title: A number of factors explain why WHO guideline developers make strong recommendations inconsistent with GRADE guidance.
abstract: OBJECTIVE
  Many strong recommendations issued by the World Health Organization (WHO) are based on low- or very low-quality (low certainty) evidence (discordant recommendations). Many such discordant recommendations are inconsistent with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance. We sought to understand why WHO makes discordant recommendations inconsistent with GRADE guidance.
  
  
  METHODS
  We interviewed panel members involved in guidelines approved by WHO (2007-2012) that included discordant recommendations. Interviews, recorded and transcribed, focused on use of GRADE including the reasoning underlying, and factors contributing to, discordant recommendations.
  
  
  RESULTS
  Four themes emerged: strengths of GRADE, challenges and barriers to GRADE, strategies to improve GRADE application, and explanations for discordant recommendations. Reasons for discordant recommendations included skepticism about the value of making conditional recommendations; political considerations; high certainty in benefits (sometimes warranted, sometimes not) despite assessing evidence as low certainty; and concerns that conditional recommendations will be ignored.
  
  
  CONCLUSIONS
  WHO panelists make discordant recommendations inconsistent with GRADE guidance for reasons that include limitations in their understanding of GRADE. Ensuring optimal application of GRADE at WHO and elsewhere likely requires selecting panelists who have a commitment to GRADE principles, additional training of panelists, and formal processes to maximize adherence to GRADE principles.
authors.affiliation: Health Research Methods (HRM), Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. Electronic address: elias98_99@yahoo.com.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Alexander
authors.affiliation: Mayo Graduate School, Mayo Clinic, Plummer 3-35, 200 First Street SW, Rochester, MN 55905, USA; Knowledge and Evaluation Research Unit, Mayo Clinic, Plummer 3-35, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Gionfriddo
authors.affiliation: Health Research Methods (HRM), Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Shelly-Anne
authors.initials: SA
authors.lastname: Li
authors.affiliation: Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales 2006, Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bero
authors.affiliation: Division of Nutritional Sciences, Cornell University, 120 Savage Hall, Ithaca, NY 14853, USA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Stoltzfus
authors.affiliation: Health Research Methods (HRM), Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, Hamilton, Ontario L8N 3Z5, Canada; Department of Internal Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Neumann
authors.affiliation: Knowledge and Evaluation Research Unit, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Plummer 3-35, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Brito
authors.affiliation: H Lee Moffitt Cancer Center, University of South Florida, FL, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Djulbegovic
authors.affiliation: Knowledge and Evaluation Research Unit, Division of Endocrinology and Diabetes, Mayo Clinic, Plummer 4-402, 200 First Street SW, Rochester, MN 55905, USA; Knowledge and Evaluation Research Unit, Health Care Policy and Research, Mayo Clinic, Plummer 4-402, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
authors.affiliation: World Health Organization, Av. Appia 20, CH-1211, Geneva 27, Switzerland.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Norris
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University Health Sciences Centre, Room 2C16, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Holger J
authors.initials: HJ
authors.lastname: Schünemann
authors.affiliation: Biostatistics Unit, Centre for Evaluation of Medicine, Department of Clinical Epidemiology & Biostatistics, PHRI, Hamilton Health Sciences, McMaster University, St. Joseph's Healthcare Hamilton, 3rd Floor, Martha Wing, Room H-325, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.
authors.forename: Lehana
authors.initials: L
authors.lastname: Thabane
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University Health Sciences Centre, Room 2C12, 1200 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Guyatt
mesh_terms: D019317:Evidence-Based Medicine; D019983:Guideline Adherence; D006801:Humans; D017410:Practice Guidelines as Topic / Q000592:standards*; D014944:World Health Organization
keywords: Discordant recommendations; GRADE methods; Inconsistent with GRADE guidance; Interviews; Qualitative descriptive study; Strong recommendations low-quality evidence; World Health Organization