Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Determination of Multiple Dosing Parameters: Loading and Maintenance Doses01:25

Determination of Multiple Dosing Parameters: Loading and Maintenance Doses

236
A loading dose is an essential pharmacological strategy to rapidly achieve the target plasma drug concentration necessary for an immediate therapeutic effect. This approach is especially critical for drugs characterized by slow absorption or extended half-lives, where delaying therapeutic plasma levels could compromise treatment outcomes. By administering a loading dose, clinicians ensure a prompt onset of drug action, even for agents with complex pharmacokinetic profiles.Achieving steady-state...
236
Multiple Comparison Tests01:13

Multiple Comparison Tests

4.5K
Multiple comparison test, abbreviated as MCT, is a post hoc analysis generally performed after comparing multiple samples with one or more tests. An MCT will help identify a significantly different sample among multiple samples or a factor among multiple factors.
It would be easy to compare two samples using a significance alpha level of 0.05. In other words, there is only one sample pair to be compared. However, it would be difficult to identify a significantly different sample if the number...
4.5K
Bioavailability Study Design: Single Versus Multiple Dose Studies01:11

Bioavailability Study Design: Single Versus Multiple Dose Studies

238
Bioavailability studies are essential for understanding how a drug is absorbed, distributed, metabolized, and excreted in the body. These studies assess the extent and rate at which the active pharmaceutical agent becomes available at the site of action. The design of bioavailability studies can involve single-dose or multiple-dose regimens, each with distinct advantages and limitations.Single-dose studies are the preferred approach due to their simplicity and reduced drug exposure for...
238
Drug Accumulation During Multiple Dosing: Repetitive IV Injections01:21

Drug Accumulation During Multiple Dosing: Repetitive IV Injections

281
Calculating drug dosage and accumulation in multiple-dose regimens is crucial for achieving therapeutic efficacy while avoiding toxicity. This involves determining the plasma drug concentrations over time to optimize dosing schedules. The principle of superposition is fundamental in this process, allowing for the prediction of drug concentration in plasma following multiple doses based on single-dose data.The principle of superposition asserts that the plasma concentration-time curves from...
281
Drug Accumulation During Multiple Dosing: Intermittent IV Infusions01:24

Drug Accumulation During Multiple Dosing: Intermittent IV Infusions

253
Intermittent intravenous (IV) infusion is a method of drug administration where medications are delivered over short infusion periods followed by intervals of no drug delivery. This approach helps to prevent sustained high drug concentrations in the bloodstream, reducing the risk of adverse effects associated with prolonged exposure. Unlike continuous infusion, steady-state concentrations may not be achieved during a single dosing cycle but can be reached through repeated...
253
Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations01:15

Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations

252
Gentamicin, an aminoglycoside antibiotic, is commonly administered via intermittent intravenous infusion to treat severe infections. An intermittent one-hour infusion of gentamicin, administered at eight-hour intervals, allows for precise control of plasma drug concentrations, minimizing toxicity while ensuring therapeutic efficacy. Pharmacokinetic principles govern the dynamics of plasma concentrations and can be mathematically described using specific equations.The plasma drug concentration...
252

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

The Acute Stroke Therapy by Inhibition of Neutrophils study - Key features and impact.

Pharmaceutical statistics·2022
Same author

Selection bias for treatments with positive Phase 2 results.

Pharmaceutical statistics·2020
Same journal

Ensuring Quality in Preclinical Research: The Importance of Being Human.

Biometrical journal. Biometrische Zeitschrift·2026
Same journal

Addressing Cluster-Level Treatment Effect Heterogeneity in Sample Size Determination for Hierarchical 2 × 2 Factorial Designs.

Biometrical journal. Biometrische Zeitschrift·2026
Same journal

A Multiple Imputation Approach to Distinguish Curative From Life-Prolonging Effects in the Presence of Missing Covariates.

Biometrical journal. Biometrische Zeitschrift·2026
Same journal

Tests for Categorical Data Beyond Pearson: A Distance Covariance and Energy Distance Approach.

Biometrical journal. Biometrische Zeitschrift·2026
Same journal

Nonparametric Estimation of the Patient-Weighted While-Alive Estimand.

Biometrical journal. Biometrische Zeitschrift·2026
Same journal

Two-Stage Multiple Test Procedures Controlling False Discovery Rate With Auxiliary Variable and Their Application to Set4 <math><semantics><mi>Δ</mi> <annotation>$\Delta$</annotation></semantics></math> Mutant Data.

Biometrical journal. Biometrische Zeitschrift·2026
See all related articles

Related Experiment Video

Updated: Feb 1, 2026

Barnes Maze Testing Strategies with Small and Large Rodent Models
12:59

Barnes Maze Testing Strategies with Small and Large Rodent Models

Published on: February 26, 2014

43.7K

Testing strategy in phase 3 trials with multiple doses.

Jianjun David Li1, Simon Kirby2

  • 1Statistics, Pfizer, Collegeville, PA, USA.

Biometrical Journal. Biometrische Zeitschrift
|December 15, 2018
PubMed
Summary
This summary is machine-generated.

This study explores multiplicity testing for two-dose phase 3 clinical trials. A new approach combining pooled and high-dose strategies is recommended for improved efficacy testing.

Keywords:
multiple testingphase 3 clinical trialstype I error rate control

More Related Videos

Minimal Erythema Dose MED Testing
06:24

Minimal Erythema Dose MED Testing

Published on: May 28, 2013

42.8K
Robotic Production of Cancer Cell Spheroids with an Aqueous Two-phase System for Drug Testing
09:58

Robotic Production of Cancer Cell Spheroids with an Aqueous Two-phase System for Drug Testing

Published on: April 23, 2015

9.5K

Related Experiment Videos

Last Updated: Feb 1, 2026

Barnes Maze Testing Strategies with Small and Large Rodent Models
12:59

Barnes Maze Testing Strategies with Small and Large Rodent Models

Published on: February 26, 2014

43.7K
Minimal Erythema Dose MED Testing
06:24

Minimal Erythema Dose MED Testing

Published on: May 28, 2013

42.8K
Robotic Production of Cancer Cell Spheroids with an Aqueous Two-phase System for Drug Testing
09:58

Robotic Production of Cancer Cell Spheroids with an Aqueous Two-phase System for Drug Testing

Published on: April 23, 2015

9.5K

Area of Science:

  • Clinical Trials
  • Biostatistics
  • Pharmaceutical Research

Background:

  • Phase 3 clinical trials often involve multiple doses to assess efficacy.
  • Ensuring robust multiplicity testing is crucial for accurate interpretation of results.
  • Existing methods may not fully leverage dose-response relationships.

Purpose of the Study:

  • To review and propose multiplicity testing procedures for two-dose phase 3 trials.
  • To introduce novel approaches by considering dose consistency.
  • To enhance the statistical power and reliability of efficacy assessments.

Main Methods:

  • Review of existing multiplicity testing procedures (e.g., Bonferroni, Hochberg).
  • Development of new procedures applying existing methods to pooled and high doses.
  • Simulation studies to compare the performance of different approaches.

Main Results:

  • The pooled dose and high dose can offer greater consistency for testing.
  • A combined procedure using the 4A method and pooling approach demonstrated superior performance.
  • The proposed methods show potential for improved statistical power in dose-efficacy evaluations.

Conclusions:

  • The recommended multiplicity testing strategy enhances the evaluation of two-dose regimens in phase 3 trials.
  • This approach offers a more consistent and powerful way to assess dose efficacy.
  • Consideration of dose pooling and high-dose specific testing is beneficial.