Britta Lang

A protocol for a systematic review on the impact of unpublished studies and studies published in the gray literature in meta-analyses

AbstractBackgroundMeta-analyses are particularly vulnerable to the effects of publication bias. Despite methodologists’ best efforts to locate all evidence for a given topic the most comprehensive searches are likely to miss unpublished studies and studies that are published in the gray literature only. If the results of the missing studies differ systematically from the published ones, a meta-analysis will be biased with an inaccurate assessment of the intervention’s effects.As part of the OPEN project (http://www.open-project.eu) we will conduct a systematic review with the following objectives:▪ To assess the impact of studies that are not published or published in the gray literature on pooled effect estimates in meta-analyses (quantitative measure).▪ To assess whether the inclusion of unpublished studies or studies published in the gray literature leads to different conclusions in meta-analyses (qualitative measure).Methods/DesignInclusion criteria: Methodological research projects of a cohort of meta-analyses which compare the effect of the inclusion or exclusion of unpublished studies or studies published in the gray literature. Literature search: To identify relevant research projects we will conduct electronic searches in Medline, Embase and The Cochrane Library; check reference lists; and contact experts. Outcomes: 1) The extent to which the effect estimate in a meta-analyses changes with the inclusion or exclusion of studies that were not published or published in the gray literature; and 2) the extent to which the inclusion of unpublished studies impacts the meta-analyses’ conclusions. Data collection: Information will be collected on the area of health care; the number of meta-analyses included in the methodological research project; the number of studies included in the meta-analyses; the number of study participants; the number and type of unpublished studies; studies published in the gray literature and published studies; the sources used to retrieve studies that are unpublished, published in the gray literature, or commercially published; and the validity of the methodological research project. Data synthesis: Data synthesis will involve descriptive and statistical summaries of the findings of the included methodological research projects.DiscussionResults are expected to be publicly available in the middle of 2013.

Detecting, quantifying and adjusting for publication bias in meta-analyses: protocol of a systematic review on methods

BackgroundHealth professionals and policymakers aspire to make healthcare decisions based on the entire relevant research evidence. This, however, can rarely be achieved because a considerable amount of research findings are not published, especially in case of ‘negative’ results - a phenomenon widely recognized as publication bias. Different methods of detecting, quantifying and adjusting for publication bias in meta-analyses have been described in the literature, such as graphical approaches and formal statistical tests to detect publication bias, and statistical approaches to modify effect sizes to adjust a pooled estimate when the presence of publication bias is suspected. An up-to-date systematic review of the existing methods is lacking.Methods/designThe objectives of this systematic review are as follows:• To systematically review methodological articles which focus on non-publication of studies and to describe methods of detecting and/or quantifying and/or adjusting for publication bias in meta-analyses.• To appraise strengths and weaknesses of methods, the resources they require, and the conditions under which the method could be used, based on findings of included studies.We will systematically search Web of Science, Medline, and the Cochrane Library for methodological articles that describe at least one method of detecting and/or quantifying and/or adjusting for publication bias in meta-analyses. A dedicated data extraction form is developed and pilot-tested. Working in teams of two, we will independently extract relevant information from each eligible article. As this will be a qualitative systematic review, data reporting will involve a descriptive summary.DiscussionResults are expected to be publicly available in mid 2013. This systematic review together with the results of other systematic reviews of the OPEN project (To Overcome Failure to Publish Negative Findings) will serve as a basis for the development of future policies and guidelines regarding the assessment and handling of publication bias in meta-analyses.

Protocol for a systematic review on the extent of non-publication of research studies and associated study characteristics

AbstractBackgroundMethodological research has found that non-published studies often have different results than those that are published, a phenomenon known as publication bias. When results are not published, or are published selectively based on the direction or the strength of the findings, healthcare professionals and consumers of healthcare cannot base their decision-making on the full body of current evidence.MethodsAs part of the OPEN project (http://www.open-project.eu) we will conduct a systematic review with the following objectives:1.To determine the proportion and/or rate of non-publication of studies by systematically reviewing methodological research projects that followed up a cohort of studies thata.received research ethics committee (REC) approval,b.were registered in trial registries, orc.were presented as abstracts at conferences.2.To assess the association of study characteristics (for example, direction and/or strength of findings) with likelihood of full publication. To identify reports of relevant methodological research projects we will conduct electronic database searches, check reference lists, and contact experts. Published and unpublished projects will be included. The inclusion criteria are as follows:a.RECs: methodological research projects that examined the subsequent proportion and/or rate of publication of studies that received approval from RECs;b.Trial registries: methodological research projects that examine the subsequent proportion and/or rate of publication of studies registered in trial registries;c.Conference abstracts: methodological research projects that examine the subsequent proportion and/or rate of full publication of studies which were initially presented at conferences as abstracts. Primary outcomes: Proportion/rate of published studies; time to full publication (mean/median; cumulative publication rate by time).Secondary outcomes: Association of study characteristics with full publication.The different questions (a, b, and c) will be investigated separately. Data synthesis will involve a combination of descriptive and statistical summaries of the included methodological research projects.DiscussionResults are expected to be publicly available in mid 2013.

Publication bias in animal research: a systematic review protocol

AbstractBackgroundSystematic reviews and meta-analyses of pre-clinical studies, in vivo animal experiments in particular, can influence clinical care. Publication bias is one of the major threats of validity in systematic reviews and meta-analyses. Previous empirical studies suggested that systematic reviews and meta-analyses have become more prevalent until 2010 and found evidence for compromised methodological rigor with a trend towards improvement. We aim to comprehensively summarize and update the evidence base on systematic reviews and meta-analyses of animal studies, their methodological quality and assessment of publication bias in particular.Methods/DesignThe objectives of this systematic review are as follows:To investigate the epidemiology of published systematic reviews of animal studies until present.To examine methodological features of systematic reviews and meta-analyses of animal studies with special attention to the assessment of publication bias.To investigate the influence of systematic reviews of animal studies on clinical research by examining citations of the systematic reviews by clinical studies. Eligible studies for this systematic review constitute systematic reviews and meta-analyses that summarize in vivo animal experiments with the purpose of reviewing animal evidence to inform human health. We will exclude genome-wide association studies and animal experiments with the main purpose to learn more about fundamental biology, physical functioning or behavior.In addition to the inclusion of systematic reviews and meta-analyses identified by other empirical studies, we will systematically search Ovid Medline, Embase, ToxNet, and ScienceDirect from 2009 to January 2013 for further eligible studies without language restrictions.Two reviewers working independently will assess titles, abstracts, and full texts for eligibility and extract relevant data from included studies. Data reporting will involve a descriptive summary of meta-analyses and systematic reviews.DiscussionResults are expected to be publicly available later in 2013 and may form the basis for recommendations to improve the quality of systematic reviews and meta-analyses of animal studies and their use with respect to clinical care.

Methods for detecting, quantifying, and adjusting for dissemination bias in meta-analysis are described

OBJECTIVE To systematically review methodological articles which focus on nonpublication of studies and to describe methods of detecting and/or quantifying and/or adjusting for dissemination in meta-analyses. To evaluate whether the methods have been applied to an empirical data set for which one can be reasonably confident that all studies conducted have been included. STUDY DESIGN AND SETTING We systematically searched Medline, the Cochrane Library, and Web of Science, for methodological articles that describe at least one method of detecting and/or quantifying and/or adjusting for dissemination bias in meta-analyses. RESULTS The literature search retrieved 2,224 records, of which we finally included 150 full-text articles. A great variety of methods to detect, quantify, or adjust for dissemination bias were described. Methods included graphical methods mainly based on funnel plot approaches, statistical methods, such as regression tests, selection models, sensitivity analyses, and a great number of more recent statistical approaches. Only few methods have been validated in empirical evaluations using unpublished studies obtained from regulators (Food and Drug Administration, European Medicines Agency). CONCLUSION We present an overview of existing methods to detect, quantify, or adjust for dissemination bias. It remains difficult to advise which method should be used as they are all limited and their validity has rarely been assessed. Therefore, a thorough literature search remains crucial in systematic reviews, and further steps to increase the availability of all research results need to be taken.

Dissemination bias in systematic reviews of animal research: a systematic review.

Background Systematic reviews of preclinical studies, in vivo animal experiments in particular, can influence clinical research and thus even clinical care. Dissemination bias, selective dissemination of positive or significant results, is one of the major threats to validity in systematic reviews also in the realm of animal studies. We conducted a systematic review to determine the number of published systematic reviews of animal studies until present, to investigate their methodological features especially with respect to assessment of dissemination bias, and to investigate the citation of preclinical systematic reviews on clinical research. Methods Eligible studies for this systematic review constitute systematic reviews that summarize in vivo animal experiments whose results could be interpreted as applicable to clinical care. We systematically searched Ovid Medline, Embase, ToxNet, and ScienceDirect from 1st January 2009 to 9th January 2013 for eligible systematic reviews without language restrictions. Furthermore we included articles from two previous systematic reviews by Peters et al. and Korevaar et al. Results The literature search and screening process resulted in 512 included full text articles. We found an increasing number of published preclinical systematic reviews over time. The methodological quality of preclinical systematic reviews was low. The majority of preclinical systematic reviews did not assess methodological quality of the included studies (71%), nor did they assess heterogeneity (81%) or dissemination bias (87%). Statistics quantifying the importance of clinical research citing systematic reviews of animal studies showed that clinical studies referred to the preclinical research mainly to justify their study or a future study (76%). Discussion Preclinical systematic reviews may have an influence on clinical research but their methodological quality frequently remains low. Therefore, systematic reviews of animal research should be critically appraised before translating them to a clinical context.

Prophylactic antibiotics before cord clamping in cesarean delivery: a systematic review

The number of clinical trials investigating the optimal timing of prophylactic antibiotics in cesarean section has increased rapidly over the last few years. We conducted a systematic review to inform up‐to‐date evidence‐based guidelines to prevent postpartum infectious morbidity in the mother and rule out any safety issues related to antepartum antibiotic exposure in infants.

Lack of controlled studies investigating the risk of postpartum haemorrhage in cesarean delivery after prior use of oxytocin: a scoping review

BackgroundPostpartum haemorrhage (PPH) is a major cause of maternal mortality and morbidity worldwide. Experimental and clinical studies indicate that prolonged oxytocin exposure in the first or second stage of labour may be associated with impaired uterine contractility and an increased risk of atonic PPH. Therefore, particularly labouring women requiring cesarean delivery constitute a subset of patients that may exhibit an unpredictable response to oxytocin. We mapped the evidence for comparative studies investigating the hypothesis whether the risk for PPH is increased in women requiring cesarean section after induction or augmentation of labour.MethodsWe performed a systematic literature search for clinical trials in Medline, Embase, Web of Science, and the Cochrane Library (May 2016). Additionally we searched for ongoing or unpublished trials in clinicaltrials.gov and the WHO registry platform. We identified a total of 36 controlled trials investigating the exogenous use of oxytocin in cesarean section. Data were extracted for study key characteristics and the current literature literature was described narratively.ResultsOur evidence map shows that the majority of studies investigating the outcome PPH focused on prophylactic oxytocin use compared to other uterotonic agents in the third stage of labour. Only 2 dose-response studies investigated the required oxytocin dose to prevent uterine atony after cesarean delivery for labour arrest. These studies support the hypotheses that labouring women exposed to exogenous oxytocin require a higher oxytocin dose after delivery than non-labouring women to prevent uterine atony after cesarean section. However, the study findings are flawed by limitations of the study design as well as the outcome selection. No clinical trial was identified that directly compared exogenous oxytocin versus no oxytocin application before intrapartum cesarean delivery.ConclusionDespite some evidence from dose-response studies that the use of oxytocin may increase the risk for PPH in intrapartum cesarean delivery, current research has not investigated the prepartal application of oxytocin in well controlled clinical trials. It was striking that most studies on exogenous oxytocin are focused on PPH prophylaxis in the third stage of labour without differing between the indications of cesarean section and hence the prepartal oxytocin status.

New members of the A{sub 2}M′M{sub 2}{sup ″} structure family (A=Ca, Sr, Yb, La; M′=In,Sn,Pb; M″=Si,Ge)

Abstract The new mixed tetrelides Sr 2 PbGe 2 and Yb 2 SnGe 2 , several mixed Ca/Sr (AII) germanides A 2 II ( Sn , Pb ) Ge 2 and two polymorphs of La 2 In Si 2 represent new members of the general structure family of ternary alkaline-earth/lanthanoid main group silicides/germanides A 2 M ′ M 2 ″ ( M ′ = In , Sn , Pb ; M ″ = Si , Ge ) . All compounds were synthesized from melts of the elements and their crystal structures have been determined by means of single crystal X-ray diffraction. Sr 2 PbGe 2 (Cmmm, a=402.36(11), b=1542.3(4), c=463.27(10) pm) crystallizes with the Mn 2 AlB 2 -type structure. In exhibiting infinite planar Ge zig-zag chains, it represents one border of the compound series. The other borderline case, where only [ Ge 2 ] dumbbells are left as Ge building units, is represented by the Ca/Yb tin germanides Ca 2 SnGe 2 and Yb 2 SnGe 2 ( Mo 2 FeB 2 -type ; P4/mbm, a=748.58(13)/740.27(7), c=445.59(8)/435.26(5) pm). In between these two border structures compounds with variable Si/Ge chain lengths could be obtained by varying the averaged size of the AII cations: Ca 0.45 Sr 1.55 PbGe 2 (new structure type; Pbam, a=791.64(5), b=2311.2(2), c=458.53(3) pm) contains planar six-membered chain segments [ Ge 6 ] . Tetrameric pieces [ Ge 4 ] are the conspicuous structure elements in Ca 1.16 Sr 0.84 SnGe 2 and La 2 In Si 2 ( La 2 InNi 2 -type ; Pbam, a=781.01(2)/762.01(13), b=1477.95(3)/1494.38(6), c=457.004(9)/442.1(3) pm). The tetragonal form of ’ La 2 In Si 2 ′ (exact composition: La 2 In 1.07 Si 1.93 , P4/mbm, a=1309.11(12), c=443.32(4) pm) also crystallizes in a new structure type, containing only [ Si 3 ] trimers as cutouts of the planar chains. In all structures the Si/Ge zig-zag chains/chain segments are connected by In/Sn/Pb atoms to form planar M layers, which are separated by pure A layers. Band structure calculations within the FP-LAPW DFT approach together with the Zintl formalism, extended by the presence of hypervalent bonding of the heavier M ′ elements, give insight into the chemical bonding of this series of p-block metallides. An analysis of the band structure for the border phases Sr 2 PbGe 2 and Ca 2 SnGe 2 shows the considerable π bonding contributions within the Ge building units, which also become apparent from the short Ge–Ge bond lengths.