Notice of Correction and Clarification to PAR-18-947 "Integrating Biospecimen Science Approaches into Clinical Assay Development (U01)"

Notice Number: NOT-CA-20-029

Key Dates
Release Date: February 10, 2020

Related Announcements
PAR-18-947

Issued by
NATIONAL CANCER INSTITUTE (NCI)

Purpose

The purpose of this Notice is to correct and clarify the nature and scope of biospecimens that can be utilized in PAR-18-947 "Integrating Biospecimen Science Approaches into Clinical Assay Development (U01)".

The following sections of the FOA have been impacted:

Part 2. Full Text of Announcement, Section I. Funding Opportunity Description, Purpose

Currently reads with corrections (in italics):

This Funding Opportunity Announcement (FOA) will support extramural research to investigate and mitigate challenges facing clinical assay development and subsequent analytical validation due to preanalytical variability in tumor tissue biopsies, blood biospecimens utilized as “liquid biopsies, or other biospecimens as described in this FOA. Extramural research funded under this FOA may include investigations of preanalytical variability associated with the procurement and study of small biopsies (core biopsies, small excision samples), blood utilized for liquid biopsies, tissue swabs, tissue secretions, pleural and esophageal aspirates, feces, or bodily fluids like sweat, urine, CSF, breast milk and saliva. Investigator-designed experiments will explore how different biospecimen preanalytical conditions affect emerging and clinically relevant biomarkers quantified by a variety of testing platforms. The results from this research program will improve the understanding of how analytical quantification of clinically relevant biomarkers is affected by variation in biospecimen collection, processing, and storage procedures. The overall goal is to expedite biomarker clinical assay development through evidence-based standardization of biopsy handling practices.

Part 2. Full Text of Announcement, Section I. Funding Opportunity Description, Background, subsection “Importance of preanalytical factors in biospecimen research”.

Currently reads with corrections (in italics):

Detection of biomarkers in blood analytes such as cfDNA (cell-free DNA) and CTCs (circulating tumor cells) is a promising approach for non-invasively tracking tumor behavior over time, potentially enhancing cancer management by assessing tumor burden, detecting recurrence, monitoring early response and identifying drug resistance. Preanalytical considerations are also challenging for such “liquid biopsies,” as inconsistency between sample handling protocols and lack of standardization among analytical techniques has created obstacles for translating cfDNA analysis to clinical practice. CTC analysis, including enumeration and characterization, is also affected by preanalytical factors. Challenges introduced by preanalytical variability also affect the isolation and analysis of exosomes and other extracellular vesicles, underscoring the need for rigorous analytical validation.

Bodily fluids such as urine and CSF have emerged as biospecimens for potential detection of biomarkers in clinical assays that can directly affect patient diagnosis, treatment, and outcomes. Tissue swabs, tissue secretions, pleural and esophageal aspirates, feces, sweat, breast milk and saliva may also have potential application in clinical biomarker research.

Differences in assay results can be a result of differences in preanalytical factors such as ischemia times, preservation method, and tumor heterogeneity. Such preanalytical factors may alter biomarker measurements and influence the performance of assay technologies. Variability and biases introduced in the early stages of biomarker assay development, if not addressed and understood, can increase the likelihood of irreproducible data and incorrect conclusions. This is of significant concern for NCI clinical research. Basic and applied biospecimen science investigation will provide valuable insights into how to limit variability in clinical assay results from small biopsies.

Part 2. Full Text of Announcement, Section I. Funding Opportunity Description, Research Objectives and Scope

Currently reads with corrections (in italics):

This Funding Opportunity Announcement (FOA) will support extramural research to investigate and mitigate challenges facing clinical assay development and subsequent analytical validation due to preanalytical variability in tumor biopsies, blood biospecimens utilized as “liquid biopsies,” and other biospecimen types as described in this FOA. This FOA will fund research to support clinical assay development and validation through the identification and mitigation of preanalytical factors associated with collection, processing, and storage that negatively influence clinical assay results and reproducibility.

Using a cooperative agreement mechanism, the research will be conducted by a collaborative, interdisciplinary network that integrates clinical researchers with academic and private sector scientists in projects that focus on preanalytical challenges specific to:

  • tumor tissue biopsies such as FNAs, core biopsies, small excisions, or pleural fluid aspirates, and/or
  • blood liquid biopsy assays targeting cfDNA, microRNA, CTC’s, exosomes and metabolites, and/or
  • other biospecimen such as tissue swabs, tissue secretions, esophageal aspirates, feces, sweat, urine, CSF, breast milk and saliva

All other aspects of PAR-18-947 remain unchanged.

Inquiries

Please direct all inquiries to:

Lokesh Agrawal, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5718
Email: Lokesh.agrawal@nih.gov

Abhi Rao, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5715
Email: abhi.rao@nih.gov