Animal drug testing: Study calls for ‘urgent action’ over quality and regulation of studies

Researchers “misrepresented” the results of animal studies in order to obtain funding and approval for human trials for a new tuberculosis vaccine, a study claims.

The investigation by the British Medical Journal examined MVA85A, a vaccine developed by a team at Oxford University which supposedly boosted the efficacy of the BCG vaccine to provide greater protection against Tuberculosis.

The drug was reported to have been effective in animal studies, but subsequently failed to show a benefit when tested in a large clinical trial in South African infants in 2009.

The concerns over methodology prompted an independent review in 2015 which concluded the results of the animal studies had been overstated.

It was also claimed that prior to human testing, a small scale trial on monkeys “should have raised doubts” about the efficacy of the drug, but the trials went ahead nonetheless.

According to the BMJ, the Oxford researchers publicly claimed the animal trials had been effective, but “played down their significance when speaking privately”.

The study, led by the BMJ’s associate editor, Dr Deborah Cohen, said the investigation highlighted the “pick and mix” approach to animal research, and raised serious questions about oversight and transparency, as well as unaccountable regulatory decision making.

She said it also revealed a lack of clarity about what data was required when deciding to move from animal (preclinical) studies to human (clinical) trials.

The BMJ said as a result of the concerns over how animal tests were used to bolster the case for MVA85A funding, major sponsors of TB research are now rethinking their funding priorities, with allegations that this has slowed progress in the entire field.

But Professor Ewan McKendrick, registrar of Oxford University, dismissed the allegations, saying "independent expert analysis has demonstrated [the claims] to be without foundation".

Three separate investigations by Oxford University cleared the researchers of "any wrong-doing", he added.

And the team behind the research said the MVA85A programme "observed the highest scientific and ethical standards, aiming to improve global control of the world’s most lethal infectious disease".

In a statement seen by The Independent, the researchers said the "misleading" accusations in the BMJ "fail to distinguish between a lengthy academic disagreement and scientific misconduct".

However, Jonathan Kimmelman, associate professor in the biomedical ethics unit at McGill University in Canada, told the journal the concerns over MVA85A were not an isolated case.

“It’s widely recognised that animal studies intended to support drug development are often riddled with flaws in design and reporting,” he said.

“But it sometimes feels as if regulators and ethics committees missed the memo. Unfortunately, there are other cases where new treatments were put into human testing on animal evidence that was foreseeably flawed, incomplete, or even negative.”

Malcolm Macleod, professor of neurology and translational neuroscience at the University of Edinburgh, said a more rigorous approach was required in establishing when a drug is ready for clinical trials.

He said the case also raised questions about how researchers and institutions respond to criticism.

“Until our institutions recognise 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.

“In these troubled times, that public trust is more important than ever.”