Essential Versus Nonessential: The Ethics of Conducting Non-COVID Research in a Population of Persons Living With Serious Illness During the COVID-19 Pandemic.

The COVID-19 pandemic has created disruptions and ethical tensions in palliative care research; however, ethical principles must continue to be applied for evaluating the safety of conducting research with seriously ill patient participants and nurse participants in an acute care setting. This randomized controlled trial is conducted in the acute care hospital and tests the effects of a narrative intervention versus usual care on the primary outcome of patients' perception of quality of communication with their nurses and the secondary outcome of biopsychosocial well-being. In accordance with local and institutional COVID-19 guidance, research activities were temporarily suspended in March 2020, and when allowed to resume, some aspects of the protocol were adapted to maximize safety for all stakeholders: patients/families, nurses, and the research team. This article (a) considers case perspectives of all stakeholders involved in a randomized controlled trial conducted in the acute care hospital setting during the COVID-19 pandemic, (b) describes the ethical dilemma and ethical principles in the context of the case, (c) discusses lessons learned while resuming clinical research activities, and (d) provides an ethical framework for the decision-making processes around vulnerability and safety in conducting research during a pandemic with persons living with serious illness.

The COVID-19 pandemic has created disruptions and ethical tensions in palliative care research; however, ethical principles must continue to be applied for evaluating the safety of conducting research with seriously ill patient participants and nurse participants in an acute care setting. In light of COVID-19, the duty for nursing research to ground itself in ethics has been imperative across many different ethical dilemmas. The dilemma presented here regards the safety of conducting research during a pandemic in an acute care setting specifically enrolling persons with serious illness, who have a higher risk of becoming severely ill from COVID-19.[1]

The pandemic surge in fall 2020[2] called into question the ethics of recruiting and enrolling seriously ill persons, compelling a palliative care research team to consider the “essential” nature of the study and examine the balance of risk and potential benefit. The research team's decision-making was facilitated through ongoing discussions about the study's ethical path and guided by the Belmont Report,[3] which contains the ethical guidelines for protecting human subjects in research. Although the system administration and the hospital permitted the study to continue, the team felt obligated to ask if it should see vulnerable, seriously ill persons for the purposes of the study[3-5] and utilized the ethical principles of the Belmont Report—respect for persons, beneficence, and justice—to answer this question.

This article (a) considers case perspectives of all stakeholders involved in a randomized controlled trial conducted in the acute care hospital setting during the COVID-19 pandemic, (b) describes the ethical dilemma and ethical principles in the context of the case, (c) discusses lessons learned while resuming clinical research activities, and (d) provides an ethical framework for the decision-making processes around vulnerability and safety in conducting research during a pandemic with persons living with serious illness.

COVID-19 INITIAL IMPACT

In response to the COVID-19 pandemic in March 2020, the leadership of University of Colorado Denver/Anschutz Medical Campus and University of Colorado Hospital temporarily suspended most clinical research activities, in order to prioritize COVID-19 research studies, ensure safety, and preserve clinical research resources. Specifically related to this study, 2 of the 3 units where recruitment had been taking place were temporarily converted to COVID-19 units beginning in March 2020. The institution created a priority group ranking to outline clinical research restrictions based on the critical nature of the research and its inherent risk (Table 1).[6]

TABLE 1

Priority Group Rankings for Resuming Research Activities

Group	Description
1	• Essential research that is critical to clinical care and safety of participants, including access to treatment or clinical research for COVID-19–positive patients and health care workers
2	• New enrollments and completing visits for active participants in therapeutic studies when no standard-of-care treatment is available • Open a new therapeutic study when no standard-of-care treatment is available • Complete visits for active participants in studies with prevention strategies to minimize disease progression • Complete visits for active participants in therapeutic or nontherapeutic studies that require on-campus processing but no participant contact
3	• New enrollments to therapeutic studies when standard of care is a viable option or when ≥2 standard-of-care treatments are being compared • New enrollments to studies with prevention strategies to minimize disease progression • Open a new therapeutic or nontherapeutic study that requires on-campus processing but no participant contact
4	• New enrollments to currently active, nontherapeutic protocols requiring minor research-only interventions • Complete visits for active participants to nontherapeutic protocols requiring complex research-only interventions • Open a new study with prevention strategies to minimize disease progression or a therapeutic study when standard-of-care treatment is available or >2 standard treatments are being compared
5	• Open a new nontherapeutic study requiring SOC and additional, complex research procedures and/or visits, or major or minor research-only interventions • New enrollments to active nontherapeutic protocols requiring complex research-only interventions

Abbreviation: SOC, standard of care.

These priority rankings guided the resumption of clinical research, which was based on the status of the pandemic, jurisdictional guidance, and personal protective equipment (PPE) availability. As a nontherapeutic protocol, the study described here was not a prioritized “essential” research protocol[6] and was granted permission to resume in the acute care setting in September 2020.

The study presented here is a randomized controlled trial to test the effects of a person-centered narrative intervention (PCNI) with seriously ill patient participants. The outcomes being tested in this trial are the patient participant's perception of quality of communication with their nurses and the patient participant's biopsychosocial well-being.[7,8] All patient participants complete a 65-item survey conducted at 3 time points. Patient participants randomized to the intervention group complete the PCNI—an audio-recorded, semistructured interview. They are asked open-ended questions about the impact of their illness on various aspects of life. The research team then creates a person-centered narrative written in the voice of the patient participant, the person living with the serious illness.[7,8] The patient participant is allowed to make changes, and the research team uploads the narrative to the electronic health record, subsequently alerting the bedside nurse that the narrative is in the chart and providing education on how to access it. Nurse participants are also recruited to provide feedback on their experience with the PCNI. For a more detailed description of the study, reference the previously published articles cited in this section.

Of note, the research team conducting this study includes all authors of this article, all of whom were part of the decision-making process described herein. The first and last authors are the research coordinator and principal investigator, respectively, and are the primary writers of this article. The third author is the study biostatistician, and the second author is a collaborator and mentor of the principal investigator. All authors contributed to ongoing discussions of maintaining integrity of the study intervention amid protocol adaptations and to the revising of this article at multiple writing stages.

CASE PERSPECTIVES

Patient/Family Considerations

Jerry is a 69-year-old person admitted to the hospital for an exacerbation of his heart failure. Because of the pandemic, he had not been allowed to have any outside visitors during his admission. He had been in the hospital for 1 week when a research coordinator approached him to enroll in the PCNI study. Although he was interested in having more interaction with others because of his social isolation, he had concerns of this “extra” person being in his hospital room and wondered if this interaction would increase his risk of getting COVID-19. After the research coordinator approached him, he spoke with his partner via phone, and she shared the same concern. She felt this would increase his COVID-19 risk and noted that she was restricted from visiting because of this precise risk. Her question was: “Why is an extra person being allowed in your room, if I cannot even come to visit you?”

Acute Care Nursing Considerations

Prior to the pandemic, this study was being conducted in person at the acute care hospital, and the research coordinator was a consistent presence on the units where patient and nurse participants were being enrolled. When the research institution put a temporary hold on recruitment in the acute care setting, the nursing staff wondered about the status of the study. Two of the 3 recruitment units were temporarily converted to COVID-19 units, and the research team kept in communication with the nurse managers and nursing staff via email throughout this time. From the nursing point of view, it seemed that during the first months of the pandemic surge, the concern for lack of PPE and the increasing numbers of admitted COVID-positive patients was a universal concern and aligned with the decision to cease study recruitment. As the health care system was able to acquire enough PPE, the research team was able to secure their own PPE, and the units had fewer COVID-positive patients, the nursing staff were hopeful the research team could continue; however, there were additional considerations for research ethics and permissions from the institution.

Research Team Considerations

In addition to thinking of their own safety, the research team considered several options for resuming study recruitment with heightened pandemic safety for the other stakeholders in mind. The most feasible was to adapt some aspects of the study for virtual conduct in order to minimize infection risks; however, this posed a number of potential issues. Adapting from in-person to virtual study conduct could impact study integrity. The research team questioned which study aspects could and should be adapted, whether these adaptations would be feasible for electronic delivery, and how these changes would affect the study's hypothesis testing (eg, intervention efficacy).

RESUMING CLINICAL RESEARCH DURING THE COVID-19 PANDEMIC

The research team was granted permission to resume clinical research activity in September 2020 and did so at that time. Aspects of the protocol were adapted in an effort to reduce exposure risks, yet new challenges arose.

Protocol Adaptations

In preparation to return to research recruitment, the research team adjusted the protocol with a focus on reducing exposure risk for seriously ill persons (potential and actual participants), acute care nurses, and themselves. These adjustments included adaptations to research procedures to minimize in-person activities by

utilizing an electronic consent form instead of paper consent forms and

completing data collection via email or phone for control group participants.

Based on discussions among the research team, including with the study biostatistician, it was decided that no adaptations would be made to the PCNI. As the PCNI utilizes a highly personal interview about topics that some persons find sensitive or emotional, the research team decided that continuing to complete this step in person was necessary for maintaining the intervention's fidelity and integrity of the efficacy statistical testing of outcomes once the study is completed.

Challenges

Although the study had been feasible prior to the pandemic,[7,8] upon reinitiating study conduct, the adapted protocols proved difficult to execute and not feasible. The primary challenges were the setting, the burden on participants, and communication. First, the schedule of treatment for seriously ill persons admitted in the acute care setting is unpredictable for many reasons, from care-team rounds to transport availability. Prior to the pandemic, the research coordinator could wait until the patient was unoccupied; postpandemic, waiting in the hospital was not feasible because of exposure risks. Second, virtually conducted study activities place more burden on the participants, who are also physically unwell: they must have access to technology (eg, iPad, laptop, or smartphone) and have the skill to navigate links and instructions. Otherwise, the research coordinator must orally administer the surveys via phone, which can fatigue participants. Third, communication challenges increased the time burden for the research team. Reaching each participant by phone typically took several attempts because of unpredictable schedules. In summary, the burden of completing study activities virtually was higher than it was when the research coordinator was physically present with participants to facilitate the research procedures.

Two results of these challenges were a decrease in enrollment and an increase in missing data. Prior to COVID-19, 23 participants were enrolled over an 18-week period: just over 1 participant per week. Missing data were rare, with 2 participants missing the final follow-up because of death or worsening disease. When the study resumed in September 2020, only 5 participants were enrolled over a 7-week period. Although it is difficult to draw conclusions from a cohort of 5 participants, one did not complete one follow-up assessment, and another did not complete either follow-up assessment. These missing data patterns compromise a standard of integrity and completeness. Virtual study conduct also affected nurse participant enrollment. Prior to COVID-19, if a potential nurse participant was busy, the research coordinator could wait; this was no longer feasible. In addition, nursing staff on the recruitment units exhibited signs of stress during COVID-19,[9,10] more often stating they were “too busy” to participate.

There are 2 potential impacts to the efficacy testing of the PCNI. First, the study's objectives include determining if the PCNI improves the participants' perception of their communication with their nurses and their biopsychosocial well-being. Regardless of their assigned group, the in-person interaction participants experienced potentially contributes to this benefit, but this was lessened with remote conduct. Second, multiple adaptations to PCNI research procedures could decrease the ability to test efficacy. Thus, to maintain the integrity of the statistical analysis plan for our pilot efficacy design of the PCNI, no changes were made to the in-person narrative interview, and the only virtual adaptations were an electronic consent form/process and phone/electronic survey completion.

ETHICAL DILEMMA

An ethical dilemma is a situation in which 2 moral principles conflict with one another,[11] and as noted above in the case perspectives, the research team faced such situations on various fronts. While resuming clinical research activity amid the COVID-19 surge in fall 2020,[2] the research team became acutely aware of further ethical concerns in the rapidly evolving pandemic landscape. In considering the appropriateness of conducting this research study in the current environment, many challenging questions arose:

What were the ethical obligations to each of the other stakeholders, to the profession of nursing, and to society?

What was the safest decision for everyone involved?

With the pandemic status ever changing, what guidance was available as they wrestled with the questions of if and how to continue study recruitment?

The research team was faced with an overarching ethical dilemma: Was it ethically sound to continue conducting research with seriously ill persons admitted to the acute care hospital setting during the COVID-19 pandemic? Throughout the COVID-19 novel pandemic, safety has been at the forefront, informed by public-health guidelines. In this vein, decisions about how to continue study conduct during the pandemic, the safety and perspectives of all stakeholders—patients/families, acute care nurses, and the research team—were considered.

ETHICAL IMPLICATIONS

Researchers have an ethical responsibility to conduct clinical research in alignment with the principles of the Belmont Report, which provides ethical guidance for clinical research conduct. Its principles are respect for persons, beneficence, and justice, and notable for nursing research in particular, these principles are similar to the ethical principles in the Code of Ethics for Nurses.[3,12] The research team grounded their discussions and decision-making in these documents, using these principles as a lens through which to consider the various ethical dilemmas presented in this unique circumstance.

Respect for Persons

Two ideas comprise the principle of respect for persons: individuals should be treated as autonomous, and those with diminished autonomy deserve protection.[3] With the COVID-19 surge, it became clear that the research team could introduce risk even by entering a patient's room for recruitment and by being another body on the unit along with the acute care nurses. Was the added risk ethical, given that recruitment was an event neither essential to the patient's clinical care or the nurses' job, nor one to which they had agreed?[3-5]

For the patient/family in this case, respect for persons, which includes autonomy and self-determination of choice to participate in research studies, should always be the priority, regardless of the status of the pandemic. Having this as the guiding principle, persons (patients and their families) need to have adequate knowledge of risks/burden of becoming a participant, ensure that all concerns are addressed through informed consent process, and have the right to decline to participate or withdraw at any time without fear of adverse consequences to their care.

In the above case perspective, the family member's concerns were valid based on the current visitation restrictions the health care system had implemented due to risks of exposure to COVID-19. In this instance, another person in the room increased exposure risk for the potential research participant (the patient), which contributed to the research team's ultimate decision to cease recruitment.

Beneficence Versus Maleficence

The conviction of beneficence goes beyond respect for person and protection, charging clinical researchers with ensuring human subjects' welfare, especially those persons with serious illness.[3-5] Beneficence has 2 actions that must be considered: “do not harm” and “maximize possible benefits and minimize possible harms,” whereas maleficence is the opposite of beneficence—“committing harm or evil.”

Prior to the pandemic, the institutional review board classified this study as a minimal-risk project and the potential risks are (a) emotional distress from discussing personal experiences and (b) fatigue from the time spent in the narrative interview. However, COVID-19 introduced the additional risk of virus exposure, which was unrelated to the research itself but became an inherent part of study conduct. In this new environment, it was unclear if the welfare of potential and actual study participants could be ensured.

In the above case perspective, the research team considered the need of the essentiality of continued recruitment when doing so could introduce harm (maleficence) to the research participants. This also contributed to the decision to discontinue recruitment until the risk to participants could be minimized, for example, until COVID-19 vaccinations were available for all stakeholders.

Justice

The tenet of justice asks, “who should receive the benefits of research and bear its burdens?”[3] Did adapting the protocol alter the study's balance of benefit and burden? Justice speaks to fairness of distribution, and there are numerous perspectives to determine this, including allocation of benefit according to equal share, individual need, or societal benefit. The research team needed to consider how “essential” the study was within the current pandemic environment and for persons with serious illness, as well as the overburdened acute care nurses. For example, should pandemic-focused research take precedence for societal benefit, focusing resources on the public-health crisis response? Alternately, would persons living with serious illness, regardless of the pandemic, still benefit from clinical research unrelated to the pandemic?

In the above case perspective, the research team did not want to place undue burden on the person living with serious illness or the acute care nurses who were already experiencing increased burdens of caring for the increasing numbers of hospitalized patients. The research team also recognized that clinical research resources were limited, and continued conduct of COVID-19 therapeutic trials should be prioritized.

LESSONS LEARNED

The Code of Ethics for Nurses and the Belmont Report have similar principles, one difference being that where the former states “patient,”[12] the latter states “research participant.”[3] Throughout the decision-making processes, the research team kept the safety and autonomy of the seriously ill patient admitted to the acute care hospital (the study's research participants) at the forefront, guided by the ethical principles of the Belmont Report and the Code of the Ethics for Nurses. Suspension and resumption of studies require careful consideration of benefit versus harm with regard to these participants. Based on the research team's experience in this case and the decision-making process described herein, this team proposes the following framework to guide the ethical decisions for conducting research with persons living with serious illness during a pandemic (Table 2).

TABLE 2

Framework for Ethical Decision-making in Clinical Research During COVID-19

Domain	Considerations	Recommendations
Participant characteristics	• What is the status and situation of potential participants when enrolling a study during a pandemic? • Are they considered vulnerable or of diminished autonomy? If so, what risk is the study introducing, and is the balance of maximizing benefit and minimizing harm being maintained?	• Keep potential benefits and harms to persons central in the decision-making process.
Status of the pandemic	• What is the current status of community spread, infection rate, and public-health recommendations?	• Frequently monitor current infection-control data and the applicable public-health guidelines of the locality and the health care system through the lens of exposure risk inherent in the research study under consideration.
Available resources	• Are resources currently being diverted to pandemic-focused protocols by necessity? Do key stakeholders have the capacity to engage in the protocol as needed? • Consider the safety of research personnel.	• Evaluate research infrastructure resources (ie, research administration, institutional review board).
Intervention complexity and possible impacts to study integrity	• Assess whether protocol adaptations are necessary to increase safety; consult with study-design experts, biostatisticians, and the study's data safety monitoring board to determine the outcomes of potential changes.	• Maintain the initial scientific design of the statistical analysis plan for integrity of the efficacy testing; other components, such as the informed consent model or outcome measure collection, could be adapted.
Document findings	• Having information about the timing of study procedures, reasons for missing data, and responses from potential participants can aid in analyzing data and in accounting for shifts in data completeness or recruitment success that may occur when conducting non–pandemic-focused research during a pandemic.	• Maintain a detailed record of observations during implementation of an adapted study protocol and process.

This framework outlines 5 domains relevant to determining whether and how to conduct such research and provides questions for research teams to consider within each. Practical recommendations are offered to aid research groups in arriving at the most ethically sound conclusion that is aligned with the principles set forth in the Belmont Report, which guides all clinical research conduct. Through this case, the research team learned that these principles provided a relevant, practical, and reliable foundation on which to base discussions about what next steps would be appropriate and ethical from the perspectives of the patients/families, acute care nurses, and the research team itself. It provided an approach to ensure that ethical and responsible conduct of research with persons living with serious illness is central in the decision-making process around “essential” and “nonessential” research in the middle of a pandemic, which is outlined and expanded upon through the presented framework. Above all, the research team found that benefits and burdens to all the key stakeholders must be considered collaboratively in order to maximize safety for all involved persons.

Unanswered Questions

Several considerations and questions remain equivocal. For example, which aspects of a study protocol can be feasibly and effectively adapted for virtual conduct while maintaining study integrity? This will depend on the particulars of the study protocol, setting, and participant population and should be thoroughly discussed with research team members who have expertise in various areas of research design, conduct, and analysis. In addition, as postulated in the “Justice” section, would persons with serious illness still benefit from such research regardless of the pandemic? This is difficult to determine, because while increased exposure to other persons increases COVID-19 exposure risk, it is also known that social isolation, more prevalent during the pandemic, is detrimental to health. This is a balance that research teams need to consider with regard to their specific participant population and study activities.

Future Considerations

This case reveals the complexities of ethical dilemmas that must be considered for research conducted in acute care hospitals, specifically with seriously ill persons and acute care nurses, in the event of a future pandemic. Based on this case experience, it is suggested that research teams consider including options for remote study conduct into their original study designs. Consulting biostatisticians and researchers who specialize in virtually conducted clinical research would allow feasible, effective options to be integrated into study protocols, resulting in a more seamless transition should the need arise. In addition, contingency planning for prioritization of study objectives and end points is encouraged. Examining which study activities or procedures are essential to the study's success is highly valuable. Are there exploratory end points that could be temporarily removed from the protocol in order to focus a team's limited time and resources on collecting the most imperative data? In the event of another long pandemic event, such prioritization could allow research teams to achieve the most relevant, useful data set possible.

Current Status

In November 2020, the research team decided to cease study recruitment in the face of the pandemic surge, as described above. Shortly after, the leadership of the University of Colorado Denver/Anschutz Medical Campus and University of Colorado Hospital paused clinical research activity for most priority-ranking groups once again because of the surge of hospitalizations due to COVID-19 (Table 1). When this occurred, the research team opted to keep study closed and shift funding for the research team from January 2021 through June 2021, until it was likely that research activities could continue uninterrupted with less safety risk to all involved after vaccination rollout. At the time of this writing, the research team has resumed study enrollment in July 2021.