by Coleen Curran
With strong backing from President Bush and Health and Human Services Secretary Tommy Thompson, the Food and Drug Administration approved a CLIA waiver for the OraQuick 20-minute, whole-blood HIV-1 test on January 31, 2003 making the test available at the 176,000 laboratories throughout the United States that are eligible to perform CLIA-waived tests.
Without the CLIA waiver, the rapid test could be performed only at the 38,000 clinical laboratories eligible to perform moderately-complex laboratory tests.
Given the giant strides in treatment since the HIV virus was discovered in 1983, it seems implausible that adults at risk would avoid knowing their HIV status. However, statistics indicate otherwise. More than one-third of the 2.2 million Americans tested for HIV at public health clinics each year do not return to learn their test results, according to the Centers for Disease Control. In fact, as many as 11,000 individuals who test positive for HIV each year do not return for their results. Of the approximately 900,000 people in the United States currently living with HIV, it is estimated that one-fourth (225,000) may not know they are infected.
“We need to do a much better job of offering testing in a more routine way,” said Donna Futterman, M.D., professor of clinical pediatrics and director of the Adolescent AIDS Program, Childrens’ Hospital at Montefiore in Bronx, N.Y. “Under current testing programs, a patient has the test one day and then has to come back on another day to get their test results and counseling. In most anonymous clinics, about 60 percent of people come back to get their HIV test results, but four out of ten people do not. In our clinic, about 20 percent of the people we test do not come back for their results. Most of them are negative, but still they are running around not knowing for sure what the answer is. So having a rapid test will really help us make sure that everyone who gets the test will find out their result.”
Futterman’s clinic will be able to perfom the OraQuick test because it is now CLIA-waived. Had OraQuick maintained its designation as a moderately complex test, the clinic could not use it.
Waiver makes test eligible for use in 176,000 labs
The waiver makes the test eligible for use in the 176,000 laboratories across the county that are allowed to perform CLIA-waived tests in addition to the 38,000 laboratories that are allowed to perform “moderately complex” tests. Since its FDA clearance Nov. 7, 2002, OraQuick had been labeled a moderately complex test. The January announcement changed that to CLIA waived.
Based on their complexity, diagnostic tests are directed under CLIA (the Clinical Laboratory Improvements Amendments of 1988) to be performed in laboratories that are certified to three levels of testing: highly complex, moderately complex or CLIA waived (the least complex type of testing done in a laboratory setting.) The certification corresponds to the laboratory’s ability to perform tests with respect to personnel and equipment.
OraQuick, the first rapid, point-of-care test designed to detect antibodies to HIV-1 in finger-stick whole blood, is made by OraSure Technologies, a $32 million company with 200 employees headquartered in Bethlehem, Pa. In June 2002, OraSure and Abbott Diagnostics entered into a co-exclusive marketing distribution agreement of OraQuick. OraSure’s small direct sales force focuses primarily on public health while Abbott is targeting hospitals and physician offices. OraSure continues to sell its oral fluid collection device for HIV testing, and Abbott is also marketing its SUDS (Single-Use Diagnostic System) test, which, unlike OraQuick, requires refrigeration.
Based on clinical data, the OraQuick test has been shown to have sensitivity (99.6%) and specificity (100%) comparable to laboratory-based tests such as Western Blot and ELISA. Sensitivity is a measure of the accuracy for detecting positive specimens, and specificity is a measure of the accuracy for identifying negative specimens.
Rapid test could help delivering moms, accidental needle-stick victims and smallpox vaccine recipients
An HIV test with 20-minute turnaround time could come in handy in a number of scenarios where current test times just don’t cut it. For example, it could help decrease mother-to-infant transmission in the 20 percent of delivering mothers who do not know their HIV status. With more than one million accidental needle-sticks occurring among healthcare workers each year, a quick “no” result can minimize stress and worrying while a quick “yes” could hasten the administration, and effectiveness, of anti-viral drugs.
The latest group to see a benefit is the U.S. Navy, which recently purchased 10,000 OraQuick Rapid HIV-1 Antibody Tests to screen personnel participating in the smallpox vaccination program directed by the federal government. The smallpox vaccine may cause complications for individuals with compromised immune systems and should not be administered to people who are infected with HIV-1. The OraQuick test will be used to screen for HIV-1 infection, thereby helping to reduce the risks associated with receiving the vaccine.
Serious concerns express by lab organizations
Despite its many supporters, the CLIA-waived HIV test has not met with universal acclaim. Robert Neri, executive vice president of CLMA, notes that the lab community, including the CLIAC, has expressed, in the past, serious quality concerns regarding a rapid HIV test. Those concerns include the lack of pre-analytical and post-analytical interventions, the lack of quality control and proficiency requirements, the lack of personnel requirements and the consequences of false-positive and false-negative test results.
CLIAC (the Clinical Laboratory Improvement Advisory Committee) was chartered in 1992 to provide HHS with scientific and technical guidance relative to quality laboratory testing. In September 2002, CLIAC sent a letter to Secretary Thompson outlining its concerns about a CLIA waiver for rapid HIV testing:
“We believe that consideration of rapid HIV tests for waiver under CLIA requires a review of objective data for the following reasons:
The results of HIV tests are of enormous consequence to the persons being tested.
Erroneous HIV test results – both false positives and false negatives – pose a substantial risk to the persons being tested and their partners.
Even the simplest HIV testing device requires oversight, training of personnel, quality control, proficiency testing, and quality assurance to provide accurate results.
Waiver under CLIA provides no mechanism to assure proper oversight, personnel training, quality control, proficiency testing, and quality assurance.
Studies performed by the Centers for Disease Control and Prevention, the Centers for Medicare & Medicaid Services and the Office of the Inspector General have shown that CLIA-waived tests are often incorrectly performed. Incorrectly performed waived tests have resulted in harm to patients.
We agree that HIV testing should be made broadly and rapidly available, and we believe this can be accomplished without waiver under CLIA. Mechanisms exist within CLIA to permit rapid HIV tests to be performed in mobile and non-traditional settings with a minimum of burden, while assuring appropriate oversight, quality control, and quality assurance.
Although we support broad dissemination of rapid HIV testing as soon as these tests are approved for market, we urge you to require careful review of objective evidence of test performance by waived testing personnel in waived settings before these tests are considered for waiver under CLIA.”
A Sept. 10, 2002 letter outlining similar concerns was sent to HHS and signed by the American Association of Bioanalysts, American Society for Clinical Laboratory Science, American Medical Association and American Society for Clinical Pathology. Their letter notes that, “a test as critical as HIV screening must be conducted in a controlled and monitored environment, and conducted by trained personnel… The rapid HIV antibody screening test has a lower specificity and sensitivity than Enzyme Linked Immunoabsorbent Assay (ELISA) tests. Unfortunately, if this test is used by members of a population with a low prevalence of HIV infection, such as normal healthy blood donors, most of the people who get a positive test result are getting a wrong test result.
We understand the desire for patient accessible HIV testing. However, due to the inaccuracy or rapid HIV tests and the implications for both patient and public safety, we respectfully ask that any recommendation for waiver of these tests be denied.”
While the concerns expressed did not ultimately prevail, they highlight a crucial element in the definition of a CLIA-waived test – one that is not of a critical nature to the patient.
“To me, it’s kind of a stretch to say that almost any laboratory test isn’t of a crucial nature in any circumstances,” Neri said. “But you have to weigh what’s in the best interest of the public against an on-paper criteria that tries to be all-encompassing. That’s why, for instance, you have to allow tests out on the open market for trained patients who can monitor themselves. The problem comes with a test like HIV when you think about the consequences of it being done in the wrong hands, by people who don’t understand procedure and are not necessarily doing it for self-monitoring purposes. The consequences for a test result that is incorrect could be quite drastic, which is another reason why it’s good that the FDA has not approved this as an over-the-counter test but rather a waived test.”
Since the FDA described its process for determining CLIA “waivered” status for the rapid HIV test, CLMA is much more comfortable with the decision, Neri said. “We believe that the restrictions imposed upon the distribution of this test appear to be sufficient and will hopefully end up with good results when it’s used in the public domain,” he added. The language to which Neri is referring says that the test can be sold only to, “an agent of a clinical laboratory.”
OraSure still working on CLIA-waived labeling for OraQuick
Currently, OraSure is working with FDA to modify the labeling for OraQuick to make sure it is compliant with the indications for a CLIA-waived product. That entails providing more information about what CLIA-waived means and making sure the training materials take into account that the people using OraQuick do not necessarily have the same level of training as that of a laboratorian to whom instructions would typically be directed.
“We’re taking the learnings we received from conducting our ‘untrained user ‘ tests and making sure we’re doing everything we can to provide a comprehensive training program to the HIV clinic administrators and others who will be using this test,” said William Bruckner, vice president of marketing for OraSure. “We also are talking with CMS and working with them to make sure we understand exactly what is expected of us in terms of what we need to do to make sure OraQuick is being used in a correct fashion.” Bruckner estimates that the labeling issues for the CLIA-waived OraQuick should be taken care of and the test available for distribution in April 2003.
One distribution route that all the stakeholders in rapid HIV testing seem to share the same negative view of is over-the-counter test kits.
“Home use is not something that we are focused on at this point,” said Bruckner. “We believe that counseling and treatment are necessary components of testing, and we would have to make sure that people would be getting that counseling and that treatment. Right now, home use is not a focus of mine nor this organization.”
The organizations representing clinical laboratories do not support OTC HIV testing and neither does Dr. Futterman, who recalled that an early over-the-counter HIV was pulled from drugstore shelves not long after it was introduced several years ago due to lack of demand. The $40 test involved placing a drop of blood on a card and mailing it to a laboratory. Tests results and counseling were provided over the telephone.
“Health information is never enough,” Futterman said. “We’ve known for a long time that cigarette smoking is dangerous, and people should get screened for breast cancer and colon cancer. It’s very hard to confront a test that will tell you some very bad news. In that sense, HIV ranks with all those other screening tests where it is an uphill fight to balance between patient empowerment and the ability to diagnose more things at home, and treatment dumping. I think the medical community still needs to be involved in helping people face and deal with serious illness.”
Bold advances in technology cry out for bold advances in counseling
In addition to new technology for testing, Futterman believes there’s room to update and improve the counseling techniques for HIV testing. The counseling requirements for HIV were developed during a time when a positive test result was the equivalent of a death sentence. With all the new anti-viral drugs available today, that’s no longer true.
“Our program, in particular the adolescent AIDS program, is moving toward a much simpler and more rapid counseling approach”, Futterman said. “Many people know what HIV is all about. HIV testing should not be viewed as so specialized and unique but just as one of the health screens that sexually active people should get. We need to update our counseling approaches as much as the testing approaches.
Most people are informed of their lab or X-ray results over the phone, even if it’s serious. If you have a bad mammogram, they don’t make you come back in person to hear the results. There’s a comfort with telling people they’re OK on the phone and advising them to see a doctor if they have something that needs a biopsy.
I see this rapid HIV test as a tremendous advance in technology, but it needs to be accompanied by a similar bold advance in counseling.”
With the CLIA waiver for OraQuick, it will now be possible to give people their test results while they remain in the clinic, and to provide appropriate counseling on the spot whether that result is positive or negative.
Coleen Curran, based in Charlotte, N.C., is a writer, healthcare consultant and former editor of CLP.
