New procedures to improve quality and usefulness of preclinical efficacy studies

Only 11% of drugs that enter clinical trials in humans are ultimately found safe and effective enough to receive regulatory approval.

One possible reason for this dismal success rate is flawed preclinical animal research. A number of recent initiatives seek to improve the design and execution of such experiments. Now, a new study led by Prof. Jonathan Kimmelman of McGill University identifies key procedures believed to address threats to the validity of preclinical findings.

The authors of the study, published this week in the journal PLOS Medicine, conducted a systematic literature search and identified 26 guidelines with 55 different procedures that groups of scientists have proposed to improve the quality and usefulness of preclinical efficacy studies for investigational drugs. They then summarized and prioritized the results.

Many of these recommendations aren't widely implemented in preclinical research. As a result, "It is quite possible that drugs are being advanced into clinical trials without reliable evidence that they are useful," Kimmelman says. "This is a problem, ethically, because trials are hugely expensive and involve burdens for patients. We're not learning all we can from the animal studies in drug development, and failed drug development means higher drug prices."

The key recommendations are contained in a new checklist, and include many procedures that are already used in human research, including use of appropriate sample sizes, use of randomization and blinding. Another key recommendation is matching animal models to the human manifestation of the disease. (If using mice to test a treatment for a childhood disease, for example, researchers should use juvenile mice.)

Kimmelman and Valerie C. Henderson, researchers in the Biomedical Ethics Unit and Experimental Medicine in McGill's Faculty of Medicine, co-authored the article with researchers from the Ottawa Hospital Research Institute, the University of Ottawa, and Western University, London, Ont.

"By identifying widely shared recommendations, we believe our analysis provides a more evidence-based rationale for design and interpretation of drug studies in animals," Kimmelman concludes. "Investigators, institutional review boards, journals, and funding agencies should give our recommendations due consideration when designing, evaluating, and sponsoring translational investigations."