Public Health Need and Performance Characteristics for Over-the-Counter Home Use HIV Test Kits

1. Public Health Need and Performance Characteristics for Over-the-Counter Home Use HIV Test Kits Blood Products Advisory Committee November 17, 2009 Elliot P. Cowan, Ph.D. Chief, Product Review Branch Division of Emerging and Transfusion Transmitted Diseases FDA/CBER/OBRR

2. Overview of this Session • Background on previous considerations of home-use HIV test kits • FDA’s current considerations on trials to support approval of home-use HIV test kits • CDC update on role of home-use HIV test kits in promoting knowledge of HIV status and public health impact of these tests • FDA discussion of risk assessment of a home-use HIV test kit, examining pubic health risks and benefits for tests at varying levels of sensitivity and specificity

3. Characteristics of Rapid HIV Tests • Results within 20 minutes • Few steps to perform; visual readout • No special storage conditions or instrumentation needed • Detect antibodies to HIV • Tests to be used as an aid in the diagnosis of HIV infection and not for blood or tissue donor screening • Currently 6 FDA-approved tests, 4 CLIA-waived

4. Characteristics of Rapid HIV Tests,cont. • Performance Expectations • Consistent with advice from BPAC in 2000, FDA has only approved rapid tests for which the lower bound of the 95% confidence interval for estimated test sensitivity and specificity is 98% or greater.

5. Rapid HIV Tests areRestricted Devices • Sale restricted to clinical laboratories that have an adequate quality assurance program and where there is assurance that operators will receive and use the instructional materials • Approved for use only by an agent of a clinical laboratory • Test subjects must receive a “Subject Information” pamphlet and counseling • Not approved for use to screen blood or tissue donors • Customer agreement with each order

6. Home-Use Tests • Tests that are used at home by untrained persons without the help of a healthcare professional • Two types • Home-use collection kits • Home-use test kits

7. Home-Use HIV Test Kits are Different from Home-Use HIV Collection Kits • Home-use collection kit • Specimen collected by the test subject • Performed and interpreted by a trained operator in a certified laboratory • Live counseling (by phone) • Home-use test kit • Specimen is collected by the test subject • Test is performed and interpreted by the test subject • No trained operator • No counseling • No medical referral

8. Currently Approved Home-Use Collection Kits and Test Kits • Home-use collection kits • HCV • HIV • Home-use test kits • Fecal occult blood • Glucose • Cholesterol • Pregnancy • Prothrombin time • No previously approved home-use test kits for any infectious diseases

9. Benefits of Home-Use HIV Test Kits • Anonymous testing potentially leads to more people knowing their HIV status • Earlier diagnosis and therefore earlier intervention • Empowerment of consumers in healthcare decisions • Potential impact on behavior and public health

10. Risks of Home-Use HIV Test Kits • Not understanding limitations • Potential adverse outcomes after obtaining a test result without live counseling • Inability to reach individuals for follow-up and to perform partner notification • Coercive testing • Testing by minors

11. Additional Issues for Home-Use HIVTest Kits • Obtaining a test result without a supplemental test • Cost

12. Public Discussions:BPAC, November 3, 2005 • In response to renewed interest in home-use HIV test kits, FDA asked BPAC to discuss and provide recommendations for the validation of OTC home-use HIV test kits. • Committee acknowledged that criteria could be established to permit FDA approval of a home-use HIV test kit.

13. Public Discussions:BPAC, March 10, 2006 • FDA sought the advice from the Committee on FDA’s proposed studies that would be needed to validate a home-use HIV test kit with regard to • test accuracy • test interpretation • medical follow-up based on the provision of informational material in place of a trained test operator and counselor.

14. BPAC, 3/10/2006Phase I Studies • Objectives • To establish the sensitivity and specificity of the test system when run under ideal conditions by trained laboratory personnel and to demonstrate that the test is capable of withstanding operational stress. • Performed by individuals trained in the use of the test system • Studies • Analytical and clinical sensitivity and specificity • Operational stress (“Flex”) studies

15. BPAC, 3/10/2006Phase I Studies, cont. • Intended users of the test system should be identified by means of qualitative research • Comprehension analysis of the test system’s proposed labeling and packaging

16. Evaluate performance • Identify issues • Modify test system to address issues • Validate modifications

17. BPAC, 3/10/2006Phase II: Intended Users/Observed Setting • Objectives: • To evaluate, in a controlled setting: • Effectiveness of sample collection by untrained users • Ability of untrained users to perform test properly • Ability of untrained users to read and interpret test results • Performance of test system (sensitivity and specificity) in the hands of untrained users • Reactions to test system results by untrained users • Phase II is divided into 2 parts: IIA and IIB

18. BPAC, 3/10/2006 Phase IIA: Running and Interpreting the Test • To evaluate the ability of the untrained users to interpret previously run devices that represent negative, invalid, strong positive, and weak positive tests • Expected correct interpretations • >98% as the lower bound of the two-sided 95% CI for negative, invalid, and strong positive • >95% as the lower bound of the two-sided 95% CI for weak positive • To evaluate the ability of the untrained users to run and interpret contrived specimens representing weak positive and negative specimens • Expected % agreement • >99% for the negative specimens • >95% for the weak positive specimens

19. BPAC, 3/10/2006 Phase IIB: Self-Testing in Observed Setting • Evaluate performance of the test system (sensitivity and specificity) in the hands of untrained users • >95% as the lower bound of the two-sided 95% CI for both sensitivity and specificity • Sensitivity may be based primarily on results of testing by individuals who know that they are infected with HIV • Evaluate reactions of study participants to their test results • Validate ability of informational materials to: • Communicate the proper use of the test and interpretation of the test result • Communicate test system limitations • Have study participant seek follow-up testing and referral to care • Effectively provide a route to counseling • Assessment of ability of informational materials to substitute for live counseling without adverse events

20. Evaluate performance • Identify issues • Modify test system to address issues • Validate modifications

21. BPAC, 3/10/2006 Phase III: Intended Users/Intended Use Setting • Evaluate performance of the test system (sensitivity and specificity) in the hands of untrained users in an uncontrolled setting • Lower bound of the two-sided 95% confidence interval at least 95% for both sensitivity and specificity • Sensitivity may be based primarily on results of testing by individuals who know that they are infected with HIV • Evaluate reactions of study participants to their test results • Validate ability of informational materials to: • Communicate the proper use of the test and interpretation of the test result • Communicate test limitations • Have study participant seek follow-up testing and referral to care • Effectively provide a route to counseling

22. Additional Comments from3/10/2006 BPAC • Ensure that groups of individuals who are most in need of testing are included in trials. • Labeling should clearly communicate the need to read the informational materials prior to conducting the test. • The reading level of the informational materials should make them easy to comprehend by potential users of the test. • The informational materials should clearly communicate the expected performance of the test kit based on the clinical studies, including information regarding observed false positive and false negative results. • The informational materials should clearly communicate the limitations of the test when the user is in the window period for HIV infection.

23. Additional Comments from 3/10/06 BPAC,cont. • The test manufacturer should offer users advice and referral mechanisms to obtain proper medical follow-up of test results. • The informational materials should clearly communicate the actions to be taken in the event of a reactive test result. • Clear and convenient methods for follow-up testing and referral should be established and communicated in the informational materials. • Counseling should be accessible by means appropriate to potential desired users and be available at any time. This information should be clearly communicated in the informational materials.

24. FDA’s Current ConsiderationsConduct of Phase III Studies • Individuals already aware of their HIV status do not represent intended or potential users of home-use HIV test kits • May introduce bias • May not be adequate group to evaluate effectiveness of informational materials to substitute for live counseling • FDA now recommends that evaluation of sensitivity in Phase III trials be based solely on prospectively identified HIV-infected individuals

25. Next • Dr. Bernard Branson, CDC • Update on the role of home-use HIV tests in promoting knowledge of HIV status, including promises and pitfalls • Dr. Richard Forshee, FDA • Results of a risk assessment to examine the public health risks and benefits of an over-the-counter HIV test at varying levels of sensitivity and specificity

26. Question Please comment on the relative importance of the test characteristics (sensitivity and specificity) as they may affect the public health utility of an over-the-counter home-use HIV test kit.