5.1.1. Four levels of evidence

Randomized trials start as high-quality evidence, observational studies as low quality (see table). ‘‘Quality’’ as used in GRADE means more than risk of bias and may also be compromised by imprecision, inconsistency, indirectness of study results, and publication bias. In addition, several factors can increase our confidence in an estimate of effect. This general approach is summarized in the table below.

In the following chapters these factors will be discussed in depth. However, it is important to emphasize again that GRADE warns against applying this upgrading and downgrading in a too mechanistic way and to leave room for judgment.

Although GRADE suggests the initial separate consideration of five categories for rating down the quality of evidence and three categories for rating up, with a yes/no decision in each case, the final rating of overall evidence quality occurs in a continuum of confidence in the validity, precision, consistency, and applicability of the estimates. Fundamentally, the assessment of evidence quality remains a subjective process, and GRADE should not be seen as obviating the need for or minimizing the importance of judgment. As repeatedly stressed, the use of GRADE will not guarantee consistency in assessment, whether it is of the quality of evidence or of the strength of recommendation. There will be cases in which competent reviewers will have honest and legitimate disagreement about the interpretation of evidence. In such cases, the merit of GRADE is that it provides a framework that guides one through the critical components of this assessment and an approach to analysis and communication that encourages transparency and an explicit accounting of the judgments involved.