By Sunnie Ning
As more COVID-19 vaccine candidates enter clinical trials, many developing countries are being tapped to participate.
But the history of clinical trials in developing countries is fraught with ethics violations and discrimination. In June, several protests broke out in South Africa over the University of Oxford’s COVID-19 vaccine trial. Demonstrators held signs that said: “We are not guinea pigs.”
In this post, I explore some of the ethics issues of clinical trials conducted by groups in developed countries but carried out in developing countries.
Clinical trials shifted to developing countries
The number of clinical trials in low-to-middle-income countries (LMIC) has surged in the past few decades. For the pharmaceutical industry, the lower costs and the availability of “treatment-naïve” patients — those who have not been exposed to drugs or trials — are the main attractions.
For developing countries, the promise of advanced medical science and access to the latest medications can outweigh the costs of participating in trials. But whether developing countries actually receive these benefits remains questionable. Some say that drugs tested in LMIC are priced too high for those living there to access them outside the context of a trial. Others worry that the trials take advantage of vulnerable populations in countries without strict standards for clinical trials.
The same is true for COVID-19 vaccine trials. Developing countries are hoping to get access to vaccines by participating in the trials. Brazil has such an agreement with Oxford and AstraZeneca. Indonesia has a similar deal with Chinese pharmaceutical company Sinovac. But there is no guarantee that these vaccines will succeed.
However, as an added benefit for the pharmaceutical industry, holding vaccine trials in developing countries —especially where COVID-19 infection rate is still high, such as Brazil — means that more volunteers may be exposed to the virus, which could speed up the trials.
Meeting Ethical Standards
Although there are international guidelines for conducting global research, specific rules and applications of the ethical standards vary. Even when trials are bound by the ethics regulations of the host countries, it is often hard for regulatory bodies to enforce these rules.
Informed consent refers to the communication process that enables a patient to make an informed and voluntary decision about participating in the study.
Several violations of informed consent have received global attention. In a clinical trial in Nigeria in the mid-1990s, the pharmaceutical company Pfizer failed to inform study participants of the risks associated with a drug meant to treat meningitis, including joint damage and liver toxicity. And in the 2014-2016 Ebola outbreak, over 250,000 blood samples were drawn from West African patients who did not give informed consent.
Regulations on informed consent often are not tailored to the local context in developing countries. For example, FDA regulations focus on the informed consent document, and require written consent. Such procedures may be impossible to implement in some areas. Further, if participants belong to severely socio-economically disadvantaged populations, they could be susceptible to undue influence, such as monetary compensation for participation in the trial, which would impact their ability to consent.
Use of Placebo
Another issue relates to the use of placebo. In the U.S., control groups in clinical trials usually have to receive some treatment, if available, so that all participants receive treatment. However, the FDA regulation on international clinical trials is much more permissive. Control groups are only entitled to the standard of care they would otherwise receive locally, which often means no treatment at all.
In the 1990s, the United States tested an antiretroviral medication on over 17,000 pregnant women in Africa to prevent the transmission of HIV to their children. Some of them only received placebo, even though a proven treatment already existed. In 2014, as part of a clinical trial for an experimental vaccine against rotavirus, over 2,000 children in India were injected with a placebo treatment, rather than an alternative vaccine that was already available.
Placebo use in vaccine trials is clearly acceptable when no efficacious and safe vaccine exists. If COVID-19 vaccines and cures become available, however, the use of placebo in other vaccine clinical trials might become contentious. This is especially true if the medicine is available in some countries, but not the countries participating in the trials.
In my next post, I will explore other ethical issues, including research design, ethics review, and post-trial benefits.