are becoming increasingly common, having several advantages over meta-analyses of summary statistics. These analyses are being undertaken in an increasing diversity of settings, often having a binary outcome. In a previous systematic review of articles published between 1999-2001, the statistical approach was seldom reported in sufficient detail, and the outcome was binary in 32% of the studies considered. Here, we explore statistical methods used for IPD-MA of binary outcomes only, a decade later.MethodsWe selected 56 articles, published in 2011 that presented results from an individual patient data meta-analysis. Of these, 26 considered a binary outcome. Here, we review 26 IPD-MA published during 2011 to consider: the goal of the study and reason for conducting an IPD-MA, whether they obtained all the data they sought, the approach used in their analysis, for instance, a two-stage or a one stage model, and the assumption of fixed or random effects. We also investigated how heterogeneity across studies was described and how studies investigated the effects of covariates.Results19 of the 26 IPD-MA used a one-stage approach. 9 IPD-MA used a one-stage random treatment-effect logistic regression model, allowing the treatment effect to vary across studies. Twelve IPD-MA presented some form of statistic to measure heterogeneity across studies, though these were usually calculated using two-stage approach. Subgroup analyses were undertaken in all IPD-MA that aimed to estimate a treatment effect or safety of a treatment,. Sixteen meta-analyses obtained 90% or more of the patients sought.ConclusionEvidence from this systematic review shows that the use of binary outcomes in assessing the effects of health care problems has increased, with random effects logistic regression the most common method of analysis. Methods are still often not reported in enough detail. Results also show that heterogeneity of treatment effects is discussed in most applications.

Project description:BackgroundMalaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy.MethodsFor this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371.FindingsWe identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92).InterpretationWe found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted.FundingMedicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

Dataset Information

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

Publications

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

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