Drug Discovery and Clinical Trials

Question 1

Drug Discovery

Answer 1

• Disease characterization
• Target selection & identification of “drug hits”
• Lead optimization
• Pharmacological profiling

Question 2

Pre-Clinical Development

Answer 2

In vitro and in vivo Animal models

• Pharmacokinetics & Toxicology
• Formulation & Synthesis scale up

Question 3

Clinical Development

Answer 3

Drug tested in human volunteers & patients

• Safety & Efficacy
• Pharmacokinetics & Toxicity

Question 4

Compound-centered approach to Drug Discovery

Answer 4

Compound with interesting activity and/or chemistry

Screen biological systems for interesting biological functional effects

Question 5

Target-centered approach to Drug Discovery

Answer 5

Identify protein target with known disease association/activity

Screen large chemical libraries to Identify drug hits that interact with target and modify activity

Question 6

Lead Optimization

Answer 6

Identified new drug lead may not have best properties for a drug. Develop chemically modified drug variants.

Screen for improved pharmacological profile.

Question 7

What is the goal of pre-clinical development?

Answer 7

To provide evidence that a drug is safe for future testing in humans

Question 8

What is safety pharmacology?

Answer 8

Evaluate drug using in vivo animal testing for the presence of any obvious acute systemic toxic effects
- two different species and two routes of administration

Question 9

No-effect dose

Answer 9

The maximum dose at which toxic effects are not seen

Question 10

LD50

Answer 10

The dose that kills 50% of animals

Question 11

What are the major steps in preclinical development?

Answer 11

A. Safety Pharmacology

B. Toxicology

C. Pharmacokinetic testing
- fully characterize pharmacokinetic parameters: ADME

D. Drug Interaction studies

• determine metabolism by CYP450 family members - identify any possible inhibitors of CYP450
• determine specificity for Drug Transporter proteins

E. Chemical & Pharmaceutical Development

Question 12

Investigational New Drug Application (IND)

Answer 12

Vehicle for providing evidence to the FDA that a new drug drug is a viable candidate for further development and appropriate for initial limited use in humans (i.e. “reasonably safe”)

Question 13

What are the components of the IND?

Answer 13

1. Animal Pharmacology and Toxicology data
2. Manufacturing information
3. Clinical Protocols and Investigator information

Question 14

Investigator IND

Answer 14

Request to study an unapproved drug

Question 15

Emergency use IND

Answer 15

Allows authorization of an experimental drug in an emergency situation for use in a single patient that has a serious or immediately life-threatening condition

Question 16

Treatment IND

Answer 16

Allows promising experimental drugs that have not yet been approved to be used in patients with serious or immediately life-threatening conditions where no other therapy is available and death is likely

Question 17

Institutional Review Board

Answer 17

Minimize potential risk to human subjects

Determine whether potential risk is reasonable relative to anticipated benefit

Question 18

Superiority Trial

Answer 18

Trial designed to demonstrate that one treatment is clinically superior to either placebo or another drug

Question 19

Non-inferiority Trial

Answer 19

A trial designed to demonstrate that one drug is not appreciably less effective than the standard

Question 20

Phase I Clinical Trial

Answer 20

20- 100 Healthy Volunteers

Is it safe? Tolerability PK

Question 21

Phase II Clinical Trial

Answer 21

100-200 Patients
Does it work in patients?
Dosing

Question 22

Phase III Clinical Trial

Answer 22

1,000-6,000 Patients

Does it work in large patient populations

Question 23

Phase IV Clinical Trial

Answer 23

Post- marketing Surveillance
Adverse effects
Interactions Compliance

Question 24

New Drug Application

Answer 24

NDA contains all pre-clinical and clinical data collected during a drug’s research & development and must be FDA approved to enter market

Question 25

What information must appear on the label?

Answer 25

Approved indications 
Clinical Pharmacology
- Dosage
- Adverse Reactions
- Contraindications
- Special warnings and precautions
e.g. not for pregnancy/specific condition

Question 26

What are the 3 classes of drug recalls and their meanings?

Answer 26

Class I: Reasonable probability that use of drug will cause serious adverse health consequences or death e.g. microbial contamination

Class II: Use of drug will cause temporary adverse health consequences, although probability of serious health consequences is remote

Class III: Use of drug is unlikely to cause adverse health consequences e.g. quantity packaging error

Question 27

How does marketing of a generic drug work once the patent is expired?

Answer 27

Once a patent has expired any company may submit an Abbreviated New Drug Application (ANDA) to allow marketing of a GENERIC VERSION of the drug with NO need to provide evidence of efficacy & safety