The underreporting of suspected adverse drug reactions remains a primary issue for contemporary post-market drug surveillance or ‘pharmacovigilance.’ Pharmacovigilance pioneer W.H.W. Inman argued that ‘deadly sins’ committed by clinicians are to blame for underreporting. Of these ‘sins,’ ignorance and lethargy are the most obvious and impactful in causing underreporting. However, recent analyses show that diffidence, insecurity, and indifference additionally play a major role. I aim to augment our understanding of diffidence, insecurity, and indifference by arguing these sins (...) are underwritten by value judgments arising via epistemic risk. I contend that ‘evidence-based’ medicine codifies these sins. (shrink)

The placebo drug reactions from controlled trials were studied for the first time systematically for efficacy and the safety in drug data pooled from randomized, placebo-controlled, multicentre studies. Results: The efficacy of placebo on clinical symptoms and outcome varied between the therapeutic indications. However, no placebo effects on laboratory values, as e.g. blood glucose or Hb1c in diabetics, were noted. The frequency and type of placebo-induced adverse reactions also varied between indication groups. The placebo side effect profile (...) was largely similar to the side effect profile of the active treatment. The mechanisms of placebo effects are manyfold and varied (e.g. endorphin release, conditioning), much lacks explanation. Conclusion: Since the prescription of non-evidence based medicines (= pseudoplacebos) may clearly also result in serious adverse effects, such practice may not only be non-beneficial but may even be harmful. In clinical research, the judicious use of placebo remains essential to establish the efficacy and safety, safeguarding that patients receiving placebo will not be subject to harm and are fully informed. (shrink)

Within the world of pharmacology, the male body has traditionally been taken as the biological norm. Coupled with this, concern about danger to the unborn foetus has meant that, until very recently, ‘women of childbearing potential’ were routinely excluded from most of the early phases of clinical drug testing. Consequently, most drugs tested during Phase I trials were initially carried out on healthy male volunteers. During subsequent phases when drugs were tested on patients, women remained largely under-represented. As a (...) result, some drugs prescribed for women have later been discovered to be lacking in efficacy, and women are more likely to suffer adverse drug reactions than men. The exclusion of women during the early phases of clinical drug trials has now been lifted and drugs are currently being more widely tested on women. This paper examines the differing political and ethical positions adopted by the pharmaceutical industry, drug regulators, pharmacologists, women's groups and patient activists in relation to the exclusion and inclusion of women in clinical drug trials. (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 underreporting of suspected adverse drug reactions hinders pharmacovigilance. Solutions to underreporting are oftentimes directed at clinicians and health care professionals. However, given the recent rise of public inclusion in medical science, solutions may soon begin more actively involving patients. I aim to offer an evaluative framework for future possible proposals that would engage patients with the aim of mitigating underreporting. The framework may also have value in evaluating current reporting practices. The offered framework is composed of three (...) criteria that are bioethical, social-epistemic, and pragmatic: (i) patients should not be exposed to undue harms, e.g., nocebo effects; (ii) data should be collected, analyzed, and communicated prioritizing pharmacovigilance’s aims, i.e., free from industry bias; and (iii) proposals should account for existing and foreseeable pragmatic constraints like clinician ‘buy in’ and existing reporting infrastructure. Proposals to engage patients in pharmacovigilance that fulfil or address these criteria are preferable to those that do not. (shrink)

The problem of collecting, analyzing and evaluating evidence on adverse drug reactions (ADRs) is an example of the more general class of epistemological problems related to scientific inference and prediction, as well as a central problem of the health-care practice. Philosophical discussions have critically analysed the methodological pitfalls and epistemological implications of evidence assessment in medicine, however they have mainly focused on evidence of treatment efficacy. Most of this work is devoted to statistical methods of causal inference with (...) a special attention to the privileged role assigned to randomized controlled trials in Evidence Based Medicine. Regardless of whether the RCT’s privilege holds for efficacy assessment, it is nevertheless important to make a distinction between causal inference of intended and unintended effects, in that the unknowns at stake are heterogonous in the two contexts. This point has been emphasized by epidemiologists in the last decade. Their main focus is methodological, and regards the fact that bias and confounding do not affect studies on intended and unintended effects in the same way. However, deeper concerns ground the intuition for such a distinction; these are related to the constraints which we impose on evidence and their epistemological justification. My thesis is that such constraints ought to be understood to be different in the case of evidence for risk vs. benefit assessment. I present the recent debate on the causal association between acetaminophen and asthma in order to illustrate the point at issue. (shrink)

The claim that individuals legitimately differ with respect to their values seems to be uncontroversial among bioethicists, yet many bioethicists nevertheless oppose right-to-try laws. This seems to be due in part to a failure to recognize that such laws are intended primarily to be political, not legal, instruments. The right-to-try movement seeks to build political support for increasing access to newly developed drugs outside of clinical trials. Opponents of right-to-try laws claim that increasing access outside of clinical trials would undermine (...) evidence-based medicine. They seek to maximize overall gains to patients by protecting them from adverse drug reactions and ensuring that drugs are more effective on average. In contrast, right-to-try activists have a point that regulatory judgments of drug safety and effectiveness impose one set of trade-offs on all individuals, regardless of their different values. That might be acceptable if determinations of safety and effectiveness were black and white, but that does not seem to be the case. This article argues that judgments of safety and effectiveness are in an important respect normative and reflect the perceived value of those ends relative to others. Such judgments, when universally imposed, harm patients who would readily make do with less knowledge of drug safety and effectiveness in exchange for more time and self-determination. The relevant moral principle is that of respect for individual autonomy. Just as that principle should lead one to substitute collective decisions for individual ones to regulate a natural monopoly, the same principle should lead one to substitute individual decisions for collective ones to avoid a government monopoly on access to newly developed drugs. It is argued that reforms should increase the number of treatment options available to patients outside of clinical trials. The final section of the article discusses ways in which current regulations might be reformed so as to provide more treatment options outside of clinical trials, without undermining evidence-based medicine. (shrink)

Side effects are ubiquitous in medicine and they often play a role in treatment decisions for patients and clinicians alike. Philosophers and health researchers often use side effects to illustrate issues with contemporary medical research and practice. However, technical definitions of ‘side effect’ differ among health authorities. Thus, determining the side effects of an intervention can differ depending on whose definition we assume. Here I review some of the common definitions of side effect and highlight their issues. In response, I (...) offer an account of side effects as jointly (i) unintended and (ii) effects due to the causal capacities or invariances of an intervention. I discuss (i) by examining the intentions or reasons behind therapeutic interventions, and I discuss (ii) by appealing to a manipulationist model of causation. The analysis here highlights that side effects are conceptually distinct from related outcomes like adverse events, adverse drug reactions, and placebo effects. The analysis also allows for reflection on the utility of ‘side effect’ as a technical term in medical research and practice. (shrink)

Definition of the problem: Recent progress in the pharmacological sciences provides a first glimpse of the development of an individual, genotype-based drug therapy in order to improve the efficiency of drug utilization. Genotyping of genetic polymorphisms in genes involved in drug response promises to optimize drug therapy fundamentally by identifying patients for whom a pharmaceutical agent may be effective and safe or contraindicated because of expected adverse drug reactions. Arguments: The new pharmacogenomic treatment strategies (...) raise complex bioethical issues, because genetic screening for drug therapy may identify asymptomatic patients who are at risk for a particular adverse outcome. Thus, pharmacogenomics will affect the relationship between the treating physician and the patient which is traditionally based on privacy, confidentiality, beneficience and non-maleficience. Conclusion: In the article presented some ethical aspects of these new pharmacogenomic approaches concerning the physician-patient relationship are discussed. (shrink)

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)

Animals are used in biomedical research to study disease, develop new medicines, and test them for safety. As the Oxford Centre for Animal Ethics’ review Normalising the Unthinkable acknowledges, many great strides in medicine have involved animals. However, their contribution has not always been positive. Decades of attempts to develop treatments for diseases including asthma, cancer, stroke, and Alzheimer’s using animals have failed to translate to humans, leaving patients with inadequate treatments or without treatments at all. As Normalising the Unthinkable (...) points out, we have to confront the fact that animal research may have hindered progress, at least in some respects. For example, animal tests have been shown to have very little ability to predict the safety of medicines for human patients. A dramatic illustration of this failing is TGN1412, which almost killed 6 clinical trial volunteers in 2006, after crab-eating macaques showed the drug to be safe, even at massive doses. This failing contributes to adverse drug reactions, which are now one of the world’s leading causes of death, killing hundreds of thousands of people every year and hospitalizing millions. A revolution in science and technology has produced a new generation of more relevant and predictive tools, which could be used to create safer medicines more quickly and at less cost: a win-win situation that should be supported by everyone. The obstacle preventing this from happening is governments’ continued insistence on animal testing. Yet the evidence is clear that reliance on animals as surrogate humans puts patients at risk, can delay medical progress, and can cause effective treatments to be wrongly discarded. There is a compelling case to be made that animal research is an ethical issue for humans as well as for animals. (shrink)

Institutional corruption is a normative concept of growing importance that embodies the systemic dependencies and informal practices that distort an institution’s societal mission. An extensive range of studies and lawsuits already documents strategies by which pharmaceutical companies hide, ignore, or misrepresent evidence about new drugs; distort the medical literature; and misrepresent products to prescribing physicians. We focus on the consequences for patients: millions of adverse reactions. After defining institutional corruption, we focus on evidence that it lies behind the epidemic (...) of harms and the paucity of benefits. (shrink)

Health care resource allocation is a complex governmental task involving political decisions that are bound to be influenced by the various needs of the population and the demands of health professionals. What influence should these different interests have on the integration of new technologies into the health care system? Pharmacogenomics, a new field in the pharmacological sciences that integrates into the drug development process genomic information developed through the Human Genome Project, has been proposed as a technology that promises (...) to make medical practices more personalized. Its integration in drug development or prescription processes could help reduce the risk of adverse drug reactions characteristic of pharmaceutical treatments. Considering the actual allocation of health care resources in Quebec, should the provincial government invest in the integration of pharmacogenomics as a new tool for drug development or drug specification? This question will be addressed using the criteria previously described by Caulfield and colleagues in order to assess the justification of public financing for genetic testing[1], i.e., moral acceptability, utility, safety and the requirement of a noticeable benefit at an acceptable cost for society. Given the proximity of the fields of genetics and genomics, these criteria are applicable to our discussion. (shrink)

In this interesting and stimulating collection, Mark Rothstein has brought together authors from a number of different disciplines to explore some of the issues surrounding pharmacogenomics: the use of genetic testing to design new drugs, and to prescribe more effectively the drugs we already have. Pharmacogenomics is an area of fevered speculation on the part of biotechnology firms and large pharmaceutical companies. Their hope is that by targeting drugs at specific populations, industry will be able to develop new products more (...) quickly, more cheaply, and with less risk of marketing something that actually kills the patient. An often cited study by Lazarou, Pomeranz, and Corey suggests that adverse drugs reactions are between the fourth and the sixth biggest causes of death in US hospitals.1As someone very familiar with the scientific and ethical literature on pharmacogenomics, I did find that a number of chapters in this collection simply rehearsed arguments that have been made elsewhere, sometimes by the same authors. Rather than seeing these as “fillers”, however, I think it is better to regard them as providing a sound introduction to the current state of …. (shrink)

The problem of collecting, analyzing and evaluating evidence on adverse drug reactions (ADRs) is an example of the more general class of epistemological problems related to scientific inference and prediction, as well as a central problem of the health-care practice. Philosophical discussions have critically analysed the methodological pitfalls and epistemological implications of evidence assessment in medicine, however they have mainly focused on evidence of treatment efficacy. Most of this work is devoted to statistical methods of causal inference with (...) a special attention to the privileged role assigned to randomized controlled trials in Evidence Based Medicine. Regardless of whether the RCT’s privilege holds for efficacy assessment, it is nevertheless important to make a distinction between causal inference of intended and unintended effects, in that the unknowns at stake are heterogonous in the two contexts. This point has been emphasized by epidemiologists in the last decade. Their main focus is methodological, and regards the fact that bias and confounding do not affect studies on intended and unintended effects in the same way. However, deeper concerns ground the intuition for such a distinction; these are related to the constraints which we impose on evidence and their epistemological justification. My thesis is that such constraints ought to be understood to be different in the case of evidence for risk vs. benefit assessment. I present the recent debate on the causal association between acetaminophen and asthma in order to illustrate the point at issue. (shrink)

Pharmacogenetics is the study of inherited variations in drug response Pharmacogenetics uses the techniques of pharmacology, population genetics, biochemical genetics and, most recently, molecular biology, to study the biological basis for individual variation in therapeutic response and in the occurrence of adverse reactions to medications. Most pharmacogenetic experiments deal with inherited differences in drug metabolism. The discussion here will review inherited variation in the activity of thiopurine methyltransferase, an enzyme that catalyzes the methyl conjugation of an important (...) group of drugs, the thiopurines. (shrink)

The placebo drug reactions from controlled trials were studied for the first time systematically for efficacy and the safety in drug data pooled from randomized, placebo-controlled, multicentre studies. Results: The efficacy of placebo on clinical symptoms and outcome varied between the therapeutic indications. However, no placebo effects on laboratory values, as e.g. blood glucose or Hb1c in diabetics, were noted. The frequency and type of placebo-induced adverse reactions also varied between indication groups. The placebo side effect profile (...) was largely similar to the side effect profile of the active treatment. The mechanisms of placebo effects are manyfold and varied (e.g. endorphin release, conditioning), much lacks explanation. Conclusion: Since the prescription of non-evidence based medicines (= pseudoplacebos) may clearly also result in serious adverse effects, such practice may not only be non-beneficial but may even be harmful. In clinical research, the judicious use of placebo remains essential to establish the efficacy and safety, safeguarding that patients receiving placebo will not be subject to harm and are fully informed. (shrink)

Some patients tolerate a given drug well, without adverse reactions. For others, though, an identical dose of the same medication can have toxic effects. Moreover, while a drug can be effective at relieving symptoms for some patients, it may fail to do the same for others suffering with the same disease. With such variability in treatment responses, tailoring medical interventions to individual patients has long been an aspiration of medicine. Until recently, however, medicine lacked a clear understanding (...) of the biological reasons for human variation in drug response. Attempting to adjust treatment to the individual patient, physicians have relied primarily on direct observation, trial-and-error, and, ultimately... (shrink)

The intensity and prevalence of viral infections are typically higher in males, whereas disease outcome can be worse for females. Females mount higher innate and adaptive immune responses than males, which can result in faster clearance of viruses, but also contributes to increased development of immunopathology. In response to viral vaccines, females mount higher antibody responses and experience more adverse reactions than males. The efficacy of antiviral drugs at reducing viral load differs between the sexes, and the adverse (...) reactions to antiviral drugs are typically greater in females than males. Several variables should be considered when evaluating male/female differences in responses to viral infection and treatment: these include hormones, genes, and gender‐specific factors related to access to, and compliance with, treatment. Knowledge that the sexes differ in their responses to viruses and to treatments for viral diseases should influence the recommended course of action differently for males and females.Editor's suggested further reading in BioEssays X‐chromosome‐located microRNAs in immunity: Might they explain male/female differences Abstract. (shrink)

The possibilities of genetic engineering, particularly as applied to human beings, have provoked considerable debate for over two decades, but more recently the focus of public concern, at least, has turned to genetically modified (GM) food. Food has occasionally caught the attention of philosophers (Telfer, 1996) and bioethicists (Mepham, 1996) but is now ripe for further attention in the light of the implications of GM for policy in health, economics and politics. Macer has identified opposing reactions to novel foods—to prefer (...) to eat down the food chain, on the one hand, and to embrace technology, on the other (Macer, 1997). One question that has given rise to some interest is why consumer attitudes to genetically modified food have been so much more strongly adverse in Europe, particularly in the UK, than in the USA. This paper explores the ways in which the food ethics debate has been constructed in recent debates in the UK, with special reference to the similarities to and differences from what are on the face of it analogous debates in medical ethics. What is special about food, as opposed to drugs, which makes it appropriate or inappropriate to construct the arguments in the terms that currently predominate? This will involve looking in particular at the application of the principle of autonomy and the argument from consumer choice. (shrink)

The possibilities of genetic engineering, particularly as applied to human beings, have provoked considerable debate for over two decades, but more recently the focus of public concern, at least, has turned to genetically modified food. Food has occasionally caught the attention of philosophers and bioethicists but is now ripe for further attention in the light of the implications of GM for policy in health, economics and politics. Macer has identified opposing reactions to novel foods—to prefer to eat down the food (...) chain, on the one hand, and to embrace technology, on the other. One question that has given rise to some interest is why consumer attitudes to genetically modified food have been so much more strongly adverse in Europe, particularly in the UK, than in the USA. This paper explores the ways in which the food ethics debate has been constructed in recent debates in the UK, with special reference to the similarities to and differences from what are on the face of it analogous debates in medical ethics. What is special about food, as opposed to drugs, which makes it appropriate or inappropriate to construct the arguments in the terms that currently predominate? This will involve looking in particular at the application of the principle of autonomy and the argument from consumer choice. (shrink)

Worries about safety of approved drugs have pushed post registration research to become the fastest growing drug research phase. Until recently, phase IV studies were mainly conducted for marketing purposes and run much like a phase III trial—at institutions with experienced investigators and a list of inclusion and exclusion criteria. Innovative phase IV studies involve ordinary physicians in research naïve communities. This brings ethical issues familiar to medical research into clinical practice. As a consequence, individual physicians are challenged to (...) protect scientific integrity and to secure the ethical conduct of research. Several ethical issues need to be addressed in the process of developing a scientifically sound and ethically high principled practice of phase IV research.PHASE IVEssential to phase IV research is the focus on how drugs work in the real world. The research goal may be to explore a specific pharmacological effect, to establish the incidence of adverse reactions, or to determine the effects of long-term administration of a drug. They may also be designed to establish a new clinical indication for a drug.1 Subjects may or may not be randomised, and the studies typically involve large numbers of patient-subjects and physicians.Doubts concerning the scientific rigor and clinical value have put postmarketing research in a poor light. However, high quality phase IV research is badly needed to further pharmaceutical science. First, because it can provide reliable data on the effectiveness, safety and optimal use of a drug in treated populations.2 3 In pre-registration clinical trials , a pharmaceutical product is studied under unrealistic circumstances. Under-representation of women and elderly are common and the concomitant use of medicines is usually extremely restrictive in these trials.4 Second, phase IV can provide much needed data for evidence-based …. (shrink)

Prospective follow-up studies have shown that even though some children outgrow the disorder, a childhood diagnosis of attention deficit hyperactivity disorder is clearly a risk factor for a broad range of adverse outcomes, with extremes including drug abuse and juvenile delinquency. This article considers the use of several spectrum concepts and some neuroethical issues. It provides a list of criterion symptoms with a threshold set for the number of symptoms required for categorical diagnoses of disorders. It gives a (...) brief review of some brain imaging and pharmacological treatment studies of ADHD to set the stage for a consideration of brain-specific issues related to neuroethics. Studies using reaction time tasks of cognitive control, response inhibition, and conflict have identified interindividual variance in task performance as one of the most prominent aspects of cognitive deficits related to ADHD. (shrink)

Various kinds of alcohol and drug testing, such as preemployment, routine, and for-cause testing, are commonly performed by employers. While healthcare organizations usually require preemployment drug testing, they vary on whether personnel will be subjected to further testing. Recently, a call has gone out for postincident testing among physicians who are involved in serious, preventable events, especially ones leading to a patient's death. This article will offer a number of counterarguments to that proposal and discuss an alternate approach: (...) that health institutions can better improve patient safety and employees’ well-being by implementing an organizational policy of “speaking up” when system operators notice work behaviors or environmental factors that threaten harm or peril. The article will conclude with a description of various strategies that facilitate speaking up, and why the practice constitutes a superior alternative to mandatory alcohol and drug testing in the wake of serious, harm-causing m.. (shrink)

It is widely claimed that climate change has increased the magnitude and the frequency of natural phenomena such as storms, droughts, and floods with the concomitant costs in terms of damages and victims. This paper using weekly data from global stock market indices in a Fama–French model, examines how and to what extent market agents and investors react to such events. As a yardstick for comparison purposes, the possible market impact of industrial accidents is also incorporated and examined in the (...) empirical investigation. The study uses in a comparative approach the STOXX Global ESG Environmental Leaders index and the STOXX Global index diversified across 1800 top companies. Results reported herein seem to indicate that natural and anthropogenic adversity have no immediate impact on the stock indices, while wildfires have an immediate reduction impact on market risk in the case of the ESG Environmental Leaders index. Moreover, wildfires and industrial accidents appear to cause a significant reduction of systematic risk over the next week following the incident. However, the magnitude of the effect is higher in the case of the ESG Environmental Leaders stock index. Finally, the effect on systematic risk by industrial accidents is temporarily without any lasting imprint. (shrink)

The benzodiazepines can produce a wide variety of abnormal mental responses and hazardous behavioral abnormalities, including rebound anxiety and insomnia, mania and other forms of psychosis, paranoia, violence, antisocial acts, depression, and suicide. These drugs can impair cognition, especially memory, and can result in confusion. They can induce dependence and addiction. Severe withdrawal syndromes with psychosis, seizures, and death can develop. The short-acting benzodiazepines, alprazolam and triazolam , are especially prone to cause psychological and behavioral abnormalities. The sources of data (...) to support these observations and conclusions are discussed in regard to the scientific method. These adverse drug effects can wreck havoc in the lives of individuals and their families. (shrink)

A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. Description: The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to (...) standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term ‘adverse event’ denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. (shrink)

We use the format of a hypothetical case study to review issues related to pharmaceutical product approval and physician prescribing practices. In this case, a new FDA-approved drug is recommended for a patient who subsequently experiences an adverse event that may or may not be related to the prescription. This case raises a number of ethical and legal considerations physicians routinely face when deciding whether to recommend such drugs for their patients. Despite the need for ongoing observation by (...) the regulatory apparatus, physicians should be cognizant of the limitations of the drug approval system and the post-approval prescription drug surveillance system. We discuss physicians’ ethical obligations when faced with a newly approved drug, including seeking out independent sources of learning, reporting adverse effects, and notifying patients about limitations in available knowledge about therapeutic recommendations. (shrink)

This book describes and analyses the activities and procedures through which the professional economist may advise on matters of public policy, specifically on the performance of an economic system. The author shows that the decision-making component within a system may be defined in terms of optimal policies for attaining well-specified objectives, but that the choice of rules by which the system is governed must remain 'outside' the system due to its dependence upon the legislative process. He proposes a 'generating mechanism' (...) for arriving at public policy choices based on the interaction between the economic system and the legislative process. (shrink)

Grunbaum claims that the remedial failure of atreatment's characteristic factors is thegeneric, objective property of a placebo. Hestipulates that a treatment is placebic if thisremedial failure exacerbates the targetdisorder. This stipulation can subsume asplacebic effects that might be solelypharmacological, e.g., paradoxical reactions tocertain psychiatric drugs. If that exacerbationcan be explained pharmacologically, then wemight question whether Grunbaum's definitionalscheme captures the core identity of what weusually intend by the placebo concept. Ipropose that this core identity is bestcaptured by a symbolic meaning hypothesis (...) inwhich psychological factors exert thedeterminative influence. (shrink)

Previous research suggests that adversity can have both adaptive and maladaptive effects, yet the emotional and working memory processes that contribute to more or less adaptive outcomes are unclear. The present study sought to investigate how updating emotional content differs in adolescents who have experienced past, recent, or no adversity. Participants who had experienced distant adversity, no adversity, or recent adversity only performed an emotion n-back task with emotional facial expressions. Results revealed that the distant adversity group exhibited significantly faster (...) reaction times than the no adversity and recent adversity only groups. In contrast, the recent adversity only group exhibited significantly slower RTs and more errors than the distant adversity and no adversity groups. These results suggest an emotion and executive control pathway by which both the benefits and negative effects of adversity may be conferred. Results also highlight the importance of time in assessing the impact of adversity. (shrink)

Promoting patient autonomy has become a key imperative in health service encounters. We will examine the potential negative effects of over-promoting patient autonomy and consider the impact on patient access, their experience and the provision of equitable services by focusing on an extreme manifestation of this trend, i.e. calls for patient involvement in health care decision making to be mandatory. Advocates of mandatory autonomy hold that patients have a duty to themselves, to society and to the medical system to make (...) decisions on their health care independently. Models of mandatory autonomy may be contrasted to those of optional autonomy that seek to ascertain patients’ decisional preferences and to understand wider limitations on their freedom to choose. Where choice as decisional responsibility becomes mandatory it ceases to promote agency and where autonomous choice is understood as an individualistic practice it will contribute to the cultural dominance of Western values. Moreover, taking a view that principlist ethics needs to take account of the social and cultural contexts of individual lives, we argue that if mandatory autonomy were to be over-emphasised as part of an ongoing move towards patient choice in UK National Health Service (NHS), educated and affluent people would be more able to exercise choices at the expense of people who are experienced in asserting preferences and who have the resources to make use of choices. We will argue that the promotion of autonomy needs to be tempered by steps to enable less powerful social, cultural and economic groups to contribute to decision making and to support individuals who may feel abandoned by having decisional responsibility transferred to them. Until constraints on individual choice can be understood and addressed, we advocate the model of optional autonomy used in shared decision making and make recommendations for practice, policy, education and research. (shrink)

This essay examines President Nixon's drug policy during the early 1970s, specifically the government's reaction to heroin use by American soldiers in Vietnam. The official response, discursively (through the employment of the drugs-as-a-disease metaphor) and on the policy level illustrated how of issues of national- and self-identity othering, and modernity intersected in the formulation and implementation of what is now termed the Drug War. Heroin using soldiers and domestic addicts, labeled as carriers of a contagious, foreign, and (...) antimodem, dangerous disease, threatened to undermine a contingent national identity an identity weighted by capitalist modernity. Unearthing how addiction's ostensibly antimodern condition contributed to the othering of addicts as a foreign danger reveals how the United States' antidrug character and policies help maintain a national identity bound to the tenets of capitalist modernity. Methodologically, this essay combines historical analysis with literary and critical theory. (shrink)

This paper outlines a phenomenological approach for describing physiological reactions occurring immediately after vital threats. This exemplified by data taken from previous studies relative to chemical intoxications of rats by a neurotoxical drug. The survival rate of the animals and the variations of their cerebral acetylcholinesterese activity are both reported as a function of the drug concentration, and with respect to their age. The collecting of the results may be described as the cusp, a bifurcation set of Thom's (...) Catastrophe Theory.The young animals react by a vital burst which modifies the shape of the cusp. A new fold or pocket takes place, changing it to the butterfly bifurcation set. This pocket supports the survival attractor concept, which appears reactional, transitory and variable in its intensity. (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)