Prof VY Pre-clinical Research in Drug Discovery Flashcards

1
Q

General approaches to conducting a study (3)

- what it means

A
  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
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2
Q

Alternative hypothesis definition

A
  • indicates 2 possible alternatives
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3
Q

Directional hypothesis definition

A
  • determine the direction of the relationship between the independent variable & dependent variable
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4
Q

Can a hypothesis be proven?

A

No

It can only be disproven

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5
Q

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

A
  • assess feasibility of the the study

- saves time & money

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6
Q

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

A
  • clear & concisely written
  • rationale & methods are sound
  • findings are novel
  • quantity & quality of the paper
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7
Q

Common problems associated with poor studies? (4)

A
  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
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8
Q

Common problems associated with poor studies? (4)

A
  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
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9
Q

Types of controls (2)

A
  1. Positive control

2. Negative control

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10
Q

Importance of positive control (3)

A
  • show that certain molecules required to be present to yield positive results
  • to prove against false -ve
  • sensitivity
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11
Q

Importance of negative control (3)

A
  • show that the absence of certain molecules that might interfere with the results
  • to prove against false +ve
  • specificity
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12
Q

Why scientific research needs to include adequate controls?

A

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

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13
Q

Sensitivity error

A

False -ve

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14
Q

Specificity error

A

False +ve

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15
Q

Poor experimental design examples (3)

A
  • inadequate sample size
  • irrational methods
  • confounders not accounted for
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16
Q

Poor experimental design examples (3)

A
  • inadequate sample size
  • irrational methods
  • confounders not accounted for
17
Q

Independent variable meaning

A
  • research variable

- variable that is changed

18
Q

Dependent variable meaning

A
  • response to changes in independent variable
19
Q

Dependent variable meaning

A
  • response to changes in independent variable
20
Q

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

A
  • 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
21
Q

Can scientific papers claim to prove certain results?

A
  • No as there are many variables that can cause the underlying phenomenon under investigation
  • Hence, the study can only suggests the results obtained
22
Q

Drug discovery process (3)

A
  1. Discovery/Screening
  2. Pre-clinical trials
  3. Clinical trials
    - 3 phases
23
Q

NCE

A

New Chemical Entity

24
Q

Discovery/Screening process (3)

A
  • target identification
  • lead generation
  • lead optimisation
25
Q

Pre-clinical process (3)

A
  • safety
  • formulation
  • biological activity
26
Q

3 Phases of clinical trials & what they assess

A
  1. Phase l
    - safety & dose
  2. Phase ll
    - safety & efficacy
    - 100-500 patients
  3. Phase lll
    - safety & efficacy
    - 1,000-5,000 patients
27
Q

IND

A

Investigational New Drug

28
Q

How to improve R&D productivity? (2)

A
  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
29
Q

Challenges of drug discovery process (4)

A
  1. Rising R&D budget
  2. Declining outputs of NCE
  3. Misunderstanding on the benefits of technology
  4. Profits > Benefits of medicinal community
30
Q

Misunderstanding on the benefits of technology (3)

A

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

31
Q

Current drug treatment & its effects (4)

A
  1. Beneficial & non-toxic
  2. Beneficial but toxic
  3. Non-beneficial but non-toxic
  4. Non-beneficial & toxic
32
Q

Current drug treatment & its effects (1+4)

A

Same diagnosis = same prescription

  1. Beneficial & non-toxic
  2. Beneficial but toxic
  3. Non-beneficial but non-toxic
  4. Non-beneficial & toxic
33
Q

Pre-clinical research main goal

A
  • determine the drug ultimate safety & efficacy profile
34
Q

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

A

Good Laboratory Practices (GLP) for safety

35
Q

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

A
  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
36
Q

Pre-clinical research on medical devices (3)

A
  • 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