Boken presenterer en helhetlig strategi for hvordan myndigheter, helsepersonell, industri og forbrukere kan redusere medisinske feil.

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To Err Is Human Building a Safer Health System

The metafor package provides functions for conducting meta-analyses in R. The package includes functions for fitting the meta-analytic fixed- and random-effects models and allows for the inclusion of moderators variables (study-level covariates) in these models. Meta-regression analyses with continuous and categorical moderators can be conducted in this way. Functions for the Mantel-Haenszel and Peto's one-step method for meta-analyses of 2 x 2 table data are also available. Finally, the package provides various plot functions (for example, for forest, funnel, and radial plots) and functions for assessing the model fit, for obtaining case diagnostics, and for tests of publication bias.

Conducting Meta-Analyses in R with the metafor Package

Background In the hierarchy of research designs, the results of randomized, controlled trials are considered to be evidence of the highest grade, whereas observational studies are viewed as having less validity because they reportedly overestimate treatment effects. We used published meta-analyses to identify randomized clinical trials and observational studies that examined the same clinical topics. We then compared the results of the original reports according to the type of research design. Methods A search of the Medline data base for articles published in five major medical journals from 1991 to 1995 identified meta-analyses of randomized, controlled trials and meta-analyses of either cohort or case–control studies that assessed the same intervention. For each of five topics, summary estimates and 95 percent confidence intervals were calculated on the basis of data from the individual randomized, controlled trials and the individual observational studies. Results For the five clinical topics and 99 r...

Randomized, controlled trials, observational studies, and the hierarchy of research designs.

The Analysis of Time Series: An Introduction, 4th edn. By C. Chatfield. ISBN 0 412 31820 2. Chapman and Hall, London, 1989. 242 pp. £13.50.

The Analysis of Time Series: An Introduction

This tutorial on advanced statistical methods for meta-analysis can be seen as a sequel to the recent Tutorial in Biostatistics on meta-analysis by Normand, which focused on elementary methods. Within the framework of the general linear mixed model using approximate likelihood, we discuss methods to analyse univariate as well as bivariate treatment effects in meta-analyses as well as meta-regression methods. Several extensions of the models are discussed, like exact likelihood, non-normal mixtures and multiple endpoints. We end with a discussion about the use of Bayesian methods in meta-analysis. All methods are illustrated by a meta-analysis concerning the efficacy of BCG vaccine against tuberculosis. All analyses that use approximate likelihood can be carried out by standard software. We demonstrate how the models can be fitted using SAS Proc Mixed.

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Advanced methods in meta-analysis: multivariate approach and meta-regression.

Objective. —To quantify the efficacy of BCG vaccine against tuberculosis (TB). Data Sources. —MEDLINE with index termsBCG vaccine, tuberculosis, andhuman. Experts from the Centers for Disease Control and Prevention and the World Health Organization, among others, provided lists of all known studies. Study Selection. —A total of 1264 articles or abstracts were reviewed for details on BCG vaccination, concurrent vaccinated and unvaccinated groups, and TB outcome; 70 articles were reviewed in depth for method of vaccine allocation used to create comparable groups, equal surveillance and follow-up for recipient and concurrent control groups, and outcome measures of TB cases and/or deaths. Fourteen prospective trials and 12 case-control studies were included in the analysis. Data Extraction. —We recorded study design, age range of study population, number of patients enrolled, efficacy of vaccine, and items to assess the potential for bias in study design and diagnosis. At least two readers independently extracted data and evaluated validity. Data Synthesis. —The relative risk (RR) or odds ratio (OR) of TB provided the measure of vaccine efficacy that we analyzed. The protective effect was then computed by 1 —RR or 1 —OR. A random-effects model estimated a weighted average RR or OR from those provided by the trials or case-control studies. In the trials, the RR of TB was 0.49 (95% confidence interval [Cl], 0.34 to 0.70) for vaccine recipients compared with nonrecipients (protective effect of 51%). In the case-control studies, the OR for TB was 0.50 (95% CI, 0.39 to 0.64), or a 50% protective effect. Seven trials reporting tuberculous deaths showed a protective effect from BCG vaccine of 71% (RR, 0.29; 95% Cl, 0.16 to 0.53), and five studies reporting on meningitis showed a protective effect from BCG vaccine of 64% (OR, 0.36; 95% Cl, 0.18 to 0.70). Geographic latitude of the study site and study validity score explained 66% of the heterogeneity among trials in a random-effects regression model. Conclusion. —On average, BCG vaccine significantly reduces the risk of TB by 50%. Protection is observed across many populations, study designs, and forms of TB. Age at vaccination did not enhance predictiveness of BCG efficacy. Protection against tuberculous death, meningitis, and disseminated disease is higher than for total TB cases, although this result may reflect reduced error in disease classification rather than greater BCG efficacy. (JAMA. 1994;271:698-702)

https://jamanetwork.com/journals/jama/articlepdf/366365/jama_271_9_038.pdf

Efficacy of BCG Vaccine in the Prevention of Tuberculosis: Meta-analysis of the Published Literature

Objective. To quantify the efficacy of vaccination of infants with bacillus Calmette-Guerin (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. Seventy articles were reviewed in depth for method of vaccine allocation used to create comparable groups, age at vaccination of study participants, comparability of surveillance and follow-up of recipient and concurrent control groups in trials, an appropriately defined control group in case-control studies, and outcome measures (tuberculosis cases and/or deaths). Five prospective trials and eleven case-control studies of vaccination during infancy were included in the present analyses. Data extraction. We recorded study design, age range of study population, number of patients enrolled, efficacy of vaccine, location of the study, and a series of items to assess the potential for bias in study design, follow-up, and diagnosis. We extracted or computed vaccine efficacy by years since vaccination wherever possible. At least two readers independently extracted data and evaluated data validity. Data synthesis. The relative risk (RR) or odds ratio (OR) for tuberculosis in vaccinated versus unvaccinated infants was the measure of vaccine efficacy analyzed. A random-effects method estimated a weighted average RR or OR from data extracted from the trials and case-control studies. The protective effect was then computed by 1 - RR or 1 - OR. Overall, the protective effect of vaccination against cases of tuberculosis was 0.74 (95% confidence interval [95% CI], 0.62 to 0.83) when estimated from four randomized controlled trials, and 0.52 (95% CI, 0.38 to 0.64) when estimated from nine case-control studies. Five trials reporting deaths from tuberculosis showed a BCG protective effect of 0.65 (95% CI, 0.12 to 0.86), five studies reporting on meningitis showed a protective effect of 0.64 (95% CI, 0.30 to 0.82), and three studies of disseminated tuberculosis showed a protective effect of 0.78 (95% CI, 0.58 to 0.88). Three case-control studies included separate results for laboratory-confirmed cases of tuberculosis. These studies documented a protective effect of 0.83 (95% CI, 0.58 to 0.93). In a random-effects regression model of the nine case-control studies, study validity score explained 15% of the heterogeneity among study-estimated protective effects, suggesting that better studies reported greater efficacy. Three trials and six case-control studies provided some age-specific information that allowed us to examine the duration of BCG efficacy. Most of this evidence suggested that BCG efficacy may persist through 10 years after infant vaccination. Conclusion. BCG vaccination of newborns and infants significantly reduces the risk of tuberculosis—by over 50%, on average. Protection has been observed across many populations, study designs, and forms of tuberculosis. Rates of protection against cases that are confirmed by laboratory tests, reflecting reduced error in disease classification and consequently more accurate estimates of BCG efficacy, are highest at 83%.

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

Madhu Pai and colleagues introduce the BCG World Atlas, an open access, user friendly Web site for TB clinicians to discern global BCG vaccination policies and practices and improve the care of their patients.

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The BCG World Atlas: A Database of Global BCG Vaccination Policies and Practices

Background Timely diagnosis of influenza can help clinical management. Purpose To examine the accuracy of rapid influenza diagnostic tests (RIDTs) in adults and children with influenza-like illness and evaluate factors associated with higher accuracy. Data sources PubMed and EMBASE through December 2011; BIOSIS and Web of Science through March 2010; and citations of articles, guidelines, reviews, and manufacturers. Study selection Studies that compared RIDTs with a reference standard of either reverse transcriptase polymerase chain reaction (first choice) or viral culture. Data extraction Reviewers abstracted study data by using a standardized form and assessed quality by using Quality Assessment of Diagnostic Accuracy Studies criteria. Data synthesis 159 studies evaluated 26 RIDTs, and 35% were conducted during the H1N1 pandemic. Failure to report whether results were assessed in a blinded manner and the basis for patient recruitment were important quality concerns. The pooled sensitivity and specificity were 62.3% (95% CI, 57.9% to 66.6%) and 98.2% (CI, 97.5% to 98.7%), respectively. The positive and negative likelihood ratios were 34.5 (CI, 23.8 to 45.2) and 0.38 (CI, 0.34 to 0.43), respectively. Sensitivity estimates were highly heterogeneous, which was partially explained by lower sensitivity in adults (53.9% [CI, 47.9% to 59.8%]) than in children (66.6% [CI, 61.6% to 71.7%]) and a higher sensitivity for influenza A (64.6% [CI, 59.0% to 70.1%) than for influenza B (52.2% [CI, 45.0% to 59.3%). Limitation Incomplete reporting limited the ability to assess the effect of important factors, such as specimen type and duration of influenza symptoms, on diagnostic accuracy. Conclusion Influenza can be ruled in but not ruled out through the use of RIDTs. Sensitivity varies across populations, but it is higher in children than in adults and for influenza A than for influenza B. Primary funding source Canadian Institutes of Health Research.

Accuracy of rapid influenza diagnostic tests: a meta-analysis.

Spontaneous reporting systems like MEDWATCH can be effective in revealing unusual or rare adverse events that occur with the use of medications, and such reports may often be sufficient to assign causality. However, spontaneous reports do not reliably detect adverse drug reactions (ADRs) that occur widely separated in time from the original use of the drug or that represent an increased risk of an adverse event that occurs commonly in populations not exposed to the drug. In these situations, spontaneous reports alone do not provide sufficient evidence to conclude that the adverse event was an ADR. Identification of ADRs associated with long-term administration of drugs for chronic diseases also remains problematic. Methods to evaluate ADRs using data from clinical trials, medical records, and computerized databases of medication users and nonusers must be developed to complement spontaneous reporting systems. Without these methods, potentially important ADRs will remain undetected, and spurious associations between adverse outcomes and medications or devices will remain unchallenged.

https://jamanetwork.com/journals/jama/articlepdf/188955/JSC80012.pdf

Timothy F. Brewer

Papers

Efficacy of BCG Vaccine in the Prevention of Tuberculosis: Meta-analysis of the Published Literature

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

The BCG World Atlas: A Database of Global BCG Vaccination Policies and Practices

Accuracy of rapid influenza diagnostic tests: a meta-analysis.

Postmarketing surveillance and adverse drug reactions: current perspectives and future needs.