Prof Randi Garcia
February 1, 2021
This experiment is interested in the blood concentration of a drug after it has been administered. The concentration will start at zero, then go up, and back down as it is metabolized. This curve may differ depending on the form of the drug (a solution, a tablet, or a capsule). We will use three subjects, and each subject will be given the drug three times, once for each method. The area under the time-concentration curve is recorded for each subject after each method of drug delivery.
In the bioequivalence example, because the body may adapt to the drug in some way, each drug will be used once in the first period, once in the second period, and once in the third period.
Treatments:
period 1 | period 2 | period 3 | |
---|---|---|---|
subject 1 | A 1799 | C 2075 | B 1396 |
subject 2 | C 1846 | B 1156 | A 868 |
subject 3 | B 2147 | A 1777 | C 2291 |
Factor diagram for the Latin Square
The actual data structure for analysis is “long” format
subject | treatment | period | group | c_curve |
---|---|---|---|---|
1 | solution | 1 | A | 1799 |
1 | capsule | 2 | C | 1846 |
1 | tablet | 3 | B | 2147 |
2 | capsule | 1 | C | 2075 |
2 | tablet | 2 | B | 1156 |
2 | solution | 3 | A | 1777 |
3 | tablet | 1 | B | 1396 |
3 | solution | 2 | A | 868 |
3 | capsule | 3 | C | 2291 |
We can make a parallel dot graph
And check for equal standard deviations
library(mosaic)
sd <- favstats(c_curve ~ treatment, data = bioequivalence)[,8]
max(sd)/min(sd)
[1] 2.387418
\[ {y}_{ijk}={\mu}+{\alpha}_{i}+{\beta}_{j}+{\tau}_{k}+{e}_{ijk} \]
Source | SS | df | MS | F |
---|---|---|---|---|
rows | \( \sum_{i=1}^{p}p(\bar{y}_{i..}-\bar{y}_{...})^{2} \) | \( p-1 \) | \( \frac{{SS}_{A}}{{df}_{A}} \) | \( \frac{{MS}_{A}}{{MS}_{E}} \) |
columns | \( \sum_{j=1}^{p}p(\bar{y}_{.j.}-\bar{y}_{...})^{2} \) | \( p-1 \) | \( \frac{{SS}_{B}}{{df}_{B}} \) | \( \frac{{MS}_{B}}{{MS}_{E}} \) |
treatment | \( \sum_{k=1}^{p}p(\bar{y}_{..k}-\bar{y}_{...})^{2} \) | \( p-1 \) | \( \frac{{SS}_{T}}{{df}_{T}} \) | \( \frac{{MS}_{T}}{{MS}_{E}} \) |
Error | \( \sum_{i=1}^{p}\sum_{j=1}^{p}({y}_{ijk}-\bar{y}_{i..}-\bar{y}_{.j.}-\bar{y}_{..k}+2\bar{y}_{..})^{2} \) | \( (p-1)(p-2) \) | \( \frac{{SS}_{E}}{{df}_{E}} \) |
ls_mod <- lm(c_curve ~ treatment + period + subject, data = bioequivalence)
anova(ls_mod)
Analysis of Variance Table
Response: c_curve
Df Sum Sq Mean Sq F value Pr(>F)
treatment 2 608891 304445 67.733 0.014549 *
period 2 928006 464003 103.231 0.009594 **
subject 2 261115 130557 29.047 0.033282 *
Residuals 2 8990 4495
---
Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
bioequivalence <- bioequivalence %>%
mutate(fitted = fitted(ls_mod),
residuals = residuals(ls_mod))
ggplot(bioequivalence, aes(x = fitted, residuals)) +
geom_point() +
geom_hline(yintercept = 0, color = "red")
How would you conduct this study?
A plant breeder wishes to study the effects of soil drainage and variety of tulip bulbs on flower production. Twelve 3m by 10m experimental sites are available in the test garden–each is a .5m deep trench. You can manipulate soil drainage by changing the ratio of sand to clay for the soil you put in a trench. After talking to your collaborator, you decided that four different levels of soil drainage would suffice. You'll be testing 15 different types of tulips, and measuring flower production in the spring.
If you suspect a design in a split-plot design, you should be able to answer the following questions:
A plant breeder wishes to study the effects of soil drainage and variety of tulip bulbs on flower production. Twelve 3m by 10m experimental sites are available in the test garden–each is a .5m deep trench. You can manipulate soil drainage by changing the ratio of sand to clay for the soil you put in a trench. After talking to your collaborator, you decided that four different levels of soil drainage would suffice. You'll be testing 15 different types of tulips, and measuring flower production in the spring.
The disease diabetes affects the rate of turnover of lactic acid in a system of biochemical reactions called the Cori cycle. This experiment compares two methods of using radioactive carbon-14 to measure rate of turnover. Method 1 is injection all at once, and method 2 is infused continuously. 10 dogs were sorted into two groups, 5 were controls and 5 had their pancreas removed (to make it diabetic). The rate of turnover was then measured twice for each dog, once for each method. The order of the two methods was randomly assigned.
Draw the factor diagram for the data on page 263.
\[ {y}_{ijk}={\mu}+{\alpha}_{i}+{\beta}_{j(i)}+{\gamma}_{k}+({\alpha\gamma})_{ik}+{e}_{ijk} \]
Source | SS | df | MS | F |
---|---|---|---|---|
Between | \( t\frac{N}{a}\sum_{i=1}^{a}(\bar{y}_{i..}-\bar{y}_{...})^{2} \) | \( a-1 \) | \( \frac{{SS}_{A}}{{df}_{A}} \) | \( \frac{{MS}_{A}}{{MS}_{B}} \) |
Blocks | \( t\sum_{i=1}^{a}\sum_{j=1}^{n}(\bar{y}_{ij.}-\bar{y}_{i..})^{2} \) | \( N-a \) | \( \frac{{SS}_{B}}{{df}_{B}} \) | \( \frac{{MS}_{B}}{{MS}_{E}} \) |
Within | \( Na\sum_{k=1}^{K}(\bar{y}_{..k}-\bar{y}_{...})^{2} \) | \( t-1 \) | \( \frac{{SS}_{T}}{{df}_{T}} \) | \( \frac{{MS}_{T}}{{MS}_{E}} \) |
Interaction | \( \sum_{i=1}^{a}\sum_{k=1}^{t}\frac{N}{a}(\bar{y}_{i.k}-\bar{y}_{i..}-\bar{y}_{..k}+\bar{y}_{...})^{2} \) | \( (a-1)(t-1) \) | \( \frac{{SS}_{AT}}{{df}_{AT}} \) | \( \frac{{MS}_{AT}}{{MS}_{E}} \) |
Error | \( \sum_{i=1}^{a}\sum_{j=1}^{N}\sum_{k=1}^{t}({y}_{ijk}-\bar{y}_{i.k}-\bar{y}_{.j.}-\bar{y}_{..k}+\bar{y}_{i..})^{2} \) | \( (N-a)(t-1) \) | \( \frac{{SS}_{E}}{{df}_{E}} \) |