Exploring the application of GRADE in formulating WHO public health guidelines: a scoping evidence review

To systematically review the utilisation of the Grading of Recommendations Assessment, Development and Evaluations (GRADE) framework within the context of WHO public health guidelines (PHGs), identifying key features, areas of concentration and potential deficiencies.

From 2007 to February 2024, a comprehensive search of the WHO website was conducted to identify PHGs that have incorporated the GRADE methodology.

The study focused on the PHGs identified through the above search.

Data extraction and analysis were independently conducted by researchers using Microsoft Excel 2019.

For each PHG, key recorded characteristics included publication details, thematic areas, the strength of recommendations, the certainty of evidence, and characteristics of the GRADE downgrading/upgrading domains.

Out of 228 PHGs examined, 9234 (90.55%) outcome indicators used the GRADE rating system, predominantly in the area of sexual and reproductive health (50%). Only 31.62% of the outcomes reported moderate and high certainty in evidence. The main clustering results were dominated by adverse events. Among the 4013 recommendations, 2067 (51.51%) were strong, while 1477 (36.81%) were weak/conditional. It is noteworthy that 46.83% of the strong recommendations were based on low or very low confidence in evidence. Among these strong recommendations, 119 met the criteria of five paradigmatic situations where it was necessary to issue a strong recommendation despite low or very low confidence in the effect estimates. Among the 13 230 instances of downgrading, 41.09% were due to the risk of bias and 35.90% were due to imprecision. Only 0.25% outcomes were upgraded by the magnitude of effect size and 0.03% by dose-response gradient.

The GRADE approach is widely used in the development of PHGs. More than half of the recommendations in PHGs are based on low or very low-quality evidence, primarily due to risks of bias and imprecision. Additionally, strong recommendations based on low-confidence or very low-confidence estimates are frequently made. Therefore, it is necessary to enhance guideline developers' understanding of the GRADE methodology and to further investigate and clarify discordant recommendations in PHGs.