Excerpt

This report evaluates the level of evidence currently available to support the effectiveness and safety of using recombinant activated coagulation factor VII (rFVIIa) for clinical indications not approved by the U. S. Food and Drug Administration (FDA). rFVIIa is approved for a variety of uses in hemophilia patients who have developed antibody inhibitors that compromise the use of standard factor replacement. Use of this costly biologic product has expanded beyond these hemophilia-related indications to encompass a range of off-label uses, most of which are in-hospital uses. These uses differ substantially from the drug’s FDA approved label. The purpose of this report is two-fold: (1) To document the full range of clinical indications for which rFVIIa is being used and the types of studies available to evaluate these uses and (2) To provide a comparative effectiveness review of rFVIIa vs. usual care for several in-hospital clinical indications: intracranial hemorrhage, massive bleeding secondary to trauma, and the selected surgical procedures of cardiac surgery, liver transplantation, and prostatectomy.

Contents

• Preface
• Acknowledgments
• Executive Summary
• Introduction
  • Organization of Report
  • Background on Off-Label Medication Use
  • Introduction to rFVIIa
  • Past Systematic Reviews as Context for the Report
  • Clinical Considerations of Heterogeneity
  • Areas of Anticipated Challenge
  • Key Questions that Guide the Current Report
• Methods
  • Topic Development
  • Framework for Analyzing Outcomes for rFVIIa Use
  • Search Strategy
  • Study Selection
  • Data Extraction
  • Quality Assessment of Individual Studies
  • Assessing the Strength of Evidence and Applicability for Each Key Question
  • Data Synthesis
  • Peer Review and Public Commentary
• Results
  • Summary of Studies and Data on In-Hospital, Off-Label rFVIIa Use
  • Key Question 1. Overview of off-label rFVIIa use in-hospital and comparative studies
  • Key Question 2. Intracranial hemorrhage and comparative effectiveness of rFVIIa
  • Key Question 3.a. Acquired, coagulopathic massive bleeding from body trauma and comparative effectiveness of rFVIIa
  • Key Question 3.b. Bleeding from brain trauma and comparative effectiveness of rFVIIa
  • Key Question 4.a. Liver transplantation and comparative effectiveness of rFVIIa
  • Key Question 4.b.i. Adult cardiac surgery and comparative effectiveness of rFVIIa
  • Key Question 4.b.ii. Pediatric cardiac surgery and comparative effectiveness of rFVIIa
  • Key Question 4.c. Prostatectomy and comparative effectiveness of rFVIIa
  • Evaluation of Harms in Patients Who Received rFVIIa: Comparing the Premier, RCT, and Observational Study Data
• Summary and Discussion
  • Findings
  • Limitations of the Premier Database Analysis
  • Limitations of the Systematic Review
• Future Research
  • Evidence Gaps
• References
• Abbreviations
• Appendixes
  • Appendix A Search Strategies
  • Appendix B List of Excluded Studies
  • Appendix C Additional Analyses, Tables, and Figures
  • Appendix D Peer Reviewers
  • Appendix E Study Abstraction Forms
  • Appendix F Strength of Evidence and Applicability Assessment Forms

Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.¹ Contract No. 290-02-0017. Prepared by: Stanford-UCSF Evidence-based Practice Center.

Suggested citation:

Yank V, Tuohy CV, Logan AC, Bravata DM, Staudenmayer K, Eisenhut R, Sundaram V, McMahon D, Stave CD, Zehnder JL, Olkin I, McDonald KM, Owens DK, Stafford RS. Comparative Effectiveness of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care. Comparative Effectiveness Review No. 21. (Prepared by Stanford-UCSF Evidence-based Practice Center under Contract No. #290-02-0017) Rockville, MD: Agency for Healthcare Research and Quality. May 2010. Available at: www.effectivehealthcare.ahrq.gov/reports/final.cfm.

This report is based on research conducted by the Stanford-UCSF Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. #290-02-0017). The findings and conclusions in this document are those of the author(s), who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help health care decision makers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.

This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.

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