Medical studies in humans often launched on faulty evidence base

(Reuters Health) - New research reveals serious flaws in the animal studies that regulators and ethicists use to decide if an experimental drug should be tested in humans.

Dr. Daniel Strech, a bioethicist and professor at Hannover Medical School in Germany and his colleagues are the first to take an independent look at so-called investigator brochures (IBs), which regulatory agencies review to weigh the risks and benefits of the experimental treatment and determine whether trials in humans should move forward.

“The way the animal studies are currently reported in the investigator brochures really strongly compromises this risk-benefit assessment,” Strech told Reuters Health in a telephone interview. “It’s hard to see how people can really do meaningful risk-benefit assessments based on the animal studies the way they are reported.”

Other investigators have found - by looking at published research and study protocols - that research in animals often doesn’t include important analyses that can make the results less biased. These elements include sample size calculation, that is, determining beforehand whether the study includes enough animals to draw statistically valid conclusions; randomization of animals to treatment and control groups; and blinding, or making sure that the investigators who assess the effects of treatment don’t know which animal received the compound being tested.

In the new study, Strech and his team reviewed 109 IBs approved by three institutional review boards in Germany in 2010-2016, which cited 708 animal studies. Half of the studies included no more than eight animals. Less than 5 percent reported randomization, sample size outcome or blinded assessment. Only 11 percent of the studies referred to published, peer-reviewed reports of preclinical efficacy.

The new analysis, published in PLoS Biology, can’t answer the question of why investigators submit such poor quality data, and why reviewers accept it, Strech noted. But from his own conversations, “the feeling I got was that ethics committees and agencies don’t really look at the preclinical efficacy data.”

Regulators focus on data about a drug’s toxicity and safety instead, he added. “They more or less trust that the funders of the clinical trial, the industry and the investigators, that they would never do a clinical study unless they were very convinced that the drug would be effective.”

Almost half of the studies in the analysis were funded by one of the 25 largest pharmaceutical companies, Strech noted, and many included research teams from outside Germany, so this is likely to be a worldwide problem.

“I would argue that the burden of proof is rather on those that would say that the picture is completely different in the United States or the UK or elsewhere,” he said.

SOURCE: PLoS Biology, online April 5, 2018.