David Jones and Walter Janssens tips on phase 1 applications
Posted by Andrew Smith on February 10, 2009
David Jones of the MHRA and Walter Janssens of the AFMPS gave their tips on successful applications for conducting phase 1 studies. Both stressed the importance of dose justification and presenting the relevent evidence clearly and without overloading the submission with superfluous information. Given the 14 day timeline and the fact that the MHRA receives a new application roughly every day, it is vital to present the right information clearly.
Both also mentioned the increasing importance of NOAEL (no observable adverse event level) dose over NOEL (no observable effect level) in dose calculations, with David saying he could not recall the last application he saw referring to NOEL.
David also discussed the importance of exploratory dose studies in bridging the gap between 100ug microdose studies and phase 1. He speculated that this would increase the number of drugs moving through into phase 1 but early proof of concept evidence might decrease the proportion of drugs failing in phase 2.
In response to another question, David Jones said that he isn’t a big fan of the US exploratory IND, feeling that it might be a bit ‘gung ho’.
Another questioner discussed speed of processing early phase applications. Both speakers said that the key step is the sponsor’s speed in responding to requests for additional information. Both speakers’ regulators benefit from having dedicated clinical trials units, and are able to prioritise these assessments, in contrast to smaller regulators who might have to balance this activity with reviewing marketing applications etc.
The final question of the session asked about transgenic animal models. While David had expressed concern about animal homologue models rather than higher animal models, he is starting to see more extensive work in this area. Inducing a disease state in an animal can make the model far more predictive of the potential for a new drug. However, there are not yet enough good biomarkers for use in this type of study. Walter Janssens added that we have very little experience with the kinetics, survival etc of transgenic or diseased state animals, which can make interpreting the resulting data more complicated.
