FDA approval provides choices for rapid testing
Second rapid test hits market; others on the way
As the second rapid detection test for tuberculosis goes to market in the United States, a Canadian biomedical company announced it also was developing a commercial rapid test based on a format developed by the University of Arkansas in Little Rock. With similar tests nearing approval, laboratories will have to closely evaluate and choose a test that best meets the needs of its facility, says a TB diagnostics researcher.
"Everyone likes to be first on the market, but as others come along, they might offer different advantages that would be attractive to the lab, and it might not be specificity and sensitivity or cost," says Kathy Eisenach, PhD, associate professor of microbiology at the University of Arkansas and a member of the U.S. Food and Drug Administration’s microbiology devices panel.
A rapid TB test developed by Gen-Probe of San Diego and called the Amplified Mycobacterium tuberculosis Direct Test or MTD, was first to hit the market with FDA approval in January 1996. Last month, Roche Molecular Systems of Branchburg, NJ, received FDA approval for its Amplicor Mycobacterium tuberculosis test (MTB). The two tests use different amplification methods Gen-probe MTD targets RNA, while Amplicor MTB targets DNA but they have comparable sensitivity and specificity rates. (See TB Monitor, February 1996, p. 13.) However, because their accuracy is not 100%, both tests are approved only for diagnosing smear-positive specimens.
"If you look at the performance of clinical trials of both Gen-probe and the Roche test, you are always going to find these tests in the 95+% range for sensitivity, and both are about 100% specific," says Riche Pinnola, vice president of global business development for Roche Molecular Systems. "Based on their indication [for smear-positive samples], I don’t think you will find much difference in performance."
The Roche test is the first rapid TB test to use the much heralded polymerase chain reaction (PCR). However, its real advantage over the Gen-probe test is its user-friendly kit, Pinnola says. The kit allows for stopping points along the three-part diagnosis process so that a technician can go back a step without redoing the entire test, he explains. Another advantage is its "AmpErase" system that prevents contamination of future tests without the extensive clean-up that the Gen-Probe test requires, he adds.
One criticism of the Gen-probe test kit is that it was sold in batches of 50 a disadvantage for low-volume labs. The Gen-probe test has a single enzyme reagent tube that must be used up within 30 days, while the 96-test kit offered by Roche has three tubes, each good for 30 days, Pinnola says.
As for cost, the Gen-probe test lists for $35, while the Roche test will list for $25, says Pinnola. (A Gen-Probe spokesperson told TB Monitor last year that its MTD test would cost between $25 and $30 depending on volume.)
Before a lab can start using the Roche test, its technicians must attend a three-day training session at Roche and pass a proficiency test. Roche plans to seek FDA approval for an automated kit, which is already available in Europe and Japan, Pinnola says.
Both Roche and Gen-Probe have begun clinical testing on second-generation tests. The improved accuracy of these refined diagnostics could expand labeling to include smear-negative as well as smear-positive sputum samples. Because the bulk of sputum tests for TB are negative, the tests now have limited benefits.
Nonetheless, studies of the tests at several research hospitals have shown that the tests possibly can save money by reducing the time patients are put in isolation, reducing unnecessary treatment and hastening contact investigations.
In New York City, for example, any suspected TB patient must be put in isolation and started on TB treatment. The rapid tests can confirm in 24 hours that positive sputum tests are indeed MTB; on the other hand, waiting for culture results can take weeks.
"Not only will earlier detection lead to improved patient care for individuals suspected of having disease, but our preliminary analysis has even shown that rapid diagnosis may lead to overall savings within the hospital as well," says Richard D’Amato, PhD, co-director of infection control at Catholic Medical Center of Brooklyn and Queens in Jamaica, NY.
Other competitors coming
Within the next year or two, labs may have two or three other rapid diagnostic TB tests to choose from. ID Biomedical Corp. of Vancouver, BC, is developing a rapid culture confirmation test for TB in collaboration with Eisenach’s research center. The test utilizes a DNA-based diagnostic system called cycling probe technology. While the test would still require that labs grow clinical samples, the company hopes to use the assay for direct detection like the Roche and Gen-Probe tests. Where it would differ is that its probe technology would make it more feasible for use in developing countries, Eisenach says.
"Probe technology is often more simple and requires less equipment, which makes it less expensive," she explains. "A major concern with assays now developed is that they are marketed for developed countries. If developing countries had a simple probe test, they could spend a lot less time at the microscope."
Becton Dickinson and Co. of Franklin Lakes, NJ, also is developing a commercial rapid TB test using the sequence strand Eisenach developed for research purposes. The test, which utilizes strand displacement amplification, is in clinical trials and is close to being put before the FDA for approval, she adds.
Abbott Labs of Abbott Park, IL, is developing a rapid TB test using a technology called ligase chain reaction. The company has completed clinical trials and is close to submitting the test to the FDA, she says.
In choosing among the new tests, Eisenach says test volume and ease of use may be the deciding factors. Most of the tests will be comparable in sensitivity and specificity, she says. But because their techniques differ, each has a unique format that may be more or less suitable to a particular lab.
"Since labs have never had anything like this before, they just have to feel their way along and figure out themselves how it isn’t going to be used," Eisenach tells TB Monitor.
For example, the Gen-Probe test is an individual tube test, which works better if a lab works with a low volume of tests. Labs that run batches of tests might find the Roche test more feasible, she says.
"If you are a high-volume lab, you might be more attracted to an automated method where you could test multiple samples simultaneously," she adds.
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