Elliott M. Antman

Bio: Elliott M. Antman is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Myocardial infarction & TIMI. The author has an hindex of 161, co-authored 716 publications receiving 179462 citations. Previous affiliations of Elliott M. Antman include Duke University & Katholieke Universiteit Leuven.

The Risk Score Profile: a novel approach to characterising the risk of populations enrolled in clinical studies

Abstract: Aims Interpreting the results and practice implications of clinical studies requires accurate characterisation of the baseline risk of the population. We evaluated the Thrombolysis in Myocardial Infarction (TIMI) risk score for STEMI as a tool to describe and compare the risk profile of populations enrolled in three clinical trials (InTIME-II, ASSENT-2 and MAGIC) and the National Registry of Myocardial Infarction. Methods and Results The risk score was calculated for each patient \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((N=121,085)\) \end{document} and the frequency distribution plotted for each population. The Risk Score Profiles were compared using the Kolmogorov–Smirnov test. The Risk Score Profile demonstrated a striking concordance between the baseline risk of patients in InTIME-II and ASSENT-2 (median scores in each=\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(3[1,4]\) \end{document}, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(P=0.11)\) \end{document}. In contrast, the distributions in MAGIC (designed to enroll high risk) and NRMI (registry) were shifted significantly toward higher risk (median scores=\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(4[3,5]\) \end{document} for MAGIC and \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(4[2,6]\) \end{document} in NRMI, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(P{<}0.0001\) \end{document} for each vs. InTIME-II). A graded relationship between the risk score and mortality was evident in each study \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((P{<}0.0001)\) \end{document}. Conclusions The frequency distribution of the TIMI Risk Score, or similar tools for risk assessment, may be used to quantify and readily compare the risk profile of populations enrolled in clinical studies.

Should evidence-based proof of efficacy as defined for a specific therapeutic agent be extrapolated to encompass a therapeutic class of agents?

Abstract: Our task as clinicians would be simple if all we had to do was to follow the logical sequence of identifying a biological target, finding a drug or treatment specifically affecting that target, testing the efficacy of the drug or treatment in appropriately designed clinical trials, and then prescribing only those drugs or treatments with proven efficacy and an acceptable safety profile. Drugs that affect a given biological target could be considered as a “class,” with those that show “efficacy” in clinical trials considered as therapeutic alternatives within that class. Unfortunately, the real world is not that simple. Defining precisely what we mean by class effect and efficacy becomes increasingly problematic, for example, as we have recently witnessed with calcium channel blockers, β-blockers, angiotensin-converting enzyme inhibitors, HMG CoA reductase inhibitors, glycoprotein IIb/IIIa antagonists, low-molecular-weight heparins, and direct thrombin antagonists.1 If we identify a drug that demonstrates efficacy, are the benefits of that drug generalizable to all drugs with similar biological targets?2 If benefits are present in one clinical circumstance, are those benefits generalizable to all circumstances in which that class of drugs can be applied?3 In the modern cost-conscious arena, can we substitute less expensive, mechanistically similar agents that may not have the same weight of clinical evidence support or even the same degree of clinical benefit? When is it acceptable to generalize to a class effect, or should we adhere strictly to evidence-based therapy with individual compounds? These issues can be viewed from both scientific and clinical perspectives. ### Definition of Biological Target As our scientific knowledge grows, our traditional grouping of drugs has become, to a large extent, obsolete. For example, there are 9 different calcium channel blockers that are approved for clinical use in the United States, which can be divided into 5 general groups on the basis of …

Measuring inconsistency in meta-analyses

Abstract: Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice? Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis. Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4 Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted? A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …

The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration

Abstract: Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.

Cochrane Handbook for Systematic Reviews of Interventions

Abstract: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.