What is hierarchical testing procedure?

In confirmatory clinical trials, the hierarchical test (also called the fixed sequence procedure) has been frequently used to test multiple ordered endpoints. The endpoints are tested in a predefined sequence, each at the significance level α, until the first nonsignificant test (Maurer, Hothorn, and Lehmacher 1995.

What does adjusting for multiplicity mean?

one of the issues in statistics field is the adjustment for multiplicity – adjustment of alpha level for multiple tests. The multiplicity can arise in many different situations in clinical trials; some of them are listed below: Multiple arms. Co-primary endpoints.

What are hierarchical endpoints?

Endpoints are predefined in the protocol in a definitive hierarchical manner (first, second, etc.). The first endpoint is analysed according to the method for testing a single primary endpoint. The risk of erroneously identifying a treatment benefit is completely controlled (limited to 5% for simplicity).

What does not controlled for multiplicity mean?

If multiplicity is not controlled for, and if both null hypotheses are actually true and independent from each other, then there is a 5.1% chance (= 1 – 0.975*0.975) that at least one of the null hypotheses is wrongly rejected. In other words, the chance of claiming something wrong increases.

What does fixed sequence mean?

Fixed Sequence Procedure is a stepwise multiple testing procedure that is constructed using a pre-specified sequence of hypotheses. When there are multiple endpoints, these endpoints can be ordered according to their importance. All tests will be performed at the 0.05 level following the pre-specified order.

What is fallback procedure?

We develop a procedure called the “fallback procedure” to control the familywise error rate when multiple primary hypotheses are tested. With the fallback procedure, the Type I error rate (alpha) is partitioned among the various hypotheses of interest.

What is a nominal P value?

The nominal p-value is a calculated observed significance based on a given statistical model. When the statistical model reflects the actual test performed the nominal and actual p-value coincide.

What is multiplicity testing?

Multiplicity refers to the potential inflation of the type I error rate as a result of multiple testing, for example due to multiple subgroup comparisons, comparisons across multiple treatment arms, analysis of multiple outcomes, and multiple analyses of the same outcome at different times.

What is primary and secondary endpoint?

The primary endpoint of a clinical trial is the endpoint for which the trial is powered. Secondary endpoints are additional endpoints, preferably also pre-specified, for which the trial may not be powered.

What is hierarchical composite endpoint?

A hierarchical composite endpoint, AVF, preserves statistical power while improving face validity. AVF is less prone to favor a treatment with discordant effects on survival and days free of ventilation. This general approach can support complex outcome hierarchies with multiple constituent outcomes.

What is the difference between primary and secondary endpoints?

What is a tertiary endpoint?

The primary endpoint(s) typically measures and addresses the main research question. Secondary endpoints support the claim of efficacy demonstrated by the primary outcomes. Tertiary endpoints typically capture outcomes that occur less frequently, or which may be useful for exploring novel hypotheses.

What is an example of FAP?

A well-studied example of a fixed action pattern occurs in ground-nesting water birds, like greylag geese. If a female greylag goose’s egg rolls out of her nest, she will instinctively use her bill to push the egg back into the nest in a series of very stereotyped, predictable, movements.

What is a probe substrate?

One drug is considered the probe substrate, and the other is the interacting drug. The probe substrate is metabolized or transported by the biological enzyme being studied (e.g. cytochrome P450 3A4, OATP1, etc.). The interacting drug affects the biological enzyme being studied by either inhibition or stimulation.

What is fallback testing?

Fallback testing is the ability of an application to transfer processing to the backup system without disrupting customer services. Fallback testing also refers to a condition to trigger a switch in real time from a primary server to a backup server so that the connected user base impact is minimized.

What does p 0.05 mean?

A statistically significant test result (P ≤ 0.05) means that the test hypothesis is false or should be rejected. A P value greater than 0.05 means that no effect was observed.

What does p 0.001 mean?

1 in a thousand
p=0.001 means that the chances are only 1 in a thousand. The choice of significance level at which you reject null hypothesis is arbitrary.

What does a Bonferroni test do?

The Bonferroni test is a statistical test used to reduce the instance of a false positive. In particular, Bonferroni designed an adjustment to prevent data from incorrectly appearing to be statistically significant.

What is post hoc test?

Post Hoc Tests. Post hoc (Latin, meaning “after this”) means to analyze the results of your experimental data. They are often based on a familywise error rate; the probability of at least one Type I error in a set (family) of comparisons.

What is difference between outcome and endpoint?

The term outcome usually refers to the measured variable (eg, peak volume of oxygen or PROMIS Fatigue score), whereas an endpoint refers to the analyzed parameter (eg, change from baseline at 6 weeks in mean PROMIS Fatigue score).