Get sample size updates by email

Receive educational sample size content

nQuery Sample Size Software Logo Q svg

CLASSICAL

Solutions for Frequentist and Fixed-term trials
nQuery Sample Size Software Logo Q svg

BAYESIAN

Sample size using Bayesian analysis
nQuery Sample Size Software Logo Q svg

ADAPTIVE

Sample size for sophisticated Adaptive clinical trials

Get sample size updates by email

Receive great industry news once a week in your inbox

Sample Size Determination Example

AREA: Means (MCP-MOD) | Psychopharmacology

nQuery In Use Background Web  Opacity 35
MCP-MOD Worked Examples

Title: A randomized, double-blind, placebo-controlled, dose-ranging study of lisdexamfetamine dimesylate augmentation for major depressive disorder in adults with inadequate response to
antidepressant therapy

Objective: This randomized, double-blind, placebo-controlled study evaluated dose-response relationships of lisdexamfetamine dimesylate when used as augmentation for major depressive disorder in individuals exhibiting inadequate responses to antidepressant monotherapy.

Year: 2017

Source: Journal of Psychopharmacology

Link: https://journals.sagepub.com/doi/10.1177/0269881117722998

Protocol: https://clinicaltrials.gov/ct2/show/NCT01435759

Clinical Area: Psychopharmacology

Sample Size Section in Paper/Protocol:

““Participants meeting all of the randomization criteria were randomized 1:1:1:1:1 to
eight weeks of augmentation therapy with LDX (10, 30, 50, or 70 mg) or LDX-matching
placebo (0 mg)”

“The pre-specified dose-response curves tested for MADRS total score change (were)
Emax, logistic, linear, and betaMod”

“If at least one candidate dose-response relationship reached a two-sided significance
value of 0.10, proof of an LDX dose-response would be considered to have been
established”

”An estimated 1890 screened individuals were expected to yield 1134 enrolled
participants, of which 425 (85 per treatment arm) would be randomized and 340 (68 per
treatment arm) would complete the study. Assuming a mean±standard deviation (SD)
maximum effect of 3.0±8.1 for MADRS total score change from augmentation baseline
for each candidate dose-response curve, 68 participants per treatment arm would
provide 80% power ”..”


Summary of Necessary Parameter Estimates for Sample Size Calculation:

 Parameter Value
 Significance Level (2-Sided) 0.1
Number of Doses 5 (0mg, 10mg, 30mg,
50mg, 70mg)
Number of Models 4 (Emax, Linear, Logistic,
Beta)
 Placebo Effect, δ 0 0.2
Max Treatment Effect, δ 1 3
Standard Deviation, σ 8.1
Power 80%
   

 

sample-size-calculator-example-nquery-example-24-img-parameters-mcp-mod

Email me this example in PDF format

Step 1:
Select the MGT5 Multiple Comparisons Procedure - Modelling (MCP-Mod) table from the Select Test window.

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

sample-size-calculator-example-nquery-example-24-img-01-mcp-mod

Step 2:
Enter the parameter values in the main table for the sample size calculation taken from the study description.

First, complete the main table. Note: Mean power criterion implies that the total power of the test will be equal to the mean power of the candidate models.

An optional random seed is also specified here to allow replicable results.

sample-size-calculator-example-nquery-example-24-img-02-mcp-mod-1

Next, complete the Dose Levels and Candidate Models side table .

sample-size-calculator-example-nquery-example-24-img-03-mcp-mod-1Step 3:
Enter the Power in the main table and the required sample size and candidate model powers will be calculated.

The analysis gives a sample size of 67 per dose group (335 in total).

A mean power of 80.29% was achieved with this sample size. The per-model powers ranged
from 75.258% (Linear Model) to 93.640% (Beta Model). The maximum effect dose was the
70mg final dose for Emax, Linear and Logistic while the Beta model achieved maximum effect at the 50mg dose.

 

Note that in the original study, the required sample size per dose group was calculated as 68 (340 total). This slight difference is likely due to rounding.

sample-size-calculator-example-nquery-example-24-img-04-mcp-mod-1

Step 4:

Once the calculation is completed, nQuery provides an output statement summarizing the results. It states:

Output Statement:

"“ A total sample size of 335 is required to ensure a mean power of 80.29% for a MCP-Mod analysis rejecting the null hypothesis of no difference between doses using the multiple comparisons procedure (MCP) assuming a placebo dose-response effect of 0, a maximum dose-response effect (in the dose range) of 3 and a common (residual) standard deviation of 8.1 per dose and two-sided family-wise error rate of 0.1.”


This analysis assumed 5 doses with the following sample sizes per dose:

Doses: 0, 10, 30, 50, 70
Sample Size: 67, 67, 67, 67, 67

The following 4 models (including input parameters) were evaluated in this MCP-Mod analysis and were found to have the following per-model power:

Emax (ED50): 10, 76.42%
Linear: 75.26%
Logistic (ED50, δ): 20, 1, 93.64%
Beta (a, b, Scale): 1.8, 1, 80, 75.85”

sample-size-calculator-example-nquery-example-24-img-05-mcp-mod-1

Email me this example in PDF format

Get a Trial

Demo Icon white
Try now - no download required
 
50k Users
Commercial, academic &
government organizations
Successful Trials
Recognized by the FDA, EMA
& other regulatory bodies

Pfizer Coronary Heart Disease Research - Sample Size Example

Tags: Agreement, Cardiology

View Example

Thrombosis Research - Sample Size Example

Tags: Agreement, Cardiology

View Example

Hepatology Research - Sample Size Example

Tags: Agreement, Oncology

View Example

Prostate Cancer Study Determine Sample Size

Tags: Agreement, Urology

View Example

Zoetis Dairy Science Research - Sample Size Example

Tags: Agreement, Veterinary

View Example

BMS Diabetes Research - Sample Size Example

Tags: Means, Cardiology

View Example

Bayer Pulmonary Hypertension Research - Sample Size Example

Tags: Means, Cardiology

View Example

Sanofi Immunology CRT Research - Sample Size Example

Tags: Means, Immunology

View Example

Baxter Nephrology Research - Sample Size Example

Tags: Means, Nephrology

View Example

Teva Multiple Sclerosis Research - Sample Size Example

Tags: Means, Neurology

View Example

BMS Lung Dieaease Research - Sample Size Example

Tags: Means, Respiratory

View Example

GSK Respiratory Research - Sample Size Example

Tags: Means, Respiratory

View Example

GSK COPD Research - Sample Size Example

Tags: Means, Respiratory

View Example

Teva Allergic Rhinitis Research - Sample Size Example

Tags: Means, Respiratory

View Example

Allergan Urinary Incontinence Research - Sample Size Example

Tags: Means, Urology

View Example

Allergan Neurogenic Detrusor Research - Sample Size Example

Tags: Means, Urology

View Example

Amgen Psoriatic Arthritis Research - Sample Size Example

Tags: Proportions, Rheumatology

View Example

Zoetis Veterinary Research - Sample Size Research

Tags: Proportions, Veterinary

View Example

Sanofi Multiple Sclerosis Research - Sample Size Example

Tags: Regression, Neurology

View Example

Pfizer Atrial Fibrillation Research - Sample Size Example

Tags: Survival Analysis, Cardiology

View Example

Amgen Metastatic Colorectal Cancer Research - Sample Size Example

Tags: Survival Analysis, Oncology

View Example

Bayer Liver Disease Research - Sample Size Research

Tags: Survival Analysis, Oncology

View Example