Table A. Levels of evidence and grades of recommendations

Table A. Levels of evidence and grades of recommendations Grade of recommendation

A

Level of evidence

Therapylprevention, Aetiologylharm

Prognosis

Diagnosis

Systematic reviews (SR)/meta-analysis (with homogeneity) o f randomized controlled trials (RCTs) based o n individual patient’s data Systematic reviewdmeta-analysis (with homogeneity’) or RCTs based o n summary effect measures

SR (with homogeneity) o f inception cohotdstudies; or a clinical prediction guide (CPGb) validated o n a test set

SR (with homogeneity) o f Level I diagnostic studies; or a CPG validated o n a test set.

Individual inception cohort, prospective study w i t h 2 80% follow-up

Individual RCT in which l o w e r limit o f confidence interval (narrow CI‘) f o r t h e treatment effect exceeds the minimally important benefit Non-RCTs w i t h dramatic treatment effectd

All or none case-seriese

Independent blind comparison o f an appropriate spectrum o f consecutive patients, all o f w h o m have undergone both the diagnostic test and t h e reference standard. Studies that produced absolute SpPins and SnNouts‘

2a

SR (with homogeneity”) o f c o h o r t studies

2b

Individual c o h o r t study, including l o w quality RCT; [e.g. < 80% follow-up, inconclusive study, or R C T in which t h e l o w e r limit o f C I f o r the treatment effect overlaps the minimally important benefit (wide Cl)]

SR (with homogeneity”) o f either retrospective c o h o r t studies or untreated control groups in RCTs. Retrospective c o h o r t study or follow-up o f untreated control patients in an RCT; or CPG n o t validated in a test set.

3a

SR (with homogeneity”) of case-control studies

3b

Individual case-control study

C

4

Case-series (and p o o r quality c o h o r t and case-control stu di esg)

Case-series (and p o o r quality prognostic c o h o r t studiesh)

Reference standard was n o t applied independently or n o t applied blindly

D

5

Expert opinion w i t h o u t explicit critical appraisal, or based o n physiology, bench research or ‘ f i r s t principles’

Expert opinion w i t h o u t explicit critical appraisal, or based o n physiology, bench research or ‘first principles’

Expert opinion w i t h o u t explicit critical appraisal, or based o n physiology, bench research or ‘ f i r s t principles’

la

Ib

Ic

Id

B

SR (with homogeneity”) o f Level 2 2 diagnostic studies

Independent blind comparison b u t either in non-consecutive patients, or confined to a narrow spectrum o f study individuals (or both), all o f w h o m have undergone both t h e diagnostic test and t h e reference standard; or a diagnostic CPG n o t validated in a test set. Independent blind comparison o f an appropriate spectrum, b u t t h e reference standard was n o t applied to all study patients

Note: Recommendations based o n this approach t o ‘average’ patients and may need t o be modified in light ofan individual patient’s unique biology (risk responsiveness, etc.) and preferences about the care they receive. a By homogeneity we mean a systematic review that is free of worrisome variations (heterogeneity) in the directions and degrees of results between individual studies. N o t all systematic reviews with statistically significant heterogeneity need be worrisome, and not all worrisome heterogeneity need be statistically significant Studies displaying worrisome heterogeneity should be tagged with a ‘ ’ at the end of their designated level. bClinical Prediction Guide. ‘See note above for advice on how t o understand, rate and use trials o r other studies with wide confidence intervals. dMet when allpatients died before the treatment became available, but some now survive on is o r when some patients died before the treatment became available, but none now die on it. Or, more realistically if 10-1 I out of 12 patients respondlsurvive o n new therapy, while only 1-2 patients would respondlsurvive t o standard treatment. ‘Met when there are no reports of anyone with this condition ever avoiding (all) o r suffering from (none) a particular outcome (such as death). ‘An ‘Absolute SpPin’ is a diagnostic finding whose Specificity is so high that a Positive result rules in the diagnosis. A n ‘absolute SnNout’ is a diagnostic finding whose Sensitivity is so high that a Negative result rules out the diagnosis. Note, however, that the sensitivity and specificity of the test is not the same as predictive value of the test (for a given disease). By poor quality cohort study we mean one that failed t o clearly define comparison groups andlor failed t o measure exposures and outcomes in the same (preferably blinded), objective way in both exposed and non-exposed individuals andlor failed t o identify o r appropriately control known confounders andlor failed t o carry out a sufficiently long and complete follow-up of patients. By poor quality case-controlstudy we mean one that failed t o clearly define comparison groups andlor failed t o measure exposures and outcomes in the same blinded, objective way in both cases and controls andlor failed t o identify o r appropriately control known confounders. hBy poor quality prognostic cohort study we mean one in which sampling was biased in favour o f patients who already had the target outcome, o r the measurement of outcomes was accomplished in < 80% of study patients, o r outcomes were determined in an unblinded, non-objective way, o r there was no correction f o r confounding factors. Source: Adapted from NHS R&D Centre for Evidence-based Medicine, University of Oxford, UK, with permission. ~

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