Evaluation Table

Perspective

T h e N EW ENGL A N D JOU R NA L o f M EDICI N E

november 26, 2020

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The only way out of today’s misery is for peo-ple to become worthy of each other’s trust.— Albert Schweitzer
As the race to develop a vaccine
for Covid-19 has reached phase 3
clinical trials, concerns are in-
creasing about the low rates of
trial participation in important
subgroups, including Black com-
munities. Recent data show that
although Black people make up
13% of the U.S. population, they
account for 21% of deaths from
Covid-19 but only 3% of enrollees
in vaccine trials. This problem
threatens both the validity and
the generalizability of the trial re-
sults and is of particular concern
in vaccine trials, in which differ-
ences in lifetime environmental
exposures can result in differenc-
es in immunologic responses that
could affect both safety and effi-
cacy. Despite long-standing calls
from the Food and Drug Admin-

istration (FDA) and the National
Institutes of Health (NIH) to im-
prove the participation of under-
represented subgroups in drug
trials, the problem persists.1

What are the barriers to great-
er participation of Black people
in Covid-19 trials? Although they
are multiple, a critical factor is the
deep and justified lack of trust
that many Black Americans have
for the health care system in gen-
eral and clinical research in par-
ticular. This distrust is often traced
to the legacy of the infamous syphi-
lis study at Tuskegee, in which
investigators withheld treatment
from hundreds of Black men in
order to study the natural history
of the disease. But the distrust is
far more deeply rooted, in centuries
of well-documented examples of

racist exploitation by American
physicians and researchers.2

How can these long-standing
barriers to trust be overcome? The
presidents of Dillard and Xavier
Universities, two of the 104 his-
torically Black colleges and uni-
versities (HBCUs) in the United
States, recently wrote to their com-
munities saying that they them-
selves were participating in one
of the vaccine trials and asking
their students, faculty, and staff
to consider doing the same. The
pushback from parents of some
students came quickly. One wrote
on Xavier’s Facebook page, “Our
children are not lab rats for drug
companies. I cannot believe that
Xavier is participating in this.
This is very disturbing given the
history of drug trials in the black
and brown communities.”3

Presidents of the four histori-
cally Black U.S. medical schools
recently called for measures to in-
crease the participation of Black

Trustworthiness before Trust — Covid-19 Vaccine Trials
and the Black Community
Rueben C. Warren, D.D.S., Dr.P.H., M.Div., Lachlan Forrow, M.D., David Augustin Hodge, Sr., D.Min., Ph.D.,
and Robert D. Truog, M.D.

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n engl j med 383;22 nejm.org november 26, 2020

patients in clinical trials, correctly
arguing that without such involve-
ment, “there will be no proof that
our patients should trust the vac-
cine.” The presidents added that
“Black doctors are the best way to
build trust in our communities”
and called on other HBCUs to join
the effort to “foster trust in com-
munities throughout the country.”4

Though we applaud these ef-
forts, we fear that once again the
responsibility for addressing the
sequelae of centuries of racism is
falling on Black people themselves.
Our country has yet to compre-
hend adequately that overcoming
racism is not primarily the re-
sponsibility of Black people; the
racist ideas and practices that
constitute today’s “structural rac-
ism” were created, and have been
sustained, primarily by White peo-
ple. It would be wrong, as well as
ineffective, to ask Black commu-
nities to simply be more trusting.
Clinicians, investigators, and phar-
maceutical companies must pro-
vide convincing evidence — suf-
ficient to overcome the extensive
historical evidence to the contrary
— that they are, in fact, trust-
worthy.

What can we do to earn and
deserve increased trust?

First, trial sponsors and regu-
latory agencies can ensure that
the informed-consent process is
exemplary, including ensuring that
all relevant aspects of the design
and conduct of the clinical trials
are maximally transparent.

Second, all clinical research
depends on people who are will-
ing to accept the risks posed by
trial participation in order to im-
prove health for the people who
come after them. Black partici-
pants who agree to enroll in these
trials have a right to expect and
trust that Black communities will

have fair access to vaccines once
they become available. The recent
guidelines from the National
Academy of Sciences (NAS) are no-
table in this regard, recommend-
ing that priority be given to “peo-
ple who are considered to be the
most disadvantaged or the worst
off,” as defined by measures such
as the Social Vulnerability Index
created by the Centers for Disease
Control and Prevention.5 Though
this approach would not directly
target people in specific racial or
ethnic groups, it is functionally
antiracist in that it prioritizes peo-
ple who have suffered from the
social determinants of poor health
that are unfortunately prevalent
in many Black communities.

Third, politicization of the vac-
cine trials has engendered wide-
spread mistrust among the gen-
eral public. The joint pledge by
nine pharmaceutical companies
that they will “stand with science”
and not submit a vaccine for ap-
proval until it has been thorough-
ly vetted for safety and efficacy is
welcome, but earning trust will
require credible evidence that this
pledge is being honored. Just as
important, however, is that the ev-
idence must not only be convinc-
ing to the general public, but —
in the words of the NAS guidelines
— also be perceived as convinc-
ing “by audiences who are socio-
economically, culturally, and ed-
ucationally diverse, and who have
distinct historical experiences with
the health system.”5

Fourth, to earn and deserve
trust from prospective trial partici-
pants, we must ensure that they
will receive appropriate medical
care if they are injured as a result
of receiving an experimental vac-
cine. In addition to often lacking
access to health care, Black peo-
ple are also disproportionately

likely to be uninsured, and phar-
maceutical sponsors in the Unit-
ed States are not required to pro-
vide compensation to people who
experience research-related inju-
ries. Even when participants have
insurance, there is no guarantee
that they will be covered for such
injuries. In many cases, injured
participants will be forced to rely
on the tort system for compensa-
tion — a situation that is morally
indefensible, especially for par-
ticipants who lack the means to
engage in this time-consuming
and expensive process. One way
to demonstrate trustworthiness
would be for the pharmaceutical
companies sponsoring these tri-
als to establish a fund to guaran-
tee health care coverage and death
benefits to patients and families
as compensation for serious vac-
cine injuries or possible deaths.

When Covid-19 vaccines are
eventually approved by the FDA,
their success in Black and other
communities will depend on
whether members of these com-
munities not only trust that they
are safe and effective, but also
believe that the organizations of-
fering them are trustworthy. Trust
could be earned more quickly by
a collaboratively designed Opera-
tion Build Trustworthiness that
matches the seriousness and scope
of Operation Warp Speed. To be
effective, this effort would need
to be firmly grounded in grass-
roots involvement of individuals
and organizations with solid, well-
earned reputations for trustwor-
thiness in Black and other mi-
nority communities, including
respected elected representatives,
trusted local and national faith
leaders, community advocates, and
others. Active, ongoing, and fully
bidirectional collaboration, learn-
ing, and communication will be

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n engl j med 383;22 nejm.org november 26, 2020

essential. Time is running short,
and trustworthiness, not trust,
must be our first and most ur-
gent priority.

Disclosure forms provided by the au-
thors are available at NEJM.org.

From the National Center for Bioethics in
Research and Health Care, Tuskegee Uni-
versity, Tuskegee, AL (R.C.W., D.A.H.); and
the Center for Bioethics, Harvard Medical
School, Boston (L.F., R.D.T.).

This article was published on October 16,
2020, at NEJM.org.

1. Warren RC, Shedlin MG, Alema-Mensah
E, Obasaju C, Augustin Hodge D. Clinical
trials participation among African Ameri-
cans and the ethics of trust: leadership per-
spectives. Ethics Med Public Health 2019; 10:
128-38.
2. Washington HA. Medical apartheid: the
dark history of medical experimentation on
Black Americans from colonial times to the
present. New York: Doubleday, 2006.
3. Moss W. Parents concerned about vac-
cine study taking place at some HBCUs:
remembering the Tuskegee experiment.
HBCUConnectcom. September 3, 2020
(https://hbcuconnect . com/ content/ 359255/
parents – concerned – about – vaccine – study

– taking – place – at – some – hbcus – remembering
– the – tuskegee – experiment).
4. Frederick WAI, Montgomery Rice V, Car-
lisle DM, Hildreth JEK. We need to recruit
more Black Americans in vaccine trials. New
York Times. September 11, 2020 (https://
www . nytimes . com/ 2020/ 09/ 11/ opinion/
vaccine – testing – black – americans . html).
5. National Academies of Sciences, Engi-
neering, and Medicine. Framework for equi-
table allocation of COVID-19 vaccine. Wash-
ington, DC: National Academies Press,
2020.

DOI: 10.1056/NEJMp2030033
Copyright © 2020 Massachusetts Medical Society.Trustworthiness before Trust

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