title: The economics of counterfeit Avastin: a geospatial and statistical analysis of demographic correlates to FDA warning letters.
abstract: OBJECTIVE
  In 2012, the Food and Drug Administration (FDA) sent warning notices to clinics and medical practitioners that may have purchased or administered counterfeited versions of the angiogenesis cancer drug Avastin Genentech, South San Francisco, California, USA. The purpose of this study was to explore potential differences in demographic, economic, and healthcare coverage characteristics between areas that received these counterfeit warning notices and those that did not receive notices. The aims of this study are to improve future counterfeit drug surveillance and better assess potential risk factors associated with counterfeit cancer drugs.
  
  
  METHODS
  Addresses for warning notices sent to healthcare practitioners were obtained from the FDA and then geocoded using arcgis. Variables chosen for statistical and geospatial analyses were then identified and assessed based on their potential association with Avastin access and affordability. These variables included demographic and economic factors (percent below the poverty line, percent uninsured, and median household income) and healthcare coverage data (percent Medicare enrollees) available from the US Center for Medicare and Medicaid Services. All variables were analyzed at the US county level.
  
  
  RESULTS
  Our analysis uncovered 401 distinct US counties where the FDA sent at least one counterfeit Avastin warning notice. A hot spot analysis of notices and variables was carried out using arcgis software to identify and visualize risk features with high and low values of clustering. In a multiple logistic regression model reassessing visually observed geospatial associations, the receipt of a notice was not significantly associated with percent uninsured (p = 0.3121), but was significantly associated with percent Medicare enrollees (OR = 0.874 per 10% increase; p = 0.0121), individuals below federal poverty line (OR = 2.990 per 10% increase; p < 0.0001), and median household income (OR = 2.698 per $10 000 increase; p < 0.0001).
  
  
  CONCLUSIONS
  Our study found that county-level economic and demographic factors are potentially associated with counterfeit Avastin warning receipt after controlling for the total number of people residing in each county. These geographic associations indicate that individuals in counties where patients have greater ability to afford more expensive treatment, and consequently where providers can seek higher reimbursement, may have been at higher risk to counterfeit Avastin exposure. These findings can help inform future efforts to improve drug safety surveillance and more proactively identify patients at the highest risk for counterfeit cancer drugs.
authors.affiliation: Joint Doctoral Program in Global Public Health, University of California, San Diego-San Diego State University, La Jolla, CA, USA.|Global Health Policy Institute, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Raphael E
authors.initials: RE
authors.lastname: Cuomo
authors.affiliation: Global Health Policy Institute, University of California, San Diego, La Jolla, CA, USA.|Department of Anesthesiology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Tim K
authors.initials: TK
authors.lastname: Mackey
authors.affiliation: School of Public Health, San Antonio Regional Campus, The University of Texas, Houston, TX, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Stigler
mesh_terms: D020533:Angiogenesis Inhibitors / Q000191:economics* / Q000600:supply & distribution; D000068258:Bevacizumab / Q000191:economics*; D058110:Counterfeit Drugs / Q000191:economics* / Q000600:supply & distribution; D003710:Demography; D004335:Drug and Narcotic Control / Q000331:legislation & jurisprudence*; D062305:Geographic Mapping; D007349:Insurance, Health, Reimbursement / Q000706:statistics & numerical data; D007356:Insurance, Pharmaceutical Services / Q000706:statistics & numerical data; D015999:Multivariate Analysis; D012044:Regression Analysis; D012959:Socioeconomic Factors; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D020533:Angiogenesis Inhibitors; D058110:Counterfeit Drugs; D000068258:Bevacizumab
keywords: Avastin; counterfeit medicine; geospatial analysis; health economics; pharmacoepidemiology