LECTURE 10: DOSE-FINDING STUDIES Flashcards
1
Q
Why can’t we just use a dose-response curve?
A
- Population-based PD curves for when the effect is binary (not continuous)
o i.e. did convulsions occur? did death occur? was treatment successful?
2
Q
We Want to Investigate a Novel Drug to See Whether it is Safe and Effective – What effects to look for
A
- quantifiable: such as BGC versus hospitalisation for diabetes drug
- surrogate markers
3
Q
Drug discovery
A
- molecule-centred design
- randomly screen large libraries of molecules prepared by medicinal chemists
- target-centred design
- identify the drug target and medicinal chemists synthesis candidate drug molecules
- “me too” drug design
- variations of existing drug molecules
4
Q
Pre human testing steps
A
- in vitro testing: assays to test mechanism, affinity, enzymes, toxicity, lipophilicity, metabolism
- animal testing - drug toxicity
5
Q
phase I drug studies
A
- 10-100 people
- healthy or focus health condition
- goal to determine PK and toxic drug concentrations
- clinical pharmacologists and research centers
6
Q
phase II drug studies
A
- 100-200
- with target disease
- proof of concept: -, +, experimental group…
- done by unis
7
Q
success rate from phase II to III
A
30%
8
Q
phase III studies
A
- thousands
- safety and efficacy at intended dose
- clinical specifialists for 3-5 years
9
Q
success rate from phase III to market
A
25-50%
10
Q
Ways to to drug testing more cheap
A
- parallel study design
- cross over study design
- continueal reassesment method (CRM)
11
Q
parallel study design
A
different groups - low, medium, high dose, placebo, a drug in market…
12
Q
advantage of parallel study deisgn
A
simple to design and implement
13
Q
disadvantages of parallel study design
A
- Each subject only receives one dosing regimen, therefore only get population average dose – not a dose-response curve for each individual (which can’t get if have binary outcome measure i.e. cured or not)
- Unlikely to determine the optimal dose – the dose selected has to be one of the doses trialled
14
Q
cross over study design
A
everyone gets placebo and drug at different times
15
Q
cross over study designs are only suitable for what type of response
A
continues - such as heart rates or urine output
