Skip Navigation
Department of Health and Human Services www.hhs.gov
Agency for Healthcare Research Quality www.ahrq.gov
AHRQ Home | Questions? | Contact Us | Site Map | What's New | Browse | Información en español | E-mail UpdatesE-mail Updates
 
Slide Tray
0 slides

Return to Slide Library

Slides

Slides: 121–132 of 673
Outcomes of Interest for Off-Label rFVIIa Use in the Hospital Setting This slide lists examples of potential outcomes of rFVIIa use. These encompass a range, from indirect outcomes—of process/resource use or intermediate/surrogate outcomes (which are perhaps the easiest to measure but are not always closely connected to patient status)—to direct clinical endpoints such as death, adverse events, or functional status (which are the most relevant to patient well-being but are often more difficult to measure or occur less frequently than the other outcomes). Ideally, the CER would focus primarily on direct clinical outcomes for each of the clinical research questions, but this is not always possible given that the studies and other data sources may only report indirect outcome measures or have few events of this type.
Add to tray Remove from tray

Outcomes of Interest for Off-Label rFVIIa Use in the Hospital Setting

Presentation: Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care
Keywords: comparative effectiveness | recombinant factor VIIa | off-label | direct outcomes | indirect outcomes | endpoints | adverse effects
Four Domains Used To Assess Relevant Studies The following four major domains were examined: risk of bias (low, medium, high), consistency (no inconsistency, inconsistency present, unknown, or not applicable), directness (direct, indirect), and precision (precise, imprecise). Each key outcome on each comparison of interest was given an overall evidence grade based on the ratings for the individual domains.
Add to tray Remove from tray

Four Domains Used To Assess Relevant Studies

Presentation: Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care
Keywords: comparative effectiveness | recombinant factor VIIa | off-label | risk of bias | consistency | directness | precision
Rating the Strength of Evidence From the CER The EPC GRADE approach, based on the standard GRADE approach, was used to assess the quality of the body of evidence for each outcome. The overall strength of evidence was graded as high (further research is very unlikely to change the confidence in the estimate of effect), moderate (further research may change the confidence in the estimate of effect and may change the estimate), low (further research is likely to change the confidence in the estimate of effect and is likely to change the estimate), or insufficient (evidence either is unavailable or does not permit estimation of an effect). The authors also independently evaluated the applicability to real-world practice of the total body of evidence within a given clinical indication using the PICOTS framework (population, intervention, comparator, outcome, timing, and setting).
Add to tray Remove from tray

Rating the Strength of Evidence From the CER

Presentation: Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care
Keywords: comparative effectiveness | recombinant factor VIIa | off-label | strength of evidence
Characteristics of Comparative Studies on Off-Label rFVIIa Use With the exception of use in ICH, study sample sizes were small (median of 24 treated patients). The doses used in the studies that are the focus of this effectiveness review varied from 5 to 956 mcg/kg of patient weight, and only for intracranial hemorrhage was there a sufficient range of doses to assess the impact of rFVIIa dosing on outcomes. Most studies used indirect endpoints as their primary outcomes, particularly red blood cell (RBC) transfusion requirements. Direct outcomes, such as mortality, functional status, or thromboembolic events, were frequently reported, but most studies were individually underpowered to evaluate them. Most clinical research on rFVIIa has been directed and sponsored by Novo Nordisk, the product’s manufacturer. The strength of evidence available from existing studies was thereby compromised by small study size, use of indirect outcomes, and heterogeneity in dosage and indication. The applicability was diminished by less acutely ill patients and a mismatch between existing research and real-world patterns of indication and types of use.
Add to tray Remove from tray

Characteristics of Comparative Studies on Off-Label rFVIIa Use

Presentation: Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care
Keywords: comparative effectiveness | recombinant factor VIIa | off-label | strength of evidence
Mean Differences in Mortality and Thromboembolic Event Rates by Study and rFVIIa Indication This figure includes indications with two or more comparative studies: ICH, body trauma (Trauma), brain trauma (TBI), liver transplantation (LvrTx), and adult cardiac surgery (AdCS). Each circle represents a study; larger circles correspond to larger studies; shaded circles represent studies on treatment use of rFVIIa, and white circles represent studies on prophylactic use of rFVIIa. The mean differences in event rates for the direct (patient-centered) outcomes of total mortality and thromboembolic events are plotted for each comparative study and according to each rFVIIa indication using circle charts, with the area of each circle approximating the total sample size of its respective study. The figures show mean differences in mortality and thromboembolic event rates, respectively, for each comparative study and according to each rFVIIa indication. ICH = intracranial hemorrhage here—although in rest of report “ICH” indicates a subset of intracranial hemorrhage, namely intracerebral hemorrhage; Trauma = body trauma; TBI = brain trauma (traumatic brain injury); LvrTx = liver transplantation; AdCS = adult cardiac surgery
Add to tray Remove from tray

Mean Differences in Mortality and Thromboembolic Event Rates by Study and rFVIIa Indication

Presentation: Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care
Keywords: mortality | off-label | recombinant factor VIIa | thromboembolic event rates | comparative effectiveness
Evidence of rFVIIa Use for Bleeding Secondary to Body Trauma vs. Usual Care Trauma is the leading cause of death in young men between the ages of 15 and 40. Hemorrhage is the leading cause of early death (within 24–48 hours) in trauma and second only to traumatic brain injury (TBI) as the overall cause of mortality. Hemorrhage after traumatic injury is associated with an acquired coagulopathy known as the “acute coagulopathy of trauma.” The coagulopathy develops when there is tissue injury in combination with hypotension. The severity of coagulopathy increases with increasing injury severity and is associated with worse outcomes. Resuscitation of these patients can worsen the coagulopathy. The dilution of blood due to rapid infusion of crystalloid, the development of hypothermia, and persistent acidosis occur during resuscitation and are known together as the “lethal triad,” which conspires to impede coagulation. Not surprisingly, the conditions which lead to the development of lethal triad are worse in cases of severe hemorrhage, particularly in those cases that require massive transfusions (most frequently defined as the use of 10 or more units of packed red blood cells [RBCs] within 24 hours of injury). This acquired coagulopathy potentiates further bleeding, which in turn leads to further physiologic derangements, increased morbidity, and increased mortality. Unfortunately, blood products that are used to replace lost blood and to treat coagulopathy can carry risks of their own. In particular, studies have highlighted increased risks of acute respiratory distress syndrome (ARDS), multiorgan failure (MOF), and sepsis with higher levels of blood product transfusions. rFVIIa has been investigated in trauma as an adjunct to control bleeding and thereby reduce the above risks.
Add to tray Remove from tray

Evidence of rFVIIa Use for Bleeding Secondary to Body Trauma vs. Usual Care

Presentation: Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care
Keywords: comparative effectiveness | recombinant factor VIIa | off-label | body trauma
Overview of rFVIIa Use in Bleeding Secondary to Body Trauma There were two randomized controlled trials (all fair quality) and three comparative observational studies (all fair quality) with 267 patients who received rFVIIa. This yielded low strength of evidence with fair applicability for treatment use in the population targeted—patients with blunt or penetrating trauma who were not censored for early in-hospital death (defined as 24 hours or 48 hours depending on the study). The findings suggest that there was no effect of rFVIIa on mortality or thromboembolism relative to usual care. There was conflicting evidence regarding RBC transfusion requirements. For acute respiratory distress syndrome, the blunt trauma RCT demonstrated a significant reduction with rFVIIa use vs. usual care, while the remaining two studies that evaluated this outcome (the penetrating trauma RCT and one observational study) showed a nonsignificant trend in the same direction. Overall, current evidence of low strength suggests the potential for benefit and little evidence of increased harm.
Add to tray Remove from tray

Overview of rFVIIa Use in Bleeding Secondary to Body Trauma

Presentation: Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care
Keywords: acute respiratory distress syndrome | body trauma | off-label | recombinant factor VIIa | comparative effectiveness
Overview of rFVIIa for Adult Cardiac Surgery: Clinical Outcomes The strength of evidence was low for the findings of no effect of rFVIIa use on mortality, units of RBCs transfused, or ICU length of stay. Among the RCTs and higher quality cohort studies, there was a trend toward reduced transfusion requirements with therapy, but no difference in ICU length of stay. Study patients were similar in age to those in the Premier database. Compared to Premier patients, those in the cohort studies had comparable mortality rates, whereas those in the RCTs had somewhat lower mortality rates. The importance and nature of interactions between the timing of treatment use of rFVIIa and important clinical outcomes remain uncertain.
Add to tray Remove from tray

Overview of rFVIIa for Adult Cardiac Surgery: Clinical Outcomes

Presentation: Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care
Keywords: comparative effectiveness | recombinant factor VIIa | off-label | adult cardiac surgery | outcomes | mortality | red blood cell transfusion | ICU length of stay
Increased Risk of Thromboembolic Events With rFVIIa Use for Adult Cardiac Surgery There is evidence of moderate strength to suggest that the use of rFVIIa in adult cardiac surgery increases the rate of thromboembolic events when compared to usual care. Thus, current evidence of moderate strength (for thromboembolic events) or low strength (for all other outcomes) suggests that neither benefits nor harms substantially exceed each other for rFVIIa use in adult cardiac surgery.
Add to tray Remove from tray

Increased Risk of Thromboembolic Events With rFVIIa Use for Adult Cardiac Surgery

Presentation: Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care
Keywords: comparative effectiveness | recombinant factor VIIa | off-label | adult cardiac surgery | thromboembolic events
Summary of Outcomes for Most Common Off-Label, In-Hospital Uses of rFVIIa Overall study quality is fair to poor and the strength of evidence is low, with the exception of meta-analyses of intracranial hemorrhage that had moderate strength of evidence for all outcomes and of a meta-analysis of adult cardiac surgery studies that had moderate strength of evidence for the thromboembolic event outcome. Clinical efficacy is often defined via indirect/surrogate outcomes, such as transfusion requirements, change in hematoma volume, or ICU length of stay. Safety is defined via thromboembolic events and mortality, but individual studies often lack the statistical power to assess these outcomes. Evidence of rFVIIa benefit is suggested for several indications, but largely via the surrogate outcomes used in the included studies and with an uncertain relationship to improved patient survival or functional status. In addition, for some uses, rFVIIa produces an increased risk of thromboembolism. Current evidence of low strength suggests the potential for benefits to exceed harms for bleeding from body trauma. There are no indications where potential risks are likely to greatly exceed the benefits. Intracranial hemorrhage: There are four RCTs and one observational study involving 968 rFVIIa-treated patients. Treatment with rFVIIa reduced expansion of intracranial hematoma volume relative to usual care, but increased the risk of arterial thromboembolic events and did not reduce the rates of mortality or poor functional outcome. Current evidence of moderate strength suggests that neither benefits nor harms substantially exceed each other. Adult cardiac surgery: There are two RCTs and four included comparative observational studies with 251 patients receiving prophylactic or therapeutic rFVIIa. These studies showed that rFVIIa likely increased the risk of thrombembolic events, but failed to show an effect of rFVIIa on other outcomes, including mortality. rFVIIa use for this indication is increasing in the U.S. Body trauma: There are two RCTs and two comparative observational studies examining rFVIIa treatment in 257 patients experiencing massive blood loss from trauma. These suggested a possible reduced rate of ARDS, most likely to be present in cases of blunt trauma, but these findings are complicated by the exclusion of patients with early mortality from both of the RCTs and one of the cohort studies. There is no evidence of effect on mortality or of increased thromboembolic events with treatment. Current evidence of low strength suggests the potential for benefit and little evidence of increased harm.
Add to tray Remove from tray

Summary of Outcomes for Most Common Off-Label, In-Hospital Uses of rFVIIa

Presentation: Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care
Keywords: off-label | recombinant factor VIIa | comparative effectiveness
Conclusions From Available Evidence For the uses examined, current evidence does not show that off-label use of rFVIIa reduces mortality or improves other direct outcomes. Thromboembolic events are increased by using rFVIIa to treat spontaneous intracranial hemorrhage and in adult cardiac surgery.
Add to tray Remove from tray

Conclusions From Available Evidence

Presentation: Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care
Keywords: comparative effectiveness | recombinant factor VIIa | off-label | conclusions
Add to tray Remove from tray

Comparative Effectiveness of Management Strategies for Adults With Gastroesophageal Reflux Disease: An Update

Presentation: Comparative Effectiveness of Management Strategies for Adults With Gastroesophageal Reflux Disease: An Update
Keywords: GERD | treatment | comparative effectiveness review | systematic review
 
 
 
 
www.ahrq.gov AHRQ Home | Questions? | Contact AHRQ | Site Map | Accessibility | Privacy Policy | Freedom of Information Act | Disclaimers
U.S. Department of Health & Human Services | The White House | USA.gov: The U.S. Government's Official Web Portal

Agency for Healthcare Research and Quality • 540 Gaither Road Rockville, MD 20850 • Telephone: (301) 427-1364