All investigators funded by the National Institutes of Health are now required to receive training about the ethics of clinical research. Based on a course taught by the editors at NIH, Ethical and Regulatory Aspects of Clinical Research is the first book designed to help investigators meet this new requirement. The book begins with the history of human subjects research and guidelines instituted since World War II. It then covers various stages and components of the (...) class='Hi'>clinical trial process: designing the trial, recruiting participants, ensuring informed consent, studying special populations, and conducting international research. Concluding chapters address conflicts of interest, scientific misconduct, and challenges to the IRB system. The appendix provides sample informed consent forms. This book will be used in undergraduate courses on research ethics and in schools of medicine and public health by students who are or will be carrying out clinical research. Professionals in need of such training and bioethicists also will be interested. (shrink)

Chasing Medical Miracles" is the first book to give readers a behind-the-scenes look at the complicated world of clinical trials, revealing how a multibillion-dollar industry of private companies conducting them with little oversight has taken root and quietly become a major part of the American medical establishment.

_Clinical Trials and the African Person_ offers an account of the African notion of the self/person within the clinical trials context. As opposed to autonomy-based principlism, this other-regarding/communalist perspective is touted as the preferred alternative model particularly in multicultural settings.

In their article published in Nanoethics, “Ethical, Legal and Social Aspects of Brain-Implants Using Nano-Scale Materials and Techniques”, Berger et al. suggest that there may be a prima facie moral obligation to improve neuro implants with nanotechnology given their possible therapeutic advantages for patients [Nanoethics, 2:241–249]. Although we agree with Berger et al. that developments in nanomedicine hold the potential to render brain implant technologies less invasive and to better target neural stimulation to respond to brain impairments (...) in the near future, we argue against presenting the development of nanobionic clinical devices in terms of a moral obligation to conduct this research. In the first part of the paper, we consider what a duty to pursue new technologies might mean, and in the second we explore some of the negative consequences of defending such development as a moral obligation based on potential benefit. We argue that promoting the advances available to brain implants through developments in nanotechnology and bionics could contribute to medical rhetoric that indirectly increases the risk of exposing patients to harm when participating in clinical trials. We argue that rather than there being a moral obligation to improve nanobionics implants because of their potential benefit, the pursuit of improved neuro implants must be balanced against the prima facie obligations to protect patients against harm and to promote and protect patient autonomy. (shrink)

There is unanimous agreement regarding the need to ethically conduct research for improving therapy for patients admitted to hospital with acute conditions, including in emergency obstetric care. We present a conceptual analysis of ethical tensions inherent in the informed consent process for randomized clinical trials for emergency obstetric care and suggest ways in which these could be mitigated. A valid consenting process, leading to an informed consent, is a cornerstone of this aspect necessary for preservation and maintenance (...) of respect for autonomy and dignity. In emergency obstetric care research, obtaining informed consent can be problematic, leading to ethical tension between different moral considerations. Potential participants may be vulnerable due to severity of disease, powerlessness or impaired decisional capacity. Time for the consent process is limited, and some interventions have a narrow therapeutic window. These factors create ethical tension in allowing potentially beneficial research while avoiding potential harms and maintaining respect for dignity, human rights, justice and autonomy of the participants. Informed consent in emergency obstetric care in low- and middle-income countries poses numerous ethical challenges. Allowing research on vulnerable populations while maintaining respect for participant dignity and autonomy, protecting participants from potential harms and promoting justice underlie the ethical tensions in the research in emergency obstetric and newborn care. Those involved in research conduct or oversight have a duty of fair inclusion, to avoid denying participants the right to participate and to any potential research benefits. (shrink)

This book considers coercion within the healing and ethical framework of therapeutic relationships and partnerships at all levels, and addresses the universal ...

Chapter One: Introduction “The ethical basis of all [medical] research is that information gained from one patient's experience should, where feasible, ...

Nanotechnology is an important platform technology which will add new features like improved biocompatibility, smaller size, and more sophisticated electronics to neuro-implants improving their therapeutic potential. Especially in view of possible advantages for patients, research and development of nanotechnologically improved neuro implants is a moral obligation. However, the development of brain implants by itself touches many ethical, social and legal issues, which also apply in a specific way to devices enabled or improved by nanotechnology. For researchers developing nanotechnology (...) such issues are rather distant from their daily work in the lab, but as soon as they use their materials or devices in medical applications such as therapy of brain diseases they have to be aware of and deal with them. This paper is intended to raise sensitivity for the ethical, legal and social aspects (ELSA) involved in applying nanotechnology in brain implants or other devices by highlighting the short term problems of testing and clinical trials within the existing regulatory frameworks (A), the short and medium-term questions of risks in the application of the devices (B) and the long-term perspectives related to problems of enhancement (C). To identify and address such issues properly nanotechnologists should involve ethical, legal and social experts and regulatory bodies in their research as early as possible. This will help to remove pressure from regulatory bodies, to settle public concern and to prevent non-acceptable developments for the benefit of the patients. (shrink)

Comprehensive in scope and research, this book will be a crucial resource for researchers in the medical sciences, as well as teachers and students alike.

Ethical Considerations When Preparing a Clinical Research Protocol, Second Edition, provides a foundation for improving skills in the understanding of ethical requirements in the design and conduct of clinical research. It includes practical information on ethical principles in clinical research, how to design appropriate research studies, how to consent and assent documents, how to get protocols approved, special populations, confidentiality issues, and the reporting of adverse events. The book's valuable appendix includes a listing of (...) web resources about research ethics, along with a glossary, making it an invaluable resource for scientists collaborating in clinical trials, physician investigators, clinical research fellows, and more. Walks investigators and trainees through the identification of the ethical aspects of each section of a clinical research protocol Includes case histories that illustrate key points Contains information on conducting clinical research within the pharmaceutical industry Includes internet resources and worldwide web addresses for important research ethics documents and regulations Contains a chapter on Study Design and Methodology that is purposely expanded to explicitly address biostatistical considerations. (shrink)

Critical Thinking in Clinical Research explains the fundamentals of clinical research in a case-based approach. The core concept is to combine a clear and concise transfer of information and knowledge with an engagement of the reader to develop a mastery of learning and critical thinking skills. The book addresses the main concepts of clinical research, basics of biostatistics, advanced topics in applied biostatistics, and practical aspects of clinical research, with emphasis on clinical relevance across (...) all medical specialties. (shrink)

In this paper, the results of a pilot interview study with 19 subjects participating in an EEG-based non-invasive brain–computer interface (BCI) research study on stroke rehabilitation and assistive technology and of a survey among 17 BCI professionals are presented and discussed in the light of ethical, legal, and social issues in research with human subjects. Most of the users were content with study participation and felt well informed. Negative aspects reported include the long and cumbersome preparation procedure, discomfort (...) with the cap and the wet electrodes, problems concerning BCI control, and strains during the training sessions. In addition, some users reflected on issues concerning system security. When asked for morally problematic issues in this field of non-invasive BCI research, the BCI professionals stressed the need for correct information transfer, the obligation to avoid unrealistic expectations in study participants, the selection of study participants, benefits and strains of participation, BCI illiteracy, the possibility of detrimental brain modifications induced by BCI use, and problems that may arise at the end of the trials. Furthermore, privacy issues were raised. Based on the results obtained, psychosocial and ethical aspects of EEG-based non-invasive BCI research are discussed and possible implications for future research addressed. (shrink)

Shows how international biomedical researchers in Sri Lanka work across cultural, epistemic, economic, and power differences to accomplish clinical trials.

Children and adults with dementia are vulnerable populations. Both groups are also relatively seldom included in biomedical research. However, including them in clinical trials is necessary, since both groups are in need of scientific innovation and new therapies. Their dependence and limited decision-making capacities increase their vulnerability, necessitating extra precautions when including them in clinical trials. Beside these similarities there are also many differences between the groups. The most obvious one is that children have an entire (...) life ahead of them and will become persons with certain ideals and preferences, while adults with dementia have lived a life in which they have expressed their ideals and preferences. Some of the available research guidelines recognize these differences, setting one list of specific requirements for groups of incapacitated adults and another list for children. Other documents, however, do not differentiate and only set requirements for subjects unable to consent as a single category of subjects. In this article we analyse to what extent the similarities and differences between the two groups are represented in legal documents and ethical guidelines. The article presents an overview and an analysis of the requirements for doing research with children and dementia patients. We conclude with suggestions about how to better incorporate the morally relevant aspects of these two groups in legislation and ethical guidelines. (shrink)

Children and adults with dementia are vulnerable populations. Both groups are also relatively seldom included in biomedical research. However, including them in clinical trials is necessary, since both groups are in need of scientific innovation and new therapies. Their dependence and limited decision‐making capacities increase their vulnerability, necessitating extra precautions when including them in clinical trials. Beside these similarities there are also many differences between the groups. The most obvious one is that children have an entire (...) life ahead of them and will become persons with certain ideals and preferences, while adults with dementia have lived a life in which they have expressed their ideals and preferences. Some of the available research guidelines recognize these differences, setting one list of specific requirements for groups of incapacitated adults and another list for children. Other documents, however, do not differentiate and only set requirements for subjects unable to consent as a single category of subjects.In this article we analyse to what extent the similarities and differences between the two groups are represented in legal documents and ethical guidelines. The article presents an overview and an analysis of the requirements for doing research with children and dementia patients. We conclude with suggestions about how to better incorporate the morally relevant aspects of these two groups in legislation and ethical guidelines. (shrink)

Clinical trials in developing countries are often beset by ethical problems that would be considered unresolvable in countries like Australia and the U.S. Nevertheless, such trials continue to go ahead throughout Asia, Africa and South America, and are often conducted in ways that could be considered to be unethical. In this article I discuss two issues, focussing on an HIV preventative trial of a vaginal gel, the Nonoxynol 9 phase three trial being held in Kenya. The (...) first of these is what makes such a trial unethical given that it has approval from the WHO and seemingly conforms with acceptable standards of consent. The second issue involves using material from such trials, if we accept that they were conducted unethically. (shrink)

Any healthcare systems during a pandemic undergo tremendous pressure in pursuit of effective treatment to treat and limit the spread of the disease and its implications. Conducting clinical trials to find the potential therapy is the only way to battle the current coronavirus disease-2019 pandemic. The majority of the countries have joined the cause and are carrying out clinical studies in various capacities. As a result, the ethical committees have encountered a sudden inflow of a large (...) number of trial proposals that have placed them under pressure. Although ethical committees play a vital role in protecting patient safety and preserving research integrity, they need to make sure the efficiency and integrity of review are preserved and the standards of review are not relaxed. Thus, the participants’ dignity is well guarded while keeping a close check on their safety. (shrink)

The upcoming Regulation No 536/2014 on clinical trials on medicinal products for human use, which will replace the current Clinical Trial Directive at the end of 2021, has triggered a significant reform of research ethics committee systems in Europe. Changes related to ethics review of clinical trials in the EU were considered to be essential to create a more favourable environment to conduct clinical trials in the EU. The concern is, however, that the (...) role of the research ethics committees will weaken in at least some of the Member States because the new Regulation allows narrowing down the scope of ethics review as compared with the currently valid Clinical Trial Directive. Although the new Regulation may lead to faster approval procedures for clinical trials, which is especially relevant in the context of pandemics, high-quality ethics reviews integrating methodological aspects of a clinical trial should nevertheless be ensured. To maintain high research ethics standards as well as to foster measures to mitigate potential negative consequences of the reform, it is therefore of vital importance to start debating and sharing the reflections about the potential consequences of these transformations and trends as soon as possible. (shrink)

Ethics boards have become obligatory passage points in today's medical science, and we forget how novel they really are. The use of humans in experiments is an age-old practice that records show goes back to at least the third century BC and, since the early modern period, as a practice it has become increasingly popular. Yet, in most countries around the world, hardly any formal checks and balances existed to govern the communal oversight of experiments involving human subjects until at (...) least the 1960s. Ethics by Committee traces the rise of ethics boards for human experimentation in the second half of the twentieth century. Using the Netherlands as a case-study, Noortje Jacobs shows how the authority of physicians to make decisions about clinical research gave way in most developed nations to formal mechanisms of communal decision-making that served to regiment the behavior of individual researchers. This historically unprecedented change in scientific governance came out of a growing international wariness of medical research in the decades after World War II. Research ethics committees were originally intended not only to make human experimentation more ethical but also to raise its epistemic quality. By examining complex negotiations over the appropriate governance of human subjects research, Ethics by Committee advances our understanding not only of the history of research ethics and the randomized controlled trial but also, more broadly, of how liberal democracies in the late twentieth century have sought to resolve public concerns over charged issues in medicine and science. (shrink)

The use of placebo as a control condition in clinical trials of major depressive disorder and anxiety disorders continues to be an area of ethical concern. Typically, opponents of placebo controls argue that they violate the beneficent-based, “best proven diagnostic and therapeutic method” that the original Helsinki Declaration of 1964 famously asserted participants are owed. A more consequentialist, oppositional argument is that participants receiving placebo might suffer enormously by being deprived of their usual medication(s). Nevertheless, recent findings (...) of potential for suicidality in young people treated with antidepressants, along with meta-analyses suggesting that antidepressants add no significant clinical benefit over placebos, warrant a re-evaluation of the arguments against placebo. Furthermore, the nature of placebo treatment in short-term clinical trials is often not well understood, and lack of understanding can foster opposition to it. This paper will show how scientific justifications for placebo use are morally relevant. The fundamental ethical importance of placebo controls is discussed in relation to several aspects of clinical trials, including detection of adverse events, accurate assessment of clinical benefit, advancing understanding of the heterogeneity of depression and anxiety disorders and respecting informed consent requirements. Prohibiting the use of placebo controls is morally concerning in that such prohibitions allow for the possibility of serious adverse public health consequences. Moral worries that research participants receiving placebo are being unduly jeopardised will be shown to be exaggerated, especially in relation to the net benefits for end-users to be gained from the quality of data resulting from using placebo controls. (shrink)

BackgroundDuring a commercial surrogacy arrangement, the event of embryo transfer can be seen as the formal starting point of the arrangement. However, it is common for surrogates to undergo a failed attempt at pregnancy conception or missed conception after an embryo transfer. This paper attempts to argue that such failed attempts can be understood as a loss. It aims to reconstruct the experiences of loss and grief of the surrogates and the intended parents as a consequence of their collective failure (...) to conceive a surrogate pregnancy.MethodsDrawing on a qualitative study conducted over a period of eight months between 2014 and 2015 at two fertility clinics in Delhi and two in Kolkata, India, this paper examines the experiences of the surrogates and the intended parents when faced with missed conceptions or failed conceptions during a surrogacy arrangement.ResultsWe argue that while the surrogate grieves the non-arrival of a ‘good news’ as an uncertain loss, the intended parents experience yet another, failure in addition to the losses they might have incurred during their previous fertility treatments. The body of the surrogate becomes a site of ‘a lost opportunity’. The surrogate embodies a loss in her quest to achieve social mobility and the intended parents experience a disembodied pregnancy loss. This very emotional experience stands in stark contrast to the conceptualisation of such failed attempts as non-events within the discourse of the surrogacy industry. The experience of loss of the intended parents is recognised but their grief is given no space. We argue that such ambiguity around the nature of losses resulting out of a missed or failed conception during surrogacy is an outcome of lack of interpersonal relationship between the surrogate and the intended parents.ConclusionsSince commercial surrogacy is a relational process, the only way in which the experiences of losses and failures of the actors at the preconception stage can be better addressed is through developing close sharing and understanding between each other through an ethics of care. Therefore, to nurture caring relationships, surrogacy needs to be understood as a moral commitment by –the surrogates and intended parents. To enable such a commitment, there is a need to reconsider the pre-defined and legally regulated professional duty of the doctors, agents and agencies. It cannot be a one-sided commitment, but has to have elements of mutuality. (shrink)

This case study discusses the economic, legal, and ethical considerations for conducting clinical trials in a controversial context. In 2010, pharmaceutical giant Roche received a shame award by the Swiss non-governmental organization Berne Declaration and Greenpeace for conducting clinical trials with organs taken from executed prisoners in China. The company respected local regulations and industry ethical standards. However, medical associations condemned organs from executed prisoners on moral grounds. Human rights organizations demanded that Roche (...) ended its clinical trials in China immediately. Students are expected to review the economic and ethical issues regarding the outsourcing of clinical trials to controversial human rights contexts, and discuss how to make business decisions when there are conflicts between making profit and ethical considerations. Was Roche complicit in the human rights violations that were related to its clinical trials? Future patients might benefit from these clinical trials. Do profit and the greater good, in general, trump morals? (shrink)

Mood disorders, including major depressive disorder and bipolar disorder, are highly prevalent, frequently disabling, and sometimes deadly. Additional research and more effective medications are desperately needed, but clinical trials research in mood disorders is fraught with ethical issues. Although many authors have discussed these issues, most do so from a theoretical viewpoint. This manuscript uses available empirical data to inform a discussion of the primary ethical issues raised in mood disorders research. These include issues of consent (...) and decision-making capacity, including patients’ motivations for participating in research. We also address drug withdrawals, placebo controls, and the overall safety of research. Finally, we examine the extant literature for studies discussing potential indirect benefits of clinical trials research to participants. Taken together, the evidence suggests that clinical trials research incorporating drug withdrawals and placebo controls can be conducted safely and ethically, even in patients with severe or treatment-resistant mood disorders. In fact, given the dearth of effective treatment options for this population, it is our opinion that a moral imperative exists to extend the offer of research participation to severely ill or treatment-resistant groups. (shrink)

Over the past 20 years, clinical research has migrated from academic medical centers to community-based settings, including rural settings. This evolving research environment may present some moral hazards or challenges that could undermine traditionally accepted standards for the protection of human subjects. The study described in this article was designed to explore the influence of motives driving the decisions to conduct clinical trial research in rural community settings. The researchers conducted semi-structured interviews with 80 participants who conducted (...) clinical trials with rural subjects. The interviews provided a way to examine the influence of budgetary factors when deciding to conduct a clinical study, how information about the budget and the purpose of the study is conveyed to research participants, and the potential willingness of clinicians and coordinators to enroll in the kinds of studies they offer. The findings suggest that clinical trial research in rural communities may challenge clinicians’ abilities to balance the needs of the patient with the needs of the research enterprise. Few respondents seemed to recognize the traditionally recognized hazards of a dual relationship, specifically the moral risks of trying to attend to the interests of both patient and industry. It seems important to re-examine how we protect human subjects and what such protection should look like as research becomes part of the way medical care is provided, even in very rural areas. (shrink)

Background If trials of therapeutic interventions are to serve society's interests, they must be of high methodological quality and must satisfy moral commitments to human subjects. The authors set out to develop a clinical - trials compendium in which standards for the ethical treatment of human subjects are integrated with standards for research methods. Methods The authors rank-ordered the world's nations and chose the 31 with >700 active trials as of 24 July 2008. Governmental (...) and other authoritative entities of the 31 countries were searched, and 1004 English-language documents containing ethical and/or methodological standards for clinical trials were identified. The authors extracted standards from 144 of those: 50 designated as ‘core’, 39 addressing trials of invasive procedures and a 5% sample of the remainder. As the integrating framework for the standards we developed a coherent taxonomy encompassing all elements of a trial's stages. Findings Review of the 144 documents yielded nearly 15 000 discrete standards. After duplicates were removed, 5903 substantive standards remained, distributed in the taxonomy as follows: initiation, 1401 standards, 8 divisions; design, 1869 standards, 16 divisions; conduct, 1473 standards, 8 divisions; analysing and reporting results, 997 standards, four divisions; and post-trial standards, 168 standards, 5 divisions. Conclusions The overwhelming number of source documents and standards uncovered in this study was not anticipated beforehand and confirms the extraordinary complexity of the clinical trials enterprise. This taxonomy of multinational ethical and methodological standards may help trialists and overseers improve the quality of clinical trials, particularly given the globalisation of clinical research. (shrink)

The European framework surrounding clinical trials on medicinal products for human use is going to change as demonstrated by the large debate at European institutional level. One of the major challenges is to overcome the lack of harmonisation of clinical trial procedures among countries. This aspect is gaining more and more importance, considering the increasing number of multicentre and multinational studies. In this work, the actual European rules governing the Clinical Trial Application have been analysed throughout (...) the different steps including the registration of the trial in the European database; the preparation of documents to be submitted and their contents; the preparation of documents related to the information and consent process; the submission to competent bodies. Specific issues related to paediatric research and trials involving non EU/EEA countries have been addressed as well. Results reveal that the European legislation offers a well defined set of European rules covering different aspects of a Clinical Trial Application. However, these are not suitable to meet the challenges from multicentre and multinational clinical studies. A stronger set of rules, such as is available in a composite European Regulation has been adopted and is expected to harmonise practices and enable sponsors to carry out well conducted trials. But will the new regulation overcome the existing criticisms of Directive 2001/20/EC? (shrink)

In this paper we argue that the consensus around normative standards for the ethics of research in clinical trials, strongly influenced by the Declaration of Helsinki, is perceived from various quarters as too conservative and potentially restrictive of research that is seen as urgent and necessary. We examine this problem from the perspective of various challengers who argue for alternative approaches to what ought or ought not to be permitted. Key themes within this analysis will examine these claims (...) and argue they have implications for the interests of the research subject, research governance and regulation. Using our work with TREAT-NMD, the neuromuscular clinical trials network, we posit that there is a place for advancing the discourse of moral rights and moral duties in the context of research, especially from the perspective of patients and their families, and for including the politics of patient activism and empowerment. At the same time we remain vigilant to the danger that the therapeutic misconception and other serious vulnerabilities for the patient population in clinical trials, are at risk of being overlooked. (shrink)

Objectives—To assess the relationship between the approval of trials by a research ethics committee and the fact that informed consent from participants was obtained, with the quality of study design and methods.Design—Systematic review using a standardised checklist.Main measures—Methodological and ethical issues of all trials published between 1993 and 1995 in the New England Journal of Medicine, the Lancet, the Journal of the American Medical Association and the British Medical Journal were studied. In addition, clinical trials (...) conducted in Spain and published by at least one Spanish author during the same period in any other journal were also included.Results—We studied the published articles of 767 trials and found the following indicators of lower methodological quality to be independent predictors for failure to disclose REC approval or ICP: absence of concealment of allocation, lack of justification for unblinded trials, not using a treatment for the patients in the control group, absent information on statistical methods, not including sample size estimation, not establishing the rules to stop the trial, and omitting the presentation of a baseline comparison of groupsConclusion—Trials of higher methodological and scientific quality were more likely to provide information about their ethical aspects. (shrink)

Ethically permissible clinical trials must not expose subjects to risks that are unreasonable in relation to anticipated benefits. In the research ethics literature, this moral requirement is typically understood in one of two different ways: as requiring the existence of a state of clinical equipoise, meaning a state of honest, professional disagreement among the community of experts about the preferred treatment; or as requiring an equilibrium between individual and collective ethics. It has been maintained that this (...) second interpretation makes it mandatory to minimize the number of patients receiving the treatment that will eventually be shown to be inferior by the trial. This requirement has led to the development of adaptive trials, i.e., trials in which treatment allocation is determined by data accumulated during interim analysis. Many statisticians argue that in some circumstances—typically with potentially high benefits, as in the much discussed ECMO trial—adaptive design is the only ethically permissible experimental design. Nevertheless, some proponents of clinical equipoise argue that adaptive trials are neither ethically required nor permissible. More specifically, they argue that clinical trials using adaptive designs fail to meet the moral requirement of clinical equipoise, since these trials presuppose an epistemic state that is incompatible with a physician’s duty of care to her subjects. This paper emphasizes that the debate is to a large extent resting on an epistemological confusion. Specifically, I argue that this response conflates two different conceptions of statistical evidence, and that recognizing this distinction elucidates an epistemological framework in which adaptive trials are both consistent with and recommended by the moral requirement of clinical equipoise. (shrink)

Neonatal extracorporeal membrane oxygenation (ECMO), a technology for the treatment of respiratory failure in newborns, is used as a case study to examine statistical and ethical aspects of clinical trials and to illustrate a proposed 'ethics of evidence', an approach to medical uncertainty within the context of contemporary biomedical ethics. Discussion includes the twofold aim of the ethics of evidence: to clarify the role of uncertainty and scientific evidence in medical decision-making, and to call attention to (...) the need to confront the irreducible nature of uncertainty. (shrink)

La Segunda Guerra Mundial y las atrocidades cometidas en investigaciones con los prisioneros en los campos de concentración nazis y japoneses, despertaron la conciencia por el desarrollo de los derechos humanos que se habían conquistado paulatinamente a lo largo de la historia. Por ello se conforman una serie de leyes, normas y declaraciones donde se tratan los aspectos bioéticos en los ensayos clínicos. Se debe prestar vital atención a la relación médico-paciente en el curso de las investigaciones y considerar la (...) relación beneficio/riesgo cuando se va a experimentar en seres humanos. La retinopatía diabética proliferativa es una de las afecciones oftalmológicas que más ensayos ha suscitado. El objetivo de este trabajo consiste en analizar algunos aspectos éticos en la experimentación en pacientes con esta afección. The Second World War and the atrocities committed in research with prisoners in Japanese and Nazi concentration camps, awakened consciousness for the development of human rights that had gradually been conquered throughout history. That´s why a series of laws, rules and statements that deal with bioethical aspects in clinical trials, were passed. Special attention must be given to the doctor-patient relationship during the research and consider the benefit/risk ratio when conducting experiments on human beings. Proliferative Diabetic Retinopathy is one of the ophthalmological disorders that has given rise to more trials. The research goal is to analyze some ethical aspects when experimenting on patients with this condition. (shrink)

Background There is longstanding consensus on the need to include pregnant women in research. The goal of clinical research is to find highly regulated, carefully controlled, morally responsible ways to generate evidence about how to effectively and safely prevent illness or treat sick people. This manuscripts present a conceptual analysis of the ethicality of clinical trials in 3 scenarios: where the pregnant is involved in clinical trials as a participant during pregnancy for data that addresses (...) pregnancy complications, where the pregnant woman consents to clinical trial participation for an unborn baby that has complications, to generate data on complications at this stage of life, and where the mother may consent for participation of their newborn child in clinical trials. Methods Conceptual analysis. Findings Investigators often choose to exclude pregnant women and newborns from research, even where there is possibility for them to benefit from the study intervention. Objections include vulnerability of pregnant women, altered pharmacokinetics and risk of adverse effects, with a need to balance potential maternal and fetal risks and benefits of research participation. While the objections may be valid, not performing research magnifies what should be a carefully controlled risk during research, pushing this risk into the clinical setting, and subsequently posing a challenge to clinicians who are faced with making treatment decisions for pregnant patients with limited evidence of efficacy and safety. The potential benefits of fair inclusion in clinical trials outweigh the potential risks. Conclusion Research involving pregnant women is necessary to provide women with effective treatment during pregnancy, to promote fetal safety, and to reduce avoidable harm from suboptimal care and to provide pregnant women, their fetuses and newborns. (shrink)

Background There is longstanding consensus on the need to include pregnant women in research. The goal of clinical research is to find highly regulated, carefully controlled, morally responsible ways to generate evidence about how to effectively and safely prevent illness or treat sick people. This manuscripts present a conceptual analysis of the ethicality of clinical trials in 3 scenarios: where the pregnant is involved in clinical trials as a participant during pregnancy for data that addresses (...) pregnancy complications, where the pregnant woman consents to clinical trial participation for an unborn baby that has complications, to generate data on complications at this stage of life, and where the mother may consent for participation of their newborn child in clinical trials. Methods Conceptual analysis. Findings Investigators often choose to exclude pregnant women and newborns from research, even where there is possibility for them to benefit from the study intervention. Objections include vulnerability of pregnant women, altered pharmacokinetics and risk of adverse effects, with a need to balance potential maternal and fetal risks and benefits of research participation. While the objections may be valid, not performing research magnifies what should be a carefully controlled risk during research, pushing this risk into the clinical setting, and subsequently posing a challenge to clinicians who are faced with making treatment decisions for pregnant patients with limited evidence of efficacy and safety. The potential benefits of fair inclusion in clinical trials outweigh the potential risks. Conclusion Research involving pregnant women is necessary to provide women with effective treatment during pregnancy, to promote fetal safety, and to reduce avoidable harm from suboptimal care and to provide pregnant women, their fetuses and newborns. (shrink)

In summary, the discussion by Professors Helmchen and Müller-Oerlinghausen of the morality of clinical trials has emphasized a point that is frequently overlooked. It is an essential to consider those situations in which it might be unethical not to conduct a trial as it is to be concerned about the ways in which trials might restrict the rights of the individuals taking part in them. They and I have dealt mainly with the first of these two issues (...) because it has been relatively neglected. The second is, of course, equally important and has rightly received much attention. Both matters deserve further public discussion. (shrink)

Outcome-adaptive randomization has been proposed as a corrective to certain ethical difficulties inherent in the traditional randomized clinical trial using fixed-ratio randomization. In particular, it has been suggested that OAR redresses the balance between individual and collective ethics in favour of the former. In this paper, I examine issues of welfare and autonomy arising in relation to OAR. A central issue in discussions of welfare in OAR is equipoise, and the moral status of OAR is crucially influenced (...) by the way in which this concept is construed. If OAR is based on a model of equipoise that demands strict indifference between competing interventions throughout the trial, such equipoise is disturbed by accruing data favouring one treatment over another; OAR seeks to redress this by weighting randomization to the seemingly superior treatment. However, this is a partial response, as patients continue to be allocated to the inferior therapy. Moreover, it rests upon considerations of aggregate harms and benefits, and does not therefore uphold individual ethics. Issues of fairness also arise, as early and late enrollees are randomized on a different basis. Fixed-ratio randomization represents a fuller and more consistent response to a loss of equipoise, as so construed. With regard to consent, the complexity of OAR poses challenges to adequate disclosure and comprehension. Additionally, OAR does not offer a remedy to the therapeutic misconception—participants’ tendency to attribute treatment allocation in an RCT to individual clinical judgments, rather than to scientific considerations—and, if anything, accentuates rather than alleviates this misconception. In relation to these issues, OAR fails to offer ethical advantages over fixed-ratio randomization. More broadly, the ethical basis of OAR can be seen to lie more in collective than in individual ethics, and overall it fares worse in this territory than fixed-ratio randomization. (shrink)

Human germline gene editing is often debated in hypothetical terms: if it were safe and efficient, on what further conditions would it then be ethically acceptable? This paper takes another course. The key question is: how can scientists reduce uncertainty about safety and efficiency to a level that may justify initiation of first-time clinical trials? The only way to proceed is by well-designed preclinical studies. However, what kinds of investigation should preclinical studies include and what specific conditions should (...) they satisfy in order to be considered well-designed? It is argued that multispecies and multigenerational animal studies are needed as well as human embryo editing without implantation. In order to be possible to translate to first-time clinical trials, animal studies need to satisfy strict conditions of validity. Moreover, embryo studies intended for translation to first-time clinical trials need to correspond to the animal studies in experimental design. Only in this way can uncertainty about risk for harm and prospect of benefit in first-time clinical trials be reduced to a modest level. If uncertainty is not reduced to such a level, first-time clinical trials in germline gene editing should not be initiated. (shrink)

Human germline gene editing is often debated in hypothetical terms: if it were safe and efficient, on what further conditions would it then be ethically acceptable? This paper takes another course. The key question is: how can scientists reduce uncertainty about safety and efficiency to a level that may justify initiation of first-time clinical trials? The only way to proceed is by well-designed preclinical studies. However, what kinds of investigation should preclinical studies include and what specific conditions should (...) they satisfy in order to be considered well-designed? It is argued that multispecies and multigenerational animal studies are needed as well as human embryo editing without implantation. In order to be possible to translate to first-time clinical trials, animal studies need to satisfy strict conditions of validity. Moreover, embryo studies intended for translation to first-time clinical trials need to correspond to the animal studies in experimental design. Only in this way can uncertainty about risk for harm and prospect of benefit in first-time clinical trials be reduced to a modest level. If uncertainty is not reduced to such a level, first-time clinical trials in germline gene editing should not be initiated. (shrink)

Voluntariness is a necessary condition of valid consent. But determining whether a person consented voluntarily can be difficult, especially when people are subjected to coercion or manipulation, placed in a situation with no acceptable alternative other than to consent to something, or find themselves in an abusive relationship. This book presents a novel view on the voluntariness of consent, especially medical consent, which the author calls Interpersonal Consenter-Consentee Justification (ICCJ). According to this view, consent is voluntary if and only if (...) the process by which it has been obtained aligns with principles of interpersonal justification. ICCJ is distinctive because it explains voluntary consent neither as a 'psychological' concept indicative of the inner states of a person's mind (e.g. willingness or reluctance) nor as a 'circumstantial' concept indicative of a person's set of options. Rather, ICCJ explains the voluntariness of consent as an 'interpersonal' concept requiring the absence of illegitimate control within the interaction between the person giving consent and the person receiving it. In so doing, ICCJ further develops the notion of interpersonal justification, known from contractualist theories in moral philosophy, and introduces it to the debate on consent. The author employs a top-down approach, defending ICCJ's key characteristics on the basis of general theoretical arguments, as well as a bottom-up approach, supporting ICCJ in its application to clinical challenges such as nudging and manipulation, living organ donation, and clinical trials. Voluntary Consent will appeal to researchers and advanced students in normative ethics, bioethics, philosophy of law, behavioural psychology, and medicine. (shrink)

The historical background of the discovery of adverse health effects of medicines, food additives, pesticides, and other chemicals is reviewed, and the development of national and international regulations and testing procedures to protect the public against the toxic effects of these drugs and chemicals is outlined. Ethical considerations of the safety evaluation of drugs and chemicals by human experimentation and animal toxicity studies, ethical problems associated with clinical trials, with the falsification of clinical and toxicological (...) data, and with inadequate experimental methodology, are reviewed, and the ethics of the marketing of drugs and their post-marketing surveillance, are similarly considered. These ethical problems are illustrated with many specific examples, including the drugs neoarsphenamine, chloramphenicol, thalidomide, diethyl stilboestrol and benoxaprofen. (shrink)

As the potential for the first human trials of somatic cell gene therapy nears, two ethical issues are examined: (1) problems of moral choice for members of institutional review boards who consider the first protocols, for parents, and for the clinical researchers, and the special protections that may be required for the infants and children to be involved, and (2) ethical objections to somatic cell therapy made by those concerned about a putative inevitable progression of (...) genetic knowledge from therapy to mass genetic engineering in human reproduction. The author's viewpoint is that a consensus exists on the required moral approach to somatic cell therapy, but that no moral approach yet exists for experiments beyond this level, especially in the germline cells of human beings. Keywords: gene therapy, somatic cells, germ cells, institutional review boards, genetic engineering CiteULike Connotea Del.icio.us What's this? (shrink)

Clinical trials of stem cell transplantation raise ethical issues that are intertwined with scientific and design issues, including choice of control group and intervention, background interventions, endpoints, and selection of subjects. We recommend that the review and IRB oversight of stem cell clinical trials should be strengthened. Scientific and ethics review should be integrated in order to better assess risks and potential benefits. Informed consent should be enhanced by assuring that participants comprehend key aspects (...) of the trial. For the trial to yield generalizable knowledge, negative findings and serious adverse events must be reported. (shrink)

For nearly two decades, the process of reviewing the ethical merit of research involving human subjects has been based on the application of principles initially described in the U.S. National Commission's Belmont Report, and later articulated more fully by Beauchamp and Childress in their Principles of Biomedical Ethics. Recently, the use of ethical principles for deliberating about moral problems in medicine and research, referred to in the pejorative sense as “principlism”, has come under scrutiny. In this paper (...) we argue that these principles can provide a foundation for the source of ethical appraisal of human research, but are not themselves wholly adequate for this purpose. Therefore, we further propose that principles should be understood as heuristics that can be “specified” as described by DeGrazia , and that the principle‐based approach should be supplemented by formally incorporating “sensitivity to context” into the evaluation of clinical trials. (shrink)

For nearly two decades, the process of reviewing the ethical merit of research involving human subjects has been based on the application of principles initially described in the U.S. National Commission's Belmont Report, and later articulated more fully by Beauchamp and Childress in their Principles of Biomedical Ethics. Recently, the use of ethical principles for deliberating about moral problems in medicine and research, referred to in the pejorative sense as “principlism”, has come under scrutiny. In this paper (...) we argue that these principles can provide a foundation for the source of ethical appraisal of human research, but are not themselves wholly adequate for this purpose. Therefore, we further propose that (1) principles should be understood as heuristics that can be “specified” as described by DeGrazia (1992), and (2) that the principle‐based approach should be supplemented by formally incorporating “sensitivity to context” into the evaluation of clinical trials. (shrink)

For nearly two decades, the process of reviewing the ethical merit of research involving human subjects has been based on the application of principles initially described in the U.S. National Commission's Belmont Report, and later articulated more fully by Beauchamp and Childress in their Principles of Biomedical Ethics. Recently, the use of ethical principles for deliberating about moral problems in medicine and research, referred to in the pejorative sense as “principlism”, has come under scrutiny. In this paper (...) we argue that these principles can provide a foundation for the source of ethical appraisal of human research, but are not themselves wholly adequate for this purpose. Therefore, we further propose that (1) principles should be understood as heuristics that can be “specified” as described by DeGrazia (1992), and (2) that the principle‐based approach should be supplemented by formally incorporating “sensitivity to context” into the evaluation of clinical trials. (shrink)

Incisively and stylishly written, this book constitutes an open challenge to reconsider the fundamental question of the relationship of law to society.

A broad critical review of national policies on biomedical research - human, epidemiologic, clinical trials, genetic, reproductive, etc.