title: Phenylpropanolamine and hemorrhagic stroke in the Hemorrhagic Stroke Project: a reappraisal in the context of science, the Food and Drug Administration, and the law.
abstract: The report of the Hemorrhagic Stroke Project (HSP), a case-control study of phenylpropanolamine (PPA) was the primary reason that the US Food and Drug Administration (FDA) requested that PPA-containing products voluntarily be withdrawn from the market. In subsequent litigation, scientific information emerged that was not available during the deliberations of the FDA and its advisory committee. Our reappraisal leads us to conclude that chance, bias, and confounding are plausible alternative explanations for the observed findings. Thus, we believe that it is not possible to conclude that there is any valid statistical association between PPA and hemorrhagic stroke, let alone make any judgment of causality. Our reappraisal suggests the FDA's regulatory request may have been premature.
authors.affiliation: Southwestern University School of Law, Los Angeles, CA 90005, USA. bstier@swlaw.edu
authors.forename: Byron G
authors.initials: BG
authors.lastname: Stier
authors.forename: Charles H
authors.initials: CH
authors.lastname: Hennekens
mesh_terms: D000293:Adolescent; D000328:Adult; D015982:Bias; D015986:Confounding Factors, Epidemiologic; D003627:Data Interpretation, Statistical; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D005260:Female; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D014663:Nasal Decongestants / Q000009:adverse effects*; D010665:Phenylpropanolamine / Q000009:adverse effects*; D011358:Product Surveillance, Postmarketing; D020521:Stroke / Q000139:chemically induced*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D014663:Nasal Decongestants; D010665:Phenylpropanolamine