According to an article published recently, officers from the US Food and Drug Administration (FDA) say that studies looking at the effects of drugs in young animal populations in contrast to their effects in adult animals are usually not helpful in guiding pediatric clinical development, particularly if such research is the basis for the launch of a clinical trial.
The authors of the article, John Leighton, Haleh Saber, Gregory Reaman and Richard Pazdur, of US FDA’s Office of Hematology and Oncology Products (OHOP) in the Center for Drug Evaluation and Research, arrived at their conclusion after analyzing data from both publicly accessible and non-public young animal studies presented to the FDA to support pediatric oncology research.
FDA and ICH Guidance
In 2006, FDA released its guidance, Nonclinical Safety Evaluation of Pediatric Drug Products, to assist sponsors design non-clinical research in animals to evaluate whether drugs’ effects are distinct in children in comparison to adults, in scenarios where it would be unethical or complicated to evaluate in pediatric studies.
Later, in 2010, the International Conference on Harmonization (ICH) designed its guidance, ICH S9: Nonclinical Evaluation for Anticancer Pharmaceuticals, which makes suggestions on what kinds of non-clinical research need to be performed prior to evaluating cancer drugs in humans. The ICH guidance favors expediency in launching pediatric participation in Phase I studies, saying, “research in young or immature animals are not generally performed to be able to support the inclusion of pediatric communities for cancer treatment.”
ICH’s suggestions are based on the rationale that data from adult sufferers and enhanced safety monitoring can offset the danger to pediatric patients registering in these studies, given the life-threatening nature of their condition.
Various recent papers have taken distinct views of the value of young animal studies used to support pediatric clinical studies. Two papers, The value of juvenile animal studies: “What have we learned from preclinical juvenile toxicity studies? II” and Juvenile animal testing in drug development–is it useful? discuss whether such studies offer helpful or actionable data, while one more paper, Use of juvenile animal studies to support oncology medicine development in children, states that the data are helpful, as nearly a one-fourth of drugs the author analyzed revealed some variations in toxicity among adult and young animals.
FDA Retrospective Analysis
To address these different viewpoints, OHOP analyzed the research pointed out by Duarte, along with non-publicly accessible studies presented to the FDA by sponsors developing cancer drugs.
“After analyzing accessible JAS data, and taking into consideration factors like the short life expectancy and the severe nature of the disease, OHOP came to the conclusion that juvenile animal studies performed to date have not offered beneficial information to support [first-in-pediatric] development for anticancer medicines, consistent with the suggestions outlined in ICH S9,” they write.
In addition, the authors identified that data from juvenile animal research did not impact how pediatric studies were performed, nor did they guide dose selection. In some situations, they write, the only effects recognized by juvenile animal research were already predicted or earlier explained in the literature.
With respect to FDA’s 2006 guidance, the one of the main goals of performing juvenile / young animal research is to identify whether medicines might have an effect on a child’s growth and development. On the other hand, because of the short life expectancy of pediatric oncology sufferers, the long-term follow up that this would require is “difficult, if at all possible.”
However, the authors say juvenile animal researches are helpful at times when “clinical and/or nonclinical data available do not offer adequate details on toxicities,” but should be performed to “address a particular safety issue.”