Ah vaccines… while there is an ongoing debate over them, there was at least one little-known case that arose late last year that should make one a little bit skeptical about the real interests of large entities and the impact that their funding has on the ethical inclination of researchers…
Professor Peter Beverly, a former principal research fellow at Oxford University (now retired), stated that in 2009 1,500 South African children had been given a tuberculosis vaccine known as MVA85A that had caused five of the six primates that it had been tested on to “die rather rapidly”.
“Certainly here in this experiment, there is no evidence whatsoever that this is an effective booster vaccine,” he said. The primate trials had gone on for only 10 months, in which time 5 out of 6 of the primates that had been given the new vaccine had to be euthanized, before a funding application was made to move onto clinical trials on babies. Almost half of 2800 babies would be given this experimental vaccine.
Professor Beverly notes that regulators were not informed of this statistic before approval was granted for the application. The University claims that it had shared all the necessary data with the South African regulators and that the vaccine had already passed the animal testing phase before this primate incident. In fact, it had apparently been tested on 424 people (adults, presumably?) before the primate study began in 2009. Oxford claimed that this group of primates had been infected with a particularly strong strain of TB. The university has however dropped the vaccine.
Regardless of its results on adult humans, and whatever the regulators in South Africa knew or did not know, the vaccine’s effects on primates should have been a red flag that further testing was necessary before it was administered to 1400 of the most vulnerable among us. How does a study go from 424 adults to 6 monkeys and then to 1400 babies?
Most damningly, the parents of these infants had not been informed of this failed primate trial; the information leaflets they were given made no mention of the failed trial and even claimed it was “safe and effective” in animals. The South African Regulator admitted that the wording “could be construed as misleading”. Poor, uneducated and intentionally deceived parents were compensated a whopping… 10 pounds for the test.
Two weeks ago the British Medical Journal concluded an investigation into the matter, calling for a tightening of the rules that regulated how animal research could be reported. The Oxford scientists were also accused of “cherry picking” scientific evidence by only caring to mention results that were favorable to their funding goals.
The investigators at the BMJ stated that they had “unearthed concerns about how the researchers, from Oxford University, used the results of animal studies selectively to gain funding and approval for human trials, publicly relying on claims that animal studies had shown the new vaccine to be protective while privately playing down or dismissing unsupportive experiments as “failed” or irrelevant. Disappointment at the apparent failure of animal models to predict the outcome of human trials has, in turn, led major funders of TB research to rethink their funding priorities, with allegations that this has slowed progress in the entire field.”
Professor Mike Turner of the Wellcome Trust, the second largest charitable foundation in the world, which funded the study, said clinical trials were carried out “to the highest standard”. “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,” he added.
“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,” he said, predictably playing down and dismissing the failed unsupportive experiment as irrelevant.
Thankfully the babies were apparently unharmed (though what long-run side effects will be observed remain unknown until they grow older) but were also left unprotected from TB anyway- similar numbers got infected by the disease to the control group (were the adults who were tested on also similarly unprotected? If so, why did they proceed with the babies knowing that the vaccine was ineffective?).
Professor Malcolm Macleod, of the University of Edinburgh, said, “We need to develop better and more systematic ways to establish when a drug is ready for clinical trials in humans – and importantly when it is not. Until our institutions recognize that their core purpose is to produce research of value to society they risk a slow decline in their reputation, and possibly a faster and more serious erosion of public trust in science.“
Jonathan Kimmelman, of McGill University in Canada, said the Oxford case was not an isolated one. “It’s widely recognized that animal studies intended to support drug development are often riddled with flaws in design and reporting,” he said.
Professor Peter Beverly has made several allegations against Professor Helen McShane, the person who developed this failed vaccine.
Of course, three Oxford-led investigations cleared her of any wrong-doing… and more:
“The third panel in 2016 not only cleared Professor McShane of any academic misconduct, but went so far as to add that on the basis of the vaccine’s proven safety in humans and positive phase 1 and phase 2A trials, it would have been unethical not to have proceeded with the phase 2 trials in infants.
“The time has come to stop the repeated repackaging of criticisms and allegations which independent(?) expert analysis has demonstrated to be without foundation.”
Helen McShane would publish a rebuttal to the investigation by the British Medical Journal. She mentions her potential conflicts of interest for writing the rebuttal: “I am supported by a diverse group of funders, including the Wellcome Trust, The Bill and Melinda Gates Foundation, Aeras and the European Commission, to develop new TB vaccines. MVA85A was developed in my laboratory.”