Evaluation of observational and controlled trials of therapy

2009 ◽  
pp. 127-152 ◽  
Author(s):  
Richard J. Glassock ◽  
Daniel C. Cattran
Keyword(s):  
Clinical Trials ◽  
False Negative ◽  
Evidence Base ◽  
Glomerular Disease ◽  
Good News ◽  
Specific Disease ◽  
Negative Results ◽  
Primary Glomerular Disease ◽  
Therapeutic Decision Making ◽  
Meta Analyses

The literature on the subject of treatment of glomerular disease is immense (over 15,000 articles in PubMed as of July, 2008). Negotiating this broad and complex panorama can be a difficult task, especially in relationship to the evaluation of the best evidence for a particular treatment strategy for a specific disease entity occurring in an individual patient. Perfection is not attainable in clinical trials of therapy and every report has some pitfall or limitation. Some studies, however, stand out as excellent examples of design and execution. Unfortunately, in the field of treatment of glomerular disease such studies are relatively uncommon. The good news is that well designed and executed studies of treatment of primary glomerular disease are being reported with increasing frequency in recent years. This has occurred in part because of increased collaboration among groups interested in furthering knowledge in this important area of inquiry, but also because of better recognition of the deficiencies of past efforts to study treatment of glomerular disease in clinical trials. Many interinstitutional collaborative studies have been aided by improvements in trial design and by more complete descriptions of the natural history of untreated disease. One of the main weaknesses of clinical studies of therapy in primary glomerular disease is the small numbers of subjects studied in individual reports. This increases the risks of confounding and of both false positive and false negative results. The purpose of this chapter is to provide a concise analysis of the strengths and weakness of the various approaches to the study of therapeutic efficacy and safety of agents used in primary glomerular disease. The focus will be on observational studies, controlled clinical trials, and meta-analyses of published reports. The specific aims are to equip the discerning reader for improved understanding of the evidence-base for therapy of primary glomerular disease. The details of the specific reports and how they can be integrated into an ‘evidence-based’ approach to therapeutic decision-making are dealt with in the chapters devoted to specific disease entities which follow.

Large-scale randomized evidence: Trials and meta-analyses of trials

2020 ◽  
pp. 51-66
Author(s):  
Colin Baigent ◽  
Richard Peto ◽  
Richard Gray ◽  
Natalie Staplin ◽  
Sarah Parish ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Large Scale ◽  
Meta Analysis ◽  
False Negative ◽  
Premature Deaths ◽  
Common Causes ◽  
The Common ◽  
Meta Analyses ◽  
Positive Results

Clinical trials generally need to be able to detect or to refute realistically moderate (but still worthwhile) differences between treatments in long-term disease outcome. Large-scale randomized evidence should be able to detect such effects, but medium-sized trials or medium-sized meta-analyses can, and often do, yield false-negative or exaggeratedly positive results. Hundreds of thousands of premature deaths each year could be avoided by seeking appropriately large-scale randomized evidence about various widely practicable treatments for the common causes of death, and by disseminating this evidence appropriately. This chapter takes a look at the use of large-scale randomized evidence—produced from trials and meta-analysis of trials—and how this data should be handled in order to produce accurate result.

Random error in cardiovascular meta-analyses: How common are false positive and false negative results?

2013 ◽  
Vol 168 (2) ◽  
pp. 1102-1107 ◽  
Author(s):  
Zaina AlBalawi ◽  
Finlay A. McAlister ◽  
Kristian Thorlund ◽  
Michelle Wong ◽  
Jørn Wetterslev
Keyword(s):  
Random Error ◽  
False Positive ◽  
False Negative ◽  
Negative Results ◽  
False Negative Results ◽  
Meta Analyses

scholarly journals Review of properties and mechanisms of action of hepatoprotective drugs

2020 ◽  
pp. 36-44
Author(s):  
Е.В. Кардаш ◽  
Е.М. Григорьева ◽  
А.Г. Емельянова ◽  
С.А. Тарасов
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Side Effects ◽  
Randomized Clinical Trials ◽  
Evidence Base ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Simultaneous Administration ◽  
Essential Phospholipids ◽  
Meta Analyses

В медицинской практике достаточно часто возникает необходимость в одновременном приеме нескольких лекарственных средств. Иногда это оказывается невозможным в силу наличия у препаратов гепатотоксических свойств, поэтому актуальными задачами фармакологии являются как поиск и разработка новых препаратов, так и оптимизация уже существующих с целью уменьшения побочных эффектов при их приеме. В настоящем обзоре были проанализированы данные о фармакологических препаратах класса гепатопротекторов, разобраны механизмы их действия и потенциал поиска новых препаратов. В заключение отмечено, что в настоящее время в клинической практике наибольшей популярностью пользуются препараты, содержащие эссенциальные фосфолипиды и препараты, улучшающие рециркуляцию и выведение желчных кислот. Существуют теоретические обоснования механизмов действия этих препаратов и перспектива накопления доказательной базы для них в виде рандомизированных клинических исследований и мета-анализов. Medical practice quite often requires simultaneous administration of several drugs. Sometimes it is impossible due to their hepatotoxicity; therefore, urgent tasks of pharmacology include searching for and developing new drugs as well as optimizing already existing products in order to reduce side effects during their administration. This review focused on pharmacological drugs of the hepatoprotector class and their mechanisms of action and evaluated the prospects of searching for new medicines. In conclusion, drugs containing essential phospholipids and those improving recirculation and removal of bile acids are currently the most popular agents in clinical practice. Mechanisms of action of these drugs are theoretically justified and there is a prospect for building an evidence base for them by randomized clinical trials and meta-analyses.

scholarly journals An investigation into the impact and implications of published papers from retracted research: systematic search of affected literature

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e031909 ◽  
Author(s):  
Alison Avenell ◽  
Fiona Stewart ◽  
Andrew Grey ◽  
Greg Gamble ◽  
Mark Bolland
Keyword(s):  
Systematic Review ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Research Misconduct ◽  
Evidence Base ◽  
Bibliographic Databases ◽  
Potential Influence ◽  
Relevant Research ◽  
Meta Analyses ◽  
The Impact

ObjectiveAnalyses of the impact of a body of clinical trial reports subject to research misconduct have been few. Our objective was to examine the impact on clinically relevant research of a group of researchers’ trial reports (‘affected trial reports’) affected by research misconduct, and whether identification of misconduct invoked a reappraisal.DesignIn 2016, we used five databases and search engines to identify ‘citing publications’, that is, guidelines, systematic and other reviews, and clinical trials citing any of 12 affected trial reports, published 1998–2011, eventually retracted for research misconduct. The affected trial reports were assessed more likely to have had impact because they had hip fracture outcomes and were in journals with impact factor >4. Two authors assessed whether findings of the citing publications would change if the affected trial reports were removed. In 2018, we searched for evidence that the citing publications had undertaken a reassessment as a result of the potential influence of the affected trial reports.ResultsBy 2016 the affected trial reports were cited in 1158 publications, including 68 systematic reviews, meta-analyses, narrative reviews, guidelines and clinical trials. We judged that 13 guidelines, systematic or other reviews would likely change their findings if the affected trial reports were removed, and in another eight it was unclear if findings would change. By 2018, only one of the 68 citing publications, a systematic review, appeared to have undertaken a reassessment, which led to a correction.ConclusionsWe found evidence that this group of affected trial reports distorted the evidence base. Correction of these distortions is slow, uncoordinated and inconsistent. Unless there is a rapid, systematic, coordinated approach by bibliographic databases, authors, journals and publishers to mitigate the impact of known cases of research misconduct, patients, other researchers and their funders may continue to be adversely affected.

scholarly journals How Powerful is the Evidence in Criminology? On Whether We Should Fear a Coming Crisis of Confidence

2017 ◽  
Author(s):  
J.C. Barnes
Keyword(s):  
Statistical Power ◽  
False Negative ◽  
Effect Sizes ◽  
Small Samples ◽  
Individual Level ◽  
Negative Results ◽  
Level Data ◽  
Key Factor ◽  
Coming Crisis ◽  
Meta Analyses

A crisis of confidence has struck the behavioral and social sciences. A key factor driving the crisis is the low levels of statistical power in many studies. Low power is problematic because it leads to increased rates of false-negative results, inflated false-discovery rates, and over-estimates of effect sizes. To determine whether these issues impact criminology, we computed estimates of statistical power by drawing 322 mean effect sizes and 271 average sample sizes from 81 meta-analyses. Results indicated criminological studies, on average, have a moderate level of power (mean = 0.605), but there is variability. This variability is observed across general studies as well as those designed to test interventions. Studies using macro-level data tend to have lower power than studies using individual-level data. To avoid a crisis of confidence, criminologists must not ignore statistical power and should be skeptical of large effects found in studies with small samples.

Rationale for heparin treatment of colon cancer

2000 ◽  
Vol 20 (03) ◽  
pp. 136-142 ◽  
Author(s):  
D. L. Ornstein ◽  
L. R. Zacharski
Keyword(s):  
Clinical Trials ◽  
Substantial Improvement ◽  
Patients With Cancer ◽  
Coagulation Mechanism ◽  
Anticoagulant Drug ◽  
Cancer Outcome ◽  
Meta Analyses ◽  
Improvement In Survival ◽  
Spectrum Of Patients ◽  
To Receive

SummaryIt is widely known that the systemic blood coagulation mechanism is often activated in malignancy, leading to an increased incidence of vascular thromboses in patients with cancer. It is not widely appreciated, however, that products of the coagulation mechanism may also support tumor growth and dissemination. Interest in this approach to cancer therapy has surged recently because of mounting evidence that the familiar anticoagulant drug, heparin, may impede tumor progression. Heparin has the capacity to modify angiogenesis, growth factor and protease activity, immune function, cell proliferation and gene expression in ways that may block malignant dissemination. Clinical trials in which heparin has been administered to a broad spectrum of patients to prevent or treat thrombosis have unexpectedly shown improvement in survival in the subset of patients with malignancy entered to these studies. Meta-analyses of clinical trials comparing unfractionated (UF) versus low molecular weight (LMW) heparin treating venous thromboembolism suggest that there may be substantial improvement in cancer outcome in patients with malignancy randomized to receive LMW heparin. These findings provide a rationale for definitive clinical trials of LMW heparin in cancer, and the results of several such studies that are currently underway are awaited with interest.

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