By Aaliyah Eaves
Given the recent FDA guidance for investigational studies using plasma from recovered COVID-19 patients (issued September 2, 2020), some healthcare networks are considering asking recovered patients to donate their plasma. Legal and ethical concerns have been raised about the appropriateness of asking patients to take on additional risk when the proposed treatment has uncertain benefits. Amid muddled politician messaging about what works against COVID-19, some urge a cautious approach. They worry official institutional promotion of experimental treatments may later be disproven and seriously undermine public trust in proven interventions, such as a vaccine. Ethicists worry about the possibility of therapeutic misconception or biases that impact outcomes given the crises conditions that justify emergency authorization for the use of unproven therapies.
These are essential legal and ethical questions to consider before implementing a policy for COVID-19 convalescent plasma. There is frequent conflation in recent discussions between donations of plasma to be used under an FDA Investigational New Drug (IND) Application and donations to be used under the Emergency Use Authorization (EUA) for clinical care. This lack of clarity between the two approaches should be of utmost concern to healthcare organizations.
Investigational New Drug
How hospitals initiate conversations with potential donors and research subjects is often guided by the desire for regulatory compliance. Studies conducted under an IND must comply with U.S. law and regulations, including good clinical practice (GCP). FDA also publishes guidance documents that pertain to clinical studies in general, and investigational COVID-19 convalescent plasma in particular.
Under the doctrine of clinical equipoise in investigational studies, it is common to ask current patients to take on a risk that has uncertain direct benefits for others. We do that every time we ask patients to become research participants or seek blood and tissue donors for biobanks. Prior to the pandemic, individuals donated plasma for future treatment and research purposes, so in that sense, this is not a novel issue. What is unique to the current public health emergency is how rapidly our understanding of this disease is evolving. Approaching current patients about plasma donations or study participation can be ethical fraught under emergency conditions. There are a few ways hospitals can reduce this real or perceived ethical ambiguity.
Donors must contact registered or licensed blood establishments collecting authorized COVID-19 convalescent plasma and make arrangements to donate plasma. Directing potential donors to entities that are independent from the healthcare institution allows the establishments collecting plasma to act as intermediaries. This built-in “cooling-off period” may mitigate the appearance of coercion or undue influence by the hospital.
The possibility of therapeutic misconception and the challenging circumstances around obtaining voluntary informed consent during a pandemic are commensurate with other FDA approved clinical studies conducted under exigent circumstances in a clinical setting. Hospitals have a duty to create the conditions for autonomous decision-making. Donors and research participants must understand that safety and efficacy of the treatment is being studied. By providing clear information, in circumstances that mitigate vulnerability or exploitation to the greatest extent practicable, patients are put in the driver’s seat to weigh the risks and benefits based on their own values. The presumption that potential donors and research subjects inherently lack the capacity to act rationally and altruistically is paternalistic at best.
Emergency Use Authorization
When COVID-19 convalescent plasma is used under the EUA it is a part of the practice of medicine during a temporary emergency. Healthcare providers that are considering presenting this treatment option to their patients should carefully read the FDA Fact Sheet for Health Care Providers. The treating provider applies his or her professional judgment to recommend treatment options based on the patient’s goals for care and the patient gives consent based on the best available information related to the risks and benefits of the options. Addressing unreasonable patient expectations about convalescent plasma is prudent and also aligned with FDA requirements for use under the EUA. Descriptive advertising or promotional material that represents or suggests it has been proven to be safe or effective is strictly prohibited.
The patient/caregiver must be given a copy of the FDA Fact Sheet for Patients and Parents/Caregivers. Sufficient time should be allocated to the review of the fact sheet and informed consent documents. Failure to adequately plan for this type of conversation is one of the leading sources of poor communication between healthcare providers and patients/caregivers. The patient, caregiver and involved family should have a meaningful opportunity to ask questions. Applicable state regulations for the practice of medicine will determine who is responsible for obtaining the patient’s written or verbal consent for treatment and who is legally authorized to provide consent when the patient lacks the capacity to make medical decisions.
There is growing alarm in the scientific community that overemployment of the EUA option may undermine current efforts to ascertain the scientific validity of COVID-19 treatments and cures. To ameliorate this risk, it is recommended that the first consideration be whether or not the patient is eligible for inclusion in an IND or expanded access protocol. If those regulatory pathways are an option, the treating physician is usually not the person who should seek to obtain informed consent for study participation to avoid actual or potential undue influence over the patient.
If inclusion in the IND/expanded access protocol is not an option, or the patient declines participation in the study, the treating physician can then determine if the patient is a candidate for treatment under the EUA. Refusal to participate in a study, or inability to meet the inclusion criteria of a study that is actively recruiting subjects should never be a reason to exclude a patient from further consideration under the EUA.
Transparency and Due Process
Community consultations can position healthcare organization to address inequalities and biases that contribute to poor health outcomes from COVID-19 that disproportionately impact Black and Latino communities. Structured community dialogues give healthcare leaders and researchers an opportunity to dispel false assumptions, understand pertinent dynamics and build trust at every stage of developing and implementing temporary emergency standards of care and policies for the investigational use of COVID-19 treatments. Policies should have efficient and effective due process mechanisms to ensure determinations are free from overt or implicit bias that may otherwise occur when decision-making is exclusively within the purview of an individual healthcare provider overburdened with crisis conditions and resource limitations.
-Aaliyah Eaves is an FDA attorney and bioethicist at Dinsmore & Shohl LLP.