title: Treatment dynamics of newly marketed drugs and implications for comparative effectiveness research.
abstract: OBJECTIVE
  Clinicians and payers require rapid comparative effectiveness (CE) evidence generation to inform decisions for new drugs. We empirically assessed treatment dynamics of newly marked drugs and their implications for conducting CE research.
  
  
  METHODS
  We used claims data to evaluate five drug-outcome pairs: 1) raloxifene (vs. alendronate) and fracture; 2) risedronate (vs. alendronate) and fracture; 3) simvastatin plus ezetimibe fixed-dose combination (simvastatin + ezetimibe) (vs. simvastatin alone) and cardiovascular events; 4) rofecoxib (vs. nonselective nonsteroidal anti-inflammatory drugs [ns-NSAIDs]) and myocardial infarction; and 5) rofecoxib (vs. ns-NSAIDS) and gastrointestinal bleed. We examined utilization dynamics in the early marketing period, including evolving utilization patterns, outcome risk among those treated with new versus established drugs, and prior treatment patterns that may indicate treatment resistance or intolerance. We addressed these challenges by replicating active CE monitoring with sequential matched cohort analysis.
  
  
  RESULTS
  Patients initiating new drugs were more likely to have used other drugs for the same indication in the past, but the majority of patients in all new drug cohorts were treatment naive (82.0% overall). Patients initiating rofecoxib had higher predicted baseline risk of gastrointestinal bleed than did patients initiating ns-NSAIDs. Patients initiating risedronate and alendronate had similar predicted baseline risks of fracture, while those initiating raloxifene and simvastatin + ezetimibe had lower risks of outcomes of interest relative to their comparators. Prospective monitoring yielded results consistent with expectation for each example.
  
  
  CONCLUSIONS
  Many challenges to assessing the CE of new drugs are borne out in empirical data. Attention to these challenges can yield valid CE results.
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.forename: Katsiaryna
authors.initials: K
authors.lastname: Bykov
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Willke
authors.forename: Kristijan H
authors.initials: KH
authors.lastname: Kahler
authors.forename: Prasun
authors.initials: P
authors.lastname: Subedi
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schneeweiss
mesh_terms: D057186:Comparative Effectiveness Research; D016903:Drug Monitoring / Q000706:statistics & numerical data; D057915:Drug Substitution / Q000009:adverse effects*; D004359:Drug Therapy, Combination / Q000009:adverse effects*; D006801:Humans; D007345:Insurance Claim Review; D009515:New Jersey; D010414:Pennsylvania; D055553:Prescription Drugs / Q000009:adverse effects*
chemical_list: D055553:Prescription Drugs
keywords: effectiveness; new drugs; prospective monitoring; validity