AI technologies may be used to facilitate certain aspects of clinical trials, or AI may be the intervention under investigation in a clinical trial or an observational study. Both applications raise questions about data privacy, the risks of non-representative and/or biased data, and the appropriate oversight mechanisms for AI in clinical research.
Decentralized clinical trials (DCTs) are clinical trials that are executed in part or in whole through remote modalities, such as telemedicine, healthcare providers who travel to participants’ homes, smart phone applications, and mobile health wearables, inter alia. Bioethics Collaborative attendees will discuss questions of justice and access, privacy, oversight for research participant safety, and the changing roles and responsibilities of various stakeholders in the research process, among other ethical challenges raised by DCTs.
Despite the potential benefits of community engagement (CE), the rigor, quality, and impact of CE are difficult to assess, in part due to the lack of a standardized understanding of what is meant by CE. Relatedly, it can be challenging to define ‘community’ in the abstract, and any decision about how to specify the relevant community will be ethically and politically significant. Other ethical challenges are connected to practical issues, such as identifying individuals who can speak on behalf of a community and/or marginalized populations within a community; engaging individuals without taxing their time or services too much; and how to ensure that there is sufficient reciprocity to the interactions. Finally, it is often difficult for sponsors, sites, and investigators and their study teams to know whether they have achieved representativeness, that is, whether they have heard from an adequate range of perspectives in a community.
Limited English proficiency (LEP) refers to a limited ability to read, speak, write, and/or understand English. The exclusion of individuals with LEP from research is a significant issue, and this exclusion raises issues of justice. Strategies to accommodate individuals with LEP in research must include consideration of the principles of autonomy and beneficence/non-maleficence; safeguards may be added to ensure that the consent and participation of individuals with LEP is informed and voluntary, and furthermore, that the safety and well-being of individuals with LEP can be maintained throughout their research participation. These ethical considerations must be weighed against the expense and delay of translation and interpreter services.
Institutional Review Boards (IRBs) are responsible for protecting research participants by reviewing the study at initial and periodic review and ensuring that risks are minimized and appropriately balanced with benefits, and that key features of research are adequately disclosed to participants. Data monitoring committees (DMCs) play a role in protecting participant safety, ensuring the integrity and credibility of a trial, identifying beneficial treatments early, and advising termination of a trial if a treatment is or is likely to be ineffective. Although IRBs and DMCs share the goal of protecting research participants, the extent to which IRB and DMC responsibilities overlap or diverge is not clear and is often difficult to navigate in practice. Further complicating the division of labor is the fact that IRBs and DMCs rarely communicate directly.
Human challenge studies are a type of research study in which participants are intentionally exposed to a pathogen. These study designs have a long and complicated history, figuring in notorious cases of research abuse (Willowbrook, Guatemala STI experiments) but also as important components in treatment advances for conditions that tend to disproportionately impact the world’s worst-off, such as dengue and malaria. The potential for human challenge studies to be leveraged ethically in relation to Sars-CoV-2 has been a matter of recent and significant debate in the bioethics community.
Governments, companies, academic research institutions, and the public are increasingly aware of the value of data, prompting a reevaluation of who “owns,” controls, and benefits from the use of an individual’s data. Discussion at the Bioethics Collaborative focused on models of data ownership and stewardship in research. The meeting scope included data collected during clinical research and health data from the medical record that are used for research.
The roles of sex, gender, and sexual orientation in clinical research are important but underexplored. Discussion at the Bioethics Collaborative focused on two types of ethical issues related to sex, gender, and sexual orientation in clinical research. First, while sexual orientation and gender identity (SOGI) are social constructs, disease risk, manifestation, and/or response to treatment may vary by SOGI characteristics.
It is important to understand that any variation in disease risk, manifestation, or response, if it exists, is likely related to other underlying differences (e.g., hormonal status). Nevertheless, collecting and analyzing data on sex, gender, and sexual orientation may point to differences that need to be understood biologically to provide safe and effective interventions across diverse populations. Second, research should be respectful and inclusive of individuals of diverse sexes, genders, and sexual orientations. The principles of respect for persons and justice must be considered in addition to that of biologic relevance.
In November 2017, the MRCT Center published the Post-Trial Responsibilities: Continued Access to Investigational Medicines Guidance Document and Toolkit. This framework outlined a case-based, principled, stakeholder approach to evaluate and guide the ethical responsibilities related to providing continued access to an investigational medicine at the conclusion of a patient’s participation in a clinical trial.
Over the past 5 years, sponsors and investigators have utilized the MRCT Center guidance to create their own internal PTR policies. While the ethical principles and main consensus points remain valid, the application of the ethical principles and implementation of consensus points continue to challenge clinical research stakeholders and study participants. It is therefore timely to revisit and update the framework. This meeting served as a launch for revisiting the MRCT Center’s 2017 Guidance Document. Starting in January 2023, the Center will be convening a monthly task force to (1) define the current issues associated with continued access to investigational drugs and maintenance of implantable devices after trial completion and (2) identify practical and actionable resources and tools needed by stakeholders.
We live in a destabilizing world, where natural disasters, wars, pandemics, and other disruptive events are becoming more common. In clinical research, such disruption is detrimental to research participants and to the advances in scientific knowledge that will benefit future patients. Emergency responses, however, can be fragmented and inefficient. The COVID-19 pandemic has impressed this point on the research community, raising awareness of the need to plan ahead and adapt in response to disaster. To date, most of the attention has focused on actual responses to the pandemic – primarily setting up new, pandemic-focused trials, or calling for changes to clinical trial infrastructure in anticipation of the next pandemic. However, other types of emergencies are often left out of these discussions.
At this meeting of the MRCT Center Bioethics Collaborative, we hope to explore sponsors’ and investigators’ ethical obligations to plan for emergencies in advance. What obligations do they have to participants? How much preparation is necessary? How much is realistic? What obligations do research teams on the ground in disruptive and potentially dangerous situations have to research participants and to maintaining research protocols? Answering these questions and more will allow the clinical research community to develop the guidelines and infrastructure necessary to prepare for future emergency situations.
