A TB vaccine linked to the deaths of monkeys was given to 1‚400 babies in the Western Cape‚ a British Medical Journal investigation has found. But academics are at odds about whether the clinical trial in Worcester was irresponsible.
A TB vaccine linked to the deaths of monkeys was given to 1‚400 babies in the Western Cape‚ a British Medical Journal investigation has found.
But academics are at odds about whether the clinical trial in Worcester was irresponsible.
Information given to the parents of the babies between 2009 and 2011 said the vaccine had been tested on animals and was “shown to be safe and effective”.
It did not mention that five out of six macaque monkeys given the MVA85A vaccine at a UK lab died prematurely. However‚ this information was given to regulators and ethics committees who approved the trial.
In editorials‚ the journal called for new guidelines to improve the conduct‚ reporting and appraisal of animal research‚ and for a review of the use of animal data to underpin clinical trials in humans.
The director of the South African Tuberculosis Vaccine Initiative disagreed with the writer of the BMJ article‚ associate editor Deborah Cohen.
Professor Mark Hatherill said he had been an investigator in the R136-million Worcester trial and was “very proud of being involved”. None of the babies involved‚ who were between four and six months old at the time‚ had suffered any ill effects‚ he said.
“It was an excellent and meticulously planned trial. The research group at Oxford University took a particularly careful approach.
“In my view the Cohen article is flawed and one-sided in that it places more weight on results from five monkeys than on the positive evidence from 14 human trials involving more than 400 people who received MVA85A.
“This sensationalist approach is not what I would have expected from a respected journal like the BMJ.”
Hatherill‚ whose organisation is based at the University of Cape Town‚ with a satellite office in Worcester‚ has co-authored a riposte to Cohen’s article‚ which has been published in the BMJ.
The developers of the vaccine‚ who had funding from the Bill and Melinda Gates Foundation‚ hoped a single dose of MVA85A given to babies who had been vaccinated at birth with Bacille Calmette Guérin (BCG) shots would act as a booster and give them some extra protection. But it made no difference to their odds of getting infected with TB.
Oxford University‚ which later dropped the vaccine‚ said it provided the results of the monkey study to the Medicines Control Council and UCT’s human research ethics committee before the Worcester trial began. It had shown no safety issues in other animal studies – in mice‚ guinea pigs and cattle.
It had also been tested in 14 studies on humans‚ involving 400 adults‚ teenagers and children in South Africa‚ the UK and Gambia before it was given to infants.
The Oxford researchers said the macaque monkeys in the 2006 study at UK government laboratories died because a stronger version of TB was used. The animals had become “very unwell” and had to be euthanased.
But experts questioned by Cohen said that should not have stopped Oxford from telling Worcester parents about the results. They accused scientists of using a “pick and mix” approach to their findings.
Jonathan Kimmelman‚ of McGill University in Canada‚ said the Oxford case was not an isolated one. “It’s widely recognised that animal studies intended to support drug development are often riddled with flaws in design and reporting‚” he told the BMJ.
“Unfortunately‚ there are other cases where new treatments were put into human testing on animal evidence that was foreseeably flawed‚ incomplete‚ or even negative.”
Kevin Urdahl‚ a Washington University specialist in immune responses to TB‚ said the prevalent view among scientists at the time was that a large MVA85A efficacy trial in humans was needed.
“Yes‚ there were some people who questioned whether it should go forward and others who felt it should go forward‚ and I think reasonable people could differ on that‚” he said.
A series of allegations were made about the trial by a former employee‚ Professor Peter Beverley‚ against the scientist who developed the vaccine‚ Professor Helen McShane.
Three investigations by the university cleared her of wrongdoing and Professor Mike Turner of the Wellcome Trust‚ which also helped to fund the study‚ told the BMJ clinical trials were carried out “to the highest standard”.
He added: “The decision to test this candidate vaccine was correct and based on robust‚ positive data from smaller trials in humans that showed that the candidate vaccine was safe and that it might be effective.
“Human trials do not always generate the same results as animal testing‚ which is why results in animal models are typically only one of a set of considerations in determining whether to move research forward.”
McShane told the BMJ: “The important fact here is that the regulators and the ethics committees saw the raw data [on the macaques] eight months before we started the infant efficacy trial. They had ample opportunity to question the data and to query them if they wanted to.”
But Jimmy Volmink‚ dean of medicine at Stellenbosch University‚ told the BMJ he was worried about the way Worcester parents were told on a leaflet that MVA85A was “safe and effective” in animals.
“I have grave concerns about communicating the evidence in this particular way‚ especially given the context in which we work in South Africa‚” he said.
The communities where the trials were done were poor‚ and people were eager to take part because they hoped to receive beneficial treatments that otherwise would not be available.
“If these claims are misleading about possible protective effects of a vaccine‚ or if investigators play down the possibility of harm from exposure to the vaccine‚ I think that would be particularly egregious in this context and one might consider this a form of exploitation of a vulnerable population‚” he said.
McShane responded: “The information sheet was reviewed by the ethics committee and by the regulators. It is their job to determine whether or not what we say in that information sheet is an accurate representation of the facts.”
TB vaccine linked to monkey deaths given to 1‚400 SA babies
A TB vaccine linked to the deaths of monkeys was given to 1‚400 babies in the Western Cape‚ a British Medical Journal investigation has found. But academics are at odds about whether the clinical trial in Worcester was irresponsible.
A TB vaccine linked to the deaths of monkeys was given to 1‚400 babies in the Western Cape‚ a British Medical Journal investigation has found.
But academics are at odds about whether the clinical trial in Worcester was irresponsible.
Information given to the parents of the babies between 2009 and 2011 said the vaccine had been tested on animals and was “shown to be safe and effective”.
It did not mention that five out of six macaque monkeys given the MVA85A vaccine at a UK lab died prematurely. However‚ this information was given to regulators and ethics committees who approved the trial.
In editorials‚ the journal called for new guidelines to improve the conduct‚ reporting and appraisal of animal research‚ and for a review of the use of animal data to underpin clinical trials in humans.
The director of the South African Tuberculosis Vaccine Initiative disagreed with the writer of the BMJ article‚ associate editor Deborah Cohen.
Professor Mark Hatherill said he had been an investigator in the R136-million Worcester trial and was “very proud of being involved”. None of the babies involved‚ who were between four and six months old at the time‚ had suffered any ill effects‚ he said.
“It was an excellent and meticulously planned trial. The research group at Oxford University took a particularly careful approach.
“In my view the Cohen article is flawed and one-sided in that it places more weight on results from five monkeys than on the positive evidence from 14 human trials involving more than 400 people who received MVA85A.
“This sensationalist approach is not what I would have expected from a respected journal like the BMJ.”
Hatherill‚ whose organisation is based at the University of Cape Town‚ with a satellite office in Worcester‚ has co-authored a riposte to Cohen’s article‚ which has been published in the BMJ.
The developers of the vaccine‚ who had funding from the Bill and Melinda Gates Foundation‚ hoped a single dose of MVA85A given to babies who had been vaccinated at birth with Bacille Calmette Guérin (BCG) shots would act as a booster and give them some extra protection. But it made no difference to their odds of getting infected with TB.
Oxford University‚ which later dropped the vaccine‚ said it provided the results of the monkey study to the Medicines Control Council and UCT’s human research ethics committee before the Worcester trial began. It had shown no safety issues in other animal studies – in mice‚ guinea pigs and cattle.
It had also been tested in 14 studies on humans‚ involving 400 adults‚ teenagers and children in South Africa‚ the UK and Gambia before it was given to infants.
The Oxford researchers said the macaque monkeys in the 2006 study at UK government laboratories died because a stronger version of TB was used. The animals had become “very unwell” and had to be euthanased.
But experts questioned by Cohen said that should not have stopped Oxford from telling Worcester parents about the results. They accused scientists of using a “pick and mix” approach to their findings.
Jonathan Kimmelman‚ of McGill University in Canada‚ said the Oxford case was not an isolated one. “It’s widely recognised that animal studies intended to support drug development are often riddled with flaws in design and reporting‚” he told the BMJ.
“Unfortunately‚ there are other cases where new treatments were put into human testing on animal evidence that was foreseeably flawed‚ incomplete‚ or even negative.”
Kevin Urdahl‚ a Washington University specialist in immune responses to TB‚ said the prevalent view among scientists at the time was that a large MVA85A efficacy trial in humans was needed.
“Yes‚ there were some people who questioned whether it should go forward and others who felt it should go forward‚ and I think reasonable people could differ on that‚” he said.
A series of allegations were made about the trial by a former employee‚ Professor Peter Beverley‚ against the scientist who developed the vaccine‚ Professor Helen McShane.
Three investigations by the university cleared her of wrongdoing and Professor Mike Turner of the Wellcome Trust‚ which also helped to fund the study‚ told the BMJ clinical trials were carried out “to the highest standard”.
He added: “The decision to test this candidate vaccine was correct and based on robust‚ positive data from smaller trials in humans that showed that the candidate vaccine was safe and that it might be effective.
“Human trials do not always generate the same results as animal testing‚ which is why results in animal models are typically only one of a set of considerations in determining whether to move research forward.”
McShane told the BMJ: “The important fact here is that the regulators and the ethics committees saw the raw data [on the macaques] eight months before we started the infant efficacy trial. They had ample opportunity to question the data and to query them if they wanted to.”
But Jimmy Volmink‚ dean of medicine at Stellenbosch University‚ told the BMJ he was worried about the way Worcester parents were told on a leaflet that MVA85A was “safe and effective” in animals.
“I have grave concerns about communicating the evidence in this particular way‚ especially given the context in which we work in South Africa‚” he said.
The communities where the trials were done were poor‚ and people were eager to take part because they hoped to receive beneficial treatments that otherwise would not be available.
“If these claims are misleading about possible protective effects of a vaccine‚ or if investigators play down the possibility of harm from exposure to the vaccine‚ I think that would be particularly egregious in this context and one might consider this a form of exploitation of a vulnerable population‚” he said.
McShane responded: “The information sheet was reviewed by the ethics committee and by the regulators. It is their job to determine whether or not what we say in that information sheet is an accurate representation of the facts.”