Still, GSK and Walter Reed went ahead with phase II trials and wanted to test the candidate vaccine on 8,000 Nepalese volunteers in Lalitpur, without a plan to further develop the vaccine and make it available to the local population if the trials were successful. The Nepalese NGO Lumanti and municipal officers protested against the tests in Lalitpur because the majority of its population is illiterate and highly vulnerable.Walter Reed then decided to test the vaccine on 2,000 soldiers offered by the Royal Nepalese Army as volunteers. However, the soldiers were also considered a vulnerable group as they are poor and potentially subject to coercion by their superiors.
12 Jan 2006
Nepal questions US Army vaccine experiments
ISN SECURITY WATCH (12/01/06) – As US pharmaceutical company GlaxoSmithKline announces that its new hepatitis vaccine has been found 96 per cent effective, medical researchers are questioning whether the vaccine experiments, conducted on 2,000 Nepalese soldiers from 2001 to 2003, were ethical.
Concerned about the outbreak of hepatitis E in developing countries like Afghanistan and Uzbekistan, where US troops are deployed, the US National Institutes of Health developed a hepatitis E vaccine in the early 1990s, but needed to prove its safety and effectiveness through clinical trials.
In 1995, the US Armed Forces Research Institute of Medical Sciences (AFRIMS), the Thai-based branch of the Walter Reed Army Institute of Research, set up a field station in the Nepalese capital, Kathmandu, to test the vaccine patented by Californian company Genelabs and licensed by GlaxoSmithKline.
After a safety test on 88 US volunteers and 44 Nepalese civilians in February 2000, the Walter Reed/AFRIMS Research Unit Nepal (WARUN) announced it would test the vaccine on 8,000 Nepalese civilian volunteers in Lalitpur, one of the three municipalities comprising Kathmandu valley.
However, the attempt triggered an outcry by Lumanti, a Nepalese nongovernmental organization working with the urban poor, some municipal officials, and the media.
The volunteers were said to be mostly poor slum dwellers with almost zero literacy. The then-deputy mayor, Ramesh Chitrakar, was reported as saying that the mayor had given his consent to the trial without consulting other officials and that the researchers had offered him watches and other luxury items in return.
The ensuing protests forced WARUN to instead test the vaccine on the Royal Nepalese Army (RNA), which offered 2,000 soldiers as volunteers for the experiment.
The experiments were concluded in the army hospital in Kathmandu, which is inaccessible to the public, in 2003.
However, the issue was raised again last month when GlaxoSmithKline announced at an international tropical medical conference that the new vaccine had been found to be 96 per cent effective.
A group of medical researchers in the US is now asking how ethical it was to use as “guinea pigs” RNA soldiers, who come from poor families and are in no position to object to any order given to them by senior officials.
Also, there is no indication how the vaccine will benefit the volunteers or the community. Nepal is one of the poorest countries in the world and the new vaccine may not be easily available or affordable.
In the 1980s, the Walter Reed Army Institute of Research sponsored the development of a typhoid vaccine in Nepal, but the vaccine is not widely used in the Himalayan kingdom.
The US has been one of the major military assistance providers to Nepal, having granted over US$29 million in foreign military aid since 2001. Observers say the RNA was not likely in a position to refuse WARUN’s request.
US medical student Jason Andrews wrote in The American Journal of Bioethics: “Noting the millions of dollars, military training, and arms that the [US] State Department and military have been giving to the RNA to help them put down the Maoist rebellion, it seems plausible that the resultant military and economic dependence of the host institution/population [RNA] upon the research sponsor [the US military] threatened the voluntary nature of the institutional and individual participation in the trial.”
Dr. Mathura Prasad Shrestha, a former Nepalese health minister and chair of the Nepal Health Research Council at the time the 44 civilians were given the vaccine in Nepal, told ISN Security Watch the test on the RNA soldiers “violated international ethics”.
“People living in military barracks, asylums, and children belong to the vulnerable groups,” he said. “Also those who are illiterate and the poorest of the poor. Trials should be conducted only on people who are fully in the know, understand the implications, and have the option to say ‘no’.”
Shrestha also alleges WARUN “misrepresented” data. “Instead of segregating data for the prevalence of different categories of hepatitis, they clubbed it together to show a high incidence and create urgency,” he said.
However, the US embassy in Kathmandu strongly defended the trial, saying it was conducted in compliance with international practices.
“The military population was selected because they were known to have many cases of hepatitis E,” the embassy told ISN Security Watch.
“The soldiers were fully informed about the trial and potential risks and possible benefits of vaccination. We know of no link between US Army medical research activities and US military aid to Nepal.
“AFRIMS has historically maintained good relationships with Nepalese physicians, scientists and governmental agencies […] There was interest on the part of the Nepalese medical community to develop a vaccine for this disease,” the embassy said.
Still, it remains unclear whether the vaccine will be available in Nepal at an affordable price.
The embassy said the US government did not manufacture any drugs or vaccines for commercial sales.
“It is unclear from our perspective how GlaxoSmithKline will pursue marketing and distribution strategies,” the embassy said.
NEPAL: Guinea Pigs in Hepatitis E Vaccine Trials
– The best way to prevent water-borne diseases is to provide people with clean water-that seems obvious. So when Dr. Sharad Onta saw United States researchers arrive in Nepal to test a vaccine for hepatitis E on local people, he started asking why the money was not being spent on that simple solution.
Now, a decade later, the company licensed to market a hepatitis-E vaccine (HEV) developed by the U.S. military, says the Nepal clinical trials were successful and it is close to marketing it. That has revived a debate over whether Nepali citizens had been used as guinea pigs for the research.
Did the people being tested clearly understand what their bodies were being used for? Will they, and other Nepalis, benefit? And, Onta’s concern: should money have been spent on creating a vaccine when it could have gone to providing the safe drinking water that is lacking in much of this poor South Asian nation?
The field trials were organised by the Thailand office of the U.S. Armed Forces Research Institute of Medical Sciences, which set up the Walter Reed-AFRIMS Research Unit Nepal (WARUN) in Kathmandu in 1995.
Hepatitis E accounts for half of all hepatitis cases in developing countries like Afghanistan, where the U.S. military is active. People in the 16-40 age group (or soldiering age) are particularly vulnerable to the virus.
Those affected are sick for two-six weeks with nausea, vomiting, fever, abdominal pain and fatigue. A vaccine was developed by the U.S. National Institutes of Health and the first field trials were carried out on 88 U.S. citizens and 44 Nepalis living in Lalitpur, next to the capital Kathmandu, in 1998. Nepal was chosen because HEV is endemic here.
For instance, researchers studied an epidemic that hit the Kathmandu Valley in 1981-1982. Nearly eight percent of households among the population of more than one million people were affected. The 15-34 age group made up 70 percent of cases and a fifth of pregnant women admitted to hospital died. “No single water source was implicated, but epidemic peaks occurred during monsoon rains,” concluded researchers.
Such findings illustrate why efforts should have focussed on supplying safe drinking water, Onta, associate professor in the department of community medicine in Tribhuvan University’s Institute of Medicine, told IPS. “We cannot always depend on a vaccine, but we could be protected via safe drinking water, which would eliminate many other health risks as well as hepatitis E,” he said.
In fact, the Nepali government received millions of dollars to provide clean water, notably from the World Bank, during the United Nations Decade of Safe Drinking Water (1981-90) but “afterwards the situation was the same”, according to Onta. Thailand, on the other hand, used the opportunity to eliminate its hepatitis E problem, he added.
In Nepal’s rural areas-more than 80 percent of the country – about one-third of the deaths of children under five are caused by water-borne diseases, according to various reports. More than 20,000 children here die of diarrhoea every year.
The results of the U.S.-Nepal trials were encouraging so WARUN readied a second, larger study on 2,000-3,000 locals of Lalitpur. But Onta and others began questioning the need for such research and the ethics of how it was being done.
Soon the media and non-governmental organizations (NGOs) heard of the plans and encouraged more queries. Ultimately the field trial was moved from Lalitpur to Kathmandu when WARUN teamed up with the Nepali Army.
“We’re not against participating in research-there have been other trials in the past. We (Nepalis) use vaccines that are developed in other countries. But if the vaccine is tested and tried in this country, minimum standards should apply,” says Onta. “Many of the people in (Lalitpur) knew nothing about the vaccines; they weren’t even clear about why their blood was being taken.”
The researchers approached Nepal’s National Health Research Council (NHRC) for guidance. “They were saying ‘there’s a problem, we need help’. But probably at that time the NHRC told them, ‘there’s nothing we can do’, says Ramesh Kant Adhikary, chief of the NHRC’s ethical review committee, who had just joined the office when the debate arose. “We thought that the research was ethically OK but if the community dissented, that was OK too,” added Adhikary, Onta’s colleague and dean at the Institute of Medicine.
The researchers moved to Kathmandu’s military hospital where, from 2001 to 2003, 2,000 Nepali soldiers participated in the trial. One thousand of them received vaccine injections at the start, after one month and then six months. The remaining 1,000 soldiers got placebos. The research price-tag: one million dollars a year.
“You’ll have to ask the soldiers how much they understood about the tests,” says Lajana Manandhar, executive director of Lumanti, one of the NGOs that opposed the earlier research. “Our concern (in Lalitpur) was that the process followed was not ethical. The volunteers had signed an agreement without knowing what they had signed because they were illiterate or semi-illiterate,” she added in an interview.
According to Adhikary, “there was some confusion about whether a captive audience could be willing subjects. Theoretically, studies should not be done on convicts, soldiers and others who aren’t in a position to say ‘no’.” But, he added, “we went to the army, we talked to some of the recruits, casually as if we were just visiting doctors. They said they were asked and consented voluntarily.”
In December 2005, the company developing the HEV, U.S.-based GlaxoSmithKline, announced that it was 96 percent effective in trials and that it was taking the next steps to market the vaccine. The company’s media office did not reply to email requests for an interview.
Adhikary says that if the HEV proposal came to the NHRC today, it would be treated differently and according to the ‘National Ethical Guidelines for Health Research in Nepal’, published in 2001. “We would probably ask ‘how are you going to ensure that our people can make use of this vaccine’…if it is 60 dollars, what is the use for Nepali people?”
But too many queries and scepticism can also scare away important research, he argues. “We have to strike a balance between ethical principles, building the capacities of local researchers and the need for the research. How much can you compromise because you are a developing country? Will a researcher from a developed country want to embark on research in a country where he is treated as if he is not trusted?”
According to Manandhar of Lumanti, which works with slum dwellers and other poor urban residents, “we asked researchers: ‘why do you always go to the poor people? Why don’t you come to people like me and try to convince us’? They didn’t seem to have an answer.”