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.

Adequacy of authors’ replies to criticism raised in electronic letters to the editor: cohort study

Abstract: Objective To investigate whether substantive criticism in electronic letters to the editor, defined as a problem that could invalidate the research or reduce its reliability, is adequately addressed by the authors. Design Cohort study. SettingBMJ between October 2005 and September 2007. Inclusion criteria Research papers generating substantive criticism in the rapid responses section on bmj.com. Main outcome measures Severity of criticism (minor, moderate, or major) as judged by two editors and extent to which the criticism was addressed by authors (fully, partly, or not) as judged by two editors and the critics. Results A substantive criticism was raised against 105 of 350 (30%, 95% confidence interval 25% to 35%) included research papers, and of these the authors had responded to 47 (45%, 35% to 54%). The severity of the criticism was the same in those papers as in the 58 without author replies (mean score 2.2 in both groups, P=0.72). For the 47 criticisms with replies, there was no relation between the severity of the criticism and the adequacy of the reply, neither as judged by the editors (P=0.88 and P=0.95, respectively) nor by the critics (P=0.83; response rate 85%). However, the critics were much more critical of the replies than the editors (average score 2.3 v 1.4, P Conclusions Authors are reluctant to respond to criticisms of their work, although they are not less likely to respond when criticisms are severe. Editors should ensure that authors take relevant criticism seriously and respond adequately to it.

Strategies for obtaining unpublished drug trial data: a qualitative interview study

Abstract: Background: Authors of systematic reviews have difficulty obtaining unpublished data for their reviews. This project aimed to provide an in-depth description of the experiences of authors in searching for and gaining access to unpublished data for their systematic reviews, and to give guidance on best practices for identifying, obtaining and using unpublished data. Methods: This is a qualitative study analyzing in-depth interviews with authors of systematic reviews who have published Cochrane reviews or published systematic reviews outside of The Cochrane Library. We included participants who 1) were the first or senior author of a published systematic review of a drug intervention, 2) had expertise in conducting systematic reviews, searching for data, and assessing methodological biases, and 3) were able to participate in an interview in English. We used non-random sampling techniques to identify potential participants. Eighteen Cochrane authors were contacted and 16 agreed to be interviewed (89% response rate). Twenty-four non-Cochrane authors were contacted and 16 were interviewed (67% response rate). Results: Respondents had different understandings of what was meant by unpublished data, including specific outcomes and methodological details. Contacting study authors was the most common method used to obtain unpublished data and the value of regulatory agencies as a data source was underappreciated. Using the data obtained was time consuming and labor intensive. Respondents described the collaboration with other colleagues and/or students required to organize, manage and use the data in their reviews, generally developing and using templates, spreadsheets and computer programs for data extraction and analysis. Respondents had a shared belief that data should be accessible but some had concerns about sharing their own data. Respondents believed that obtaining unpublished data for reviews has important public health implications. There was widespread support for government intervention to ensure open access to trial data. Conclusions: Respondents uniformly agreed that the benefit of identifying unpublished data was worth the effort and was necessary to identify the true harms and benefits of drugs. Recent actions by government, such as increased availability of trial data from the European Medicines Agency, may make it easier to acquire critical drug trial data.

Big pharma often commits corporate crime, and this must be stopped

Abstract: When a drug company commits a serious crime, the standard response from the industry is that there are bad apples in any enterprise. Sure, but the interesting question is whether drug companies routinely break the law. I googled the names of the 10 largest drug companies in combination with the term “fraud” and looked for offences on the first page for each company. The most common recent crimes were illegal marketing by recommending drugs for non-approved (off label) uses, misrepresentation of research results, hiding data on harms, and Medicaid and Medicare fraud.1 All cases were related to the United States and involved huge settlements or fines, exceeding $1bn (£620.6m; €769m) each for four companies. It was easy to find additional crimes committed by these same companies and committed outside the US.1 As the crimes were widespread and repetitive, they are probably committed deliberately—because crime pays. Pfizer, for example, agreed in 2009 to pay $430m to resolve charges related to illegal marketing of gabapentin (Neurontin), but as sales were $2.7bn in 2003 alone, and as about 90% was for off label use, such …

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