Ethical decision-making is inherent to the research ethics committee deliberation process. While ethical codes, regulations, and research standards are indispensable in guiding this process,...

Randomized controlled trial trial designs exist on an explanatory-pragmatic spectrum, depending on the degree to which a study aims to address a question of efficacy or effectiveness. As conceptualized by Schwartz and Lellouch in 1967, an explanatory approach to trial design emphasizes hypothesis testing about the mechanisms of action of treatments under ideal conditions, whereas a pragmatic approach emphasizes testing effectiveness of two or more available treatments in real-world conditions. Interest in, and the number of, pragmatic trials has grown substantially (...) in recent years, with increased recognition by funders and stakeholders worldwide of the need for credible evidence to inform clinical decision-making. This increase has been accompanied by the onset of learning healthcare systems, as well as an increasing focus on patient-oriented research. However, pragmatic trials have ethical challenges that have not yet been identified or adequately characterized. The present study aims to explore the views of key stakeholders with respect to ethical issues raised by the design and conduct of pragmatic trials. It is embedded within a large, four-year project that seeks to develop guidance for the ethical design and conduct of pragmatic trials. As a first step, this study will address important gaps in the current empirical literature with respect to identifying a comprehensive range of ethical issues arising from the design and conduct of pragmatic trials. By opening up a broad range of topics for consideration within our parallel ethical analysis, we will extend the current debate, which has largely emphasized issues of consent, to the range of ethical considerations that may flow from specific design choices. Semi-structured interviews with key stakeholders, across multiple jurisdictions, identified based on their known experience and/or expertise with pragmatic trials. We expect that the study outputs will be of interest to a wide range of knowledge users including trialists, ethicists, research ethics committees, journal editors, regulators, healthcare policymakers, research funders and patient groups. All publications will adhere to the Tri-Agency Open Access Policy on Publications. (shrink)

We examine the ethical, social, and regulatory barriers that may hinder research on therapeutic potential of certain controversial controlled substances like marijuana, heroin, or ketamine. Hazards for individuals and society and potential adverse effects on communities may be good reasons for limiting access and justify careful monitoring of these substances. Overly strict regulations, fear of legal consequences, stigma associated with abuse and populations using illicit drugs, and lack of funding may, however, limit research on their considerable therapeutic potential. We review (...) the surprisingly sparse literature and address the particular ethical concerns pertinent to research with illicit and addictive substances, such as undue inducement, informed consent, therapeutic misconception, and risk to participants, researchers, and institutions. We consider the perspectives of key research stakeholders and explore whether they may be infected with bias. We conclude by proposing an empirical research agenda to provide an evidentiary basis for ethical reasoning. (shrink)

BackgroundInstitutional review boards (IRBs) have been criticised for delays in approvals for research proposals due to inadequate or inexperienced IRB staff. Artificial intelligence (AI), particularly large language models (LLMs), has significant potential to assist IRB members in a prompt and efficient reviewing process.MethodsFour LLMs were evaluated on whether they could identify potential ethical issues in seven validated case studies. The LLMs were prompted with queries related to the proposed eligibility criteria of the study participants, vulnerability issues, information to be disclosed (...) in the informed consent document (ICD), risk–benefit assessment and justification of the use of a placebo. Another query was issued to the LLMs to generate ICDs for these case scenarios.ResultsAll four LLMs were able to provide answers to the queries related to all seven cases. In general, the responses were homogeneous with respect to most elements. LLMs performed suboptimally in identifying the suitability of the placebo arm, risk mitigation strategies and potential risks to study participants in certain case studies with a single prompt. However, multiple prompts led to better outputs in all of these domains. Each of the LLMs included all of the fundamental elements of the ICD for all case scenarios. Use of jargon, understatement of benefits and failure to state potential risks were the key observations in the AI-generated ICD.ConclusionIt is likely that LLMs can enhance the identification of potential ethical issues in clinical research, and they can be used as an adjunct tool to prescreen research proposals and enhance the efficiency of an IRB. (shrink)

Background The review of human participant research by Research Ethics Committees or Institutional Review Boards is a complex multi-faceted process that cannot be reduced to an algorithm. However, this does not give RECs/ IRBs permission to be inconsistent in their specific requirements to researchers or in their final opinions. In England the Health Research Authority coordinates 67 committees, and has adopted a consistency improvement plan including a process called “Shared Ethical Debate” where multiple committees review the same project. Committee reviews (...) are compared for consistency by analysing the resulting minutes. Methods We present a description of the ShED process. We report an analysis of minutes created by research ethics committees participating in two ShED exercises, and compare them to minutes produced in a published “mystery shopper” exercise. We propose a consistency score by defining top themes for each exercise, and calculating the ratio between top themes and total themes identified by each committee for each ShED exercise. Results Our analysis highlights qualitative differences between the ShED 19, ShED 20 and “mystery shopper” exercises. The quantitative measure of consistency showed only one committee across the three exercises with more than half its total themes as top themes. The average consistency scores for the three exercises were 0.23, 0.35 and 0.32. There is a statistically significant difference between the ShED 19 exercise, and the ShED 20 and mystery shopper exercises. Conclusions ShED exercises are effective in identifying inconsistency between ethics committees and we describe a scoring method that could be used to quantify this. However, whilst a level of inconsistency is probably inevitable in research ethics committee reviews, studies must move beyond the ShED methodology to understand why inconsistency occurs, and what an acceptable level of inconsistency might be. (shrink)

Introduction The bioethics literature reflects significant interest in and concern with the use of genetic and genomic information in various settings. Because psychiatric treatment and research raises unique ethical, legal, and social issues, we conducted a scoping review of the biomedical, bioethics, and psychology literature regarding the application of genetic and genomic tools to psychiatric disorders (as listed in the DSM-5) and two associated behaviors or symptoms to provide a more detailed overview of the state of the field. Objectives The (...) primary objective was to examine the available bioethics, biomedical, and psychology literature on applying genetic and genomic tools to psychiatric disorders (other than neurodevelopmental disorders) and two behaviors or symptoms sometimes associated with them (aggression or violence and suicidality) to identify the disorders to which these tools have been applied, the contexts in or purposes for which they have been applied, the ethical, legal, or social concerns associated with those uses, and proposed recommendations for mitigating those concerns. Methods We used Arksey and O’Malley’s scoping review framework: (1) identify the research question; (2) identify relevant studies; (3) select studies; (4) chart the data; and (5) collate, summarize, and report results (2005). We relied on Levac et al. to inform our application of the framework (2010). The PRISMA extension for scoping reviews checklist informed our reporting (2018). We searched three electronic databases MEDLINE (PubMed), Embase, and PsycInfo (EbscoHost) for peer-reviewed journal articles in English to identify relevant literature. One author screened the initial results and additional screening was done in consultation with other authors. A data extraction form using DSM-5 diagnostic categories (excluding neurodevelopmental disorders) was developed and two authors independently each reviewed approximately half of the articles. Inter-rater reliability was ensured by double-coding approximately 10% of the papers. An additional author independently coded 10% of the articles to audit the data. Results In 365 coded publications, we identified 15 DSM-5 diagnostic categories in addition to the two pre-selected behaviors or symptoms (aggression or violence and suicidality) to which genetic or genomic tools have been applied. We identified 11 settings in or purposes for which these tools were applied. Twenty-two types of ethical, legal, or social concerns associated with the application of genetic or genomic tools to these disorders or behaviors/symptoms were identified along with 13 practices or policies that could mitigate these concerns. Conclusion Genetic and genomic tools have been applied to a wide range of psychiatric disorders. These raise a range of ethical, legal, and social concerns. Additional research is warranted to better understand the concerns and effective ways to address them. Advancing the literature to identify relevant ethical, legal, or social concerns and solutions to those problems likely requires greater attention to specific applications of genetic or genomic tools to particular psychiatric disorders and associated behaviors/symptoms as well as broad stakeholder engagement. (shrink)

Recent progress in synthetic biology has enabled the development of novel therapeutic opportunities for the treatment of human disease. In the near future, first-in-human trials will be indicated. FIH trials mark a key milestone in the translation of medical SynBio applications into clinical practice. Fostered by uncertainty of possible adverse events for trial participants, a variety of ethical concerns emerge with regards to SynBio FIH trials, including ‘risk’ minimization. These concerns are associated with any FIH trial, however, due to the (...) novelty of the approach, they become more pronounced for medical applications of emerging technologies like SynBio. To minimize potential harm for trial participants, scholars, guidelines, regulations and policy makers alike suggest using ‘risk assessment’ as evaluation tool for such trials. Conversely, in the context of emTech FIH trials, we believe it to be at least questionable to contextualize uncertainty of potential adverse events as ‘risk’ and apply traditional risk assessment methods. Hence, this issue needs to be discussed to enable alterations of the evaluation process before the translational phase of SynBio applications begins. In this paper, we will take the opportunity to start the debate and highlight how a misunderstanding of the concept of risk, and the possibilities and limitations of risk assessment, respectively, might impair decision-making by the relevant regulatory authorities and research ethics committees, and discuss possible solutions to tackle the issue. (shrink)