Indian Journal of Medical Ethics Vol VI No 2 April-June 2021
[118]
Placebo control in Covid-19 trials: A missed opportunity for international
guidance
URBAN WIESING, HANSJÖRG EHNI
________________________________________________________________________________________________________
Abstract
Vaccines preventing Covid19 have been approved in several
countries. Is it still ethically acceptable to use placebo controls
during the development of other vaccine options? If two of the
most influential international guidelines of biomedical research
are consulted, the Declaration of Helsinki and the CIOMS
guidelines, the answer is “no” . We discuss the implications for
ongoing vaccine research, and how placebo controls might be
justified nevertheless. However, the ethical conflict remains highly
problematic. We suggest that such ethical dilemmas should be
avoided in the future by the introduction of a new system of
global governance. Once vaccines are approved, a global
regulation should oblige producers to provide the necessary
amount of vaccine doses for the control groups of ongoing
vaccine research.
Key words: Research ethics, Declaration of Helsinki, CIOMS
Guidelines, placebo control, Covid19 vaccine
Introduction
From time to time an interesting phenomenon can be
observed in medical ethics: Ethicists struggle with a problem
for a long time without finding a solution acceptable to all.
Then the problem may disappear for a certain time, only to
suddenly resurface at the centre of a current debate. One such
problem is the ethical permissibility of placebo controls in
clinical trials even if a standard therapy is available. This
question is gaining urgency yet again in Covid-19 vaccine
trials, as recently approved vaccines have become available.
In the literature, this problem has been discussed extensively
in the context of studies in sub-Saharan Africa and Thailand (1).
There, the prevention of HIV transmission from mother to
unborn child was tested against placebos, although a costly
and complicated standard therapy was available in wealthy
countries. This therapy, however, was not available in poor
regions of the world. Proponents of placebo controls argued
that, in such cases, these were methodologically superior and
that clinical researchers had no obligation to offer a
therapeutic option in research. Moreover, they argued, in poor
regions the risk-benefit ratio of participation in the trial would
be no worse than that of non-participation. However, their
opponents considered it an obligation to offer existing
therapeutic options as comparator, feared the exploitation of
poor countries for the benefit of the rich, and set a very low
threshold for acceptable risks in this context. As is often the
case in applied ethics, neither side could fully prevail.
The issue led to several revisions of the Declaration of Helsinki
(DoH). After lengthy discussions, a compromise was reached in
Fortaleza for the 2013 version, which a majority of delegates to
the General Assembly of the World Medical Association
accepted (2). The CIOMS guidelines were also adapted
accordingly, to say: If a standard therapy is available, trials with
a placebo may proceed only for compelling scientific reasons
and with low risks involved (3). The actual controversy
subsided without being resolved decisively.
Now the question of whether placebo controls are ethically
permissible has arisen again within the context of Phase 3
trials of vaccines against Covid-19. The development of various
vaccines has been dramatically fast, in that Phase 3 trials were
ongoing when the medical approval of one vaccine in
December 2020 and another in January 2021 changed the
situation. The question arises equally for trials starting after the
first approval of a vaccine: Should ongoing placebo-controlled
trials be allowed to continue unchanged? And should
additional placebo-controlled trials be permitted? What do the
Declaration of Helsinki (DoH) and CIOMS guidelines say about
this?
The authors are aware that both documents have a different
status in different countries. The spectrum ranges from vague
recommendations, soft law to legislation. Therefore, one
cannot readily conclude that there is a legal obligation in a
Authors: Urban Wiesing (corresponding author - urban.wiesing@uni-
tuebingen.de), Director, Institut für Ethik und Geschichte der Medizin,
Gartenstrasse, Tübingen, GERMANY; HansJörg Ehni (hans-joerg.ehni@uni-
tuebingen.de), Deputy Director, Institut für Ethik und Geschichte der
Medizin, Gartenstrasse, Tübingen, GERMANY.
To cite: Wiesing U, Ehni H-G. Placebo control in Covid-19 trials: A missed
opportunity for international guidance. Indian J Med Ethics. 2021 Apr-Jun;
6(2) NS: 118-121. DOI: 10.20529/IJME.2021.22.
Published online first on March 22, 2021.
Manuscript Editors: Ruth Macklin, Amar Jesani.
Peer reviewer: An anonymous peer reviewer.
© Indian Journal of Medical Ethics 2021