The facilitation of tight regulatory frameworks necessary to ensure that new drugs are safe and effective have yet to be effectively applied within the paediatric population. Utilization of unlicensed and off-label drugs in children results in a variety of problems ranging from inefficacy, adverse reactions and in some cases death. This ethically questionable behaviour has led the European government to legally force pharmaceutical companies to propose paediatric applications and carry out clinical studies at early stages of drug development. (...) The new European Paediatric Regulation implemented in 2007 opens a new era of paediatric drug development and will offer the opportunity to vastly improve children's health. However, this brighter outlook for the paediatric community might encourage potentially unethical behaviour in a pharmaceutical industry that finds itself in economically unstable times. The article records the gradual evolution of the US Paediatric Exclusivity Plan and the underlying principle of the newly introduced European Paediatric Regulation. It discusses some of the potential drawbacks and detrimental consequences of implementing the new European regulation, and the prospects of avoiding these by critically evaluating the difficulties experienced by the US. (shrink)

Kwaku Marfo, Danielle Garcia, Saira Khalique, Karen Berger, Amy LuMontefiore Medical Center, Bronx, NY, USABackground: Medication errors are a prime concern for all in healthcare. As such the use of information technologies in drug prescribing and administration has received considerable attention in recent years, with the hope of improving patient safety. Because of the complexity of drug regimens in renal transplant patients, occurrence of medication errors is inevitable even with a well adopted computerized physician order entering system. Our (...) objective was to quantify medication error type and frequency in an inpatient renal transplant unit.Methods: Systemic evaluation of all medication errors during an initial 10-day audit and a 28-day follow-up audit in an inpatient renal transplant unit. Each error was concurrently evaluated for potential to result in adverse patient consequences, error type and associated medication class.Results: A total of 103 clinically significant medication errors were detected during the 10-day and 28-day audit time periods. The most common errors were wrong medication dose ordered and wrong time of drug administration. Thirty-six out of 66 prescribing/ordering errors reached the patient.Conclusions: Even with utilization of computerized physician order entry system in an inpatient renal transplant unit, post-kidney transplant patients are at risk for adverse outcomes due to medication errors. The risk factors may be multifactorial and will require both organizational and technical approaches to resolve.Keywords: medication errors, CPOE, inpatient, renal transplant patients. (shrink)

A relatively healthy forty-six-year-old woman with mild hypertension receives a prescription for an antihypertensive medication. One of the medication's adverse effects is its potential to cause severe depression. Four months later, she is diagnosed with anxiety, an early manifestation of depression. An antianxiety drug is prescribed, but her anxiety worsens. Her physician then diagnoses her as having a depressive disorder, and prescribes a new antidepressant medication. She is still on the same antihypertensive.A seventy-two-year-old man is given furosemide and digoxin (...) to control a mild case of congestive heart failure and hypertension. Because furosemide deletes potassium from the body, his physician also places him on a potassium supplement. Six months later, the physician tells the patient to stop taking the furosemide and prescribes an angiotensin converting enzyme inhibitor. An effect of ACE inhibitors is to reduce the body's excretion of potassium thereby reducing the digoxin's effectiveness. (shrink)

A relatively healthy forty-six-year-old woman with mild hypertension receives a prescription for an antihypertensive medication. One of the medication's adverse effects is its potential to cause severe depression. Four months later, she is diagnosed with anxiety, an early manifestation of depression. An antianxiety drug is prescribed, but her anxiety worsens. Her physician then diagnoses her as having a depressive disorder, and prescribes a new antidepressant medication. She is still on the same antihypertensive.A seventy-two-year-old man is given furosemide and digoxin (...) to control a mild case of congestive heart failure and hypertension. Because furosemide deletes potassium from the body, his physician also places him on a potassium supplement. Six months later, the physician tells the patient to stop taking the furosemide and prescribes an angiotensin converting enzyme inhibitor. An effect of ACE inhibitors is to reduce the body's excretion of potassium thereby reducing the digoxin's effectiveness. (shrink)

This article evaluates the oversight of drugs and medical devices by the U.S. Food and Drug Administration using an integration of public policy, law, and bioethics approaches and employing multiple assessment criteria, including economic, social, safety, and technological. Criteria assessment and expert elicitation are combined with existing literature, case law, and regulations in an integrative historical case studies approach. We then use our findings as a tool to explore possibilities for effective oversight and regulatory mechanisms for nanobiotechnology. Section I (...) describes oversight mechanisms for human drugs and medical devices and presents current nanotechnology products. Section II describes the results of expert elicitation research. Section III highlights key criteria and relates them to the literature and larger debate. We conclude with broad lessons for the oversight of nanobiotechnology informed by Sections I-III in order to provide useful analysis from multiple disciplines and perspectives to guide discussions regarding appropriate FDA oversight. (shrink)

This article evaluates the oversight of drugs and medical devices by the U.S. Food and Drug Administration using an integration of public policy, law, and bioethics approaches and employing multiple assessment criteria, including economic, social, safety, and technological. Throughout, assessments employing both the multiple criteria and a method of expert elicitation are combined with the existing literature, case law, and regulations providing an integrative historical case study approach. The goal is to provide useful information from multiple disciplines and perspectives (...) to guide discussions regarding appropriate oversight frameworks for nanobiotechnology applications under the FDA’s purview. (shrink)

“Female sexual dysfunction” is the type of contested disease that has sparked concern about the role of the pharmaceutical industry in medical science. Many policies have been proposed to manage industry influence without carefully evaluating whether the proposed policies would be successful. We consider a proposal for incorporating citizen stakeholders into scientific research and show, via a detailed case study of the pharmaceutical regulation of flibanserin, that such programs can be co-opted. In closing, we use Holman’s asymmetric arms race framework (...) as a tool for evaluating policies in industry-funded science. (shrink)

Although China’s wind industry has made great progress in recent years, the wind abandonment phenomenon caused by the unbalanced development of regional wind power is still prominent. It is particularly important for the scientific development of wind power to accurately measure the utilization efficiency of wind power and understand its regional differences in China. This study establishes the improved super-efficiency slack-based measure model and long short-term memory network models, systematically and comprehensively measures and predicts the wind power utilization (...) efficiency of 30 regions in China from 2013 to 2020, and explores regional differences in wind power utilization efficiency. Our results show the following: China’s overall wind power utilization efficiency is relatively low but has been on a steady upward trend since 2013. Regional differences are obvious, showing that the spatial distribution pattern of wind power utilization efficiency is greatest in Northeast China, followed by North China, East China, South China, Northwest China, and Central China. The “Three-North” region with abundant wind energy resources has relatively high wind power utilization efficiency and exhibits a good development trend. East China, South China, and Central China, where wind energy resources are relatively poor, have low wind power utilization efficiency, and their development trends are not stable and are more prone to change. The utilization efficiency of wind power in coastal areas is generally better than that in inland areas. There are also differences among the thirty Chinese regions studied. Inner Mongolia and Shandong have achieved real efficiency in wind power utilization efficiency, with optimal allocation of input and output, and a good development trend. The other 28 regions have varying degrees of inefficiency, and there is still room for improvement. (shrink)

Science has needed a dispassionate valuation of psychoactive drugs, but a motivational analysis should be conducted with respect to long-term reward rather than reproductive fitness. Because of hyperbolic overvaluation of short-term rewards, an individual's valuation depends on the time she forms it and the times she will revisit it, sometimes making her best long-term interest lie in total abstinence.

An increasing number of drugs removed from the market because of unacceptable toxicity raises concerns regarding preapproval testing of drug safety. In the present paper it is postulated that the non-inferiority type of trial should be abandoned in favor of the superiority trial with active controls and less stringent (p<0.1, both for efficacy and toxicity) statistics. This approach will increase sensitivity of detection of drug-induced adverse effects at the expense of increasing false positive results regarding the difference in (...) efficacy between the tested and reference drug. Such a move will increase the protection of future patients. In addition, the proposed design is far more acceptable from the clinical (e.g. no need to specify the statistically expected “unimportant” number of deaths) and ethical points of view, as well as being favored by the strong incentive of involved parties. In the second part of this paper arguments are presented in favor of the hypothesis that placebo (still used in some superiority trials) does not induce adverse effects. The assertion that placebo may induce adverse effects is probably biased by the nature of the clinical experiment. Such a conclusion is supported by studies indicating that placebo-induced adverse effects are disease — and treatment — specific. The modification of clinical trials according to the proposed changes may increase the trials’ sensitivity at detecting adverse effects of drugs. (shrink)

Background U.S. federal regulations require that certain ethical elements be followed to protect human research subjects. The location and clinical circumstances of a proposed research study can differ substantially and can have significant implications for these ethical considerations. Both the location and clinical circumstances are particularly relevant for research in intensive care units (ICUs), where patients are often unable to provide informed consent to participate in a proposed research intervention. Purpose Our goal is to elaborate on the updated 2013 U.S. (...) Food and Drug Administration (FDA) guidance document regarding an exemption from the requirement of obtaining informed consent from patients or their surrogates and to address certain elements within that document, thereby assisting clinicians in developing a framework for emergency research in accordance with the regulatory bodies at their own institutions and in the United States. Methods Review of the 2011 and updated FDA guidance document on exemption from informed consent. Results The current process of obtaining informed consent within ICUs needs to be revisited, especially for research in which timely informed consent is not likely. In particular, the process of obtaining informed consent may not be appropriate or even ethical for critically ill patients in extremis who require an intervention for which there is no current acceptable standard of care and clinical equipoise exists. We provide clinicians with a viewpoint that further elaborates on the FDA guidance document. Limitations The viewpoints provided herein are those of the authors and are therefore inherently limited by the personal views of a selected few. Other clinicians or researchers may not interpret the FDA guidelines in a similar manner. Moreover, the discussion of a guideline document is a limitation in and of itself. The guidelines set forth by the FDA are precisely that—guidelines. Therefore, they may not be followed as outlined in the guidance document within one’s own institution. Our goal is that, by elaborating on the guidelines for planned research involving human subjects in the ICU, institutional regulatory bodies may gain a better understanding in drafting their own document when faced with a clinician or a researcher who wishes to conduct planned research in an ICU. Conclusions We believe that the interpretations provided will allow clinicians to safely undertake planned research in ICUs without endangering the main tenets of ethical research involving human participants. This research is needed for the advancement of care in the critically ill. (shrink)

Chloroquine-resistant plasmodium falciparum malaria is a serious public health threat that is spreading rapidly across Sub-Saharan Africa. It affects over three quarters (80%) of malarial endemic countries. Of the estimated 300-500 million cases of malaria reported annually, the vast majority of malarial-related morbidities occur among young children in Africa, especially those concentrated in the remote rural areas with inadequate access to appropriate health care services. In Liberia, in vivo studies conducted between 1993 and 2000 observed varying degrees of plasmodium falciparum (...) malaria infections that were resistant to chloroquine, including sulfadiazine-pyrimethamine. As the country emerges from a prolonged civil war, the health care delivery system may not be adequately prepared to implement an effective nation-wide malarial control strategy. As a result, the management of uncomplicated malaria in Liberia poses a significant public health challenge for the government-financed health care delivery system. Therefore, based on extensive literature review, we report the failure of chloroquine as an effective first-line drug for the treatment of uncomplicated plasmodium falciparum malaria in Liberia and recommend that national health efforts be directed at identifying alternative drug(s) to replace it. (shrink)

This article seeks to provide insights into appropriate FDA oversight of nanotechnology. This commentary identifies limitations in the methodology employed and concludes that the analysis would be stronger with a more in-depth institutional dimension based on administrative law and political science research.

Recent publications on policy theories, similarities and dissimilarities of auditing and evaluation research and on the utilization of policy research by government officials.

Alcohol and other drug-related stigma is a growing concern. Many organizations have called for a reduction in such stigma through law reform, but there is little sense of how, precisely, this might be achieved. This paper reports on a new method to examine the relationship between stigma and the law and establish a framework that can guide and inform future law reform efforts.

The U.S. Food and Drug Administration (FDA) announced recently that food products derived from some animal clones and their offspring are safe for human consumption. In response to criticism that it had failed to engage with ethical, social, and economic concerns raised by livestock cloning, the FDA argued that addressing normative issues prior to issuing a final ruling on animal cloning is not part of its mission. In this article, the authors reject the FDA's claim that its mission to (...) protect and advance public health can be accomplished without considering ethical issues or without making value judgments. The authors offer two arguments in support of their position. First, the agency's mission statement presupposes significant normative commitments and judgments. Second, the FDA's risk assessment of food products from cloned animals and their offspring is itself clearly shaped by a variety of normative commitments. (shrink)

The basic hypothesis tested in the article is that the existence of Freedom of Information legislation in a state enhances utilization of evaluation research. The investigation of this research question leads to a tentative rejection of this hypothesis. Factors such as weak Freedom of Information Acts, unsympathetic implementation, and the lack of useful and timely information in agency-sponsored evaluations may discourage legislatures from actively using Freedom of Information provisions to obtain such studies.

The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been acknowledged for many years and validated by the clinical use of several drugs. Recently, the crystal structures of all but one of the enzymes in the pathway from GTP to dihydrofolate have been determined. Given that structure‐based drug design strategies are now widely employed, these recent developments have prompted a re‐evaluation of the potential of each of the enzymes in the (...) pathway as a target for development of specific inhibitors. Here, we review the current knowledge of the structure and mechanism of each enzyme in the bacterial folic acid biosynthesis pathway from GTP to dihydrofolate and draw conclusions regarding the potential of each enzyme as a target for therapeutic intervention. BioEssays 24:637–648, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Ethical clinical practice requires cultural competency. In the United States, Hispanics report stronger attitudinal barriers to drug abuse treatment than any other racial/ethnic group. Hispanics report feeling that drug abuse treatment providers do not understand their unique cultural needs and are unfamiliar with their experiences of discrimination and immigration. Using this case study to explore broader ethical and policy issues, this study investigates the extent to which US universities train counselors to address the culturally specific needs of Hispanic (...) patients and how this is reflected in practice in Los Angeles County. Based on a content analysis of the required courses, syllabi, and course descriptions at 30 universities related to culture/race/racism/ethnicity/diversity at the undergraduate and graduate levels on the addiction therapist track, and thematic analysis of eight in-depth interviews with counselors working in outpatient rehabilitation centers in Los Angeles, I argue that cultural competency education for drug abuse counselors is too surface level and infrequent to adequately prepare students for a career in addiction counseling for Hispanic clients. Significant changes must be made to how cultural diversity is valued and prioritized in the field of psychology to provide better care for Hispanic people with a substance use disorder and fulfill the moral obligation to eliminate this health disparity. Although this study focuses on counselors in Los Angeles, these findings are relevant for professionals and healthcare systems across the United States and beyond who seek to provide equitable and effective care for Hispanic patients. (shrink)

This commentary reviews the effects of nicotine on mood and cognition in support of the drug utilization concept of Müller & Schumann (M&S). Specifically, it amplifies the concept with the nicotine utilization hypothesis (NUH), which opposes the nicotine withdrawal hypothesis (NWH). Evidence against NWH comes from changes in mood after abstinence and the performance effects of nicotine supporting drug utilization.

As nanotechnology emerges as an important public policy issue, the FDA's relationship with society is about to be tested. Most would agree that fostering public input will be critical to developing effective public policy for nanotechnology. Yet, it will not be easy. Low public confidence in the FDA, the general lack of knowledge about nanotechnology among ordinary Americans, and the way in which the “average” citizen obtains and evaluates knowledge about a public policy issue all pose serious challenges to any (...) public outreach by the FDA. It will be necessary for the FDA to be attentive to not only its own public messages, but also to who is listening and how those messages are being perceived. (shrink)

Coastlines play an important role in human activity and economic development. Reasonably allocating shoreline resources and addressing contradictions between ecological protection and development are critical issues. In this study, positive and negative factors affecting the natural, environmental, and socioeconomic status of the coastal zone while considering land and sea effects were comprehensively analyzed using ecological theories and methods, and an improved restrictive composite index model was constructed. We quantitatively analyzed the comprehensive utilization pattern of the Bohai Rim coastline, China, (...) in terms of the coastline utilization type and spatial agglomeration characteristics. The comprehensive utilization pattern of the Bohai Rim coastline is as follows: ecological areas are present in the north and south, and industrial areas are present in the east and west. Industrial production areas along the coastline are mainly distributed in the East Liaodong and Bohai bays, and ecological protection areas are located in the estuaries of the Liaohe and Yellow River. The improved restricted comprehensive index method model weakens the interaction among variables and makes the calculation results closer to the real situation. The results of the comprehensive utilization pattern of Bohai Rim coastline obtained by quantitative evaluation are of great significance for the coordinated development of coastline ecological protection and development and utilization. (shrink)

We conducted a scoping review to map and critically examine the knowledge, perceptions and utilization of generics and biosimilars, among physicians, pharmacists, patients, the general population, and other stakeholders from LAC.

A cost analysis of the utilization of new expensive vascular grafts is performed, applying the methodology of decision analysis to the theoretical case of a sixty year old male patient undergoing femoropopliteal grafting for limb threatening ischemia. The problem is presented graphically as a decision tree, uncertainties are quantified in terms of probabilities and end outcomes are evaluated in monetary terms. This informations is then utilized to calculate cost values associated with alternative actions.Based on initial cumulative patency figures of (...) the new more expensive grafts and the known performance of the older grafts, the initial high expense for the new grafts is justified economically, if the saphenous vein is not available. This analysis, apart from giving an answer to a specific clinical problem, can be viewed as a general model for cost analysis of surgical procedures. (shrink)

"Cluster randomized trials," in which groups of patients are randomly assigned to different therapeutic interventions, provide a powerful way of evaluating drugs. CRTs have not been widely used, in good part because of concerns about whether patients must give informed consent to participate in them. A better understanding of how CRTs fit into clinical practice resolves the concerns.