Clinical Trials

Question 1

What are the principle 3 stages of drug development and ediscovery?

Answer 1

1. drug discovery
   - disease characterization
   - target selection and identification of drug hits
   - lead optimization
   - pharmacological profiling
2. Preclinical development
   - in vitro and in vivo animal models
   - pharmacokinetics and toxicology
   - formulation and synthesis scale up
3. clinical development
   - drug tested in human volunteers and patients
   - safety and efficacy
   - pharmacokinetics and toxicology

Question 2

WHat is the difference between compound centered approach and target centered approach?

Answer 2

compound: compound with interesting activity or chemistry–>screen for biological functional effects
target: identify protein target with known disease association–>screen large chemical libraries to identify drug hits that interact with target and modified activity

Question 3

What is the lead optimization drug development process?

Answer 3

1. identify new drug lead may not exhibit ideal drug properties
2. develop chemical modified drug variants
3. screen for improved pharmacological profile

–>New chemical entity: NCE

Question 4

What is the goal of pre-clinical development?

Answer 4

1. to provide evidence that a drug is safe for future testing in humans
   - -determine no effect dose and median lethal dose
2. toxicology
   - anti-target testing
3. Pharmacokinetic testing
   - ADME
4. Drug interaction studies
   - met by CYP 450 members
5. Chemical and Pharmaceutical Dev
   - chemical stability and how to scale up

Question 5

How does a new drug candidate become an approved new drug?

Answer 5

1. investigational new drug application (IND)
2. FDA IND review
3. IRB Review ethics
4. clinical trial: Phase 1,2,3
5. New Drug Application (NDA)
6. FDA and NDA review

Question 6

What does the FDA do in the drug approval process?

Answer 6

CDER

• make sure drugs are safe and effective
• review all applications for new and generic drugs
• monitor the compliance of pharm manuf with current good manufacturing practice

Question 7

Emergency IND vs treatment IND vs investigator IND

Answer 7

emergency: single patient life threat
treatments: patients life threat
Investigator: request to study an unapproved drug

Question 8

IRB

Answer 8

• all clinical trials must be reviewed, approved and monitored by an IRB
• > 5 experts +lay members
• ensure rights and welfare of those participating in the clinical trials
• document informed consent

Question 9

What is the purpose of an IND and the major required components?

Answer 9

-vehicle for providing evidence to the FDA that a new drug is a viable candidate and reasonably safe

1. Animal pharmacology and toxicological data (saying its likely to be safe)
2. Manufacturing info (stable and consistently man)
3. clinical protocol and investigator information

Question 10

What are the 
-number of part
-setting
-typical trail design 
-endpoints
-primary objective 
of phase 1?

Answer 10

1. Phase 1
   - 20-100
   - Healthy volunteers
   - Inpatient
   - open label with escalating dosing
   - Is it safe, tolerability, PK

Question 11

What are the 
-number of part
-setting
-typical trail design 
-endpoints
-primary objective 
of phase 2?

Answer 11

2. Phase 2
   - 100-200
   - patients
   - either single or double blind random controlled trial, evaluated against placebo or standard of care
   - does it work and safety and dosing
   - endpoint-either:
   a. definitive endpoint: actual goal of therapy
   b. surrogate end point-associated with disease

Question 12

What are the 
-number of part
-setting
-typical trail design 
-endpoints
-primary objective 
of phase 3?

Answer 12

3. Phase 3
   - 1,000-6,000 patients
   - reflect the final target population
   - double blind randomized control
   - multiple clinical site similar setting to where it will be used
   - does it work in large populations, efficacy and safety
   - definitive or surrogate endpoint

——-Regulatory Approval

Question 13

What are the 
-number of part
-setting
-typical trail design 
-endpoints
-primary objective 
of phase 4?

Answer 13

4. Phase 4
   - post marketing surveillance
   - adverse effects, interactions, compliance

Question 14

What is the purpose of an NDA?

Answer 14

• contains all preclinical and clinical data collected during a drugs research and development
• either approved, not approved, or approvable

Question 15

What are the FDA approved data that must be included on the approved drug packing label?

Answer 15

approved indications
clinical pharmacology
-dosage
-adverse reactions
-contraindications
-special warnings

Question 16

What are the three classes of drug recall?

Answer 16

class 1: reasonable prob that use of the drug will cause serious adverse health consequences or death
-eg microbial contam

class2: use of drug will cause temp adverse health consequences, although prob of serious health consequences is remote

Class 3: use of drug is unlikely to cause adverse health cons
-eg quantity packaging error

Question 17

What clinical pharm info needs to be provided to get approved as generic drug?

Answer 17

bioequivalence

• equal active ingredients
• comparative pharmacokinetics and dynamics
• similar rate and extent of absorption into the blood
• GMP compliance with manufacturing process and facilities

Question 18

What is alternative strategy to this whole process?

Answer 18

drug repurposing

• just need to show efficacy
• dont need lengthy pre-clinical studies