Detailed Information on the
HIV/AIDS Research Assessment

Initiate a Phase IIb trial of a promising vaccine candidate that may protect across viral clades (or subtypes).

Begin analyzing final data from a phase III trial of a second generation vaccine.

Track, monitor, and budget for trans-NIH AIDS research, utilizing the enhanced ARIS database, to more efficiently conduct portfolio analysis of 100% of expiring grants to determine reallocation of resources for priority research.

Track, monitor, and budget for trans-NIH AIDS research, utilizing the enhanced ARIS database, to more efficiently conduct portfolio analysis of 100% of expiring grants to determine reallocation of resources for priority research.

[FY10] Track, monitor, and budget for trans-NIH AIDS research, utilizing the enhanced ARIS database, to more efficiently conduct portfolio analysis of 100% of expiring grants to determine reallocation of resources for priority research.

Adopt the revised goal of extending the timeline for developing an AIDS vaccine from 2007 to 2010, to more realistically reflect the state of the science.

Expand breeding of non-human primates at 3 Centers by 2005.

Develop 3 anti-HIV compounds by 2005.

Initiate 1 new Phase IIb trial to determine if a third generation vaccine candidate has efficacy.

Evaluate interventions to reduce mother-to-child transmission of HIV and assess the impact of these interventions on future treatment options for women and children.

Initiate another Phase II/IIb trial(s) of the most promising third generation vaccine candidate.

Achieve goal of evaluating the efficacy of three new treatment strategies for HIV infection in clinical trials in an effort to identify agents or combinations of agents that are more effective, less toxic, and/or simpler to use than the current recommended HIV treatment regimens.

Track, monitor, and budget for trans-NIH AIDS research, utilizing the enhanced ARIS database, to more efficiently conduct portfolio analysis of 100% of expiring grants to determine reallocation of resources for priority research.

Track, monitor, and budget for trans-NIH AIDS research, utilizing the enhanced ARIS database, to more efficiently conduct portfolio analysis of 100% of 728 expiring grants to determine reallocation of resources for priority research.

Measure: By 2010, develop an HIV/AIDS vaccine. 2005 Target: Expand breeding of non-human primates at 12 Centers. 2006 Target: Initiate 1 new Phase IIb trial to determine if a third generation vaccine candidate has efficacy. 2007 Target: Continue development and evaluation of candidate vaccines.

Explanation:The development of a safe and effective vaccine against HIV is critical to worldwide efforts to control AIDS and is the best hold for halting the pandemic.

Measure: By 2007, evaluate the efficacy of 3 new treatments. 2005 Target: Develop 3 anti-HIV compounds. 2006 Target: Evaluate interventions to reduce mother-to-child transmission (MTCT) of HIV and assess the impact of these interventions on future treatment options for women and children.

Explanation:Complications are emerging from the current HAART therapy regimen so there is an urgent need for the discovery and development of new drugs that are less toxic, simpler to use, and affordable.

Measure: By 2010, utilize enhanced AIDS Research Information System database to more efficiently conduct portfolio analysis to invest in priority AIDS research.

Explanation:Improve database to more efficiently conduct portfolio analysis through better tracking, monitoring, and budgeting for trans-NIH AIDS research.

Measure: Evaluate an HIV candidate in a test of concept (phase IIB) efficacy trial.

Explanation:

Measure: Develop and evaluate two new interventions for the prevention and/or treatment of HIV disease utilizing the newly restructured HIV/AIDS clinical trials networks.

Explanation:

Is the program purpose clear?

Explanation: Authorizing statute established the NIH Office of AIDS Research (OAR) and explicitly designates OAR as the primary Federal entity with responsibility to oversee (including plan, coordinate, and evaluate) all AIDS research conducted or supported by the NIH Institutes. Subsequent appropriations bills and report language further clarifies/strengthens OAR's responsibility to determine jointly with the NIH Director on the annual allocation of AIDS funding among NIH Institutes.

Evidence: Section 2351 of the National Institutes of Health Revitalization Act of 1993, P.L. 103-43; OAR mission statement; OAR provisions in L/HHS/Ed appropriations bills and report language from fiscal years 1998-2003.

Does the program address a specific and existing problem, interest, or need?

Explanation: The NIH AIDS research program was established in direct response to an emerging public health threat. Nearly 60 million people worldwide cumulatively have been infected with HIV; AIDS has killed more than 22 million people. OAR's role is to identify scientific areas within the HIV/AIDS portfolio that require focused research and facilitate multi-Institute research efforts to address them. While the disease continues to expand and evolve in the U.S. and world-wide overtime, the overarching priorities that continue to frame the NIH AIDS research agenda are: 1) prevention research to reduce HIV transmission, including the development of vaccines, microbicides, and behavioral interventions; 2) therapeutics research to develop simpler, less toxic, and cheaper drugs adn drug regimens to treat HIV infection and its associated illnesses, malignancies, and other complications; 3) international research in developing counties; and 4) research targeting the disproportionate impact of AIDS on minority populations in the United States.

Evidence: CDC Surveillance Reports (www.cdc.gov/hiv/stats/hasr1302.htm); USAID "Report on the Global HIV/AIDS Espidemic"; CIA National Intelligence Estimate "The Global Infectious Disease Threat and Its Implications for the United States"; CIA Report "The Next Wave of HIV/AIDS: Nigeria, Ethiopia, Russia, India, and China."; annual NIH Plan for HIV-Related Research.

Is the program designed so that it is not redundant or duplicative of any Federal, state, local or private effort?

Explanation: The NIH AIDS research program is the largest public investment in AIDS research in the world. The 1996 Levine Report concluded that "Without a strong stimulous from NIH that includes much needed basic information, the waning private sector interest in an HIV vaccine may vanish altogether." NIH's therapeutic research and prevention strategies are the foundation for HRSA. CDC, SAMHSA, CMS, USAID and others to implement their own agency goals. A few foundations, such as Gates, the American Foundation for AIRS Research, Elizabeth Glaser Pediatric AIDS Foundation and IAVI have small targeted research programs that do not compete with NIH, but rather often supplements or complements NIH research. None of these efforts compare to the size, volume, comprehensiveness, or collective achievement of the NIH AIDS research program.

Evidence: Document: NIH Sponsored Studies Effecting Progression to AIDS; Kalichman et al. Prevention of sexually transmitted HIV infection: a meta-analytic review of the behavioral outcome literature. Annals of Behavioral Medicine 1996; 18:6-15.; Pendergast et al. Meta-analysis of HIV risk-reduction interventions within drug abuse treatment programs. Journal of Consulting and Clinical Psychology. 2001; 69:389-405.; CDC Research Synthesis Project. JAIDS. 2002, 30:S94-S105.; Card et al. The HIV/AIDS Prevention Program Archive: A collection of promising prevention programs in a box. AIDS Education and Prevention. 2001;13:1-28.; "Discovery Lays Groundwork for Potential New Class of Anti-HIV Drugs (NIAID News 3/31/03).; Citations Data reflecting the prolific citations of NIH investigated AIDS research published by ScienceWatch.

Is the program design free of major flaws that would limit the program's effectiveness or efficiency?

Explanation: NIH AIDS research is supported by nearly every NIH Institute and Center, according to its mission and expertise both extramurally and intramurally through a wide variety of research grant mechanisms. This flexible and crosscutting design allows scientists to research AIDS from multiple perspectives and are consistent with recommendations from independent evaluations. Based on a comprehensive strategic plan that clearly establishes the areas of scientific endeavor and the research priorities, the program design of peer-reviewed, competitive grants allow NIH to respond in a balanced way to close knowledge gaps by issuing directed research program announcements, support emerging scientific opportunities, and address foreseen changes in the disease and unforseen public health contingencies. Peer-reviewed, investigator-initiated research is the accepted gold standard for funding the most meritorious, diverse, and productive science. OAR's three percent transfer authority gives OAR the ability to fully coordinate the diverse AIDS-related research carried out by all NIH Institutes.

Evidence: 1991 Institute of Medicine Study on The AIDS Research Program of the National Institutes of Health; 1996 Report of the NIH Research Program Evaluation Task Force; 1997 NIH Plan to Implement Recommendations of the NIH AIDS Research Program Evaluation Task Force; Section 208 of the L/HHS General Provisions -- OAR 3 percent transfer authority.

Is the program effectively targeted, so program resources reach intended beneficiaries and/or otherwise address the program's purpose directly?

Explanation: The AIDS-related research portfolio is based on the annual comprehensive NIH Plan for HIV-Related Research, which targets: 1) emphasis areas such as Natural History and Epidemiology, Etiology and Pathogenesis, Therapeutis, Vaccines, and Behavioral and Social Science; 2) cross-cutting science areas such as Racial and Ethnic Minorities, Microbicides, Prevention Science, Women and Girls, International Research, Training, Infrastructure/Capacity Building, and Information Dissemination; 3) scientific priorities and opportunities; and 4) populations at risk. This Plan drives the budget development process. Institutes develop individual strategic plans to implement initiatives, based on the overarching OAR HIV-Related Plan, specific to their missions. A standing general provision permits the OAR Director, jointly with the NIH Director, to transfer between NIH Institutes up to three percent of the funding determined by NIH to be related to AIDS research. The AIDS Research Information System enables the OAR to track and monitor all AIDS research expenditures according to the objectives of the Plan.

Evidence: 1992 Institute of Medicine Study on The AIDS Research Program of the National Institutes of Health; 1996 Report of the NIH Research Program Evaluation Task Force; 1997 NIH Plan to Implement Recommendations of the NIH AIDS Research Program Evaluation Task Force; research that shows balanced priorities between treatment for those already infected and prevention strategies for those at risk; peer review to ensure meritorious science is supported; outside expert advice to help establish ongoing five scientific priorities; increased emphasis on vaccine research based on the state of the science; and increased emphasis on women, minorities, and international, based on disease burden.

Does the program effectively articulate potential public benefits?

Explanation:  

Evidence:  

If an industry-related problem, can the program explain how the market fails to motivate private investment?

Explanation:  

Evidence:  

Does the program have a limited number of specific long-term performance measures that focus on outcomes and meaningfully reflect the purpose of the program?

Explanation: The two long-term performance goals signaled out for GPRA purposes are: 1) Develop an HIV/AIDS vaccine by 2007, and 2) By 2007, evaluate the efficacy of three new treatment strategies for HIV infection in phase II/III clinical trials in an effort to identify drugs that are more effective, less toxic and/or simpler to use that the current recommended HIV treatmetn regimen.

Evidence: NIH OAR GPRA plan (www.nih.gov/od/oar/public/pubs/fy2004/fy2004CJ.pdf); OAR Strategic Plan (www.nih.gov/od/oar/public/pubs/fy2004/i_overview.pdf )

Does the program have ambitious targets and timeframes for its long-term measures?

Explanation: VACCINE: At present there is no HIV/AIDS vaccine. An effective vaccine is critical to worldwide efforts to control HIV/AIDS and offers the best hope of halting the HIV/AIDS pandemic. THERAPUETICS: Complications are emerging from the current HAART therapy regimen so there is an urgent need for the discovery and development of new drugs that are less toxic, simpler to use, and affordable. Both the vaccine and therapeutics goals have established time frames.

Evidence: NIH OAR GPRA plan (www.nih.gov/od/oar/public/pubs/fy2004/fy2004CJ.pdf); OAR Strategic Plan (www.nih.gov/od/oar/public/pubs/fy2004/i_overview.pdf )

Does the program have a limited number of specific annual performance measures that demonstrate progress toward achieving the program's long-term measures?

Explanation: NIH has identified several annual targets that tie back to the OAR strategic plan for both vaccines and therapeutics. For vaccines, the OAR strategic plan includes basic research, vaccine development, study populations and infrastructure development, and clinical trials. For Therapeutics, the OAR strategic plan includes basic research, clinical trials, drug complications, coinfections and manifestations, and mother-to-child transmission.

Evidence: OAR Strategic Plan This can be found on the internet at: www.nih.gov/od/oar/public/pubs/fy2004/i_overview.pdf Therapeutics are covered in Chapter IV and Vaccines in Chapter V.

Does the program have baselines and ambitious targets and timeframes for its annual measures?

Explanation: The baseline is the state of the science for the year proceeding the annual targets. The program has quanitifiable targets for the year that are necessary for achieving the long-term performance goals.

Evidence: OAR Strategic Plan This can be found on the internet at: www.nih.gov/od/oar/public/pubs/fy2004/i_overview.pdf Therapeutics are covered in Chapter IV and Vaccines in Chapter V.

Do all partners (including grantees, sub-grantees, contractors, cost-sharing partners, etc.) commit to and work toward the annual and/or long-term goals of the program?

Explanation: NIH's government partners (CDC, DOD, VA) serve on the OAR Advisory Council. Government partners also frequently serve on Planning Groups for the annual NIH Plan for HIV-Related Research. NIH Institutes and Centers commit to OAR goals by issuing RFAs, PAs, and RFPs that have been reviewed by OAR so that they are consistent with the NIH Plan for HIV Related Research. AIDS Research Information System (ARIS) is a early notification system that codes the grant to an objective in the plan. All intramural and extramural grant awardees are required to submit annual reports outlining their scientific progress toward the achievement of the grant or project's objectives.

Evidence: ARIS (including an IC funding sheet for coding); Institute and Center Strategic Plans that tie to the OAR Strategic Plan; Example of an RFP from NHLBI

Are independent and quality evaluations of sufficient scope and quality conducted on a regular basis or as needed to support program improvements and evaluate effectiveness and relevance to the problem, interest, or need?

Explanation: Evaluations of the AIDS program are conducted by outside experts on an ongoing basis on multiple levels: 1) The broad AIDS program objectives are evaluated by congressionally-mandated Advisory Councils that are appointed by the Secretary; 2) Program areas with multi-institute support are subjected to OAR sponsored reviews of program areas; 3) Specific extramural targeted programs are reviewed by Institute convened groups that evaluate projects, including site visits by program staff and outside reviewers; 4) The Levine Report recommended the formation of working groups to critically examine extramural AIDS research. These groups are not FACAs, but rather are independent investigators that examine the state of the NIH portfolio and provide recommendations; 5) Intramural AIDS research projects are reviewed by Boards of Scientific Counselors, comprised of scientific experts from academia and industry.

Evidence: The evidence corresponds to the numbers in the Explanation box: 1) The Levine Report is the most recent example of a comprehensive review (1996), The Prevention Science Working Group and the Therapeutics Research Working Groups rosters, missions, and reports; 2) OAR reviews and reports; 3) IC-specific program reviews; 4) An example of a working group, including links to the meeting minutes: www.niaid.nih.gov/daids/vaccine/avrc.htm; 5) Examples of intramural projects reviewed by Boards of Scientific Counselors every four years

Are Budget requests explicitly tied to accomplishment of the annual and long-term performance goals, and are the resource needs presented in a complete and transparent manner in the program's budget?

Explanation: The NIH has been budgeting by its strategic plan. This presentation does not explicitly tie budget resource levels to annual and long-term performance targets. The budget requests do not show how much it would cost to achieve the performance results.

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Has the program taken meaningful steps to correct its strategic planning deficiencies?

Explanation: Currently, NIH does not have a plan to address how the agency would revamp its budget requests to explicitly tie the accomplishment of goals to resource levels.

Evidence:  

If applicable, does the program assess and compare the potential benefits of efforts within the program to other efforts that have similar goals?

Explanation: As discussed in detail in question 1.3, the NIH AIDS Research program is the largest public investment in AIDS research, and therefore, is not comparable to other programs.

Evidence:  

Does the program use a prioritization process to guide budget requests and funding decisions?

Explanation: OAR workshops utilize input from non-NIH experts from academia, foundations, industry, and the community. Annually, Planning Groups assess the state of the science in view of the previous year's plan and then strategies/objectives are reviewed and updated, eliminating, adding and reprioritizing objectives. Scientific priorities narrowly define key areas deemed worthy of new/expanded funding based on current knowledge, opportunities, or gaps. The Budget explicitly ties to these priorities. ICs submit AIDS-related research budget requests to OAR focusing on new/expanded program initiatives for each scientific area. Proposals are reviewed in relation to the Plan and to other IC missions to eliminate redundancy and assure cross-institute collaboration. Awards are made based on the scientific priority of the proposed initiatives at each step of the budget process up to the final congressional appropriation. There is no funding formula for when funding levels change. Rather, dollars are allocated and balanced based on scientific opportunity and IC capacity to absorb and expend resources to the most meritorious science.

Evidence: NIH OAR GPRA plan (www.nih.gov/od/oar/public/pubs/fy2004/fy2004CJ.pdf) OAR Spending by the NIH Plan for HIV-Related Research table; OAR AIDS funding by Institute and Center table; OAR AIDS Research Priorities as the Respond to the AIDS epidemic graph; IC funding codes table

Does the agency regularly collect timely and credible performance information, including information from key program partners, and use it to manage the program and improve performance?

Explanation: Performance data are collected when grants/contracts are submitted (peer-reviewed baseline data) and during the award, both extramurally and intramurally. Monitoring includes: progress reports, correspondence, audit reports, site visits, annual invention utilization reports, lobbying disclosures, specialized programmatic reports, and publications of objectives, methodology, and findings. A reduction in budget, withholding support, or termination may and has resulted from substandard data, insufficient patient accrual/retention into clinical studies, inadequate progress in fulfilling the research agenda, noncompliance with Federal regulations, or the Term of Award. Contract project officers monitor the performance/quality of deliverables to ensure the statement of work is fullfilled within the designated time and those that don't are terminated. Since 1956, NIH Intramural research is periodically reviewed by a Board of Scientific Counselors that assess research activities, progress, and the future direction of labs. Recommendations affect future resources such that some intramural labs are expanded, contracted, or even closed.

Evidence: Example of redacted portion of a recommendation memo from an NIH Board of Scientific Counselors; Example of a Request for Application (RFA) for an adult therapeutic AIDS clinical trials program that shows specific eligibility/review criteria for the network (of grantees) to establish procedures for assessing performance of individual sites and the entire network (e.g., procedures on adding/eliminating sites or laboratories based on performance, redistributing resources, establishing site-specific and overall group plans to ensure enrollment of demographically diverse populations, especially women and minorities, and establishing community advisorty boards); Letters from Congress regarding failure of sites to successfully recompete in Pediatric AIDS Clinical Trials Network; Dec. 22, 1999 NIAID newsletter on five existing sites being "phased-out" as a result of recompetition.

Are Federal managers and program partners (grantees, subgrantees, contractors, cost-sharing partners, etc.) held accountable for cost, schedule and performance results?

Explanation: All NIH employees have performance plans or contracts, assessed twice yearly by supervisors, to evaluate job performance. Sustained unsatisfactory performance, violation of Federal laws/regulations, or gross negligence leads to suspension and/or dismissal from Federal employment. Grant administration is the joint responsibility of the NIH Institute Program Director and the Grants Management Specialist. Program Directors are responsible for the grant's scientific, technical, and programmatic issues and receive annual reports documenting progress, proprietary information relative to patent applications, and scientific articles submitted/published in peer reviewed journals. The Grants Management Specialist is responsible for the grant's business aspect and is authorized to obligate NIH at the expenditure of funds and permit changes to approved projects. The contract's administration is the joint responsibility of the NIH Institute Project Officer and Contract Officer. The Project Officer monitors the technical aspects of the project and the Contract Officer is empowered to execute or modify a contract.

Evidence: DHHS Grants Admnistration Manual (www.hhs.gov/grantsnet); NIH Grants Policy Statement (grants1.nih.gov/grants/policy/policy.htm); Compendium of Findings from proactive compliance site visits (grants1.nih.gov/grantscompliance/compendium 2002.htm); Grant application (PHS 398); and Financial Status report Standard Forms 269 & 269A.

Are all funds (Federal and partners') obligated in a timely manner and spent for the intended purpose?

Explanation: Authorizing legislation P.L. 103-43 requires OAR to allocate appropriated funds to the Institute "...to the extent practicible, be made no later than 15 days after the date on which the Director receives amounts..." Historically, OAR has allocated th eappropriated funds within one week of appropriation. An allocation letter from OAR is transmitted to the Institutes and Centers to inform their overall funding allocation along with a list of programmatic priorities approved for funding. AIDS grants are also subject to "expedited review" required by law to be processed and reviewed within 6 months from receipt deadline to funding decisions as opposed to the standard 9 months for non-AIDS grants. OAR tracks and monitors the actual expenditure of funds by area of emphasis/object codes. Careful program management planning and employment of strict financial management procedures ensure the limited amounts of unobligated funds remain at the end of each fiscal year. OAR records show that historically, less than $10,000 has remained unobligated by the end of each fiscal year.

Evidence: FY 2003 allocation letter fro the OAR Director to an NIH Institute Director; schedule of AIDS application receipt dates.

Does the program have procedures (e.g., competitive sourcing/cost comparisons, IT improvements, approporaite incentives) to measure and achieve efficiencies and cost effectiveness in program execution?

Explanation: Intramural labs use competitive bidding to purchase equipment, supplies, and reagents so that AIDS funding achieves the maximum cost-efficiency in advancing scientific progress. Basic lab supplies and chemical reagents are stocked in central stores on the NIH campus permiting competitive pricing for large quantities of common items. NIH uses a contracting mechanism to acquire supplies, services, equipment, construction, and IT. Services include the conduct of clinical trials, breeding, maintenance/provision of non-human primates, production/testing of specific reagents, and manufacture of doses of vaccine candidates. RFPs or Invitation for Bids (IFBs) are issued for specific goods and services and are announced through the Federal Business Opoportunities website, the single government point-of-entry for Federal Government procurement opporunities over $25,000. OAR also has an IT system (ARIS) that prevents redundant funding of grants.

Evidence: www.FedBizOpps.gov; www.arnet.gov/far; "The Guide to the NIH Acquisition Process," www.hhs.gov/ogam/oam/procurement/hhsar.html; OAR proposal for a new ARIS database system.

Does the program collaborate and coordinate effectively with related programs?

Explanation: The Global AIDS Research Strategy Group established by the OAR provides a forum for information exchange and discussion of current and planned international HIV research efforts. Participants include CDC, FDA, PHAP, DHHS, DOD, DoS-USAID, ONAP, the World Bank, and USAID. NIH collaborates with DoD, CDC, AHRQ, FDA, HRSA, and the Pan American Health Organization (PAHO) on natural history and epidemiology studies. NIH works closely with FDA to monitor drug development and expedite approval of new drugs. The NIH-sponsored HIV Vaccine Trials Network (HVTN) is a coordinated global network for conducting phase I, II, and II clinical trials of HIV vaccine candidates in 17 domestic and 10 international sites. Sub-studies designed by NIH and CDC are performed within HVTN clinical protocols. The NIH-sponsored HVTN is a comprehensive multi-center network of 9 U.S. and 16 international sites dedicated to research on non-vaccine methods to prevent HIV transmission. In collaboration with CDC, NIH supports the AIDS International Training and Research Progeram to address research training for scientists and health care workers from 55 resource-poor countries.

Evidence: Since the beginning of the epidemic, the NIH AIDS research program has collaborated with otehr government agencices, industry, community organizations, international organizations, foundations, and scientific societies in the U.S. and overseas to plan, coordinate, carry out resaerch, train sicentists, and disseminate research information. Provided as evidence are ongoing and previous NIH trans-government collaborations in HIV-related research.

Does the program use strong financial management practices?

Explanation: The most recent audit cited NIH's financial reporting and processes as a material weakness. NIH's Central Accounting System (CAS) lacks intergration with its subsidiary systems. The report stated that the financial reporting systems and processes used by NIH were not capable of producing reliable financial statements in a timely manner. Reconciliation of certain accounts were not done in a timely manner, which required extensive research and analysis of various account balances before NIH's fiscal 2002 financial statements were considered completed.

Evidence: NIH Independent Auditor's Report and Financial Satements, September 30, 2002 and 2001; NIH FY 2003 Third Quarter Financial Management Progress Report.

Has the program taken meaningful steps to address its management deficiencies?

Explanation: NIH has implemented a detailed financial management corrective action plan with milestones, appointed responsible offices and points of contact, target dates, and completion dates. The plan is on track to fully implement NIH's new NBRSS financial management system (a part of the larger HHS-wide Unified Financial Management System effort) by FY 2005.

Evidence: FY 2002 NIH Corrective Action Plan

Does the program allocate funds through a competitive, merit-based process, or, if not, does it justify funding methods and document how quality is maintained?

Explanation: Research grants are awarded competitively for a finite amount of time, at the end of which they must recompete through peer review. Key criteria considered by the peer-review group in making recommendations for continuation include past performance and scientific progress in reaching the goals established in the individual project application. Grant applications may be unsolicited (investigator-initiated) or in response to targeted initiatives (Program Announcements, Request for Applications, and Request for proposals), all of which are peer-reviewed for quality. Grant applications/contract proposals submitted in response to a specific task or service are subjected to dual level peer review. Criteria may include the need to demonstrate that an applicant has previous clinical trial experience, a definitive plan for the recruitment/enrollment of diverse populations, or plans to establish and maintain a community advisory board to ensure community involvement in the planning, design, and conduct of clinical studies.

Evidence: DHHS Grants Admnistration Manual (www.hhs.gov/grantsnet); NIH Grants Policy Statement (grants1.nih.gov/grants/policy/policy.htm).

Does competition encourage the participation of new/first-time performers through a fair and open application process?

Explanation:  

Evidence:  

Does the program adequately define appropriate termination points and other decision points?

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Evidence:  

If the program includes technology development or construction or operation of a facility, does the program clearly define deliverables and required capability/performance characteristics and appropriate, credible cost and schedule goals?

Explanation:  

Evidence:  

Has the program demonstrated adequate progress in achieving its long-term outcome performance goals?

Explanation: VACCINES: By NIH's own admission, the vaccine goal will not be achieved by 2007. However, significnat progress has been made. In humans, NIH has conducted more than 50 Phase I and Phase II clinical trials of more than 30 vaccine products. At least 10 new candidates will enter Phase I trials in the next two years. The VRC recently launched the first Phase I clinical trial of a multi-clade, multi-gene vaccine candidate. Since January 2003, 3 vaccine candidates have entered trials in the US or international sites. THERAPEUTICS: Since 1996, several new classes of antiretroviral drugs, including fusion inhibitors (FI), protease inhibitors (PI), and nucleotide analogues (NA) have been developed and proved to be safe:1 FI, 6 PIs, 1 NA, 2 nucleoside reverse transcriptase inhibitors, and 3 non-nucleoside reverse transcriptase inhibitors have been licensed. Several combination drug therapies have recently been approved. In the past 6 years, the FDA has approved more than 10 new treatments targeting HIV-related OIs and cancers.

Evidence: Vaccine pipeline charts indicate progress toward achieving a safe and efficacious vaccine; PHaRMA therapeutics document; JAMA, July 25, 2001; NIH Stories of Discovery

Does the program (including program partners) achieve its annual performance goals?

Explanation: New annual targets were identified through the PART that are quantifiable and more ambitious. NIH has a systematic process to collect information about scientific advances and achievements as they relate to these targets. Prior to their development, NIH reported annual progress in the NIH GPRA plan. While these old targets were too vague, they do relate to the revised annual targets and the progress is applicable. VACCINES: Design and development advances of vaccine strategies to fuel the pipeline of promising vaccine candidates include: emergence of new vaccine concepts; advancement into preclinical testing; successful use of animal models; the initiation of new clinical trials; and collaborations with scientists in developing countries. THERAPEUTICS: While no specific GPRA targets existed, the OAR Strategic Plan does chronicle annual progress to improved treatment strategies, including reduction of patient viral loads, increased CD4 cells counts, decreased opportunistic infections, and improved immune functions in patients who are able to adhere to treatment regimens and tolerate toxicities.

Evidence: Highlights of NIH Scientific Accomplishments and Advances in AIDS Research During the Era of the Five-Year Doubling; NIH GPRA Plans 1999 to 2004; Science Advances/Stories of Discovery.

Does the program demonstrate improved efficiencies or cost effectiveness in achieving program performance goals each year?

Explanation: Examples of NIH's improved efficiencies: Expedited Follow-up: VAXGEN's overall efficacy failed, but it did possibly provide immune protection in minority populations. NIH's large repository of samples from vaccinated volunteers allowed it to take stored frozen samples and rapidly confirm immunogenicity in minorities/women in previous trials, resulting in time and cost savings from eliminating an additional Phase II trial before staging a larger Phase III trial. ARIS: the system is being improved/upgraded to accomodate all budget functions and to improve the tracking and monitoring of the AIDS portfolio. New Procedures: 1) Expedited Review ensures all AIDS grants are processed/reviewed in 6 months as opposed to the standard 9 months for non-AIDS grants. 2) Streamlining allows grant reviewers to unanimously agree on applications in the lower half that will not be discussed or scored at the meeting. Prospective grantees do receive the reviewer's comments. 3) NIH-managed AIDSinfo is a collaborative effort with CDC, CMS, and HRSA to provide a single, searchable resource for HIV/AIDS treatment and prevention guidelines.

Evidence: Expedited Follow-up can be found at Section 2302 of the Public Health Service Act; Streamlining is described in two CSR documents, "Review Procedures for Scientific Review Group Meetings" and "Streamlined Review Procedures Used in CSR"; NIH FY 2004 Plan for HIV-Related Research; ARIS redesign plan; AIDSinfo: http://aidsinfo.nih.gov

Does the performance of this program compare favorably to other programs, including government, private, etc., that have similar purpose and goals?

Explanation: Per discussion in questions 1.3 and 2RD1, the NIH AIDS research program is the largest public investment in AIDS research, and therefore, is not comparable to other programs.

Evidence:  

Do independent and quality evaluations of this program indicate that the program is effective and achieving results?

Explanation: NIH regularly ulitizes independent evaluations to assess both program structure and performance on multiple levels. The last comprehensive study, the Levine Report (1996) concluded that NIH investment in AIDS research is of the highest quality and relevance. The NIH AIDS investment has yielded the natural history of the disease, prevention strategies, and clinical and basic research advancements. A 1991 IOM report "The AIDS Research Program of the NIH" states: The committee has carefully examined NIH's organizational and procedural arrangements for reviewing and awarding AIDS-related research grants and concludes that currently they are adequate." A 1999 CFAR focus group reported that the program "has been successful in a number of areas, particularly with regard to fostering collaboration between existing research programs related to HIV and AIDS."

Evidence: Report of the NIH AIDS Research Program Evaluation Working Group of the OAR Advisory Council, 1996. Report of the Working Group to Review the NIH Perinatal, Pediatric, and Adolescent HIV Research Priorities, 1999.; Report of the Focus Group to Review the Centers for AIDS Research Program, 1999.; Selected Outside Reviews of NIH AIDS Research Programs from 1993 to date.

If the program includes construction of a facility, were program goals achieved within budgeted costs and established schedules?

Explanation:  

Evidence: