Dear members

I would like to hear your thoughts on what safety margins you believe we need when evaluating results from ex vivo action potential recordings (e.g. GP papillary muscle APD90).

Any references would also be greatly appreciated.

Also, how big an effect do you consider to be relevant?

Best regards, Morten - H. Lundbeck A/S

Webinar

I found the Webinar on ICH S9 very interesting and informative. The Panel discussion was particularly interesting to me. There seems to be a preference for rolling large molecule work into the Toxicology studies. Here are my questions.

1) If we perform Cardiovascular, CNS and Respiratory studies in toxicology studies, should the model all be tested with positive controls to indicate that the study design would detect an effect if it was present?

2) Are the standards for sensitivity the same for these add-ons to Toxicology studies the same as for safety pharmacology?

3) What would be a reasonable positive control study to show the sensitivity and specificity?

I look forward to your insights.

How do others handle the issue of loosing a telemetry animal in a 4×4 Latin square design. For example if you loose one animal after two doses and still have two additional dosing periods.

What is the current practice in the industry when this occurs? One suggestion was to substitute in an animal and simply finish out the study in the normal 4 doses. Another was to substitute in an animal and give 4 more doses. Yet another is to continue on with missing cells. What is your opinion or experience?

I would also like to get the perspective on how you feel these options might impact the statistics.

Prior to candidate recommendation from discovery, most groups conduct some sort of “ancillary” cardiovascular study. The question is in what model?

Could folks share the in vivo model or models that are typically used (eg. dog, monkey, rat, conscious/anesthetized, etc) to support the advancement of a compound into the toxicology phase of development.  Also, if any models used are established in the company, or outsourced.