GRADE concept 6: a novel application of external indirect evidence into GRADE ratings of evidence certainty in network meta-analysis

Objectives: We describe how consideration of external evidence may play an important role in judging certainty in the process of establishing the certainty of the evidence. Our example is a network meta-analysis (NMA) addressing treatment for Ebola virus disease, which informed a World Health Organization guideline. Study Design and Setting: Through Grading of Recommendations Assessment, Development, and Evaluations (GRADE) project group iterative online, in-person and email discussions, we developed this GRADE concept and obtained approval from the GRADE working group. Using the null as a threshold, we rated our certainty for network estimates in mortality, including consideration of evidence external to the NMA (i.e., did not meet eligibility criteria) and formal logical construction. Results: Based on the existing GRADE guidance, we rated the network estimate for one indirect comparison as low certainty. The formal logical construction that lead us reevaluate the certainty of the ev...