Natural Standard: Grading Rationale
reflect the level of available scientific evidence in support of the
efficacy of a given therapy for a specific indication.
opinion and folkloric precedent are not included in this assessment,
and are reflected in a separate section of each monograph ("Strength
of Expert Opinion and Historic/Folkloric Precedent").
of harm is considered separately; the below grades apply only to evidence
significant evidence of benefit from >2 properly randomized trials (RCTs),
OR evidence from one properly conducted RCT AND one properly conducted meta-analysis,
OR evidence from multiple RCTs with a clear majority of the properly conducted
trials showing statistically significant evidence of benefit AND with supporting
evidence in basic science, animal studies, or theory.
significant evidence of benefit from 1-2 properly randomized trials, OR
evidence of benefit from >1 properly conducted meta-analysis OR
evidence of benefit from >1 cohort/case-control/non-randomized trials
AND with supporting evidence in basic science, animal studies, or theory.
of benefit from >1 small RCT(s) without adequate size, power,
statistical significance, or quality of design by objective criteria,* OR
conflicting evidence from multiple RCTs without a clear majority of the
properly conducted trials showing evidence of benefit or ineffectiveness,
OR evidence of benefit from >1 cohort/case-control/non-randomized
trials AND without supporting evidence in basic science, animal studies,
or theory, OR evidence of efficacy only from basic science, animal studies,
significant negative evidence (i.e., lack of evidence of benefit) from cohort/case-control/non-randomized
trials, AND evidence in basic science, animal studies, or theory suggesting
significant negative evidence (i.e. lack of evidence of benefit) from >1
properly randomized adequately powered trial(s) of high-quality design by
to evaluate efficacy due to lack of adequate available human data.
instruments for evaluating study quality, including the 5-point scale
developed by Jadad et al., in which a score below 4 is considered to indicate
AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ.
Assessing the quality of reports of randomized clinical trials: is blinding
necessary? Controlled Clinical Trials 1996; 17:1-12). Listed separately in monographs in the "Historical
or Theoretical Uses which Lack Sufficient Evidence" section.