Showing papers by "Alessandro Liberati published in 2008"

Going from evidence to recommendations

Abstract: The GRADE system classifies recommendations made in guidelines as either strong or weak. This article explores the meaning of these descriptions and their implications for patients, clinicians, and policy makers

Incorporating considerations of resources use into grading recommendations

Abstract: Guideline panellists have differing opinions on whether resource use should influence decisions on individual patients. As medical care costs rise, resource use considerations become more compelling, but panellists may find dealing with such considerations challenging

Clinical evidence continuous medical education: a randomised educational trial of an open access e-learning program for transferring evidence-based information – ICEKUBE (Italian Clinical Evidence Knowledge Utilization Behaviour Evaluation) – study protocol

Abstract: In an effort to ensure that all physicians have access to valid and reliable evidence on drug effectiveness, the Italian Drug Agency sponsored a free-access e-learning system, based on Clinical Evidence, called ECCE. Doctors have access to an electronic version and related clinical vignettes. Correct answers to the interactive vignettes provide Continuing Medical Education credits. The aims of this trial are to establish whether the e-learning program (ECCE) increases physicians' basic knowledge about common clinical scenarios, and whether ECCE is superior to the passive diffusion of information through the printed version of Clinical Evidence. All Italian doctors naive to ECCE will be randomised to three groups. Group one will have access to ECCE for Clinical Evidence chapters and vignettes lot A and will provide control data for Clinical Evidence chapters and vignettes lot B; group two vice versa; group three will receive the concise printed version of Clinical Evidence. There are in fact two designs: a before and after pragmatic trial utilising a two by two incomplete block design (group one versus group two) and a classical design (group one and two versus group three). The primary outcome will be the retention of Clinical Evidence contents assessed from the scores for clinical vignettes selected from ECCE at least six months after the intervention. To avoid test-retest effects, we will randomly select vignettes out of lot A and lot B, avoiding repetitions. In order to preserve the comparability of lots, we will select vignettes with similar, optimal psychometric characteristics. ISRCTN27453314

Developing Clinical Recommendations for Breast, Colorectal, and Lung Cancer Adjuvant Treatments Using the GRADE System: A Study From the Programma Ricerca e Innovazione Emilia Romagna Oncology Research Group

Abstract: Purpose In the area of anticancer drugs, the legitimate search for effective interventions can be jeopardized by the strong pressure for accelerated approval, which may hinder the full assessment of their benefit-risk profile. We aimed to produce drug-specific recommendations using an explicit approach that separates the judgments on quality of evidence from the judgment about strength of recommendations. Materials and Methods We used the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system to develop recommendations for the use of specific anticancer drugs/regimens; 12 clinical questions relevant to adjuvant treatment of breast (three), colorectal (four) and lung (five) cancer have been assessed by multidisciplinary panels supported by a group of methodologists. Results For nine of 12 questions, recommendations were produced (one strong and six weak in favor and one weak and one strong against the index treatment); for the remaining three questions no specific course of action could be recommended. The perceived benefits to risk balance of the treatment was the most important and statistically significant (P .01) predictor of panels’ recommendations and of their strength, whereas panelists’ personal (age, sex) and professional (specialty) characteristics were not statistically associated. Conclusion Because the GRADE system sets out an explicit process going from evaluation of the quality of evidence and benefit-risk profile to the judgment of the strength of recommendations, in this experience, it proved very useful to combine methodologic rigor with the interdisciplinary participation that is important in the definition of evidence based clinical policies. J Clin Oncol 26:1033-1039. © 2008 by American Society of Clinical Oncology

CoCanCPG. Coordination of cancer clinical practice in Europe.

Abstract: All European countries are facing common challenges for delivering appropriate, evidence-based care to patients with cancer. Despite tangible improvements in diagnosis and treatment, marked differences in cancer survival exist throughout Europe. The reliable translation of new research evidence into consistent patient-oriented strategies is a key endeavour to overcome inequalities in healthcare. Clinical-practice guidelines are important tools for improving quality of care by informing professionals and patients about the most appropriate clinical practice. Guideline programmes in different countries use similar strategies to achieve similar goals. This results in unnecessary duplication of effort and inefficient use of resources. While different initiatives at the international level have attempted to improve the quality of guidelines, less investment has been made to overcome existing fragmentation and duplication of effort in cancer guideline development and research. To provide added value to existing initiatives and foster equitable access to evidence-based cancer care in Europe, CoCanCPG will establish cooperation between cancer guideline programmes. CoCanCPG is an ERA-Net coordinated by the French National Cancer Institute with 17 partners from 11 countries. The CoCanCPG partners will achieve their goal through an ambitious, stepwise approach with a long-term perspective, involving: 1. implementing a common framework for sharing knowledge and skills; 2. developing shared activities for guideline development; 3. assembling a critical mass for pertinent research into guideline methods; 4. implementing an appropriate framework for cooperation. Successful development of joint activities involves learning how to adopt common quality standards and how to share responsibilities, while taking into account the cultural and organisational diversity of the participating organisations. Languages barriers and different organisational settings add a level of complexity to setting up transnational collaboration. Through its activities, CoCanCPG will make an important contribution towards better access to evidence-based cancer practices and thus contribute to reducing inequalities and improving care for patients with cancer across Europe.

Rimonabant for overweight and “metabolic syndrome”: the attempt to supersize disease and risk by pharmaceutical marketing

Abstract: A Cochrane systematic review explored the potential role of rimonabant for overweight and obesity [1]. On the basis of surrogate outcomes reported in the included RCTs, rimonabant has been a candidate (by its producer) to act as a pleiotropic agent for the entire cardiovascular risk spectrum. Is this compelling evidence to consider rimonabant the new panacea for the ‘‘metabolic syndrome’’ or are we facing another attempt of disease mongering by a new market frontier? Rimonabant has been shown to reduce food intake, appetite and body weight in overweight or obese people. Four randomized controlled trials (RIO-Europe [2], RIONorth America [3], RIO-diabetes [4], RIO-lipids [5]) evaluated rimonabant 20 mg versus rimonabant 5 mg versus placebo. All interventions were given over 1 year and included the addition of a hypocaloric diet. All trials were designed, conducted and reported with the contribution of Sanofi-Aventis drug company. The Cochrane review (‘‘Rimonabant for overweight and obesity’’) [1] includes evidence from these four trials.

When drug companies select what they want to publish patients are denied relevant therapeutic information

Abstract: The methodologist’s point of viewGraziella Filippini, Lorenzo Moja, Alessandro LiberatiCochrane ReviewType-1 interferons are recommended as the first-linetreatment of multiple sclerosis (MS) in North Americanand European guidelines [1–3]. The efficacy of interferonson delaying disability progression—the most importantgoal of treatment in this 30–40 year disease—has beenevaluated in one Cochrane Review including five ran-domized, placebo control trials of either interferon beta-1b (two trials), or interferon beta-1a (three trials)involving 1,130 patients with relapsing-remitting MS(RRMS) [4]. From the available data in three of thesetrials, the authors of the review calculated an absolute riskreduction (ARR) of 9% (95% CI: 3.14%) of RRMSpatients who progressed in 2 years. However, when allpatients randomised in the trials were re-analysed bysensitivity analysis (overall 20% of patients had beenexcluded after randomization or were lost to follow-upduring the intervention), statistical significance was lost,providing an ARR of -10% (95% CI -38.18%). At2 years’ follow-up data were not robust or dropoutscompromised interpretation: for instance, in one trialfollow-up data were available on less than 40% of ran-domised patients. The number of patients who hadrelapses during the first 2 years fell significantly in theper protocol analysis (ARR 14%; 95% CI 8.19%), but,again, results were inconclusive after sensitivity analyses.All extended trials’ observations beyond 2 years wereopen, hampering an evaluation of long-term effect of in-terferons in delaying progression of RRMS patients.All individual studies included in this review weresponsored by the pharmaceutical companies producinginterferon beta: the data presented by companies in medicaljournal publications were actually selective reporting ofpatients who adhered to the interferons. This approach isknown as a per protocol analysis (also known as efficacy orexplanatory analysis) which counts the outcomes of thepatients who adhered to the research protocol [5]. Notsurprisingly these patients tended to have a better prognosisas opposed to the patients that had not adhered. Excludingdropouts from the analysis influenced the nature of the finalresults (both in terms of direction and/or magnitude). The

Selecting references that match constructs: the difficult job of citing the parachute hyperbole.

Abstract: The large scale availability of clotting factor concentrates and the organization of comprehensive care centres prompted a progressive increase in the life expectancy and quality of life of western world haemophilia patients [1, 2]. The best treatment regimen for haemophilia, across the world being considered, is regular prophylactic replacement with clotting factor concentrates. Strong observational evidence has been available since long time in support of this widely established pattern of practice; 26 unique observational studies of varying quality for a total of 1,612 patients on prophylaxis compared to 1,191 patients treated ondemand were reported through 2005 [3]. Notwithstanding this evidence and in front of several open questions about optimization of prophylactic regimen (i.e., onset, frequency, intensity, duration, patient selection), the directors of the Canadian Association of Haemophilia Centres prompted and sponsored a Cochrane Review on the topic. The systematic review found very little randomized controlled trial (RCT)-based evidence in this field; there were only four trials with a total of 37 patients [3]. All trials enrolled adult patients already affected by various degree of arthropathy, so that virtually no direct RCT-based information was available about primary prophylaxis in young children devoid of any joint damage [4]. The authors concluded that ‘‘There is insufficient evidence from randomised controlled trials to determine whether prophylactic clotting factor concentrates decrease bleeding and bleeding-related complications in hemophilia A or B, compared to placebo, ondemand treatment, or prophylaxis based on pharmacokinetic data from individuals. Well-designed RCTs are needed to assess the effectiveness of prophylactic clotting factor concentrates. Two clinical trials are ongoing.’’ The aforementioned Cochrane Review prompted a sustained debate about the need and ethicality of RCTs in the haemophilia field. A popular BMJ paper by Smith and Pell about the lack of evidence that parachutes are worth wearing if jumping from airplanes [5] was cited in support by those claiming against the need of RCTs [6]. The clever and humorous BMJ paper is widely cited, but it was miscited in the specific case of the haemophilia review as in many others. This commentary will try to put ‘‘the parachute hyperbole’’ in the right perspective, offering a brief discussion about how to go from particular instance (i.e., RCTs to experimentally test parachute) to the high order A. Iorio Stroke Unit and Division of Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy