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 Experiment Videos

The evaluation of multiple surrogate endpoints.

J Xu1, S L Zeger

  • 1Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland, USA. jane_2_xu@sbphrd.com

Biometrics
|March 17, 2001
PubMed
Summary

Using multiple biomarkers as surrogate endpoints can improve treatment effect inferences over single markers. This study introduces a joint model to assess the benefit of multiple surrogates in clinical trials.

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

Continuous treatment with nicotine increases diazepam binding inhibitor (DBI) and its mRNA in the mouse brain.

Brain research. Molecular brain research·1998
Same author

Upregulation of pleiotrophin gene expression in developing microvasculature, macrophages, and astrocytes after acute ischemic brain injury.

The Journal of neuroscience : the official journal of the Society for Neuroscience·1998
Same author

Dynamic cross-linking by alpha-actinin determines the mechanical properties of actin filament networks.

The Journal of biological chemistry·1998
Same author

Does weather confound or modify the association of particulate air pollution with mortality? An analysis of the Philadelphia data, 1973-1980.

Environmental research·1998
Same author

Screening for overlapping bacterial artificial chromosome clones by PCR analysis with an arbitrary primer.

Proceedings of the National Academy of Sciences of the United States of America·1998
Same author

Mechanical properties of actin filament networks depend on preparation, polymerization conditions, and storage of actin monomers.

Biophysical journal·1998

Area of Science:

  • Biostatistics
  • Clinical Trial Design
  • Pharmacometrics

Background:

  • Surrogate endpoints accelerate clinical trials by reducing the need for large sample sizes and long follow-up periods.
  • Current research predominantly validates single biomarkers as surrogates, overlooking the potential of combined markers.
  • The validity and utility of multiple surrogate markers for predicting clinical outcomes remain underexplored.

Purpose of the Study:

  • To investigate the enhanced inference capabilities of using multiple biomarkers as surrogate endpoints compared to single markers.
  • To propose and evaluate a statistical framework for assessing the benefit of multiple surrogates in treatment efficacy studies.
  • To extend existing joint modeling approaches for clinical events and repeated biomarker measures.

Main Methods:

  • Development of a joint statistical model for time-to-clinical-event data and longitudinal repeated measures on multiple potential surrogate biomarkers.
  • Extension of established joint modeling formulations (Xu and Zeger, 2001; Fawcett and Thomas, 1996).
  • Implementation of Markov chain Monte Carlo (MCMC) methods for parameter estimation.

Main Results:

  • The proposed joint model effectively incorporates multiple biomarkers to improve inferences on treatment effects.
  • Two novel measures quantify the relative advantage of employing multiple surrogates over a single surrogate.
  • The methodology demonstrates practical application through an analysis of a schizophrenia clinical trial dataset.

Conclusions:

  • Multiple biomarkers, when jointly modeled, offer superior insights into treatment effects on clinical endpoints compared to single surrogates.
  • The developed statistical framework provides a valuable tool for optimizing clinical trial design and analysis.
  • This approach enhances the efficiency and reliability of evaluating therapeutic interventions.

Related Experiment Videos