Fair Subject Selection Research Articles

Ethics of research

Ethics of research

Are enrollment criteria for phase II and III clinical trials in acute myeloid leukemia arbitrarily restrictive?

6525 Background: Ethical clinical research requires fair subject selection and a favorable risk-benefit ratio. Enrollment criteria can unfairly exclude patients if they are not based in safety. There are few data regarding variability within criteria, which can also represent unfair exclusion, or for acute myeloid leukemia (AML). Methods: We assessed enrollment criteria use and variability for frontline phase II and III therapeutic AML trials from 2010-2019 listed on Clinicaltrials.gov. Drug safety profiles were obtained from protocols, publications, and FDA labels. FDA publications guided a standardized abstraction and coding process. Associations between criteria and safety profiles were identified using X2 and t-tests. Regression modeling identified differences in infectious disease (ID) exclusion by sponsor adjusted for trial phase, year, size, and safety profiles. Results: 190 trials were eligible; 159 (84%) were phase II and 32 (17%) phase III. Trials were sponsored by the National Institutes of Health (NIH; 50; 26%), industry (109; 57%), and academic investigators (AI; 108; 57%). Exclusions and variability are shown in the table. ID exclusions were for HIV (96; 51%) and hepatitis B (60; 32%) and C (64; 34%). Older adults were considered as over 60 (42 trials; 39%), 65 (23; 21%), 70 (13; 12%), or 75 years (18; 17%). There was no association between QTc limits and the use of QTc prolonging drugs (criteria presence p=0.2; mean 450 vs 474 ms, p=0.3) or renal function limits and nephrotoxic drugs (presence p=0.2; mean 1.65 vs 1.67 ULN, p=0.8). Hepatitis B and C exclusions were associated with the use of drugs linked to viral reactivation (OR 2.1 [95% CI 1.1,3.9], 2.0 [95% CI 1.1,3.7]). This was not the case for HIV (OR 1.2 [95% CI 0.7,2.2]). Industry sponsorship was independently associated with hepatitis B and C exclusion (OR 3.0 [95% CI 1.2,7.3], 3.3 [95% CI 1.4,4.7]) and AI sponsorship with HIV exclusion (OR 2.5 [95% CI 1.4,5.5]). Conclusions: There is substantial variability in enrollment criteria for AML clinical trials. Many criteria are related to risks, but some exclusions and variability are not clearly based in safety. Avoiding arbitrary exclusions will likely enhance trial representativeness and enrollment rates. [Table: see text]

Contextual Vulnerability Should Guide Fair Subject Selection in Xenotransplantation Clinical Trials

Contextual Vulnerability Should Guide Fair Subject Selection in Xenotransplantation Clinical Trials

Institutional Review Boards and Public Justification

Ethics committees like Institutional Review Boards and Research Ethics Committees are typically empowered to approve or reject proposed studies, typically conditional on certain conditions or revisions being met. While some have argued this power should be primarily a function of applying clear, codified requirements, most institutions and legal regimes allow discretion for IRBs to ethically evaluate studies, such as to ensure a favourable risk-benefit ratio, fair subject selection, adequate informed consent, and so forth. As a result, ethics committees typically make moral demands on researchers: require them to act in a way the committee considers ethically right or appropriate. This paper argues that moral demands are legitimate only if publicly justifiable; and as a result, committee decisions are subject to a public justification requirement. Ethics committees can permissibly request for more information, changes to the research protocol or that the research is delayed or even stopped only if these demands are publicly justifiable. This latter claim is in turn justified on the basis that moral demands to φ are permissible only if we are in a position to know that the addressee ought to φ and that we are in a position to know a proposition only if it is publicly justifiable.This argument suggests that ethics committees must consciously and explicitly appeal to public reasons in their decision-making. In cases where public reasons cannot be offered, committees would not be permitted to reject a given study or make approval conditional on an amendment.

Reviewing fair subject selection considerations for the unique case of post sequelae COVID-19 translational studies.

Fair inclusion of research subjects is necessary to ensure that post-acute sequelae COVID-19 (PASC) research results benefit all members of society. Scientists should conduct research on a broad sample of individuals who represent clinically relevant factors influencing a disease. Without demographic diversity and sociological and environmental variability, research outputs are less likely to apply to different populations and would thus increase health disparities. The goal of this narrative literature review and ethical analysis is to apply fair selection criteria to PASC research studies. We briefly highlight the importance of fair subject selection in translational research and then identify features of PASC, as well as PASC research, that hinder fair inclusion of research participants. We will demonstrate that determining an adequate and representative sample is not simply a matter of ensuring greater diversity; rather, fairness requires a broader evaluation of risks, burdens, and benefits specific to underrepresented populations. We provide recommendations to ensure fair subject selection in PASC research and promote translation toward positive health outcomes for all individuals, including the most vulnerable.

Animal Research that Respects Animal Rights: Extending Requirements for Research with Humans to Animals.

The purpose of this article is to show that animal rights are not necessarily at odds with the use of animals for research. If animals hold basic moral rights similar to those of humans, then we should consequently extend the ethical requirements guiding research with humans to research with animals. The article spells out how this can be done in practice by applying the seven requirements for ethical research with humans proposed by Ezekiel Emanuel, David Wendler, and Christine Grady to animal research. These requirements are (1) social value, (2) scientific validity, (3) independent review, (4) fair subject selection, (5) favorable risk-benefit ratio, (6) informed consent, and (7) respect for research subjects. In practice, this means that we must reform the practice of animal research to make it more similar to research with humans, rather than completely abolish the former. Indeed, if we ban animal research altogether, then we would also deprive animals of its potential benefits-which would be ethically problematic.

Critiquing the ethics review process in the 2019 Nieuwoudt et al. study on the impact of age and education on cognitive functioning among coloured South African women

In April 2019, Nieuwoudt et al . published an article on the impact of age and education on cognitive functioning among coloured women in the Western Cape Province, South Africa (SA). The study reported that coloured women in SA have increased risk for low cognitive functioning, as a result of limited education and unhealthy lifestyles. The article was widely criticised, and the journal subsequently withdrew the piece. It was argued that the study was unethical as it perpetuated racial stereotypes through its failure to recognise the distinction between race and ethnicity when undertaking biological research on a race group. The study had received ethical approval, which raised pertinent questions about the ethics review process. This article looks at ( i ) the role of research ethics committees (RECs); and ( ii ) the normative framework within which ethics committees operate. It avers that an understanding of the ethical issues of scientific validity, fair subject selection and minimising harms must be viewed in the light of the complex social issues surrounding the construction of coloured identity in SA. The article finds that the REC should have considered this study unapprovable, because its methodology was based on racist assumptions, and its focus on one race or ethnic group posed social risks for that community. The REC ought to have interrogated why researchers were unclear in their distinction between race and ethnicity, and have been mindful of race being a social rather than a biological construct.

Fair and equitable subject selection in concurrent COVID-19 clinical trials

Clinical trials emerged in rapid succession as the COVID-19 pandemic created an unprecedented need for life-saving therapies. Fair and equitable subject selection in clinical trials offering investigational therapies ought to...

Selecting participants fairly for controlled human infection studies.

Controlled human infection (CHI) studies involve the deliberate exposure of healthy research participants to infectious agents to study early disease processes and evaluate interventions under controlled conditions with high efficiency. Although CHI studies expose participants to the risk of infection, they are designed to offer investigators unique advantages for studying the pathogenesis of infectious diseases and testing potential vaccines or treatments in humans. One of the central challenges facing investigators involves the fair selection of research subjects to participate in CHI studies. While there is widespread agreement that investigators have a duty to select research participants fairly, this principle also yields conflicting ethical imperatives, for example requiring investigators to both exclude potential participants with co-morbidities since they face increased risks, but also to include them in order to ensure generalizability. In this paper we defend an account of fair subject selection that is tailored to the context of CHI studies. We identify the considerations of fairness that bear directly on selecting participants for CHI studies and provide investigators and members of IRBs and RECs with a principled way to navigate the conflicting imperatives to which these considerations give rise.

Four Faces of Fair Subject Selection

Although the principle of fair subject selection is a widely recognized requirement of ethical clinical research, it often yields conflicting imperatives, thus raising major ethical dilemmas regarding participant selection. In this paper, we diagnose the source of this problem, arguing that the principle of fair subject selection is best understood as a bundle of four distinct sub-principles, each with normative force and each yielding distinct imperatives: (1) fair inclusion; (2) fair burden sharing; (3) fair opportunity; and (4) fair distribution of third-party risks. We first map out these distinct sub-principles, and then identify the ways in which they yield conflicting imperatives for the design of inclusion and exclusion criteria, and the recruitment of participants. We then offer guidance for how decision makers should navigate these conflicting imperatives to ensure that participants are selected fairly.

EL-15 - New Ethical Guideline for Medical and Health Research Involving Human Subjects

Recently there has been a series of scientific misconduct in clinical researches. In response to these scandals, new Ethical Guideline for Medical and Health Research Involving Human Subjects has been activated since April 2015. While participant protection was regarded as most important in the previous ethical guideline, the new guideline requires higher study quality especially for invasive/interventional studies. In the beginning of the guideline, the famous 7 basic principles of research ethics (Emanuel et al. JAMA 2000) were introduced which include: i) Social value, ii) Scientific validity, iii) Fair subject selection, iv) Favorable risk/benefit ratio, v) Independent review, vi) Informed consent and vii) Respect for potential and enrolled subjects. In addition to the 7 principles, viii) Study quality and transparency were also incorporated. Among major changes in the new guideline, obligation of study monitoring for invasive/interventional studies seems to be crucial for many clinical investigators. In this educational lecture, how to implement study monitoring will be discussed in detail. The difference of central monitoring and site visit monitoring are explained and how to use these two methods properly will be discussed. Typical ways of study monitoring depends on study characteristics such as the number of planned sample size, the number of participating institutions, required data quality. In accordance with these characteristics, appropriate way of study monitoring should be selected in each trial and described in the study protocol. Other major changes in the new ethical guideline will also be presented in the lecture, which includes: i) Conservation of study materials, ii) Conflict of interests, iii) IRB review for observational studies.

Fair subject selection in clinical research: formal equality of opportunity

In this paper, I explore the ethics of subject selection in the context of biomedical research. I reject a key principle of what I shall refer to as the standard...

Ethical Issues of Fair Subject Selection in the Research

Ethics and ethical principles extend to all spheres of human activity. They apply to our dealings with each other, with animals and the environment. They should govern our interactions not only in conducting research but also in commerce, employment and politics. Ethics serve to identify good, desirable or acceptable conduct and provide reasons for those conclusions. Fair subject selection is the first and foremost concern which must be ensured before initiating a research project. Which subjects may enroll in the research is determined by the study’s inclusion or exclusion criteria. One of the important aspects of fair subject selection is to have an oversight system through International Review Board (IRB) to review to conduct the research and to have approval whether subject selection is fair or not.

Editorial Vol.6(3)

Editorial Vol.6(3)

Clinical research: Should patients pay to play?

Permitting patients to pay for participation in clinical research threatens the principles of social value and fair subject selection as well as robust clinical trial design.

Ethics of genetic and biomarker test disclosures in neurodegenerative disease prevention trials.

Prevention trials for neurodegenerative diseases use genetic or other risk marker tests to select participants but there is concern that this could involve coercive disclosure of unwanted information. This has led some trials to use blinded enrollment (participants are tested but not told of their risk marker status). We examined the ethics of blinded vs transparent enrollment using well-established criteria for assessing the ethics of clinical research. Normative analysis applying 4 key ethical criteria-favorable risk-benefit ratio, informed consent, fair subject selection, and scientific validity-to blinded vs transparent enrollment, using current evidence and state of Alzheimer disease (AD) and other prevention trials. Current evidence on the psychosocial impact of risk marker disclosure and considerations of scientific benefit do not support an obligation to use blinded enrollment in prevention trials. Nor does transparent enrollment coerce or involve undue influence of potential participants. Transparent enrollment does not unfairly exploit vulnerable participants or limit generalizability of scientific findings of prevention trials. However, if the preferences of a community of potential participants would affect the rigor or feasibility of a prevention trial using transparent enrollment, then investigators are required by considerations of scientific validity to use blinded enrollment. Considerations of risks and benefits, informed consent, and fair subject selection do not require the use of blinded enrollment for AD prevention trials. Blinded enrollment in AD prevention trials may sometimes be necessary because of the need for scientific validity, not because it prevents coercion or undue influence.

Fair Subject Selection and HIV Vaccine Efficacy Trials: Canada's Global and Domestic Responsibilities

Fair Subject Selection and HIV Vaccine Efficacy Trials: Canada's Global and Domestic Responsibilities

Researchers’ perceptions of ethical challenges in cluster randomized trials: a qualitative analysis

BackgroundCluster randomized trials (CRTs) pose ethical challenges for investigators and ethics committees. This study describes the views and experiences of CRT researchers with respect to: (1) ethical challenges in CRTs; (2) the ethics review process for CRTs; and (3) the need for comprehensive ethics guidelines for CRTs.MethodsDescriptive qualitative analysis of interviews conducted with a purposive sample of 20 experienced CRT researchers.ResultsInformants expressed concern over the potential for bias that may result from requirements to obtain informed consent from research participants in CRTs. Informants suggested that the need for informed consent ought to be related to the type of intervention under study in a CRT. Informants rarely expressed concern regarding risks to research participants in CRTs, other than risks to privacy. Important issues identified in the research ethics literature, including fair subject selection and other justice issues, were not mentioned by informants. The ethics review process has had positive and negative impacts on CRT conduct. Informants stated that variability in ethics review between jurisdictions, and increasingly stringent ethics review in recent years, have hampered their ability to conduct CRTs. Many informants said that comprehensive ethics guidelines for CRTs would be helpful to researchers and research ethics committees.ConclusionsInformants identified key ethical challenges in the conduct of CRTs, specifically relating to identifying subjects, seeking informed consent, and the use of gatekeepers. These data have since been used to identify topics for in-depth ethical analysis and to guide the development of comprehensive ethics guidelines for CRTs.

Requirements for ethical justification of clinical trials

Conduction of the clinical trials on human subjects in order to gain data about efficiency and safety of the new drugs, medical devices and behavioral interventions is the essential part of the process of improvement in medical science. Yet, there are many potential risks of mistreat or abuse of the subject's legal rights and safety once they are involved in these trials. Determinations of generally accepted demands of ethical justification for clinical trials provide decrease of risks for subjects that undergo the clinical trials. After analyzing the content of the international and regional declarations, ethical guidelines and local legal regulations, author finds that basic ethical requirements for conduction of the clinical trials are: scientific and social values and scientific validity, risk benefit ratio, fair subject selection, voluntary informed consent, respect of the subject's personal rights and independent ethical comity review. In this work, author explains the purpose of these demands, determines their correlation and conclude that all of them stand in mutual connection and interrelation. Only cumulative fulfillment of all of the named requirements allows ethically acceptable approach to conduction of clinical trials with avoiding the exploitation and providing the fair and dissent environment for subjects with full respect to their legal rights and safety.

Nine key functions for a human subjects protection program for community-engaged research: points to consider.

The ethical conduct of Community-Engaged Research (CEnR), of which the Community-Based Participatory Research (CBPR) model is the partnership model most widely discussed in the CEnR literature and is the primary model we draw upon in this discussion, requires an integrated and comprehensive human subjects protection (HSP) program that addresses the additional concerns salient to CEnR where members of a community are both research partners and participants. As delineated in the federal regulations, the backbone of a HSP program is the fulfillment of nine functions: (1) minimize risks; (2) reasonable benefit-risk ratio; (3) fair subject selection; (4) adequate monitoring; (5) informed consent; (6) privacy and confidentiality; (7) conflicts of interest; (8) address vulnerabilities; and (9) HSP training. The federal regulations, however, do not consider the risks and harms that may occur to groups, and these risks have not traditionally been included in the benefit: risk analysis nor have they been incorporated into an HSP framework. We explore additional HSP issues raised by CEnR within these nine ethical functions. Various entities exist that can provide HSP---the investigator, the Institutional Review Board, the Conflict of Interest Committee, the Research Ethics Consultation program, the Research Subject Advocacy program, the Data and Safety Monitoring Plan, and the Community Advisory Board. Protection is best achieved if these entities are coordinated to ensure that no gaps exist, to minimize unnecessary redundancy, and to provide checks and balances between the different entities of HSP and the nine functions that they must realize. The document is structured to provide a "points-to-consider" roadmap for HSP entities to help them adequately address the nine key functions necessary to provide adequate protection of individuals and communities in CEnR.