Appendix 4 Generic levels of evidence and guideline statement grades, appropriate across all types of clinical questions

Evidence levelDefinitionExample of study providing this level of evidence for a therapy questionGuideline statement grade
IaA good recent systematic review of studies designed to answer the question of interestCochrane systematic review of randomised controlled trials studying the effectiveness of flu vaccinesA+
IbOne or more rigorous studies designed to answer the question, but not formally combinedRandomised controlled trial of effectiveness of a flu vaccineA−
II*One or more prospective clinical studies which illuminate, but do not rigorously answer, the questionProspective cohort study comparing pneumonia rates in patients who are and are not vaccinated against flu; non-randomised controlled trialB+
III†One or more retrospective clinical studies which illuminate but do not rigorously answer the questionAudit or retrospective case control study, comparing flu vaccination history in patients who did and did not present with pneumoniaB−
IVa‡Formal combination of expert viewsDelphi study of UK expert recommendations for flu vaccinationC
IVbOther informationExpert opinion, informal consensus; in vitro or in vivo studies on related topicsD
  • *Hard to differentiate Agency for Health Care Policy and Research’s “well designed controlled study without randomisation” (level IIa) from “other type of well-designed experimental study” (level IIb).

  • †Major criterion is retrospective versus prospective data collection, since non-experimental designs are better suited than even randomised clinical trials for answering certain questions.

  • ‡Distinguish formal consensus from informal consensus methods according to the Health Technology Assessment 1998 systematic review.