What is LAN DeMets?

Lan and DeMets (1983) first published the method of using spending functions to set boundaries for group sequential trials. In this publication they proposed two specific spending functions: one to approximate an O’Brien-Fleming design and the other to approximate a Pocock design.

What is the O’Brien-Fleming boundary?

O′Brien-Fleming bounds use more conservative stopping boundaries at early stages. These bounds spend little alpha at the time of the interim looks and lead to boundary values at the final stage that are close to those from the fixed sample design, avoiding the problem with the Pocock bounds.

What are group sequential boundaries?

Group sequential designs allow stopping a clinical trial for meeting its efficacy objectives based on interim evaluation of the accumulating data. Various methods to determine group sequential boundaries that control the probability of crossing the boundary at an interim or the final analysis have been proposed.

How is Pocock boundary calculated?

Alpha spending functions that approximate O’Brien-Fleming or Pocock Boundaries are as follows: O ‘ Brien – Fleming : α 1 ( t ∗ ) = 2 – 2 Φ ( Z α / 2 / t ∗ ) , Pocock : α 2 ( t ∗ ) = α ln ( 1 + ( e – 1 ) t ∗ ) , where Φ denotes the standard normal cumulative distribution function.

What is group sequential design?

Group sequential design is an example of a statistical approach in clinical trial design. It means that the sample size of the trial is not fixed in advance, and data is sequentially evaluated as it is collected. This is known as interim analysis, and might be carried out at several points in time.

What is Alpha spending?

Alpha-spending is an approach of distributing (spending) the type I error (denoted alpha) over the duration of a sequential A/B test. Alpha-spending makes it possible to perform sequential testing while maintaining the overall error probability of the procedure.

What is the Haybittle Peto rule?

In short, the Haybittle–Peto boundary states that if an interim analysis shows a probability of equal to a very small alpha or greater than a very large critical value that a difference as extreme or more between the treatments is found, given that the null hypothesis is true, then the trial should be stopped early.

What is a sequential design?

Sequential designs are developmental research designs that include elements of both cross-sectional and longitudinal studies; they are configured in ways to address confounds between age, cohort, and time of measurement.

What is futility boundary?

A futility boundary (futility stopping boundary, rarely futility limit) is a statistical decision boundary used in sequential testing such as an AGILE A/B test. It is built in such a way that it maintains the type II error probability (beta β) larger than a specified level, on average.

What is group sequential analysis?

What are group sequential trials?

Group sequential trials are used in clinical trials. A group sequential design is a type of adaptive design where the number of patients isn’t set in advance. Patients are divided into an equal number of groups and data is analyzed at pre-determined points in the trial.

What is a futility boundary?