Prof VY Pre-clinical Research in Drug Discovery Flashcards
General approaches to conducting a study (3)
- what it means
- Deductive
- draw conclusions from data
- may follow after inductive approach - Inductive
- set up alternative hypotheses & devise experiment to draw conclusion - Empirical
- discovery
Alternative hypothesis definition
- indicates 2 possible alternatives
Directional hypothesis definition
- determine the direction of the relationship between the independent variable & dependent variable
Can a hypothesis be proven?
No
It can only be disproven
Why is there a need to do “pilot study” ? (2)
- assess feasibility of the the study
- saves time & money
How to differentiate “good” from “not so good” scientific paper? (4)
- clear & concisely written
- rationale & methods are sound
- findings are novel
- quantity & quality of the paper
Common problems associated with poor studies? (4)
- Failure to include adequate controls
- Poor experimental design
- Failure to recognise multiple causes underlying a phenomenon
- confounders - Conclusion not completely warranted by the data
Common problems associated with poor studies? (4)
- Failure to include adequate controls
- Poor experimental design
- Failure to recognise multiple causes underlying a phenomenon
- confounders - Conclusion not completely warranted by the data
Types of controls (2)
- Positive control
2. Negative control
Importance of positive control (3)
- show that certain molecules required to be present to yield positive results
- to prove against false -ve
- sensitivity
Importance of negative control (3)
- show that the absence of certain molecules that might interfere with the results
- to prove against false +ve
- specificity
Why scientific research needs to include adequate controls?
To serve as positive & negative controls to prove sensitivity & specificity
Sensitivity error
False -ve
Specificity error
False +ve
Poor experimental design examples (3)
- inadequate sample size
- irrational methods
- confounders not accounted for
Poor experimental design examples (3)
- inadequate sample size
- irrational methods
- confounders not accounted for
Independent variable meaning
- research variable
- variable that is changed
Dependent variable meaning
- response to changes in independent variable
Dependent variable meaning
- response to changes in independent variable
Why is it difficult to control for the variables in the study? (3)
- 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
Can scientific papers claim to prove certain results?
- No as there are many variables that can cause the underlying phenomenon under investigation
- Hence, the study can only suggests the results obtained
Drug discovery process (3)
- Discovery/Screening
- Pre-clinical trials
- Clinical trials
- 3 phases
NCE
New Chemical Entity
Discovery/Screening process (3)
- target identification
- lead generation
- lead optimisation
Pre-clinical process (3)
- safety
- formulation
- biological activity
3 Phases of clinical trials & what they assess
- Phase l
- safety & dose - Phase ll
- safety & efficacy
- 100-500 patients - Phase lll
- safety & efficacy
- 1,000-5,000 patients
IND
Investigational New Drug
How to improve R&D productivity? (2)
- Improve R&D efficiency
- more affordable drugs with less cost
- optimise resources
- input to output - Improve R&D efficacy
- develop drugs that have more values for patients
- output to outcomes
Challenges of drug discovery process (4)
- Rising R&D budget
- Declining outputs of NCE
- Misunderstanding on the benefits of technology
- Profits > Benefits of medicinal community
Misunderstanding on the benefits of technology (3)
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
Current drug treatment & its effects (4)
- Beneficial & non-toxic
- Beneficial but toxic
- Non-beneficial but non-toxic
- Non-beneficial & toxic
Current drug treatment & its effects (1+4)
Same diagnosis = same prescription
- Beneficial & non-toxic
- Beneficial but toxic
- Non-beneficial but non-toxic
- Non-beneficial & toxic
Pre-clinical research main goal
- determine the drug ultimate safety & efficacy profile
Regulations the pre-clinical studies must adhere to (1)
Good Laboratory Practices (GLP) for safety
Pre-clinical data information of NCE required by FDA (3)
- Pharmacological profile of the drug
- Determine acute toxicities of the drug
- at least on 2 species - Determine short-term toxicities of the drug
- ranging from 2 weeks - 3 months
Pre-clinical research on medical devices (3)
- 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
