• Benjamin Djulbegovic, Tea Reljic, Shira Elqayam, Adam Cuker, Iztok Hozo, Qi Zhou, Shelly-Anne Li, Paul Alexander, Robby Nieuwlaat, Wojtek Wiercioch, Holger Schünemann, and Gordon Guyatt.
• Department of Supportive Care Medicine, City of Hope, 1500 East Duarte Rd, Duarte, CA, USA; Department of Hematology, City of Hope, 1500 East Duarte Rd, Duarte, CA, USA. Electronic address: bdjulbegovic@coh.org.
• J Clin Epidemiol. 2019 Jun 1; 110: 23-33.

Background And ObjectivesThe determinants of guideline panels' recommendations remain uncertain. The objective of this study was to investigate factors considered by members of 8 panels convened by the American Society of Hematology (ASH) to develop guidelines using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.Study Design And SettingWeb-based survey of the participants in the ASH guidelines panels.Analysistwo-level hierarchical, random-effect, multivariable regression analysis to explore the relation between GRADE and non-GRADE factors and strength of recommendations (SOR).ResultsIn the primary analysis, certainty in evidence [OR = 1.83; (95CI% 1.45-2.31)], balance of benefits and harms [OR = 1.49 (95CI% 1.30-1.69)] and variability in patients' values and preferences [OR = 1.47 (95CI% 1.15-1.88)] proved the strongest predictors of SOR. In a secondary analysis, certainty of evidence was associated with a strong recommendation [OR = 3.60 (95% CI 2.16-6.00)] when panel members recommended "for" interventions but not when they made recommendations "against" interventions [OR = 0.98 (95%CI: 0.57-1.8)] consistent with "yes" bias. Agreement between individual members and the group in rating SOR varied (kappa ranged from -0.01 to 0.64).ConclusionGRADE's conceptual framework proved, in general, to be highly associated with SOR. Failure of certainty of evidence to be associated with SOR against an intervention, suggest the need for improvements in the process.Copyright © 2019 Elsevier Inc. All rights reserved.

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