Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2001)

Lev el
1a 1(

Therapy/Prevention, Aetiology/Harm
S !"ith homogeneity#$ of %Ts

Prognosis
S !"ith homogeneity#$ of inception cohort studies& %D ' validated in different populations )ndividual inception cohort study "ith + ,-. follo"/up& %D ' validated in a single population All or none case/series S !"ith homogeneity#$ of either retrospective cohort studies or untreated control groups in %Ts etrospective cohort study or follo"/ up of untreated control patients in an %T& Derivation of %D ' or validated on split/sample111 only 89utcomes8 esearch

Diagnosis S !"ith homogeneity#$ of Level 1 diagnostic studies& %D ' "ith 1( studies from different clinical centres 0alidating## cohort study "ith good''' reference standards& or %D ' tested "ithin one clinical centre A(solute SpPins and Sn2outs'' S !"ith homogeneity#$ of Level +3 diagnostic studies E7ploratory## cohort study "ith good'''reference standards& %D ' after derivation, or validated only on split/sample111 or data(ases

Differential diagnosis/symptom prevalence study S !"ith homogeneity#$ of prospective cohort studies Prospective cohort study "ith good follo"/up####

Economic and decision analyses S !"ith homogeneity#$ of Level 1 economic studies Analysis (ased on clinically sensi(le costs or alternatives& systematic revie"!s$ of the evidence& and including multi/"ay sensitivity analyses A(solute (etter/value or "orse/value analyses '''' S !"ith homogeneity#$ of Level +3 economic studies Analysis (ased on clinically sensi(le costs or alternatives& limited revie"!s$ of the evidence, or single studies& and including multi/"ay sensitivity analyses Audit or outcomes research S !"ith homogeneity#$ of :( and (etter studies Analysis (ased on limited alternatives or costs, poor 4uality estimates of data, (ut including sensitivity analyses incorporating clinically sensi(le variations5 Analysis "ith no sensitivity analysis E7pert opinion "ithout e7plicit critical appraisal, or (ased on economic theory or 8first principles8

)ndividual %T !"ith narro" %onfidence )nterval*$

1c 3a 3(

All or none1 S !"ith homogeneity#$ of cohort studies )ndividual cohort study !including lo" 4uality %T& e5g5, 6,-. follo"/up$

All or none case/series S !"ith homogeneity#$ of 3( and (etter studies etrospective cohort study, or poor follo"/up

3c :a :(

89utcomes8 esearch& Ecological studies S !"ith homogeneity#$ of case/ control studies )ndividual %ase/%ontrol Study

Ecological studies S !"ith homogeneity#$ of :( and (etter studies 2on/consecutive study& or "ithout consistently applied reference standards S !"ith homogeneity#$ of :( and (etter studies 2on/consecutive cohort study, or very limited population

; <

%ase/series !and poor 4uality cohort and case/control studies11$ E7pert opinion "ithout e7plicit critical appraisal, or (ased on physiology, (ench research or 8first principles8

%ase/series !and poor 4uality prognostic cohort studies###$ E7pert opinion "ithout e7plicit critical appraisal, or (ased on physiology, (ench research or 8first principles8

%ase/control study, poor or non/ independent reference standard E7pert opinion "ithout e7plicit critical appraisal, or (ased on physiology, (ench research or 8first principles8

%ase/series or superseded reference standards E7pert opinion "ithout e7plicit critical appraisal, or (ased on physiology, (ench research or 8first principles8

Produced (y =o( Phillips, %hris =all, Dave Sac>ett, Doug =adenoch, Sharon Straus, =rian Haynes, ?artin Da"es since 2ovem(er 1@@,5

Notes
Asers can add a minus/sign 8/8 to denote the level of that fails to provide a conclusive ans"er (ecause ofB

# ' * 1 11

E)THE a single result "ith a "ide %onfidence )nterval !such that, for e7ample, an A (enefit or harm$ 9 a Systematic evie" "ith trou(lesome !and statistically significant$ heterogeneity5

in an %T is not statistically significant (ut "hose confidence intervals fail to e7clude clinically important

Such evidence is inconclusive, and therefore can only generate Crade D recommendations5 =y homogeneity "e mean a systematic revie" that is free of "orrisome variations !heterogeneity$ in the directions and degrees of results (et"een individual studies5 2ot all systematic revie"s "ith statistically significant heterogeneity need (e "orrisome, and not all "orrisome heterogeneity need (e statistically significant5 As noted a(ove, studies displaying "orrisome heterogeneity should (e tagged "ith a 8/8 at the end of their designated level5 %linical Decision ule5 !These are algorithms or scoring systems "hich lead to a prognostic estimation or a diagnostic category5 $ See note D3 for advice on ho" to understand, rate and use trials or other studies "ith "ide confidence intervals5 ?et "hen all patients died (efore the 7 (ecame availa(le, (ut some no" survive on it& or "hen some patients died (efore the 7 (ecame availa(le, (ut none no" die on it5 =y poor 4uality cohort study "e mean one that failed to clearly define comparison groups and/or failed to measure e7posures and outcomes in the same !prefera(ly (linded$, o(Eective "ay in (oth e7posed and non/e7posed individuals and/or failed to identify or appropriately control >no"n confounders and/or failed to carry out a sufficiently long and complete follo"/up of patients5 =y poor 4uality case/control study "e mean one that failed to clearly define comparison groups and/or failed to measure e7posures and outcomes in the same !prefera(ly (linded$, o(Eective "ay in (oth cases and controls and/or failed to identify or appropriately control >no"n confounders5 Split/sample validation is achieved (y collecting all the information in a single tranche, then artificially dividing this into 8derivation8 and 8validation8 samples5 An 8A(solute SpPin8 is a diagnostic finding "hose Specificity is so high that a Positive result rules/in the diagnosis5 An 8A(solute Sn2out8 is a diagnostic finding "hose Sensitivity is so high that a 2egative result rules/out the diagnosis5 Cood, (etter, (ad and "orse refer to the comparisons (et"een treatments in terms of their clinical ris>s and (enefits5 Cood reference standards are independent of the test, and applied (lindly or o(Eectively to applied to all patients5 Poor reference standards are haphaFardly applied, (ut still independent of the test5 Ase of a non/independent reference standard !"here the GtestG is included in the GreferenceG, or "here the GtestingG affects the GreferenceG$ implies a level ; study5 =etter/value treatments are clearly as good (ut cheaper, or (etter at the same or reduced cost5 Horse/value treatments are as good and more e7pensive, or "orse and the e4ually or more e7pensive5 0alidating studies test the 4uality of a specific diagnostic test, (ased on prior evidence5 An e7ploratory study collects information and tra"ls the data !e5g5 using a regression analysis$ to find "hich factors are GsignificantG5 =y poor 4uality prognostic cohort study "e mean one in "hich sampling "as (iased in favour of patients "ho already had the target outcome, or the measurement of outcomes "as accomplished in 6,-. of study patients, or outcomes "ere determined in an un(linded, non/o(Eective "ay, or there "as no correction for confounding factors5 Cood follo"/up in a differential diagnosis study is +,-., "ith ade4uate time for alternative diagnoses to emerge !eg 1/I months acute, 1 / < years chronic$

111 '' ** ''' ''' ' ## ### ####

Grades of Recommendation consistent level 1 studies consistent level 3 or : studies or e7trapolations from level 1 studies level ; studies or e7trapolations from level 3 or : studies level < evidence or trou(lingly inconsistent or inconclusive studies of any level

! C "

"Extrapolations" are where data is used in a situation which has potentially clinically important differences than the original study situation.