Drug trials: Beyond the dark side
Daniel Altman
International Herald Tribune
For drug companies, globalization has brought a double boon: new markets and new testing grounds for clinical trials. Better information technology and transport infrastructure have made monitoring the ethics of those trials somewhat easier, but experts say problems are still proliferating. One Swedish-Tanzanian trial of an HIV vaccine seems to be doing things right, however.
The issue of unethical testing in developing countries received extra attention with the release last year of "The Constant Gardener," a film based on John Le Carré's novel about a Western company using Kenyans as unknowing guinea pigs for a tuberculosis drug. But real-life cases of questionable behavior have been popping up with increasing frequency, too.
Pfizer, based in New York, tested a meningitis drug called trovafloxacin in Nigeria in 1996, during an epidemic of the killer infection. Later, Nigerian families sued the company in the United States, saying their children had been entered into the study without their consent. The cases collapsed last summer over technical and jurisdictional details.
More recently, the American military's Walter Reed Army Institute of Research and GlaxoSmithKline of Britain came under fire for testing a hepatitis E drug on thousands of Nepalese soldiers. The researchers first tried to test the drug on civilians in Lalitpur, but rumors of bribes led to protests. Later, experts started asking whether the soldiers - many of whom may have been illiterate - could have understood the consent agreements they had signed and whether the effective but expensive drug would ever be available to Nepalese.
"Companies in the later clinical phases of drug development are increasingly going to developing countries, for example India, where it is basically cheaper to do it," said Dr. Hans Hogerzeil, director of medicine policy and standards at the World Health Organization in Geneva. "You have a huge number of treatment-naïve patients who have never been treated before and a lot of highly educated people and good infrastructure."
India is not the only popular destination for Western drug companies, however. Eastern Europe, Thailand, China, Brazil and Argentina are also favorite locations for trials, said Peter Lurie, deputy director of the health research group at Public Citizen, a watchdog organization in Washington.
"Before, you couldn't get back and forth to these countries the way you can now," Lurie said. "You couldn't share data electronically the way you can now. Even if people had the temptation to go overseas before because of less regulation, more compliant populations or study designs that they couldn't pull off locally, logistically it was not possible until recently. That's where globalization comes in."
Globalization has also made monitoring overseas trials easier, Lurie added, but the problem is still a long way from being solved.
"A given study in Malawi is easier to monitor now than it was before," he said. "Still, the ability to monitor what's going on in Malawi is so poor that, over all, the ability to monitor the totality of studies that are going on in the world has gone down."
That is why it's important to have clear international guidelines, with national laws backing them up, Hogerzeil said. India has been making especially good progress in this area, he said. Yet even when those standards exist, practice does not always follow policy.
"The patient really has to be informed what is being asked," Hogerzeil said. "You have to sit there. You have to explain it to them. You have to have material written in the local language."
Lurie said that even drug trials undertaken by public and nonprofit agencies sometimes fell victim to ethical problems. Still, he said, these trials almost always meet one important criterion that often is missing from corporate trials: that the local population would actually be able to buy and benefit from the drug if it proved successful.
A clear example is the Swedish-Tanzanian effort to develop a DNA-based vaccine against HIV. A prototype vaccine was tested first on Swedish citizens to make sure it did not have harmful side effects. But the prototype is not intended to treat HIV in Sweden; it is aimed at the subtypes of HIV that are most prevalent in East Africa. Later, the researchers may use the same platform to treat other subtypes.
A decade ago, the research project, which received generous funding both from Sweden's official aid agency and from the Walter Reed institute, approached a group of Tanzanian policemen to gauge the prevalence of HIV, which was higher than in Sweden. Now, after lengthy consultations in Tanzania, the researchers have contacted the same group again to test the vaccine.
Transparency has been a hallmark of the trial, said Eric Sandstrom, a professor in the department of infectious diseases at Karolinska University Hospital in Stockholm and a director of the study. He noted that the research offered no guarantee of medical benefits.
"We are very clear on that point," he said. "Anybody who volunteers for the study does it for the good of the development of the vaccine. There is no reassurance that any vaccine today can offer any protection."
The trials, which are the latest part of a 20-year history of cooperation between the two countries, are also intended to build infrastructure.
"It is as much a capacity-building exercise as it is a vaccine exercise," Sandstrom said. "The trial will not be performed as many others, that we take the specimens back to Sweden or any other country. They will be performed locally, and the local investigators will be performing the test."
Pharmaceutical companies may not be quite so altruistic, but they may still have a powerful reason for sticking to ethical practices.
"It's not in anyone's interest to do anything that would ultimately result in a drug being recalled," said a spokeswoman for Pfizer, Kate Robins. "You wouldn't spend a billion dollars if you're going to cut corners and it's going to ultimately be recalled."
"You're going to go into places where you can hold up to standards that are international," she said. "There is no easier, softer way. There just isn't."
International Herald Tribune
For drug companies, globalization has brought a double boon: new markets and new testing grounds for clinical trials. Better information technology and transport infrastructure have made monitoring the ethics of those trials somewhat easier, but experts say problems are still proliferating. One Swedish-Tanzanian trial of an HIV vaccine seems to be doing things right, however.
The issue of unethical testing in developing countries received extra attention with the release last year of "The Constant Gardener," a film based on John Le Carré's novel about a Western company using Kenyans as unknowing guinea pigs for a tuberculosis drug. But real-life cases of questionable behavior have been popping up with increasing frequency, too.
Pfizer, based in New York, tested a meningitis drug called trovafloxacin in Nigeria in 1996, during an epidemic of the killer infection. Later, Nigerian families sued the company in the United States, saying their children had been entered into the study without their consent. The cases collapsed last summer over technical and jurisdictional details.
More recently, the American military's Walter Reed Army Institute of Research and GlaxoSmithKline of Britain came under fire for testing a hepatitis E drug on thousands of Nepalese soldiers. The researchers first tried to test the drug on civilians in Lalitpur, but rumors of bribes led to protests. Later, experts started asking whether the soldiers - many of whom may have been illiterate - could have understood the consent agreements they had signed and whether the effective but expensive drug would ever be available to Nepalese.
"Companies in the later clinical phases of drug development are increasingly going to developing countries, for example India, where it is basically cheaper to do it," said Dr. Hans Hogerzeil, director of medicine policy and standards at the World Health Organization in Geneva. "You have a huge number of treatment-naïve patients who have never been treated before and a lot of highly educated people and good infrastructure."
India is not the only popular destination for Western drug companies, however. Eastern Europe, Thailand, China, Brazil and Argentina are also favorite locations for trials, said Peter Lurie, deputy director of the health research group at Public Citizen, a watchdog organization in Washington.
"Before, you couldn't get back and forth to these countries the way you can now," Lurie said. "You couldn't share data electronically the way you can now. Even if people had the temptation to go overseas before because of less regulation, more compliant populations or study designs that they couldn't pull off locally, logistically it was not possible until recently. That's where globalization comes in."
Globalization has also made monitoring overseas trials easier, Lurie added, but the problem is still a long way from being solved.
"A given study in Malawi is easier to monitor now than it was before," he said. "Still, the ability to monitor what's going on in Malawi is so poor that, over all, the ability to monitor the totality of studies that are going on in the world has gone down."
That is why it's important to have clear international guidelines, with national laws backing them up, Hogerzeil said. India has been making especially good progress in this area, he said. Yet even when those standards exist, practice does not always follow policy.
"The patient really has to be informed what is being asked," Hogerzeil said. "You have to sit there. You have to explain it to them. You have to have material written in the local language."
Lurie said that even drug trials undertaken by public and nonprofit agencies sometimes fell victim to ethical problems. Still, he said, these trials almost always meet one important criterion that often is missing from corporate trials: that the local population would actually be able to buy and benefit from the drug if it proved successful.
A clear example is the Swedish-Tanzanian effort to develop a DNA-based vaccine against HIV. A prototype vaccine was tested first on Swedish citizens to make sure it did not have harmful side effects. But the prototype is not intended to treat HIV in Sweden; it is aimed at the subtypes of HIV that are most prevalent in East Africa. Later, the researchers may use the same platform to treat other subtypes.
A decade ago, the research project, which received generous funding both from Sweden's official aid agency and from the Walter Reed institute, approached a group of Tanzanian policemen to gauge the prevalence of HIV, which was higher than in Sweden. Now, after lengthy consultations in Tanzania, the researchers have contacted the same group again to test the vaccine.
Transparency has been a hallmark of the trial, said Eric Sandstrom, a professor in the department of infectious diseases at Karolinska University Hospital in Stockholm and a director of the study. He noted that the research offered no guarantee of medical benefits.
"We are very clear on that point," he said. "Anybody who volunteers for the study does it for the good of the development of the vaccine. There is no reassurance that any vaccine today can offer any protection."
The trials, which are the latest part of a 20-year history of cooperation between the two countries, are also intended to build infrastructure.
"It is as much a capacity-building exercise as it is a vaccine exercise," Sandstrom said. "The trial will not be performed as many others, that we take the specimens back to Sweden or any other country. They will be performed locally, and the local investigators will be performing the test."
Pharmaceutical companies may not be quite so altruistic, but they may still have a powerful reason for sticking to ethical practices.
"It's not in anyone's interest to do anything that would ultimately result in a drug being recalled," said a spokeswoman for Pfizer, Kate Robins. "You wouldn't spend a billion dollars if you're going to cut corners and it's going to ultimately be recalled."
"You're going to go into places where you can hold up to standards that are international," she said. "There is no easier, softer way. There just isn't."
