title: A systematic review of immune-related adverse event reporting in clinical trials of immune checkpoint inhibitors.
abstract: BACKGROUND
  There are limited data about the quality of immune-related adverse event (irAE) reporting in immune checkpoint inhibitor (ICI) clinical trial publications.
  
  
  METHODS
  A systematic search of citations from Medline, EMBASE and Cochrane databases identified prospective clinical trials involving ICIs in advanced solid tumors from 2003 to 2013. A 21-point quality score (QS) was adapted from the CONSORT harms extension statement. Linear regression was used to identify factors associated with quality reporting.
  
  
  RESULTS
  After a review of 2628 articles, 50 trial reports were included, with ICIs as either monotherapy (54%) or part of a combination regimen (46%). The mean QS was 11.21 points (range 3.50-17.50 points). The median grade 3/4 AE rate reported was 21% (range 0%-66%) and 29/50 (58%) trials concluded that irAEs were tolerable. Multivariate regression analysis revealed that year of publication (within last 5 years, P = 0.01) and journal impact factor >15 (P = 0.004) were associated with higher QS. Complete reporting of specific characteristics of irAEs including onset, management and reversibility were reported by 14%, 8% and 6% of studies, respectively. The incidence of grade 3/4 adverse events was higher for inhibitors against CTLA-4 compared with other immune checkpoints (P < 0.001).
  
  
  CONCLUSIONS
  The reporting of irAEs is suboptimal. A standardized reporting method of irAEs that accounts for tolerability, management and reversibility is needed and would enable a more precise evaluation of the therapeutic risk benefit ratio of ICIs.
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre-University Health Network, Toronto; Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: T W
authors.initials: TW
authors.lastname: Chen
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre-University Health Network, Toronto; Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: A R
authors.initials: AR
authors.lastname: Razak
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre-University Health Network, Toronto; Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: P L
authors.initials: PL
authors.lastname: Bedard
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre-University Health Network, Toronto; Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: L L
authors.initials: LL
authors.lastname: Siu
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre-University Health Network, Toronto; Department of Medicine, University of Toronto, Toronto, Canada. Electronic address: aaron.hansen@uhn.ca.
authors.forename: A R
authors.initials: AR
authors.lastname: Hansen
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D002986:Clinical Trials as Topic / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects*; D009369:Neoplasms / Q000188:drug therapy*; D011786:Quality Control
keywords: adverse event; immune checkpoint inhibitors; quality control; systematic review