Do chronic studies in two species provide significant value in drug development?
Chronic studies in rodent (6 months) and non rodent (9 months) are required for approval of a new drug. Results of these studies are not required until the NDA is submitted, i.e. all the clinical trials are complete. The results of these studies are rarely included in the drug label. Since we generally have subchronic data in two species and long-term exposures in carcinogenicity studies, are the required chronic studies adding to patient safety?
Regulatory and Safety Evaluation
Jordana Andrade
Yes! Chronic animal studies aim to observe the cumulative effects of repeated daily exposure and carcinogenicity. These are different endpoints than those observed in sub-chronic tests. And the use of different species is important since different species may respond in different ways, and the use of more than one species aims to minimize the failure rate of observing toxic effects.
Thomas W. Jones, Ph.D.
I am joining this party a bit late allowing me the opportunity reflect on the opinions of those that answered before me. My short answer to the question, as stated, is that these studies can be very important in providing additional insights regarding adverse effects of development candidate at a time when patient enrollment is expanding dramatically. I am also going to dissect the question a bit in order to emphasize the importance of performing these studies in two species (as an aside, I agree with Mary Ellen's comment that 6 mo studies in both species is sufficient). I have long felt that, as toxicologists, we have not done a good job of explaining the reasoning behind the two-species nonclinical testing paradigm making it easy for critics to question its utility. Without getting too deep in the analytical aspects of combination testing, a no-finding outcome in both test species enhances the Negative Predictive Value of the testing program and should provide assurance of target organ safety helping a development team manages low-level/frequency clinical safety signals of concern. On the other hand, a similar target organ-related nonclincal safety finding in both test species dramatically enhances the Positive Predictive Power of the testing combination and should raise significant concern regarding the relevance of similar human safety signals.
Mouse Doctor
Yes. No model system is perfect, thus appropriate testing in two species lends confidence to the results.
Mary Ellen Cosenza
The premise is incorrect. Chronic tox studies in two species are required to also support clinical trials of 3-months or longer duration. Carcinogenicity studies are not generally required until the NDA. The data over many years and collected by several expert working groups continues to support the use of two species (one rodent and one non-rodent) for investigation of small molecule drugs. In most cases 6-months is two species is probably sufficient.
Biologics and other modalities are a different question.
Biologics and other modalities are a different question.
SOUTERRA
Yes, chronic studies in two species provide significant value in drug development by providing a better understanding of long-term effects and safety profiles.
Saira siddique
Yes, it provides because chronic exposure means repeated doses for a specific duration..which not only tells about the protective effects but also the any other side effects of that novel drug. And different species have their own physiology and they behave differently to different drugs ..this species difference experiment also be more helpful in drug development
Rajat Sandhir