Kennedy School of Government CR16-04-1724.

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Case Program

Placebo Trials in Africa:

The African American Dilemma at the Centers for Disease Control

In 1997, a small group of African American doctors and scientists on the staff of the
Centers for Disease Control and Prevention (CDC) found themselves on the horns of a painful
dilemma. For months, they had been making known their objections to clinical trials the CDC was
sponsoring in Africa. The trials sought to reduce the rate of mother-to-infant transmission of the
human immunodeficiency virus (HIV), the virus that causes AIDS, through short courses of
treatment with the drug Zidovudine (AZT). While applauding the goal of the studies which, if
successful, could potentially save the lives of millions of African newborns at risk of infection, the
members of the group were troubled by the means to that end: placebo-controlled trials in which
some mothers would be given no treatment at all. Because studies in the US and elsewhere had
already shown that a longer course of treatment with AZT was effective in cutting HIV
transmission rates, they argued, it was unnecessary, and unethical, to have a control group that
would go untreated.

The group had brought their concerns to the leadership of CDC; but while they had been
granted a respectful hearing, they had not succeeded in altering the design of the clinical trials.
Now, they faced the choice of making their objections public or acquiescing to the trials. Taking
the latter course would, for them, raise the specter of complicity in the kind of research in which
African Americans themselves had once been the victims, in a notorious study of syphilis. But
taking the former course would bring them into open conflict with two prominent and respected
officials in CDC, themselves African American and one of them, David Satcher, head of the agency
and a rising star in the Clinton administration. Public sparring over ethical issues could be
crippling to Satcher and compromise his chance of being named to the post of Surgeon General.

This case was written by Kimberlee Wyche, MD, MPH; Luc Joseph, MD, MPH; and Joan Reede, MD, MPH, MS;
and edited by Esther Scott, for use in Leadership in Minority Health: A Commonwealth Fund Workshop at the John F.
Kennedy School of Government, Harvard University. Funding for the case was provided by the Commonwealth Fund.
Additional funding was provided by the Robert Wood Johnson Foundation. (0104)

Copyright © 2004 by the President and Fellows of Harvard College. No part of this publication may be
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Placebo Trials in Africa CR16-04-1724.0

With the clock ticking on the clinical trials, the group debated among themselves about how, or
whether, they should proceed.

Background: The AIDS Crisis in Africa

While the scourge of AIDS was felt around the globe, nowhere was its touch more deadly
than in sub-Saharan Africa. The region was home to only ten percent of the world’s population,
but it harbored nearly 65 percent of all HIV-infected people. By 1996, according to World Health
Organization estimates, 14 million people in sub-Saharan Africa had been infected with the AIDS
virus. The young were particularly hard hit. In rural Uganda, for example, 80 percent of the deaths
among men and women ages 25 to 44 were attributable to HIV, and it was estimated that more
than 33 percent of all young adults were infected. Perhaps most alarming of all, the vertical
transmission of HIV—from mother to infant—accounted for 30 to 45 percent of all new cases. If
this trend were to continue, an entire generation could be lost to the ravages of HIV and AIDS.

As a result of recent clinical trials in the US and France, a drug therapy had been
developed that proved effective in preventing mother-to-infant transmission of HIV. The studies
showed that a regimen of AZT, administered prenatally to HIV-positive women and then to their
babies after birth, reduced the rate of vertical transmission by fully 67 percent. But the cost of the
treatment was high—$800 to $1000 for the AZT alone—and beyond the reach of most women in
sub-Saharan Africa, where the average annual per capita expenditure on health in many countries
was $11. Moreover, few nations in the region had the clinical infrastructure needed to administer
the lengthy and complicated regimen of oral and intravenous doses of AZT.

For these and other reasons, there was a general consensus that the full AZT regimen
would be impracticable in sub-Saharan Africa, and in much of the developing world. In view of
the bleak prospects facing HIV-infected pregnant women in poor nations, a panel convened by the
World Health Organization in 1994 urgently called for new research efforts in developing
countries to find simpler and less costly drug therapies for reducing mother-to-infant HIV
transmission. The international research community responded with alacrity. Within a year,
agencies in several countries and the UN stepped forward to support sixteen clinical trials, all but
a handful in sub-Saharan Africa. Nine of the studies were conducted under the sponsorship of two
US agencies—the National Institutes of Health and the Centers for Disease Control. All but one of
the sixteen studies included a control arm that would receive placebos.

When details of these trials began to circulate at CDC, some African Americans on the
professional staff were troubled by what they learned. They believed that morally questionable
choices had been made in the conduct of the trials, which they felt should not go unchallenged.
Their subsequent efforts to call attention to what they considered unethical practices would lead to
months of debate and division within the small and close community of African American
professionals in CDC.

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African Americans and the CDC

Originally established in the 1940s, within the US Public Health Service, to fight
communicable diseases, CDC had evolved into “the nation’s prevention agency,” with the mission
of promoting health by preventing and controlling disease, injury and disability. The agency was
part of the giant US Department of Health and Human Services, but was headquartered in Atlanta;
it encompassed eleven different centers, institutes, and offices, and employed roughly 7,800
people.

Until recently, few African Americans held professional-level jobs at CDC, and even fewer
had been promoted to leadership positions. Although CDC had an image as a progressive
organization, the perception of many of the African Americans was different. They still recalled an
environment in which the “old boy” system of promotion and entitlement had prevailed, and
African Americans had few opportunities for advancement. One epidemiologist remembers that in
1980 there were at most twenty African Americans in professional positions at the agency, and
they were sometimes confused with support staff. One of her colleagues, she says, told her that,
unlike his white professional counterparts, he never wore casual dress to work. “He said,” she
recalls, “that if he didn’t wear a tie when he came to work, somebody would ask him to empty
their trash bins.”

It was in part to provide a system of support for their small cohort that African American
professionals at CDC formed the Social Health Society (SHS), a social organization that offered its
members an opportunity to meet informally; it also served as a platform for networking and
mentoring, which helped the 10-15 original members cope in an environment in which they were
greatly under-represented. “The initial process,” says epidemiologist Bill Jenkins, a founding
member of SHS, “was to get together and get to know each other. African Americans in
professional positions were very isolated and not very trustful of each other.” The SHS began
meeting in 1981 and gradually evolved into a forum for discussing public health issues of
particular interest to its members. Over the years, says Diane Rowley, deputy chief of the
pregnancy and infant health branch at the time, the group sought to identify topics “that we think
need additional attention, and we come up with a list of strategies about how to do that.” Thus, for
example, SHS members produced reports on “racial differences in health outcomes” and helped
make public early data showing alarmingly high rates of HIV infection among African Americans.

By the mid-1990s, the population of professional African Americans at CDC had swelled
to more than 50, and the SHS had grown with it. It continued to be an informal organization whose
membership participated in discussions, via e-mail as well as in meetings, according to their
interests and inclinations. “The people who want to pursue an issue,” Rowley explains, “pursue it,
and the others remain silent if they don’t want to get involved in it.” The debate could be lively.
Often, says Rowley, “the issues we bring up are controversial, even within the group and within

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CDC.” This would especially be the case when some members of SHS began talking about the AZT
clinical trials in Africa.

The Ethical Debate

The issue of the African trials first surfaced sometime in 1996 in an e-mail from one SHS
member to others in the group. It expressed concern, Rowley recalls, “about the fact that CDC was
involved in a series of trials and that the intent of the trials was to compare a short-term AZT
treatment with a control group that wouldn’t receive any treatment.” For some, this news set off
alarm bells, and a flurry of phone calls and e-mails.

No one who objected to the trials disputed the need to find shorter, cheaper treatments to
attack the problem of vertical transmission of HIV in developing nations. Epidemiologist Bill
Jenkins recalls that his first reaction to news of the trials was, “Great, they’re going to do
something to save the lives of babies in Africa.” The goal of the study, he continues, “was laudable.
… I would encourage studies that would allow interventions that are appropriate and
economically feasible in developing countries to be carried out.” But Jenkins and others quarreled
with the decision of study designers to test these interventions against a placebo. In earlier AZT
studies in the US, Rowley points out, the trials had been halted once the benefits of the treatment
emerged, and all participants, including those in the control arm, had been given the drug. In light
of that, she says, “we felt it was unethical to conduct a study that involved a placebo when a
known, successful treatment was available, particularly in this case because of the high mortality
[rates] for this illness.”

Jenkins attributed the decision to do placebo-controlled trials to the “medical domination

of public health,” which relied too heavily on the use of control groups to get quick answers to
research questions. Speed, he argues, would be desirable in clinical trials when “you had an
intervention ready to go,” which was not the case, he asserts, in the AZT trials in Africa. “The
motivation,” Jenkins continues, “was hugely positive, because they were absolutely concerned
about saving these lives in Africa. My problem was you didn’t have to do it in a way that involved
observing what ultimately would be the positive infection [with HIV] among some of the subjects
that we would be following.” Some countered that “these babies are being infected anyway,” he
recalls. “Yes, absolutely, but we’re sitting there watching them. … If it was necessary to sit there
and watch them being infected, I would be supportive of it; my problem was, methodologically, it
was not necessary to do. …”

In the eyes of some, the design of the African AZT trials bore an unmistakable resemblance
to one of the ugliest chapters in modern American medicine. “It sounded,” says one
epidemiologist, “like it was a repeat of the Tuskegee study.” In that study, begun in the 1930s,
poor African Americans in the rural south were denied treatment for syphilis—even after
penicillin was proven to be an effective and affordable treatment—so that doctors in the US Public

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Health Service (of which CDC would later be part) could observe the natural course of the disease.
The Tuskegee study went on for decades, until it was finally halted in the 1970s, but the bitter
after-effects lingered on.1 Even while granting better motives in the AZT trials, some opponents
believed that a detached and clinical approach could lead to the same results. “I do not doubt for
one minute the concern and the goodness of the people who supported [the trials],” says Jenkins,
who was involved earlier in his career in bringing the details of the Tuskegee study to light, “[but]
I think within the CDC there has been and always will be some shadow of the Tuskegee
physicians, where we have researchers who are far more interested in the bug than in the people.”

Taking It To CDC Leadership. As Rowley recalls, about 10-15 people on the SHS e-mail list
were “active discussants” on the issue of the AZT trials. After talking among themselves, they took
their concerns to Dr. Helene Gayle, director of the CDC’s National Center for HIV, STD, and TB
Prevention, under whose auspices the trials were being conducted. Gayle was one of the highest-
ranking African Americans at CDC and herself an early member of SHS. In the formative days of
the group, she recalls, members—like Bill Jenkins, who also worked in her center—often “met
around my kitchen table.” Now she found herself at odds with Jenkins and others in SHS.

Gayle had already grappled, she says, with the ethical issues during the period when the
AZT trials were being designed. “I was very much a part of planning, organizing, being part of the
thinking that went into almost a year-long debate about the ethics of it,” she recalls, and she
strongly defended the choices that had been made. “The crux of the matter,” according to Gayle,
“was, is it appropriate to do research in another country when a different standard of care exists in
the country that’s doing the research. And are we obligated to always supply the best technology
available anywhere to the setting in which you’re doing the research, particularly when the
country that is paying for the research has a different standard of care.”

As she listened to the criticisms of the trials by her fellow SHS members, Gayle believed
that many were acting more under the sway of their feelings than hard facts. “I think the specter of
Tuskegee constantly comes up for black folks,” she observes, “and I think it raises emotion that
sometimes doesn’t allow people to examine the full information.” For example, she says,
“everybody was up in arms about this being done to Africans, not realizing that the other major
trial was in Thailand.2 [There were] a lot of accusations that people are willing to do this to
Africans, but not to other people. That just was not true. … People didn’t understand all of the
consultation that had gone on, including the fact that the countries themselves had been very
much a part of the research design, very much involved in the discussion around the ethics, very
much thought these trials were appropriate.”

1 In 1997, President Clinton issued a formal apology to survivors of the Tuskegee study.
2 CDC specifically sponsored trials in two locations: the Ivory Coast and Thailand.

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Gayle provided Rowley and others with correspondence and documents on the AZT trials
to explain and buttress her position on the ethics of the studies. She also agreed to participate in a
debate on the issue with Bill Jenkins. The debate took place before some 15-20 members of the
SHS, after which those present broke up into small groups to talk over what they had heard. In the
end, few minds appeared to have been changed as a result of the debate; those who opposed the
trials were still dissatisfied. “Most people were even more strongly convinced that there were
some ethical problems with the trials,” says Rowley. Accordingly, they next took their case to the
top: Dr. David Satcher, director of CDC.

About five people from SHS attended the session with Satcher. It was, as Jenkins recalls, “a
fairly intense conversation,” but not, according to Rowley, acrimonious. Satcher heard them out
and, like Gayle, strongly defended the trials. He was “very open to hearing our concerns,” Rowley
recalls. “… He was very challenging and very critical, and it actually helped us develop our clarity
around some of the ethical issues.” Satcher and Gayle, who also attended the meeting, did agree to
look into some issues—in particular, according to Rowley, they promised to “redouble their
efforts” to have an implementation plan in place—but they “were still not convinced to end the
trials.” This left opponents of the trials pondering their next step. “We felt that we had adequately
presented our concerns to the CDC administration,” Rowley notes, “but that our responsibility
didn’t end there.” They began to consider, says George Roberts, a senior behavioral scientist in
CDC’s National Center for Injury Prevention and Control, “a host of possible strategies that would
be directed at interrupting the trials.” These included writing editorials in professional journals, or
contacting an outside organization, such as the National Bioethics Advisory Committee, with an
eye to drawing national attention to their concerns. But taking the controversy beyond the walls of
CDC, was an “uncomfortable” idea, Rowley acknowledges, with the potential for creating deep
divisions among African Americans within CDC and for undermining their leaders’ prospects
outside it.

The Dilemma

Within SHS, there were differences over both the conduct of the AZT trials and the way
criticisms of it were couched. While acknowledging that the decision to include a control arm
could be “argued on both sides,“ one epidemiologist nonetheless supported the trials and found
the analogy to Tuskegee inapt. In the Tuskegee case, he says, study subjects were being denied the
standard of care in their own country; this was not the issue in the AZT trials in Africa, where no
treatment of any kind was available for HIV. The epidemiologist also took issue with the way
objections to the trials were presented, essentially as a position the society had taken; the SHS, he
argues, never voted on the issue, nor did many of its members necessarily want to belong to the
kind of organization that engaged in political activity. There were “people [in SHS],” he says,
“who think they’re part of a society which is basically apolitical, and other people who … think

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that’s not correct and the society, by nature of being African American in the United States, [has] to
be political. It is that element of SHS which I think wanted to drive the process.”

Others were concerned about the tone of the debate. Bob Robinson, acting associate
director of minority health at CDC at the time, recalls he did not take a position on the trials
themselves. The issues “were complex,” he recalls, and further complicated by “the indication that
there was African consent” to the studies. “So there was enough mud in the situation,” he says, “to
make it cloudy, and not an easy right/wrong, black/white situation.” Instead, Robinson took a
mediating role in the debate. He recollects that “there were attacks going against Helene Gayle,
accusations,” and that he sought to “defuse the rhetoric that I thought people were engaging in,
making accusations that were not necessarily founded, at least not so much in terms of information
that I thought had been presented.”

But even for the group of 10-15 SHS members who actively opposed the trials, the
internecine nature of the dispute was troubling. Some were old friends who had been in SHS
together from its earliest days. They respected Gayle and Satcher, and found it difficult to reconcile
their high regard for these pioneering leaders with their decision to support placebo-controlled
trials in Africa. “I was confused,” one epidemiologist recalls, “as to why particularly Helene,
who’s a friend, was defending the trials.” The epidemiologist second-guessed herself, thinking, as
she remembers it, “maybe there are circumstances that I’m not familiar with, and surely she and
Dr. Satcher wouldn’t support something of this nature that was truly unethical.” Dr. Satcher, in
particular, had a strong record of commitment to helping African nations in their struggle against
AIDS. “He had worked very hard to support the development of the trials,” says Rowley, “because
he saw Africa as being neglected. It had very high rates of HIV infection and terrible mortality
figures, and he was committed to trying to do the right thing to improve the situation.”

There were other considerations that made opponents of the trials hesitant to press their
case further. People worried, Roberts recalls, about “damaging [their] own professional
relationships and positions.” Moreover, he adds, there were “those of us who were concerned
about the implications of attacking indirectly African American leadership.” This was especially
the case with Dr. Satcher, who was under consideration at the time for the post of Surgeon
General, which had remained vacant since 1994, when Dr. Joycelyn Elders resigned in a cloud of
controversy. “We didn’t want to at all interfere with that process,” says Rowley, “because we all
agreed that he clearly had the leadership and the experience that was needed to be Surgeon
General. … That was one of the concerns I discussed with at least a couple of people in the group:
how can we do this in a way that won’t be used to undermine his prospects?”

As the group considered what to do, the discussions were at times “heated,” according to
Roberts. People were torn between “personal allegiances [and] very strong professional
opposition, if you will, to the studies.” Against the wish to avoid alienating their colleagues in
SHS, and to support prominent and respected African Americans in their field, was the

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determination not to let history repeat itself. “Were we at CDC at the time [the Tuskegee studies]
were going forth,” asks Roberts, “would we have been silent, or would we have registered our
outrage and begun the process of challenging those studies?”