VY 3 Flashcards
Main Learning Outcome for L3 Drug Discovery and Pre-Clinical Research
To gain a brief understanding of the drug discovery process and the challenges ahead
A brief introduction to “pre-clinical research”
What are the 3 types of research approaches?
- Deductive: conclusions reached by reasoning from general laws to a particular case (testing an existing theory)
- Inductive: method of reasoning which obtains general laws from particular facts or examples (use the data to develop a theory)
- Empirical approach: discovery by chance, or systematic screening
How to prove a hypothesis?
Hypotheses can never be proven, only disproven
What are the 4 types of hypotheses?
- Null hypothesis: H0 (no relationship btw x and y)
- Correlative hypothesis: H1 (there is a relationship btw x and y)
- Alternative hypothesis: 2 possible alternatives (x1, x2)(confirm one alternative), NOT typical hypothesis type
- Directional hypothesis: there is a direction of the relationship btw x and y
What are the common problems associated with poor studies?
- failure to include adequate controls
- poor experimental design
- failure to recognise multiple causes underlying a phenomenon
- Conclusion not completely warranted by the data
How to prevent ‘failure to include adequate controls’?
“Controls” are the most impt ingredients in scientific experiments
Use positive and negative controls
What are the importance of positive and negative controls?
- Reference (gold standard): independent method to detect all true positives
- False-negative (concern): result -ve but actually +ve
- False positive: result +ve but actually -ve
Sensitivity: probability that a signal (Readout) that should actually BE there (=true positive) is PRESENT
Specificity: Probability that a signal that should actually NOT be there (= true negative) is ABSENT
When to use positive and negative controls?
Sensitivity: to detect false-negative results (use positive control)
Specificity: to detect a false positive result (use negative control)
Why is there poor experimental design in research?
- exclusion of other factors
- might need to de-challenge and re-challenge
- pattern (historical)
- correlation w exposure
there could be causation or correlation
- not enough sample size
- no time period to see whether toxicity develops
What should be done to recognise multiple causes of a phenomenon?
these multiple causes are equally valid for explaining the phenomenon.
Thus, need to design more experiments to reject all other possible causes.
What is the challenge in knowing and controlling variables?
Limitation in formulating hypothesis in resolving natural and biological phenomenon (in contrast to phenomenon associated with man-made objects)
- difficult to control all known variables
we should say: our data SUGGEST (we should not use the word prove)
Conclusions cannot be drawn due to _______
very limited results
A landmark piece of scientific work can solely be based on ________ data
- descriptive data (observation-driven)
- -> can drive to formulate novel hypothesis
does not always need to be hypothesis-driven
- a study can answer a specific question (discovery-driven) or test a hypothesis (hypothesis-driven)
How is a new chemical entity launched?
- Screening
- Preclinical
- Phase I
- Phase II
- Phase III
- Launch of NCE (new chemical entity) (not previously tested in humans; diagnostic agents excluded)
What are the steps of drug development process?
- discovery (target id, lead generation, lead optimisation, lab tests)
- preclinical (access safety, biological activity, and formulation; animal studies)
- IND
- Clinical (I, II, III)
I: determine safety and dosage (healthy volunteers)
II: evaluate safety and efficacy (pts)
III: confirm safety and efficacy (more pts) - NDA
- Approval (review application and approval)
