Program on Prevention Outcomes and Practices

Effectiveness and Off-label Use of
Recombinant Factor VIIa

Principal Investigator: Randall S. Stafford
Funding Agency: Agency for Healthcare Research and Quality
Duration: 2/1/2008 - 06/31/2009

Under the Evidence-based Practice Centers (EPC) Program of the Agency for Healthcare Research and Quality (formerly the Agency for Health Care Policy and Research—AHCPR), 5-year contracts are awarded to institutions in the United States and Canada to serve as EPCs. The EPCs review all relevant scientific literature on clinical, behavioral, and organization and financing topics to produce evidence reports and technology assessments. These reports are used for informing and developing coverage decisions, quality measures, educational materials and tools, guidelines, and research agendas. The EPCs also conduct research on methodology of systematic reviews.

This EPC project investigates recombinant factor VIIa.  Recombinant factor VIIa is being administered and studied in an increasingly wide range spectrum of disease conditions and patient populations beyond the scope of its current labeled indications.  With the intent providing an overview of the range of off-label  clinical conditions for which rFVIIa has been administered and or  studied.  This project is a collaborative effort between researchers in the Program on Prevention Outcomes and Practices and the Center for Primary Care and Outcomes Research.  The primary questions being investigated include:

Key Question 1.

1.      What are the different indications and populations for which recombinant Factor VIIa has been used and or studied outside the currently labeled indications?

2.      What is the clinical setting, dosage range of rfVIIa,  study  design/size, comparator, and outcomes measured (i.e., volume of red  cell products, ICU and ventilator use, ARDS, Multi-organ system failure) in existing, off-label studies of rFVIIa?

Key Question 2:

Considering patients with intracranial bleeding;

1.      Does rFVIIa use reduce mortality and/or disability compared with usual care?

2.      Are there subpopulations of patients based on demographic (i.e., ethnicity, sex, age) or clinical factors (i.e., intraventricular hemorrhage, size of bleed, time from onset to treatment) who are more likely to benefit from rFVIIa use?

3.      Does rFVIIa use increase thrombosis-related events (i.e., DVT, PE, thrombotic stroke, MI, other thrombotic events) compared with usual care?

4.      Are there subpopulations of patients based on demographic (i.e., ethnicity, sex, age) or clinical factors who are more likely to experience harm from the use of rFVIIa?

5.      In whom do the benefits of rFVIIa use outweigh the harms (evidence of net benefit) and does net benefit vary by issues such as timing and dosage used?

Key Question 3:

Considering patients with (acquired) coagulopathic massive bleeding including trauma-related hemorrhagic shock:

1.      Does rFVIIa use reduce mortality and/or disability and treatment-related outcomes (volume of red cell and component products, ICU, dialysis and ventilator use, ARDS and multi-organ failure incidence) compared with usual care?

2.      Are there subpopulations of patients based on demographic (i.e., ethnicity, sex, age) or clinical factors (i.e., acidosis, levels, platelet count and fibrinogen level, nature of clinical disorder such as-blunt vs penetrating trauma) who are more likely to benefit from rFVIIa use?

3.      Does rFVIIa use increase thrombosis-related events (i.e., DVT, PE, thrombotic stroke, MI, other thrombotic events) compared with usual care?

4.      Are there subpopulations of patients based on demographic (i.e., ethnicity, sex, age) or clinical factors who are more likely to experience harm from the use of rFVIIa?

5.      In whom do the benefits of rFVIIa use outweigh the harms (evidence of net benefit) and does net benefit vary by issues such as timing and dosage used?

Key Question 4:

Considering patients with non-coagulopathic and acquired coagulopathic states undergoing surgeries including liver transplants, cardiac surgery or prostatectomy:

1.      Does salvage and/or prophylactic rFVIIa use reduce mortality  and/or disability and treatment-related outcomes (volume of red cell  products, requirement for return to operating room, ICU and   ventilator use, ARDS and multi-organ failure) compared with usual care?

2.      Are there subpopulations of patients based on demographic (i.e., ethnicity, sex, age) or clinical factors who are more likely to benefit from rFVIIa use?

3.      Does rFVIIa use increase thrombosis-related events (i.e., DVT, PE, thrombotic stroke, MI, other thrombotic events) compared with usual care?

4.      Are there subpopulations of patients based on demographic (i.e., ethnicity, sex, age) or clinical factors who are more likely?  

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