Table ASummary of results and conclusions from overview and Comparative Effectiveness Review

Number of studiesTotal number of patientsOutcomea and strength of evidencebEffectiveness review conclusions
RCT OBSrFVIIa Usual careMortalityTE eventsOther direct outcomeUnits RBCs transfusedOther indirect outcome
KQ1a. Overview of Premier database information on in-hospital off-label use
NArFVIIa: 73,746 hospital cases, 2000–2008

UC: Not available from Premier database
By KQ indication: NANANANA
  • The majority of use of rFVIIa occurs in the outpatient setting, and the majority of outpatient use is for on-label indications related to hemophilia.
  • In-hospital rFVIIa cases (any application during a given discharge) in the U.S. have increased since 2000 almost solely due to rising off-label use. This use was estimated to be 125 cases in 2000, underwent a slow increase until 2005 when use became more frequent and was estimated to be 11,057 cases, and by 2008 was estimated to be 17,813 cases (97 percent of all of the estimated 18,311 in-hospital cases), although the slope of increase may be leveling off for many indications.
  • In 2008, cardiac surgery, trauma, and intracranial hemorrhage were the leading off-label indications, while there was limited use in liver transplantation and none in prostatectomy. Other off-label uses included GI bleeding, primary/secondary clotting disorders, and aortic aneurysm/other vascular procedures.
KQ1b. Overview of published literature
RCT: 24

OBS: 31
rFVIIa: 937 in non-KQ studiesc (N=10)

UC: 589 in non-KQ studiesc (N=7)
NANANANANA
  • Published studies of rFVIIa are often limited by small study size, inconsistent study quality, use of indirect outcomes, and heterogeneity by dosage and indication.
KQ2. Intracranial hemorrhage
RCT: 4

OBS: 1
rFVIIa: 968

UC: 414



Moderate rFVIIa:
0.08–0.22
UC:
0.13–0.29



Moderate rFVIIa:
0.04–0.11
UC:
0–0.13
Poor functional statusd

Moderate rFVIIa:
0.44–0.53
UC:
0.46–0.69
NAPercent hematoma expansion

Moderate

rFVIIa:
4–79
UC:
11–29
Use of rFVIIa compared to usual care, within the ICH subgroup of intracranial hemorrhage
  • Did not affect mortality or rate of poor functional status
  • Was associated with an increased rate of arterial TE events
  • Was associated with a decrease in the percent hematoma expansion
In summary, current evidence of moderate strength suggests that neither benefits nor harms substantially exceed each other
KQ3a. Body trauma
RCT: 2

OBS: 3
rFVIIa: 267

UC: 429



Low

rFVIIa:
0.07–0.31
UC:
0–0.51



Low

rFVIIa:
0.03–0.12
UC:
0–0.08
ARDS

Low

rFVIIa:
0.02–0.06
UC:
0.04–0.16



Low

rFVIIa:
6.9–16.0
UC:
7.7–14.0
NAUse of rFVIIa compared to usual care
  • Did not affect mortality or TE event rate
  • May decrease the rate of ARDS
  • Had an unclear impact on RBC transfusion requirements
In summary, current evidence of low strength suggests the potential for benefit and little evidence of increased harm
KQ3b. Brain trauma
RCT: 1

OBS: 1
rFVIIa: 79

UC: 53



Low

rFVIIa:
0.12–0.33
UC:
0.11–0.53



Low

rFVIIa:
0.15–0.22
UC:
0.08–0.18
NANAAbsolute hematoma expansion (mL)

Low

rFVIIa:
7.0
UC:
10.4
Use of rFVIIa compared to usual care
  • Did not affect mortality or TE event rate
  • Did not reduce hematoma growth but may reduce the time to neurosurgical intervention (e.g., by normalizing the INR to an acceptable level)
In summary, current evidence of low strength is too limited to compare harms and benefits
KQ4a. Liver transplantation
RCT: 4

OBS: 1
rFVIIa: 215

UC: 117



Low

rFVIIa: 0–0.08
UC: 0–0.02



Low

rFVIIa: 0–0.22
UC: 0–0.16
NA

Low

rFVIIa: 1.2–13.0
UC: 2.3–11.1
OR time (min)

Low

rFVIIa: 268–554
UC: 432–598

ICU LOS(day)

Low

rFVIIa: 3.0–4.8
UC: 3.0–5.2
Use of rFVIIa compared to usual care
  • Did not affect mortality or TE event rate
  • May reduce RBC transfusion requirements
  • Did not reduce OR time or ICU length of stay
In summary, current evidence of low strength is too limited to compare harms and benefits
KQ4bi. Adult cardiac surgery
RCT: 2

OBS: 4
rFVIIa: 251

UC: 216



Low

rFVIIa: 0–0.33
UC: 0.06–0.33



Moderate rFVIIa: 0–0.22
UC: 0–0.20
NA


Low

rFVIIa: 0–9.1
UC: 2–17
ICU LOS (day)

Low

rFVIIa: 2.5–14
UC: 1–18.5
Use of rFVIIa compared to usual care
  • Did not affect mortality
  • Was associated with a higher TE event rate
  • May reduce RBC transfusion requirements
  • Had an unclear impact on ICU length of stay
In summary, current evidence of moderate strength (TE event rate outcome) or low strength (all other outcomes) suggests that neither benefits nor harms substantially exceed each other
KQ4bii. Pediatric cardiac surgery
RCT: 1

OBS: 0
rFVIIa: 40

UC: 36
Not reported


Insufficient
rFVIIa: 0
UC: 0
NAmL RBC transfused

Insufficient
rFVIIa: 77
UC: 127
Time to chest closure (min)

Insufficient
rFVIIa: 98.8
UC: 55.3
The one included study cannot comment on use of rFVIIa compared to usual care on mortality (because these data were not reported) or on TE event rate (because there were limited events).
Use of rFVIIa compared to usual care
  • May reduce RBC transfusion requirements
  • Was associated with an increase in time to chest closure
In summary, current evidence is insufficient for comparing harms and benefits
KQ4c. Prostatectomy
RCT: 1

OBS: 0
rFVIIa: 24

UC: 12



Insufficient
rFVIIa: 0
UC: 0



Insufficient
rFVIIa: 0–0.13
UC: 0
NA


Insufficient
rFVIIa: 0–0.6
UC: 1.5
OR time (min)

Insufficient
rFVIIa: 120–126
UC: 180
The one included study cannot comment on use of rFVIIa compared to usual care on mortality or TE event rate because there were limited events.
Use of rFVIIa compared to usual care
  • Was associated with reduced RBC transfusion requirements and OR time
In summary, current evidence is insufficient for comparing harms and benefits

KQ=Key Question; RCT=randomized controlled trial; OBS=comparative observational study; TE=thromboembolic; RBC=red blood cell; NA=not applicable; UC=usual care; ARDS=acute respiratory distress syndrome; OR=operating room; ICU LOS=intensive care unit length of stay; GI=gastrointestinal; ICH=intracerebral hemorrhage.

a

Outcome is given as a range of rates, unless otherwise stated. Each outcome range encompasses the lowest and highest rate/unit measured across all studies and, as such, should not be used to directly compare between the rFVIIa and UC care groups. Direct comparisons between groups are described in detail in the main report and are summarized in the “conclusions” column of this table.

b

Strength of evidence is based on scores within four evidence domains (risk of bias, consistency, directness, and precision) and is rated as “low,” “moderate,” “high,” or “insufficient.”

c

Only non-KQ studies are listed here because the studies on Key Questions 2–4 are subsequently reviewed lower in the table.

d

Poor functional status is defined as a modified Rankin Scale (mRS) score of 4–6.

From: Executive Summary

Cover of Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care
Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care [Internet].
Comparative Effectiveness Reviews, No. 21.
Yank V, Tuohy CV, Logan AC, et al.

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