recting our research and dissemination efforts toward several specific groups, including health care providers, care givers, and communitybased AIDS organizations. This information includes knowledge of the psychological and psychosocial issues related to the high risk groups, those in contact with AIDS patients, and those with AIDS or AIDS-related complex as well as the medical/psychiatric complication of HTLV-III and their clinical manifestations, such as delirium and dementia. These dissemination activities continue to be conducted through a variety of mechanisms including the press and other media, and utilizing national professional association contacts and efforts to work with local radio and television.

Mr. Chairman, this concludes my formal statement. I would be pleased to answer any questions you might have.

Senator WEICKER. Next witness, Dr. Frank Young, Commissioner of the Food and Drug Administration.

STATEMENT OF DR. FRANK YOUNG

Dr. YOUNG. Mr. Chairman, I would like to submit my full statement for the record. In order to have more time for questions, I will just summarize briefly the major points in the testimony of FDA.

The FDA plays a very important and supportive role in the study of AIDS. Our primary responsibilities are the approval of drugs and devices, assurance of the safety and effectiveness of the blood and plasma supply, and virology and vaccine studies with scientists at NIH and CDC. Perhaps the best indication of the type of successful public and private partnership that has occurred for this particular and most dreaded disease is the development of the blood screening test for HTLV-III antibody.

In this sense, in less than 1 year from the isolation of the virus, we had in collaboration with NIH the ability for the mass production of the virus, and with the efforts of the Secretary to secure interaction with the private sector, applications were let for licenses for this test. In less than 1 year, the blood test was able to be approved and it is now implemented widely in blood banks and plasma centers. That could only occur if there was a rapid sharing of information and a deep cooperation between the research scientists in the National Institutes of Health, the academic community, and those within the private sector.

FDA will continue to pledge this type of cooperation in meeting the crisis in AIDS which we view as the most significant public health problem facing the Nation today.

In regard to the issues dealing with therapy, much has already been developed in the previous testimony. I will only highlight a few issues. Of the drugs that are currently in clinical trials in AIDS patients, there are yet not sufficient data to establish their effectiveness in the treatment of AIDS. There are a few compounds, many of which were mentioned by Dr. Wyngaarden, for which there is some preliminary clinical evidence of possible usefulness in the treatment of AIDS or opportunistic infections. I must point out, however, a number of the antiviral

drugs may have significant toxicity. In the case of immune modulator symptoms there is a danger of providing enhancement to viral replication and shortening the time of the disease progression so that we must study these very carefully to be sure of the side effects.

We go through a very careful phase I study of investigation of new drugs and then in expanded clinical trials in phase II and phase III. Despite these complexities of clinical investigations in a disease in which the natural history is not entirely understood, we are prepared to review expeditiously all investigational and marketing applications for products for AIDS, AIDS-related complex and opportunistic infections as we have for HPA-23 and are now doing for the recently filed new drug application for isoprinosine. It is our goal to have what Dr. Harry Meyer calls a zero timing IND. We will work with the private sector during the development of these new drugs and, as expeditiously as we possibly can, turn these applications around.

I am pleased to tell you the first two that we did under this mode were approved in less than 1 week, as far as investigations of new drugs.

I also wish to stress that we remain most concerned about facilitating the availability of any product that appears to be useful in treating AIDS victims and alleviating the suffering it causes, and we are prepared to work with anyone willing to sponsor clinical investigations consistent with our obligation to safeguard patients used as research subjects.

Similarly, we will be working with NIH in related areas of vaccine development. Here the development of animal models capable of measuring the immunogenicity of the HTLV-III component proteins is most important. Skilled virus research teams in FDA will collaborate with NIH and CDC in the development of such vaccines. Thus, it is important to emphasize the integration of FDA into the total AIDS effort of PHS which has been important in developing the HTLV-III antibody test in the past and the excellent leadership of Dr. Mason coordinating the entire PHS effort which will be extremely important in the future.

I appreciate this opportunity to discuss this before this committee. As you know, FDA falls under the jurisdiction of the Appropriations Subcommittee on Agriculture and Related Agencies in the Senate and the House. Fortunately, these subcommittees and their chairmen have been extremely responsible and responsive whenever we have come to them with requests for funds urgently needed to cope with significant public health problems. In fact, Mr. Whitten personally sponsored a floor amendment to include an additional $2,145,000 to support other additional AIDS activities for FDA in fiscal year 1986. This amendment was passed and these resources were included in the appropriation act passed by the House on July 24. I am also pleased to report this amount was included in a bill reported out of the Senate Appropriations Committee on September 24.

Let me briefly discuss with you our plans to utilize these resources in 1986. During the past 12 months, several major developments relevant to transmission, prevention, and control of HTLV-III infection and AIDS have occurred. Serologic tests to detect HTLV-III antibodies have been licensed, and tests are being used to screen donated blood and plasma. Furthermore, a number of therapeutic products have entered into clinical trials and are under active investigation. Our resources will be used to expedite the approval of IND's and the approval of new drug applications so we can bring to the market as fast as it is safe and reasonable, new therapeutic agents to aid those most critically ill and suffering victims and, most importantly, to aid in the prevention of this disease.

The pace of these developments requires that FDA expand surveillance and monitoring efforts. Activities undertaken as part of this request will increase our knowledge regarding the screening test to enhance our ability to assure the safety of the Nation's blood supply and expand the capacity for review and approval of new diagnostic and treatment products.

Additionally, we communicate frequently with the physicians in the country and with health professionals with our drug bulletin. I would like to submit for the record the recent "Dear Doctor" letter I sent out to 175,000 physicians in the country and the upcoming FDA bulletin, if I could, sir, to provide additional information for the record.

Senator WEICKER. Without objection, they will be placed in the record at this point.

[The information follows:]

DEAR DOCTOR LETTER

Dear Doctor:

The Public Health Service (PHS) recently published provisional recommendations for screening donated blood and plasma for antibodies to the HTLV-III virus which causes the acquired immunodeficiency syndrome (AIDS). A copy of those recommendations is attached to this letter for your information, and I strongly suggest that you keep this letter and the attachments on file for future reference. Test kits using the ELISA* technology for detecting HTLV-III antibodies will soon be licensed by FDA and will be commercially available. Blood and plasma collecting facilities will begin testing soon thereafter. Although this is NOT a test for AIDS, there will be individual donors who are found to be reactive in a test for antibodies to the HTLV-III virus and, as suggested in the PHS recommendation, those donors will be referred to a physician for further evaluation. The purpose of this letter is to alert you to the possibility that one or more such donors may be referred to you, and to provide you with as much information as we currently have on how to evaluate such an individual. Based on preliminary information, we expect that less than 1 percent of donors will be reactive for HTLV-III antibodies after repeat testing at the blood or plasma collecting facility. Reactive HTLV-III tests may be due to subclinical infection, to immunity, to an active carrier state, or may represent biologically false-positive reactions such as cross-reactivity to antigens or other viruses. We do not yet know how many blood and plasma donors will fall into each category.

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Additional PHS suggestions for the medical evaluation of referred donors are included with this letter. You will also find a sample information sheet which will serve as a model to educate donors at blood and plasma collecting facilities about the antibody test and sample information sheet for donors with a positive antibody test. The PHS has placed a very high priority on expediting the development and approval of the HTLV-III antibody test so that it could be used to screen blood and plasma prior to use. Used in that context, the test achieves an important public health goal. However, it is vital that both physicians and patients understand that the antibody test is NOT a test for AIDS. As with any serologic test, there will be some false-positive results, even in samples which are repeatably reactive. When true HTLV-III antibody is present in an otherwise asymptomatic individual, it could mean that infection with the virus has occurred without any clinical evidence of disease. Limited observations indicate that only a small proportion of those individuals will go on to develop AIDS. The natural history of HTLV-III infection is not completely understood at present, and it is not possible to identify by laboratory or other means those asymptomatic persons with antibody to HTLV-III who will eventually develop AIDS. Therefore your clinical judgement is the most important aspect of the evaluation of individuals with antibody to HTLV-III, especially since the test is primarily designed to screen blood and plasma.

Whenever there is a reactive test for antibody to HTLV-III in blood. and plasma donors, the PHS recommends that additional serologic testing be considered to clarify the significance of the screening

*ELISA is an acronym for enzyme-linked immunosorbent assay. This assay utilized the principle of a solid phase (e.g., beads or microtiter plate wells) coated with antigen or antibody and an indicator reagent, antibody or antigen, respectively, to which an enzyme has been conjugated or "linked".

A typical ELISA test such as that used for the detection of antibody to HTLV-III utilizes beads or microtiter wells coated with disrupted, inactivated HTLV-III virus antigens and goat anti-human Ig conjugated or "linked" to an enzyme which on incubation with the appropriate substance will produce a color.

When an unknown serum or plasma sample is tested for the presence of antibodies, it is placed in the antigen-coated wells; the antibody in the sample links to the antigen on the solid-phase carrier and is detected by the anti-human antibodies conjugated to the enzyme.

test results. The Western blot* technique has been the most extensively used test for HTLV-III antibody specificity in the research setting. Based on data available to date, minimal criteria that define a positive Western blot test have been established by the PHS, as described in the attached Provisional Recommendations. Western blot testing will be available through most of the manufacturers of the antibody test kits. Further information about the availability of Western blot testing can be obtained through your local blood bank. You may also be able to get additional information through your State Health Department. It is important to recognize, however, that the Western blot test is still considered a research tool which has not yet been fully standardized. Furthermore, when the HTLV-III screening test is positive, negative Western blot result does not necessarily mean that antibody specific to HTLV-III is absent because the relative sensitivity of each of the tests varies among laboratories. In addition to blood or plasma donors who might be referred to you as the result of a reactive screening test for HTLVIII antibody other patients may ask you to determine their HTLV-III antibody status because of concern that they may be at risk of developing AIDS. Such individuals should be given information about the implications of the ELISA test BEFORE being tested, with particular emphasis on the significance of a positive result. addition, physicians and other health professionals should recognize the need for assuring the confidentiality of test results because disclosure could lead to serious social and employment consequences. Loss of employment or insurability may occur if positive test results become a part of the medical record.

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Because, as noted above, the natural history of the disease is not completely understood at the present time, the medical significance of a positive result is unknown in terms of its predictive value for an asymptomatic individual. Furthermore, there may be biologically false-positive reactions due to cross-reactivity to antigens of other viruses. Individuals who seek testing should also recognize that a negative antibody test result does not necessarily mean that they are free of virus. Antibody may not have developed, or be undetectable, if exposure was recent. There is at least one report that 4 of 96 individuals carried the virus for 6 months without developing detectable antibodies. Because a positive test result can be difficult to interpret for an asymptomatic individual, consideration also should be given to the severe psychological stress which would be placed on the individual if the test for antibody to HTLV-III is positive. Appropriate counseling should be available if HTLV-III testing is done.

As significant new information is developed and new products become available to help in the diagnosis and treatment of AIDS, we will continue to take steps to inform the medical community.

*The term "Western blot" refers to a technique for identifying antibodies to proteins of specific molecular weight. The technique therefore allows the identification of antibodies to specific proteins associated with the HTLV-III virus. Based on available data, the Western blot should be considered positive for antibody to HTLV-III if band p24 or gp41 is present (alone or in combination with other bands). In general this test is less sensitive than the ELISA but more specific if positive.