Last updated April 6, 2018 at 9:30 am
We need to improve how we do animal studies, for the sake of science.
The substandard design and reporting of animal studies is compromising the ethical review of human drug trials, according to international researchers.
In order to assess the potential effectiveness of a new drug being tested on humans for the first time, regulatory authorities and ethics committees consult documents called “investigator brochures”, which contain descriptions of studies where the same drug was tested on animals. Independently-assessed animal studies are therefore key to ensuring that human patients are not exposed to unnecessary risks while participating in medical trials.
But when researchers from Hannover Medical School in Germany and McGill University in Canada analysed investigator brochures from three prominent German medical research centres, they found a startling lack of quality.
“Our analysis shows that the vast majority of these documents lack the information needed to systematically appraise the strength of evidence supporting trials,” says Daniel Strech, professor of bioethics at Hannover Medical School and lead author of the research.
Substandard animal studies
Less than one fifth of the documents referenced animal studies that had undergone a peer-reviewed publication process — a standard process for almost all scientific journals, where impartial experts rigorously assess research to ensure quality.
Another fifth of the animal studies did not describe the use of standard scientific techniques such as sample size calculation, randomisation or blinding, which are usually employed to reduce bias.
Even more concerningly, out of the total of 700 animal studies analysed, only 4% did not show positive effects of the drug being tested. This rarity of ‘negative’ studies made Strech and his team suspicious.
“With a median group size of 8 animals, these studies had limited ability to measure treatment effects precisely,” says Susanne Wieschowski, a postdoctoral fellow at Hannover. “Chance alone should have resulted in more studies being negative — the imbalance strongly suggests publication bias.”
This bias could be intentionally used to gain funding and approval for human trials. Even if unintentional, it can still send clinical research down the wrong path, wasting time, money and resources and potentially putting the patients involved at risk.
We should do better
“Why do regulatory agencies and other bodies involved in risk-benefit assessment for early human research accept the current situation?” Strech asks. “Why do they not complain about the lack of information needed to critically appraise the rigour of the preclinical efficacy studies and about the concerning lack of efficacy studies demonstrating no effects?”
Strech is not the first to ask these questions. Researchers have long raised concerns about the rigour of preclinical (animal) trials and how this influences clinical (human) trials. Clinical trials are currently more strictly regulated than preclinical trials — a fact that this research team say must be changed in order to more clearly establish when a drug is ready for human trials.
The team strongly recommend that regulators should develop and enforce new standards to ensure that preclinical animal studies are rigorously planned, reviewed and published before human trials of new drugs begin.
The research is published in PLOS Biology.