Lecture 7 Analysing Dose-Response Data Flashcards
What is a graded dose-response?
Measures the degree of response of an individual to a drug, can be an any number along a spectrum so is continuous
What is a quantal dose-response?
Measures the frequency of response in a population. Within that population, an individual can only respond or non-respond. So the quantal dose-response quantifies the number of individuals in a population responding, is a discrete integer.
How is a frequency distribution different to a cumulative distribution for quantal dose-response curves?
Frequency distribution curve looks like a normal curve, because there will be a peak range where most people respond, and on either side it will tail off because most won’t respond to small dose and most will already have responded (died) at high dose.
Whereas cumulative distribution curve is a sigmoid curve.
How is a frequency distribution curve usually skewed? And how do we make this approximate to normal distribution?
Usually skewed to the right (upward skew).
Log scale the dose will approximate the curve to normal
In contrast, how can we correct a downward skew (skew to the left) to normal distribution? (Tukey’s Ladder of Transformations)
x^2
antilog(x)
What is LD50 used for?
Used to classify toxicity of known toxic substances, but is not necessary to show toxic potential of new chemical entity.
When considering LD50 what is important to note?
Hint: what affects LD50 of the same toxic substance?
LD50 is specific to species, great differences between species.
Also weight, sex, age, husbandry (how they were housed)
What are the key rules when choosing dosage groups for an LD50 study?
Widely spaced doses - choose one dose causing 100% lethality, another with marginal lethality, then one in between.
Large number of animals in each group.
TRUE OR FALSE: Trevan recommends dose ranges be experimented with few animals, then more animals be used for confirmation.
TRUE
Name the LD50 Rules of Thumb (4)
Dosage groups of same size (suggests 10animals/group)
4-6 dose levels
20-80% portion of the curve must respond
Probit analysis widely used, encourages fewer animals
On the cumulative curve, what range of cumulative response represents 1 SD away from midpoint (50% response = LD50?
16-84%
Represents 68.3% of population on either side of LD50
At 84% response, what is the corresponding NED? (normal equivalent distribution)
And similarly what is the NED at 16%?
+ 1 NED
- 1 NED
How do we convert NED to probit units?
NED + 5 = probit units
At dose LD50, probit unit = 5 because at LD50 NED = 0
What does a steep probit slope indicate?
Small increases in dose produce large increases in mortality.
