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Defining certainty of net benefit: a GRADE concept paper
  1. Brian S Alper1,2,
  2. Peter Oettgen1,3,
  3. Ilkka Kunnamo4,5,
  4. Alfonso Iorio6,
  5. Mohammed Toseef Ansari7,
  6. M Hassan Murad8,
  7. Joerg J Meerpohl9,10,
  8. Amir Qaseem11,
  9. Monica Hultcrantz12,13,
  10. Holger J Schünemann14,
  11. Gordon Guyatt14
  12. on behalf of The GRADE Working Group
  1. 1 EBSCO Health, DynaMed Plus, EBSCO Information Services Inc., Ipswich, Massachusetts, USA
  2. 2 Department of Family and Community Medicine, University of Missouri-Columbia School of Medicine, Columbia, Missouri, USA
  3. 3 Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
  4. 4 Duodecim Medical Publications Ltd., Helsinki, Finland
  5. 5 The Finnish Medical Society, Helsinki, Finland
  6. 6 Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
  7. 7 School of Epidemiology, Public Health and Preventive Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
  8. 8 Evidence-Based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
  9. 9 Institute for Evidence in Medicine, Medical Center - University of Freiburg, Freiburg, Germany
  10. 10 Cochrane Germany, Cochrane Germany Foundation, Freiburg, Germany
  11. 11 Department of Clinical Policy, American College of Physicians, Philadelphia, Pennsylvania, USA
  12. 12 Karolinska Institute, Stockholm, Sweden
  13. 13 Statens beredning for medicinsk utvardering, Stockholm, Sweden
  14. 14 Departments of Health Research Methods, Evidence, and Impact and of Medicine, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada
  1. Correspondence to Dr Brian S Alper; balper{at}


Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology is used to assess and report certainty of evidence and strength of recommendations. This GRADE concept article is not GRADE guidance but introduces certainty of net benefit, defined as the certainty that the balance between desirable and undesirable health effects is favourable. Determining certainty of net benefit requires considering certainty of effect estimates, the expected importance of outcomes and variability in importance, and the interaction of these concepts. Certainty of net harm is the certainty that the net effect is unfavourable. Guideline panels using or testing this approach might limit strong recommendations to actions with a high certainty of net benefit or against actions with a moderate or high certainty of net harm. Recommendations may differ in direction or strength from that suggested by the certainty of net benefit or harm when influenced by cost, equity, acceptability or feasibility.

  • evidence-based medicine
  • decision analysis
  • evidence synthesis
  • clinical decision making
  • guideline development

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  • Contributors At a GRADE Working Group (GWG) meeting, GG and MH presented a complex method to rate the certainty of evidence for an outcome when fully contextualised with respect to other outcomes related to a decision or recommendation. HJS had introduced the concept of rating certainty in a range of effects based on all GRADE domains. BSA introduced the concept of certainty of net benefit to clarify and simplify methodology to report and assess the balance of benefits and harms in the context of fully contextualising certainty of evidence across outcomes. The GWG formed a subcommittee for this conceptual development. BSA and Lehana Thabane developed the statistical model for a simple decision analysis and sensitivity analysis. BSA, IK, AI and Lehana Thabane provided examples to demonstrate the model (Appendix). The GWG had in-person meetings in three countries (with up to 100 people in attendance) in which the wider audience provided in-depth review, feedback and discussion to refine the concepts. BSA, PO, IK, AI, MTA, MHM, JJM, AQ, MH, HJS and GG met frequently to iteratively refine the concepts, meet the authorship requirements and approve the final version. BSA is the guarantor of the article.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests All authors are members of the GRADE Working Group and conduct scholarly activity or professional services related to the concepts in this article. BSA and PO are employed by EBSCO Information Services and IK is employed by Duodecim Medical Publications Ltd.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data available.

  • Patient consent for publication Not required.

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