Clinical Trials

Question 1

Whats the ABC’s of clinical trial design?

Answer 1

A = Assignment
B = Blinding
C = Comparison
s = Sequence

Question 2

What are the two types of assignment?

Answer 2

• First come first served

- Randomized (inc; balanced, stratified)

Question 3

What does the first come first served method involve?

Answer 3

• Range of possibilites that will induce bias

- Main source of bias is the lack of blinding I.e everyone knows whos getting treatment vs placebo etc

Question 4

What is the randomized assignment method?

Answer 4

Subjects are randomized into control and subject groups

• Can be done evenly (balanced)
• Or stratified based on age, gender etc

Question 5

What is blinding used for?

Answer 5

To reduce bias

Question 6

What are the types of blinding?

Answer 6

• Open
• Single Blind (subjects dont know)
• Double blind
  
  • Double dummy (two physically different treatments i.e inhaler vs tablet)
• Triple blind (randomized sequence is lost or misinterpreted) - nobody ever knows what treatment was given

Question 7

What are the types of comparison?

Answer 7

• Active
• Placebo
• Standard treatment

Question 8

What is is active comparison?

Answer 8

• Dose controlled
• Concentration controlled
• Biomarker controlled i.e cholesterol level

Comparing the treatments based on their differences. To learn about the relationship between intensity of treatment and outcome

Question 9

What is standard treatment comparison?

Answer 9

• All subjects recieve the treatment and then some get an add-on (testing drug)

(non-inferiority) refers to trial that shows that the new treatment is no worse than the standard.

Question 10

What is sequence?

Answer 10

The sequence of treatments can influenced what is learned from a trial and the kind of bias that can araise

Question 11

What are the types of sequence?

Answer 11

• Parallel
• Crossover
• Titration

Question 12

What is parallel sequence?

Answer 12

Different treatments given to different groups at the same time

Question 13

Whats the upside and downside to parallel sequence?

Answer 13

Answers the does the drug work question but cant answer learning questions such as shape of the dose response curve

Question 14

What is crossover sequence?

Answer 14

Two or more treatments in each subject

Allows formation of dose-reponse curve and may be more statistically valuable

Question 15

Whats wrong with the crossover design?

Answer 15

There may be carryover affect i.e during the time of off medication

Question 16

What is the titration design?

Answer 16

Fixed sequential doses (Forced)

Change in dose till therapeutic response level is achieved (flexible)

Question 17

What is analysis?

Answer 17

Two questions

Does it work? (confirming Qs) i.e does it lower BP

How well does it work? (learning Qs) - scales i.e what does is needed to produce this response..

Question 18

What are some methods for determining does it work?

Answer 18

Simple comparison i.e drug vs placebo

• t-test (two groups)
• Anova (several)
• log rank test (survival)

Question 19

What factors are considered in the size of the response?

Answer 19

Cl
V
Emax
ED50

How much Q’s - i.e how much drug to produce this response

Question 20

What are the methods behind how well does it work questions?

Answer 20

PK and PD methods

Question 21

Why are PK, PD and PKPD models for how well does it work questions, better than hypothesis testing?

Answer 21

They account for:

Execution differences i.e

• Adherence (stop taking meds)
• Drop out

Co-variates (inter-individual differences)
- Renal function, size, gender

Question 22

What is a power analysis?

Answer 22

A power analysis is used to determine the likelihood that a clinical trial will detect a drug effect if the drug effect really exists

Question 23

Why would we use a power analysis?

Answer 23

We would use a power analysis because of human variability that means the testing does not show the true effect of the drug because its effect is lost to “noise”

It generates a % likelihood that the null hypothesis will be rejected (good) based on criteria

Question 24

What questions are asked in a power analysis?

Answer 24

• What is the size of the effect
• What is the variability in the response
• What is the desired p value
• What is the desired power i.e 0.8 (good)

Question 25

What are the two analysis perspectives for analyzing clinical trials?

Answer 25

• Intention to treat

- As treated

Question 26

What does the intention to treat perspective encompass?

Answer 26

• Only takes into account treatment assessment
• Doesnt take into account if the subject took the treatment or not “use effectiveness”
• Good for pharmacoeconomics

Question 27

What does the as treated perspective encompass?

Answer 27

• Whether or not the subject took the meds (Method effectiveness)
• Development of scientific perspective