ICH E9- Statistical Principals for Clinical Trials Flashcards
What are the (3) aims of a development plan?
- 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
What variable should be capable of providing the most clinically relevant and convincing evidence directly related to the primary objective of the trial?
The primary variable (‘target’ variable, primary endpoint)
T/F There should generally be more than one primary variable.
False, There should generally be only one primary variable.
What variable should generally be the one used when estimating the sample size?
The primary variable
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?
Composite Variables
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?
Bias
What may seriously compromise the ability to draw valid conclusions from clinical trials?
Bias
Sources of bias may arise from what aspects of a trial?
1) Trial Design - such as treatment assignment
2) During the Conduct & Analysis of a trial
What is the sensitivity of the overall conclusions to various limitations of the data, assumptions, and analytic approaches to data analysis?
Robustness
What statistical approaches are commonly implemented for trials?
1) Frequentist Methods
2) Bayesian Approach
What type of trials are necessary to provide firm evidence of efficacy or safety?
Confirmatory
What type of trial is an adequately controlled trial in which the hypotheses are stated in advance and evaluated?
Confirmatory
What is a goal of confirmatory trials?
Demonstrate that the IP under investigation has clinical benefits
What is the primary objective of most confirmatory trials?
Provide strong scientific evidence of efficacy
What variables are either supportive measurements related to the primary objective or measurements of effects related to the secondary objectives?
Secondary variables
What type of variable is utilized when a single primary variable cannot be selected from multiple measurements associated with the primary objective?
Composite variable
Which type of variables are developed to measure the overall safety, efficacy, and/or usefulness of a treatment?
Global Assessment variables
When is it appropriate to utilize surrogate variables?
When the direct assessment of the clinical benefit to the subject through observing actual clinical efficacy is not practical.
What is the method for allocating patients to treatment in a multi-arm clinical trial?
Dynamic allocation procedure
With whom should the randomization schedule be filed?
Sponsor and third party (if applicable)
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?
Generalizability
What type of trial demonstrates that IP is equal or differs by an amount that is clinically unimportant, in efficacy to active control?
Equivalence Trial
What type of trial demonstrates that the efficacy of an IP is no worse than the active comparator?
non-superiority trial
Conventionally, the probability of Type I error is set at what percentage?
5% or less
