individual participant data meta-analysis of randomised trials study protocol

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 CRD4201300352

An individual participant data meta-analysis of 13 randomized trials to evaluate the impact of prophylactic use of heparin in oncological patients

Background: Parenteral anticoagulants may improve outcomes in patients with cancer by reducing the risk of venous thromboembolism (VTE) and through a direct anti-tumour effect. Study-level meta-analysis indicates a reduction in VTE and provide moderate certainty that a small survival benefit exists; it is unclear if patients with specific cancers benefit more or less. Utilizing data from randomized controlled trials (RCT), this individual participant data meta-analysis examines the impact of heparin on survival, VTE and major bleeding in oncological patients randomized to low-molecular weight heparin (LMWH) or no LMWH

The Khorana Score for the prediction of venous thromboembolism in patients with solid cancer: An individual patient data meta-analysis

Background: Guidelines suggest the use of the Khorana score to select patients with solid cancer receiving chemotherapy for thromboprophylaxis to prevent venous thromboembolism (VTE), but its performance in different types of cancers remains uncertain

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

39sinoneIntroduction: 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.noneSchünemann, Holger J; Ventresca, Matthew; Crowther, Mark; Briel, Matthias; Zhou, Qi; Garcia, David; Lyman, Gary; Noble, Simon; Macbeth, Fergus; Griffiths, Gareth; Di Nisio, Marcello; Iorio, Alfonso; Beyene, Joseph; Mbuagbaw, Lawrance; Neumann, Ignacio; Es, Nick Van; Brouwers, Melissa; Brozek, Jan; Guyatt, Gordon; Levine, Mark; Moll, Stephan; Santesso, Nancy; Streiff, Michael; Baldeh, Tejan; Florez, Ivan; Alma, Ozlem Gurunlu; Solh, Ziad; Ageno, Walter; Marcucci, Maura; Bozas, George; Zulian, Gilbert; Maraveyas, Anthony; Lebeau, Bernard; Buller, Harry; Evans, Jessica; Mcbane, Robert; Bleker, Suzanne; Pelzer, Uwe; Akl, Elie ASchünemann, Holger J; Ventresca, Matthew; Crowther, Mark; Briel, Matthias; Zhou, Qi; Garcia, David; Lyman, Gary; Noble, Simon; Macbeth, Fergus; Griffiths, Gareth; Di Nisio, Marcello; Iorio, Alfonso; Beyene, Joseph; Mbuagbaw, Lawrance; Neumann, Ignacio; Es, Nick Van; Brouwers, Melissa; Brozek, Jan; Guyatt, Gordon; Levine, Mark; Moll, Stephan; Santesso, Nancy; Streiff, Michael; Baldeh, Tejan; Florez, Ivan; Alma, Ozlem Gurunlu; Solh, Ziad; Ageno, Walter; Marcucci, Maura; Bozas, George; Zulian, Gilbert; Maraveyas, Anthony; Lebeau, Bernard; Buller, Harry; Evans, Jessica; Mcbane, Robert; Bleker, Suzanne; Pelzer, Uwe; Akl, Elie A