The discussion—led by a panel brought together by MDS Pharma Services—focused on biomarker use in both oncology and cardiac evaluations in clinical trials, and how biomarker use can be used moving forward.

Samir Khleif, MD, Chief, Cancer Vaccine Section for the NIH’s National Cancer Institute, described three already identified and used biomarkers within the oncology arena. These include PSA, approved in 1994 as a biomarker for the early detection of prostate cancer; Her-2-neu approved as a biomarker for selection of therapy for breast cancer; and EGFR, approved in tandem with Erbitux for the selection of therapy in NSCLC, pancreatic cancer and other types of cancer.

However, the actual issue of how to develop biomarkers remains “broken,” according to Khleif. Contributing factors include a lack of understanding of scientific pathway to clinical use; lack of understanding of regulatory pathway; lack of a viable business model; and a disconnect between development and delivery.

Drilling down to real-life application, Patrice Hugo, PhD, VP Scientific Affairs, Global Central Lab, MDS Pharma Services, told panel attendees that in its role as a CRO, it has a lot of insight into biomarkers use and application across many indications and studies. However, it legally often
cannot fully share information because it is proprietary to the sponsor. Nonetheless, central labs have a wealth of experience in biomarker assay set up and validation, required assay specification for a given therapeutic area and cost management.

ECG as a Biomarker
In the ECG and monitoring of a drug’s cardiac safety in patients, there is more sharing of information between sponsors, based on FDA intervention. The ECG Warehouse, a centralized repository archives ECGs that are directly uploaded from a sponsor’s clinical database. Data can be mined for trends, rare events, and other indicators of risk, according to panel presenter Wendy Sanhai, PhD, Senior Scientific Advisor, Office of the Commissioner for the FDA. As of 2005, this warehouse has existed from which reviewers can access via Web browser.

Another initiative, the THEW (Telemetric and Holter ECG Warehouse) is similar to the ECG Warehouse and is hosted by the Heart Research Follow-Up Program and the University of Rochester Medical Center.

Hugo later told Applied Clinical Trials that the situation is different outside of cardiac biomarkers. He said, “Unfortunately, although Central Labs are testing hundreds of biomarkers on thousands of patients per year, the lack of access to basic patient medical information makes it almost impossible to perform a macro-analysis across all trials for a given indication to evaluate the clinical utility of a biomarker. In addition, for confidentiality purposes, such analyses might not be possible. The ECG warehouse project, launched by the FDA under the Critical Path Initiative, is a way to circumvent those hurdles. It allows for the macro-analysis of 400,000 ECG profiles to identify Indicators of cardiac toxicity that can be used in drug development and clinical decision-making regarding safety.”

However, Hugo added, “I believe that such projects could also be prioritized to review biomarkers in oncology trials, or other therapeutic areas, to evaluate their clinical use with 100,000s of data points across multiple trials.”

This list from Hugo’s presentation at the panel, indicates current initiatives to address biomarkers:

FDA Predictive Safety Testing Consortium
FDA Critical Path Initiative
NIH RoadMap Initiative
NCI/FDA/AACR Cancer Biomarker Collaborative
Biomarker Consortium
NCI Early Detection Research Network
CriticalPath(C-Path) Institute
Health and Human Services (HHS) Personalized Health Care Initiative
Standards for Reporting Diagnostic Accuracy (STARD)
International Cancer Biomarker Consortium
Secretary’s Advisory Committee on Genetics, Health and Society (SACGHS)
Personalized Medicine Coalition
Advamed
Coalition for the 21stCentury Medicine