26
Levels of Evidence
Level Diagnosis Therapy/Prevention/Etiology
1 Systematic review of cross sectional
studies with consistently applied reference
standard and blinding
Systematic review of randomized
trials or n-of-1 trials
2 Individual cross sectional studies with
consistently applied reference standard
and blinding
Randomized trial or observational
study with dramatic effect
3 Cohort study or control arm of
randomized trial
a
Non-randomized controlled
cohort/follow-up study
b
4 Case-series or case control studies, or poor
quality prognostic cohort study
b
Case-series, case-control studies, or
historically controlled studies
b
5 Not applicable Mechanism-based reasoning
a
Level may be graded down on the basis of study design, inconsistency between studies, indirectness
of evidence, imprecision, or because the absolute effect size is very small; level may be graded up if
there is a large or very large effect size or if a significant dose-response relationship is demonstrated.
b
As always, a systematic review is generally better than an individual study.
Aggregate Grade of Evidence
Grade Research Quality
A Well-designed RCTs
B RCTs with minor limitations
Overwhelming consistent evidence from observational studies
C Observational studies (case control and cohort design)
D Expert opinion
Case reports
Reasoning from first principles
For topics with more limited evidence, the evidence-based review (EBR) process was completed with
the evidence table. For those topics with sufficient evidence to produce a recommendation
(i.e., an evidence-based review with recommendations [EBRR]), a recommendation using the
American Academy of Pediatrics (AAP) guidelines was produced. It is important to note that each
evidence-based recommendation took into account the aggregate grade of evidence along with the
balance of benefit, harm, and costs (AAP Defined Strateg y for Recommendation Development).
