Level Therapy/Prevention,

Aetiology/Harm
Prognosis Diagnosis Differential diagnosis/symptom
prevalence study
Economic and decision analyses
1a S !"ith homogeneity#$ of %Ts S !"ith homogeneity#$ of inception
cohort studies& %D' validated in
different populations
S !"ith homogeneity#$ of Level 1
diagnostic studies& %D' "ith 1(
studies from different clinical
centres
S !"ith homogeneity#$ of
prospective cohort studies
S !"ith homogeneity#$ of Level
1 economic studies
1( )ndividual %T !"ith narro"
%onfidence )nterval*$
)ndividual inception cohort study "ith
+ ,-. follo"/up& %D' validated in
a single population
0alidating## cohort study "ith
good''' reference standards& or
%D' tested "ithin one clinical
centre
Prospective cohort study "ith good
follo"/up####
Analysis (ased on clinically
sensi(le costs or alternatives&
systematic revie"!s$ of the
evidence& and including multi/
"ay sensitivity analyses
1c All or none1 All or none case/series A(solute SpPins and Sn2outs'' All or none case/series A(solute (etter/value or "orse/
value analyses ''''
3a S !"ith homogeneity#$ of cohort
studies
S !"ith homogeneity#$ of either
retrospective cohort studies or
untreated control groups in %Ts
S !"ith homogeneity#$ of Level +3
diagnostic studies
S !"ith homogeneity#$ of 3( and
(etter studies
S !"ith homogeneity#$ of Level
+3 economic studies
3( )ndividual cohort study !including
lo" 4uality %T& e5g5, 6,-.
follo"/up$
etrospective cohort study or follo"/
up of untreated control patients in an
%T& Derivation of %D' or
validated on split/sample111 only
E7ploratory## cohort study "ith
good'''reference standards& %D'
after derivation, or validated only on
split/sample111 or data(ases
etrospective cohort study, or poor
follo"/up
Analysis (ased on clinically
sensi(le costs or alternatives&
limited revie"!s$ of the evidence,
or single studies& and including
multi/"ay sensitivity analyses
3c 89utcomes8 esearch& Ecological
studies
89utcomes8 esearch Ecological studies Audit or outcomes research
:a S !"ith homogeneity#$ of case/
control studies
S !"ith homogeneity#$ of :( and
(etter studies
S !"ith homogeneity#$ of :( and
(etter studies
S !"ith homogeneity#$ of :(
and (etter studies
:( )ndividual %ase/%ontrol Study 2on/consecutive study& or "ithout
consistently applied reference
standards
2on/consecutive cohort study, or
very limited population
Analysis (ased on limited
alternatives or costs, poor 4uality
estimates of data, (ut including
sensitivity analyses incorporating
clinically sensi(le variations5
; %ase/series !and poor 4uality
cohort and case/control
studies11$
%ase/series !and poor 4uality
prognostic cohort studies###$
%ase/control study, poor or non/
independent reference standard
%ase/series or superseded
reference standards
Analysis "ith no sensitivity
analysis
< E7pert opinion "ithout e7plicit
critical appraisal, or (ased on
physiology, (ench research or
8first principles8
E7pert opinion "ithout e7plicit critical
appraisal, or (ased on physiology,
(ench research or 8first principles8
E7pert opinion "ithout e7plicit
critical appraisal, or (ased on
physiology, (ench research or 8first
principles8
E7pert opinion "ithout e7plicit
critical appraisal, or (ased on
physiology, (ench research or 8first
principles8
E7pert opinion "ithout e7plicit
critical appraisal, or (ased on
economic theory 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
E)THE a single result "ith a "ide %onfidence )nterval !such that, for e7ample, an A in an %T is not statistically significant (ut "hose confidence intervals fail to e7clude
clinically important (enefit or harm$
9 a Systematic evie" "ith trou(lesome !and statistically significant$ heterogeneity5
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
1 ?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
11 =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
111 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$
Grades of Recommendation
A consistent level 1 studies
B consistent level 3 or : studies or e7trapolations from level 1 studies
C level ; studies or e7trapolations from level 3 or : studies
D level < evidence or trou(lingly inconsistent or inconclusive studies of any level
"Extrapolations" are where data is used in a situation which has potentially clinically important differences than the original study situation.