Informed Consent by Any Other Name: Consent Processes for Emergency Use Authorization.

Abstract

The current coronavirus pandemic has necessitated the US Food and Drug Administration (FDA) issuance of Emergency Use Authorization (EUA) to expedite the development of diagnostics and the availability of convalescent plasma, monoclonal antibodies, vaccines, and antivirals as potentially lifesaving therapies. To date, 327 EUAs have been authorized by the FDA to diagnose or treat severe acute respiratory syndrome coronavirus 2.1 The availability of these essential products in a critical time frame reflects the diligent work of scientists and the successful functioning of the complex drug development systems even under the pandemic environment. The authority to use an EUA is established by the Federal Food, Drug, and Cosmetic Act, which allows for the special “use of drugs and products in public health emergencies to diagnose, treat, or prevent serious or life-threatening diseases or conditions when there are no adequate, approved, and available alternatives.”2 The FDA Guidance states, “Although informed consent as generally required under the FDA is not required for administration or use of an EUA product, Section 564 does provide EUA conditions to ensure that recipients are informed about the medical countermeasures they receive under an EUA.”3 In spite of this guidance that appears to minimize the important role of informed consent during a public health crisis, health care professionals maintain an obligation to core ethical commitments in medicine, including respect of patients, and patients’ rights to make informed, voluntary choices about their medical care.4 The FDA guidance echoes oft-heard conclusions among health care professionals that some medical treatments do not require informed consent, potentially reflecting the mistaken assumption that the form is the consent, rather than the process.5, 6 This is particularly problematic because the issue is never whether informed consent is required for the administration of drugs or products―all treatments and procedures require a patient's prior voluntary informed consent. Rather, the misunderstanding appears to arise from the role of the patient's signature in the informed consent process. For example, even if a patient never signs a form consenting to an intravenous antibiotic, the health care professional is still obtaining informed consent if they have discussed the indication, harm, benefits, and alternatives with the patient. The question is not whether informed consent should occur before administration of EUA-approved treatments or procedures, but more a question of whether the essential process requires the patient's oral or signature consent. Although there are distinct legal differences between consent for products authorized by EUA and consent for clinical trials, from an ethics perspective, the importance of the consent applies to both situations. The FDA guidance for clinical trials emphasizes that process clearly. The FDA Informed Consent for Clinical Trials patient resource states, “To many, the term informed consent is mistakenly viewed as the same as getting a research participant's signature on the consent form.”7 This document further recognizes that the informed consent process in research trials should include provision of adequate information to facilitate informed decision making, facilitation of understanding, investment of time for conversational exchange, obtainment of voluntary agreement, and continued provision of information as the investigation progresses or as the situation or subject requires.7 One way in which many health care systems have operationalized the informed consent process is to categorize treatments or procedures as requiring oral consent when they are low risk and within broadly accepted standards of medical practice (eg, administration of most antibiotics, routine lab work, radiographs), whereas products and procedures that have significant risk of complication, morbidity, or mortality can be reasonably expected to produce significant discomfort or pain or are substantial enough to require sedation or anesthesia require signature consent. Although the 2 processes differ in terms of documentation, the process of adequate disclosure, patient understanding, and ensuring voluntariness is identical. How then should health systems decide what type of informed consent is sufficient for products or treatments authorized by an EUA? Conceptually, a requirement for signed informed consent could be determined on the basis of the existing adverse event and side effect profile of the actual EUA. In other words, the determination for signed informed consent could be based not on elements related to whether a product was investigational and approved through an EUA but rather on the established criteria for signed consent. After review of the scientific evidence in totality, the risk profile should then be clinically assessed to determine whether that specific product requires signed or oral informed consent. Complicating this assessment is that products authorized by an EUA may still have significant harms that are unknown and may not be known until further assessment is done. Regardless, the expectation remains for high-quality informed consent whether the patient verbalized consent or provided a signed consent. If time later reveals the product authorized as an EUA has a higher risk or harm profile than originally thought, then the appropriate transition would be toward seeking a signed consent for that product. By any other name, the process and practice described by the FDA in depicting the provider-patient exchange in EUA administration would be recognized and called informed consent. For example, the EUA for baracitinib requires that the health care provider communicate to the patient the potential risk and benefit information included in the FDA Fact Sheet and inform the patient of treatment alternatives and that the treatment is authorized for the unapproved use under the EUA. Informed consent between a health care professional and a patient (or patient's surrogate) occurs when the health care professional discloses the relevant risks, benefits, and alternatives of a recommended treatment; confirms patient understanding, including the opportunity to ask questions; and ensures that the choice is voluntary. Similarly, for a nasal swab diagnostic test approved under the EUA, a description of the procedure to physically obtain the specimen, a mention of any comparable and available alternatives to the diagnostic test, and information about the potential for false positives and false negatives represents good practice in fostering the patient's informed and voluntary engagement about whether to have the test. The safety and effectiveness of investigational products approved under the EUA continue to be evaluated with potential for retraction if the risk profile exceeds benefit (eg, hydroxychloroquine). A minimum requirement for products approved under this FDA mechanism is that the known and potential benefits of the product outweigh the known potential risks. Each item approved by EUA includes a well-documented summary of the available evidence regarding safety profile and risks, including adverse event profile, which is a necessary part of the dialogue with patients before administration. Admittedly, there is an element of “unknown” in the risk-benefit profile early after EUA release, which time clarifies through accumulating additional outcomes-based evidence. This evolving clarification of risk-benefit ratio warrants consideration about whether signed consent should be considered in clinical settings while awaiting further definitive data. In the real-world scenario of coronavirus disease 2019 immunization clinics, many community members are receiving EUA-authorized vaccinations with differing brands, mechanisms, schedule, and efficacy in settings often outside of an established treatment relationship with a health care professional. The sign-up process for the vaccine involves language relevant to informed consent, such as a statement affirming information exchange, agreeing to the immunization service, and authorizing voluntary inclusion in a state vaccination registry at the time of patient scheduling. In the flow of “pop-up” immunization clinics, the patient may receive an FDA information sheet explaining the vaccine mechanism and describing possible side effects a few minutes before the actual injection or even after the patient has already been injected. Patients are typically offered a vaccination information statement, which is a recommendation by the Centers for Disease Control and Prevention. The statement covers vaccine risks and benefits and also useful information about what to do in the case of an adverse reaction. The Centers for Disease Control and Prevention suggests that patients check with their state and local health authorities for additional education and guidance. This setup does not necessarily reflect the traditional informed consent process.8 Ideally, before presenting to the pop-up immunization clinic, patients would have already engaged in prior dialogue with a trusted provider. However, the urgency of pandemic processes may have tilted the traditional patient-practitioner dialogue toward direct public messaging and handouts about risks-benefits of vaccinations, fostering a sense of community-based information sharing rather than individual informed consent engagement. In a time of contingency standards and health system stretch, informed consent warrants awakened attentiveness to ensure that it remains a grounding and guiding principle of medical practice. Even (and especially) during a pandemic, the integrity of our fundamental communication processes for informed consent remains. Although workflows are required to promote timely, efficient access to care, that should not be achieved with any minimization toward respecting and honoring patients’ right to be informed about—and given a meaningful opportunity to make decisions about—their medical care, whether oral or written. The authors declare no conflicts of interest. No funding was received for this article. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the US Department of Veterans Affairs, the US government, or the VA National Center for Ethics in Health Care.