L16: VY Lecture 3

Question 1

What are the three types of research approaches?

Answer 1

• deductive (provide data -> draw logical conclusions)
• inductive (set up alternative hypotheses -> devise crucial experiments to exclude one or more of the hypotheses)
• empirical (discovery by chance, or systematic screening)

Question 2

Can we prove a hypothesis?

Answer 2

Hypotheses can never be proven, only disproven or retained.

Question 3

What are the different types of hypotheses?

Answer 3

• null hypothesis
• correlative hypothesis
• alternative hypothesis
• directional hypothesis

Question 4

What is a pilot study for?

Answer 4

To assess feasibility of the proposed study.

Question 5

What are some common problems associated with poor studies?

Answer 5

1. Failure to include adequate controls
2. Poor experimental design
3. Failure to recognize multiple causes underlying a phenomenon (need to design more experiments to reject all other possible causes; however, biological systems are very complex and we have limited understanding of the variables that control the system or links to the phenomenon under study)
4. Conclusion not completely warranted by the data

Question 6

What is sensitivity?

Answer 6

Probability of a true positive –> use positive control

Question 7

What is specificity?

Answer 7

Probability of a true negative –> use negative control

Question 8

What are some potential contributing factors to the rising cost, but declining output of NCEs?

Answer 8

• pressure from shareholders (expect rapid and substantial returns)
• marketing executive with no scientific background calling the shots)
• merger mania
• blockbuster mania
• drug approval policies are inconsistent and erratic

Question 9

What kind of technology is beneficial?

Answer 9

Future advance in genomic and proteomic medicine

- disease subclassification -> differentiate responders from non-responders

Question 10

Should companies separate their R&D divisions?

Answer 10

No, this reduces communication, cross-fertilization, co-operation and teamwork.
It diminishes the potential for basic researchers to solve problems arising during development.

Question 11

What should the future of pharma companies be?

Answer 11

Should shift R&D away from novel discovery towards development in areas which they excel eg improved formulations, superior PK/PD profiles and analogs with significant improved benefits.
May not be as lucrative as new and possibly blockbuster drugs, but cost and risks in R&D will be drastically reduced

Question 12

Should there be a larger role for non profit institutions for creating novel drugs?

Answer 12

Yes, should invest in nonprofit institutions such as universities and government laboratories. These institutions have the appropriate climate for creative and innovative science. Their science is not dictated by marketing or commercial objectives.

Question 13

What is the main goal of preclinical research?

Answer 13

Determine safety

Question 14

What do preclinical studies concerning safety require?

Answer 14

Good Laboratory Practice (GLP) –> data acceptable for submission to FDA

Question 15

What is a typical pre-clinical data package for NCE?

Answer 15

minimum:
- pharmacological profile of the drug
- acute toxicity of the drug in at least two species of animals
- short term toxicity studies ranging from two weeks to three months