Prof VY Pre-clinical Research in Drug Discovery

Question 1

General approaches to conducting a study (3)

- what it means

Answer 1

1. Deductive
   - draw conclusions from data
   - may follow after inductive approach
2. Inductive
   - set up alternative hypotheses & devise experiment to draw conclusion
3. Empirical
   - discovery

Question 2

Alternative hypothesis definition

Answer 2

• indicates 2 possible alternatives

Question 3

Directional hypothesis definition

Answer 3

• determine the direction of the relationship between the independent variable & dependent variable

Question 4

Can a hypothesis be proven?

Answer 4

No

It can only be disproven

Question 5

Why is there a need to do “pilot study” ? (2)

Answer 5

• assess feasibility of the the study

- saves time & money

Question 6

How to differentiate “good” from “not so good” scientific paper? (4)

Answer 6

• clear & concisely written
• rationale & methods are sound
• findings are novel
• quantity & quality of the paper

Question 7

Common problems associated with poor studies? (4)

Answer 7

1. Failure to include adequate controls
2. Poor experimental design
3. Failure to recognise multiple causes underlying a phenomenon
   - confounders
4. Conclusion not completely warranted by the data

Question 8

Common problems associated with poor studies? (4)

Answer 8

1. Failure to include adequate controls
2. Poor experimental design
3. Failure to recognise multiple causes underlying a phenomenon
   - confounders
4. Conclusion not completely warranted by the data

Question 9

Types of controls (2)

Answer 9

1. Positive control

2. Negative control

Question 10

Importance of positive control (3)

Answer 10

• show that certain molecules required to be present to yield positive results
• to prove against false -ve
• sensitivity

Question 11

Importance of negative control (3)

Answer 11

• show that the absence of certain molecules that might interfere with the results
• to prove against false +ve
• specificity

Question 12

Why scientific research needs to include adequate controls?

Answer 12

To serve as positive & negative controls to prove sensitivity & specificity

Question 13

Sensitivity error

Answer 13

False -ve

Question 14

Specificity error

Answer 14

False +ve

Question 15

Poor experimental design examples (3)

Answer 15

• inadequate sample size
• irrational methods
• confounders not accounted for

Question 16

Poor experimental design examples (3)

Answer 16

• inadequate sample size
• irrational methods
• confounders not accounted for

Question 17

Independent variable meaning

Answer 17

• research variable

- variable that is changed

Question 18

Dependent variable meaning

Answer 18

• response to changes in independent variable

Question 19

Dependent variable meaning

Answer 19

• response to changes in independent variable

Question 20

Why is it difficult to control for the variables in the study? (3)

Answer 20

• complexity in biological phenomenon
• limited understanding of the variables that controls that may affect the study (dk which variable to control for)
• even if the variables are known, it is also difficult to control for all known variables
  eg even with in-bred mice with minimal genetic variations

Question 21

Can scientific papers claim to prove certain results?

Answer 21

• No as there are many variables that can cause the underlying phenomenon under investigation
• Hence, the study can only suggests the results obtained

Question 22

Drug discovery process (3)

Answer 22

1. Discovery/Screening
2. Pre-clinical trials
3. Clinical trials
   - 3 phases

Question 23

NCE

Answer 23

New Chemical Entity

Question 24

Discovery/Screening process (3)

Answer 24

• target identification
• lead generation
• lead optimisation

Question 25

Pre-clinical process (3)

Answer 25

• safety
• formulation
• biological activity

Question 26

3 Phases of clinical trials & what they assess

Answer 26

1. Phase l
   - safety & dose
2. Phase ll
   - safety & efficacy
   - 100-500 patients
3. Phase lll
   - safety & efficacy
   - 1,000-5,000 patients

Question 27

IND

Answer 27

Investigational New Drug

Question 28

How to improve R&D productivity? (2)

Answer 28

1. Improve R&D efficiency
   - more affordable drugs with less cost
   - optimise resources
   - input to output
2. Improve R&D efficacy
   - develop drugs that have more values for patients
   - output to outcomes

Question 29

Challenges of drug discovery process (4)

Answer 29

1. Rising R&D budget
2. Declining outputs of NCE
3. Misunderstanding on the benefits of technology
4. Profits > Benefits of medicinal community

Question 30

Misunderstanding on the benefits of technology (3)

Answer 30

Thought to be beneficial in the long run only
However, there are benefits in the early drug discovery process too
- develop useful fingerprints for disease sub-classification
- differentiate responders & non-responders
- improve drug discovery efficiency

Question 31

Current drug treatment & its effects (4)

Answer 31

1. Beneficial & non-toxic
2. Beneficial but toxic
3. Non-beneficial but non-toxic
4. Non-beneficial & toxic

Question 32

Current drug treatment & its effects (1+4)

Answer 32

Same diagnosis = same prescription

1. Beneficial & non-toxic
2. Beneficial but toxic
3. Non-beneficial but non-toxic
4. Non-beneficial & toxic

Question 33

Pre-clinical research main goal

Answer 33

• determine the drug ultimate safety & efficacy profile

Question 34

Regulations the pre-clinical studies must adhere to (1)

Answer 34

Good Laboratory Practices (GLP) for safety

Question 35

Pre-clinical data information of NCE required by FDA (3)

Answer 35

1. Pharmacological profile of the drug
2. Determine acute toxicities of the drug
   - at least on 2 species
3. Determine short-term toxicities of the drug
   - ranging from 2 weeks - 3 months

Question 36

Pre-clinical research on medical devices (3)

Answer 36

• might not need the additional tests (pharmacology, toxicities)
• can go directly to GLP testing for safety
• may undergo compatibility tests to show sustainability in a living model