Regulatory Dilemma Research Articles

The occurrence of the herbicide dalapon (2,2-dichloropropionate) in potable water as a disinfection by-product

Salts of 2,2-dichloropropionic acid, such as dalapon, are well known as herbicides and are regulated as such in potable water in Australia and elsewhere. It is also an identified disinfection by-product (DBP), but little is known about the compound's formation and typical levels from this source. This work presents results from a sampling campaign where 2,2-dichloropropionate was found at levels between 0.1 and 0.5 µg l(-1) in potable water samples from a major treatment plant in South East Queensland, Australia. However, levels were below the reporting limit (0.01 µg l(-1)) in the immediate source water for the plant. Also, temporal trends in 2,2-dichloropropionate observed in treated water during sampling mirrored those of trihalomethanes albeit at much lower concentrations, suggesting that the occurrence is due to in situ formation as a DBP. This could present a regulatory dilemma in some jurisdictions.

Understanding the Relative Roles of Pharmacogenetics and Ontogeny in Pediatric Drug Development and Regulatory Science

Understanding the dose-exposure-response relationship across the pediatric age spectrum from preterm and term newborns to infants, children, adolescents, and adults is a major challenge for clinicians, pharmaceutical companies, and regulatory agencies. Over the past 3 decades, clinical investigations of many drugs commonly used in pediatric therapeutics have provided valuable insights into age-associated differences in drug disposition and action. However, our understanding of the contribution of genetic variation to variability in drug disposition and response in children generally has lagged behind that of adults. This article proposes a systematic approach that can be used to assess the relative contributions of ontogeny and genetic variation for a given compound. Application of the strategy is illustrated using the current regulatory dilemma posed by the safety and effectiveness of over-the-counter cough and cold remedies as an example. The results of the analysis can be used to aid in the design of studies to yield maximally informative data in pediatric populations of different ages and developmental stages and thereby improve the efficiency of study design.

Stochastic frontier panel data modelling for regulatory benchmarking: An application to the Turkish electricity distribution sector

This paper considers stochastic frontier panel data methods for regulatory benchmarking that allow for both latent heterogeneity and inefficiency, encapsulating the regulatory dilemma in comparative efficiency analysis for incentive regulation. It applies a distance function model with appropriate concavity properties for econometric estimation to a panel of electricity distribution utilities in Turkey since, in preparation for accession to the European Union, Turkey is required to align the sector with incentive benchmarking regulation that characterizes the European Union. The results confirm the importance of allowing simultaneously for heterogeneity and inefficiency and emphasize the need for specific time-invariant heterogeneity information, such as geographical data, on regulated companies in different regions.

Tyler’s Herbs of Choice: The Therapeutic Use of Phytomedicinals

Contents Preface Chapter 1. Basic Principles Definitions Differences Between Herbs and Other Drugs Herbal Quality Paraherbalism Homeopathy Rational Herbalism General Guidelines in the Use of Herbal Medicines Herbal Dosage Forms Herbal Medicine Information Sources Chapter 2. The Herbal Regulatory Dilemma A Regulatory Tower of Babel Drug Regulation 1906-1962 Implementing Safety and Efficacy Regulations FDA's Herbal Regulatory Initiative Reaction to FDA's Herb Regulations The Dietary Supplement Health and Education Act The Proposal for Reform Chapter 3. Contents and Use of Subsequent Chapters Chapter 4. Digestive System Problems Nausea and Vomiting (Motion Sickness) Appetite Loss Constipation Diarrhea Indigestion--Dyspepsia Hepatotoxicity (Liver Damage) Peptic Ulcers Chapter 5. Kidney, Urinary Tract, and Prostate Problems Infections and Kidney Stones Benign Prostatic Hypertrophy (Prostrate Enlargement) Chapter 6. Respiratory Tract Problems Bronchial Asthma Colds and Flu Sore Throat Chapter 7. Cardiovascular System Problems Congestive Heart Failure (CHF) Arteriosclerosis Peripheral Vascular Disease Venous Disorders Chapter 8. Nervous System Disorders Anxiety and Sleep Disorders Depression Pain (General) Headache Toothache Sexual Impotence Chapter 9. Endocrine and Metabolic Problems Hormones in Endocrine and Metabolic Disorders Gynecological Disorders Hyperthyroidism Diabetes Mellitus Chapter 10. Arthritic and Musculoskeletal Disorders Arthritis Muscle Pain Gout Chapter 11. Problems of the Skin, Mucous Membranes, and Gingiva Dermatitis Contact Dermatitis Burns, Wounds, and Infections Lesions and Infections of the Oral Cavity and Throat Chapter 12. Performance and Immune Deficiencies Performance and Endurance Enhancers Cancer Communicable Diseases and Infections Index

A Plant Virus as a Bioherbicide for Tropical Soda Apple, <I>Solanum Viarum</I>

© 2007. Research Information Ltd. All rights reserved DOI: 10.1564/18aug07 Tropical soda apple (Solanum viarum, Figure 1; abbreviated: TSA) is an exotic, thorny, perennial shrub that has become a highly invasive weed in the southern USA. TSA is native to Brazil, but has spread to several countries of South and Central America, the Caribbean, Africa, and the Indian subcontinent. In Florida, improved pastures, cattle feedlots, citrus groves, ditches, sod farms, and natural areas are seriously affected by this weed (Ferrell & Mullahey 2007, Mullahey et al. 1993). TSA has been reported to occur also in Alabama, Georgia, Mississippi, Louisiana, Texas, North Carolina, South Carolina, Tennessee, and Pennsylvania (NAPIS, 2003). While some of these infestations have been eradicated, the threat of continued influx has not diminished because cattle, deer, wild hogs, birds, and contaminated hay help to disseminate the seed. TSA has the potential to spread throughout the continental USA (Patterson 1996). The realization of the threat posed by TSA has led to its designation as a “noxious weed” under the Federal and Florida noxious weed statutes. In efforts to stop the weed at its source, namely, the infestations in Florida, all potentially effective methods of control, including biological control, are being examined (DOACS-Florida 2007). TSA infestations in pastures cause the cattle stocking rates to be lowered due to the reduced access and available area for grazing. The livestock production costs go up, and out-of-state cattle shipments face a regulatory dilemma since the cattle are partly implicated in spreading the weed to their destinations. Although TSA foliage is inedible due to the presence of sharp thorns on all parts of the shoot, livestock, feral hogs, deer, raccoons, and birds eat the fruits and disperse the seeds (Coile 1993). Contaminated equipment, hay, grass seed, composted manure, and sod from TSA-infested areas also disperse the seeds. TSA seed is highly viable even after passage through animals’ digestive tracts and is the principal means of initial establishment as well as secondary increases in TSA populations. Mature plants can also sucker and re-establish following mowing and chemical treatment. Besides its weediness, TSA is a potential reservoir of several cropdamaging insects and pathogens (McGovern et al. 1994). A PLANT VIRUS AS A BIOHERBICIDE FOR TROPICAL SODA APPLE, SOLANUM VIARUM

Dinitrophenol and obesity: An early twentieth-century regulatory dilemma

In the early 1930s, the industrial chemical dinitrophenol found widespread favor as a weight-loss drug, due principally to the work of Maurice Tainter, a clinical pharmacologist from Stanford University. Unfortunately the compound’s therapeutic index was razor thin and it was not until thousands of people suffered irreversible harm that mainstream physicians realized that dinitrophenol’s risks outweighed its benefits and abandoned its use. Yet, it took passage of the Food, Drug, and Cosmetic Act in 1938 before federal regulators had the ability to stop patent medicine men from selling dinitrophenol to Americans lured by the promise of a drug that would safely melt one’s fat away.

A Framework Convention for Nanotechnology?

With nanotechnology now a major funding priority for governments and industry around the world, devising the manner and timing of regulation presents a challenge. Too much regulation too soon could hinder development of beneficial technologies, while too little regulation too late may allow dangerous technologies to enter the market. Kenneth Abbott, Gary Marchant, and Douglas Sylvester argue that any solution to this regulatory dilemma must have four basic characteristics: the solution must be flexible, innovative, international, and official. In this Article, they advocate a framework convention on nanotechnology as a regulatory tool meeting these four requirements. The authors use a series of case studies to reveal framework convention best practices, and conclude with a summary of how a nanotechnology framework convention might be structured.

'Optimism' Vs 'Big Bath' Accounting - A Regulatory Dilemma in Chinese Financial Reporting Practices

Although China's accounting system has experienced an evolution during the last three decades, its financial reporting practices are still not satisfactory. Optimism, by means of overstating companies' profits and assets value, has always been criticized in China. Therefore, the principle of Conservatism may provide a means of minimizing such improper behavior. With such concern, the paper systematically reviews the financial reporting problems in China. However, through analysis, it is found that although Optimism exists, the extremely contrary case - Big Bath accounting also exists. Hence, this paper argues that Conservatism may not be applicable in contemporary China's financial reporting environment.

How Modeling and Simulation Have Enhanced Decision Making in New Drug Development

The idea of model-based drug development championed by Lewis Sheiner, in which pharmacostatistical models of drug efficacy and safety are developed from preclinical and available clinical data, offers a quantitative approach to improving drug development and development decision-making. Examples are presented that support this paradigm. The first example describes a preclinical model of behavioral activity to predict potency and time-course of response in humans and assess the potential for differentiation between compounds. This example illustrates how modeling procedures expounded by Lewis Sheiner provided the means to differentiate potency and the lag time between drug exposure and response and allow for rapid decision making and dose selection. The second example involves planning a Phase 2a dose-ranging and proof of concept trial in Alzheimer's disease (AD). The issue was how to proceed with the study and what criteria to use for a go/no go decision. The combined knowledge of AD disease progression, and preclinical and clinical information about the drug were used to simulate various clinical trial scenarios to identify an efficient and effective Phase 2 study. A design was selected and carried out resulting in a number of important learning experiences as well as extensive financial savings. The motivation for this case in point was the "Learn-Confirm" paradigm described by Lewis Sheiner. The final example describes the use of Pharmacokinetic and Pharmacodynamic (PK/PD) modeling and simulation to confirm efficacy across doses. In the New Drug Application for gabapentin, data from two adequate and well-controlled clinical trials was submitted to the Food and Drug Administration (FDA) in support of the approval of the indication for the treatment of post-herpetic neuralgia. The clinical trial data was not replicated for each of the sought dose levels in the drug application presenting a regulatory dilemma. Exposure response analysis submitted in the New Drug Application was applied to confirm the evidence of efficacy across these dose levels. Modeling and simulation analyses showed that the two studies corroborate each other with respect to the pain relief profiles. The use of PK/PD information confirmed evidence of efficacy across the three studied doses, eliminating the need for additional clinical trials and thus supporting the approval of the product. It can be speculated that the work by Lewis Sheiner reflected in the FDA document titled "Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products" made this scientific approach to the drug approval process possible.

Neurotoxicity and substance abuse: further fuel for regulatory dilemma.

Neurotoxicity and substance abuse: further fuel for regulatory dilemma.

New Directions: TEOMs and the volatility of UK non-urban PM 10: a regulatory dilemma

New Directions: TEOMs and the volatility of UK non-urban PM 10: a regulatory dilemma

The Regulatory Dilemma Surrounding Interstate Practice

One of the changes with which all health care providers and regulators are grappling is the increasing use of telecommunication technology in the health care delivery system. Historically, regulation of health professionals has been a state-based function. However, the combination of telehealth and the current state-based model of regulation poses a potential problem of widespread unlicensed practice. This paper will offer an historical overview of health care regulation and identify four specific areas of concern related to the regulation of interstate nursing practice, namely, state sovereignty, discipline, information sharing and regulation of advanced practice registered nurses.

Food and Drug Administration Regulation of Spinal Implant Fixation Devices

The role of the Food and Drug Administration in regulating medical devices generally is not well understood by physicians. The practice of medicine does not fall under Food and Drug Administrations's regulatory purview. Nevertheless, the Food and Drug Administration and its regulation of medical devices can influence physicians' activities. This article provides an overview of the scope of the Food and Drug Administration's authority and the agency's regulatory framework, with particular focus on orthopaedic medical devices as related to spinal implant devices. During the past 10 years, a regulatory dilemma has arisen surrounding the use of bone screws in the pedicles of the spine. Except for recent clearances for a limited treatment indication, the Food and Drug Administration has not cleared these devices to be labeled for pedicle screw fixation and, therefore, has restricted industry supported educational activities pertaining to this type of treatment. In spite of the Food and Drug Administration's regulatory position, physicians have chosen to use pedicle screw fixation in treating patients who have a variety of spinal disorders. This use is now considered an accepted (state of the art) medical practice by many physicians for certain spinal conditions. This article explores this specific Food and Drug Administration regulatory issue, its impact on physicians and manufacturers (especially as it pertains to medical education), and recent actions taken to resolve it.

Patient Safety During Radiofrequency Catheter Ablation: A Clinical and Regulatory Dilemma

<b>Patient Safety During Radiofrequency Catheter Ablation:</b> A Clinical and Regulatory Dilemma

Racemates or enantiomers: regulatory approaches.

1. Racemic drugs contain enantiomers which can differ substantially in pharmacological and dispositional properties. The development of chemical methods to separate and analyse drug enantiomers has led to a growing understanding of their biological properties and a regulatory dilemma as to whether only enantiomerically pure drugs should be marketed. 2. Advantages of enantiomerically pure drugs include more selective pharmacological profiles leading to better therapeutic indices, less complex pharmacokinetics and interactions, and simpler interpretation of plasma concentration response relationships. 3. As racemic drugs that are currently marketed and reaching marketing were developed when knowledge of drug enantiomers was less sophisticated, a flexible regulatory approach is required. At present, it is probably reasonable to require substantial information on the properties of enantiomers of racemic drugs but the balance is on the side of regulatory agencies needing to justify, provided adequate information is submitted, requirements for enantiomerically pure drugs. 4. This balance will gradually change to a situation where enantiomerically pure drugs will be the standard, and a strong case will need to be put by sponsors wishing to market racemic drugs.

Environmental Regulatory Dilemma of Oil and Gas Industry: ABSTRACT

Environmental Regulatory Dilemma of Oil and Gas Industry: ABSTRACT

The questionable value of long-term animal toxicity studies: a regulatory dilemma.

Recommendations for the minimum period of repeated dose administration to animals to support marketing authorization of pharmaceuticals vary from 6 months in the EEC to 18 months in Canada. The value of studies lasting longer than 6 months has not, however, been established. In order to enable retrospective analyses to be carried out, the Centre for Medicines Research has established a toxicology databank containing comprehensive data from repeated dose animal safety evaluation studies on 124 compounds, provided by 21 pharmaceutical companies in Europe (Lumley and Walker 1985a). There are 214 case studies (1 compound tested in 1 species for 1 or more time periods), and in 100 of these tests lasted for longer than 6 months. In 88 long-term studies comparable short-term data are available and these have been analysed to determine what new findings, if any, became apparent after 6 months. The data do not support the need for animal toxicity studies of longer than 6 months, apart from those designed to investigate carcinogenicity. Safety evaluation studies should be of value in predicting adverse drug reactions for man. Unless it can be established that these longer-term studies more accurately define potential target organ effects, the scientific rationale for conventional long-term studies must be questioned.

COMPARATIVE BASES OF INDUSTRY POLLUTION ABATEMENT AND COMMERCIAL INNOVATION: IMPLICATIONS FOR WATER RESOURCES MANAGEMENT1

ABSTRACT: Adoption, maintenance, and operation of pollution control technology by manufacturing firms is essential to effective water resource management. In this study of 102 industries, we find that company adoption of pollution control technology and practices is primarily associated with two factors: (1) the overall company capacity for innovation in its production technology; and (2) company relationships with state and federal pollution control agencies, local government officials and professionals. Managerial attitudes about pollution and government regulation are not associated with either pollution control or commercial innovation, but are seen as basic to industry‐government relationships. The data suggest an important regulatory dilemma, the problem of regulating a large number of small companies with a low capacity for innovation, but which when taken together account for large volumes of toxic effluent.

The new video marketplace and the impending regulatory identity crisis

The emergence of a diverse video marketplace, in which a number of technologies compete with television to deliver entertainment and information to the home has created a regulatory dilemma for the FCC. To a certain extent, the FCC has shown reluctance to depart from the traditional regulatory classification. However, the Commission seems to be moving toward greater licensee autonomy. This approach may, ultimately, be the most effective response to an era of rapid technological change and the regulatory identity crisis.

Cumulative silvicultural impacts on watersheds: A hydrologic and regulatory dilemma

Because of the nature of watersheds, the hydrologic and erosional impacts of logging and related road-building activities may move offsite, affecting areas downslope and downstream from the operation. The degree to which this occurs depends on the interaction of many variables, including soils, bedrock geology, vegetation, the timing and size of storm events, logging technology, and operator performance. In parts of northwestern California, these variables combine to produce significant water quality degradation, with resulting damage to anadromous fish habitat.