Levels of evidence

The key recommendations and levels of evidence incor­porated in the COPD-X guidelines were originally based largely on the Global Initiative for Chronic Obstructive Lung Disease (GOLD), which used the evidence ranking system of the US National Heart, Lung and Blood Institute (NHLBI) (NHLBI/WHO Workshop Report April 2001). The NHLBI scheme is shown in Box 1. For comparison, the National Health and Medical Research Council (NHMRC) (National Health and Medical Research Council 1998) levels of evidence are also shown, along with the equivalent NHLBI categories.

For this update, the COPD-X Guidelines Committee reclassified NHLBI level A as NHMRC level I and NHLBI level B as NHMRC level II evidence. All citations to NHLBI level C were individually reviewed and reclassified as NHMRC level II, III-2, III-3 or IV evidence. On closer examination, some references originally classified as level C were actually considered level D. As NHLBI level D is not recognised in the NHMRC classification, these levels were removed whilst the bibliographic citations were retained.

Box 1: Levels of evidence
a) National Heart, Lung, and Blood Institute (NHLBI) categories
NHLBI category Sources of evidence Definition

A


Randomised controlled trials (RCTs) extensive body of data


Evidence is from endpoints of well-designed RCTs that provide a consistent pattern of findings in the population for which the recommendation is made. Category A requires substantial numbers of studies involving substantial numbers of participants.

B Randomised controlled trials (RCTs) limited body of data Evidence is from endpoints of intervention studies that include only a limited number of patients, post-hoc or subgroup analysis of RCTs, or meta-analysis of RCTs. In general, category B pertains when few randomised trials exist, they are small in size, they were undertaken in a population that differs from the target population of the recommendation, or the results are somewhat inconsistent.
C Non-randomised trials, observational studies Evidence is from outcomes of uncontrolled or non-randomised trials or from observational studies.
D Panel consensus, judgement The panel consensus is based on clinical experience or knowledge that does not meet the above criteria.



b) National Health and Medical Research Council (NHMRC) Evidence Hierarchy: designations of ‘levels of evidence’ according to type of research question
Level Intervention Diagnostic accuracy Prognosis Aetiology Screening intervention
I A systematic review of level II studies A systematic review of level II studies A systematic review of level II studies A systematic review of level II studies A systematic review of level II studies
II A randomised controlled trial A study of test accuracy with:

an independent, blinded comparison with a valid reference standard, among consecutive persons with a defined clinical presentation

A prospective cohort study A prospective cohort study A randomised controlled trial
III-1 A pseudorandomised controlled trial (i.e. alternate allocation or some other method) A study of test accuracy with:

an independent, blinded comparison with a valid reference standard, among non-consecutive persons with a defined clinical presentation

All or none of the people with the risk factor(s) experience the outcome; and the data arises from an unselected or representative case series which provides an unbiased representation of the prognostic effect All or none of the people with the risk factor(s) experience the outcome; and the data arises from an unselected or representative case series which provides an unbiased representation of the prognostic effect A pseudorandomised controlled trial (i.e. alternate allocation or some other method)
III-2 A comparative study with concurrent controls:

  • Non-randomised, experimental trial
  • Cohort study
  • Case-control study
  • Interrupted timer series with a control group
A comparison with reference standard that does not meet the criteria required for Level II and III-1 evidence Analysis of prognostic factors amongst persons in a single arm of a randomised controlled trial A retrospective cohort study A comparative study with concurrent controls:

  • Non-randomised, experimental trial
  • Cohort study
  • Case-control study
III-3 A comparative study without concurrent controls:

  • Historical control study
  • Two or more single arm study
  • Interrupted time series without a parallel control group
Diagnostic case-control study A retrospective cohort study A case-control study A comparative study without concurrent controls:

  • Historical control study
  • Two or more single arm study

 

IV Case series with either post-test or pre-test/post-test outcomes Study of diagnostic yield (no reference standard) Case series, or cohort study of persons at different stages of disease A cross-sectional study or case series Case series