Topic 3: Trial Design

Question 1

What is a Superiority Trial

Answer 1

Demonstrates an improvement in clinical outcome compared to the control group

Question 2

What is a Non-inferiority Trial

Answer 2

Demonstrate the treatment is not inferior to the control

Question 3

What analysis population does a superiority trial typically use

Answer 3

Intention to Treat

Question 4

Why should you do both intention to treat and per-protocol

Answer 4

As a kind of sensitivity analysis, compare results and conclusions

Question 5

What bias can intention to treat analysis population cause

Answer 5

Bias towards no treatment effect, potentially leading to a false conclusion of non-inferiority

Question 6

What bias can per-protocol cause

Answer 6

Allows for exclusions of patients, so potentially leads to biased estimate of treatment effect.

Question 7

Three types of trial design

Answer 7

Parallel, Crossover and Factorial

Question 8

What is a crossover trial

Answer 8

Patients are randomised to a sequence of treatments and act as their own control.

Question 9

What is a positive of crossover trials

Answer 9

Since patients are acting as their own control, requires fewer patients

Question 10

What is a washover period and what does it avoid

Answer 10

A period of time between treatments where the participant receives no treatment. Avoids carryover effect, where the effect of treatment A impacts the effect of treatment B.

Question 11

What is the duration of the washout period

Answer 11

The time it takes to return the participant to the original disease state, needs to be at the same baseline values as at the start of period 1. Depends on how long the drug remains active in the body.

Question 12

What does the AB/BA crossover design mean

Answer 12

Patients are randomised to recieve either A first then B, or B first then A.

Question 13

What is a factorial Design

Answer 13

Where combinations of interventions are tested

Question 14

What is a 2x2 factorial design

Answer 14

patients are randomised to one of four combinations of two distinct interventions. Each treatment has two doses or levels

Question 15

What is the objective of the factorial design

Answer 15

determine which combination is the optimum treatment. Testing combinations of interventions efficiently, needs less patients.

Question 16

When is a factorial design appropriate

Answer 16

When treatments can be given in combination

Question 17

What does a factorial design allow

Answer 17

Interactions to be detected. Can power for interactions.

Question 18

How is the sample size for a factorial design determined

Answer 18

Determine sample size when there is no interaction then increase sample size to detect an interaction if needed. Do separate sample size calculations for each intervention, then choose the larger of these as the sample size.

Question 19

What do we test in an equivalence trial

Answer 19

Whether the treatment is neither worse nor better.

Question 20

In an equivalence trial, when do we conclude equivalence

Answer 20

When the confidence intervals lies entirely between some range delta and -delta, since the alternative hypothesis is that the treatment difference is bigger than -delta and less than delta.

Question 21

What is the null hypothesis in an equivalence trial

Answer 21

The treatment is less than -delta, or more than delta, so its essentially outside of the range [-delta , delta].

Question 22

When would we conclude non-inferiority

Answer 22

When the lower end of the confidence interval is greater than the non-inferiority margin.

Question 23

What is the null hypothesis in a non-inferiority trial

Answer 23

The treatment difference is less than or equal to -delta

Question 24

What is the alternative hypothesis in a non-inferiority trial

Answer 24

The treatment difference is greater than - Delta.