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

Dosage Regimens: Partial Pharmacokinetic Parameters01:01

Dosage Regimens: Partial Pharmacokinetic Parameters

It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...
Methods of Medium Optimization01:28

Methods of Medium Optimization

Optimizing growth media enhances microbial proliferation and maximizes product yield. Statistical experimental design methodologies provide structured and reproducible approaches, offering progressively higher levels of robustness and efficiency.The One-Factor-at-a-Time (OFAT) MethodThe One-Factor-at-a-Time (OFAT) method involves adjusting a single variable while keeping all others constant. However, it cannot detect interactions between variables, often leading to suboptimal outcomes when...
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...
Kaplan-Meier Approach01:24

Kaplan-Meier Approach

The Kaplan-Meier estimator is a non-parametric method used to estimate the survival function from time-to-event data. In medical research, it is frequently employed to measure the proportion of patients surviving for a certain period after treatment. This estimator is fundamental in analyzing time-to-event data, making it indispensable in clinical trials, epidemiological studies, and reliability engineering. By estimating survival probabilities, researchers can evaluate treatment effectiveness,...
Dose-Response Relationship: Potency and Efficacy01:22

Dose-Response Relationship: Potency and Efficacy

The potency of a drug is the measure of its ability to produce a biological response and can be compared by looking at the half-maximum effective concentration or EC50 values of different drugs. A lower EC50 value indicates higher potency of the drug. In the dose–response curve of two antihypertensive drugs, candesartan and irbesartan, a significant difference is observed in their EC50 values. A lower EC50 value for candesartan indicates that it is more potent than irbesartan, as it produces...
Pharmacokinetic–Pharmacodynamic Relationship: Problems01:24

Pharmacokinetic–Pharmacodynamic Relationship: Problems

The empirical approach to drug therapy optimization relies on correlating pharmacological response with administered dosage. Such an approach can be costly, time-consuming, and often yields poor correlation due to variables like formulation factors and drug elimination characteristics. A more precise approach correlates response with plasma drug concentration or the amount of drug in the body, rather than dosage. This is achieved through pharmacokinetic-pharmacodynamic (PK/PD) modeling, which...

You might also read

Related Articles

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

Sort by
Same author

Assessing Benefit in Patients With Heart Failure and Reduced Ejection Fraction: Analysis of the VICTORIA Trial Using Novel Prognostic Risk Stratification.

Journal of cardiac failure·2025
Same author

Analysis of composite time-to-event endpoints in cardiovascular outcome trials.

Clinical trials (London, England)·2024
Same author

Is inadequate risk stratification diluting hazard ratio estimates in randomized clinical trials?

Clinical trials (London, England)·2024
Same author

Applying polygenic risk score methods to pharmacogenomics GWAS: challenges and opportunities.

Briefings in bioinformatics·2023
Same author

Calculation of Phase 2 dose-finding study sample size for reliable Phase 3 dose selection.

Pharmaceutical statistics·2023
Same author

Statistical assessment of biomarker replicability using MAJAR method.

Statistical methods in medical research·2023
Same journal

Interpretable Bayesian Modeling for Multireader Multicase Studies: Addressing Overdispersion and Limited Sample Size in Diagnostic Enhancement Evaluation.

Statistics in medicine·2026
Same journal

Adaptive Sequential Multiple Hypotheses Testing for Concomitant Vaccine Safety Surveillance.

Statistics in medicine·2026
Same journal

Novel Distance Regression for Repeated Outcomes With Missing Data: Applications to Longitudinal and Crossover Studies of Microbiome Beta-Diversity.

Statistics in medicine·2026
Same journal

Optimal Weighted Tests for Replication Studies and the 'Two-Trials Rule' With Multiple Hypotheses.

Statistics in medicine·2026
Same journal

Identifiable Copula-Double-Cox Models: A Fully Parametric Framework for Dependent Right-Censored Survival Data.

Statistics in medicine·2026
Same journal

Moving From Individualized Risk-Based Prevention to Benefit-Based Prevention: Estimating Individualized Life-Years Gained From Prevention Services as a Basis for Eligibility.

Statistics in medicine·2026
See all related articles

Related Experiment Video

Updated: Jul 2, 2026

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
09:41

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells

Published on: July 15, 2015

An efficient method for accommodating potentially underpowered primary endpoints.

Jianjun Li1, Devan V Mehrotra

  • 1Merck Research Labs., UG1CD-44, 351 N. Sumneytown Pike, North Wales, PA 19454, USA. davidli2001@gmail.com

Statistics in Medicine
|September 2, 2008
PubMed
Summary
This summary is machine-generated.

This study introduces a novel method for clinical trials with multiple primary endpoints. It enhances the probability of achieving a positive trial outcome for clinically important but potentially underpowered endpoints.

More Related Videos

Inverse Probability of Treatment Weighting (Propensity Score) using the Military Health System Data Repository and National Death Index
06:55

Inverse Probability of Treatment Weighting (Propensity Score) using the Military Health System Data Repository and National Death Index

Published on: January 8, 2020

Related Experiment Videos

Last Updated: Jul 2, 2026

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
09:41

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells

Published on: July 15, 2015

Inverse Probability of Treatment Weighting (Propensity Score) using the Military Health System Data Repository and National Death Index
06:55

Inverse Probability of Treatment Weighting (Propensity Score) using the Military Health System Data Repository and National Death Index

Published on: January 8, 2020

Area of Science:

  • Biostatistics
  • Clinical Trial Design
  • Statistical Methodology

Background:

  • Clinical trials often face challenges with multiple primary endpoints, especially when some are underpowered.
  • Current approaches may lead to negative trial outcomes or reduced power when accommodating underpowered endpoints.

Purpose of the Study:

  • To propose a novel statistical method for handling clinically important but potentially underpowered primary endpoints in clinical trials.
  • To increase the likelihood of a positive trial outcome while maintaining statistical rigor.

Main Methods:

  • A new adaptive alpha allocation strategy is proposed for testing primary endpoints.
  • Endpoint A is tested at a prespecified level alpha(1) = alpha - epsilon, and endpoint B at an adaptive level alpha(2) based on the p-value of A.
  • The method controls the familywise type I error rate (FWER) at level alpha.

Main Results:

  • The proposed method increases the probability of achieving a positive trial compared to fixed alpha allocation schemes.
  • It offers a significant improvement over traditional methods like Hochberg's procedure for primary endpoint families.
  • Allows for conclusive interpretation of results for potentially underpowered primary endpoints.

Conclusions:

  • The novel adaptive alpha allocation method provides an effective solution for managing multiple primary endpoints in clinical trials.
  • This approach enhances trial power and the interpretability of results for all primary endpoints.
  • It offers a more flexible and powerful framework for clinical trial design and analysis.