Children who experience well-being are engaging more confidently and positively with their caregiver and peers, which helps them to profit more from available learning opportunities and support current and later life outcomes. The goodness-of-fit theory suggests that children’s well-being might be a result of the interplay between their temperament and the environment. However, there is a lack of studies that examined the association between children’s temperament and well-being in early childhood education and care, and whether this association is affected by (...) ECEC process quality. Using a multilevel random coefficient approach, this study examines the association between toddlers’ temperament and well-being in Norwegian ECEC and investigates whether process quality moderates this association. Results reveal an association between temperament and well-being. Staff-child conflict moderates the association between shyness and well-being, and between activity and well-being. Moreover, high emotional behavioral support moderates the association between activity and well-being. Extra attention should be paid by the staff to these children’s needs. (shrink)

The paper presents major ethical, legal and methodological problems related to the use of placebo in mental disorders, especially in depression. It is pointed out that although authoritative groups of experts and numerous publications in the field of psychopharmacology indicate advisability of the double blind design with placebo in clinical trials of antidepressants, in recent years there have been more and more voices questioning legitimacy of this method. Objections of an ethical nature are raised, and reliability of this approach is (...) put into doubt from the methodological viewpoint. These issues are discussed in more detail in the paper. Available alternative solutions should be implemented in psychotropic drug studies. The author shares these objections and doubts of an ethical nature, and believes that the placebo procedure is not a necessity in clinical trials of antidepressants. (shrink)

Philosophical and empirical research on bodily awareness has mostly focused so far on bodily disorders – such as anorexia nervosa, somatoparaphrenia, or xenomelia (body integrity dysphoria) – and bodily illusions induced in an experimental setting – such as the rubber hand illusion, or the thermal grid illusion. Studying these conditions can be illuminating to investigate a broad range of issues about the nature, function, and etiology of bodily experience. However, a number of psychoactive compounds can also induce a remarkably wide (...) variety of bodily effects that have received little attention despite their relevance to these issues. Some of these effects are similar to those associated with bodily disorders or experimental bodily illusions, while others appear to be unique. The purpose of this chapter is to provide an overview of these lesser known bodily effects of psychoactive compounds, and outline some ways in which they can bear on recent debates regarding bodily awareness and bodily ownership. (shrink)

Objectives: The aim of this study was to investigate the actual condition of the students of University of Rajshahi (RU) regarding drug abuse and addiction. Using case study method the research was conducted with four objectives: (a) to find out how respondents began drug abuse; (b) to discover the causes of their drug addiction; (c) to understand the process of their drug abuse; and (d) to find out the economic, social and health effects of drug abuse. Methods: Case study method (...) was used in this research. Through snowball sampling 18 drug- addicted students of RU were selected as respondents. In-depth interview with a schedule was used to collect data from the respondents in January 2019. Results: Findings of the study show that the causes of drug addiction included curiosity, frustration, friends’ request, neglect from family and friends etc. The drugs which they usually abused were Yaba, Phensydyle, Ganja (Weed), Chuani etc. Their average monthly expenditure for collecting drugs was in between Taka 8,000-10,000. They collected those drugs from rickshaw pullers at different points within the campus and from Mizaner Mor, Budhpara slum and other places outside the campus. The respondents opined that drugs were available if sufficient money could be spent. The respondents had senior and junior fellow students and local boys as companions while taking drugs. Most of them faced physical problems after taking drugs, and some of them tried to get rid of this curse of drug addiction. Conclusion: The findings of this research show that the rate of drug addiction among the students of RU was quite alarming. Therefore, all stakeholders including the students, guardians, teachers, university authority, the law makers and law enforcing agencies, researchers, civil society, NGO’s and the state must come forward together to combat this formidable foe. (shrink)

New technologies regularly bring about profound changes in our daily lives. Romantic relationships are no exception to these transformations. Some philosophers expect the emergence in the near future of love drugs: a theoretically achievable biotechnological intervention that could be designed to strengthen and maintain love in romantic relationships. We investigated laypeople’s resistance to the use of such technologies and its sources. Across two studies (Study 1, French and Peruvian university students, N after exclusion = 186; Study 2, Amazon Mechanical Turk (...) sample, N after exclusion = 693, pre-registered), we found that the use of love drugs designed to strengthen and maintain love in romantic relationships are considered as more morally problematic than psychological therapy with the same aim. In Study 2, we show that this last effect is partially due to the fact that the love resulting from the use of love drugs is perceived as less authentic, intense, and durable. We discuss the specific role of authenticity in the relative moral disapproval of love drugs. (shrink)

Do pharmaceutical companies have a moral obligation to expand access to investigational drugs to patients outside the clinical trial? One reason for thinking they do not is that expanded access programs might negatively affect the clinical trial process. This potential impact creates dilemmas for practitioners who nevertheless acknowledge some moral reason for expanding access. Bioethicists have explained these reasons in terms of beneficence, compassion, or a principle of rescue, but their arguments have been limited to questions of moral permissibility, (...) leaving for future research the question of whether expanded access is morally obligatory. We take up this further question and argue that pharmaceutical companies have a moral obligation to expand access. Our defense is not based on beneficence, compassion, or rescue, but instead on a reciprocal moral expectation resulting from existing social commitments that help ensure a robust pharmaceutical practice within the broader healthcare system. Our aim is to give this obligation, along with several others, a coherent and plausible structure within the wider clinical trial process so that one might better explain the sources of the dilemmas and their possible resolutions. (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)

When seriously ill patients reach the end of the standard treatment trajectory for their condition, they may qualify for the use of unapproved, investigational drugs regulated via expanded access programs. In medical-ethical discourse, it is often argued that expanded access to investigational drugs raises ‘false hope’ among patients and is therefore undesirable. We set out to investigate what is meant by the false hope argument in this discourse. In this paper, we identify and analyze five versions of the (...) false hope argument which we call: (1) the limited chance at benefit argument, (2) the side effects outweighing benefits argument, (3) the opportunity costs argument, (4) the impossibility of making informed decisions argument, and (5) the difficulty of gaining access argument. We argue that the majority of these five versions do not provide normative ground for disqualifying patients’ hopes as false. Only when hope is rooted in a mistaken belief, for example, about the likelihood of benefits or chances on medical risks, or when hope is directed at something that cannot possibly be obtained, should it be considered false. If patients are adequately informed about their odds of obtaining medical benefit, however small, and about the risks associated with an investigational treatment, it is unjustified to consider patients’ hopes to be false, and hence, to deny them access to investigational drug based on that argument. (shrink)

Up till now, China has not enacted any legal mechanisms governing certification or supervision for ethics committees. This article analyses deficiencies in the protection of subjects in clinical drug trials under China’s current laws and regulations; it emphasizes that investigators, as practitioners who have direct contact with subjects, play significant roles in protecting and safeguarding subjects’ rights and interests. The paper compares the status quo in China in this area to that of other countries and discusses ways China might enhance (...) the protection of rights and interests of trial subjects, such as enhancing the ethical awareness of investigators through training, improving laws and regulations, and strengthening the communication between investigators and ethics committees. (shrink)

Drawing on ethical and legal frameworks in the Netherlands, the United States and France, we examine whether physicians are expected to inform patients about potentially relevant opportunities for expanded access to investigational drugs. While we found no definitive legal obligation, we argue that physicians have a moral obligation to discuss opportunities for expanded access with patients who have run out of treatment options to prevent inequality, to promote autonomy, and to achieve beneficence.

BackgroundExpanded access is the use of investigational drugs (IDs) outside of clinical trials. Generally it is performed in patients with serious and life-threatening diseases who cannot be treated satisfactorily with authorized drugs. Legal regulations of expanded access to IDs have been introduced among others in the USA, the European Union (EU), Canada and Australia. In addition, in the USA an alternative to expanded access is treatment under the Right-to-Try law. However, the treatment use of IDs is inherently associated with (...) a number of ethically relevant problems.Main textThe objective of this article is to present a coherent framework made up of eight requirements which have to be met for any treatment use of an ID to be ethical. These include a justified need for the use of an ID, no threat to clinical development of the ID, adequate scientific evidence to support the treatment, patient’s benefit as the primary goal of the use of an ID, informed decision of a patient, fair access of patients to IDs, independent review, as well as the dissemination of treatment results.ConclusionsWhile this framework is essentially consistent with the legal regulations of expanded access of the USA, the EU, Canada and Australia, it is substantially wider in scope because it addresses some important issues that are not covered by the regulations. Overall, the framework that we developed minimizes the risks and threats, and maximizes potential benefits to each of the four key stakeholders involved in the treatment use of IDs including patients, doctors, drug manufacturers, and society at large. (shrink)

Coronavirus disease 2019 is a fast-developing viral pandemic spreading across the globe. Due to lack of availability of proven medicines against COVID-19, physicians have resorted to treatments through large trials of investigational drugs with poor evidence or those used for similar diseases. Large trials randomize 100–500+ patients at multiple hospitals in different countries to either receive these drugs or standard treatment. In order to expedite the process, some regulatory agencies had also given permission to use drugs approved for other (...) diseases, despite a lack of evidence of efficacy in COVID-19. In this review, we highlight the potential ethical issues that should be addressed during the use of investigational drugs with little prior evidence as a treatment options during a pandemic. We discuss the impact of design of randomized clinical trials using LOTUS trial as an example and that of off-label use of drugs like chloroquine/hydroxychloroquine on the safety of patients during COVID-19. We conclude that the adaptive randomized clinical trial designs offer a flexible and efficient approach, enabling patients to quickly switch to successful treatments, while minimizing the number of patients on standard of care. Randomized clinical trial design should consider blinding of investigators and only representative patients who can provide consent should be included. We also conclude the emergency approvals of drugs should be carefully issued and off-label use should be restricted in pandemics. Streamlined regulatory guidelines for emergency drug use in a pandemic can also help in providing benefit and minimizing harm to patients in the future. (shrink)

The possibility that industry is exerting an undue influence on the culture of medicine has profound implications for the profession's public health mission. Policy analysts, investigative journalists, researchers, and clinicians have questioned whether academic-industry relationships have had a corrupting effect on evidence-based medicine. Psychiatry has been at the heart of this epistemic and ethical crisis in medicine. This article examines how commercial entities, such as pharmaceutical companies, influence psychiatric taxonomy and treatment guidelines. Using the conceptual framework of institutional corruption, we (...) show that organized psychiatry's dependence on drug firms has led to a distortion of science. We describe the current dependency corruption and argue that transparency alone is not a solution. We conclude by taking the position that the corruption of the evidence base in diagnostic and practice guidelines has compromised the informed consent process, and we suggest strategies to address this problem. (shrink)

This article investigates the distribution of power in Poland’s drug reimbursement policy in the early 2000s. We examine competing theoretical expectations suggested by neopluralism, historical institutionalism, corporate domination, and clique theory of the post-communist state, using data from a purposive sample of 109 semi-structured interviews and documentary sources. We have four concrete findings. First, we uncovered rapid growth in budgetary spending on expensive drugs for narrow groups of patients. Second, to achieve these favorable policy outcomes drug companies employed two prevalent (...) methods of lobbying: informal persuasion of key members of local cliques and endorsements expressed by patient organizations acting as seemingly independent “third parties.” Third, medical experts were co-opted by multinational drug companies because they relied on these firms for scientific and financial resources that were crucial for their professional success. Finally, there was one-way social mobility from the state to the pharmaceutical sector, not the “revolving door” pattern familiar from advanced capitalist countries, with deleterious consequences for state capacity. Overall, the data best supported a combination of corporate domination and clique theory: drug reimbursement in Poland was dominated by Western multinationals in collaboration with domestically based cliques. (shrink)

The US Food and Drug Administration (FDA) is fraught with controversies over the role of values and politics in regulatory science, especially with drugs in the realm of reproductive health. Philosophers and science studies scholars have investigated the ways in which social context shapes medical knowledge through value judgments, and feminist scholars and activists have criticized sexism and injustice in reproductive medicine. Nonetheless, there has been no systematic study of values and gender norms in FDA drug regulation. I focus on (...) three questions about values in regulatory science. First, how have societal values and gender norms shaped the way that the FDA regulates drugs in the realm of reproductive health, specifically with drug labels? Second, what are the ethical, epistemic, and social consequences of these influences on regulation for women and other marginalized groups? Third, which societal values and gender norms ought to influence drug regulation about reproductive health, and how ought this happen? Integrating philosophical analysis with historical archival research and in-depth interviews, I conduct three case studies of drug labeling about reproductive health: (1) the “drug fact” about the mechanism of the morning-after pill; (2) the package inserts for patients about the health risks of oral contraceptives; and (3) the special physician labels made for prescribing drugs to pregnant women. I identify three challenges for the FDA and suggest ways to reduce the influence of sexist values and facilitate feminist alternatives. First, across these cases, I have found that there are many ways in which other concerns in reproductive medicine (such as zygotic life, fetal health, and population control) have devalued women’s health. Second, both knowledge and ignorance xvi about their reproductive health have contributed to women’s oppression, especially poor women and women of color. Finally, by avoiding the epistemic dimensions of ethics, powerful, mostly male parties in medicine (such as doctors, pharmaceutical companies, and religious institutions) have misused “informed consent,” “religious freedom,” and “paternalism” for unethical purposes. For improvement, I suggest extracting sexist values and gender norms from regulatory science that cause epistemic injustices, and I point to success stories for reforming sexism with feminism at the FDA. (shrink)

This paper1 uses concepts of anxiety and Foucauldian governmentality to investigate the ways that the discourses supporting the ban on performance-enhancing drugs in sport have been manipulated and broadened to treat this issue as a public policy and health issue rather than an example of rule violation in sport. Some effects of this expansion include the broadening of drug testing to include testing for recreational drugs, the intrusion of both central governments and scientific experts into the issue and the curtailment (...) of civil liberties for athletes. A further effect has been the perpetration of injustices against athletes under the guise of such injustices being necessary to maintain the integrity of sport. (shrink)

Many children in the USA are prescribed psychotropic drugs that have not been fully investigated in paediatric clinical trials. The common practice of prescribing psychotropic drugs off-label poses unknown and potentially serious short- and long-term consequences for these children. This paper briefly reviews the factors associated with the lack of paediatric clinical trials. We advocate a shift toward increasing paediatric trials with psychotropic drugs through a combination of adequate safety controls, additional reimbursement/compensation, a more organised and large-scale effort to collate (...) results and outcomes across researchers and studies and additional public education about the importance of this research. In addition, we encourage the re-examination of the ethical standards for children's participation in phase 1 clinical trials as well as argue for longitudinal developmental studies on children who are prescribed off-label psychotropic drugs. (shrink)

Drug phenomenon is relatively new in our country; it became relevant only in the ninth decade of the last century. A new phenomenon or a process is usually dynamic in the initial stages and only later does it acquire features of stability and the main trends that have become prominent several years ago remain unchanged. The author shows the data of drugs crime and other indicators and the aspects of their perspectives. In the article, a question about drug crimes in (...) Lithuania is considered in all aspects. The author maintains that the rapid emergence of many new non‑controlled psychoactive substances represents an increasing challenge for current models of drug control. (shrink)

Submission of study protocols to research ethics committees constitutes one of the earliest stages at which planned trials are documented in detail. Previous studies have investigated the amendments requested from researchers by RECs, but the type of issues raised during REC review have not been compared by sponsor type. The objective of this study was to identify recurring shortcomings in protocols of drug trials based on REC comments and to assess whether these were more common among industry-sponsored or non-industry trials.

Conflicts of interest are common and exist in academia, government, and many industries, including pharmaceutical development. Medical journal editors and others have recently criticized “the pharmaceutical industry,” citing concerns over investigator access to data, approaches to analysis of clinical trial data, and publication practices. Merck & Co., Inc. is a global, research-driven pharmaceutical company that discovers, develops, manufactures, and markets a broad range of human and animal health products, directly and through its joint ventures. Although part of its mission is (...) to provide a superior rate of return to its investors, Merck does not believe this creates an irreconcilable conflict of interest, particularly in activities concerning clinical drug development. We employ rigorous scientific methods to design, conduct, analyze, and report results of clinical trials in the development of innovative drugs and vaccines, with a focus on meeting unmet medical needs and with an ethic that puts the interests of the patient first. This article describes Merck’s approaches to potential conflicts of interest in drug development, particularly with regard to clinical trials. We believe that proprietary interests of the Company can be respected while observing objectivity and transparency in communicating clinical research results. The standards for the review of manuscripts reporting such trials for peer-reviewed publication should be the same, whether they are from Merck or elsewhere. (shrink)

Studies have reported high rates of childhood maltreatment among individuals with drug addiction problems; however, investigation about the potentially protective factors to mitigate the effects of maltreatment experiences on motivation to engage in addiction treatment has received less attention. This study aims at exploring the mediating effects of forgiveness and self-efficacy on the association between childhood maltreatment and treatment motivation among drug addicts. A total of 360 male drug addicts were recruited from three mandatory inpatient rehabilitation centers in Malaysia. Participants (...) completed a package of self-report questionnaires including measures of childhood maltreatment experiences, forgiveness, self-efficacy, and motivation for treatment. The analysis conducted using the structural equation model revealed that childhood maltreatment significantly predicted lower treatment motivation, while forgiveness and self-efficacy played a fully mediating role regarding the effect of childhood maltreatment on treatment motivation. In conclusion, these findings suggest that combining the element of forgiveness and self-efficacy in treatment programs appears to benefit the drug addicts with childhood maltreatment history. (shrink)

This paper seeks to understand the treatment effect of Prescription Drug Monitoring Programs on opioid prescription rates. Using county-level panel data on all opioid prescriptions in the U.S. between 2006 and 2015, we investigate whether state interventions like PDMPs have heterogeneous treatment effects at the sub-state level, based on regional and temporal variations in policy design, extent of urbanization, race, and income. Our models comprehensively control for a set of county and time fixed effects, countyspecific and time-varying demographic controls, potentially (...) endogenous time-series trends in prescription rates, and other state-level opioid interventions such as Naloxone Access and Good Samaritan laws, Medicaid expansion, and the provision of Methadone Assistance Treatment. We find that PDMPs are only effective in reducing prescription rates if they obligate doctors to check for patients' history prior to filling out a prescription, but the frequency at which a state requires its PDMP to be updated is irrelevant to its effectiveness. Moreover, the significant treatment effects of PDMPs are almost exclusively driven by urban and predominantly white counties, with the relatively more affluent regions showing greater responsiveness than their less affluent counterparts. (shrink)

This paper builds on previous work that investigated anticancer drugs as ‘informed materials’, i.e., substances that undergo an informational enrichment that situates them in a dense relational web of qualifications and measurements generated by clinical experiments and clinical trials. The paper analyzes the recent transformation of anticancer drugs from ‘informed’ to ‘informing material’. Briefly put: in the post-genomic era, anti-cancer drugs have become instruments for the production of new biological, pathological, and therapeutic insights into the underlying etiology and evolution of (...) cancer. Genomic platforms characterize individual patients’ tumors based on their mutational landscapes. As part of this new approach, drugs targeting specific mutations transcend informational enrichment to become tools for informing their targets, while also problematizing the very notion of a ‘target’. In other words, they have become tools for the exploration of cancer pathways and mechanisms. While several studies in the philosophy and history of biomedicine have called attention to the heuristic relevance and experimental use of drugs, few have investigated concrete instances of this role of drugs in clinical research. (shrink)

The experience of having to suffer debilitating pain is far too common in the United States, and many patients continue to be inadequately treated by their doctors. Although many physicians freely admit that their pain management practices may have been somewhat lacking, many more express concern that the prescribing of heightened levels of opioid analgesics may result in closer regulatory scrutiny, criminal investigation, or even criminal prosecution.Although several researchers have examined the regulatory environment and the threat of sanction or harm (...) it poses to physicians and patients, few have examined the likelihood of investigation or prosecution stemming from the aggressive use of opioids in physician-directed pain management. Accordingly, in an effort to assess whether the fear of prosecution is realistic and, if so, what factors contribute to its likelihood, we surveyed chief prosecutors in four states about their knowledge, opinions, and attitudes concerning opioids and the prosecution of physicians stemming from the treatment of patients who were either terminally ill or suffering from chronic noncancer pain. (shrink)

The experience of having to suffer debilitating pain is far too common in the United States, and many patients continue to be inadequately treated by their doctors. Although many physicians freely admit that their pain management practices may have been somewhat lacking, many more express concern that the prescribing of heightened levels of opioid analgesics may result in closer regulatory scrutiny, criminal investigation, or even criminal prosecution.Although several researchers have examined the regulatory environment and the threat of sanction or harm (...) it poses to physicians and patients, few have examined the likelihood of investigation or prosecution stemming from the aggressive use of opioids in physician-directed pain management. Accordingly, in an effort to assess whether the fear of prosecution is realistic and, if so, what factors contribute to its likelihood, we surveyed chief prosecutors in four states about their knowledge, opinions, and attitudes concerning opioids and the prosecution of physicians stemming from the treatment of patients who were either terminally ill or suffering from chronic noncancer pain. (shrink)

This study explored drug users’ attitudes toward and understanding of randomized controlled trials testing addiction therapies. A video portraying a fictional consent conference for a randomized controlled trial with placebo arm was shown to poor male and female drug users of diverse ethnic status and sexual orientation. The video stimulated focus group discussion in which participants’ comments often reflected “experimental realism”—a realistic view of the trial—and adequate understanding of the uncertain efficacy of the treatment being tested, as well as the (...) concepts of randomization and placebo control. However, participants’ comprehension of the nature of placebos was compromised by the widespread view that placebos are a way of testing a subject’s willpower and personal control over his or her addiction. Comments also showed a mistrust of the video investigator’s integrity and competence and signs of therapeutic misconception and misestimation. The study’s findings underscore the importance of tailoring informed consent encounters to the personal and sociohistorical context of participants’ lived experiences. (shrink)

Today's clinical AIDS research is in trouble. Principal investigators are confronted with young and frequently highly knowledgeable patients. Many of these people with AIDS are often unwilling to adhere to the trial protocols. These PWAs believe they are ethically justified in breaching trial protocols because they do not consider themselves true volunteers in such trials. PWAs argue that they do not really volunteer because existing legislation prevents them from buying and using experimental drugs or from testing alternative treatment strategies. Their (...) only access to such agents is participation in clinical trials. (shrink)

Malaria is a disease of developing countries whose local health services do not have the time, resources or personnel to mount studies of drugs or vaccines without the collaboration and technology of western investigators. This investigative collaboration requires a unique bridging of cultural differences with respect to human investigation. The following debate, sponsored by The Institute of Medicine and The American Society of Tropical Medicine and Hygiene, raises questions concerning the conduct of trans-cultural clinical malaria research. Specific questions are raised (...) about the difficulties of informed consent in different cultural settings and whether there is any role for community involvement. Discussants debate whether drug and vaccine trials not approved in an industrialised country are ever defensible if performed in a third-world setting. Potential conflicting priorities between investigators are discussed and ideas regarding conflict resolution are offered. (shrink)

Hospital systems commonly face the challenge of determining just ways to allocate scarce drugs during national shortages. There is no standardised approach of how this should be instituted, but principles of distributive justice are commonly used so that patients who are most likely to benefit from the drug receive it. As a result, clinical indications, in which the evidence for the drug is assumed to be established, are often prioritised over research use. In this manuscript, we present a case of (...) a phase II investigational trial of intravenous thiamine for delirium prevention in patients undergoing haematopoietic stem cell transplantation to emphasise several shortcomings in the overarching prioritisation of clinical over research uses of scarce drugs. Specifically, we present the following considerations: clinical use may not have stronger evidence than research use; a strong scientific rationale for research use may outweigh the claim for clinical indications in which there is weak evidence; treatment within the context of a clinical trial may be the standard of care; and research use may not only benefit patients receiving the treatment but also offers the prospect of improving future clinical care. In summary, we argue against allocation schemes that prohibit all research uses of scarce drugs and instead recommend that allocation schemes include a balanced approach that weighs risks and benefits of access to scarce drugs irrespective of the research versus clinical use designation. (shrink)

Definition of the problem Compassionate use is the use of unapproved drugs in groups of patients suffering from a disease that, in the absence of an alternative treatment option, is life-threatening or leads to severe disability. Physicians are not in charge because access to the drug is only granted by pharmaceutical companies, which comes along with many ethical issues. Launched in 2020, the program of Onasemnogenum abeparvovecum against spinal muscular atrophy in children reached a new dimension. The intent of this (...) drug is to stop the progression of the disease with just a single dose, but the company limited the doses in the program to only 100. The global allocation was by lottery, which was considered a novelty in compassionate use history and therefore widely criticized. This paper investigates alternative allocation principles. Arguments Each possible principle is accompanied by many aspects that need to be considered with regard to urgency and global distribution. This makes some principles like first-come-first-served seem negligible. Remaining principles are ordered hierarchically to derive an algorithm that can represent an alternative to a lottery. A combination of willingness to participate in research, urgency, and likelihood of success (relative to the availability of supportive treatment options) may be considered in similar cases in future global compassionate use programs with children. Conclusion Since universal algorithms are difficult to define, allocation criteria should always be discussed by an independent panel of experts. Both the constitution of such a panel and its mandatory consultation are necessary in order to decrease the burden for all those involved and to prevent arbitrariness. (shrink)

Background and objectivesThe study of brain functional connectivity alterations in children with Attention-Deficit/Hyperactivity Disorder has been the subject of considerable investigation, but the biological mechanisms underlying these changes remain poorly understood. Here, we aim to investigate the brain alterations in patients with ADHD and Typical Development children and accurately classify ADHD children from TD controls using the graph-theoretical measures obtained from resting-state fMRI.Materials and methodsWe investigated the performances of rs-fMRI data for classifying drug-naive children with ADHD from TD controls. Fifty (...) six drug-naive ADHD children and 56 age matched TD controls were included in this study. The graph measures extracted from rs-fMRI functional connectivity were used as features. Extracted network-based features were fed to the RFE feature selection algorithm to select the most discriminating subset of features. We trained and tested Support Vector Machine, Random Forest, and Gradient Boosting using Peking center data from ADHD-200 database to classify ADHD and TD children using discriminative features. In addition to the machine learning approach, the statistical analysis was conducted on graph measures to discover the differences in the brain network of patients with ADHD.ResultsAn accuracy of 78.2% was achieved for classifying drug-naive children with ADHD from TD controls employing the optimal features and the GB classifier. We also performed a hub node analysis and found that the number of hubs in TD controls and ADHD children were 8 and 5, respectively, indicating that children with ADHD have disturbance of critical communication regions in their brain network. The findings of this study provide insight into the neurophysiological mechanisms underlying ADHD.ConclusionPattern recognition and graph measures of the brain networks, based on the rs-fMRI data, can efficiently assist in the classification of ADHD children from TD controls. (shrink)

Over the past decade, the management of clinical trials of pharmaceuticals has become a veritable industry, as evidenced by the emergence and proliferation of contract research organizations (CROs) that co‐ordinate and monitor trials. This article focuses on work performed by one CRO involved in the introduction of new software, modelled on industrial production processes, into clinical trial practices. It investigates how this new management technique relates to the work performed in the clinic to ensure that trial participants comply with the (...) protocol. Using an analytical distinction between ‘classical’ management work and invisible work, the article contextualizes the meaning of compliance in the clinic and suggests that the work involved in producing compliance should be taken into consideration by those concerned with validity of trials, as clinical trials are put under private industrial management. The article builds on participant observation at a Swedish university hospital and interviews the nurses, dieticians, doctors and a software engineer, all part of a team involved in pharmaceutical drug trials on a potential obesity drug. (shrink)

In recent years the issue of whether mysticism can be induced by drugs has been pursued by both scholars of mystical literature and psychological researchers. R. C. Zaehner is perhaps the best known among the scholars of religious literature who have addressed the issues of drug-induced mysticism. While on the side of empirical psychology investigators such as Walter N. Pahnke, R. E. L. Masters, and Jean Houston have pursued some of the same issues using the techniques of laboratory experimentation. Zaehner, (...) who was familiar with both Eastern and Western mysticism, argued that drug-induced experiences are not the same as religious mystical experiences of the theistic variety. It was farcical, he argued, for Aldous Huxley to posit a connection between his preternatural feeling of oneness with his chair and the Beatific Vision. The issue between Zaehner and Huxley was not over the veridicality of Huxley's mystical experience. It was over the significance of Huxley's experience: Was it or was it not a drug-induced mystical experience of the sort attained by mystics after heroic struggles of self-discipline? This was the issue again when Zaehner came to address himself to the claims of Timothy Leary, a chief proponent of ‘the LSD experience’, and, in general terms, this has been the central issue pursued by the psychological researchers. (shrink)

In recent years the issue of whether mysticism can be induced by drugs has been pursued by both scholars of mystical literature and psychological researchers. R. C. Zaehner is perhaps the best known among the scholars of religious literature who have addressed the issues of drug-induced mysticism. While on the side of empirical psychology investigators such as Walter N. Pahnke, R. E. L. Masters, and Jean Houston have pursued some of the same issues using the techniques of laboratory experimentation. Zaehner, (...) who was familiar with both Eastern and Western mysticism, argued that drug-induced experiences are not the same as religious mystical experiences of the theistic variety. It was farcical, he argued, for Aldous Huxley to posit a connection between his preternatural feeling of oneness with his chair and the Beatific Vision. The issue between Zaehner and Huxley was not over the veridicality of Huxley's mystical experience. It was over the significance of Huxley's experience: Was it or was it not a drug-induced mystical experience of the sort attained by mystics after heroic struggles of self-discipline? This was the issue again when Zaehner came to address himself to the claims of Timothy Leary, a chief proponent of ‘the LSD experience’, and, in general terms, this has been the central issue pursued by the psychological researchers. (shrink)

In recent years, the issue of accepting a higher cost per health improvement for orphan drugs has been the subject of discussion in health care policy agencies and the academic literature. This article aims to provide an analysis of broadly egalitarian arguments for and against accepting higher costs per health improvement. More specifically, we aim to investigate which arguments one should agree upon putting aside and where further explorations are needed. We identify three kinds of arguments in the literature: considerations (...) of substantial equality, formal equality, and opportunity cost. We argue that considerations of substantial equality do not support higher costs per health improvement orphan drugs, even if such considerations are considered valid. On the contrary, arguments of formal equality may support accepting a higher cost per health improvement for orphan drugs. However, in order to do so, a number of both normative and empirical issues must be resolved; these issues are identified in the article. For instance, it must be settled to what extent the opportunity cost in terms of foregone health for other patients is acceptable in order to uphold formal equality. We conclude that certain arguments can be set aside, and future focus should be put on the unresolved normative and empirical issues related to formal equality and opportunity cost. (shrink)

Individual differences in moral views are often explained as the downstream effect of ideological commitments, such as political orientation and religiosity. Recent studies in the U.S. suggest that moral views about recreational drug use are also influenced by attitudes toward sex and that this relationship cannot be explained by ideological commitments. In this study, we investigate student samples from Belgium, The Netherlands, and Japan. We find that, in all samples, sexual attitudes are strongly related to views about recreational drug use, (...) even after controlling for various ideological variables. We discuss our results in light of reproductive strategies as determinants of moral views. (shrink)

ObjectiveThis study aims to investigate anxiety and its influencing factors in patients with drug-induced liver injury (DILI).Materials and MethodsNinety-four patients with DILI were enrolled and evaluated with a self-rating anxiety scale (SAS). According to the anxiety score, they were divided into four groups: the non-anxiety, mild anxiety, moderate anxiety, or severe anxiety groups, and the scores were analyzed based on demographic and biochemical indicators.ResultsOf the 94 patients with DILI, 63 did not have anxiety and 31 had anxiety (32.9%), of which (...) 27 had mild, 3 had moderate, and 1 had severe anxiety. There were no statistically significant differences in gender, age, occupation, and level of education between the groups (F= 1.42,H= 2.361,H= 6.751,H= 1.796, andP> 0.05); anxiety score and degree of anxiety between the types of drugs that led to the liver injury (H= 0.812,H= 1.712, andP> 0.05); anxiety score between the different degrees of liver injury (H= 2.836,H= 4.957,P> 0.05); or length of hospital stay or prognosis between the degrees of anxiety (F= 1.487,H= 0.761,P> 0.05). However, there were statistically significant differences in the degree of anxiety between different degree and types of liver injury (H= 7.981,H= 8.208,P< 0.05).ConclusionPatients with DILI may have anxiety, especially mild anxiety. The occurrence of anxiety in patients with DILI is not related to gender, age, occupation, or level of education but may be related to the degree and type of liver injury. Anxiety has no impact on the length of stay in hospital or the prognosis of the DILI. These findings may contribute to the development of management strategies for patients with DILI. (shrink)

Scholars such as Simon (2007; 2004) and Loland (2002) as well as the authors of the World Anti-Doping Code (2001) argue that using performance-enhancing substances is unhealthy and unfairly coercive for other athletes. Critics of the anti-doping position such as Hoberman (1995), Miah et al. (2005) and Tamburrini (2007) are quick to argue that such prohibitions, even though well-intended, constitute an unjustifiable form of paternalism. However, advocates for both of these positions assume that preserving good health and, conversely, avoiding health-related (...) harms, lie at the centre of the debate. Given the apparent stalemate in the debate over the validity of health concerns on performance-enhancing drugs, in this essay, I investigate ethical issues of ‘harm-free’ pharmaceutical performance enhancement. Beginning with the hypothesis that a harm-free performance-enhancing drug may be produced in the future, I ask if there would still be compelling reasons for prohibiting such a drug. I address this question by providing two arguments against allowing athletes to use pharmaceutical performance-enhancing drugs – the damage to the testing and contesting of sport and the loss of internal goods that are intrinsically satisfying. These two arguments taken together, I argue, are sufficient to sustain the prohibition of pharmaceutical performance-enhancing drugs without citing their harmful side effects. (shrink)

Patients have received experimental pharmaceuticals outside of clinical trials for decades. There are no industry-wide best practices, and many companies that have granted compassionate use, or ‘preapproval’, access to their investigational products have done so without fanfare and without divulging the process or grounds on which decisions were made. The number of compassionate use requests has increased over time. Driving the demand are new treatments for serious unmet medical needs; patient advocacy groups pressing for access to emerging treatments; internet (...) platforms enabling broad awareness of compelling cases or novel drugs and a lack of trust among some that the pharmaceutical industry and/or the FDA have patients’ best interests in mind. High-profile cases in the media have highlighted the gap between patient expectations for compassionate use and company utilisation of fair processes to adjudicate requests. With many pharmaceutical manufacturers, patient groups, healthcare providers and policy analysts unhappy with the inequities of the status quo, fairer and more ethical management of compassionate use requests was needed. This paper reports on a novel collaboration between a pharmaceutical company and an academic medical ethics department that led to the formation of the Compassionate Use Advisory Committee. Comprising medical experts, bioethicists and patient representatives, CompAC established an ethical framework for the allocation of a scarce investigational oncology agent to single patients requesting non-trial access. This is the first account of how the committee was formed and how it built an ethical framework and put it into practice. (shrink)

Provides theories and techniques behind the investigations of intoxication and how subjective experiences relate to addictive potential, which should help ...

Parental substance use is a major risk factor for child development, heightening the risk of drug problems in adolescence and young adulthood, and exposing offspring to several types of traumatic event. First, prenatal drug exposure can be considered a form of trauma itself, with subtle but long-lasting sequalae at the neuro-behavioural level. Second, parents’ addiction often entails a childrearing environment characterised by poor parenting skills, disadvantaged contexts and adverse childhood experiences, leading to dysfunctional outcomes. Young adults born from/raised by parents (...) with drug problems and who develop a Substance Used Disorder (SUD) themselves might display a particularly severe condition in terms of cognitive deficits and impaired personality function. This preliminary study aims to investigate the role of early exposure to drugs as a traumatic event, capable of affecting the psychological status of young drug addicts. In particular, it intends to examine the neuropsychological functioning and personality profile of young adults with severe SUDs who were exposed to drugs early in their family context. The research involved 3 groups each consisting of 15 young adults (aged 18-24): a group of inpatients diagnosed with SUDs and exposed to drugs early, a comparison group of non-exposed inpatients and a group of non-exposed youth without SUDs. A neuropsychological battery (Esame Neuropsicologico Breve-2), an assessment procedure for personality disorders (Shedler-Westen Assessment Procedure-200) and the Symptom CheckList-90-Revised were administered. According to present preliminary results, young drug addicts exposed to drugs during their developmental age were characterised by elevated rates of neuropsychological impairments, especially at the expense of attentive and executive functions; personality disorders were also common but did not differentiate them from non-exposed young people with SUDs. Alternative multi-focused prevention and intervention programs are needed for children of drug-misusing parents, addressing executive functions and adopting a trauma-focused approach. (shrink)

The mental illness of substance dependence or addiction is responsible for major economic, social, and personal costs. If we are to elucidate its etiology, understand its mechanisms, and eventually bring it under control, scientific investigation is essential. Research in animals and humans has enhanced our understanding of this disease through examination of genetic, neurophysiological, biochemical, and behavioral factors. But because animals cannot verbalize their subjective responses to drugs and because significant symptoms of addiction cannot be observed in non-drug-dependent humans, it (...) is not surprising that certain investigations of substance dependence have required the participation of addicted or substance-dependent humans. (shrink)