Medical Research Ethics

Given the sordid history of injustices linking genetics to race and ethnicity, considerations of justice are central to ensuring the responsible development of precision medicine programmes around the world. While considerations of justice may be in tension with other areas of concern, such as scientific value or privacy, there are also be tensions between different aspects of justice. This paper focuses on three particular aspects of justice relevant to this context: social justice, distributive justice and human rights. The implications of (...) each for the use of race and ethnicity in precision medicine is described, along with how they intersect and potentially conflict with one another. By attending to these intersections, we aim to enrich and add nuance to debates over how best to proceed with precision medicine initiatives. (shrink)

كان يمشي في الأرض مرحًا، مُصعرًا خده للطبيعة، ومُنتشيًا برفاهيات حضاراته؛ أو يخطو فوق أديمها مهمومًا بضنك العيش، يعتصره ألم البحث عن قوت يومه، قبل أن يُفاجئه الفيروس التاجي ليقلب حياته رأسًا على عقب. إنه الإنسان، ذلك المجهول لنفسه، الجاهل بعلمه، المغرور بعقله، الضعيف بقوته، المتناقض مع ذاته، الفقير بثرواته الضخمة! فجأة باتت تعتمل بداخله مشاعر الحيرة والخوف والقلق، تؤرقه تساؤلات تسخر من عجزه الصارخ عن الإجابة عنها: ما أصل هذا الفيروس؟ هل هو نبتٌ طبيعي أم مؤامرة من بني جلدته؟ (...) ما هو أفضل علاج لمكافحته؟ لماذا يحصد الأرواح غير مًبالٍ؟ وكيف يمكن لكائن متناه في الصغر، غير مرئي، أن يشن حربًا ضد البشر بكل هذه القوة في القرن الحادي والعشرين، ورغم كل ما تحقق من تقدمٍ علمي وطبي مذهل؟ يعجز العلم عن الإجابة، ويعجز الساسة عن التبرير، ويعجز الدعاة عن المواساة، ويعجز العائل عن حماية رعيته، وينكفئ المرء على نفسه باحثًا عن الإجابات في منطقةٍ فكرية مُهملة: الفلسفة! أجل، فتساؤلات الجائحة تُشبه كثيرًا تلك المنطقة الحدودية التي حدثنا عنها الفيلسوف الألماني «كارل ياسبرز»، والتي لا يمكن أن نتجاوزها بالطرقة العلمية والتجريبية، عندها يُواجه المرء خيارين لا ثالث لهما: إما أن يستسلم لأمواج اليأس العاتية، أو يتوضأ من أنهار الحكمة التي تناساها ردحًا طويلاً من الزمن! لا شك أن ثمة نظريات عديدة عن أصل الفيروس: بعضهم يعتقد أنه مُنتج بشري تم تخليقه في المختبرات لاستخدامه كسلاح بيولوجي يُعزز الهيمنة، لكنه فرَّ من مخترعيه فأصابهم، سواء عن غير قصد، أو مع سبق الإصرار والترصد؛ وبعضهم يعتقد أنه مجرد أداة تحصنت بها الطبيعة ضد عبث الإنسان وإفساده اللامنقطع في البر والبحر ... لكن الفيروس في كل الأحوال يتحدانا بقوة، ويكشف لنا بوحشية عن مدى هشاشتنا، سواء كنا أفرادًا أو جماعات، ويدفعنا إلى إعادة تقييم لحظتنا الوجودية: مَن نحن؟ وما مكاننا في الكون؟ وهل ثمة ما يمكن أن يُهدد بقاءنا كنوعٍ في أي وقت؟! لقد أظهر لنا الفيروس مدى أهمية الحياة، ومدى غباء انخراطنا الدائم في الصراع بدلاً من البحث عن سُبلٍ للتفاهم والتعاون! وعندما ينسحب الجميع في معازلهم، سواء أكانت مختبرات ومشافي تموج بأشرس معارك العلم ضد الفيروس، أو منازل تتضخم فيها مخاوف القدرة على اجتياز الجائحة، تتحول معازل الفلاسفة إلى خلايا فكرية تبسط أشرعة المعنى والمغزى والهدف على الجميع. هذا ما نحاول تبيانه في هذا المقال؛ من عزاء الفلسفة للحيارى والقانطين والموجوعين؛ إلى حالة الطبيعة الهوبزية البادية في الأفق وشروط تجاوزها؛ إلى المعضلات الأخلاقية المنبثقة في غيابات التيه الفيروسية الجديدة؛ إلى معنى الوجود والبقاء والهوية؛ إلى العدو المُكتشف والمُنتظَر في عالم كورونا وما بعده: اللامساواة، والعبث بالاستقرار المُناخي! (shrink)

Governments are increasingly using randomized controlled trials (RCTs) to evaluate policy interventions. Such studies are often understood to provide the highest quality evidence regarding the causal efficacy of an intervention. While randomization plays an essential epistemic role in the context of policy RCTs however, it also plays an important distributive role. By randomly assigning participants to either the intervention or control arm of an RCT, people are subjected to different policies and so, often, to different types and levels of benefits. (...) In this paper, I aim to identify a set of conditions under which it is permissible, in the context of government policy experiments, for investigators to randomly assign participants to intervention and control arms of policy RCTs. I argue first that random assignment is permissible in cases where investigators occupy a state of genuine equipoise regarding all arms of the experiment and the policy to which citizens have a claim of justice to be subject. I then defend a set of conditions under which random assignment is permissible in cases where investigators know that one or more arms of a policy RCT are either superior or inferior to this policy. (shrink)

The future of health research will be characterised by three continuing trends: rising demand for health data; increasing impracticability of obtaining specific consent for secondary research; and decreasing capacity to effectively anonymise data. In this context, governments, clinicians and the research community must demonstrate that they can be responsible stewards of health data. IRBs and RECs sit at heart of this process because in many jurisdictions they have the capacity to grant consent waivers when research is judged to be of (...) particular value. However, several different terms are used to refer to this value, indicating a lack of conceptual clarity regarding the appropriate test for access to health data for research without consent. In this paper we do three things. First we describe the current confusion and instability in terminology relating to public interest in the context of consent waivers. Second we argue for harmonisation of terminology on the grounds of clarity, transparency and consistency. Third we argue that the term ‘public interest’ best reflects the normative work required to justify consent waivers because it is the broadest of the competing terms. ‘Public interest’ contains within its scope positive and negative implications of a study, as well as welfare, justice and rights considerations. In making this argument, we explain the normative basis for consent waivers, and provide a starting place for further discussion about the precise conditions in which a given study can be said to advance the public interest. Ipsos MORI study found that: … the public would be broadly happy with administrative data linking for research projects provided Those projects have social value, broadly defined. Data are de-identified. Data are kept secure. Businesses are not able to access the data for profit. (shrink)

Worldwide populations are aging with economic development as a result of public health initiatives and advances in therapeutic discoveries. Since 1850, life expectancy has advanced by 1 year for every four. Accompanying this change is the rapid development of anti‐aging science. There are three schools of thought in the field of aging science. One perspective is the life course approach, which considers that aging is a good and natural process to be embraced as a necessary and positive aspect of life, (...) where the aim is to improve the quality of existing lifespan and “compress” morbidity. Another view is that aging is undesirable, and that rejuvenation and indeed immortality are possible since the biological basis of aging is understood, and therefore, strategies are possible for engineering negligible senescence. Finally, a hybrid approach is that life span can be extended by anti‐aging medicines but with uncertain effects on health. While these advances offer much promise, the ethical perspectives are seldom discussed in cross‐disciplinary settings. This article discusses some of the key ethical issues arising from recent advances in biogerontology. (shrink)

A large proportion of the total global burden of disease is caused by emergency medical conditions. Emergency care research is essential to improving emergency medicine but this research can raise some distinctive ethical challenges, especially with regard to (1) standard of care and risk–benefit assessment; (2) blurring of the roles of clinician and researcher; (3) enrolment of populations with intersecting vulnerabilities; (4) fair participant selection; (5) quality of consent; and (6) community engagement. Despite the importance of research to improve emergency (...) care in low-income and middle-income countries (LMICs) and the widely acknowledged ethical challenges, very little has been written on the ethics of emergency care research in LMICs. This paper examines the ethical and regulatory challenges to conducting emergency care research with human participants in LMICs. We outline key challenges, present potential solutions or frameworks for addressing these challenges, and identify gaps. Despite the ethical and regulatory challenges, conducting high-quality, ethical emergency care research in LMICs is possible and it is essential for global health. (shrink)

The episodes of cowpox inoculation (1798) and rabies preventive treatment (1885) are celebrated as the landmark of modern medicine. Paradoxically, these two advances have been accomplished without any theoretical breakthrough in the understanding of immunity. Going further, they were made possible by a long past of empirical procedures among which smallpox inoculation played an outstanding role. The paper explores the paradox of 'Immunization without Immunology' and Pasteur's reconstruction of the past, through his successful use of a metaphor. 'Vaccine', originally linked (...) to the jennerian method, was meant by Pasteur to designate a general program of virus attenuation. The paper investigates the scientific factors accounting for why viruses played such a leading role in immunization. The longlasting immunity, the easy transmission from man to man characteristic of smallpox allowing in vivo experimentation, may explain how crude procedures of early immunizers shaped scientific ideologies and strategies of public health and family initiated modern 'vaccinology'. (shrink)

The numerous researches devoted to 'jaundice' during the Second World War have brought to light the existence of an infectious type of hepatic jaundice or 'homologous serum jaundice' following parenteral injection of vaccines containing human serum and blood transfusions, which were carried out on a large scale at the time. This type of serum jaundice was then gradually differentiated from 'catarrhal', contagious or epidemic jaundice by clinical trials along with large series of animal studies. Finally, the epidemiological, clinical and biological (...) data obtained made it possible to establish, between 1944 and 1954, the viral etiology of these two types of jaundice: the A virus, present in the patients' blood and stools, was considered to be the agent responsible for epidemic hepatitis; the B virus, present primarily in the blood, was held to be responsible for serum hepatitis. (shrink)

Summary This volume undertakes to determine the fundamentals and limits of an ethical assessment of the methods of modern medical technology with regard to the concepts of human dignity and human image, which are particularly important for this purpose. It shows that the philosophical-legal foundation of the term human dignity has not yet been clearly clarified; one even has to ask whether the term is (still) suitable for assessing ethical problems in medical technology. The term human image also needs clarification (...) and clarification in order to be taken seriously as a topos in the medical ethical discussion. The volume emerged from the work of an interdisciplinary and international research group at the Center for Interdisciplinary Research (ZiF), Bielefeld. It deals primarily with the theoretical foundation of the terms human dignity and human image and is supplemented by a volume, the contributions of which illustrate the problems of practice using examples from different areas of medical technology. (shrink)

This book makes an important contribution to ongoing efforts in the fields of medical law and bioethics to answer the challenges posed by the limitations of the principle of respect for autonomy, especially as these pertain to human research ethics. The principle of respect for autonomy seems to have become firmly embedded in human research ethics since its inclusion in the 1947 Nuremberg Code, which was a response to atrocities committed by Nazi doctors. Nonetheless, there is an increasing awareness of (...) the limitations of the principle of respect for autonomy and the underlying conceptualisations of human autonomy. (shrink)

This chapter examines the explicit and implicit roles that the concept of beneficence plays in the guidelines that govern biomedical research involving humans. We suggest that the role beneficence is actually playing in the guidelines is more comprehensive than is commonly assumed. The broader conceptualisation of beneficence proposed here clarifies the relationship of beneficence to respect for autonomy. It does this by showing how respect for autonomy is at the service of beneficence rather than in tension with it.

This book makes an important contribution to ongoing efforts in the fields of medical law and bioethics to answer the challenges posed by the limitations of the principle of respect for autonomy, especially as these pertain to human research ethics. The principle of respect for autonomy seems to have become firmly embedded in human research ethics since its inclusion in the 1947 Nuremberg Code, which was a response to atrocities committed by Nazi doctors. Nonetheless, there is an increasing awareness of (...) the limitations of the principle of respect for autonomy and the underlying conceptualisations of human autonomy. (shrink)

Since the end of World War II, most guidelines governing human research seem to have relied on the principle of respect for autonomy as a key, though not sole, criterion in assessing the moral validity of research involving human participants.1 One explanation for this apparent reliance on respect for autonomy may be that respect for autonomy, made effective through the practice of obtaining informed consent, functions as a useful proxy when dealing with competent adults for the more complex principle of (...) respect for human dignity that underpins much of the moral discourse in this area. If this explanation holds, then assessment of the moral licitness of research involving human individuals whose autonomy is limited in some way requires a deeper analysis of the ‘thicker’ concepts of human dignity, since we cannot rely on respect for autonomy to do the work of respect for human dignity where autonomy (understood as a capacity to consent based on adequate information) is not present, is limited or is compromised. (shrink)

Respect for autonomy has become a fundamental principle in human research ethics. Nonetheless, this principle and the associated process of obtaining informed consent do have limitations. This can lead to some groups, many of them vulnerable, being left understudied. This book considers these limitations and contributes through legal and philosophical analyses to the search for viable approaches to human research ethics. It explores the limitations of respect for autonomy and informed consent both in law and through the examination of cases (...) where autonomy is lacking (infants), diminished (addicts), and compromised (low socio-economic status). It examines alternative and complementary concepts to overcome the limits of respect for autonomy, including beneficence, dignity, virtue, solidarity, non-exploitation, vulnerability and self-ownership. It takes seriously the importance of human relationality and community in qualifying, tempering and complementing autonomy to achieve the ultimate end of human research - the good of humankind. (shrink)

BackgroundSeveral jurisdictions, including Singapore, Australia, New Zealand and most recently Ireland, have a public interest or public good criterion for granting waivers of consent in biomedical research using secondary health data or tissue. However, the concept of the public interest is not well defined in this context, which creates difficulties for institutions, institutional review boards and regulators trying to implement the criterion.Main textThis paper clarifies how the public interest criterion can be defensibly deployed. We first explain the ethical basis for (...) requiring waivers to only be granted to studies meeting the public interest criterion, then explore how further criteria may be set to determine the extent to which a given study can legitimately claim to be in the public interest. We propose an approach that does not attempt to measure magnitude of benefit directly, but rather takes into account metrics that are more straightforward to apply. To ensure consistent and justifiable interpretation, research institutions and IRBs should also incorporate procedural features such as transparency and public engagement in determining which studies satisfy the public interest requirement.ConclusionThe requirement of public interest for consent waivers in secondary biomedical research should be guided by well-defined criteria for systematic evaluation. Such a criteria and its application need to be periodically subject to intra-committee and intra-institution review, reflection, deliberation and amendment. (shrink)

The burgeoning field of biomedical research involving the mixture of human and animal materials has attracted significant ethical controversy. Due to the many dimensions of potential ethical conflict involved in this type of research, and the wide variety of research projects under discussion, it is difficult to obtain an overview of the ethical debate. This paper attempts to remedy this by providing a systematic review of ethical reasons in academic publications on human-animal chimera research. We conducted a systematic review of (...) the ethical literature concerning human-animal chimeras based on the research question: “What ethical reasons have been given for or against conducting human-animal chimera research, and how have these reasons been treated in the ongoing debate?” Our search extends until the end of the year 2017, including MEDLINE, Embase, PhilPapers and EthxWeb databases, restricted to peer-reviewed journal publications in English. Papers containing ethical reasons were analyzed, and the reasons were coded according to whether they were endorsed, mentioned or rejected. Four hundred and thirty-one articles were retrieved by our search, and 88 were ultimately included and analyzed. Within these articles, we found 464 passages containing reasons for and against conducting human-animal chimera research. We classified these reasons into five categories and, within these, identified 12 broad and 31 narrow reason types.15% of the retrieved passages contained reasons in favor of conducting chimera research, while 85% of the passages contained reasons against it. The reasons against conducting chimera research fell into four further categories: reasons concerning the creation of a chimera, its treatment, reasons referring to metaphysical or social issues resulting from its existence and to potential downstream effects of chimera research. A significant proportion of identified passages fell under Category C. We hope that our results, in revealing the conceptual and argumentative structure of the debate and highlighting some its most notable tendencies and prominent positions, will facilitate continued discussion and provide a basis for the development of relevant policy and legislation. (shrink)

Ethical decision-making frameworks assist in identifying the issues at stake in a particular setting and thinking through, in a methodical manner, the ethical issues that require consideration as well as the values that need to be considered and promoted. Decisions made about the use, sharing, and re-use of big data are complex and laden with values. This paper sets out an Ethics Framework for Big Data in Health and Research developed by a working group convened by the Science, Health and (...) Policy-relevant Ethics in Singapore Initiative. It presents the aim and rationale for this framework supported by the underlying ethical concerns that relate to all health and research contexts. It also describes a set of substantive and procedural values that can be weighed up in addressing these concerns, and a step-by-step process for identifying, considering, and resolving the ethical issues arising from big data uses in health and research. This Framework is subsequently applied in the papers published in this Special Issue. These papers each address one of six domains where big data is currently employed: openness in big data and data repositories, precision medicine and big data, real-world data to generate evidence about healthcare interventions, AI-assisted decision-making in healthcare, public-private partnerships in healthcare and research, and cross-sectoral big data. (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)

The article by MacKay and Saylor (2020) claims that the principle of fair subject selection yields conflicting imperatives (e.g. in the case of pregnant women) and should be understood as “a bundle of four distinct sub-principles” (i.e. fair inclusion, burden sharing, opportunity, distribution of third-party risks), each having conflicting normative recommendations (MacKay and Saylor 2020). The authors also offer guidance as to how we should navigate between subprinciples that may conflict with each other. The problem is a crucial one since (...) fair subject selection is one of the principles regulating clinical research that produces generalizable knowledge with the potential of improving people’s health. Therefore, there may be cases where the way in which participants are selected directly influences the generalizability (or its lack) of the clinically relevant knowledge and its value (if any) to different groups. In my commentary article, written from the philosophical perspective, I notice a number of interrelated problems which I believe have not been discussed thoroughly in the target article: (1) the precise way in which health care priority setting should influence the content of health research priority setting and fair inclusion principles; (2) the distinction between group and individual benefits and burdens from clinical research; (3) the reference class problem in medical research. (shrink)

The concordance of results that are “robust” across multiple scientific modalities is widely considered to play a critical role in the epistemology of science. But what should we make of those cases where such multimodal evidence is discordant? Jacob Stegenga has recently argued that robustness is “worse than useless” in these cases, suggesting that “different kinds of evidence cannot be combined in a coherent way.” In this article I respond to this critique and illustrate the critical methodological role that robustness (...) plays as an aim of scientific inquiry. (shrink)

Unlike its friendly cousin the placebo effect, the nocebo effect (the effect of expecting a negative outcome) has been almost ignored. Epistemic and ethical confusions related to its existence have gone all but unnoticed. Contrary to what is often asserted, adverse events following from taking placebo interventions are not necessarily nocebo effects; they could have arisen due to natural history. Meanwhile, ethical informed consent (in clinical trials and clinical practice) has centred almost exclusively on the need to inform patients about (...) intervention risks with patients to preserve their autonomy. Researchers have failed to consider the harm caused by the way in which the information is conveyed. In this paper, I argue that the magnitude of nocebo effects must be measured using control groups consisting of untreated patients. And, because the nocebo effect can produce harm, the principle of non-maleficence must be taken into account alongside autonomy when obtaining (ethical) informed consent and communicating intervention risks with patients. (shrink)

Novel therapeutics enter human testing after they show promise in animal and in vitro studies. They then begin a life cycle that extends from early phase trials without control groups, to randomized trials, to approval by regulatory authorities, to coverage by payers, to use in clinical practice. At each stage, scientific evidence is critical to determining whether to progress to the next step in this life cycle. Each of these decisions also implicitly involves issues of value and ethical norms based (...) on how the decision-makers weigh the risks of two types of errors: false positives and false negatives. For example, in determining whether to approve a new molecular entity based on evidence submitted by a.. (shrink)

Survival of the fittest in evolutionary biology has a counterpart in the evolution of research paradigms. It’s called survival of the funded, and there is a sense in which paradigms are even more adaptable than species. Whereas species may become extinct if their fitness declines below a critical threshold, paradigms can rise again, perhaps with a new name, following fiscal collapse, provided only that funding is once again made available.A current example is the born-again concept of comparative effectiveness research , (...) which achieved resurrection status with the passage of the Affordable Care Act of 2010. The ACA established a private, nonprofit entity to oversee publicly financed CER. According to .. (shrink)

An apparent ethical dilemma arises when physicians consider enrolling their patients in randomized clinical trials. Suppose that a randomized clinical trial comparing two treatments is in progress, and a physician has an opinion about which treatment is better. The physician has a duty to promote the patient's best medical interests and therefore seems to be obliged to advise the patient to receive the treatment that the physician prefers. This duty creates a barrier to the enrollment of patients in randomized clinical (...) trials.1-10 Two strategies are often used to resolve the dilemma in favor of enrolling patients in clinical trials. (shrink)

The subject matter of ethics is morality, and ethics deals with it in four different though closely related ways: by analysis, by criticism, by norm construction, and by moral pragmatics.