scholarly journals The Impact of Drug Trials With Financial Conflict of Interests on the Meta-Analyses: A Meta-Epidemiological Study

2021 ◽  
Author(s):  
Na Zhang ◽  
Peijing Yan ◽  
Haitong Zhao ◽  
Lufang Feng ◽  
Xiajing Chu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Epidemiological Study ◽  
Evidence Synthesis ◽  
Drug Trials ◽  
Included Trial ◽  
Conflict Of Interests ◽  
Financial Conflict ◽  
Meta Analyses ◽  
The Impact ◽  
Major Adverse Events

Background: Drug trials with potential financial conflict of interests (FCOIs) may influence trial design, drug dosage, comparators, and promising results are more likely to be reported. The objective of this study was to assess the impact of trials with FCOIs on evidence synthesis in meta-analyses (MAs). Methods: A total of 96 MAs from the Cochrane Library about drug trials were investigated. The primary outcomes examined the proportion of conclusions that would change with the exclusion of trials with potential FCOIs. If the proportion of changed conclusions was below the non-inferiority margin of 10%, we considered that it was not inferior to include the trials with potential FCOIs in the MAs. Results: Only 54.17% of MAs reported the funding sources of each included trial, and in 21.88% of MAs, the author-industry-related financial ties of each included trial were reported. When trials with FCOIs were excluded, the changed conclusions of effectiveness and major adverse events were 13.16% and 11.11%, respectively, and the I 2 decreased by 13.56% and 10.09%, respectively. For serious adverse events, the exclusion of FCOIs trials did not lead to any change in conclusions; however, the I 2 decreased by 24.24%. The impact of trials without reported FCOIs was also examined on evidence synthesis, and the results showed that the changed conclusions of effectiveness and major adverse events were 5.26% and 6.25%, respectively, indicating non-inferiority. However, the I 2 increased by 13.60% and 12.37%, respectively. Conclusion: In this meta-epidemiological study, we demonstrated that trials with FCOIs may not only influence the final outcome of MAs but may also increase the heterogeneity of results. It is suggested that all MAs fully report the FCOIs involved in evidence-based research and explore the impact of its FCOIs to better provide a more valuable reference for patients, clinicians, and policymakers.

Network vs. Pairwise Meta-Analyses: A Case Study of the Impact of an Evidence-Synthesis Paradigm on Value of Information Outcomes

2014 ◽  
Vol 32 (10) ◽  
pp. 995-1004 ◽  
Author(s):  
Zafar Zafari ◽  
Kristian Thorlund ◽  
J. Mark FitzGerald ◽  
Carlo A. Marra ◽  
Mohsen Sadatsafavi
Keyword(s):  
Value Of Information ◽  
Evidence Synthesis ◽  
Meta Analyses ◽  
The Impact

Description of a pharmacist-driven safety algorithm in Staphylococcus aureus bacteremia: Compliance, interventions, and good saves

2020 ◽  
Vol 41 (8) ◽  
pp. 921-925
Author(s):  
Tara H. Lines ◽  
Whitney J. Nesbitt ◽  
Matthew H. Greene ◽  
George E. Nelson
Keyword(s):  
Staphylococcus Aureus ◽  
Adverse Events ◽  
Academic Medical Center ◽  
Tertiary Care ◽  
Safety Net ◽  
Definitive Therapy ◽  
Before And After ◽  
Bundle Compliance ◽  
The Impact ◽  
Major Adverse Events

AbstractObjective:To evaluate the impact of a pharmacist-driven Staphylococcus aureus bacteremia (SAB) safety bundle supported by leadership and to compare compliance before and after implementation.Design:Retrospective cohort study with descriptive and before-and-after analyses.Setting:Tertiary-care academic medical center.Patients:All patients with documented SAB, regardless of the source of infection, were included. Patients transitioned to palliative care were excluded from before-and-after analysis.Methods:A pharmacist-driven safety bundle including documented clearance of bacteremia, echocardiography, removal of central venous catheters, and targeted intravenous therapy of at least 2 weeks duration was implemented in November 2015 and was supported by leadership with stepwise escalation for nonresponse. A descriptive analysis of all patients with SAB during the study period included pharmacy interventions, acceptance rates, and escalation rates. A pre–post implementation analysis of 100 sequential patients compared bundle compliance and descriptive parameters.Results:Overall, 391 interventions were made in the 20-month period following implementation, including 20 “good saves” avoiding potentially major adverse events. No statistically significant differences in complete bundle compliance were detected between the periods (74% vs 84%; P = .08). However, we detected a significant increase in echocardiography after the bundle was implemented (83% vs 94%; P = .02) and fewer patients received suboptimal definitive therapy after the bundle was implemented (10% vs 3%; P = .045).Conclusions:This pharmacist-driven SAB safety bundle with leadership support showed improvement in process measures, which may have prevented major adverse events, even with available infectious diseases (ID) consultation. It provides a critical safety net for institutions without mandatory ID consultation or with limited antimicrobial stewardship resources.

scholarly journals Prone Positioning of Non-intubated Patients with COVID-19 - A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Mallikarjuna Reddy PONNAPA REDDY ◽  
Ashwin SUBRAMANIAM ◽  
Zheng Jie LIM ◽  
Alexandr ZUBAREV ◽  
Afsana AFROZ ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Prone Positioning ◽  
Serious Adverse Events ◽  
Lack Of Control ◽  
The Impact ◽  
Substantial Heterogeneity ◽  
Major Adverse Events

Abstract Purpose: Several studies have reported adopting prone positioning (PP) in non-intubated patients with COVID-19-related hypoxaemic respiratory failure. This systematic review and meta-analysis evaluated the impact of PP on oxygenation and clinical outcomes.Methods: We searched PubMed, Embase and the COVID-19 living systematic review from December 1, 2019 to July 23, 2020. We included studies that reported using PP in hypoxaemic, non-intubated adult patients with COVID-19. Primary outcome measureed was the weighted mean difference (MD) in oxygenation parameters (PaO2/FiO2, PaO2 or SpO2) pre and post-PP. Results: Fifteen single arm observational studies reporting PP in 449 patients were included. Substantial heterogeneity was noted in terms of, location within hospital where PP was instituted, respiratory supports during PP, and frequency and duration of PP. Significant improvement in oxygenation was reported post-PP: PaO2/FiO2 (MD 37.6, 95% CI 18.8-56.5); PaO2 (MD 30.4 mmHg, 95% CI 10.9 to 49.9); and SpO2 (MD 5.8%, 95% CI 3.7 to 7.9). Patients with a pre-PP PaO2/FiO2 ≤150 experienced greater oxygenation improvements compared with those with a pre-PP PaO2/FiO2 >150 (MD 40.5, 95% CI -3.5 to 84.6) vs. 37, 95% CI 17.1 to 56.9). Respiratory rate decreased post-PP (MD -2.9, 95% CI -5.4 to -0.4). Overall intubation and mortality rates were 21% (90/426) and 26% (101/390) respectively. There were no major adverse events reported. Conclusions: Despite the significant variability in frequency and duration of PP and respiratory supports applied, PP was associated with improvements in oxygenation parameters without any reported serious adverse events. The results are limited by lack of control arm and adjustment for confounders. Clinical trials are required to determine the effect of awake PP on patient-centred outcomes.Systematic review registration: Registration/protocol in PROSPERO (CRD42020194080).

scholarly journals Impact of investigator initiated trials and industry sponsored trials on medical practice (IMPACT): rationale and study design

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
E. Nury ◽  
K. Bischoff ◽  
K. Wollmann ◽  
K. Nitschke ◽  
S. Lohner ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Systematic Reviews ◽  
Medical Practice ◽  
Research Impact ◽  
Study Cohort ◽  
Drug Trials ◽  
Study Characteristics ◽  
Investigator Initiated Trials ◽  
Meta Analyses ◽  
The Impact

Abstract Background The German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF) initiated large research programs to foster high quality clinical research in the academic area. These investigator initiated trials (IITs) cover important areas of medical research and often go beyond the scope of industry sponsored trials (ISTs). The purpose of this project was to understand to what extent results of randomized controlled IITs and ISTs have an impact on medical practice, measured by their availability for decisions in healthcare and their implementation in clinical practice. We aimed to determine study characteristics influencing a trial’s impact such as type of sponsor and place of conduct. In this article, we describe the rationale and design of this project and present the characteristics of the trials included in our study cohort. Methods The research impact of the following sub-cohorts was compared: German IITs (funded by DFG and BMBF or by other German non-commercial organizations), international IITs (without German contribution), German ISTs, and international ISTs. Trials included were drawn from the DFG−/BMBF-Websites, the German Clinical Trials Register, and from ClinicalTrials.gov. Research impact was measured as follows: 1) proportion of published trials, 2) time to publication, 3) proportion of publications appropriately indexed in biomedical databases, 4) proportion of openly accessible publications, 5) broadness of publication’s target group, 6) citation of publications by systematic reviews or meta-analyses, and 7) appearance of publications or citing systematic reviews or meta-analyses in clinical practice guidelines. We also aimed to identify study characteristics associated with the impact of trials. Results We included 691 trials: 120 German IITs, 200 International IITs, 171 German ISTs and 200 International ISTs. The median number of participants was 150, 30% were international trials and 70% national trials, 48% drug-trials and 52% non-drug trials. Overall, 72% of the trials had one pre-defined primary endpoint, 28% two or more (max. 36). Conclusions The results of this project deepen our understanding of the impact of biomedical research on clinical practice and healthcare policy, add important insights for the efficient allocation of scarce research resources and may facilitate providing accountability to the different stakeholders involved.

scholarly journals Long-term safety of prenatal and neonatal exposure to paracetamol: a protocol for a systematic review

2020 ◽  
Vol 4 (1) ◽  
pp. e000907
Author(s):  
Samira Samiee-Zafarghandy ◽  
Katelyn Sushko ◽  
John Van Den Anker
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Systematic Reviews ◽  
Evidence Synthesis ◽  
Knowledge Exchange ◽  
Newborn Infants ◽  
Assessment Tools ◽  
Neonatal Exposure ◽  
Meta Analyses

IntroductionA surge in the use of paracetamol in neonates has resulted in growing concerns about its potential long-term adverse events. In this study, we conduct a systematic review of the long-term safety of prenatal and neonatal exposure to paracetamol in newborn infants.Methods and analysisWe will follow the Joanna Briggs Institute Manual for Evidence Synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements to conduct and report this review. We will conduct a systematic search of Embase, MEDLINE, Web of Science and Google Scholar for studies with data on long-term adverse events in neonates that were exposed to paracetamol in the prenatal and/or neonatal period. We will not apply language or design limitations. We will use standardised risk of bias assessment tools to perform a quality assessment of each included article.Ethics and disseminationThis systematic review will only involve access to publicly available data, and therefore ethical approval will not be required. The results of this study will be communicated to the target audience through peer-reviewed publication as well as other knowledge exchange platforms, such as conferences, congresses or symposia.Trial registrationThe protocol for this systematic review is submitted for registration to international database of prospectively registered systematic reviews (PROSPERO, awaiting registration number).

Increasing age as a major determinant of major adverse outcomes in patients with atrial fibrillation: the EURObservational research programme in atrial fibrillation general long-term registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Boriani ◽  
M Proietti ◽  
C Laroche ◽  
O Piot ◽  
D.A Lane ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Adverse Events ◽  
Adverse Outcomes ◽  
Major Determinant ◽  
Funding Source ◽  
Ageing Population ◽  
Kaplan Meier ◽  
The Impact ◽  
Major Adverse Events

Abstract Introduction Increasing age is a well-known determinant for incident atrial fibrillation (AF) as well as for adverse outcomes. With a progressively ageing population in Europe (and elsewhere), contemporary data are needed to investigate the impact of age in relation to major adverse events in AF patients. Purpose To evaluate the impact of increasing age on major adverse outcomes in a contemporary European AF cohort. Methods Patients enrolled in the EORP-AF Long Term General Registry were categorized by age: <65, 65–74, 75–84, and ≥85 years. Any thromboembolic event (TE)/acute coronary syndrome (ACS)/cardiovascular (CV) death, CV death, all-cause mortality were considered as outcomes. Results Among the 9762 patients included in this analysis, 2946 (30.2%) were <65 years, 3288 (33.7%) were 65–74 years, 2954 (30.3%) were 75–84 years and 574 (5.9%) were ≥85 years. With increasing age categories, there was a progressively higher prevalence of most risk factors and comorbidities. Accordingly, both mean CHA2DS2-VASc and HAS-BLED scores were progressively higher across the age categories (both p<0.0001). At discharge, use of any oral anticoagulant (OAC) drug was lower in patients ≥85 years compared to those aged 65–74 or 75–84 years (83.6% vs. 89.4% and 88.8%, respectively) but significantly higher than in those <65 years (80.2%) [p<0.001]. Rate of all major adverse events progressively increased across the age categories, being higher in those aged ≥85 (all p<0.001). Kaplan-Meier curves showed an increasing cumulative risk across the age groups for all the outcomes (p<0.0001) (Figure 1). A fully adjusted Cox regression analysis demonstrated a progressively increasing association between age categories and the risk of all major adverse outcomes (Table 1). Conclusions In a large contemporary cohort of European AF patients, increasing age was a major determinant of major adverse outcomes. Figure 1. Kaplan-Meier Curves for All-Cause Death Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Since the start of EORP programme, several companies supported its activities with unrestricted grants.

scholarly journals Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study

BMJ ◽  
2020 ◽  
pp. l6802 ◽  
Author(s):  
Helene Moustgaard ◽  
Gemma L Clayton ◽  
Hayley E Jones ◽  
Isabelle Boutron ◽  
Lars Jørgensen ◽  
...  
Keyword(s):  
Epidemiological Study ◽  
Systematic Reviews ◽  
Treatment Effects ◽  
Healthcare Providers ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Cochrane Database ◽  
Patient Reported ◽  
Meta Analyses ◽  
The Impact

Abstract Objectives To study the impact of blinding on estimated treatment effects, and their variation between trials; differentiating between blinding of patients, healthcare providers, and observers; detection bias and performance bias; and types of outcome (the MetaBLIND study). Design Meta-epidemiological study. Data source Cochrane Database of Systematic Reviews (2013-14). Eligibility criteria for selecting studies Meta-analyses with both blinded and non-blinded trials on any topic. Review methods Blinding status was retrieved from trial publications and authors, and results retrieved automatically from the Cochrane Database of Systematic Reviews. Bayesian hierarchical models estimated the average ratio of odds ratios (ROR), and estimated the increases in heterogeneity between trials, for non-blinded trials (or of unclear status) versus blinded trials. Secondary analyses adjusted for adequacy of concealment of allocation, attrition, and trial size, and explored the association between outcome subjectivity (high, moderate, low) and average bias. An ROR lower than 1 indicated exaggerated effect estimates in trials without blinding. Results The study included 142 meta-analyses (1153 trials). The ROR for lack of blinding of patients was 0.91 (95% credible interval 0.61 to 1.34) in 18 meta-analyses with patient reported outcomes, and 0.98 (0.69 to 1.39) in 14 meta-analyses with outcomes reported by blinded observers. The ROR for lack of blinding of healthcare providers was 1.01 (0.84 to 1.19) in 29 meta-analyses with healthcare provider decision outcomes (eg, readmissions), and 0.97 (0.64 to 1.45) in 13 meta-analyses with outcomes reported by blinded patients or observers. The ROR for lack of blinding of observers was 1.01 (0.86 to 1.18) in 46 meta-analyses with subjective observer reported outcomes, with no clear impact of degree of subjectivity. Information was insufficient to determine whether lack of blinding was associated with increased heterogeneity between trials. The ROR for trials not reported as double blind versus those that were double blind was 1.02 (0.90 to 1.13) in 74 meta-analyses. Conclusion No evidence was found for an average difference in estimated treatment effect between trials with and without blinded patients, healthcare providers, or outcome assessors. These results could reflect that blinding is less important than often believed or meta-epidemiological study limitations, such as residual confounding or imprecision. At this stage, replication of this study is suggested and blinding should remain a methodological safeguard in trials.

scholarly journals Overview of Federated Facility to Harmonize, Analyze and Management of Missing Data in Cohorts

2019 ◽  
Vol 9 (19) ◽  
pp. 4103 ◽  
Author(s):  
Hema Sekhar Reddy Rajula ◽  
Veronika Odintsova ◽  
Mirko Manchia ◽  
Vassilios Fanos
Keyword(s):  
Missing Data ◽  
Cohort Studies ◽  
Fixed Effects ◽  
Statistical Power ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
Database Systems ◽  
Contributing Factors ◽  
Meta Analyses ◽  
The Impact

Cohorts are instrumental for epidemiologically oriented observational studies. Cohort studies usually observe large groups of individuals for a specific period of time to identify the contributing factors to a specific outcome (for instance an illness) and create associations between risk factors and the outcome under study. In collaborative projects, federated data facilities are meta-database systems that are distributed across multiple locations that permit to analyze, combine, or harmonize data from different sources making them suitable for mega- and meta-analyses. The harmonization of data can increase the statistical power of studies through maximization of sample size, allowing for additional refined statistical analyses, which ultimately lead to answer research questions that could not be addressed while using a single study. Indeed, harmonized data can be analyzed through mega-analysis of raw data or fixed effects meta-analysis. Other types of data might be analyzed by e.g., random-effects meta-analyses or Bayesian evidence synthesis. In this article, we describe some methodological aspects related to the construction of a federated facility to optimize analyses of multiple datasets, the impact of missing data, and some methods for handling missing data in cohort studies.

scholarly journals Transfusion of fresher vs older red blood cells in hospitalized patients: a systematic review and meta-analysis

Blood ◽  
2016 ◽  
Vol 127 (4) ◽  
pp. 400-410 ◽  
Author(s):  
Paul E. Alexander ◽  
Rebecca Barty ◽  
Yutong Fei ◽  
Per Olav Vandvik ◽  
Menaka Pai ◽  
...  
Keyword(s):  
Adverse Events ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Meta Analysis ◽  
Risk Difference ◽  
Current Evidence ◽  
Current Standard ◽  
Changing Practices ◽  
Meta Analyses ◽  
The Impact

Abstract The impact of transfusing fresher vs older red blood cells (RBCs) on patient-important outcomes remains controversial. Two recently published large trials have provided new evidence. We summarized results of randomized trials evaluating the impact of the age of transfused RBCs. We searched MEDLINE, EMBASE, CINAHL, the Cochrane Database for Systematic Reviews, and Cochrane CENTRAL for randomized controlled trials enrolling patients who were transfused fresher vs older RBCs and reported outcomes of death, adverse events, and infection. Independently and in duplicate, reviewers determined eligibility, risk of bias, and abstracted data. We conducted random effects meta-analyses and rated certainty (quality or confidence) of evidence using the GRADE approach. Of 12 trials that enrolled 5229 participants, 6 compared fresher RBCs with older RBCs and 6 compared fresher RBCs with current standard practice. There was little or no impact of fresher vs older RBCs on mortality (relative risk [RR], 1.04; 95% confidence interval [CI], 0.94-1.14; P = .45; I2 = 0%, moderate certainty evidence) or on adverse events (RR, 1.02; 95% CI, 0.91-1.14; P = .74; I2 = 0%, low certainty evidence). Fresher RBCs appeared to increase the risk of nosocomial infection (RR, 1.09; 95% CI, 1.00-1.18; P = .04; I2 = 0%, risk difference 4.3%, low certainty evidence). Current evidence provides moderate certainty that use of fresher RBCs does not influence mortality, and low certainty that it does not influence adverse events but could possibly increase infection rates. The existing evidence provides no support for changing practices toward fresher RBC transfusion.

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