Pre-Clinical Research in Drug Discovery

Question 1

Types of general research approaches

Answer 1

1) Deductive
- draw logical conclusions from data provided

2) Inductive
- set up alt hypothesis
- devise crucial experiments to exclude 1/more of the hypothesis (clean answer)

3) Empirical
- discovery by chance/systematic screening

Question 2

Types of hypotheses

Answer 2

1) Null
- no r/s btwn independent & dependent variable

2) Correlative
- a r/s btwn independent & dependent variable but exact nature of r/s not specified

3) Alternative
- indicates 2 possible alt as a logic consequence of a postulated new fact

4) Directional
- requires direction of the r/s btwn independent & dependent variable to be specified

Question 3

Pilot studies

Answer 3

• To assess feasibility of the proposed study

- saves valuable time & $$$

Question 4

Problems associated with poor studies

Answer 4

1) Fail to include adequate controls
- +ve control: Detect false -ve
- -ve control: Detect false +ve

2) Poor experimental design

3) Fail to recognise multiple causes underlying a phenomenon
- need to design > experiments to reject other possible causes

4) Conclusion not completely warranted by data

Question 5

Challenge in knowing & controlling variables

Answer 5

• Limitation in formulating hypothesis in resolving natural & biological phenomenon
• -> Limited understanding of the variables that controls the system or links to the phenomenon under study
• supportive data gathered can only serve as evidence (not proof)

Question 6

Type of approaches driving publishable research work

Answer 6

1) Hypothesis-driven approach
- can only be performed when you can formulate a hypothesis

2) Descriptive (observation-driven research)
- illustrate interesting phenomenon that may drive the formulation of novel hypothesis

Question 7

Potential contributing factors to the rising cost

Answer 7

• pressures from shareholders
• change in approach to management
• merger mania
• blockbuster mania
• drug approval policies are inconsistent & erratic
• technologies???

Question 8

What is drug development effort hampered by?

Answer 8

• Understanding of disease @ molecular level

- Genetic variations in pt responses

Question 9

How should we approach R&D since predicting commercial success is difficult?

Answer 9

• Focus on novelty & relevance of science
• Involve scientists in decision-making
• Define value in terms of conviction, science & benefit to medical community & not just $$$

Assess “separation of R from D” approach

• Most pharmas separate R&D divisions organisationally, operationally & geographically
• reduces communication, cooperation
• -> diminishes potentials for basic researches to solve probs that arise during development
• -> “hands-off” mentality is a unrealistic presumption that development can be predictably managed

Question 10

Why are majority of drugs discarded during development?

Answer 10

Commonly for reasons NOT technical/scientific

Due to: Market reassessment/ management discontent

• Deem project as of low priority
• Resources are scarce

Question 11

Shift in focus of pharma?

Answer 11

• From novel discovery to incremental improvements

- May not be as lucrative as new & blockbuster drugs, but $ & risks in R&D will be drastically reduced

Question 12

FDA requirement for pre-clinical data package for NCE

Answer 12

• Pharmacological profile
• Acute toxicity in at least 2 animal species
• Short-term toxicity studies ranging from 2wks-3mths

Question 13

Types of studies during Pre-Clinical Research

Answer 13

• In-vitro & in-vio laboratory animal testing
• genotoxicity testing
• extensive ADME profiling in animals