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Approximately 33 percent of the ACTG protocols are evaluating anti-oi therapies, which have an enrollment of 2,800 patients.

CPCRA has two active of protocols and is developing 4 additional OI studies.

Recent initiatives relative to increasing underrepresented populations in the clinical trials effort include: establishment of a committee in the ACTG and CPCRA to focus on specific needs of women; development of women-specific endpoints; supplements to increase recruitment of underrepresented populations; expansion of pediatric clinical trials as part of the $22.6 million increase by Congress with an additional $7.8 million increase in basic research on pediatric HIV disease; and collaboration with HRSA in the development of a pilot project under the Ryan White Comprehensive AIDS Resources Emergency ACT of 1990 (C.A.R.E.), Title IV legislation providing for increasing access to experimental therapeutics and primary health care by the provision of ancillary services to HIV infected pediatric patients and their families.

Major Accomplishments in the NIH-funded clinical trials:

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Establishment of a national clinical trials network in
both academic medical centers and universities, the
AIDS Clinical Trials Group (ACTG) and a community based
program, the Community Programs for clinical Research
on AIDS (CPCRA) capable of testing new anti-HIV and
agents for the treatment of opportunistic infections.

AZT effectively slows disease progression in HIV-
infected individuals.

Extension of the use of AZT for individuals with early
and asymptomatic infections including HIV-infected
children down to 3 months of age.
IV gamma globulin (IVIG) effectively reduces the number
of OIs in children with CD4+ counts >200.

Aerosolized pentamidine effectively used for
prophylaxis of PCP.

ddI phase I clinical trials funded through NCI have demonstrated that survival has been significantly prolonged, with the actuarial 2-year survival reaching 80 percent even in patients with advanced stages of AIDS.

Phase II/III studies of ddi are ongoing in
collaboration with the ACTG.

ddi has been made available through expanded access programs for AZT-intolerant patients with CD4 counts less than 200/mm as well as for patients who have failed AZT therapy and whose disease is progressive , despite AZT therapy. .

Fluconazole has been demonstrated to be effective for
Cryptococcal meningitis.

Foscarnet has been demonstrated to be effective for CMV retinitis.

Interferon-alpha has been shown to be effective in
reducing the rate of OIS in symptomatic patients.


The development of safe and efficacious vaccines is a public health priority. Intensified efforts to decrease mortality from AIDS and AIDS-associated malignancies and ultimately to prevent HIV infection continues to emphasize the development of an FDA approved vaccine.

NIH-funded researchers continue to advance the understanding of the immune system that may be important in the development of potential vaccine candidates. The efforts include the collaboration of NCI, NIAID, Walter Reed Army Institute of Research, and industry.

The AIDS Vaccine clinical Trials Network (AVCTN) sponsored by NIAID has established five AIDS Vaccine Evaluation Units that are designed for the evaluation of potential vaccines. Six vaccines are currently under investigation by the AVCTN.

Recent significant progress has been made in the development of potential vaccines for the prevention of AIDS including:

Three potential AIDS vaccines currently in NIAIDsponsored Phase I clinical trials have been shown to elicit an immune response.

Native or recombinant HIV subviral envelope (env) glycoproteins inoculated into chimpanzees induced both cellular and humoral immunity.

A whole virus SIV vaccine demonstrated protection in monkeys.

Inactivated whole virus HIV vaccine studies supported by NIH in chimpanzees persistently infected with HIV developed antibody responses and were cleared of viremia following virus challenge.

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A synthetic peptide of the HIV-1 is under investigation in an NIH-sponsored study to determine its ability to prevent AIDS in individuals already infected with HIV.

Animal models are being developed for the evaluation of potential vaccine candidates including the SIV/macaque model for the comparative evaluation of vaccine approaches and adjuvants and the Severe Combined Immunodeficiency (SCID) mouse model for vaccine development.


Dissemination of information concerning ongoing research and research results is crucial to the management of patients with HIV infection.

The National Library of Medicine (NLM) currently sponsors three AIDS-related on-line databases on its MEDLARS network, AIDSLINE, AIDSDRUGS, and AIDSTRIALS:

AIDSLINE, an on-line computer file of more than 40,000 references to the published literature on AIDS, is updated weekly and is growing at the rate of about 800 new citations a month. NLM plans to continue to expand the coverage of AIDSLINE, not only with more source journals and meeting abstracts, but with other forms of information such as monographs and audiovisuals.

AIDSTRIALS and AIDSDRUGS were created in response to
the mandate of the Health Omnibus Programs Extension
Act of 1988, containing descriptions of clinical trials
being conducted to test the safety and efficacy of AIDS
therapeutics, and descriptions of the agents being

tested in the clinical trials, respectively.
In addition, the information has been disseminated through:

The NIAID AIDS Clinical Trials Information Service
(ACTIS) which provides information on NIH- and
industry-sponsored clinical trials of new therapies to
HIV-infected people and health care workers, with
information on over 156 NIH-sponsored and 94 industry-
sponsored protocols from the FDA. Additionally, the
ACTIS maintains data records on specific drugs, their
mode of action and toxicity.

A series of 1990 AIDS technology transfer meetings, initiated to enhance the sharing of state-of-the-art information on treatment and management of symptomatic and asymptomatic patients. These programs will continue targeting areas that do not have a major medical research effort such as Puerto Rico and rural areas of the U.S.

An NIH-sponsored workshop held on January 15 to address
the issue of expedited dissemination of information
with immediate positive or negative public health
impact such as AIDS related clinical trials results.
Based upon the workshop discussion and with additional
input from physicians, patients, and other Federal
agencies, NIH policy and guidelines for information
dissemination will be developed.


Question. Dr. Raub, does the President's budget include sufficient funds to support research project grants and center grants at their fully approved level? If not, what is the

estimated downward negotiation rate for research project grants and center grants? How do these rates compare with FY 1989 and 1990? How do they vary Institute by Institute?

Answer. As we have outlined in the forthcoming report, "A Plan for Managing the Costs of Biomedical Research", we are working toward eliminating the imposition of arbitrary reductions. This policy change will take place gradually as we move through the transition year of 1991. Therefore, neither commitments on grants previously awarded nor study section recommended levels for competing grants will be fully met.

Elimination of the arbitrary reductions will be accomplished by undertaking a concerted effort to heighten the sensitivity of Initial Review Group members to cost issues. If NIH financial management objectives cannot be met by accepting IRG recommended budgets, Councils and Boards, working with staff, will develop those cost control practices necessary to manage their research portfolios. We also will improve our capability for cost analysis. In those instances where Councils/Boards may determine that the cost of addressing a particular scientific question exactly as proposed is too great relative to its programmatic relevance, they will have the option to recommend changes to the scope of certain projects or to recommend a lower-cost strategy. The full effect of these practices will be closely evaluated during the coming year. These practices apply to competing research project grants.

For noncompeting research project grants, we now are estimating future years' costs based on the first year's adjusted cost plus a growth factor averaging four percent as opposed to the study section recommended level. Based on this new policy, we intend in the future to pay the commitment level.


Question. Dr. Raub, last year the NIH responded to several Congressional initiatives on women's health by creating an Office of Research on Women's Health within the Office of the Director. What level of funding does the NIH plan for the Office in FY 92?

Answer. The President's budget request for FY 1992 provides $2.5 million for the Office of Research on Women's Health. The funds are included in the overall request for the Office of the Director, NIH, and represent an increase of $1 million over those provided to the Office through the Director's discretionary fund in FY 1991.

Question. Is there a plan for creating a permanent advisory committee to assist the office with its mission?

Answer. The significant role of this Office is in assisting the NIH in increasing research activities related to women's health. This role requires consultation at the highest levels within the NIH advisory system. Thus, in its early stages, the Office of Research on Women's Health is seeking guidance from the Advisory Committee to the Director, NIH. NIH believes that

this reflects the importance placed on the activities of this new office.

The Task Force on Opportunities for Research on Women's Health has been constituted as a subcommittee of the Advisory Committee to the Director. This group has initiated a planning process that will culminate in recommendations for a trans-NIH research agenda for women's health. This process will include both a public meeting in June at which organizations interested in women's health will. present their views and a major scientific conference in September 1991.

The Task Force then will report to the Advisory Committee to the Director and propose à plan for research on women's health for the next decade. Until that plan and its recommendations are completed and accepted by the NIH Director, we expect that guidance to the office will be provided by the Task Force and the Advisory Committee to the Director. Upon completion of the report, NIH will consider whether these efforts might be served better by a separate advisory body.

Question. How will such an advisory Committee be constituted?

Answer. Based on the research priorities to be established in the Task Force report to the NIH Director, NIH will determine the best structure and membership for an advisory Committee. We will, however, be mindful of the views of the many organizations interested in women's health. The Office of Research on Women's Health expects to have an ongoing dialogue with these groups.

Question. Does the NIH plan to use the expertise of women's hospitals as it further develops an agenda for the Office of Research on Women's Health or as it establishes an advisory committee?

Answer. NIH plans to draw on the advice and expertise of leaders in the broad array of scientific areas, medical specialties and other fields related to research on women's health. Our efforts will address diseases, conditions, and disorders as they affect women throughout all the stages of life--birth to the geriatric years. NIH intends to seek advice from leading researchers, clinicians, and women's health advocacy organizations. Some of these experts undoubtedly will have experience in service at women's hospitals as well as in other health care settings.



Question. How does the quality of science education in the United States affect the ability of NIH to fulfill its mission?

Answer. The mission of the National Institutes of Health is to improve the health of the citizens of this Nation by conducting and supporting research into the factors underlying

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