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OraSure HIV Test Has Risks of False Results, FDA Says
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bloomberg, By Anna Edney on May 11, 2012

FDA Reviews & published study attached:

People who use what could be the first completely at-home HIV test under development by OraSure Technologies Inc. (OSUR) (OSUR) risk receiving false results, U.S. regulators said in a report.

Outside advisers to the Food and Drug Administration should weigh whether the benefits of the kit are greater than the potential risk of false negative and false positive results, agency staff said in the report today ahead of a May 15 advisory panel meeting. Regulators are considering approval of the OraQuick In-Home HIV Test, which would be sold without a prescription and provide users with their HIV status at home in a similar fashion to pregnancy tests.

"There is considerable personal and public health value in informing infected, but otherwise untested, persons of their true positive HIV status," FDA staff wrote. "However, this benefit is offset in some measure by HIV-positive individuals who receive an incorrect message that they are not infected."

OraSure fell 14 percent to $9.65 at 3:15 p.m. New York time, the largest intraday decline in two years.

About 1.2 million people in the U.S. have HIV, the virus that causes AIDS, and 20 percent of those people are unaware they are infected, according to the Centers for Disease Control and Prevention. The test made by Bethlehem, Pennsylvania-based OraSure would be the first of its kind. Other kits, such as Home Access Health Corp.'s Express HIV Test System, require users to anonymously send blood samples to a laboratory for testing.

Clinical Trial Findings

A clinical trial of OraSure's test identified 100 previously undiagnosed people infected with HIV of 5,800 patients who used the product, according to the company. OraSure markets the only FDA-approved rapid HIV test that detects HIV antibodies in oral fluid and provides results in a clinic or doctor's office within 20 minutes.

OraQuick would produce one false negative result for every 13 true positive tests, FDA staff said. That would total an estimated 3,800 people with HIV who falsely test negative each year, according to the report. In addition, the test would produce one false positive result for every 3,750 true negative tests resulting in 1,100 people a year who aren't infected believing they are, the report said.

The false negatives reported were higher than what the FDA considers a "minimum acceptable performance" while the false positives were lower.

'Confident' in Test

"We are very confident in the efficacy, safety and performance of the OraQuick In-Home HIV Test, which has been proven to have a calculated accuracy of 99 percent in extensive self-test clinical studies," Ron Ticho, a spokesman, said in an e-mail.

OraQuick would identify 9,087 previously undiagnosed HIV- positive individuals for each 1 million who use the test, Ticho said.

OraSure doesn't have an estimate for when the FDA may decide on the home-results test, said Susan Brophy, of Golin Harris, who is a spokeswoman for the company.

The FDA cleared the Home Access test in 1996. Results can be obtained the day a sample arrives at a laboratory and retrieved anonymously using a pin number, according to the Hoffman Estates, Illinois-based company. The FDA stresses the benefit of having medical professionals help users interpret the results and understand treatment options on its website.

The FDA staff expressed concern that people who may have gotten tested professionally would turn to the "less sensitive, but more private," alternative. No studies have been done to test the potential impact, according to the report.

"Counseling, which uses both printed material and telephone interaction, provides the user with an interpretation of the test result," the FDA said on its website about the Home Access test system.

Counseling also can provide information on preventing transmission of the disease for people who are infected and on treatment options and doctor referrals, the FDA said.

More than 16,000 people with AIDS were estimated to have died in 2008, the CDC said.

To contact the reporter on this story: Anna Edney in Washington at

To contact the editor responsible for this story: Reg Gale at


US gov checks first rapid, take-home test for HIV: On May 15, 2012, the committee will discuss as a device panel the evaluation of the safety and effectiveness of the OraQuick In-Home HIV Test.

May 11, 2012 12:50pm

Topic: Safety and effectiveness of the proposed OraQuick® In-Home HIV Test

Blood Products Advisory Committee

102nd Meeting, May 15, 2012

The Hilton Washington DC North/Gaithersburg

620 Perry Parkway

Gaithersburg, Maryland, 20877

WASHINGTON (AP) - The U.S.Food and Drug Administration is considering approval of the first over-the-counter HIV test that would allow people to test themselves for the virus at home, quickly and without medical supervision.

FDA reviewers said Friday the OraQuick In-Home HIV test could play a significant role in slowing the spread of HIV, according to briefing documents posted online. They also raised concerns about the accuracy of the test, a mouth swab that returns results in about 20 minutes.

The review comes one day after an FDA advisory panel endorsed the HIV pill Truvada for preventive use. If FDA follows the group's advice, the daily medication would become the first drug approved to prevent healthy people from becoming infected with the virus that causes AIDS.

Public health experts estimate one-fifth, or about 240,000 people, of the 1.2 million HIV carriers in the U.S. are not aware they are infected. Testing is one of the chief means of slowing new infections, which have held steady at about 50,000 per year for two decades.

In a trial conducted by the company OraSure Technologies Inc., the test correctly detected HIV in those carrying the virus 93 percent of the time. That rate is below the FDA-recommended 95 percent threshold for accuracy.

The FDA estimates the test would miss about 3,800 HIV-positive people per year, if approved for U.S. consumers.

The test was more accurate at correctly clearing patients who do not have the disease. In company studies, OraQuick correctly identified HIV-negative users 99 percent of the time.

In their briefing documents, FDA scientists noted both the benefits and risks of expanding HIV testing with the take-home diagnostic kit.

"There is considerable personal and public health value in informing infected, but otherwise untested, persons of their true positive HIV status," the reviewers state. "However, this benefit is offset in some measure by HIV-positive individuals who receive an incorrect message that they are not infected."

The lukewarm endorsement apparently spooked investors. OraSure's stock tumbled $1.47, or 13 percent, to $9.70 in the hours after the review was posted.

On Tuesday, the FDA will ask a panel of outside experts whether the test should be approved for over-the-counter sales in the United States. The agency is not required to follow the group's advice, although it usually does.

Based in Bethlehem, Pennsylvania, OraSure has marketed a version of OraQuick to doctors, nurses and other health care practitioners since 2004. The test sells for $17.50, though OraSure declined to discuss how it would price the consumer version. When used by professionals, the test is shown to identify both carriers and non-carriers accurately 99 percent of the time.


Excerpts Document from FDA website attached:


Knowledge of one's HIV status, linked to behavior change, is a major step that contributes both to personal health and to stemming the spread of HIV infection. However, knowledge of HIV status depends on access to and utilization of accurate HIV testing. Approaches to HIV testing have evolved with changing needs and advancing technology. Beginning in 1985 clinical laboratory-based testing for HIV came with rigorous oversight, namely pre-test counseling, quality controlled laboratory testing, confirmation prior to notification, post-test counseling and medical referral. However, this type of testing also came with potential hurdles to testing based on costs, logistics, the need to interface with the medical system and fears of stigma. In response to these concerns, FDA was approached in 1989 and 1990 by sponsors seeking over-the-counter (OTC) claims1 for their test systems, but the state of technology and public health thinking at that time was not conducive to such a claim. Later, in 1996, FDA approved two OTC home-use blood specimen collection kits for HIV testing; with a specimen collection kit, the lay user collects his/her own sample, mails it to a laboratory, and receives a result over the phone or in the mail. For these collection kits, printed materials (instead of live pre-test counseling) contained important information for the lay user about the testing; test results and post-test counseling and referral were available by phone.

Since 2001, FDA has approved a number of rapid (e.g., 20 minute) HIV tests, (including some that were granted CLIA waiver2) for use by trained operators in outreach settings. In outreach settings, individuals are promptly given the results of a screening test by a health care practitioner, prior to confirmation. These tests are highly sensitive and specific, exceeding the Blood Products Advisory Committee (BPAC)-recommended, and FDA-accepted, criteria for sensitivity and specificity of 98%, expressed as the lower bound of the 95% confidence interval. Of the seven currently FDA-approved rapid tests, five make use of a fingerstick blood specimen and one test is also approved for use with an oral fluid specimen. These test characteristics have facilitated testing in outreach settings by providing an unconfirmed screening test result in a single visit (a reactive or "preliminary positive" result should be confirmed by additional testing), and four of the tests qualified for CLIA waiver, expanding test accessibility.

In 2005 OraSure Technologies approached FDA to discuss marketing its approved OraQuick ADVANCE HIV-1/2 rapid antibody test as a self-administered OTC test kit for home-use with oral fluid specimens, to further expand public access to testing. At this time there are no FDA-approved OTC home-use test kits for HIV or any other infectious agent. Since 2005, there have been several discussions at public meetings of BPAC of issues related to OTC home-use test kits for HIV. In November 2005 the committee discussed and provided recommendations for the validation of OTC home-use HIV test kits and asked FDA to outline a pre-clinical and clinical trial proposal and criteria for an OTC claim.(2) A study plan consisting of observed self-testing and interpretation (Phase II), followed by unobserved self-testing in an intended use setting (Phase III) was discussed at BPAC in March 2006.(3) BPAC recommended acceptable minimal performance for sensitivity and specificity each as 95%, expressed as the lower bound of the 95% confidence interval. This reduction of the performance that was expected in comparison to professional use tests was considered to represent a reasonable balance between risk and benefit. At the November 2009 BPAC meeting FDA presented a formal risk analysis of the performance characteristics for OTC home-use HIV test kits at various levels of sensitivity and specificity. (4) This model highlighted the benefit of HIV-infected individuals knowing their status versus the risks of false positive and false negative results both in terms of individual and public health.

The OraQuick® In-Home HIV Test System:

OraSure Technologies, Inc. has filed a premarket approval application for their OraQuick® In-Home HIV Test. This test is a modified version of their currently approved OraQuick® ADVANCE Rapid HIV-1/2 Antibody Test for use with oral fluid specimens (approved and then CLIA-waived in 2004). The OTC kit consists of the testing device and reagents, step-by-step instructional material to assist an untrained user (the individual seeking to know his/her HIV status) in the testing process, information on interpreting the test results, and contact information for the OraQuick® Answer Center for support and local medical referral.

To perform the test, an oral fluid specimen is collected directly onto the test device pad by swabbing the upper and lower gums once each. The device is then inserted into a vial of developer solution. The developer solution flows through the device carrying with it a colored reagent that binds to antibodies in the specimen. If antibodies to HIV-1 or HIV-2 are present in the sample, they become immobilized by binding to a line on the membrane strip that contains HIV-1/2 antigens, generating a visible line. As the solution continues to flow along the strip, antibodies are captured nonspecifically by control material at a separate line on the membrane, also generating a visible line. The test result is read after 20 minutes but not longer than 40 minutes after inserting the device into the vial of developer solution. If antibodies to HIV-1 or HIV-2 are present in the oral fluid specimen, a line appears in the bottom (test) portion of the device window, along with a line in the upper (control) portion of the device window, thus generating two distinct lines. The result is interpreted as "you may have HIV." If no antibodies to HIV-1 or HIV-2 are present, then only the control line is present and indicates that an adequate specimen was collected with the device and that the test is functioning properly. The result is interpreted as "negative."

According to the clinical trials performed to support the original device approval, the sensitivity of the OraQuick® ADVANCE Rapid HIV-1/2 Antibody Test in the hands of trained users was 99.3% (95% confidence interval [CI]: 98.4% -99.7%) and the specificity was 99.8% (95% CI: 99.6% - 99.9%). The test device and developer solution in the OTC kit are identical to those in the OraSure rapid HIV test. The test kit for OTC use includes step-by-step instructional materials, a stand for the developer solution vial, and a drawer containing the test device (all integrated into the kit box), all device components, and two informational booklets (HIV, Testing & Me and What your results mean to You!). Also included in the instructional materials is contact information for the OraQuick® Answer Center, which is available 24 hours a day, seven days a week.

Summary of OraSure In-Home HIV Test Clinical Trial Study Results:

OraSure conducted its clinical trials for the OraQuick® In-Home HIV Test using the phased approach proposed by FDA and recommended by BPAC in 2006.2

Phase I established performance of the test in the hands of trained users, characterizing the inherent sensitivity and specificity of the test. This was accomplished through studies conducted in support of the original approval in 2004 and was supplemented with additional studies to demonstrate that the test is robust under varying conditions that would potentially affect specimen and test integrity (e.g., temperature and humidity extremes, exposure to food, drink, and chemicals, human factors, sampling variations).

· Phase II established performance of the test system as a whole in the hands of untrained intended and expected users under observation (determined through qualitative research), prior to conducting studies of self-testing in an uncontrolled, intended use setting (Phase III), which presents a potentially higher risk to study participants due to lack of counseling when obtaining the test result. Phase II consisted of two parts:

Phase IIA: Test result interpretation of devices that were designed to indicate either high positive, low positive, negative, or invalid results. Acceptable agreement with the correct result was expected to be at least 98% for the positive, negative, and invalid devices and at least 95% for the weak positive devices.

The initial results from the Phase IIA studies showed that performance expectations (lower bound of 95% confidence interval for agreement of interpretation) were not met (93.9% for the positive devices, 92.6% for the negative devices, 90.8% for the invalid devices, and 80.2% for the weak positive devices). To mitigate the risks of incorrectly interpreting the test result, OraSure modified the text of the labeling and improved the pictures to aid in interpretation.

However, the results from the repeat of the Phase IIA studies showed that performance expectations (lower bound of 95% confidence interval for agreement of interpretation) were still not met (93.9% for the positive devices, 93.0% for the negative devices, 90.8% for the invalid devices, and 78.0% for the weak positive devices).

Phase IIB: Self-testing by individuals at high risk, unknown risk and low risk for HIV infection, and individuals known to be infected with HIV. Study participants conducted and interpreted the test on their own, but under observation. According to BPAC, the sensitivity and specificity in these studies should be at least 95%, expressed as the lower bound of the 95% confidence interval.

The results from the Phase IIB studies showed that performance expectations were met for both specificity (lower 95% confidence bound of 98.8%) and sensitivity (lower 95% confidence bound of 95%).

Phase III was designed to establish performance of the test system as a whole in the hands of untrained intended and expected users in the actual intended use (in-home) setting. In Phase III sensitivity was to be based only on prospectively identified HIV-infected individuals and not from those known to be infected with HIV, to better represent the sensitivity of the test in the hands of intended users. .........see attachment

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