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. Off-label drug use refers to any use of a medication that deviates from the product labeling approved and required by the FDA. The FDA drug approval process mandates randomized clinical trials that demonstrate efficacy and safety for specific indications prior to marketing. Once approval is given, however, the FDA does not regulate whether drugs are prescribed for off-label indications. In most instances, the data supporting off-label drug use falls short of the rigor that accompanies FDA review. This uncertainty may be acceptable, as when a drug’s use is infrequent. Nevertheless, concerns increase when off-label use is clinically distinct from approved indications, when off-label use becomes frequent, when a drug is costly, or when a drug is used in different clinical settings (e.g., shifts from outpatient to in-hospital use). rFVIIa is a form of human factor VII produced by recombinant technology. The purpose of this report is to define current patterns of in-hospital, off-label rFVIIa use through the analysis of U.S. hospital practice patterns of its administration and to conduct an effectiveness review of five selected off-label indications for rFVIIa use. Our goal is to answer the following Key Questions: Key Question 1. Current Patterns of rFVIIa Use Note that this focus on “patterns of use” is directed at in-hospital populations (for whom off-label rFVIIa is more prominent): Which clinical populations are receiving off-label rFVIIa and which populations have been scientifically examined? What are the characteristics of comparative studies evaluating off-label rFVIIa use? Key Question 2. Use of rFVIIa for Selected Indications in Patient With/Undergoing Intracranial Hemorrhage Key Question 3. Use of rFVIIa for Selected Indications in Patient With/Undergoing Massive Bleeding from Trauma Key Question 4a. Use of rFVIIa for Selected Indications in Patient With/Undergoing Liver Transplantation Key Question 4b. Use of rFVIIa for Selected Indications in Patient With/Undergoing Cardiac Surgery Key Question 4c. Use of rFVIIa for Selected Indications in Patient With/Undergoing Prostatectomy Key Questions 2-4. For each of these clinical areas we will answer the following questions: Does the use of rFVIIa reduce mortality and disability compared to usual care? Are there patient subpopulations more likely to benefit from rFVIIa use? Does rFVIIa use increase thrombosis-related events? Are there patient subpopulations where harms are more likely? Which patient subpopulations experience net benefits of rFVIIa and does this vary by timing and dosage?