This article examines the regulation of nonsteroidal anti-inflammatory drugs, with particular focus on products approved for marketing in the United Kingdom, while denied marketing approval in the United States on safety grounds, and then subsequently withdrawn from the UK market on those grounds. Using international comparison of regulatory data never before accessed outside government and companies, together with interviews with relevant industry scientists and regulators, the article demonstrates the importance of regulatory expectations, deficits and paradigms. It is argued both (...) that these sociological concepts can be enriched by their application to detailed comparative case study of regulatory science, and that they provide an important policy-relevant framework with which to understand discrepant drug regulatory processes in a sociohistorical context. It is found that regulatory expectations and paradigms may be regarded as mediating factors between political culture and structural interests, on the one hand, and the outcomes of regulatory science, on the other. (shrink)

Drug Safety Communications are used by the Food and Drug Administration to inform health care providers, patients, caregivers, and the general public about safety issues related to FDA-approved drugs. To assess patient knowledge of the messaging contained in DSCs related to the sleep aids zolpidem and eszopiclone, we conducted a large, cross-sectional patient survey of 1,982 commercially insured patients selected by stratified random sampling from the Optum Research Database who had filled at least two prescriptions for (...) either zolpidem or eszopiclone between July 1, 2012 and June 30, 2013. Among the 594 respondents, two-thirds reported hearing generally about drug safety information prior to starting a new drug, with the remaining one-third “rarely” or “never” hearing such information. Providers and pharmacists were primary sources of drug safety information. Two-thirds of zolpidem users and half of eszopiclone users reported having heard about the related DSC messages, ability to accurately identify the major factual messages was limited. Respondents reacted to new drug safety information about their sleep aids by reporting that they would want to learn about alternative ways to help them sleep and seek out more information about the safety of their specific sleeping pill. Opportunities may exist for the FDA to work with providers and pharmacies to help ensure the DSC information is more widely received and is more fully understood by those taking the affected medications. (shrink)

The primary responsibility of the US Food and Drug Administration is to protect public health by ensuring the safety of the food supply. To that end, it sometimes conducts risk assessments of novel food products, such as genetically modified food. The FDA describes its regulatory review of GM food as a purely scientific activity, untainted by any normative considerations. This paper provides evidence that the regulatory agency is not justified in making that claim. It is argued that the (...) FDA’s policy stance on GM food is shaped by neoliberal considerations. The agency’s review of a genetically engineered animal, the AquAdvantage salmon, is used as a case study to track the influence of neoliberalism on its regulatory review protocol. After that, an epistemic argument justifying public engagement in the risk assessment of new GM food is outlined. It is because risk evaluations involve normative judgments, in a democracy, layperson representatives of informal epistemic communities that could be affected by a new GM food should have the opportunity to decide the ethical, political or other normative questions that arise during the regulatory review of that entity. (shrink)

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 emphasis in human pluripotent stem cell (hPSC) technologies has shifted from cell therapy to in vitro disease modelling and drug screening. This review examines why this shift has occurred, and how current technological limitations might be overcome to fully realise the potential of hPSCs. Details are provided for all disease‐specific human induced pluripotent stem cell lines spanning a dozen dysfunctional organ systems. Phenotype and pharmacology have been examined in only 17 of 63 lines, primarily those that model neurological (...) and cardiac conditions. Drug screening is most advanced in hPSC‐cardiomyocytes. Responses for almost 60 agents include examples of how careful tests in hPSC‐cardiomyocytes have improved on existing in vitro assays, and how these cells have been integrated into high throughput imaging and electrophysiology industrial platforms. Such successes will provide an incentive to overcome bottlenecks in hPSC technology such as improving cell maturity and industrial scalability whilst reducing cost. (shrink)

In The Ethics of Food, Gregory E. Pence brings together a collection of voices who share the view that the ethics of genetically modified food is among the most pressing societal questions of our time. This comprehensive collection addresses a broad range of subjects, including the meaning of food, moral analyses of vegetarianism and starvation, the safety and environmental risks of genetically modified food, issues of global food politics and the food industry, and the relationships among food, evolution, and (...) human history. (shrink)

Drugs addressing unmet medical needs can change the lives of millions. Developing and validating new drugs can, however, take many years. To streamline the assessment of new drugs, regulatory agencies have long established shortened review pathways. Among these programs, Accelerated Approval (AA) has recently come under scrutiny due to the U.S. Food and Drug Administration's decision to authorize Aducanumab, the first Alzheimer's disease drug. This decision attracted fierce criticism due to the allegedly insufficient evidence about the (...) class='Hi'>safety and efficacy of the drug. While considerable scholarly attention has been devoted to this case, the ethical aspects of the AA regulatory pathway have so far remained relatively unexplored. In this paper, we set out to fill this gap. We illustrate six conditions that should be met for AA to be ethically acceptable: moral solicitude, evidence, risk mitigation, impartiality, sustainability, and transparency. We discuss such conditions and suggest practical steps to implement them in regulatory and oversight processes. Taken together, our six conditions represent a benchmark for assessing the ethical validity of AA processes and decisions. (shrink)

BackgroundInternational guidelines recommend ethical and scientific quality standards for managing and reporting adverse events occurring during clinical trials to competent research ethics committees and regulatory authorities. The purpose of this study was to determine whether clinical trial protocols in Cameroon are developed in line with national requirements and international guidelines as far as detecting, reporting and investigating of adverse events is concerned.MethodsIt was a documentary review of all approved clinical trial protocols that were submitted at the Cameroon National Ethics Committee (...) for evaluation from 1997 through 2012. Data were extracted using a preconceived and validated grid. Protocol review process targeted the title, abstract, objectives, methodology, resources, and the chapter on safety.ResultsIn total, 106 clinical trial protocols were identified from 2173 protocols seen in the archive and 104 included for review. Seventy six trials did not include the surveillance of adverse events as part of their objective. A total of 91 protocols did not budget for adverse event surveillance, 76 did not have a data safety management board, 11 included insurance for participants, 47 did not include a case definition for serious adverse events, 33 described procedures to detect adverse events, 33 described procedure for reporting and 22 described procedure for investigating adverse events.DiscussionsMost clinical trial protocols in Cameroon are developed to focus on benefits and pay little attention to harms. The development of national guidelines can improve the surveillance of adverse events in clinical trial research conducted in Cameroon. Adverse events surveillance tools and a budget are critical for an adequate planning for adverse event surveillance when developing trial protocols.ConclusionClinical trial protocols submitted in the Cameroon National Ethics Committee do not adequately plan to assess adverse events in clinical trial protocols. In order to improve on the safety of participants and marketed drug, there is a need to develop national guidelines for clinical trials by the government, and to improve evaluation procedures and monitoring of ongoing trials by the ethics committee. (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)

Drug regulatory bodies aim to ensure that patients have access to safe and effective drugs; however, no matter the quality of pre-licensure studies, uncertainty will remain regarding the safety and effectiveness of newly approved drugs until a large and diverse population uses those drugs. Recent analyses of Canada’s post-market drug surveillance system have found that Canada is not keeping pace with international requirements for PMDS, and have noted that efforts must be improved to monitor and address the (...) safety and effectiveness of approved drugs among vulnerable populations. Given the uncertainty that exists when drugs enter the market, some have suggested that the precautionary principle is relevant to guiding decision-making in this context. This paper responds to recommendations that the Canadian PMDS system should be responsive to the health needs of vulnerable populations by assessing the utility of deploying the precautionary principle to guide a post-market strategy for vulnerable populations. (shrink)

The assessment of nanotechnology applications such as nanocarrier-based targeted drug delivery has historically been based mostly on toxicological and safety aspects. The use of nanocarriers for TDD, a leading-edge nanomedical application, has received little study from the angle of experts’ perceptions and acceptability, which may be reflected in how TDD applications are developed. In recent years, numerous authors have maintained that TDD assessment should also take into account impacts on ethical, environmental, economic, legal, and social issues (...) in order to lead to socially responsible innovation. Semi-structured interviews were conducted with French and Canadian researchers and research trainees with diverse disciplinary backgrounds and involved in research related to emerging technologies. The interviews focussed on scenarios presenting two types of TDD nanocarriers in two contexts of use. Content and inductive analyses of interviews showed how facets of perceived impacts such as health, environment, social cohabitation, economy, life and death, representations of the human being and nature, and technoscience were weighed in acceptability judgments. The analyses also revealed that contextual factors related to device, to use, and to user influenced the weighting assigned to perceived impacts and thus contributed to variability in interviewees’ judgments of acceptability. Giving consideration to researchers’ perspective could accompany first steps of implementation and development of nanomedicine by producing a first, but wide, picture of the acceptability of nanocarrier-based TDD. (shrink)

Over the last decade, philosophers of science have extensively criticized the epistemic superiority of randomized controlled trials for testing safety and effectiveness of new drugs, defending instead various forms of evidential pluralism. We argue that scientific methods in regulatory decision-making cannot be assessed in epistemic terms only: there are costs involved. Drawing on the legal distinction between rules and standards, we show that drug regulation based on evidential pluralism has much higher costs than our current RCT-based system. We (...) analyze these costs and advocate for evaluating any scheme for drug regulatory tests in terms of concrete empirical benchmarks, like the error rates of regulatory decisions. (shrink)

Background: Evidence suggesting adverse drug reactions often emerges unsystematically and unpredictably in form of anecdotal reports, case series and survey data. Safety trials and observational studies also provide crucial information regarding the (un-)safety of drugs. Hence, integrating multiple types of pharmacovigilance evidence is key to minimising the risks of harm. Methods: In previous work, we began the development of a Bayesian framework for aggregating multiple types of evidence to assess the probability of a putative causal link between (...) drugs and side effects. This framework arose out of a philosophical analysis of the Bradford Hill Guidelines. In this article, we expand the Bayesian framework and add “evidential modulators,” which bear on the assessment of the reliability of incoming study results. The overall framework for evidence synthesis, “E-Synthesis”, is then applied to a case study. Results: Theoretically and computationally, E-Synthesis exploits coherence of partly or fully independent evidence converging towards the hypothesis of interest (or of conflicting evidence with respect to it), in order to update its posterior probability. With respect to other frameworks for evidence synthesis, our Bayesian model has the unique feature of grounding its inferential machinery on a consolidated theory of hypothesis confirmation (Bayesian epistemology), and in allowing any data from heterogeneous sources (cell-data, clinical trials, epidemiological studies), and methods (e.g., frequentist hypothesis testing, Bayesian adaptive trials, etc.) to be quantitatively integrated into the same inferential framework. Conclusions: E-Synthesis is highly flexible concerning the allowed input, while at the same time relying on a consistent computational system, that is philosophically and statistically grounded. Furthermore, by introducing evidential modulators, and thereby breaking up the different dimensions of evidence (strength, relevance, reliability), E-Synthesis allows them to be explicitly tracked in updating causal hypotheses. (shrink)

The U.S. Food and Drug Administration's drug advisory committees provide expert assessments of the safety and efficacy of new therapies considered for approval. A committee hears from a variety of speakers, from six groups, including voting members of the committee, FDA staff members, employees of the pharmaceutical company seeking approval of a therapy, patient and consumer representatives, expert speakers invited by the company, and public participants. The committees convene at the request of the FDA when the risks (...) and harms of novel products are not immediately clear, and their final decisions carry significant weight, as most therapies that receive advisory committee approval are subsequently approved by the FDA. In recent years, across a series of diverse publications, the financial conflicts of interest of each category of participants in the meetings have been investigated. Here, we summarize these findings and their ethical implications, focusing on the FDA Oncologic Drugs Advisory Committee, and we suggest ways to move toward more transparent and impartial advisory committee meetings. (shrink)

Treating physicians have key roles to play in expanded access to investigational drugs, by identifying investigational treatment options, assessing the balance of risks and potential benefits, informing their patients, and applying to the regulatory authorities. This study is the first to explore physicians’ experiences and moral views, with the aim of understanding the conditions under which doctors decide to pursue expanded access for their patients and the obstacles and facilitators they encounter in the Netherlands. In this mixed-methods study, semi-structured interviews (...) and a questionnaire were conducted with medical specialists across the country and analysed thematically. Typically, our respondents pursue expanded access in “back against the wall” situations and broadly support its classic requirements. They indicate practical hurdles related to reimbursement, the amount of time and effort required for the application, and unfamiliarity with the regulatory process. Some physicians are morally opposed to expanded access, with an appeal to safety risks, lack of evidence, and “false hope.” Some of these moral concerns and practical obstacles may be essential targets for change, if expanded access to unapproved drugs is to become available for wider groups of patients for whom standard treatment options are not—or no longer—available, on a more consistent and equal basis. (shrink)

Introduction: Physical distancing under the coronavirus disease 2019 pandemic had a significant impact on lifestyles, including exercise routines. In this study, we examined the relationship between mental health and addictive behaviors, such as excessive exercise and the use of image and performance enhancing drugs across 12 sport disciplines.Materials and methods: A large cross-sectional sample of the adult population was surveyed. The mean age was 33.09. The number of male participants was 668. The use of IPEDs was assessed in conjunction with (...) psychometric measures such as the Exercise Addiction Inventory and the Appearance Anxiety Inventory. The participants were grouped into activity group and non-activity group according to the presence or absence of their exercise habits. The results were compared between these groups, as well as across sport disciplines, while taking into account the relationship between different psychological measures and IPEDs consumption.Results: The frequency of IPEDs use was higher among AG than NAG, although AG participants reported less history of addictions than NAG. The logistic regression analysis revealed that scores equal to or above cutoff points, in both the EAI and AAI, predicted the IPEDs use. Regarding the differences across the various sport disciplines, those who were involved in practicing Weight Lifting and Cross Fit were found to be more at risk of excessive exercising and more inclined to use a wide range of IPEDs.Conclusions: Although exercise could help to increase well-being and prevent addictions during the COVID-19 pandemic, our results show that those in the AG are particularly vulnerable to excessive IPEDs use. Sport disciplines associated with higher EAI and AAI scores have also shown a higher tendency to excessive IPEDs use. Furthermore, the factor of having above the cutoff scores in EAI or AAI in each sport could indicate larger IPEDs consumption regardless of the discipline. In light of the current findings, it is necessary to better define the “non-excessive” levels of exercise in various sport disciplines and an adequate intake of IPEDs to ensure the safety and well-being of people during a pandemic. (shrink)

This article presents and evaluates arguments supporting that an approval procedure for genome-edited organisms for food or feed should include a broad assessment of societal, ethical and environmental concerns; so-called non-safety assessment. The core of analysis is the requirement of the Norwegian Gene Technology Act that the sustainability, ethical and societal impacts of a genetically modified organism should be assessed prior to regulatory approval of the novel products. The article gives an overview how this requirement has been (...) implemented in the regulatory practice, demonstrating that such assessment is feasible and justified. Even in situations where genome-edited organisms are considered comparable to non-modified organisms in terms of risk, the technology may have—in addition to social benefits—negative impacts that warrant assessments of the kind required in the Act. The main reason is the disruptive character of the genome editing technologies due to their potential for novel, ground-breaking solutions in agriculture and aquaculture combined with the economic framework shaped by the patent system. Food is fundamental for a good life, biologically and culturally, which warrants stricter assessment procedures than what is required for other industries, at least in countries like Norway with a strong tradition for national control over agricultural markets and breeding programs. (shrink)

BackgroundHealthcare professionals are exposed to advertisements for prescription drugs in medical journals. Such advertisements may increase prescriptions of new drugs at the expense of older treatments even when they have no added benefits, are more harmful, and are more expensive. The publication of medical advertisements therefore raises ethical questions related to editorial integrity.MethodsWe conducted a descriptive cross-sectional study of all medical advertisements published in the Journal of the Danish Medical Association in 2015. Drugs advertised 6 times or more were compared (...) with older comparators: comparative evidence of added benefit; Defined Daily Dose cost; regulatory safety announcements; and completed and ongoing post-marketing studies 3 years after advertising.ResultsWe found 158 medical advertisements for 35 prescription drugs published in 24 issues during 2015, with a median of 7 advertisements per issue. Four drug groups and 5 single drugs were advertised 6 times or more, for a total of 10 indications, and we made 14 comparisons with older treatments. We found: ‘no added benefit’ in 4 of 14 comparisons, ‘uncertain benefits’ in 7, and ‘no evidence’ in 3 comparisons. In no comparison did we find evidence of ‘substantial added benefit’ for the new drug; advertised drugs were 2 to 196 times more expensive per Defined Daily Dose; 11 safety announcements for five advertised drugs were issued compared to one announcement for one comparator drug; 20 post-marketing studies were requested for the advertised drugs versus 10 studies for the comparator drugs, and 7 studies assessed both an advertised and a comparator drug at 3 year follow-up.Conclusions and relevanceIn this cross-sectional study of medical advertisements published in the Journal of the Danish Medical Association during 2015, the most advertised drugs did not have documented substantial added benefits over older treatments, whereas they were substantially more expensive. From January 2021, the Journal of the Danish Medical Association no longer publishes medical advertisements. (shrink)

For the purposes of conservation or suppression of species, gene drive technology has significant potential. Theoretically speaking, with the release of even relatively few animals with gene drive systems in an ecosystem, beneficial or harmful genes could be introduced into the entire wild-type population of that species. Given the profound impact that gene drives could have on species and ecosystems, their use is a highly contentious issue. Communities and groups have differing beliefs about nature and its conservation or preservation, as (...) well as concerns about the ecological safety of the eradication, replacement or enhancement of particular species of animals by means of genetic engineering. For all those reasons, the rigorous regulation of insects and other animals with gene drive systems is crucial. In this paper, we consider the question of whether the United States Food and Drug Administration is prepared to effectively regulate insects and other animals with gene drives. (shrink)

Focusing on the controversial birth control pills Yaz and Yasmin, this article explores how debates about the safety of these drugs have materialized in risk evaluations and the management of technological risk. Drawing on in-depth interviews with stakeholders and content analysis of legal, medical, and regulatory documents, I highlight how professional contraceptive risk assessment is characterized by systemic uncertainty and doubt, resulting in increased responsibility for users themselves to manage the drugs’ potentially increased risks of venous thromboembolism. The (...) analysis centers on three key areas in the assessment process that denote disagreement: risk measurement in postmarket surveillance data, the distinctiveness of the drugs’ benefits when compared to other contraceptive technologies, and the weighing of the risks and benefits against each other. While professionals negotiate uncertainty both in epidemiological research and in clinical practice, users are constructed as agents who should manage risk individually. Such processes are underlined by a diffusion of responsibility in the systemic management of contraceptive risk. This article suggests, more broadly, that medical technologies can be conceptualized as artifacts that are instrumental in the dispersion of risks. (shrink)

In September 2012, news broke of a developing drug disaster in the United States. Health authorities had linked a fungal meningitis outbreak to a contaminated steroid made by a company called the New England Compounding Center. The contaminated steroid was a compounded drug that had not been approved by the Food and Drug Administration, differing from three others that had been approved in that it lacked preservatives present in those agents. Factory inspections revealed unsanitary conditions at NECC's (...) drug production facility. By the time the source of the outbreak was identified, an estimated fourteen thousand people had been injected with the drug. As of December 2012, thirty‐nine had died of meningitis, and hundreds more had been diagnosed with meningitis and other drug‐related conditions. Many factors contributed to this disaster. One was a 2002 Supreme Court decision holding that a law prohibiting providers of compounded drugs from promoting their products through advertising and other means impermissibly restricted commercial speech. (shrink)

This article examines how scientists and regulators distribute the benefit of the doubt about drug safety under conditions of scientific uncertainty. The focus of the empirical research is the regulatory controversy over the hepatorenal toxicity of benoxaprofen in the United Kingdom and the United States. By scrutinizing the technical coherence of the arguments put forward by industrial and government scientists, it is concluded that these scientists are willing to award the commercial interests of the pharmaceutical industry an enormous (...) benefit of the sccentific doubt, which is not consistent with the best interests of patients. Interpretative flexibility, the burden of proof falling on regulators and their trust in, and dependence on, industrial scientists facilitates that distribution of the benefit of the scientific doubt. However, regulatory authorities' need for viability and the rationality common to opposing scientific views suggest that it is possible, in principle, to alter this dominant trend. To achieve adequate patient protection, drug regulation in the United Kingdom and the United States requires extensive reform. Some preliminary policy changes are sketched. (shrink)

The seriousness of the COVID-19 pandemic requires a look into the implementation of drug registration rules for COVID-19 vaccines. Amidst the surrounding exigencies, vaccines being a biological product, require comprehensive and continuing pre and post registration rules to ensure their safety and efficacy. The study focuses on Malaysia which has rules on drug registration that have been successfully applied to vaccines. The study shows that the rules have been tailor-made to emergency situations. At the moment, special rules (...) have been introduced including to allow use of COVID-19 vaccines as unregistered product. Recognition of COVID-19 Vaccines Global Access (COVAX) facility and requirement for government sale only, are among the safety valves. The study shows that these however are temporary measures against the backdrops of possible entry of private players in the vaccination process. Therefore, regulatory responses to intellectual property (IP) related conditions underlying drug registration, and measures to ensure risk management involved in vaccine production, approval and administration are needed in the progressive rules pending further development of research in the area. (shrink)

This article probes the advisability of regulating U.S. food and drug safety according to the precautionary principle. To do so, a precautionary regulatory regime is formulated on the basis of the beliefs that motivate most proponents of this initiative. That hypothetical regime is critically analyzed on the basis of an actual instantiation of a similarly stylized initiative. It will be argued that the precautionary principle entails regulatory constraints that are apt to violate basis tenets of political legitimacy. The (...) modifications that would change this finding would also change precautionary regulation to the point that it would be indistinguishable from orthodox safety protocols. It is concluded on the basis of its impoverished content that the precautionary principle should not be taken seriously as a formal approach to the regulation of U.S. food and drug safety. (shrink)

Children deserve optimal medical care. Although prescription drugs play a prominent and essential role in pediatric health care delivery, health care providers often must make prescribing decisions for their young patients based on imperfect or absent safety and efficacy data for pediatric populations. Until relatively recently, the Food and Drug Administration made surprisingly little effort to improve the quality or quantity of clinical research data for this patient group. Despite recent agency efforts to improve the situation, only one-third (...) of drugs prescribed to children currently have been studied for safety and efficacy in pediatric populations. Moreover, recent agency initiatives to encourage pediatric drug research have generated mixed results and unintended consequences. The complex of issues surrounding the testing and prescribing of prescription drugs used for children will require that pharmaceutical companies, the FDA, and health care providers examine current practices, acknowledge their shortcomings, and consider cooperative, creative solutions. (shrink)

Transgenic plants are now being used to develop pharmaceutical and industrial products in addition to their use in crop improvement. Using confinement requirements, these transgenic plants are grown and processed under conditions that prevent intermixing with commodity crops. Regulatory agencies in the United States have provided guidance of zero tolerance of these new industrial crops with commodity crops. While this is a worthy goal, it is theoretically unattainable. In spite of the best containment practices, there is a potential risk using (...) any system of production due to unforeseen incidences including natural disasters or exposure to workers. The precautionary principle has been used for numerous regulated articles in addressing the potential risks of new products and technology based on a risk assessment in similar situations. We present here a risk assessment model that could be used as a start to develop an accepted model for the industry. The model is based on current risk models used for other regulated articles, but adapted for these types of products. This could be used to determine action levels in the event of an unintended exposure or to ensure that detection or confinement methods are adequate to avoid risks. As an example, aprotinin, a therapeutic protein now being produced in maize, was evaluated for potential risk to humans using this model. (shrink)

Children deserve optimal medical care. Although prescription drugs play a prominent and essential role in pediatric health care delivery, health care providers often must make prescribing decisions for their young patients based on imperfect or absent safety and efficacy data for pediatric populations. The safe and effective use of prescription drugs in children depends on a thorough understanding of the physiologic differences between children and adults. Currently, only one-third of drugs prescribed to children have been studied for safety (...) and efficacy in pediatric populations. Until relatively recently, the Food and Drug Administration made surprisingly little effort to improve the quality or quantity of clinical research data for this patient group. Recent agency efforts to encourage pediatric drug research have generated mixed results and created unintended consequences. The development, prescribing, and safety evaluation of prescription drugs for children will require that the FDA and health care providers examine current practices, acknowledge their shortcomings, and consider creative solutions to the challenges associated with gathering additional data through pediatric drug research. (shrink)

The recent withdrawals of Vioxx, Celebrex, and other drugs from the market have spurred high-profile hearings in Congress and increased concern over the state of drug regulation in consumer protection and academic circles. This renewed focus on national drug safety has translated ineluctably into new legislation designed to mitigate that outcry. The most notable example, the passage of the Food and Drug Administration Amendments Act this past September, is at least partly intended as a response to (...) an apparent lack of public confidence in existing drug safety practices.Of the many provisions in the FDAAA, perhaps none carries greater implications for drug safety than the reauthorized Prescription Drug User Fee Act. Now in its fourth iteration, the newest PDUFA differs in important respects from the statute it supersedes. (shrink)

In the wake of several highly publicized lawsuits over drugs recalled for safety – most notably, Vioxx and Paxil – the Food and Drug Administration and the pharmaceutical industry have faced increasingly intense public scrutiny over the drug testing and approval process. Critics blame the FDA's shorter pre-market approval process that has resulted from the enactment of the Prescription Drug User Fee Act, which effected, among other changes, an increased number of reviewers, a higher review load (...) for each reviewer, and the implementation of “user fees” from companies submitting drugs for review. While many have posited that the lack of safety in some FDA-approved drugs was caused by the enactment of PDUFA, the results of a recent study from the Tufts Center for the Study of Drug Development have indicated that there is no statistically significant correlation between the number of drugs recalled for safety and the enactment of PDUFA. (shrink)

Biotechnological advance is speeding the development of drugs. The approval processes for new drugs will inevitably involve a regulatory agency in making political-economic and scientific choices. Interests of specific patients and the public in general are to be considered, and enormous stakes are involved for companies concerned. A medical regulatory authority must be at once insulated from and responsive to many different mixes of singular and general interests and pressures. Access to new drugs can be spurred by the press of (...) patient advocacy groups, but if there are well organized groups to monitor the testing and approval process for such as AIDS or cancer drugs there is often no similar group to represent patient needs. If there is no organized patient advocacy group, compassionate responsibility by a medical regulatory authority is indeed called for. Delay in the approval of new drugs for fighting severe blood infections raises the question of how to insure the compassionate responsibility of a regulatory authority. (shrink)

In the mid-1980s, social scientists compared outcome measures of related drug studies, some funded by private companies and others by nonprofit organizations or government agencies. The concept of a “funding effect” was coined when it was discovered that study outcomes could be statistically correlated with funding sources, largely in drug safety and efficacy studies. Also identified in tobacco research and chemical toxicity studies, the “funding effect” is often attributed, implicitly or explicitly, to research bias. This article discusses (...) the meaning of scientific bias in research, examines the strongest evidence for the “funding effect,” and explores the question of whether the “funding effect” is an indicator of biased research that is driven by the financial interests of the for-profit sponsor. This article argues that the “funding effect” is merely a symptom of the factors that could be responsible for outcome disparities in product assessment. Social scientists should not suspend their skepticism and choose as a default hypothesis that bias is always or typically the cause. (shrink)

Development of biopharmaceuticals is a challenging issue in bioethics. Unlike conventional, small molecular weight drugs, biopharmaceuticals are proteins derived from DNA technology and hybrid techniques with complex three dimensional structures. Immunogenicity of biopharmaceuticals should always be tested in clinical settings due to low predictive value of preclinical animal models. However, non-human primates and transgenic mice could be used to address certain aspects of immunogenicity. Substantial efforts have been made to reduce NHP use in biopharmaceutical drug development, e.g. study design (...) improvements and changes in regulatory policy. In addition, several expert groups are active in this field. Despite that, there is an increasing trend of use of NHP in preclinical safety testing of biopharmaceuticals, especially regarding monoclonal antibodies. Other potential bioethical issues related biopharmaceutical drug development are their cost/effectiveness ratio, clinical safety assessment, production of biosimilars, and comparison of their efficacy with placebo in countries without intention to market. Identification of the human genome has opened many new bioethical issues. Development of biopharmaceuticals is an important bioethical issue for several reasons. It connects all aspects of contemporary bioethics: bio?medicine, animal welfare and the most recent ad?vances in biotechnology. In particular, biopharmaceutical drug development is a challenging issue regarding treatment of rare diseases. Razvoj biofarmaceutika predstavlja izazov u bioetici. Za razliku od uobicajenih lekova male molekulske mase, biofarmaceutici su proteini kompleksne trodimenzionalne strukture koji se dobijaju tehnologijom rekombinantne DNK i tehnikom hibridoma. Imunogenost biofarmaceutika treba uvek proveriti u klinickim studijama zbog male prediktivne prednosti pretklinickih animalnih modela. Medjutim, primati i transgeni sojevi miseva mogu se upotrebiti da bi se naznacili neki aspekti imunogenosti. Znacajni napori su ucinjeni u cilju smanjenja upotrebe primata u razvoju biofarmaceutika, npr. poboljsanja dizajna istrazivanja i promene u zakonskoj regulativi. Osim toga, u ovoj oblasti su aktivne i pojedine ekspertske grupe. Uprkos tome, postoji rastuci trend upotrebe primata izuzev coveka u pretklinickom ispitivanju bezbednosti biofarmaceutika, posebno kada su u pitanju monoklonska antitela. Druga bioeticka pitanja koja se mogu dovesti u vezu sa razvojem biofarmaceutika su odnos njihove cene i efikasnosti, procena bezbednosti u klinickim uslovima, proizvodnja bioloski slicnih lekova i uporedjivanje njihove efikasnosti sa placebom u zemljama u kojima ne postoji namera o plasmanu. Upoznavanje humanog genoma otvorilo je mnoga bioeticka pitanja. Razvoj biofarmaceutika je vazno bioeticko pitanje iz vise razloga. Ono povezuje sve aspekte savremene bioetike: biomedicinu, dobrobit zivotinja i najnovija dostignuca u biotehnologiji. Posebno, razvoj biofarmaceutika je izazov kada je u pitanju lecenje retkih bolesti. (shrink)

Drowning has been the cause of over 2.5 million preventable deaths in the past decade. Despite the fact that the majority of drownings occur in open water, assessment of water safety competency typically occurs in swimming pools. The assessment of water safety competency in open water environments brings with it a few difficulties, but also promises tremendous benefits. The aim of this position paper is to discuss the benefits and caveats of conducting assessments in open water (...) environments as opposed to closed and controlled environments, and to provide recommendations for evidence-based practice. The first theoretical section discusses the effects of the environment and key variables on various factors of assessment. These discussions are linked to the two perspectives of representative learning design and information processing theory. The second section presents two pilot studies of relevance and provides practical implications for assessment of water safety competency. It seems that a combination of pool-based practice and open water education may be ideal in assessing aquatic skills competency. Assessment in open water presents clear benefits regarding validity, but often poses seemingly unsurmountable barriers, which providers may have reservations about in the absence of clear evidence. Hence this article provides a robust discussion about competency assessment and signals the practical importance of faithfully reproducing the environment in which skilled behavior is most relevant. (shrink)

Volume 20, Issue 4, May 2020, Page 111-113.

This article develops a historico-critical analysis of uncertainty and accuracy in measurement through a case-study of the adjustment of the fundamental physical constants, in order to investigate the sceptical “problem of unknowability” undermining realist accounts of measurement. Every scientific result must include a “measurement uncertainty”, but uncertainty cannot be be eval- uated against the unknown, and therefore cannot be taken as an assessment of “accuracy”, defined in the metrological vocabulary as the closeness to the truth. The way scientists use (...) and interpret uncertainty in the adjustment activity illustrates how they try to overcome this predicament. I iden- tify two operative roles of measurement uncertainty, in the comparison and in the combination of measurement results. This duality implies a tension between selection and combination when aggregating results, leading to a crucial question: should the evaluation of uncertainties favour safety over precision? I present contrasting answers and identify a specific account of physicists who implicitly try to conciliate realism with the problem of unknowability. I argue that this invites us to reconsider accuracy from a dynamical standpoint, as the gradual achievement of scientific progress through error correction. Finally, I present two interpretations of measurement uncertainty, objective and epistemic, which I criticize and suggest improvements to. (shrink)

BackgroundThe complexities of the workplace environment in the downstream oil and gas industry contain several safety-risk factors. In particular, instituting stringent safety standards and management procedures are considered insufficient to address workplace safety risks. Most accident cases attribute to unsafe actions and human behaviors on the job, which raises serious concerns for safety professionals from physical to psychological particularly when the world is facing a life-threatening Pandemic situation, i.e., COVID-19. It is imperative to re-examine the (...) class='Hi'>safety management of facilities and employees’ well-being in the downstream oil and gas production sector to establish a sustainable governance system. Understanding the inherent factors better that contribute to safety behavior management could significantly improve workplace safety features.ObjectiveThis study investigates employees’ safety behavior management model for the downstream oil and gas industry to consolidate the safety, health and wellbeing of employees in times of COVID-19.MethodsNominal Group Technique was first employed to screen primary behavioral factors from 10 workplace health and safety experts from Malaysia’s downstream oil and gas industry. Consequently, 18 significant factors were identified for further inquiry. Next, the interpretive structural modeling technique was used to ascertain the complex interrelationships between these factors and proposed a Safety Behavioral Management Model for cleaner production.ResultsThis model shows that management commitment, employee knowledge and training, leadership, and regulations contribute significantly to several latent factors. Our findings support the Social Cognitive Theory, where employees, their environment, and their behaviors are related reciprocally.ConclusionIt is postulated that identifying safety factors and utilizing the proposed model guides various stakeholder groups in this industry, including practitioners and policymakers, for achieving long-term sustainability. (shrink)

A series of structural constitutional arguments lodged in multiple cases against Centers for Medicare and Medicaid Services’ (CMS) authorities to negotiate prescription drug prices via the 2022 Inflation Reduction Act threaten the legitimacy of CMS program and federal agency powers.

Although testing for substance abuse can be intrusive, inaccurate, and ineffective at ferreting out those who are a threat to others, it can be morally justified in certain carefully circumscribed cases.

The process of risk assessment of biotechnologies, such as genetically modified organisms (GMOs), has normative dimensions. However, the US’ Food and Drug Administration (FDA) seems committed to the idea that such evaluations are objective. This essay makes the case that the agency’s regulatory approach should be changed such that the public is involved in deciding any ethical or social questions that might arise during risk assessment of GMOs. It is argued that, in the US, neither aggregative nor (...) deliberative (representative) democracy ought to be used to make such determinations. Instead, participatory (deliberative) democracy should be the means by which members of the polity decide which normative concerns ought to underlie FDA’s assessment of GMOs. This paper uses a hypothetical case involving a new GM seed to make that argument. (shrink)

The South-to-North Water Diversion Project consists of long-distance water delivery channels and a complicated geological environment along the way. To deal with the operation safety of the water conveyance channels in the middle route of the South-to-North Water Diversion Project, this study analyzes six failure modes: structural cracks, poor water delivery during ice periods, instability of canal slopes, material aging, abnormal leakage, and foundation defects. Based on FMEA, a multigranularity language evaluation method that can be converted into interval intuitionistic (...) fuzzy numbers is used to evaluate the severity, occurrence, and detection difficulty of the six failure modes. Interval intuitionistic fuzzy entropy is used to calculate the weights of the risk factors. Finally, a ranking model of each failure mode is built based on the TODIM method. The final ranking results show that the risk of abnormal leakage is the largest, and the risk of poor water delivery during ice periods is the smallest. The feasibility and validity of the calculation results are verified by comparing them with the ranking results of the traditional RPN and TOPSIS methods. The TODIM-FMEA risk assessment model offers a new solution to the problem of risk assessment for water transfer projects. (shrink)

Volume 20, Issue 4, May 2020, Page 106-108.

The “hijacking” and “drug instrumentalization” models of psychoactive drug use predict opposite outcomes in terms of adaptive behavior and fitness benefits. Which is the range of applicability of each model? To answer this question, we need more data than those reported by studies focusing on medical, psychiatric, and legal problems in addicted users. An evolutionary analysis requires a much wider focus.

The salience of social risks and the incidence of various crises in China have induced widespread concerns among urban residents. Encountering frequent risks places higher demands on the cognition of urban residents. The concept of safety cognition capability is defined within the context of urban residents' daily life, and measurement instruments are developed and tested to lay the foundation for grasping the current safety cognition capability of urban residents and conducting further research. In this study, the five-dimensional structure (...) of urban residents' safety cognition capability was proposed by using the grounded theory method to sort out the interview transcript of interviews with 30 urban residents, and a 38-item URSCC scale was designed and used for surveys conducted in China. The results show that the scale can be used as a valid tool to measure the URSCC, and it can help city managers to better understand the safety needs of residents, as well as monitor the effectiveness of policy implementation. (shrink)