From protectionism to inclusion: A New Zealand perspective on health‐related research involving adults incapable of giving informed consent

The revision of the Council of International Organizations of Medical Sciences (CIOMS) International ethical guidelines for health‐related research (2016) heralds a paradigm shift from the ‘protectionist’ policies that emerged following historical research atrocities of the 20th century, towards a more nuanced and inclusive approach to research participation. Adopting this modified approach will enable countries to secure the benefits of research for individuals and for society as a whole, while at the same time minimizing the potential for exploitation and research‐related harms. This article considers the potential impact of Guideline 16 of the CIOMS 2016 from a New Zealand perspective, with respect to research involving adults with impaired capacity and who are incapable of giving informed consent. While the CIOMS 2016 apply a ‘minimal risk’ threshold to guide research involving adults who lack capacity to consent, New Zealand law currently adopts a ‘best interests’ standard which significantly restricts the scope of permissible research that may be performed in this context. This article argues that the CIOMS 2016 should influence change to New Zealand’s legal framework for ethical review of research. CIOMS 2016 provides useful guidance for the necessary standards and processes to enable the responsible and ethical inclusion of adults with impaired capacity in research.     

Investigating assumptions of vulnerability: A case study of the exclusion of psychiatric inpatients as participants in genetic research in low‐ and middle‐income contexts

Psychiatric genetic research investigates the genetic basis of psychiatric disorders with the aim of more effectively understanding, treating, or, ultimately, preventing such disorders. Given the challenges of recruiting research participants into such studies, the potential for long‐term benefits of such research, and seemingly minimal risk, a strong claim could be made that all non‐acute psychiatric inpatients, including forensic and involuntary patients, should be included in such research, provided they have capacity to consent. There are tensions, however, regarding the ethics of recruiting psychiatric inpatients into such studies. In this paper our intention is to elucidate the source of these tensions from the perspective of research ethics committee interests and decision‐making. We begin by defining inpatient status and outline some of the assumptions surrounding the structures of inpatient care. We then introduce contemporary conceptions of vulnerability, including Florencia Luna’s account of vulnerability which we use as a framework for our analysis. While psychiatric inpatients could be subject to consent‐related vulnerabilities, we suggest that a particular kind of exploitation‐related vulnerability comes to the fore in the context of our case study. Moreover, a subset of these ethical concerns takes on particular weight in the context of genetic research in low‐ and middle‐income countries. At the same time, the automatic exclusion of inpatients from research elicits justice‐related vulnerabilities.     

Toward an integrated map of genetic interactions in cancer cells

Cancer genomes often harbor hundreds of molecular aberrations. Such genetic variants can be drivers or passengers of tumorigenesis and create vulnerabilities for potential therapeutic exploitation. To identify genotype‐dependent vulnerabilities, forward genetic screens in different genetic backgrounds have been conducted. We devised MINGLE, a computational framework to integrate CRISPR/Cas9 screens originating from different libraries building on approaches pioneered for genetic network discovery in model organisms. We applied this method to integrate and analyze data from 85 CRISPR/Cas9 screens in human cancer cells combining functional data with information on genetic variants to explore more than 2.1 million gene‐background relationships. In addition to known dependencies, we identified new genotype‐specific vulnerabilities of cancer cells. Experimental validation of predicted vulnerabilities identified GANAB and PRKCSH as new positive regulators of Wnt/β‐catenin signaling. By clustering genes with similar genetic interaction profiles, we drew the largest genetic network in cancer cells to date. Our scalable approach highlights how diverse genetic screens can be integrated to systematically build informative maps of genetic interactions in cancer, which can grow dynamically as more data are included.     

Adjusting the focus: A public health ethics approach to data research

This paper contends that a research ethics approach to the regulation of health data research is unhelpful in the era of population‐level research and big data because it results in a primary focus on consent (meta‐, broad, dynamic and/or specific consent). Two recent guidelines – the 2016 WMA Declaration of Taipei on ethical considerations regarding health databases and biobanks and the revised CIOMS International ethical guidelines for health‐related research involving humans – both focus on the growing reliance on health data for research. But as research ethics documents, they remain (to varying degrees) focused on consent and individual control of data use. Many current and future uses of health data make individual consent impractical, if not impossible. Many of the risks of secondary data use apply to communities and stakeholders rather than individual data subjects. Shifting from a research ethics perspective to a public health lens brings a different set of issues into view: how are the benefits and burdens of data use distributed, how can data research empower communities, who has legitimate decision‐making capacity? I propose that a public health ethics framework – based on public benefit, proportionality, equity, trust and accountability – provides more appropriate tools for assessing the ethical uses of health data. The main advantage of a public health approach for data research is that it is more likely to foster debate about power, justice and equity and to highlight the complexity of deciding when data use is in the public interest.     

Principlism and the ethical appraisal of clinical trials

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 De Grazia (1992), and (2) that the principle-based approach should be supplemented by formally incorporating "sensitivity to context" into the evaluation of clinical trials.     

PRINCIPLISM AND THE ETHICAL APPRAISAL OF CLINICAL TRIALS

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     

Reviews of Functional MRI: The Ethical Dimensions of Methodological Critique

Neuroimaging studies involving human subjects raise a range of ethics issues. Many of these issues are heightened in the context of neuroimaging research involving persons with mental health disorders. There has been growing interest in these issues among legal scholars, philosophers, social scientists, and as well as neuroimagers over the last decade. Less clear, however, is the extent to which members of the neuroimaging community are engaged with these issues when they undertake their research and report results. In this study, we analyze the peer-reviewed review literature involving fMRI as applied to the study of mental health disorders. Our hypothesis is that, due to the critical orientation of reviews, and the vulnerability of mental health population, the penetrance of neuroethics will be higher in the review literature in this area than it is in the primary fMRI research literature more generally. We find that while authors of reviews do focus a great deal of attention on the methodological limitations of the studies they discussed, contrary to our hypothesis, they do not frame concerns in ethical terms despite their ethical significance. We argue that an ethics lens on such discussion would increase the knowledge-value of this scholarly work.     

A human rights approach to an international code of conduct for genomic and clinical data sharing

Fostering data sharing is a scientific and ethical imperative. Health gains can be achieved more comprehensively and quickly by combining large, information-rich datasets from across conventionally siloed disciplines and geographic areas. While collaboration for data sharing is increasingly embraced by policymakers and the international biomedical community, we lack a common ethical and legal framework to connect regulators, funders, consortia, and research projects so as to facilitate genomic and clinical data linkage, global science collaboration, and responsible research conduct. Governance tools can be used to responsibly steer the sharing of data for proper stewardship of research discovery, genomics research resources, and their clinical applications. In this article, we propose that an international code of conduct be designed to enable global genomic and clinical data sharing for biomedical research. To give this proposed code universal application and accountability, however, we propose to position it within a human rights framework. This proposition is not without precedent: international treaties have long recognized that everyone has a right to the benefits of scientific progress and its applications, and a right to the protection of the moral and material interests resulting from scientific productions. It is time to apply these twin rights to internationally collaborative genomic and clinical data sharing.     

Ethical hurdles for translational research

The notion of translational research has gained considerable currency over the past few years. While such an approach promises great scientific and clinical advances, the penumbra of translational research tends to incorporate prioritizing scientific projects based upon their potential for translation; tight financial connections between sponsors, scientists and clinical investigators; and sometimes research involving biological approaches for which there is little experience determining safety. It is these aspects of translational research that raise some serious ethical challenges. In this report, we examine three specific areas that raise ethical questions: (1) the potential implications of prioritizing research objectives based on the potential for translation; (2) cautions related to moving from bench to bedside (and back again); and (3) unique questions for translational research initiatives in academic medical centers. Based on this examination, it is clear that the financial and ethical costs as well as benefits of taking a translational approach need to be considered. In the meantime, exquisite attention needs to be paid whenever translational research is likely to affect the traditional fiduciary responsibilities of scientists, clinicians and institutions to research subjects, patients and students. Successful mechanisms that might be developed to address any untoward effects should be shared and evaluated.     

道德规范与动物学

道德规范教育如今已经提升到了专业的水平。因此在专业领域里 (例如工程学和医学 ) ,道德规范教育应作为必修课程。但至今很多理科课程仍没有把它列为必修课。这就给我们提出了一个疑问 :理科是专业课程吗 ?如果是的话 ,那么科学家例如动物学家需不需要熟悉他们职责范围内的道德准则和尺度呢 ?动物学家对医学上暴露的一些问题很敏感———包括我们怎样对待动物以及我们怎样或者是否开展基因工程。但是从道德观念上来看 ,道德规范教育的实行是比这两件事更实际的。这篇论文就以上观点进行了进一步的论述 ,并且对把道德规范教育加入理科课程的需求和可能性做了评估。在现实社会里 ,动物科学家是被敬重的专业人士。他们每天面对着许多极可能影响我们生活环境的决策。有鉴于此 ,动物科学家必需掌握道德规范的标准 ,并且有能力做出与此相符合的决策。这才能使我们在动物学的教学过程中确保动物学家持续稳定的专业发展方向     

Module three: vulnerable/special participant populations

ABSTRACT This module is designed to sensitise you to the special needs of participants who belong to populations that are more vulnerable than other participant populations. These populations typically include incompetent persons women who may or may not be pregnant, children, prisoners and refugees, impoverished people, and ethnic minorities. These and similar groups deserve special consideration for a number of important ethical and historical reasons, specifically those that surround the potential for exploitation, problems with informed consent, and concerns about respect for participant autonomy. This module introduces modus operandi that are based on national and international research guidelines for dealing with vulnerable/special participant populations, offering contextually-dependent advice and relevant ethical considerations/arguments for and against their involvement in scientific research endeavours.     

CRISPR Ethics: Moral Considerations for Applications of a Powerful Tool

With the emergence of CRISPR technology, targeted editing of a wide variety of genomes is no longer an abstract hypothetical, but occurs regularly. As application areas of CRISPR are exceeding beyond research and biomedical therapies, new and existing ethical concerns abound throughout the global community about the appropriate scope of the systems' use. Here we review fundamental ethical issues including the following: 1) the extent to which CRISPR use should be permitted; 2) access to CRISPR applications; 3) whether a regulatory framework(s) for clinical research involving human subjects might accommodate all types of human genome editing, including editing of the germline; and 4) whether international regulations governing inappropriate CRISPR utilization should be crafted and publicized. We conclude that moral decision making should evolve as the science of genomic engineering advances and hold that it would be reasonable for national and supranational legislatures to consider evidence-based regulation of certain CRISPR applications for the betterment of human health and progress.     

Tailor-made pharmacotherapy: future developments and ethical challenges in the field of pharmacogenomics

Pharmacogenomics is the study of the myriad interactions between genes and pharmacotherapy. Developments in pharmacogenomics have changed and will affect pharmaceutical research, drug development and the practice of medicine in a significant way. In this article, we make an inventory of the ethical implications that might arise as a result of possible developments in pharmacogenomics and investigate whether the present ethical framework will be able to adequately answer arising questions. We think that many of the questions related to the consequences of pharmacogenomics are answerable along the lines of present ethical thinking. We also believe, however, that many 'changes of degree' may result in a 'change of kind.' We therefore think that pharmacogenomics may potentially have such a profound influence on scientific research and the pharmaceutical industry, the practice of medicine and society at large, that this will generate its own unique dynamic, which will require new ethical research. We suggest that the notion of 'responsibility' will be a major focus of such research.     

The ethics of biobanking: Assessing the right to control problem for broad consent

The biobank consent debate is one with deeply held convictions on both the ‘broad’ and ‘specific’ side with little sign of resolution. Recently, Thomas Ploug and Soren Holm have developed an alternative to both specific and broad consent: a meta‐consent framework. The aim here is to consider whether meta‐consent provides a ‘solution’ to the biobank consent debate. We clarify what ‘meta‐consent’ actually is (arguing that the label is a misnomer and ‘consent à la carte’ is more accurate). We identify problems with Ploug and Holm's arguments, and some challenges for meta‐consent. We focus on whether there is any ethical obligation to provide consent à la carte. There may seem to be so, especially if we draw upon an unclear appeal to the ethical significance of ‘respect for autonomy’. Similarly, there might seem to be an intuitive inference from the fact that ethically legitimate research requires informed consent to the conclusion that it thereby requires consent à la carte. It is shown that this line of inference is mistaken.     

Ethical issues surrounding controlled human infection challenge studies in endemic low-and middle-income countries

Controlled human infection challenge studies (CHIs) involve intentionally exposing research participants to, and/or thereby infecting them with, micro-organisms. There have been increased calls for more CHIs to be conducted in low- and middle-income countries (LMICs) where many relevant diseases are endemic. This article is based on a research project that identified and analyzed ethical and regulatory issues related to endemic LMIC CHIs via (a) a review of relevant literature and (b) qualitative interviews involving 45 scientists and ethicists with relevant expertise. In this article we argue that though there is an especially strong case for conducting CHIs in endemic (LMIC) settings, certain ethical issues related to the design and conduct of such studies (in such settings) nonetheless warrant particularly careful attention. We focus on ethical implications of endemic LMIC CHIs regarding (a) potential direct benefits for participants, (b) risks to participants, (c) third-party risks, (d) informed consent, (e) payment of participants, and (f) community engagement. We conclude that there is a strong ethical rationale to conduct (well-designed) CHIs in endemic LMICs, that certain ethical issues warrant particularly careful consideration, and that ethical analyses of endemic LMIC CHIs can inform current debates in research ethics more broadly.     

AUTHORIZING PSYCHIATRIC RESEARCH: PRINCIPLES,PRACTICES AND PROBLEMS

Psychiatric research is advancing rapidly, with studies revealing new investigative tools and technologies that are aimed at improving the treatment and care of patients with psychiatric disorders. However, the ethical framework in which such research is conducted is not as well developed as we might expect. In this paper we argue that more thought needs to be given to the principles that underpin research in psychiatry and to the problems associated with putting those principles into practice. In particular, we comment on some of the difficulties posed by the twin imperatives of ensuring that we respect the autonomy and interests of the research subject and, at the same time, enable potentially beneficial psychiatric research to flourish. We do not purport to offer a blueprint for the future; we do, however, seek to advance the debate by identifying some of the key questions to which better answers are required.     

Module one: introduction to research ethics

This module will introduce you to the ethical concepts underlying applied ethical decision-making in the area of research involving human participants. We will also learn what the issues are that people involved in research on research ethics are concerned with. Ethics without an understanding of historical and legal context makes arguably little sense. It is for this reason that this module will begin with a brief history of research ethics and ends with a brief overview of the relevant national and international guidelines pertaining to ethical issues in research involving human participants.     

Biobanking and deceased persons

Early biomedical research focused primarily on the study of specific diseases or sets of diseases within small groups of living research participants. Accordingly, the first ethical frameworks governing biomedical research addressed short-term, limited-scope research involving living research participants. Due to recent interest in longitudinal population studies and biobanking, research is increasingly long term. This shift raises several ethical and legal issues concerning the impact of a participant’s death on research. This paper offers an overview of these issues in the context of longitudinal biobanking genetic research. Our first part outlines the legal and ethical frameworks that govern the effect of the participants’ death on consent. This will be followed by an analysis of the legal and ethical frameworks that govern the secondary use of deceased participants’ data and samples and the return of deceased participants’ individual research results to biological family members. In our second part, we will review the current literature and discuss the above mentioned issues using the bioethics “principlism” theory before concluding.