Studies of therapy
Level	Risk of bias	Study design	Criteria
I	Low risk Study adheres to commonly held tenets of high quality design, execution and avoidance of bias	Good quality RCT	• Random sequence generation • Allocation concealment • Intent-to-treat analysis • Blind or independent assessment for important outcomes • Co-interventions applied equally • F/U rate of 80%+ • Adequate sample size
II	Moderately low risk Study has potential for some bias; study does not meet all criteria for level I, but deficiencies not likely to invalidate results or introduce significant bias	Moderate or poor quality RCT Good quality cohort	• Violation of one of the criteria for good quality RCT • Blind or independent assessment in a prospective study, or use of reliable dataa in a retrospective study • Co-interventions applied equally • F/U rate of 80%+ • Adequate sample size • Controlling for possible confoundingb
III	Moderately high risk Study has significant flaws in design and/or execution that increase potential for bias that may invalidate study results	Moderate or poor quality cohort Case-control	• Violation of any of the criteria for good quality cohort • Any case-control design
IV	High risk Study has significant potential for bias; lack of comparison group precludes direct assessment of important outcomes	Case series	• Any case series design

^aOutcome assessment is independent of healthcare personnel judgment. Reliable data are data such as mortality or re-operation.

^bAuthors must provide a description of robust baseline characteristics, and control for those that are unequally distributed between treatment groups.