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Proposal 657

Title of the Proposed Research

Use of Heparins in patients with Cancer: Individual patient-data meta-analysis of randomized trials

Lead Researcher

Holger Schunemann, MD, MSc, PhD

Affiliation

McMaster University

Funding Source

Canadian Institutes of Health Research
Institution paid: McMaster University
Title: Use of Heparins in Cancer: Individual patient data meta-analysis
Primary Inst.: Cancer Research
Competition Outcome: Knowledge Synthesis Grant
Decision on your application: Approved
Predictors of Prostate Cancer Progression Among Men on Active Surveillance

Potential Conflicts of Interest

None

Data Sharing Agreement Date

24 Jul 2014

Lay Summary

Background: Solid cancers are a common health problem worldwide and cancer related complications such as deep venous thrombosis (DVT) and pulmonary embolism (PE) are a cause of mortality and morbidity. Parenteral anticoagulants, including heparin, low molecular weight heparins (LMWH), fondaparinux, and danaparoid, may improve outcomes in cancer patients not only by reducing the risk of venous thromboembolic disease but also through a direct antitumor effect. Study level systematic reviews on this topic indicate a reduction in venous thromboembolism and provide moderate confidence that a small survival benefit exists. In addition to the remaining uncertainty about the survival benefit, it remains uncertain which, if any, patient subgroups experience that potential benefit.

Methods: We will conduct a systematic review with an individual participant data (IPD) meta-analysis (MA). First, we will perform a systematic and comprehensive electronic search using various databases (Medline, EMBASE, Cochrane Library), hand search the abstracts of relevant scientific conferences and check registries of clinical trials. We will then perform an IPDMA to explore the magnitude of the suggested survival benefit and address whether or not specific subgroups and characteristics of cancer 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 the analysis for important prognostic patient baseline characteristics such as age and comorbidities. To investigate whether or not intervention effects vary by pre-defined subgroups of patients, we will additionally test appropriate interaction terms in the statistical model. Furthermore, we will develop a risk prediction model for venous thromboembolism with a focus on patients in the control groups of the randomized trials.

Results and Discussion: We anticipate data from more than 9000 participants will contribute to this IPDMA. This study will provide important evidence for the individualized or targeted treatment of patients with cancer and will directly influence recommendations in clinical practice guidelines about the use of heparins in patients with solid cancers. Furthermore, we will work with the McMaster Health Forum to prepare an evidence brief and convene a stakeholder dialogue to engage policymakers and stakeholders in acting on the findings.

Study Data Provided

Study FRX106365: A randomized, controlled trial to evaluate the effects of nadroparin on survival and disease progression in patients with advanced malignancies of the lung, pancreas, or prostate

Statistical Analysis Plan

This will be added after the research is published.

Publication Citation