Use of heparins in patients with cancer: Individual participant data metaanalysis of randomised trials study protocol

Holger J. Schünemann, Matthew Ventresca, Mark Crowther, Matthias Briel, Qi Zhou, David Garcia, Gary Lyman, Simon Noble, Fergus Macbeth, Gareth Griffiths, Marcello Di Nisio, Alfonso Iorio, Joseph Beyene, Lawrance Mbuagbaw, Ignacio Neumann, Nick Van Es, Melissa Brouwers, Jan Brozek, Gordon Guyatt, Mark LevineStephan Moll, Nancy Santesso, Michael Streiff, Tejan Baldeh, Ivan Florez, Ozlem Gurunlu Alma, Ziad Solh, Walter Ageno, Maura Marcucci, George Bozas, Gilbert Zulian, Anthony Maraveyas, Bernard Lebeau, Harry Buller, Jessica Evans, Robert Mcbane, Suzanne Bleker, Uwe Pelzer, Elie A. Akl

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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 metaanalysis 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 participantdata 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.

Original languageEnglish (US)
Article numbere010569
JournalBMJ open
Volume6
Issue number4
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Medicine(all)

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