Hypothesis Testing Example - Allergan Urinary Incontinence Research

Allergan Urinary Incontinence Research

Title: Anticholinergic Therapy vs. OnabotulinumtoxinA for Urgency Urinary Incontinence

Objective: We performed a double-blind, double-placebo–controlled, randomized trial involving women with idiopathic urgency urinary incontinence who had five or more episodes of urgency urinary incontinence per 3-day period, as recorded in a diary. For a 6-month period, participants were randomly assigned to daily oral anticholinergic medication (solifenacin, 5 mg initially, with possible escalation to 10 mg and, if necessary, subsequent switch to trospium XR, 60 mg) plus one intradetrusor injection of saline or one intradetrusor injection of 100 U of onabotulinumtoxinA plus daily oral placebo. The primary outcome was the reduction from baseline in mean episodes of urgency urinary incontinence per day over the 6-month period, as recorded in 3-day diaries submitted monthly. Secondary outcomes included complete resolution of urgency urinary incontinence, quality of life, use of catheters, and adverse events.

Year: 2012

Source: New England Journal of Medicine

Link: http://www.nejm.org/doi/full/10.1056/NEJMoa1208872

Clinical Area: Urology

Sample Size Section in Paper/Protocol:

“A sample size of 242 subjects (121 per treatment group) provides at least 80% power to detect a relative difference of 53% between botulinum toxin A and standardized anticholinergic therapy, assuming a treatment difference of -0.80 and a common SD of 2.1 (effect size = 0.381), and a two-sided type I error rate of 5%. Sample size has been adjusted to allow for a 10% loss to follow-up over the 6-months of treatment as well as one interim analysis to stop early for benefit.”

Note:
From Table 6 of Protocol:
Mean for ACH Group: -1.5, Mean for OnabotulinumtoxinA group: -2.3

Summary of Necessary Parameter Estimates for Sample Size Calculation:

Parameter	Value
Significance Level (2-Sided)	0.05
Expected OnabotulinumtoxinA Mean	-2.3
Expected Antichollnergic Therapy Mean	-1.5
Standard Deviation (Both Groups)	2.1
Power	80%
Number of Interim Analyses	1
Alpha Spending Function (from Protocol)	O'Brien-Fleming
Expected Dropout	10%

Step 1:
Select the Group Sequential Test of Two Means table from the Select Test Design & Goal window.

This can be done using the radio buttons or alternatively, you can use the search bar at the end of the Select Test Design & Goal window.

Step 2:
Enter the parameter values for sample size calculation taken from the study protocol.

Setting the “Number of looks” row to two specifies one interim analysis and one endpoint analysis.

Step 3:
Click Run to solve for Sample Size

This analysis calculates a sample size of 109 patients per group with a power of 80.15%.

Step 4:
Once the calculation is completed, nQuery Advanced provides an output statement summarizing the results. It States:

Output Statement:

Sample sizes of 109 in group 1 and 109 in group 2 are required to achieve 80.16% power to detect a difference in means of -0.8 (the difference between group 1 mean, μ1, of -2.3 and group 2 mean, μ2, of -1.5) assuming that the standard deviation in group 1 is 2.1 and in group 2 is 2.1 using a two-sided z-test with 5% significance level.

These results assume that the group sequential design has 1 interim sequential tests (2 total interim looks including final analysis) and the O'Brien-Fleming spending function is used to determine the efficacy test boundary.

The drift parameter for this design equals 2.813. The drift parameter defines the increase in sample size needed over a fixed term design and equals square root of the maximum information level by the difference.

Sample Size Calculator Example- nQuery- Example 15- Img 04- Group Sequential Test of Two Means

Step 5:
Calculate the sample size adjusted for expected 10% dropout, as outlined in protocol.

Sample Size Calculator Example- nQuery- Example 15- Img 05- Group Sequential Test of Two Means

This gives a final sample size of 121 per group as per study design in protocol.

Sample Size Determination Example

AREA: Means | Urology

Allergan Urinary Incontinence Research

Title: Anticholinergic Therapy vs. OnabotulinumtoxinA for Urgency Urinary Incontinence

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