Safety/Toxicology

Question 1

What must be considered during a risk assessment?

Answer 1

• Hazard identification
• Dose-response relationship
• Exposure assessment
• Risk characterization

Question 2

When is a risk-assessment needed?

Answer 2

OEL/EXP ≤ 1

Question 3

What is an uncertainty factor used for?

Answer 3

For extrapolation between intra-species and inter-species

Question 4

Which studies are performed before the clinical studies?

Answer 4

Non-clinical safety studies

Question 5

What are the objectives of phase 1 trials?

Answer 5

• Access tolerance/safety
• Define/describe pharmacokinetics and pharmacodynamic
• Explore drug metabolism and drug interactions
• Early measurement of drug activity

It involves less than 30 people.

Question 6

What are the objectives of phase 2 trials?

Answer 6

• Explore use for the targeted indication
• Estimate dosage for subsequent studies
• Provide basis for confirmatory study design, endpoints, methodologies

It involves around 100 volunteers and some patients.

Question 7

What are the objectives of phase 3 trials?

Answer 7

• Demonstrate / confirm efficacy
• Establish a safety profile
• Provide an adequate basis for assessing the benefit/risk relationship to support licensing

It involves around 1000 people.

Question 8

What are the objectives of phase 4 trials?

Answer 8

• Refine understanding of benefit/risk relationship in general or special populations
• Identify less common adverse effects

Question 9

What are exploratory clinical trials?

Answer 9

Clinical trials performed early in phase 1 prior to dose escalation, safety and tolerability trials.

Question 10

What kind of exploratory clinical trials can be performed?

Answer 10

• Microdose trials
• Single-dose trials at sub-therapeutic range or the anticipated therapeutic range
• Multi-dose trials

Question 11

Why and when is a repeated dose toxicity experiment performed?

Answer 11

It is performed to support the conduct of clinical trials, so it is a preclinical experiment.

Question 12

When are genotoxicity trials performed?

Answer 12

Some genotoxicity studies are performed prior to phase 1, but all must be performed prior to phase 2.

Question 13

What is an ames test?

Answer 13

A well characterized assay for gene mutations

Question 14

For which drugs should carcinogenicity studies be performed?

Answer 14

It should be performed for pharmaceuticals whose expected clinical use is continuous for at least 6 months

Question 15

When should the required carcinogenicity studies be completed?

Answer 15

It should be completed before the application for marketing approval

Question 16

Are carcinogenicity studies always required?

Answer 16

They are generally not needed for endogenous substances given as replacement therapy

Question 17

What are the problems with animal studies?

Answer 17

• Problems with extrapolation of data from animals to humans
• They are not sufficient to evaluate adverse drug reactions in humans

Question 18

Why is testing in humans necessary?

Answer 18

It provides information about the most common occurring adverse drug reaction

Question 19

What is the difference between an adverse event and an adverse drug reaction?

Answer 19

An adverse event is an untoward medical occurrence in a patient or clinical trial subject administered a medical product, which does not have a causal relationship with the treatment

Question 20

Which safety measures are noted in phase 1?

Answer 20

Adverse drug reactions and tolerability

Question 21

Which safety measures are noted in phase 2?

Answer 21

Adverse drug reactions and toxicity

Question 22

Which safety measures are noted in phase 3?

Answer 22

Adverse drug reaction, benefit/risk, SUSAR

Question 23

Who is phase 1 trials conducted on?

Answer 23

Healthy male volunteers

Question 24

Who is phase 1 trials conducted on?

Answer 24

Healthy male volunteers

Question 25

What is a clinical outcome / clinical endpoint?

Answer 25

Direct measure of whether people in the trial feel or function better or liver longer

Question 26

What are surrogate endpoints?

Answer 26

Measure of effect of a specific treatment that may correlate with a clinical endpoint but does not necessarily have a guaranteed relationship.

An example is cholesterol lowering drugs.

Question 27

When is benefit/risk performed?

Answer 27

During the clinical trial and post registration (Phase 4)