By Louise Lazear

Access Genetics brings genetic testing to the clinical lab
Providing in-vitro diagnosis at the point-of-care is relative to the technology employed and the application — consider, for example, glucose at the bedside, blood gases in critical care settings, or cardiac markers in the emergency department. While many of these technologies now reflect a routine standard of care, initial implementation often presented monumental challenges that required the combined efforts of diverse professionals with the common view of the potential benefits these technologies would bring to their patients.

With the advent of new technologies for molecular diagnosis, clinicians and laboratorians are now challenged with providing genetic testing to their communities. While some rely on relationships with reference laboratories, many are investigating the prospect of bringing some of these assays into the clinical laboratory, with the ultimate goal of improving patient care by providing local access to esoteric testing.

While most medium to high-complexity clinical laboratories possess the expertise to perform these assays, many lack access to expert interpretation, as well as the ability to provide consultation with ordering physicians. Recognizing both the need for this expertise, as well as the expanding market for clinically relevant genetic testing, Access Genetics (AG) of Minneapolis, Minn. offers a service that allows laboratories to provide genetic testing to their communities.

“Our approach is to provide genetic testing in a very accessible and straightforward way to get clinically relevant information into the hands of practitioners,” said Ronald G. McGlennen, MD, PhD, a molecular geneticist and president of AG. “We’ve focused on genetic assays that provide ‘meat and potatoes’ information. And we feel that by improving the availability of off-the-shelf genetic technologies, more laboratories will be able to provide these tests, resulting in greater accessibility.”

McGlennen points out that while genetic testing technology has become less complex and more available, the number of DNA diagnostic laboratories in the US has increased by only 30 since 1998, for a total of about 190 laboratories. Reasons for this apparent lack of mainstream genetic testing include a gap in knowledge about how to use this information to improve patient care, and a perception of high cost associated with training time and capital investment required to perform the tests in the clinical laboratory.

Other hurdles to implementation at the local level have also been identified. “The real reason why more laboratories are not involved in genetic testing is that they can’t get their arms around the technology. To offer a complete service, we realized we had to address this concern. Our process reduces the complexity of both DNA extraction and amplification, as well as interpretation of results,” said McGlennen. Through a sophisticated yet streamlined combination of hardware, software, and telemedicine, AG combines the expertise of the clinical laboratory with the company’s experience in assay performance and results interpretation. Using a scalable, all-inclusive test kit, the hospital laboratory performs a DNA extraction based on Gentra Capture column technology. After extraction, the DNA is amplified using Third Wave Technologies Invader chemistry. The sample is then placed into a high-throughput fluorometer, and results are transmitted via a HIPAA-compliant secure internet access for interpretation by Dr. McGlennen or one of his colleagues. Reports are sent back via the internet to the laboratory for distribution to the referring physician, with same-day turn-around in most cases.

“The best turn-around time that we have had so far is seven hours, which is remarkable when you consider that it takes about one and a half hours of hands-on laboratory technician work and four additional hours of incubation,” said Naomi Williamson, COO at Access. “Compare this with sending a sample to a reference laboratory, where turn-arounds can take anywhere from three to four days to three weeks, depending upon when the result is interpreted,” she added.

To provide and maintain this rapid response, Dr. McGlennen or one of his associates receives notifications by both pager and email when a test result hits the Access server. Test results are reviewed, and an interpretation of the genotype is reported. AG has also developed an expert database of relevant information from the current medical literature that discusses both implications of the test result and treatment options. Using patient demographics and the reason for testing, the Access physician customizes the report to the specific patient. “Right now, the test report goes to the ordering physician through the laboratory that performs the assay. The report is the laboratory’s product, with the laboratory’s logo. We are the consultant, but we also provide telephone consultations for the ordering physician as part of our service,” Williamson explained. The company is currently exploring options to help laboratories incorporate reports directly into the hospital information system and the electronic medical record.

Both the hardware configuration and the assay kit were developed to help laboratories offer genetic tests with minimal capital investment. The kit provides prepackaged materials to enable the lab to turn patient samples into a signal that can be read and interpreted remotely. The kit has been designed for the clinical setting and can accommodate testing done in batches as small as three or four, as well as larger batches. The hardware includes a fluorometer and desktop client interface that may either be purchased or leased on a monthly basis. AG has developed relationships with suppliers, allowing them to purchase in bulk and pass these savings to their partner laboratories. “We’ve used the principals of supply-chain management to minimize the cost footprint. Combined with a very competitive per test consultation fee, we help laboratories enter this market with an emphasis on higher quality reports and competitive costs,” said Williamson.

In addition to assay development, interpretation, and consultative support, Access also assist laboratories by providing information on test pricing in the marketplace, CPT codes for optimal reimbursement, and extra detail for insurers in the event that additional information is required for reimbursement. Break-evens for the laboratory depend on test volumes, prices, and reimbursement levels. With genetic testing for thrombophilia, for example, Access estimates that a laboratory can break even with as few as 20 to 25 tests per month.

According to McGlennen, key strategies in successfully performing genetic testing at the point of care are to focus on high volume, simple tests which also provide therapeutic value. Currently, AG offers testing for both Factor V Leiden (FVL) and Factor II/Prothrombinen, single point mutations that are the first and second most common risk factors for venous thrombosis, respectively. FVL has a high incidence rate, from two to ten percent in most northern European populations, and determination of risk for venous thrombosis (VT) has significant impact on patient management. The presence of FVL is especially important in the management of women taking oral contraceptives, for targeting patients for anticoagulant therapy, and for postoperative treatment of surgical patients at risk for thrombosis.

Currently, clinicians rely on measuring activated protein C resistance (aPCR), a modified PTT that measures time to clot formation in the presence and absence of aPCR. Results are reported in terms of sensitivity or normalized ratios, with patients having shorter time to clot formation exhibiting smaller ratios. Other factors can affect results including lupus inhibitors, reduced levels of prothrombin and Factor X, and increased levels of Factor VIII. According to McGlennen, contrary to testing for FVL, aPCR does not, in and of itself, define a specific diagnosis. “If you are tested for FVL mutation and the results are positive, then one can directly infer your risk of developing thrombosis,” he said.

Williamson views their service as a way to expand the genetic testing market by making information from genetic tests relevant and available to physicians in near real time. “Because of our turn-around time on thrombophilia tests, for example, a surgeon in an emergency situation can now better assess a patient’s tendency for blood clots, and plan accordingly for post-operative treatment. This makes genetic testing relevant in situations that haven’t been explored before,” she said. Access Genetics continues to grow its test menu, and plans to offer both testing for cystic fibrosis and HPV within the coming months.

Louise Lazear is a freelance writer based in Charlotte, N.C.