L11 Drug Discovery and Clinical Trials

Question 1

What are the three broad processes in the pathway to a new drug?

Answer 1

1. Drug discovery
2. Pre-clinical development
3. Clinical development

Question 2

What are the 4 major aspects of the drug discovery process?

Answer 2

1. Disease characterization
2. Target selection and identification of drug hits
3. Lead optimization
4. Pharmacological profiling

Question 3

What are the 3 major aspects of pre-clinical development?

Answer 3

1. In-vitro and in-vivo animal models
2. Pharmacokinetics and toxicology
3. Formulation and synthesis scale up

Question 4

What are the 3 major aspects of clinical development?

Answer 4

1. Clinical trials
2. Safety and efficacy
3. Pharmacokinetics and toxicity

Question 5

What are the two possible approaches to the drug discovery process?

Answer 5

1. Compound-centered

2. Target-centered

Question 6

What is the compound-centered approach?

Answer 6

Take a compound with interesting activity/chemistry and screen biological systems for interesting biological functional effects

Question 7

What is the target-centered approach?

Answer 7

Identify a protein target with known disease association/activity and screen large chemical libraries to identify drug hits that interact with the target and modify activity

Question 8

What happens in lead optimization?

Answer 8

A new drug lead is identified; it may not exhibit ideal drug properties. Chemically-modified variants are developed and screened for an increased pharmacological profile.

Question 9

What is the outcome of the lead optimization process?

Answer 9

New Chemical Entity (NCE)

Question 10

After a new drug lead is optimized, what happens?

Answer 10

It is tested for efficacy in pre-clinical animal and cellular models of disease.

Question 11

What is the primary role of the CDER?

Answer 11

Ensure all prescription and OTC drugs are safe and effective; review all applications for new and generic drugs; monitor compliance with good manufacturing practice

Question 12

Describe the process of a drug candidate becoming an approved new drug.

Answer 12

1. Investigational New Drug (IND) application
2. FDA IND review/IRB review
3. Clinical trial phase I, II, III
4. NDA
5. FDA NDA Review
6. New drug

Question 13

What provides exemption from the federal law that only approved drugs may be shipped across state lines?

Answer 13

Investigational New Drug (IND) Application

Question 14

What are the three types of investigational new drug application (IND)?

Answer 14

1. Investigator: study an unapproved drug/approved drug for new indication or some other change
2. Emergency use: authorizes an experimental drug for a single patient with a serious condition
3. Treatment: allows promising experimental drugs not yet approved to be used in patients with serious conditions

Question 15

What is a set of conditions that must be met in order to participate in a clinical trial?

Answer 15

Inclusion critera

Question 16

What are standards used to determine whether a person may or may not participate in a trial?

Answer 16

Exclusion criteria

Question 17

What is the gold standard trial for causality?

Answer 17

Randomized controlled clinical trial

Question 18

What is something not directly related to the endpoint that can influence the outcome?

Answer 18

Confounder

Question 19

What is a trial where both physician and patient know which treatment is administered?

Answer 19

Open label

Question 20

What is a trial designed to demonstrate that one treatment is clinically better to either the placebo or another drug?

Answer 20

Superiority trial

Question 21

What is a trial designed to demonstrate that one drug is not appreciably less effective than the standard therapy?

Answer 21

Non-inferiority trial

Question 22

What is done in a crossover study?

Answer 22

Alternating period of administration of placebo and test drug; reduces problems with confounders

Question 23

Describe the number and type of volunteer, the questions asked, and the length of time for a Phase I clinical trial.

Answer 23

1. 20-100 healthy volunteers
2. Is it safe and tolerable? What are the pharmacokinetic parameters?
3. Months

Question 24

Describe the number and type of volunteer, the questions asked, and the length of time for a Phase II clinical trial.

Answer 24

1. 100-200 patients
2. Does it work in patients? What is the appropriate dosing?
3. 1-2 years

Question 25

Describe the number and type of volunteer, the questions asked, and the length of time for a Phase III clinical trial.

Answer 25

1. 1000-6000 patients
2. Does it work in large patient populations?
3. 3-5 years

Question 26

What happens after Phase III trials?

Answer 26

Regulatory approval

Question 27

What is Phase IV?

Answer 27

Post-marketing surveillance for adverse effects, interactions, and complications

Question 28

What happens after the completion of Phase II trials?

Answer 28

FDA meets with the drug sponsor to establish the safety of proceeding with Phase III

Question 29

When does a drug withdrawal happen?

Answer 29

Unacceptable toxicity or new adverse reactions; manufacturer agrees to cease marketing

Question 30

What is a drug recall?

Answer 30

Temporary removal of a drug from the market

Question 31

What is a Class I recall?

Answer 31

Reasonable probability that use of drug will cause serious health consequences of death

Question 32

What is a Class II recall?

Answer 32

Use of drug will cause temporary adverse health conditions, although probability of serious health consequences is remote

Question 33

What is a Class III recall?

Answer 33

Use of drug is unlikely to cause adverse health consequences

Question 34

How long is patent protection for new drugs?

Answer 34

20 years

Question 35

What is an abbreviated new drug application used for?

Answer 35

Marketing of a generic version of the drug