title: Use of heparins in patients with cancer
title: individual participant data meta-analysis of randomised trials study protocol
titleType: Subtitle
Creators: name: Schunemann, Holger J.
name: Ventresca, Matthew
name: Crowther, Mark
name: Briel, Matthias
name: Zhou, Qi
name: Garcia, David
name: Lyman, Gary
name: Noble, Simon
name: Macbeth, Fergus
name: Griffiths, Gareth
name: DiNisio, Marcello
name: Iorio, Alfonso
name: Beyene, Joseph
name: Mbuagbaw, Lawrance
name: Neumann, Ignacio
name: Van Es, Nick
name: Brouwers, Melissa
name: Brozek, Jan
name: Guyatt, Gordon
name: Levine, Mark
name: Moll, Stephan
name: Santesso, Nancy
name: Streiff, Michael
name: Baldeh, Tejan
name: Florez, Ivan
name: Alma, Ozlem Gurunlu
name: Solh, Ziad
name: Ageno, Walter
name: Marcucci, Maura
name: Bozas, George
name: Zulian, Gilbert
name: Maraveyas, Anthony
name: Lebeau, Bernard
name: Buller, Harry
name: Evans, Jessica
name: McBane, Robert
name: Bleker, Suzanne
name: Pelzer, Uwe
name: Akl, Elie A.
Publisher: name: Charité - Universitätsmedizin Berlin
Year: 2016
Subjects: subject: 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit

description: Introduction Parenteral anticoagulants may improve outcomes in patients with cancer by reducing risk of venous thromboembolic disease and through a direct antitumour effect. Study-level systematic reviews indicate a reduction in venous thromboembolism and provide moderate confidence that a small survival benefit exists. It remains unclear if any patient subgroups experience potential benefits. Methods and analysis First, we will perform a comprehensive systematic search of MEDLINE, EMBASE and The Cochrane Library, hand search scientific conference abstracts and check clinical trials registries for randomised control trials of participants with solid cancers who are administered parenteral anticoagulants. We anticipate identifying at least 15 trials, exceeding 9000 participants. Second, we will perform an individual participant data meta-analysis to explore the magnitude of survival benefit and address whether subgroups of patients are more likely to benefit from parenteral anticoagulants. All analyses will follow the intention-to- treat principle. For our primary outcome, mortality, we will use multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We will adjust analysis for important prognostic characteristics. To investigate whether intervention effects vary by predefined subgroups of patients, we will test interaction terms in the statistical model. Furthermore, we will develop a risk-prediction model for venous thromboembolism, with a focus on control patients of randomised trials. Ethics and dissemination Aside from maintaining participant anonymity, there are no major ethical concerns. This will be the first individual participant data meta-analysis addressing heparin use among patients with cancer and will directly influence recommendations in clinical practice guidelines. Major cancer guideline development organisations will use eventual results to inform their guideline recommendations. Several knowledge users will disseminate results through presentations at clinical rounds as well as national and international conferences. We will prepare an evidence brief and facilitate dialogue to engage policymakers and stakeholders in acting on findings. Trial registration number PROSPERO CRD42013003526