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

Dose Size and Dosing Frequency: Determination Methods01:21

Dose Size and Dosing Frequency: Determination Methods

Determining the optimal dose size and dosing frequency in pharmacotherapy is crucial for achieving therapeutic effectiveness while minimizing adverse effects. This article explores the methodologies employed in determining these parameters, focusing on their significance and interplay to tailor dosing regimens.Dose Size: Dose size refers to the amount of a drug administered in a single dose. It is determined based on the drug's pharmacodynamics and pharmacokinetics properties and...
Determination of Multiple Dosing Parameters: Loading and Maintenance Doses01:25

Determination of Multiple Dosing Parameters: Loading and Maintenance Doses

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...
Crossover Experiments01:16

Crossover Experiments

Crossover experiments, also called the repeated-measurements design, is a study design in which all experimental units are exposed to all treatments in different periods. Crossover experiments are generally used in psychology, the pharmaceutical industry, agriculture, and medicine.
Crossover designs are performed even with smaller sample sizes since the samples can act as their controls. These are better than simple randomized trials since patients are exposed to all the treatments.
Dosage Regimens: Designs and Approaches01:28

Dosage Regimens: Designs and Approaches

Designing a dosage regimen, which refers to the manner of drug administration, is a complex process involving the selection of drug dose, route, and frequency. This process is underpinned by pharmacokinetic parameters derived from tests and population averages. These parameters are then tailored to patient-specific variables such as diagnosis, demographics, and allergy status. Once therapy commences, therapeutic response monitoring is critical and achieved through clinical and physical...
Dose Response Curve: Conventional Versus Nonmonotonic01:21

Dose Response Curve: Conventional Versus Nonmonotonic

The correlation between a drug's dosage and its impact on a biological system is a cornerstone of pharmacology and toxicology. Conventional dose–response curves, which include graded and quantal relationships, are key to this understanding. Graded dose–response curves depict the spectrum of a biological reaction to different doses within an individual, indicating that as the drug dosage increases, so does the intensity of the response. On the other hand, quantal dose–response relationships...
Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations01:15

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

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...

You might also read

Related Articles

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

Sort by
Same author

Balancing the effective sample size in prior across different doses in the curve-free Bayesian decision-theoretic design for dose-finding trials.

Journal of biopharmaceutical statistics·2026
Same author

A curve free Bayesian decision-theoretic design for phase Ia/Ib trials considering both safety and efficacy outcomes.

Statistics in biosciences·2021
Same author

Two for the price of one: a dual treatment benefit of long-acting octreotide in occult bleeding and diuretic intractable ascites.

Frontline gastroenterology·2017
Same author

A simple Bayesian decision-theoretic design for dose-finding trials.

Statistics in medicine·2012
Same author

Design issues in dose-finding Phase I trials for combinations of two agents.

Journal of biopharmaceutical statistics·2009
Same author

Respiratory infections with Pseudomonas aeruginosa in children with cystic fibrosis: early detection by serology and assessment of risk factors.

JAMA·2002

Related Experiment Video

Updated: May 21, 2026

Diagonal Method to Measure Synergy Among Any Number of Drugs
12:08

Diagonal Method to Measure Synergy Among Any Number of Drugs

Published on: June 21, 2018

A two-dimensional search algorithm for dose-finding trials of two agents.

Bee Leng Lee1, Shenghua Kelly Fan

  • 1Department of Mathematics, San José State University, San José, CA 95192, USA. beeleng.lee@sjsu.edu

Journal of Biopharmaceutical Statistics
|June 2, 2012
PubMed
Summary
This summary is machine-generated.

This study introduces a novel two-dimensional algorithm for drug combination trials, improving patient safety by considering toxicity source for dose adjustments. The new method enhances safety in clinical trials without increasing sample size.

More Related Videos

Expedited Radiation Biodosimetry by Automated Dicentric Chromosome Identification (ADCI) and Dose Estimation
10:33

Expedited Radiation Biodosimetry by Automated Dicentric Chromosome Identification (ADCI) and Dose Estimation

Published on: September 4, 2017

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
11:15

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations

Published on: July 24, 2021

Related Experiment Videos

Last Updated: May 21, 2026

Diagonal Method to Measure Synergy Among Any Number of Drugs
12:08

Diagonal Method to Measure Synergy Among Any Number of Drugs

Published on: June 21, 2018

Expedited Radiation Biodosimetry by Automated Dicentric Chromosome Identification (ADCI) and Dose Estimation
10:33

Expedited Radiation Biodosimetry by Automated Dicentric Chromosome Identification (ADCI) and Dose Estimation

Published on: September 4, 2017

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
11:15

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations

Published on: July 24, 2021

Area of Science:

  • Clinical Pharmacology
  • Biostatistics
  • Drug Development

Background:

  • Current dose-finding algorithms for two agents are limited, often relying solely on toxicity frequency.
  • This one-dimensional approach may not fully capture complex dose-toxicity relationships.

Purpose of the Study:

  • To develop a more robust and safer dose-finding algorithm for two-agent combination therapies.
  • To enhance patient safety during early-phase clinical trials by refining dose escalation/deescalation strategies.

Main Methods:

  • A novel two-dimensional algorithm is proposed, incorporating both the frequency and source of dose-limiting toxicities (DLTs).
  • The algorithm modifies dose escalation/deescalation rules based on DLT origin.
  • A more conservative design is implemented for simultaneous dose escalations of both agents.

Main Results:

  • The proposed algorithm offers a more nuanced approach to dose finding compared to existing methods.
  • Simulations indicate improved patient safety profiles during dose escalation.
  • The conservative design for simultaneous escalation aims to prevent overly aggressive dosing.

Conclusions:

  • The new two-dimensional algorithm enhances patient safety in two-agent dose-finding trials.
  • Incorporating DLT source provides a more informative basis for dose adjustments.
  • This approach balances safety with trial efficiency, potentially avoiding larger sample sizes.