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Blood Products Advisory Committee |
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November 3, 2005 |
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Elliot P. Cowan, Ph.D. |
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Chief, Product Review Branch |
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Division of Emerging and Transfusion Transmitted
Diseases |
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FDA/CBER/OBRR |
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FDA seeks advice regarding the conditions
necessary to support approval of a home-use HIV test kit. |
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In particular, we will ask the Committee to
consider what studies are needed to validate |
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test accuracy |
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test interpretation and |
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medical follow-up |
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based on the provision of informational
material in place of a trained test operator and counselor. |
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Prior public discussions of home-use HIV tests |
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History of point-of-care testing for HIV: Rapid HIV tests |
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Issues to be addressed for home-use HIV test
kits |
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Overview of this session |
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Questions for the Committee |
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Tests that are used at home by untrained persons
without the help of a healthcare professional |
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Two types |
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Home-use collection kits |
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You take your own sample, mail it to a
laboratory, and get your result over the phone |
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Home-use test kits |
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You take your own sample, test the sample, and
read your own result |
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Home-use collection kits |
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Hepatitis C virus infection |
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HIV |
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Home-use test kits |
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Fecal occult blood |
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Glucose |
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Cholesterol |
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Pregnancy |
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Prothrombin time |
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No previously approved home-use test kits for
infectious diseases |
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Home-use collection kit |
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Specimen is collected by the test subject |
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Test is performed and interpreted by a trained
operator in a certified laboratory |
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Live counseling |
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Home-use test kit |
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Specimen is collected by the test subject |
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Test is performed and interpreted by the test
subject |
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Lack of a trained operator |
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Lack of live pre-test counseling and post-test
counseling at the time the test result is provided |
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Lack of medical referral |
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Companies first expressed interest in developing
and marketing home-use blood collection kits for HIV testing |
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FDA and AIDS advocacy groups raised public
health concerns about |
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Test accuracy in the hands of an untrained
individual |
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The way users would be notified of test results
– patient confidentiality and adequacy of telephone counseling |
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Effective counseling deemed critical to ensure
that HIV-infected people understand what HIV infection means and receive
vital information about recommended treatment and coping methods |
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FDA notified, by letter, manufacturers and other
interested parties of requirements for approval of such systems |
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Based on consultation with other US public
health agencies and private sector advisory groups |
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Federal Register notice |
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Criteria for HIV specimen collection systems |
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Professional use only |
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Results of testing reported to professional
health care provider for reporting and interpretation of test result to
person requesting test, as well as counseling of individual |
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Use of licensed HIV test, etc. |
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Announcement of public meeting to discuss |
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Collection and shipping of blood specimens by
laypersons |
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Return of results directly to person from whom
sample collected |
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Counseling outside of medical health care
environment |
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Availability of blood collection systems OTC |
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Kits for collection and home testing of blood
for evidence of HIV-1 infection |
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Open Public Meeting: Blood Collection Kits Labeled for Human Immunodeficiency
Virus Type 1 Antibody Testing |
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Agenda |
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Invited speakers on regulatory issues, CDRH
experience in home testing, counseling, ethical issues, state experience |
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Public commentors |
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Extensive discussion on risks and benefits of
blood collection kits and home-use test kits |
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Federal Register notice |
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FDA considered data and comments from 4/6/89
meeting |
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FDA reiterated that HIV specimen collection kits
should remain for professional use only |
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FDA stated willingness to work with
manufacturers on requirements for a
premarket approval application and to review data for home collection kits |
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BPAC considers approval of premarket approval
application from Direct Access Diagnostics (University Hospital
Laboratories) for its home collection system |
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Recommendation against approval |
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Application lacked sufficient data |
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Questions remained regarding possible problems
with such issues as confirmatory testing of positive samples, adequacy of
telephone counseling, and compliance with state notification requirements
while maintaining patient confidentiality |
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FDA discussed OTC home specimen collection kits
extensively with other US public health agencies and with product sponsors |
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Change in circumstances |
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Advances in technology = potential for improved
accuracy |
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Change in treatment methods (availability of
therapy for asymptomatic individuals) |
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Public’s increasing desire for greater
involvement in personal health care decisions |
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BPAC re-examination of home-use specimen
collection systems |
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Agreement that benefit of having alternative
means of reaching previously unreachable populations for HIV testing
outweighed potential risks |
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Concerns expressed about |
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Accessibility of a home-use kit for target groups |
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Adequacy of counseling while maintaining
confidentiality |
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Effectiveness of education and follow-up |
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Recommendation for pilot studies to evaluate
these issues |
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Federal Register notice |
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FDA revising guidance for specimen collection
kits labeled for HIV antibody testing set forth in 2/17/89 FR notice |
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OTC specimen collection kit systems may be
approvable |
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Listed specific kinds of data sponsors should
submit for review of safety and effectiveness |
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Did not address kits for home testing of
specimens for evidence of HIV infection |
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Tests that: |
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Have an extremely low risk of an incorrect
result (unaffected by changes in operating conditions or conditions that
could affect the integrity of the specimen) |
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Are simple to use |
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Do not require special storage conditions |
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Results within 20 minutes |
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Use of oral fluid eliminates concerns about
biohazardous conditions (no blood and sharps) |
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Experience with these tests in non-traditional
testing settings |
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Early detection translates into better outcomes |
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Changes in social awareness of HIV infection |
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Traditional testing for HIV requires two visits
to a clinic/healthcare provider |
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Provide sample |
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Receive test result ~1 week later |
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CDC has estimated that each year approximately
8,000 HIV positive individuals do not return to receive their test results |
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Point-of-care testing |
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Tests that can provide a test result in a
relatively short time so that only a single visit is required |
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Results within 20 minutes |
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Few steps to perform; visual readout |
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No special storage conditions or instrumentation
needed |
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Detect antibodies to HIV |
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Tests to be used as an aid in the diagnosis of
HIV infection and not for blood donor screening |
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4 FDA-approved tests at this time |
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Performance standards and clinical
trial/non-clinical requirements for rapid HIV tests: BPAC discussed/concurred on June 15,
2000 |
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Performance |
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Sensitivity:
98% (lower bound of the 95% confidence interval) |
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Specificity:
98% (lower bound of the 95% confidence interval) |
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Non-reactive = Negative |
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Reactive = Preliminary Positive |
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All reactive results should be confirmed using
an appropriate supplemental test |
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Consistent with concept that although screening
test results are highly accurate, reactive test result should be confirmed
by supplemental testing |
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Sale restricted to clinical laboratories |
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that have an adequate quality assurance program
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where there is assurance that operators will
receive and use the instructional materials |
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Approved for use only by an agent of a clinical
laboratory |
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i.e., not for self-testing |
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Test subjects must receive a “Subject
Information” pamphlet and pre-test counseling prior to specimen collection,
and appropriate counseling when test results are provided |
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Not approved for use to screen blood or tissue
donors |
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Customer letter included with all kits |
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“By purchasing this device, you are doing so as
an agent of a clinical laboratory and agree that you or any of your
consignees will abide by the…restrictions on the sale, distribution, and
use of the device…” |
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Who is permitted to use rapid HIV tests? |
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Device classification |
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Clinical Laboratory Improvement Amendments of
1988 (CLIA) |
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Classifies devices according to complexity |
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High |
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Moderate |
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Waived |
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To perform CLIA-waived tests, entities must: |
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Enroll in CLIA program |
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Obtain a Certificate of Waiver |
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Pay a biennial fee |
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Follow manufacturers’ instructions |
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Meet state requirements |
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Sponsor must apply for CLIA waiver |
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Application is made after initial approval |
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Studies to demonstrate that device is simple and
accurate in the hands of intended users |
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Impact of CLIA waiver |
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Use of rapid tests permits notification of
preliminary test results without the need for the subject to be
re-contacted |
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Fewer laboratory restrictions permits wider use |
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June 14, 2001 BPAC discussion on CLIA waiver for
rapid HIV tests |
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CLIA Criteria for In Vitro Diagnostic
Tests: FDA Perspectives on
Applicability of Waivers to HIV Rapid Tests |
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Tests that are waived under CLIA |
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OraQuick® for use with whole blood
(1/31/03) |
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OraQuick® for use with oral fluid
(6/25/04) |
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Uni-GoldTM for use with venipuncture
whole blood (6/23/04) |
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Uni-GoldTM for use with fingerstick
whole blood (11/5/04) |
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Sales and use restrictions apply to waived rapid
HIV tests |
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Benefits |
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Anonymous testing potentially leads to more
people knowing their HIV status |
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Earlier diagnosis and therefore earlier
intervention |
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Empowerment of consumers in healthcare decisions |
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Potential impact on behavior and public health |
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Risks |
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Inappropriate use of test or test result |
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Misinterpretation (relying on test to provide
accurate result after a very recent exposure) |
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Potential adverse outcomes after obtaining a
test result without live counseling |
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Inability to reach individuals for follow-up and
to perform partner notification |
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Coercive testing |
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Testing by minors |
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Additional issues |
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Obtaining a test result without a supplemental
test |
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False positive rate significant in low
prevalence populations |
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Availability for those who need the test most |
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Potential conflict with state and/or federal
health reporting requirements |
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Proposal by OraSure Technologies, Inc. for an
OTC claim for the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test for use with
oral fluid specimens |
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Proposed studies to validate adequate
performance in the hands of intended users |
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Populations to be studied reflecting intended
users? |
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Ability of informational materials to provide
counseling and other information in a comprehensible manner by intended
users |
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Accuracy of testing |
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Correct test interpretation |
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Management of psychological and social issues |
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Medical referral |
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Discussion of changes in HIV testing practices
and counseling recommendations |
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Dr. Bernard Branson, CDC |
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Role of quality systems for diagnostic tests |
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Dr. Devery Howerton, CDC |
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Psychological and social issues associated with
HIV testing and OTC home-use tests |
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Dr. Joseph Inungu, Central Michigan University |
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Overview of the OTC review process and human
factors considerations |
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Arleen Pinkos, FDA/CDRH/OIVD |
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Are FDA’s previously established criteria for
sensitivity and specificity for rapid HIV tests also appropriate to support
OTC use for home-use HIV test kits? |
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Please comment on the design of clinical studies
necessary to validate the safety and effectiveness of an OTC home-use HIV
test kit. |
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Please comment on the proposed content of the
informational materials and the steps that should be taken to validate the
adequacy of the informational materials to communicate or provide pathways
to adequately address issues including: |
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Accuracy of testing |
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Correct test interpretation |
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The importance of supplemental testing for
confirmation of positive results |
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Management of psychological and social issues |
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Availability of counseling |
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Medical referral |
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Notes