A Critical Examination of the FDA’s Efforts to Preempt Failure-to-Warn Claims

This article explores the legality and wisdom of the FDA’s effort to persuade courts to find most failure-to-warn claims preempted. The article first analyzes the FDA’s justifications for reversing its long-held views to the contrary and explains why the FDA’s position cannot be reconciled with its governing statute. The article then examines why the FDA’s position, if ultimately adopted by the courts, would undermine the incentives drug manufacturers have to change labeling to respond to newly-discovered risks. The background possibility of failure-to-warn litigation provides important incentives for drug companies to ensure that drug labels reflect accurate and up-to-date safety information. The article next explains why the agency’s view that it is capable of singlehandedly regulating the safety of drugs is unrealistic. The agency does not have the resources to perform the Herculean task of monitoring the performance of every drug on the market. Both the Institute of Medicine and the Government Accountability Office have explained the shortcomings in the FDA’s recent performance, and they express doubt that the FDA is in capable of facing an increasingly challenging future. The article then explains how state damages litigation helps uncover and assess risks that are not apparent to the agency during a drug’s approval process, and why this “feedback loop” enables the agency to better do its job. FDA approval of drugs is based on clinical trials that involve, at most, a few thousand patients and last a year or so. These trials cannot detect risks that are relatively rare, affect vulnerable sub-populations, or have long latency periods. For this reason, most serious adverse effects do not become evident until a drug is used in larger population groups for periods in excess of one year. Time and again, failure-to-warn litigation has brought to light information that would not otherwise be available to the FDA, to doctors, to other health care providers, and to consumers. And failure-to-warn litigation often has preceded and clearly influenced FDA decisions to modify labeling, and, at times, to withdraw drugs from the market

Cell response to RGD density in cross-linked artificial extracellular matrix protein films

This study examines the adhesion, spreading, and migration of human umbilical vein endothelial cells on cross-linked films of artificial extracellular matrix (aECM) proteins. The aECM proteins described here were designed for application in small-diameter grafts and are composed of elastin-like structural repeats and fibronectin cell-binding domains. aECM-RGD contains the RGD sequence derived from fibronectin; the negative control protein aECM-RDG contains a scrambled cell-binding domain. The covalent attachment of poly(ethylene glycol) (PEG) to aECM substrates reduced nonspecific cell adhesion to aECM-RDG-PEG but did not preclude sequence-specific adhesion of endothelial cells to aECM-RGD-PEG. Variation in ligand density was accomplished by the mixing of aECM-RGD-PEG and aECM-RDG-PEG prior to cross-linking. Increasing the density of RGD domains in cross-linked films resulted in more robust cell adhesion and spreading but did not affect cell migration speed. Control of cell-binding domain density in aECM proteins can thus be used to modulate cell adhesion and spreading and will serve as an important design tool as these materials are further developed for use in surgery, tissue engineering, and regenerative medicine

Quantifying the Morphologies and Dynamical Evolution of Galaxy Clusters. I. The Method

We describe and test a method to quantitatively classify clusters of galaxies according to their projected morphologies. This method will be subsequently used to place constraints on cosmological parameters ($\Omega$ and the power spectrum of primordial fluctuations on scales at or slightly smaller than that of clusters) and to test theories of cluster formation. We specifically address structure that is easily discernible in projection and dynamically important to the cluster. The method is derived from the two-dimensional multipole expansion of the projected gravitational potential and yields dimensionless {\it power ratios} as morphological statistics. If the projected mass profile is used to characterize the cluster morphology, the power ratios are directly related to the cluster potential. However, since detailed mass profiles currently exist for only a few clusters, we use the X-ray--emitting gas as an alternative tracer of cluster morphology. In this case, the relation of the power ratios to the potential is qualitatively preserved. We demonstrate the feasibility of the method by analyzing simulated observations of simple models of X-ray clusters using the instrument parameters of the ROSAT PSPC. For illustrative purposes, we apply the method to ROSAT PSPC images of A85, A514, A1750, and A2029. These clusters, which differ substantially in their X-ray morphologies, are easily distinguished by their respective power ratios. We discuss the suitability of this method to address the connection between cluster morphology and cosmology and to assess whether an individual cluster is sufficiently relaxed for analysis of its intrinsic shape using hydrostatic methods. Approximately 50 X-ray observations of Abell clusters with the PSPC will be amenable to morphological analysis using the method of this paper.Comment: To appear in ApJ October 20, 1995. 29 pages (7 figures missing), PostScrip