title: Prospective Benefit-Risk Monitoring of New Drugs for Rapid Assessment of Net Favorability in Electronic Health Care Data.
abstract: BACKGROUND
  Benefit-risk assessment (BRA) methods can combine measures of benefits and risks into a single value.
  
  
  OBJECTIVE
  To examine BRA metrics for prospective monitoring of new drugs in electronic health care data.
  
  
  METHODS
  Using two electronic health care databases, we emulated prospective monitoring of three drugs (rofecoxib vs. nonselective nonsteroidal anti-inflammatory drugs, prasugrel vs. clopidogrel, and denosumab vs. bisphosphonates) using a sequential propensity score-matched cohort design. We applied four BRA metrics: number needed to treat and number needed to harm; incremental net benefit (INB) with maximum acceptable risk; INB with relative-value-adjusted life-years; and INB with quality-adjusted life-years (QALYs). We determined whether and when the bootstrapped 99% confidence interval (CI) for each metric excluded zero, indicating net favorability of one drug over the other.
  
  
  RESULTS
  For rofecoxib, all four metrics yielded a negative value, suggesting net favorability of nonselective nonsteroidal anti-inflammatory drugs over rofecoxib, and the 99% CI for all but the number needed to treat and number needed to harm excluded the null during follow-up. For prasugrel, only the 99% CI for INB-QALY excluded the null, but trends in values over time were similar across the four metrics, suggesting overall net favorability of prasugrel versus clopidogrel. The 99% CI for INB-relative-value-adjusted life-years and INB-QALY excluded the null in the denosumab example, suggesting net favorability of denosumab over bisphosphonates.
  
  
  CONCLUSIONS
  Prospective benefit-risk monitoring can be used to determine net favorability of a new drug in electronic health care data. In three examples, existing BRA metrics produced qualitatively similar results but differed with respect to alert generation.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: jgagne1@partners.org.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Gagne
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Katsiaryna
authors.initials: K
authors.lastname: Bykov
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Najafzadeh
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Niteesh K
authors.initials: NK
authors.lastname: Choudhry
authors.affiliation: University of Washington, Department of Health Services Research, Seattle, WA, USA.
authors.forename: Diane P
authors.initials: DP
authors.lastname: Martin
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Kristijan H
authors.initials: KH
authors.lastname: Kahler
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Rogers
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schneeweiss
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077144:Clopidogrel; D000069448:Denosumab / Q000627:therapeutic use; D006801:Humans; D007256:Information Systems / Q000706:statistics & numerical data*; D007783:Lactones / Q000627:therapeutic use; D000068799:Prasugrel Hydrochloride / Q000627:therapeutic use; D011358:Product Surveillance, Postmarketing / Q000379:methods*; D011446:Prospective Studies; D019057:Quality-Adjusted Life Years; D018570:Risk Assessment; D013450:Sulfones / Q000627:therapeutic use; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D050071:Bone Density Conservation Agents; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D000069448:Denosumab; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: benefit risk assessment; new drugs; prospective monitoring