Alessandro Liberati

Bio: Alessandro Liberati is an academic researcher from University of Modena and Reggio Emilia. The author has contributed to research in topics: Breast cancer & Systematic review. The author has an hindex of 46, co-authored 144 publications receiving 167184 citations. Previous affiliations of Alessandro Liberati include Mario Negri Institute for Pharmacological Research & Cochrane Collaboration.

Renaissance of ares publica clinical research: Global access to trial registers

Abstract: The pivotal importance of registering clinical trials is increasingly accepted, and several governmental and non-governmental bodies, including the Italian Ministry of Health, have developed guidelines or set up registries in recent years and months1. Three initiatives at the international level seem to us to foster the global awareness of the ethical and scientific obligation to register clinical trials. First, the International Committee of Medical Journal Editors (ICMJE) initiative2. Several decades since the idea of registering clinical trials was first proposed, the ICMJE took a significant step to urge academics and researchers to use the registers: after July 1, 2005, trials that are not registered will not be considered for publication in the medical journals that adhere to the ICMJE initiative. Which studies are eligible then? All trials in which volunteers are prospectively assigned to a medical intervention or a control, and in which a causal-relationship between the intervention and an outcome is the focus2. Medical interventions include drugs as well as surgical procedures, behavioural treatments and quality improvement processes. Only trials looking at pharmacokinetics and early toxicity are clearly excluded. To maintain an accessible and informative process, the ICMJE is supporting freely accessible and not for profit registers, and the 20 item World Health Organisation (WHO) minimum data set that requires key clinical and methodological fields3. The WHO minimal data set is part of the second landmark initiative to build up the International Clinical Trial Registry Platform4. This WHO entity coordinates an international network of primary registers to harmonise registration across the world. The national and international registers ensure the collection of all required items, data entry validation and other aspects of quality assurance. Several registers expanded their list of items in response to this initiative. We particularly recommend registering trials in two international registers: the US National Library of Medicine’s ClinicalTrials.gov5 and the UK’s Current Controlled Trials International Standard Randomised Controlled Trials Number Register (ISRCTN)6. Both are widely known, and ensure a process to update data and reduce the possibility of duplicate registration. The third initiative, known as the Ottawa Statement, is a consensus document from an international group of researchers with a close connection to and support by The Cochrane Collaboration7. The aim of this group of researchers is to provide a set of guiding principles for the development of trial registers. The first document lists principles for development, while the second document makes the principles operational8. For example, the first principle states that every trial should have a unique ID assigned by a single international source. The proposed mechanism to make this operational is that WHO assigns a Universal Reference Trial Number for a global unique ID. The Italian translation of the Ottawa Statement, Part One (Principles for international registration of protocol information and results from human trials of health-related interventions) will be published in the supplement “Medicina Italia” of the first 2007 issue of Internal and Emergency Medicine as well in the Ottawa Statement website (http:// ottawagroup.ohri.ca). What’s the situation in Italy? Italy has been one of the first countries to legislate a universal compulsory trials’ registration. Through Local Ethic Committees (LECs) all trials are registered at the National Monitoring Centre for Clinical Trials (OsSC)9. Unfortunately not all the information is in the public domain; only funding bodies and the LECs have unrestricted access, while the public has access to only very selected information. This status quo does not comply with the principles and the policies of the above three initiatives. We urge the Ministry of Health to seriously consider revisiting the limitations in the amount of information that is available to the public to foster full transparency. In the meantime Italian researchers should duplicate their efforts, registering their trials within the OsSC and in an international open access register. We are aware that in the past two years many important goals have been achieved toward a global registration of and access to clinical trials. We are even more conscious that there is much room for improvement. Trial registers will only be useful if they increase the accessibility and transparency of evidence. The real test for trial registers is Cochrane’s corner

Selective decontamination of the digestive tract.

Abstract: EDITOR, - M J M Bonten and colleagues agree with us that meta-analysis helps to clarify the methodological quality and clinical consistency of published research.1 They also acknowledge the merits of our recent review of trials of selective decontamination of the digestive tract in making clear important differences in study design, population, and methods that may explain why results of different studies differ.2 They criticise us, however, for using the “number to be treated” as a measure of the effect of …

Breast Cancer: Minimalists, Maximalists, Other Neoplasms

Abstract: To the Editor.— Drs Schapira and Urban 1 and Dr Wertheimer 2 discuss the worth of a minimal surveillance policy in patients with early-stage breast cancer. In both articles, the argument in favor or against minimalist follow-up is based on each authors opinions and beliefs rather than on scientific evidence; in fact, no experimental data (ie, results from randomized clinical trials) are yet available. In 1985 in Italy, the controversy over intensive vs minimal follow-up was rampant. The impossibility of reaching a consensus led to setting up a randomized clinical trial. Two cooperative groups designed a trial independently but with the explicit intent of prospectively pooling their results, comparing an intensive vs a minimalist approach (Table). Overall, 43 Italian hospitals joined the two projects. 3-5 From 1985 to 1987, the two trials accrued 1250 and 1450 patients, respectively, and the median follow-up time is now 5 and 3.5 years. Both

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

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 …