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Alira Health

Calculator for Simon’s Two-Stage Design and Its Modifications

Get Quick Results on Your Small Population Study

What Is Simon’s Two-Stage Design

The traditional method presents a two-stage trial design: a small group of patients is enrolled in the first stage; in the second stage, a second group of patients joins the trial based on the outcome of the first. If at the end of the first stage, only a few responses are observed, the trial is stopped for futility; otherwise, it proceeds to the second stage. 

Compared to the traditional methods, Simon’s two-stage design modifications allow sample size adjustment during the course of the trial and enables companies to dynamically monitor the data and possible study outcome.

This method is especially applicable to rare diseases and in Phase IIa oncology clinical trials.

Simon’s Two-Stage Design in Rare Disease

Simon’s two-stage trial design is designed to work specifically with small sample sizes, making it ideal for rare diseases. The two-stage approach allows developers to first enroll a small group of patients and test the treatment. Then the enrollment of the second group of patients is conditioned on the outcome of the first group. Sample size adjustment is also possible.

This method allows you to work with small sample sizes and, where appropriate, to increase the sample size in the second stage. It also allows companies to stop the trial early for efficacy and futility, decreasing costs and time and maximizing patient resources.

How to Use the Calculator

Our statisticians developed this calculator for a rapid evaluation of the trial. You can get an early futility assessment and modify the design while the trial is still going on. The calculator can also be used at the design stage to evaluate various scenarios and operating characteristics.

The “theory” panel provides an overview of the methods and has links to publications for more details. You then choose the values on the left panel:

  • Nmin and Nmax for the minimum and maximum number of patients required
  • p1: minimum acceptable probability of response
  • p0: maximum unacceptable probability of response
  • alpha: type I probability error
  • 1-beta: power

Then the “Simon two-stage design panel” provides the design description and finally the “Modified Simon two-stage design panel” shows suggestions on how and whether to continue the trial according to the following parameters chosen on the left panel:

  • n1 star: the number of patients at the first stage
  • Xn1 star:  the number of positive responses seen at the first stage
  • CP: hopeful region upper and lower limits

The plots show the first stage result: if this result falls within the positive region, the application provides the new sample size and rejection boundary to carry on the trial. Otherwise, the application suggests halting the study (either for futility or overwhelming efficacy).

In all, only a few clicks are needed!

Additional Materials

Additional Materials

Click here to download the tutorial to the calculator

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