18
Grades of Aggregate Evidence
a
Grade
OCEBM
level Treatment Harm Diagnosis Prognosis
A
1 Systematic
review
b
of
randomized
trials
Systematic
review
b
of
randomized
trials, nested
case-control
studies, or
observational
studies with
dramatic
effect
b
Systematic
review
b
of
cross-sectional
studies with
consistently
applied
reference
standard and
blinding
Systematic
review
b
of
inception
cohort studies
c
B
2 Randomized
trials, or
observational
studies with
dramatic
effects or
highly
consistent
evidence
Randomized
trials, or
observational
studies with
dramatic
effects or
highly
consistent
evidence
Cross-sectional
studies with
consistently
applied
reference
standard and
blinding
Inception
cohort studies
c
C
3–4 Non-
randomized
or historically
controlled
studies,
including case-
control and
observational
studies
Non-
randomized
controlled
cohort or
follow-up
study (post-
marketing
surveillance)
with sufficient
numbers to
rule out a
common harm,
case-series,
case-control,
or historically
controlled
studies
Non-
consecutive
studies, case-
control studies,
or studies with
poor, non-
independent,
or
inconsistently
applied
reference
standards
Cohort study,
control arm of
a randomized
trial, case
series, or case-
control studies,
or poor-quality
prognostic
cohort study
D
5 Case reports, mechanism-based reasoning, or reasoning from first
principles
X
n/a Exceptional situations where validating studies cannot be performed
and there is a clear preponderance of benefit over harm
OCEBM, Oxford Centre for Evidence-Based Medicine.
a
Adapted with permission from e Oxford Levels of Evidence 2 developed by the OCEBM Levels
of Evidence Working Group.
b
A systematic review may be downgraded to level B because of study limitations, heterogeneity, or
imprecision.
c
A group of individuals identified for subsequent study at an early, uniform point in the course of
the specified health condition, or before the condition develops.
