African Bioethicist Urges More Oversight for Clinical Trials
By Carolyn Cosmos Uploaded on January 31, 2013
A few years ago, medical ethics expert Paul Ndebele, a noted African scholar, saw something at a malaria research site in Malawi that disturbed him: The project was using junior staff as bait to collect mosquitoes for research colonies and feeding the malaria-carrying insects human blood — straight from the source.
When the staffers offered their arms at mosquito mealtimes, they naturally risked infection, Ndebele said, warning that those who continued doing this while taking drugs to prevent or treat malaria were potentially sparking malarial drug resistance in mosquito populations.
Using humans as insect bait — a practice that has its own scientific label, Human Landing Catch (HLC) — is considered the most effective way to capture adult mosquitoes, but Ndebele questioned the ethics of it in an article for the Malawi Medical Journal in 2011.
Ndebele, assistant director for research ethics at the University of Botswana, was recently tapped to be a bioethicist contractor by the Henry Jackson Foundation in Bethesda, Md. With research sponsors at the National Institutes of Health and the European Commission, he's a well-connected, peripatetic activist and academic.
Paul Ndebele and his wife Sharon attend a reception for international scholars at Michigan State University. After political unrest in his native Zimbabwe threatened his work on bioethics, Ndebele was able to leave the country in 2003 with the help of a fellowship from the Institute of International Education's Scholar Rescue Fund.
He alerted his networks throughout sub-Sahara Africa about the issue of HLCs. He visited multiple malaria study sites in a number of nations. He brainstormed at his workshops for professionals and laypeople who monitor medical research.
Ndebele's resulting report dealt with the tensions between existing scientific standards and the principles of justice and "human dignity" written into contemporary medical research worldwide. "It was an ethical choice involving mosquitoes, humans and science," Ndebele told The Washington Diplomat.
Still, his report was labeled an opinion piece. Human Landing Catches are considered common medical practice — and are even called the gold standard for estimating malaria transmission by mosquitoes. A 2012 study on the incidence of malaria among mosquito collectors in western Kenya conducted by the Centers for Disease Control and Prevention and other health groups found that if properly treated, "concern about increased risk of malaria among collectors should not be an impediment to conducting HLC studies."
But Ndebele questions the practice, and his report offers practical alternatives, such as using anesthetized animals to feed mosquitoes or getting blood from transfusion services. It also suggested ways to use existing products to protect workers from bites.
In addition to being a dogged problem solver, Ndebele doesn't mince words when it comes to thorny bioethical issues.
He chastised the principal investigators and other researchers in malaria vector studies for "resting in their comfortable homes" while their low-literacy and poorly paid staffers endured mosquito bites overnight for hours on end — and he even listed the bite rates to make his point.
Not only were such things ethically dubious, he warned, they could stir public controversy and thus do serious harm to important research.
Bioethics itself is a critical field of research that tackles the murky moral quandaries spurred by the ever-advancing march of medicine — a field that's been around as long as medicine has been in existence. Though debated in ancient times, bioethics grabbed the public's attention after the Nazis' horrifying medical experiments on humans during World War II. The subsequent Nuremberg Code outlined a set of international standards for research involving human subjects.
But bioethics as an academic interdisciplinary field evolved and solidified throughout the 1960s and '70s in the wake of game-changing advances such as organ transplants and end-of-life care. Key standards for governing ethics in medical research were set by the 1967 Helsinki Declaration and by groups such as the World Medical Association, World Health Organization, the Council for International Organizations of Medical Sciences, the Council of Europe and the U.S. Department of Health and Human Services, which has established extensive regulations on human testing.
But just because standards have been set and regulations adopted doesn't mean they've always been followed — or that they've kept up with the rapid pace of medical innovation.
In 2010, a six decade-old injustice resurfaced when the U.S. government apologized to Guatemala for deliberately infecting hundreds of Guatemalans with venereal diseases in an attempt to study the effectiveness of penicillin. The experiments, conducted between 1946 and 1948, were particularly egregious. As documented by the New York Times, "American tax dollars, through the National Institutes of Health, even paid for syphilis-infected prostitutes to sleep with prisoners, since Guatemalan prisons allowed such visits. When the prostitutes did not succeed in infecting the men, some prisoners had the bacteria poured onto scrapes made on their penises, faces or arms, and in some cases it was injected by spinal puncture."
Today, though not as extreme, clinical trials on human subjects continue around the world — and particularly in the developing world. An eye-opening 2011 exposé by Vanity Fair called "Deadly Medicine" investigated how pharmaceutical companies scour far-flung corners of the globe to test their products on communities where recruiting patients is cheap and safety standards are lax or nonexistent — all in the hopes of eventually marketing their drugs to Americans for a healthy profit.
Though the ultimate destination is America, human drug testing in the United States has dwindled, while the number of such clinical trials abroad has skyrocketed — nearly 60,000 in more than 170 countries, according to the National Institutes of Health.
"Throw a dart at a world map and you are unlikely to hit a spot that has escaped the attention of those who scout out locations for the pharmaceutical industry," wrote Vanity Fair's Donald L. Barlett and James B. Steele, noting that China and India are home to hundreds of drug trials. Other popular pharmaceutical testing grounds include Russia, Thailand and Turkey.
Africa, of course, is also represented in this cocktail of questionable clinical trials — and that's where Ndebele's specialty lies.
Ndebele, who's worked in Botswana and Malawi, began his career in Zimbabwe, where he'd been a researcher with the principal monitoring agency for all medical and clinical trials in the country. But Ndebele was not immune to Zimbabwe's political unrest, which made his work increasingly impossible. He was able to leave the country in 2003 with the help of a fellowship from the Institute of International Education's Scholar Rescue Fund. The fund supports "persecuted academics" at risk around the world — 450 of them in 48 countries over 10 years. In 2012, it highlighted Ndebele as one of 10 scholars featured to celebrate its decade of work.
African scholar and bioethics expert Paul Ndebele gives a lecture on responsible authorship at the Harry Oppenheimer Okavango Research Centre at the University of Botswana. Ndebele has pushed for greater oversight of research ethics committees that monitor clinical trials and other studies using human subjects.
But the scholar wears many hats, serving on the editorial boards of journals and advising governments about medical research. However, his most important contribution, colleagues say, may be his campaign to train and strengthen the various boards, committees and agencies in developing nations that are supposed to oversee medical research that recruits their citizens — much of it spearheaded by large international corporations, including many based in the United States.
Monitoring of such research is done by research ethics committees, or RECs, that can approve, reject and track a medical project. (They're called institutional review boards, or IRBs, in the United States.) However, in many countries their oversight has been unsophisticated, and even in nations with tough regulations, including the United States, scandals are not uncommon.
"In the 1980's and '90s, there was an expansion of international medical research conducted by developed countries in less developed nations," Ndebele said. "I became concerned about weak local oversight of this research and issues of justice, and asked myself, 'What can I do?'"
His work started in 2001 with improvements he initiated at the Medical Research Council of Zimbabwe. His efforts to strengthen REC oversight have continued throughout sub-Sahara Africa ever since — with, he says, some success.
The extent of the problem became painfully clear to Ndebele in 2007 when he became part of a group that examined studies of RECs and IRBs around the world and took a detailed look at research ethics committees in nine African nations. The results were not encouraging.
Most African committees they examined were weak, with poorly trained staff and insufficient funds. So Ndebele set out to strengthen them, focusing on training, support and, through his published research, creating new cross-cultural understandings of the ethics involved.
Sorrell L. Schwartz, professor emeritus of pharmacology at Georgetown University Medical Center in Washington, D.C., and an expert on RECs, praised Ndebele for his granular approach, bringing specifics and sophistication to the recruitment and training of people on research review boards.
This is particularly important in countries that don't have regulations controlling oversight, Schwartz added — because very detailed understandings are needed to monitor and judge the merits of a clinical trial.
"You can be a Nobel Prize winner and still lack the insight to understand good human research protections," Schwartz noted.
Much of that insight comes down to culture. To that end, Ndebele has studied the issue of "informed consent" and whether trial participants know what they're getting into. For example, he's written finely grained field studies of medical confidentiality in cultures where family members share everything and examined the independence of women who must offer informed consent before enrolling their children in medical research.
In addition, he's questioned the meaning of "voluntary" participation in medical studies conducted in regions where health care is scarce and researchers entice participants with access to high-quality Western medicine as part of the deal.
One of his papers took a hard look at a clinical trial for two new drugs to prevent HIV transmission (they ultimately didn't work). The research was conducted in a farming community in Africa, and Ndebele found that most participants didn't understand the basic concepts behind scientific trials. Most had a poor grasp of three key research fundamentals — "randomization," "double-blinding" and "placebo use" — which was so poor that many felt cheated or deceived at the end of the trial.
Ndebele and colleagues then developed research explanations that used story-telling techniques popular in the local culture and everyday examples taken from their farming employment to help participants understand the scientific concepts behind clinical trials.
One factor in Ndebele's persistence to advocate for vulnerable trial subjects — and wade into territory fraught with thorny ethical debates and unglamorous research analysis — is his family's roots. Ndebele says his native Tonga ethnic group of Zimbabwe, a culturally distinct people who have traditionally lived by farming in a harsh climate, has an ethos of hard work. His father, a farmer, eventually became a pastor "and encouraged me and my brothers to work hard in school as well. It's the reason why we all went to university."
And perhaps it's why the quiet scholar continues the hard work of asking tough questions to hold the medical industry accountable. "I'm glad I can say I've contributed an African voice internationally in my professional work."
About the Author
Carolyn Cosmos is a contributing writer for The Washington Diplomat .