Pre-clinical trials

Question 1

What happened during the sulfanilamide disaster?

Answer 1

Was distributed without testing, and diethyl glycol caused over 100 deaths, many in children

Question 2

What is the drug regulatory agency in Canada?

Answer 2

Therapeutic products directorate

Question 3

What phase is supporting First Administration to Humans? What is a prerequisite?

Answer 3

Phase I

Happens after the IND/CTA is filed

Question 4

What 3 things do preclinical studies assess?

Answer 4

1. What does the body do to the drug?
2. What does the drug do to the body?
3. Risk benefit analysis?

Question 5

What is molecular attrition?

Answer 5

Start with a bunch of molecules and screen them for activity
Some enter non clinical testing
A couple enter clinical testing
One is approved by the FDA

Question 6

What is the critical aim on non-clinical trials?

Answer 6

Gathering evidence for the initial (phase I) studies in humans (clinical trials)

Question 7

What are the aims of preclincal trials?

Answer 7

No clinical data yet,
Identify major organs and systems that may be targets
Characterize dose and time relationships of AEs
Seek markers of activity/effect/toxicity

Question 8

What key info is gathered from safety/toxicity studies in animals?

Answer 8

Identify target organs and nature of toxicity
Information about mechanism
Dose-response profile
Time-response profile
**reversibility of toxic effects
Special safety monitoring needs in clinical trials

Question 9

How do we select the right species to do preclinical trials in?

Answer 9

Extensive historical database
Pharmacological relevance
Appropriate systemic exposure available
Metabolism of drug relevant to that in humans

Question 10

How are doses selected for clinical trials?

Answer 10

Dose response curves

NOAEL calculated

Question 11

What are alternatives to testing in animals?

Answer 11

In vitro toxicology (problem: difficulty demonstrating effects involving multiple organs or tissues)
In silico technology (computers)