New Molecular Pathology Tests Advance Precision Medicine

Advancing precision medicine is a challenging endeavor for an institution. Daniel H. Farkas, PhD, HCLD, Section Head of Molecular Pathology in the Pathology & Laboratory Medicine Institute, is working with colleagues to complement Cleveland Clinic’s precision medicine testing through a program called RAMP — Revitalization and Acceleration of Molecular Pathology.

RAMP is a plan to invest in both the instrumentation needed for advanced testing and the personnel required to make it a reality. “RAMP will take molecular diagnostics at Cleveland Clinic to new heights by adding important precision medicine tests to help our patients,” says Dr. Farkas. “It will also modernize how we manage genomic information.”

Better data management

RAMP is based on several pillars; the first, a Laboratory Information Management System (LIMS), will dramatically reorganize how Molecular Pathology manages data. Precision medicine generates a significant amount of data that will now be handled through an automated laboratory system that provides end-to-end workflow tracking and integration.

Molecular oncology and NGS tests

Molecular oncology is another RAMP pillar and is composed of three next-generation sequencing (NGS)-based panel tests. A hematologic neoplasm (acute myeloid leukemia, acute lymphocytic leukemia, etc.) panel, launched in late June, is used to interrogate 62 relevant genes and will now be done in house, expanding upon the replaced send-out gene panel. The second NGS laboratory-developed molecular oncology test available later in 2018 interrogates 34 genes for diagnosis and classification of sarcomas in support of the Department of Pathology’s renowned sarcoma service. A third panel, a 170-gene, pan-solid tumor test will be available to replace expensive send-out tests later in 2018.

These NGS-based tests will improve patient care by covering more targets and enabling improved turnaround time, a critical aspect of managing patients with a diagnosis of cancer. Local storage of these complex genomic data will facilitate discussion among caregivers at Genomics Tumor Boards and enable rich opportunities for discovery, data-mining, improved care and research.

Carrier screening panel

Yet another RAMP pillar is a carrier screening panel developed with significant input from physicians and genetic counselors in obstetrics and maternal-fetal medicine. This panel will not only simplify logistics for our ordering physicians but also may provide resources to launch more low-volume but medically important tests in the future.

Pharmacogenomics

Pharmacogenomics (PGx) is another important RAMP component. PGx test results can be used to more rationally administer many drugs that are metabolized differently by individuals based on their genetics. Two key applications include using PGx testing to help manage the administration of pain medication and antidepressants; there are many more examples of test utility. Jennifer Hockings, PharmD, PhD, a pharmacogenomics clinical specialist, has developed a panel of 43 genes, representing a mixture of genes that are clinically relevant and on the cusp of demonstrated clinical utility. The PGx panel will start with a soft launch in an abdominal surgery research study. In addition, Belinda Udeh, PhD, is developing health economics outcomes models to evaluate the hypothesis that more rapid pain management benefits the patient and could perhaps lead to earlier inpatient discharges.

Noninvasive prenatal testing

The Molecular Pathology Section is also exploring noninvasive prenatal testing (NIPT), a prenatal screening test for sex chromosomes and autosomal aneuploidy disorders, as part of RAMP. The test is used to analyze circulating, cell-free, fetal DNA purified from a pregnant woman’s blood. Testing with this analyte was perfected and made available in the U.S. earlier this decade and has become extremely popular. With very high positive predictive value, this screening test, performed on blood collected via a simple venipuncture, allows amniocentesis and chorionic villus sampling to be used only as a necessary diagnostic test to confirm positive screening results.

An ongoing effort

The pillars of RAMP will roll out throughout 2018 (the first test launched in late June 2018) and will also be offered as reference lab tests through Cleveland Clinic Labs. Ultimately, Dr. Farkas is optimistic that RAMP and its tail programs will allow Cleveland Clinic to offer patients and other health systems tools that can transform prevention, diagnosis and treatment. Click here for more information about the tests offered.