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.