Researchers compile systematic list of recommendations for investigational-drug studies

Fewer than 5% of promising basic science discoveries that claim clinical relevance lead to approved drugs within a decade, and only 11% of investigational drugs are ultimately licensed.

One possible reason for this dismal success rate is flawed pre-clinical 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. Dr. Daniel Hackam, assistant professor in clinical pharmacology, clinical neurological sciences and epidemiology and biostatistics at Western's Schulich School of Medicine & Dentistry, is a co-author.

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 had 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 patient volunteers. 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.

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.

"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."

Funding for the study was provided by the Canadian Institutes of Health Research.

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001489