By Arthur L. Caplan and Jerrold L. Abraham.

We responded to the review in JME by Monrad about ethical issues in vaccine trials, in which the discussion was limited to secondary vaccine trials (i.e. testing additional vaccines after one or more vaccines have been approved). We are concerned that the ethics of ongoing primary vaccine trials for covid-19 have not been well addressed.

Subject protection must override all other concerns. As such, there needs to be, as part of any study design and informed consent, a plan to let participants know when a vaccine from another manufacturer is approved, and whether or not the participant had received a placebo or not, in order to allow the participant the necessary basis for an informed decision as whether to withdraw from the study they are in and take the new effective vaccine or not.

These concerns are analogous to a trial for a disease with no current effective treatment in which, during the trial, another treatment is shown to be effective. The first trial might therefore be stopped, as it would be unethical to withhold effective treatment from the participants. Or when a subject receives gene therapy but cannot subsequently be redosed with another gene therapy due to the formation of powerful antibodies.

There are concerns not only for those receiving a placebo in ongoing primary vaccine trials – but also for those who receive the test vaccine. There are immunological concerns that the immunity raised by the test vaccine might or might not cross react with the immunity raised by the new, approved vaccine. The participants who received the test vaccine would have to exercise care in deciding whether or not to withdraw from the ongoing study and receive the new, approved vaccine. In the absence of the possibility of any such a priori testing, this should raise concerns about potentially serious side effects of receiving a second vaccine.

The potential ‘fallout’ of these ethical requirements is obvious in prematurely ending ongoing studies and in increasing the economic risk for the vaccine manufacturers. But the primary ethical concerns for the participants’ safety and health must prevail.

These concerns came to the authors independently, and one of them (JLA), a pathologist for over 50 years, and not a trained medical ethicist, was considering participating in a trial of a new vaccine when he saw that no such discussion was included in the informed consent for that trial. He reached out with his concerns to a well-known bio-ethicist (ALC), who mentioned also having such concerns. This discussion led the two authors to prepare the response to the Monrad JME article.

Paper title: Ethical considerations for protecting the options of subjects in primary epidemic vaccine trials

Authors: Arthur L. Caplan and Jerrold L. Abraham.

Affiliations:

ALC: Drs. William F. and Virginia Connolly Mitty Professor of Bioethics, Department of Population Health, NYU Grossman School of Medicine, NYU Langone Health.

JLA: Professor of Pathology, Director of Environmental and Occupational Pathology, SUNY Upstate Medical University.

Competing interests: None declared