CEO SUMMARY: In past years, it was customary for laboratories to shift away from performing or ordering “home brew” tests in favor of FDA-approved test kits as they became available. However, new marketing models for diagnostic testing are shifting this long-standing practice. HIV resistance testing is one type of testing where this battle between “home brew” and approved test kit is playing out.
IT’S AN UNEXPECTED DEVELOPMENT in the lab testing marketplace. Some “home brew” assays are failing to yield to assays which have gone through the Food and Drug Administration (FDA) review and clearance process.
To the contrary, labs offering home brew versions of selected assays have chosen to continue marketing those assays in competition with test kits which have undergone regulatory scrutiny and approval.
Probably the most widely-ordered home brew tests involve HIV genotyping which differentiates HIV resistance. During the past year, Visible Genetics, Inc. gained FDA clearance to bring its TRUGENE™ HIV-1 Genotyping Test Kit to market. However, the arrival of this product has not stopped several national labs from continuing to aggressively market their home brew versions of HIV-1 genotyping throughout the country.
Currently, a hospital laboratory seeking to provide HIV-1 resistance typing has three options. One, it can buy a home brew version. In recent years, three important sources of these home brew HIV-1 resistance tests have been Laboratory Corporation of America, Quest Diagnostics Incorporated, and Specialty Laboratories. Two, it can buy the TRUEGENE HIV-1 test from a reference lab which offers this assay. Three, it can decide to set up and perform the TRUEGENE HIV-1 test in its own laboratory.
“This presents some interesting problems for pathologists,” stated Michael Mihalov, Director of the Molecular Diagnostics Center at Resurrection Medical Center in Chicago, Illinois. “First, it makes it tougher for them to understand the level of expertise and quality they get from each different lab’s home brew version of the same test.
“Second, referring pathologists don’t always understand the specific methodologies used by different reference laboratories,” he said. “Different test methodologies have different clinical implications. Pathologists need to know the clinical implications of each test methodology if they are to properly support the clinicians using these test results.”
Dr. Mihalov points out an interesting fact about the potential quality differences in home brew HIV resistance testing. “At the Clinical Virology Symposium in April this year, doctors from a lab and a clinic in California reported on a study they undertook to evaluate the quality of tests results from various versions of HIV-1 resistance typing, both home brew and FDA-approved,” he noted.
Differences In Test Results
“To compare reference lab detection proficiency, the study authors first collected blood, under informed consent, from five patients with HIV-1. Under different patient names, over a period of two weeks, they submitted 10 aliquots from each patient to each of four reference labs as routine clinical samples,” explained Dr. Mihalov. “For samples with a viral load greater than 1,000 copies of RNA/ml, the accuracy of reported drug resistance mutations ranged from a high of 99% to a low of 64%.
“Certainly this range of detection rates has implications for clinicians,” Dr. Mihalov observed. “But I doubt most pathologists handling such test referrals would believe the variability in test results would be this great.”
THE DARK REPORT observes that home brew testing has grown in scope and complexity during recent years. It was designed to allow research labs to develop new test technology. But certain lab industry experts believe that offering home brew assays to clinicians in a commercial setting stretches the original intent of existing laws.
Infectious Disease Markets
Like HIV, other common infectious diseases are seen as huge markets for a new generation of genotyping tests. In particular, HPV and HCV are expected to find widespread clinical application once they demonstrate effectiveness in guiding decisions about diagnosis, therapy, and patient monitoring. Under current circumstances, the lab industry may see home brew test versions for these diseases selling in the marketplace along with FDA-approved test kits.
There’s a simple reason why laboratories offering a home brew HIV-1 resistance test have not shifted to using the FDA-approved TRUEGENE HIV- 1 kit. Home brew tests are significantly more profitable to these labs than buying a kit from Visible Genetics. The public lab companies offering home brew HIV resistance testing are unwilling to take the revenue hit that would occur when they set up and begin offering the Visible Genetics’ version of the test.
Not surprisingly, these national reference labs maintain that they have proprietary expertise in their particular version of HIV-1 resistance testing they offer clinicians. However, to date, none of these lab companies has opted to submit their home brew recipe to the FDA for review and clearance.
Until the FDA approved the Visible Genetics test for HIV-1 genotyping in 2001, the only source of HIV resistance testing was home brew testing offered by a handful of laboratories. Under those circumstances, regulators would have found it politically troublesome to restrict access by AIDS patients to the types of tests which are becoming integral to managing their disease.
However, the arrival of an FDA-approved test kit for HIV-1 resistance typing begins to change that situation. Now a diagnostic test that has undergone the FDA approval process is available to compete against home brew tests. Because the FDA has a charter to “protect the public,” it is possible that officials within the FDA would: 1) consider an assay that had undergone the FDA review and approval process to be a “better” product than a home brew version of the same type of test; and, 2) as regulators, they might have liability, either political or legal, from taking no action on the issue of home brew testing.
Many lab administrators and pathologists recognize that a regulatory battle over home brew testing is taking shape. Intuitively, it is understood that active commercialization of tests developed under the home brew exception moves past the original intent of these regulations.
Maximizing Test Integrity
FDA regulators will probably get lots of support from the diagnostics industry should they move to further restrict the use of the home brew exemption by commercial laboratory companies. After all, diagnostics manufacturers pay substantial amounts of money to meet FDA regulations designed to insure standardized protocols for approved tests with reagents manufactured under GMP (Good Manufacturing Protocols). If all this effort and expense is to maximize the integrity of test results which are reliable and reproducible, then why should commercial laboratories be allowed to aggressively market home brew tests which have not met those same criteria?
Evolving Business Model
In recent years, a number of national reference and esoteric laboratories have given greater emphasis to developing home brew tests, then marketing these tests aggressively to clinicians. This is an evolving business model and relies on a specific interpretation of existing statutes and regulations.
However, the very growth of this business model may well motivate Congress or regulators within the FDA to decide to change these regulations. This would make it tougher for a lab to “commercialize” an assay developed under home brew guidelines.
HIV Resistance Testing Involves Several Steps
PHYSICIANS TREATING AIDS PATIENTS use three basic diagnostic tools to proactively manage their patients.
“The first step is to measure the quantity of HIV virus in the patient,” stated Michael L. Mihalov, Medical Director of Laboratories at Resurrection Medical Center in Chicago, Illinois. “Most labs use the Roche assay to perform this test.
“Typically, viral load tests are done several times per year on an AIDS patient,” he continued. “It is common to also measure immune system status using the count for CD-4 and CD-8 lymphocytes. A flow cytometer is frequently used for this test.
If the patient’s viral load is increasing, the physician can test to determine what types of drug-resistant mutations have developed. Besides the Visible Genetics TRUGENE HIV kit, there are home brew assays available which use genotyping or phenotyping to identify drug-resistance strains,” explained Dr. Mihalov.
“Our hospital laboratory is set up to perform the TRUEGENE HIV-1 test,” he noted. “We can pay a minimum of $450 to send out these specimens. We calculate our cost to do the test in-house is about $275.
“However, what is more important than cost is our expertise and control over the test methodology,” added Dr. Mihalov. “TRUGENE also has an interpretative section on the test report which is generated by a rules-based software program that is regularly updated by a panel of physician-experts as well as a 24/7 help desk.”