key: cord-1006623-tv270vxh
authors: Lapid, Maria I.; Meagher, Karen M.; Giunta, Hannah C.; Clarke, Bart L.; Ouellette, Yves; Armbrust, Tamyra L.; Sharp, Richard R.; Wright, R. Scott
title: Ethical Challenges in COVID-19 Biospecimen Research: Perspectives From Institutional Review Board Members and Bioethicists a
date: 2020-10-23
journal: Mayo Clin Proc
DOI: 10.1016/j.mayocp.2020.10.021
sha: eff8136110013fb02ebe7dfcfe892686d0fdf88b
doc_id: 1006623
cord_uid: tv270vxh

Biospecimen research is a prominent investigative strategy that aims to provide novel insights into coronavirus disease 2019 (COVID-19), inform clinical trials, and develop effective, life-saving treatments. However, COVID-19 biospecimen research raises accompanying ethical concerns and practical challenges for investigators and participants. In this special article, we discuss the ethical issues that are associated with autonomy, beneficence, and justice in COVID-19 biospecimen research and describe strategies to manage the practical challenges, with an emphasis on protecting the rights and welfare of human research participants during a pandemic response. Appropriate institutional review board oversight and bioethics guidance for COVID-19 biospecimen research must maintain their focus on protecting the rights and welfare of research participants, despite the urgent need for more knowledge about the virus and the threat it poses to communities and nations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the newly identified virus that causes coronavirus disease 2019 (COVID-19). As of September 28, 2020, SARS-CoV-2 has infected more than 33.2 million individuals worldwide and has been associated with 999,298 deaths. 1 It is imperative to find an intervention that successfully prevents or mitigates morbidity and mortality, especially to avoid overwhelming of critical healthcare infrastructure. Although clinical trials are ongoing to investigate therapeutic options and preventive strategies for COVID-19, biospecimen research has become a prominent investigative strategy to further understand the disease, improve testing, and inform clinical trials that are assessing treatment and prevention strategies, including a vaccine.

Biospecimen research encompasses the practices of collecting, storing, and utilizing biological specimens (eg, tissue, blood, urine, body fluids) and clinical data for research purposes. Biospecimen research is essential in the COVID-19 era because these studies can help provide novel insights into viral infectivity, generation of and duration of immune response, and effect of treatments on viral load, thereby providing a deeper understanding of the disease for the benefit of public health. In contrast to clinical trials, one advantage of such research is minimal risk; after collection it can proceed without imposing any additional risk of SARS-CoV-2 exposure on donors.

Although biospecimen research may contribute to discoveries which ultimately can lead to life-saving results, pandemic biospecimen research is associated with some important and unique ethical issues. Ongoing discourse in the biorepository and biospecimen literature captures a variety of ethical and regulatory concerns distinct to pandemic biospecimen research including: donor vulnerability at the time of collection, potential disruption of already overwhelmed clinical institutions, laboratory biosafety, the need for large and harmonized data specimen collection and data sharing, and the J o u r n a l P r e -p r o o f sustainability of utilization once the pandemic subsides. [2] [3] [4] [5] In this article, we emphasize how ethical and practical challenges of COVID-19 biospecimen research appear from the perspective of those involved in human subjects research protection, and consider strategies to manage these challenges for those involved in biorepository oversight.

The 1978 Belmont Report established the foundation for research oversight, and articulate three ethical principles. These provide a default theoretical framework that Institutional Review Board (IRB) professionals and members often turn to when dealing with novel questions not addressed more directly by regulations. These principles include:

• Respect for Persons: "Respect for persons incorporates at least two ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection." • Justice: This principle is most often implemented in relation to subject selection: "the selection of research subjects needs to be scrutinized in order to determine whether some classes (e.g., welfare patients, particular racial and ethnic minorities, or persons confined to institutions) are being systematically selected simply because of their easy availability, their compromised position, or their manipulability, rather than for reasons directly related to the problem being studied."

The basic ethical principle of respect for persons, otherwise known as respect for an individual's autonomy, is to ensure that individuals are truly informed about their research participation. This principle is divided into two moral requirements -(1) the J o u r n a l P r e -p r o o f diminished autonomy. [6] [7] [8] Thus, autonomy refers to the right of a person to decide freely and independently whether they wish to participate in research, and this decision is informed by the accurate and relevant information that is provided to them.

Different models of informed consent in biospecimen research have been proposed, with various supporting and opposing arguments. These models range from broad consent to study-specific (traditional) consent to hybrid models. 9 The adequacy of broad consent authorizations in biospecimen research is intensely debated because it involves giving consent to the future use of samples, uses that are unknown at the time of the initial consent. In addition, anonymous or deidentified biospecimens can be used for research, and although this practice is common (and established long before the current novel coronavirus pandemic), it was among the most debated topics during the recent revisions to human subjects research protections (the Common Rule). 10 In the revised Common Rule, "broad consent" is a new type of regulatory consent that permits collection, storage, and secondary use of data for future unspecified research. The National Institutes of Health provides guidance on consent for future research use and broad sharing of genomic research data. 11 However, it is not mandatory, and the significant changes in systems and processes that are needed in order to use broad consent have presented implementation barriers to institutions. Moreover, available data on patient opinions are mixed because biospecimen contributors have expressed support for various consent models and positions on using deidentified clinical biospecimens for research. [12] [13] [14] Concerns about several aspects of biospecimen research were already being discussed because of events that occurred before the current pandemic. Substantial time is required to review and discuss the regulatory requirements, the bioethical principles that must be met, and the relative merit of the impact of the discovery as a trade-off for reduced autonomy. We recommend that IRBs work closely with research ethics consultation services to ensure preservation of autonomy and respect for persons as guiding and overarching principles, and IRBs must remain flexible as they face new and emerging situations that may challenge these principles in the course of scientific innovation.

Beneficence is an ethical principle in research that requires protection of research participants from harm and exploitation, as well as maximizing possible benefits from participating in research. 8 medical record review, it may be designated as minimal risk research. However, if collection of biospecimens is established without proper disclosure or consent, biospecimen research may not be as low risk as it initially appears. It is important to note that autonomy is a compelling but not overriding principle. Informed consent (or the lack thereof) is only one layer of protection, and autonomy alone can never provide sufficient protection for potential participants. 35 There are risks which accompany biospecimen research and it is important to focus on them briefly.

Violation of participant privacy and breach of confidentiality are major risks in biospecimen research. Health records are private and patients expect their confidentiality will be maintained. 36 

Specialists in human subjects protections, such as IRB members, should work collaboratively with bioethicists and investigators to ensure that the principles of respect for persons, beneficence and justice are met prior to research approval. Formal institutional policies and study-specific approaches must strive to balance the need to conduct biomedical research with the need to preserve the rights and autonomy of research participants. These strategies should include consideration of creative methods for discussing study involvement and obtaining informed consent from participants or their LARs in a manner that preserves patient autonomy, honors respect for persons, and advances our understanding of this dangerous new virus while minimizing risks to participants. In the extreme context of a pandemic response, situations may arise in which prospective participant consent is waived until the public health crisis subsides and J o u r n a l P r e -p r o o f consent authorizations are retroactively sought (ie, after biospecimen collection).

However, research use of such biospecimens should not occur until patient consent (or LAR authorization) is documented.

When creating institutional guidelines, bioethicists and IRBs must also consider the health risks to staff from obtaining in-person written consent when participants have a highly contagious and potentially fatal illness. Bioethicists and IRBs must also consider how to weigh empirical evidence about public attitudes. For example, some researchers involved in pandemic planning have solicited public opinion on how research could be conducted during pandemics, including assessing the public's willingness to accept simplified study enrollment or delayed consent for biospecimen research. 45 Although such findings are valuable when shaping IRB policy, public attitudes about hypothetical issues can diverge substantially from real-life preferences, especially when individuals are influenced by their illness experience. 46, 47 Conclusion Ethical concerns about autonomy, beneficence, and justice are evident in COVID-19 biospecimen research. Appropriate IRB oversight and bioethics guidance must center on protecting the rights and welfare of research participants, despite the urgent need for more knowledge about the virus and its impact. IRBs must continue their essential role in protecting human research participants, especially those who are now more vulnerable because of the impact of COVID-19−related disease and the social isolation necessary for its management. In serving this role, IRBs must also be flexible with regard to the specific policies that they adopt for the purpose of protecting human research participants so that scientific innovation and discovery can proceed and guide future care. IRB decisions should ensure that COVID-19 biospecimen research is J o u r n a l P r e -p r o o f

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