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InSource Diagnostics Clinical Trial Explores Pharmacogenetics


NEW YORK (GenomeWeb) – InSource Diagnostics, a CLIA-certified clinical laboratory that performs blood, urine, and saliva testing, is enrolling patients in a clinical trial designed to validate biomarkers in urine that screen for patients who would likely benefit from DNA tests and could then receive more precise and beneficial drug prescriptions.

The biomarkers, measured in a routine urine test, would provide a more targeted approach for physicians selecting people within a patient population who could benefit from genetic testing.

InSource Diagnostics uses a measurement technique, liquid chromatography mass tandem mass spectrometry, to establish ratios between a parent drug and metabolite. If a patient has a genetic mutation expressed within the 2D6 enzyme, for example, a change in the ratio of parent (hydrocodone) to metabolite (hydromorphone) is expected. The firm has established metabolic ratios for all the drugs included in the trial that indicate ultra-rapid or poor metabolism.

Liver enzymes with underlying genetic mutations can increase side effects for patients taking certain drugs or reduce the therapeutic benefits of those drugs, according to InSource Diagnostics. In some cases, patients properly metabolize the drugs they are taking, but in other cases, the drugs are metabolized too rapidly, causing toxicity and adverse effects, or they are metabolized at a slow pace, leaving the patient feeling little or no effect. In the latter example, patients frequently seek higher doses or more drugs, and they become suspects for drug abuse, Sky Countryman, CEO of InSource Diagnostics, told GenomeWeb.

Pharmacogenetic tests are available that enable physicians to reduce adverse side effects by giving them information that allows them to prescribe drugs, or drug doses, that are more precisely matched to a patient’s metabolic profile. The challenge here is that the tests tend to be expensive and payors are often reluctant to reimburse costs, Countryman said.

The urine drug test, a standard part of patient care for assessing compliance or potential abuse in patients who are prescribed controlled substances, measures biomarkers reflecting the presence of genetic mutations expressed in the cytochrome P450 family of liver enzymes. The biomarkers would enable physicians to identify patients who may have the genetic factors leading to abnormal drug metabolism, Countryman said, and the patients would therefore be good candidates for genetic testing. 

Insurance providers, including Medicare, have been reluctant to support pharmacogenetic testing as a screening technique, because only about 10 percent of the population has a genetic mutation expressed in the cytochrome P450 family of enzymes, according to InSource Diagnostics.

Studies show that if one can identify early in patients’ lives that they are poor metabolizers or rapid metabolizers of drugs they have been prescribed, it will save the healthcare system because the number of adverse drug events is going to significantly decrease over patients’ lifetimes.

When some pharmacogenetic testing was curtailed by Medicare and commercial payors, Countryman said, he understood what they were saying and why they were saying it. “Physicians treating patients having adverse side effects saw the benefit of genetic testing, and then they wanted to test everybody,” Countryman said. “That is exactly the opposite to what payors wanted, which was to selectively identify patients with adverse events and then work with them from there.”

Executives at InSource Diagnostics considered what they could do from a scientific standpoint to try to bridge that gap from broadscale testing to tests that payors would find reasonable to reimburse, Countryman said.

“Our team looked for markers in urine that would potentially tell if somebody has a genetic abnormality and came up with a screening technique that is much more cost effective than a full genetic test,” Countryman said, “and that would allow us to find that 10 to 15 percent of the population that really would benefit from the genetic test.”

The team identified urine-based biomarkers for a list of common medications, including opioids, benzodiazepines, tricyclic antidepressants, and muscle relaxants. These include frequently prescribed pain drugs, such as hydrocodone and oxycodone.

For its clinical trial, InSource Diagnostics is recruiting physicians and patients who would help it validate the biomarkers. “We've validated them ourselves, but they are not really validated until you've tested them on a large number of people and shown in a peer reviewed article that this is a true result,” Countryman said.

The study duration is two years, and InSource Diagnostics is looking to recruit 14,000 patients, each for a 90-day trial.

“During that 90 days, the first thing we're trying to prove is that these urine biomarkers are a good screening tool to identify ultra slow or ultra rapid metabolism,” Countryman said.

Patients enrolling in the study receive a baseline test. Each randomly selected patient is then allocated to a control group or a test group. When the testing team identifies potential genetic abnormalities in people within the test group, it orders and pays for a genetic test. At the end of 90 days, the testing team analyzes whether there was a reduction in adverse drug events because the physicians knew about the genetic status of the patients and were able to prescribe suitable drugs and drug doses.

“What we hope to achieve at the end of this is to validate urine as a screening tool and validate genetics as a way to reduce adverse drug events,” Countryman said. Providing this kind of data to payors responsible for reimbursing tests would justify having the genetic test done, he added.

The added cost to the healthcare system to test for biomarkers in a urine sample is minimal, because this form of testing is considered the standard of care for people taking controlled substances for more than 90 days, he noted, while the costs to the healthcare system of over-prescribing genetic testing and the effects of therapies that lead to adverse side effects on patients are significant.

“If we can give physicians additional information from a test that they are already utilizing, we think that there is a benefit to physicians, patients, and to the medical community at large,” he said. “Right now, the only option is to move to a genetic test.”

As an additional benefit, biomarker urine testing can also identify whether medicines are safe to prescribe along with other medicines, or whether a particular drug is safe to prescribe because the patient is already taking another drug that could generate an adverse effect.

According to InSource Diagnostics, the study will be of great interest to physicians in pain management, psychiatry, general and family practice, internal medicine, addiction, and rheumatology.

InSource Diagnostics is enrolling patients for the study by way of the Sphere registry. Physicians who prescribe listed medications may enroll patients in the study and receive an honorarium of $50 for each patient who completes the 90-day trial. Qualifying patients receive a free genetic test.