title: A Drug Safety Rating System Based on Postmarketing Costs Associated with Adverse Events and Patient Outcomes.
abstract: BACKGROUND
  Given the multiple limitations associated with relatively homogeneous preapproval clinical trials, inadequate data disclosures, slow reaction times from regulatory bodies, and deep-rooted bias against disclosing and publishing negative results, there is an acute need for the development of analytics that reflect drug safety in heterogeneous, real-world populations.
  
  
  OBJECTIVE
  To develop a drug safety statistic that estimates downstream medical costs associated with serious adverse events (AEs) and unfavorable patient outcomes associated with the use of 706 FDA-approved drugs.
  
  
  METHODS
  All primary suspect case reports for each drug were collected from the FDA's Adverse Event Reporting System database (FAERS) from 2010-2014. The Medical Dictionary for Regulatory Activities (MedDRA) was used to code serious AEs and outcomes, which were tallied for each case report. Medical costs associated with AEs and poor patient outcomes were derived from Agency for Healthcare Research and Quality (AHRQ) survey data, and their corresponding ICD-9-CM codes were mapped to MedDRA terms. Nonserious AEs and outcomes were not included. For each case report, either the highest AE cost or, if no eligible AE was listed, the highest outcome cost was used. All costed cases were aggregated for each drug and divided by the number of patients exposed to obtain a downstream estimated direct medical cost burden per exposure. Each drug was assigned a corresponding 1-100 point total.
  
  
  RESULTS
  The 706 drugs showed an exponential distribution of downstream costs, and the data were transformed using the natural log to approximate a normal distribution. The minimum score was 8.29, and the maximum score was 99.25, with a mean of 44.32. Drugs with the highest individual scores tended to be kinase inhibitors, thalidomide analogs, and endothelin receptor antagonists. When scores were analyzed across Established Pharmacologic Class (EPC), the kinase inhibitor and endothelin receptor antagonist classes had the highest total. However, other EPCs with median scores of 75 and above included hepatitis C virus NS3/4A protease inhibitor, recombinant human interferon beta, vascular endothelial growth factor-directed antibody, and tumor necrosis factor blocker. When Anatomical Therapeutic Chemical classifications were analyzed, antineoplastic drugs were outliers with approximately 80% of their individual scores 60 and above, while approximately 20%-30% of blood and anti-infective drugs had scores of 60 and above. Within-drug class results served to differentiate similar drugs. For example, 6 serotonin reuptake inhibitors had a score range of 35 to 53.
  
  
  CONCLUSIONS
  This scoring system is based on estimated direct medical costs associated with postmarketing AEs and poor patient outcomes and thereby helps fill a large information gap regarding drug safety in real-world patient populations.
authors.affiliation: Advera Health Analytics, 3663 N. Laughlin Rd., Ste. 102, Santa Rosa, CA 95403. keith@adverahealth.com.
authors.forename: Keith B
authors.initials: KB
authors.lastname: Hoffman
authors.forename: Mo
authors.initials: M
authors.lastname: Dimbil
authors.forename: Robert F
authors.initials: RF
authors.lastname: Kyle
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Tatonetti
authors.forename: Colin B
authors.initials: CB
authors.lastname: Erdman
authors.forename: Andrea
authors.initials: A
authors.lastname: Demakas
authors.forename: Dingguo
authors.initials: D
authors.lastname: Chen
authors.forename: Brian M
authors.initials: BM
authors.lastname: Overstreet
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000191:economics* / Q000706:statistics & numerical data; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000175:diagnosis / Q000191:economics* / Q000453:epidemiology / Q000628:therapy; D017048:Health Care Costs / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D061214:Patient Safety / Q000191:economics* / Q000706:statistics & numerical data; D004364:Pharmaceutical Preparations / Q000145:classification*; D011358:Product Surveillance, Postmarketing / Q000191:economics* / Q000706:statistics & numerical data; D018570:Risk Assessment; D012307:Risk Factors; D009626:Terminology as Topic; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D004364:Pharmaceutical Preparations