5.1.3. GRADE and meta-analysis

GRADE relies on the judgment about our confidence in a (beneficial or adverse) effect of an intervention and therefore it is impossible to apply GRADE correctly if a meta-analysis is not at least considered and the necessary judgments are made on (statistical, methodological and clinical) heterogeneity. It is possible that no pooled effect can or should be calculated if there is evidence of heterogeneity, be it clinical, methodological or merely statistical, but meta-analysis should always be attempted. Otherwise, it is impossible to gather sufficient elements to make the necessary GRADE judgments. Note that heterogeneity is in most cases a reason to downgrade the body of evidence, with some exceptions that will be explained later.

In order to apply GRADE (but actually in order to make a sound judgment on evidence in general) it is essential that at least one person implicated in the development of the guideline understands this guidance and is able to apply it.

GRADE remains rather vague about what to do if only one study is available. We recommend to downgrade the evidence with at least one level, except when the single study is a multicentre study where sample size in the individual centres is sufficient to demonstrate heterogeneity if there is any. Any decision not to downgrade must be explained and justified.

If the primary studies do not allow the calculation of a confidence interval, consider downgrading as judging precision and heterogeneitiy becomes difficult. There are some rare exceptions, when the confidence interval is not needed as all studies point clearly in the same direction.  In some cases non-parametric tests are used because the assumption of normality is violated. In these case, the non-parametric measure of uncertainty should be used (most of the time an interquartile range) and interpreted.  Decisions taken around these issues should be justified.