title: Acting on black box warnings requires a GRADE evidence table and an implementation guide: the case of teriparatide.
abstract: OBJECTIVE
  To assess how well do the black box warnings present and communicate evidence in a way that is consistent with evidence-based patient-centered practice, through evaluating the boxed warning on teriparatide-induced osteosarcoma.
  
  
  METHODS
  We critically appraised teriparatide black box warning for osteosarcoma by reviewing human and animal studies that were used as basis for the warning. We also evaluated the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation framework.
  
  
  RESULTS
  We found that this warning was based on very low-quality evidence that was derived primarily from animal studies. The quality of evidence was rated down because of high risk of bias in addition to inconsistency, indirectness, and imprecision of the estimates. The warning does not provide sufficient guidance for practice like an implementation tool or an evidence profile to clarify the limitations of the evidence.
  
  
  CONCLUSIONS
  Black box warning for teriparatide-associated osteosarcoma does not explicitly present the quality of evidence, and therefore, it could be of limited use in evidence-based practice. We propose that black box warnings should include an evidence profile and an implementation guide to be more useful in evidence-based patient-centered practice.
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Knowledge and Evaluation Research Unit, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Tarig
authors.initials: T
authors.lastname: Elraiyah
authors.affiliation: Knowledge and Evaluation Research Unit, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Mayo Graduate School, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Gionfriddo
authors.affiliation: Knowledge and Evaluation Research Unit, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Center for the Science of Healthcare Delivery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Electronic address: Murad.mohammad@mayo.edu.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Murad
mesh_terms: D000818:Animals; D004348:Drug Labeling; D019317:Evidence-Based Medicine; D006284:Health Plan Implementation / Q000379:methods; D006801:Humans; D012516:Osteosarcoma / Q000139:chemically induced* / Q000517:prevention & control*; D051381:Rats; D018570:Risk Assessment; D019379:Teriparatide / Q000009:adverse effects*; D014481:United States
chemical_list: D019379:Teriparatide
keywords: Black box warning; Evidence-based practice; GRADE; Implementation; Osteosarcoma; Quality of evidence; Teriparatide