Bioequivalence (2) [Uncomplicated Drugs]

Question 1

For Average BE studies, what is the minimum percentage difference b/w the test and reference drugs?

Answer 1

+/- 20%

Question 2

For Average BE studies, what’s the sig. level?

Answer 2

0.05

Question 3

For Average BE studies, what’s the power of the test set to?

Answer 3

0.8 (prob of detecting a diff if it truly exists b/w Test and Ref drugs)

Question 4

For Average BE studies, what’s the typical sample size range?

Answer 4

24-36

Question 5

For Average BE studies, do we typically use healthy or sick volunteers?

Answer 5

Healthy

Question 6

In PK-BE studies, how many t1/2’s do we sample for?

Answer 6

at least 3 half lives

Question 7

In PK-BE studies, when do we want to take more frequent blood samples from pts?

Answer 7

Around Cmax

Question 8

In PK-BE studies, when assessing our data, what important PK parameters do we want to calculate? (3)

Answer 8

AUC, Cmax, Tmax

Question 9

For BE to be established, drugs must be equivalent wrt ___ and ____ of drug absorption

Answer 9

rate, extent

Question 10

What does Cmax represent?

Answer 10

peak exposure

Question 11

What does AUC represent?

Answer 11

total exposure

Question 12

In the past, how was BE established?

Answer 12

Mean AUC or Cmax of test drug was within +/- 20% of that of reference drug

Question 13

What approach is used today to determine BE?

Answer 13

Confidence Interval approach

Question 14

What is the ratio of means of the T and R drugs in a 90% confidence interval?

Answer 14

0.80-1.20

Question 15

What is the ratio of means of the T and R drugs in a 90% confidence interval when the data are log transformed?

Answer 15

0.80-1.25

Question 16

Why Log transform BE metrics (AUC, Cmax, Cp vs t)?

Answer 16

It makes the data normally distributed

Question 17

T or F: Most PK parameters yield normal distributions

Answer 17

F

Mostly skewed dists

Question 18

3 approaches to BE comparisons?

Answer 18

1. Average BE
2. Population BE
3. Individual BE

Question 19

T or F: Individual BE is the simplest approach to BE comparisons.

Answer 19

F

Average BE is the simplest approach

Question 20

What’re the two types of study design?

Answer 20

1. Crossover

2. Parallel

Question 21

When is a parallel group design utilized?

Answer 21

When…

1. drug causes physiological change that persists to the next treatment arm
2. drug has long t1/2
3. drug shows flip-flop kinetics

Question 22

Does crossover or parallel study design allow examination of intrasubject variation?

Answer 22

Crossover

Question 23

Which study design is preferred - crossover or parallel?

Answer 23

Crossover

Question 24

Most common single oral dose design?

Answer 24

2-product, 2-period, 2-sequence, crossover

Question 25

The Cmax value is used to evaluate ___ of absorption

Answer 25

rate

Question 26

The AUC value is used to evaluate ___ of absorption

Answer 26

extent

Question 27

When is BE of uncomplicated drugs concluded via the confidence interval approach?

Answer 27

When the 90% confidence intervals of both Cmax’s and AUC’s geometric mean ratios of the two fmlations fall within the BE range of 80-125%.

Question 28

Which is worse: 90% Confidence Interval failing for AUC or Cmax?

Answer 28

AUC

Question 29

Are t tests one sided or two sided for BE studies?

Answer 29

One-sided w/ 95% Confidence