Deterring Inefficient Pharmaceutical Litigation: An Economic Rationale for the FDA Regulatory Compliance Defense

This Article examines the interaction between direct regulation of pharmaceuticals under the Federal Food Drug and Cosmetic Act (FDCA) and the indirect regulation of pharmaceuticals provided by common law tort incentives. The Article concludes that tort liability is generally inappropriate in cases where manufacturers have complied with the FDCA. The Article begins with a description of the FDCA's operation, and provides an overview of the Food and Drug Administration's (FDA) role in the drug approval process and drug labeling. This overview will demonstrate the need for centralized control over drug labeling. Moreover, we will provide an explanation of the costs and benefits of the drug approval process. Next, we will focus on the regulatory effects of tort law from an economics perspective. The role of tort law in deterring inefficient accidents depends on the extent and stringency of government regulation. We will examine the sufficiency of regulatory deterrence under various regulatory schemes, including the FDCA. This economic analysis will demonstrate that tort law's applicability should be limited to those regulatory schemes that inadequately deter risks. Since the FDCA adequately deters risk, the proper role for tort law should be to provide incentives for ensuring regulatory compliance. We then provide a critical review of the legal rules applied to pharmaceutical litigation in American courts. The uncertainty present in current pharmaceutical litigation stems largely from the failure to adopt regulatory compliance in a strict liability world.Examination of labeling litigation suggests that courts have yet to establish meaningful standards. In addition, design defect litigation, by protecting only those drugs without side-effects, leads to untoward consequences. Furthermore, the tort system has a propensity for error. Our current litigation system generates perverse incentives, which we document. Finally, we conclude that because of the strict nature of the FDCA, the role of tort liability should be limited through federal legislation

Biodegradation of alkyl branched aromatic alkanoic naphthenic acids by Pseudomonas putida KT2440

The majority of the world's crude oil reserves consist of highly biodegraded heavy and super heavy crude oils and oil sands that have not yet been fully exploited. These vast resources contain complex mixtures of carboxylic acids known as naphthenic acids (NAs). NAs cause major environmental and economic problems, as they are recalcitrant, corrosive and toxic. Although aromatic acids make up a small proportion of most NA mixtures, they have demonstrable toxicities to some organisms (e.g. some bacteria and algae) and ideally need to be removed or reduced by remediation. The present study analysed the ability of Pseudomonas putida KT2440 to degrade highly recalcitrant aromatic acids, as exemplified by the alkyl phenylalkanoic acid (4'-t-butylphenyl)-4-butanoic acid (t-BPBA) and the more degradable (4'-n-butylphenyl)-4-butanoic acid (n-BPBA). n-BPBA was completely metabolized after 14 days, with the production of a persistent metabolite identified as (4'-n-butylphenyl)ethanoic acid (BPEA) which resulted from removal of two carbon atoms from the carboxyl side chain (beta-oxidation) as observed previously with a mixed consortium. However, when n-BPBA concentration was increased two-fold, degradation decreased by 56% with a concomitant six-fold decrease in cell numbers, suggesting that at greater concentrations, n-BPBA may be toxic to P. putida KT2440. In contrast, P. putida KT2440 was unable to degrade the highly recalcitrant t-BPBA even after 49 days. These findings have implications for NA bioremediation in the environment. © 2011

The effect of oil sands process-affected water and model naphthenic acids on photosynthesis and growth in Emiliania huxleyi and Chlorella vulgaris

Naphthenic acids (NAs) are among the most toxic organic pollutants present in oil sands process waters (OSPW) and enter marine and freshwater environments through natural and anthropogenic sources. We investigated the effects of the acid extractable organic (AEO) fraction of OSPW and individual surrogate NAs, on maximum photosynthetic efficiency of photosystem II (PSII) (FV/FM) and cell growth in Emiliania huxleyi and Chlorella vulgaris as representative marine and freshwater phytoplankton. Whilst FV/FM in E. huxleyi and C. vulgaris was not inhibited by AEO, exposure to two surrogate NAs: (4'-n-butylphenyl)-4-butanoic acid (n-BPBA) and (4'-tert-butylphenyl)-4-butanoic acid (tert-BPBA), caused complete inhibition of FV/FM in E. huxleyi (≥10 mg L-1 n-BPBA; ≥50 mg L-1 tert-BPBA) but not in C. vulgaris. Growth rates and cell abundances in E. huxleyi were also reduced when exposed to ≥10 mg L-1 n- and tert-BPBA; however, higher concentrations of n- and tert-BPBA (100 mg L-1) were required to reduce cell growth in C. vulgaris. AEO at ≥10 mg L-1 stimulated E. huxleyi growth rate (p ≤ 0.002), yet had no apparent effect on C. vulgaris. In conclusion, E. huxleyi was generally more sensitive to NAs than C. vulgaris. This report provides a better understanding of the physiological responses of phytoplankton to NAs which will enable improved monitoring of NA pollution in aquatic ecosystems in the future

Abrupt climate changes for Iceland during the last millennium: evidence from high resolution sea ice reconstructions

International audienceA high resolution account of Icelandic sea ice over the last millennium has been constructed using a novel proxy based on the presence in sediments of a biomarker (IP25) produced by sea ice algae. Comparison with historical sea ice records demonstrates a strong correlation between documented sea ice occurrences and the IP25 proxy. An excellent agreement is also observed between the IP25 record and a diatom-based sea surface temperature reconstruction obtained from the same core and the Crowley and Lowery Northern Hemisphere temperature reconstruction. Using this approach, we provide new historical sea ice data for periods where records are scarce or absent and evidence for abrupt changes to sea ice and/or climate conditions around Iceland during the Little Ice Age

Emergence of Epizootic Ulcerative Syndrome in Native Fish of the Murray-Darling River System, Australia: Hosts, Distribution and Possible Vectors

Epizootic ulcerative syndrome (EUS) is a fish disease of international significance and reportable to the Office International des Epizootics. In June 2010, bony herring Nematalosa erebi, golden perch Macquaria ambigua, Murray cod Maccullochella peelii and spangled perch Leiopotherapon unicolor with severe ulcers were sampled from the Murray-Darling River System (MDRS) between Bourke and Brewarrina, New South Wales Australia. Histopathology and polymerase chain reaction identified the fungus-like oomycete Aphanomyces invadans, the causative agent of EUS. Apart from one previous record in N. erebi, EUS has been recorded in the wild only from coastal drainages in Australia. This study is the first published account of A. invadans in the wild fish populations of the MDRS, and is the first confirmed record of EUS in M. ambigua, M. peelii and L. unicolor. Ulcerated carp Cyprinus carpio collected at the time of the same epizootic were not found to be infected by EUS, supporting previous accounts of resistance against the disease by this species. The lack of previous clinical evidence, the large number of new hosts (n = 3), the geographic extent (200 km) of this epizootic, the severity of ulceration and apparent high pathogenicity suggest a relatively recent invasion by A. invadans. The epizootic and associated environmental factors are documented and discussed within the context of possible vectors for its entry into the MDRS and recommendations regarding continued surveillance, research and biosecurity are made

Accumulation and toxicity of monoaromatic petroleum hydrocarbons in early life stages of cod and haddock

A multitude of recent studies have documented the detrimental effects of crude oil exposure on early life stages of fish, including larvae and embryos. While polycyclic aromatic hydrocarbons (PAHs), particularly alkyl PAHs, are often considered the main cause of observed toxic effects, other crude oil derived organic compounds are usually overlooked. In the current study, comprehensive two-dimensional gas chromatography coupled to mass spectrometry was applied to investigate the body burden of a wide range of petrogenic compounds in Atlantic haddock (Melanogrammus aeglefinus) and cod (Gadus morhua) embryos that had been exposed to sublethal doses of dispersed crude oil. Several groups of alkylated monoaromatic compounds (e.g. alkyl tetralins, indanes and alkyl benzenes), as well as highly alkylated PAHs, were found to accumulate in the fish embryos upon crude oil exposure. To investigate the toxicity of the monoaromatic compounds, two models (1-isopropyl-4-methyltetralin and 1-isopropyl-4-methylindane) were synthesized and shown to bioaccumulate and cause delayed hatching in developing embryos. Minor developmental effects, including craniofacial and jaw deformations and pericardial edemas, were also observed at the highest studied concentrations of the alkylindane.acceptedVersio

Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease

BACKGROUND: The objective of this study was to develop and psychometrically evaluate a general measure of patients' satisfaction with medication, the Treatment Satisfaction Questionnaire for Medication (TSQM). METHODS: The content and format of 55 initial questions were based on a formal conceptual framework, an extensive literature review, and the input from three patient focus groups. Patient interviews were used to select the most relevant questions for further evaluation (n = 31). The psychometric performance of items and resulting TSQM scales were examined using eight diverse patient groups (arthritis, asthma, major depression, type I diabetes, high cholesterol, hypertension, migraine, and psoriasis) recruited from a national longitudinal panel study of chronic illness (n = 567). Participants were then randomized to complete the test items using one of two alternate scaling methods (Visual Analogue vs. Likert-type). RESULTS: A factor analysis (principal component extraction with varimax rotation) of specific items revealed three factors (Eigenvalues > 1.7) explaining 75.6% of the total variance; namely Side effects (4 items, 28.4%, Cronbach's Alpha = .87), Effectiveness (3 items, 24.1%, Cronbach's Alpha = .85), and Convenience (3 items, 23.1%, Cronbach's Alpha = .87). A second factor analysis of more generally worded items yielded a Global Satisfaction scale (3 items, Eigenvalue = 2.3, 79.1%, Cronbach's Alpha = .85). The final four scales possessed good psychometric properties, with the Likert-type scaling method performing better than the VAS approach. Significant differences were found on the TSQM by the route of medication administration (oral, injectable, topical, inhalable), level of illness severity, and length of time on medication. Regression analyses using the TSQM scales accounted for 40–60% of variation in patients' ratings of their likelihood to persist with their current medication. CONCLUSION: The TSQM is a psychometrically sound and valid measure of the major dimensions of patients' satisfaction with medication. Preliminary evidence suggests that the TSQM may also be a good predictor of patients' medication adherence across different types of medication and patient populations