Correlative Science - page 2

Clinical Applications of Correlative Science - cont.

Leadership is needed in the following areas

• Determining whether correlative marker collection should be mandatory for patients to enter a clinical trial.
  • The future of targeted therapy depends on tying tissue biomarker research to patient outcomes. The best way to do this is within a clinical trial where outcomes are tracked and measured.
  • Is this 'future good' explanation enough reason to require 'current' trial participants mandatory tissue donation?
• Creation of standardization guidelines needed for patient consent, collection and processing of samples.
  • See image below showing various steps that tissue moves through. If all of these are not standardized, you may end up comparing apples to oranges as values may change due to poor processing and storage.
• Standardizing clinical information from patients donating samples so that information can be tied to outcomes. Privacy issues are involved as well and must be addressed.
  • Again if clinical information is not identical across samples you may end up comparing apples to oranges with no transferable new knowledge gained.
• Developing better guidelines: some FDA guidelines do not adequately distinguish biomarkers used as surrogate endpoints from those used for treatment selection and are inappropriate for the latter applications.
  • Treatment selection using biomarkers is based on responders vs. non-responders and/or different side effect profiles.
  • Surrogate endpoints are entirely different and have a focus on time to recurrence and/or survival.
• Determining whether groups that receive government funding should be able to keep the data derived from correlative science studies private rather than adding it to the caBIG data bank; examples of these groups are cooperative groups, cancer centers and individual academic researchers.
• Creating a mechanism so that the data used to develop a predictive classifier must be distinct from the data used to test hypotheses about treatment effect in subsets determined by the classifier.

The image below depicts the various steps that a tissue sample must undergo: from the patient through collection, processing, storage and analysis. It is hoped that this process will provide answers that help patients in the future. Image courtesy the National Cancer Institute.

The Future of Correlative science

The promise of genomic and personalized medicine lies in the ability to forge a connection between patient clinical data and scientific measurements on collected biospecimens such as the results of a SNP, transcriptional profile, or sequencing assay.

Research is shifting toward focus on molecular profiling, in which specific assays are conducted on large numbers of diseased and normal specimens to aid in the search for genetic, protein, and transcriptional clues to the origin and pathways of disease.

Because of this trend, the need for integration of large amounts of clinical data with scientific results has become critical to the process of identifying the criteria for subpopulations that may best benefit from a new drug or treatment.

Long-term longitudinal studies, such as government-managed biobanks, in which populations are followed for a long periods of time to uncover population trends, require the ability to operationally track millions of specimens.

Image courtesy of The Office of Biorepositories and biospecimen Research (OBBR)

Many pharmaceutical companies are also creating patient registries, which are prospective banks of large numbers of samples from particular patient populations. Companies hope to examine genetic or transcriptional trends that may yield clues to potential treatments or drug response profiles. Together, these trends have increased the number of samples that have been collected for the purpose of discovery.

 

Correlative Science Projects

We have only included a couple of projects below but many individual cancer centers, universities and commercial companies have projects/programs already in place.

1) The NCI Office of Biorepositories and Biospecimen Research (OBBR):

The Office of Biorepositories and Biospecimen Research (OBBR) was established in 2005 in recognition of the critical role that biospecimens play in cancer research.

The OBBR is responsible for developing a common biorepository infrastructure that promotes resource sharing and team science in order to facilitate multi-institutional, high-throughput genomic and proteomic studies. OBBR has published guidelines for the standardization of collecting, processing and testing patient tumor samples.

For more information see: http://biospecimens.cancer.gov

2) caHUB:

caHUB is a unique, centralized, non-profit public resource sponsored by the National Cancer Institute that works to ensure an adequate, continuous supply of human biospecimens and associated data that is measurable, high quality and acquired within an ethical framework.

Funding:

The following is copied from the NCI site and is used as an example of one funding mechanism that is encouraging biomarker exploration.

"PA-08-134 Expiration Date: May 8, 2012

This Funding Opportunity Announcement (FOA) is intended to support translational correlative studies that utilize annotated tumor and/or other biospecimens collected during large-scale multiinstitutional clinical and/or prevention trials, respectively. The Cancer Therapy Evaluation Program (CTEP), the Cancer Diagnosis Program (CDP), and the Cancer Biomarkers Research Group (CBRG) of the NCI are cooperatively sponsoring this FOA with the overarching goal to facilitate predictions of responses to current interventions, and inspire future development of improved therapeutic and preventive strategies.

Projects proposed in response to this FOA should address:

• The correlations between intervention outcomes and cancer patients
• Disease characteristics determined at various cellular/molecular levels. For example, disease progression patterns may be correlated with tumor genotypic and/or phenotypic profiles (at the levels of the genome, epigenome, gene expression and/or protein and non-protein molecular markers."

CISN Summary

• Correlative science discoveries hold the promise of personalized medicine.
• Success depends on having donated tissue that has been collected, processed, stored and analyzed in a standardized way.