Challenges to informed consent for COVID-19 vaccine studies
Informed consent procedures for vaccine trials commonly include disclosure of very minor risks such as injection site reactions, rare risks from past, unrelated vaccines/viruses, such as Guillan-Barre syndrome for swine flu and generic statements about the risk of serious idiosyncratic systemic adverse events and death. Specific risks to research participants derived from biological mechanism are rarely included, often due to ambiguity about their applicability16. Given the overwhelming evidence in the extant literature, however, all COVID-19 vaccine trials are unlikely to meet the required threshold of patient comprehension if clear and specific disclosure, in the informed consent, of the risk of worsened COVID-19 clinical course or death from acute lung, blood, cardiac or other tissue injury upon SARS-CoV-2 viral exposure due to vaccine-elicited antibodies is not provided to research subjects. These risks should be clearly and emphatically distinguished in the study informed consent from risks observed rarely as well as the more obvious risk of lack of efficacy, which is unrelated to the specific risk of ADE. Based on the extant literature, it should have been obvious to any skilled medical practitioner in 2020 that there is a significant risk to vaccine research subjects that they may experience severe disease once vaccinated, while they might only have experienced a mild, self-limited disease if not vaccinated. The limited benefit of immunogenicity endpoints for investigational COVID-19 vaccines should also, perhaps, be clearly disclosed. The consent should also clearly distinguish the specific risk of worsened COVID-19 disease from generic statements about risk of death and generic risk of lack of efficacy of the vaccine. Given the “laundry list” nature of informed consents, disclosure of the specific risk of worsened COVID-19 disease from vaccination calls for a specific, separate, informed consent form and demonstration of patient comprehension. The alarming rumors of emergency consideration in COVID-19 vaccine trials of unprecedented “viral challenge clinical trial” designs, wherein subjects would be intentionally challenged with live virus after vaccination, call for this level of consent to protect the moral and legal rights of human subjects recruited to participated in these vaccine trials. While the COVID-19 global health emergency justifies accelerated vaccine trials of candidates with known liabilities, such an acceleration is not inconsistent with additional attention paid to heightened informed consent procedures specific to COVID-19 vaccine risks.