Comparing results of large clinical trials to those of meta-analyses.

We consider methods for assessing agreement or disagreement between the results of a meta-analysis of small studies addressing a clinical question and the result of a large clinical trial (LCT) addressing the same clinical question. We recommend basing conclusions about agreement upon the difference between the two results (relative risk, log-odds ratio or similar summary statistic), in the light of the estimated standard error of that difference. To estimate the standard error of the meta-analytic result we recommend a random effects analysis, and where a between-studies variance component is found, that component of variance should be used twice: once in the estimated standard error for the meta-analytic result and again in the standard error of the LCT result (augmenting the internal standard error of that statistic).

Meta-analysis of multiple outcomes by regression with random effects.

Earlier work showed how to perform fixed-effects meta-analysis of studies or trials when each provides results on more than one outcome per patient and these multiple outcomes are correlated. That fixed-effects generalized-least-squares approach analyzes the multiple outcomes jointly within a single model, and it can include covariates, such as duration of therapy or quality of trial, that may explain observed heterogeneity of results among the trials. Sometimes the covariates explain all the heterogeneity, and the fixed-effects regression model is appropriate.

The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials.

Unlabelled: We performed meta-analyses of randomized, control trials to assess the effects of seven analgesic therapies on postoperative pulmonary function after a variety of procedures: epidural opioid, epidural local anesthetic, epidural opioid with local anesthetic, thoracic versus lumbar epidural opioid, intercostal nerve block, wound infiltration with local anesthetic, and intrapleural local anesthetic. Measures of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), vital capacity (VC), peak expiratory flow rate (PEFR), PaO2, and incidence of atelectasis, pulmonary infection, and pulmonary complications overall were analyzed. Compared with systemic opioids, epidural opioids decreased the incidence of atelectasis (risk ratio [RR] 0.

Comparative efficacy of epidural, subarachnoid, and intracerebroventricular opioids in patients with pain due to cancer.

Background And Objectives: Although rarely used, intracerebroventricular opioid therapy (ICV) is an option for the control of intractable pain due to cancer when systemic treatments have failed. The aim of the present study is to use available data from published trials to compare ICV with the more common epidural (EP) and subarachnoid (SA) opioid treatments in an attempt to establish the utility and safety of ICV.

Methods: Because there are no published controlled trials comparing these routes of administration, the combined data from multiple uncontrolled trials were used, with differences between the treatments analyzed statistically.

Uncertainty of the time of first significance in random effects cumulative meta-analysis.

We propose a process for evaluating quantities of clinical and statistical interest in cumulative meta-analysis. We use Monte Carlo simulation studies to assess the error variance of the time to significance in cumulative meta-analysis. For the specific cumulative meta-analyses that we simulated, the 95% confidence interval of the treatment effect, estimated by the random effects method at the time of earliest significance, appears to be approximately appropriate except when the hypothesized treatment effect is near the null.

Simple robust procedures for combining risk differences in sets of 2 x 2 tables.

Meta-analyses often use a random-effects model to incorporate unexplained heterogeneity of study results. Trimmed versions of meta-analytic estimators for the risk difference, adapted from procedures designed for a random-effects analysis, can resist the impact of a few anomalous studies. A simulation study compared untrimmed and trimmed versions of four meta-analytic procedures that give weighted averages of risk differences.

Understanding research synthesis (meta-analysis).

Synthesis of research findings has long been a part of reviewing and summarizing a field of study. Public health decisions are made on the available evidence. We summarize the approaches to research synthesis that draw on the best available evidence and the use of quantitative summaries through meta-analysis.

The efficacy of bacillus Calmette-Guérin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature.

Objective: To quantify the efficacy of vaccination of infants with bacillus Calmette-Guérin (BCG) against tuberculosis.

Data Sources: MEDLINE with index terms BCG vaccine, tuberculosis, and human; lists of all known studies provided by experts at the Centers for Disease Control and Prevention, the World Health Organization, and other organizations.

Study Selection: A total of 1264 articles and abstracts were reviewed for details on BCG vaccination, the availability of concurrent vaccinated and unvaccinated groups, and a tuberculosis outcome.

Multiple-outcomes meta-analysis of treatments for periodontal disease.

The results of periodontal therapy vary by disease severity, outcome measure, and method of data analysis. Several clinical trials and a subsequent meta-analysis have demonstrated that, for teeth with severe disease, surgery decreases probing depth (PD) and increases attachment level (AL) more than non-surgical treatment. For other disease levels, the choice of therapy depends on the outcome measure.

A random-effects regression model for meta-analysis.

Many meta-analyses use a random-effects model to account for heterogeneity among study results, beyond the variation associated with fixed effects. A random-effects regression approach for the synthesis of 2 x 2 tables allows the inclusion of covariates that may explain heterogeneity. A simulation study found that the random-effects regression method performs well in the context of a meta-analysis of the efficacy of a vaccine for the prevention of tuberculosis, where certain factors are thought to modify vaccine efficacy.

A survey of current problems in meta-analysis. Discussion from the Agency for Health Care Policy and Research inter-PORT Work Group on Literature Review/Meta-Analysis.

The United States Agency for Health Care Policy and Research brought together representatives from each of the Patient Outcomes Research Teams (PORTs) as the Inter-PORT Meta-Analysis Work Group. The purpose of the meeting was to discuss a wide range of problems the panel had encountered in the area of meta-analysis. Several actual problems were presented, and tentative solutions to those problems were given.

The Tennessee study of class size in the early school grades.

The Tennessee class size project is a three-phase study designed to determine the effect of smaller class size in the earliest grades on short-term and long-term pupil performance. The first phase of this project, termed Project STAR (for Student-Teacher Achievement Ratio), was begun in 1985, when Lamar Alexander was governor of Tennessee. Governor Alexander, who later served as secretary of education in the cabinet of President George Bush, had made education a top priority for his second term.

Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain: a meta-analysis.

Purpose: To assess the efficacy and safety of nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of cancer pain by meta-analyses of the published randomized control trials (RCTs).

Patients And Methods: Twenty-five studies met inclusion criteria for analysis. Of these, 13 tested a single-dose effect, nine multiple-dose effects, and three both single- and multiple-dose effects of 16 different NSAIDs in a total of 1,545 patients.

Guidelines for meta-analyses evaluating diagnostic tests.

Objectives: To introduce guidelines for the conduct, reporting, and critical appraisal of meta-analyses evaluating diagnostic tests and to apply these guidelines to recently published meta-analyses of diagnostic tests.

Data Sources: Based on current concepts of how to assess diagnostic tests and conduct meta-analyses. They are applied to all meta-analyses evaluating diagnostic tests published in English-language journals from January 1990 through December 1991, identified through MEDLINE searching and by experts in the field.

Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature.

Objective: To quantify the efficacy of BCG vaccine against tuberculosis (TB).

Data Sources: MEDLINE with index terms BCG vaccine, tuberculosis, and human. Experts from the Centers for Disease Control and Prevention and the World Health Organization, among others, provided lists of all known studies.

Improving health: measuring effects of medical care.

The impact of medical care on the quality and length of life of the population has been poorly documented. The rapid growth of evidence of efficacy of therapy for individual medical conditions now offers the opportunity to create an inventory of benefits. A method for creating such an inventory is described, as is its application to a selection of condition-treatment pairs, chosen for their high incidence of prevalence, their serious outcomes, and the demonstrated efficacy of their treatment.

Postoperative patient-controlled analgesia: meta-analyses of initial randomized control trials.

Study Objective: To compare outcomes during conventional analgesia (as-needed intramuscular dosing) and patient-controlled analgesia (PCA) in postoperative patients by analyzing data from published comparative trials.

Design: Meta-analyses of 15 randomized control trials.

Patients: Seven hundred eighty-seven adult patients (aged 16 to 65) undergoing various operative procedures.

Vitamin A supplementation and child mortality. A meta-analysis.

Objective: A two-part meta-analysis of studies examining the relationship of vitamin A supplementation and child mortality.

Data Sources: We identified studies by searching the MEDLARS database from 1966 through 1992 and by scanning Current Contents and bibliographies of pertinent articles.

Study Selection: All 12 vitamin A controlled trials with data on mortality identified in the search were used in the analysis.

Assessing the effectiveness of ambulatory cardiac monitoring for specific clinical indications. Introduction.

This introduction and the three essays that follow examine ambulatory cardiac monitoring for specific clinical indications. They also examine the ways in which evidence from the literature may be synthesized through the framework of decision analysis to guide its appropriate use and identify areas in which more research is needed. The essays discuss ambulatory cardiac monitoring for evaluation of syncope in the elderly; detection of silent ischemia after a myocardial infarction; and selection of antiarrhythmic drugs for malignant ventricular arrhythmias.

The prospect of data-based medicine in the light of ECPC.

A new effort in medical information has gathered and organized data from randomized clinical trials and other sources in obstetrics and made them available in several forms. This accomplishment implies the possibility of data-based medical practice that depends on systematic organization of medical findings. Possible limitations in data-based medical practice are treated and the benefits of such an approach are discussed.

Laminectomy and the treatment of lower-back pain in Massachusetts.

During 1984-85, laminectomy rates in Massachusetts demonstrated a 2.2-fold variation among districts. Thirty-five percent of laminectomies occurred in 7 of the 108 hospitals studied.

Survival from localized breast cancer. Variability across trials and registries.

Age-specific (< 50, 50-69 years) 10-year survival proportions in four European trials for node-negative, Stage I and II breast cancer patients differ significantly. These patients, identified as having the same stage as localized-breast cancer patients in the End Results Registry of the U.S.