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Appendix Classification of proof levels Grades of suggestions 1++ High-quality meta-analyses,systematic At least one meta-evaluation,systematic evaluate or critiques of randomised controlled trials A randomised managed trial rated as 1++ and or randomised controlled trials with a immediately relevant to the target population;or very low danger of bias A systematic evaluate of randomised controlled 1+ Well-performed meta-analyses,systematic trials or a physique of evidence consisting reviews of randomised managed trials principally of research rated as 1+ immediately or randomised managed trials with a applicable to the goal inhabitants and low threat of bias demonstrating overall consistency of outcomes 1– Meta-analyses,systematic critiques of A body of proof together with studies rated as randomised managed trials or B 2++ immediately relevant to the goal randomised managed trials with a excessive inhabitants,and demonstrating total threat of bias consistency of outcomes;or 2++ High-high quality systematic critiques of case– Extrapolated proof from studies rated as management or cohort studies or high-quality 1++ or 1+ case–control or cohort research with a very low risk of confounding,bias or A body of evidence including studies rated as C probability and a excessive probability that the two+ immediately applicable to the goal inhabitants relationship is causal and demonstrating general consistency of outcomes;or 2+ Well-carried out case–control or cohort research with a low risk of confounding, Extrapolated proof from research rated as bias or chance and a reasonable 2++ likelihood that the relationship is causal Evidence degree three or 4;or D 2 Case–control or cohort studies with a Extrapolated evidence from research rated as 2+ excessive threat of confounding,bias or probability and a significant danger that the relationship is not causal Good follow level three Non-analytical studies,e. 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