Thursday, July 30, 2020

Research Revisited: "Quality of Evidence is a Key Determinant for Making a Strong GRADE Guidelines Recommendation" (2015)

This month in 2015, Djulbegovic and colleagues published a paper that examined the impact of quality of evidence, balance between benefits and harms, patient values and preferences, and resource use (the four GRADE factors) on the strength of resulting clinical recommendations.

The four major GRADE factors that drive clinical recommendations 






















The authors circulated a survey among 18 members of a guideline panel of the American Association of Blood Banking (AABB) who had recently convened to develop guidelines for the use of prophylactic versus therapeutic platelet transfusion in patients with thrombocytopenia. Using the panel members’ assessments of the GRADE factors with regards to the evidence that had been presented and their resulting recommendations for strong or weak recommendations, a logistic regression was conducted in order to examine the relative impact of each of the four GRADE factors.

The guideline panel had reviewed the evidence for ten key questions. Overall, the consistency of judgments across panel members was good (Cronbach’s alpha = 0.86). Those questions with a high quality of evidence were 4.5 times more likely to result in a strong recommendation (p < 0001), whereas none of the three remaining GRADE factors were significantly associated with the strength of the resulting recommendations. Moreover, the model suggested that in cases where the quality of evidence was high, there was a 90% chance of the resulting recommendation being strong; when the quality of evidence was very low, this chance dropped to 10%.

The figure from Djulbegovic shows the associations between increasing quality of evidence and strength of resulting recommendations

The authors concluded that the quality of evidence was far and away the most important contributing factor to the resulting strength of recommendations, at least within the studied guideline panel. However, it’s important to note that patient values and preferences, the balance between benefits and harms, and issues of resource use should all be involved in the process of moving from evidence to decisions, but the relative nebulousness around these considerations and a lack of determined structures for eliciting the data they require (such as the use of a patient panel or survey) likely make them less impactful on the overall strength of recommendation. 

The Evidence-to-Decision framework, which makes these additional considerations more explicit in the formulation of recommendations, was introduced just a year later. It’s worth wondering whether the relative impact of the remaining three GRADE factors has changed since the introduction and adoption of this framework – perhaps presenting an opportunity to revisit this research.

Djulbegovic, B., Kumar, A., Kaufman, R.M., Tobian, A., and Guyatt, G.H. Quality of evidence is a key determinant for making a strong GRADE guidelines recommendation. J Clin Epidemiol 68(7): 727-732. 

Manuscript is available at the publisher's website here.