ICH E9- Statistical Principals for Clinical Trials

Question 1

What are the (3) aims of a development plan?

Answer 1

• To find out whether there is a dose range and schedule at which the drug can be shown to be simultaneously safe and effective, to the extent that the risk-benefit relationship is
  acceptable.
• The particular subjects who may benefit from the drug
• The specific indications for its use

Question 2

What variable should be capable of providing the most clinically relevant and convincing evidence directly related to the primary objective of the trial?

Answer 2

The primary variable (‘target’ variable, primary endpoint)

Question 3

T/F There should generally be more than one primary variable.

Answer 3

False, There should generally be only one primary variable.

Question 4

What variable should generally be the one used when estimating the sample size?

Answer 4

The primary variable

Question 5

If a single primary variable cannot be selected from multiple measurements
associated with the primary objective, another useful strategy is to integrate or combine the multiple measurements into a what variable?

Answer 5

Composite Variables

Question 6

What is the systematic tendency of any factors associated with the design, conduct, analysis and interpretation of the clinical trial results to make the estimate of a treatment effect deviate from its true value?

Answer 6

Bias

Question 7

What may seriously compromise the ability to draw valid conclusions from clinical trials?

Answer 7

Bias

Question 8

Sources of bias may arise from what aspects of a trial?

Answer 8

1) Trial Design - such as treatment assignment

2) During the Conduct & Analysis of a trial

Question 9

What is the sensitivity of the overall conclusions to various limitations of the data, assumptions, and analytic approaches to data analysis?

Answer 9

Robustness

Question 10

What statistical approaches are commonly implemented for trials?

Answer 10

1) Frequentist Methods

2) Bayesian Approach

Question 11

What type of trials are necessary to provide firm evidence of efficacy or safety?

Answer 11

Confirmatory

Question 12

What type of trial is an adequately controlled trial in which the hypotheses are stated in advance and evaluated?

Answer 12

Confirmatory

Question 13

What is a goal of confirmatory trials?

Answer 13

Demonstrate that the IP under investigation has clinical benefits

Question 14

What is the primary objective of most confirmatory trials?

Answer 14

Provide strong scientific evidence of efficacy

Question 15

What variables are either supportive measurements related to the primary objective or measurements of effects related to the secondary objectives?

Answer 15

Secondary variables

Question 16

What type of variable is utilized when a single primary variable cannot be selected from multiple measurements associated with the primary objective?

Answer 16

Composite variable

Question 17

Which type of variables are developed to measure the overall safety, efficacy, and/or usefulness of a treatment?

Answer 17

Global Assessment variables

Question 18

When is it appropriate to utilize surrogate variables?

Answer 18

When the direct assessment of the clinical benefit to the subject through observing actual clinical efficacy is not practical.

Question 19

What is the method for allocating patients to treatment in a multi-arm clinical trial?

Answer 19

Dynamic allocation procedure

Question 20

With whom should the randomization schedule be filed?

Answer 20

Sponsor and third party (if applicable)

Question 21

What defines the extent to which findings of a clinical trial can be reliably extrapolated from the subjects who participated in the trial to a broader patient population and a broader range of clinical settings?

Answer 21

Generalizability

Question 22

What type of trial demonstrates that IP is equal or differs by an amount that is clinically unimportant, in efficacy to active control?

Answer 22

Equivalence Trial

Question 23

What type of trial demonstrates that the efficacy of an IP is no worse than the active comparator?

Answer 23

non-superiority trial

Question 24

Conventionally, the probability of Type I error is set at what percentage?

Answer 24

5% or less

Question 25

The probability of type II error is set at what percentage range?

Answer 25

10-20%

Question 26

What document contains more technical and detailed elaboration of the principal features of the analysis described in the protocol, and includes detailed procedures for executing the statistical analysis of the primary and secondary variables and other data?

Answer 26

Statistical Analysis Plan

Question 27

For confirmatory trials, which analysis set is used?

Answer 27

Both per protocol and full analysis sets

Question 28

In superiority trials, which analysis set is used?

Answer 28

Full analysis set

Question 29

In an equivalence or non-inferiority trial, which analysis set is used?

Answer 29

Per protocol set

Question 30

What is used to define safety and tolerability variables?

Answer 30

-Type of adverse event
- Severity
- Onset
- Duration

Question 31

What is the extent to which a variable measures what it’s supposed to measure?

Answer 31

Content Validity

Question 32

What is the single variable, usually a scale of ordered categorical ratings, which integrates objective variables and the investigator’s overall impression about the state or change in state of a subject?

Answer 32

Global Assessment Variable

Question 33

What type of variable provides an indirect measurement of effect in situations where direct measurement of clinical effect is not feasible or practical?

Answer 33

Surrogate variable

Question 34

Which error type is the chance that we fail to detect differences that do exist?

Answer 34

Type II

Question 35

Which error type is the chance that we observe differences that do not exist?

Answer 35

Type I