Mar 31, 2016

Genomic and clinical predictors for improving estimator precision in randomized trials of breast cancer treatments

Contemporary Clinical Trials Communications
Prasad PatilMichael Rosenblum

Abstract

The hope that genomic biomarkers would dramatically and immediately improve care for common, complex diseases has been tempered by slow progress in their translation beyond bioinformatics. We propose a novel use of genomic information where the goal is to improve estimator precision in a randomized trial. We analyze the potential precision gains from the popular MammaPrint genomic signature and clinical variables in simulations of randomized trials analyzed using covariate adjustment. We apply an estimator for the average treatment effect in the trial that adjusts for prognostic baseline variables to improve precision [1]. This precision gain can be translated directly into sample size reduction and corresponding cost savings. We conduct simulation studies based on resampling genomic and clinical data of breast cancer patients from four publicly available observational studies. Separate simulation studies were conducted based on each of the four data sets, with sample sizes ranging from 115 to 307. Adjusting only for clinical variables provided gains of -1%, 5%, 6%, 17%, compared to the unadjusted estimator. Adjusting only for the MammaPrint genomic signature provided gains of 2%, 4%, 4%, 5%. Simultaneously adjusting for clinic...Continue Reading

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Biological Markers
Observational Study
Size
Genome
Genomic Stability
Clinical Trials, Randomized
Bio-Informatics
Protein Biosynthesis
Objective (Goal)
Genomics

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Bone Marrow Neoplasms

Bone Marrow Neoplasms are cancers that occur in the bone marrow. Discover the latest research on Bone Marrow Neoplasms here.

IGA Glomerulonephritis

IgA glomerulonephritis is a chronic form of glomerulonephritis characterized by deposits of predominantly Iimmunoglobin A in the mesangial area. Discover the latest research on IgA glomerulonephritis here.

Cryogenic Electron Microscopy

Cryogenic electron microscopy (Cryo-EM) allows the determination of biological macromolecules and their assemblies at a near-atomic resolution. Here is the latest research.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

LRRK2 & Immunity During Infection

Mutations in the LRRK2 gene are a risk-factor for developing Parkinson’s disease. However, LRRK2 has been shown to function as a central regulator of vesicular trafficking, infection, immunity, and inflammation. Here is the latest research on the role of this kinase on immunity during infection.

Antiphospholipid Syndrome

Antiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by the presence of antibodies directed against phospholipids.

Meningococcal Myelitis

Meningococcal myelitis is characterized by inflammation and myelin damage to the meninges and spinal cord. Discover the latest research on meningococcal myelitis here.

Alzheimer's Disease: MS4A

Variants within membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease by recent genome-wide association studies. Here is the latest research.