Peter C Gøtzsche

Bio: Peter C Gøtzsche is an academic researcher from Cochrane Collaboration. The author has contributed to research in topics: Systematic review & Placebo. The author has an hindex of 90, co-authored 413 publications receiving 147009 citations. Previous affiliations of Peter C Gøtzsche include University of Copenhagen & Copenhagen University Hospital.

Do protocols for new randomised trials take previous similar trials into account? Cohort study of contemporary trial protocols.

Abstract: Objective To investigate to what extent evidence from previous similar trials or systematic reviews was considered before conducting new trials. Design Cohort study of contemporary protocols for trials with ethical approval. Methods All protocols for randomised trials approved by the five ethical committees in Denmark between January 2012 and March 2013 were screened for eligibility. Included protocols were read in full to determine whether a systematic search had been conducted and references were checked to evaluate whether trial rationale and design could be challenged for not adequately considering previous evidence. To investigate whether protocols cited relevant trials, we used simple search strategies that could easily be conducted by researchers without experience with literature searches. Results Sixty-seven protocols were included. Only two (3%) of the protocols explicitly stated to have conducted a literature search and only one (1%) provided information that allowed the search to be replicated. Eleven (16%) of the protocols described trials where we found the information insufficient to judge if the trial was ethically justified, either due to a comparator that was not supported by the presented evidence (six protocols), because they did not present a rationale for conducting the trial (two protocols), or for both reasons (three protocols). For eight (12%) of the protocols, our search identified trials that could have been relevant to cite as justification. Conclusions While most protocols seem to adequately consider existing evidence, a substantial minority of trials might lack a sufficient evidence base. Very few trials seemed to have been based on a literature search which makes it impossible to know whether all relevant previous trials had been considered. Rules for ethical approval should include requirements for systematic literature searches to ensure that research participants are not exposed to sub-optimal treatments or unnecessary harms as well as to reduce research waste.

Decreased Short-Term Production of Tumor Necrosis Factor-α and Interleukin-1β in Human Immunodeficiency Virus-Seropositive Subjects

Abstract: Tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b) were measured by ELISA in 4.5h, lipopolysaccharide-stimulated whole blood cultures of 347 human immunodeficiency virus type 1 ‐ infected patients and 107 healthy seronegative controls. The production of TNF-a was decreased in both AIDS and non-AIDS patients, whereas the production of IL-1b was decreased in AIDS patients only. The production of TNF-a and IL-1b was positively affected by the concentrations of CD14 / monocytes and CD8 / lymphocytes; however, in patients, the concentration of CD4 / lymphocytes and the presence of AIDS had a negative effect on cytokine production as determined by multiple linear regression analysis. It is concluded that low whole blood cytokine production is mainly caused by low numbers of cells, but a functional defect may also exist. The inflammatory cytokines tumor necrosis factor-a (TNFHIV-1‐infected patients (32%) had AIDS. AIDS-defining sympa) and interleukin-1b (IL-1b) stimulate the replication of hu- toms were Pneumocystis carinii pneumonia in 55 patients; candidiman immunodeficiency virus (HIV) by activating nuclear fac- asis of the esophagus, trachea, bronchi, or lungs in 26; Kaposi’s tor-kb [1], and infusion of TNF-a or IL-1b induces a cachectic sarcoma in 26; toxoplasmosis of the brain in 19; cytomegalovirus state [2]. The possible detrimental effects of TNF-a and IL- infection in 11; HIV wasting syndrome in 8; disseminated atypical 1b have led to the hypothesis that these cytokines are important mycobacteriosis in 6; and other AIDS-defining events in 23. Of in the pathogenesis of HIV infection [3, 4]. However, conflict- the 347 study patients, 176 received zidovudine and 21 received ing results have been obtained regarding the production of didanosine before enrollment. TNF-a [3, 5], and the causative role of the two cytokines in Cytokine detection. Whole blood supernatants were generated HIV pathogenesis remains to be proved. The purpose of this by incubating 2 mL of anticoagulated blood (10 mL of heparin 5000 IU/mL; SAD, Copenhagen) with 20 mg of lipopolysaccharide

STROBE Statement: linee guida per descrivere gli studi osservazionali

Abstract: Much of biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study’s generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, casecontrol, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed “Explanation and Elaboration” document is published separately and is freely available on the web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

Abstract: David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.

Abstract: Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field,1,2 and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research,3 and some health care journals are moving in this direction.4 As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews. Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in 4 leading medical journals in 1985 and 1986 and found that none met all 8 explicit scientific criteria, such as a quality assessment of included studies.5 In 1987, Sacks and colleagues6 evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in 6 domains. Reporting was generally poor; between 1 and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement.7 In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials.8 In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1). Box 1 Conceptual issues in the evolution from QUOROM to PRISMA

Bias in meta-analysis detected by a simple, graphical test

Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure