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

Evidence level	Definition	Example of study providing this level of evidence for a therapy question	Guideline statement grade
Ia	A good recent systematic review of studies designed to answer the question of interest	Cochrane systematic review of randomised controlled trials studying the effectiveness of flu vaccines	A+
Ib	One or more rigorous studies designed to answer the question, but not formally combined	Randomised controlled trial of effectiveness of a flu vaccine	A−
II*	One or more prospective clinical studies which illuminate, but do not rigorously answer, the question	Prospective cohort study comparing pneumonia rates in patients who are and are not vaccinated against flu; non-randomised controlled trial	B+
III†	One or more retrospective clinical studies which illuminate but do not rigorously answer the question	Audit or retrospective case control study, comparing flu vaccination history in patients who did and did not present with pneumonia	B−
IVa‡	Formal combination of expert views	Delphi study of UK expert recommendations for flu vaccination	C
IVb	Other information	Expert opinion, informal consensus; in vitro or in vivo studies on related topics	D

*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.