QUESTIONS SUBMITTTED BY SENATOR ARLEN SPECTER RESEARCH FUNDING Question. Dr. Raub, in meetings with many of your colleagues in the research community they have raised deep concern over young investigators becoming discouraged and leaving the research field because of an inability to compete successfully for limited research funds. What is the extent of this problem? Is funding the only factor contributing to this phenomenon? Answer. The general perception in the scientific community of a funding crisis at the NIH often has focused on concern that young investigators are becoming discouraged about pursuing careers in biomedical research. In order to place the status of young investigators in perspective, a brief summary of the nature of this "funding crisis" is in order. The general perception of a crisis, has come about because the number of new and competing renewal research project grants that the NIH has been able to award in recent years has fallen below 6,000 grants. The principal reasons for these decreases are twofold. Costs of conducting research have escalated at a faster rate than have the funds appropriated for this purpose. In addition, besieged by concerns in the biomedical community that award periods were too short, the NIH began to increase the terms of awards, from an average of 3.4 years in 1985 to 4.2 years in 1990. The effect of this increase was the utilization of an increasing portion of the extramural budget for noncompeting awards, with fewer funds available to fund new and competing renewal awards. Despite decreases in competing awards, the total number of research project grants in the NIH portfolio continued to grow throughout most of this period. About the time that the NIH began to lengthen the term of awards, the First Independent Research Support and Transition (FIRST) Award for beginning investigators was initiated. This was a revision of the previous three-year New Investigator Research Award. The FIRST award provided for five years of support at a maximum level of $350 thousand for the entire period. Data collected since the initiation of this new instrument show that success rates for FIRST award applicants are much higher than are those for applicants for regular research project grants (RO1s). In fiscal year 1990, the success rates for the FIRST award and new RO1 award applicants were 27.6 and 16.7 percent, respectively. In that same fiscal year, the fourth full year that the award had been in effect, the NIH was supporting a total of 2,083 FIRST awards for $191.5 million. Many beginning investigators choose to apply for an R01 award, rather than a FIRST award, choosing to either avoid the dollar limitation or in the belief that they can be successful in competition with established investigators. In fiscal year 1989, the NIH awarded 335 first-time RO1s, compared to 502 FIRSTS, indicating that many beginning investigators were successful in this competition. AIDS RESEARCH Question. Dr. Raub, a recent study by the Institute of Medicine urged/recommended that funding for research on AIDS be increased immediately by $200,000,000. Are you familiar with this report and do you concur in its findings? What areas of research does the report indicate require additional resources? What progress has been made with the funds which have been appropriated over the last several years? Answer. I am familiar with the Institute of Medicine (IOM) Report on the AIDS Program of the NIH. This study was performed at the request of the Associate Director for AIDS Research and the Office of AIDS Research, National Institutes of Health (NIH), for an unbiased, objective review of the NIH's AIDS research activities. As the study was ongoing and the report was being prepared, the NIH AIDS research program was continuing to evolve; thus, many of the changes recommended in the IOM report have already been implemented. Others will require further review for future action. In general, the NIH concurs with the recommendations made in the IOM report. However, there are two areas of concern cited in the report regarding behavioral research and clinical trials that require NIH clarification. Specifically, the report identifies behavioral research as an area where the NIH should increase funding. We feel also that more can be done in this area. However, we believe the IOM panel's assessment of our level of funding for AIDS behavioral studies does not adequately reflect the level of this research actually being conducted. Behavioral research is conducted as a component of most of the major NIH-supported HIV epidemiological studies. In addition, other behavioral research such as risk assessment and research on nursing interventions would be captured under other budget categories, although directly relevant. In the area of clinical trials, the IOM panel expressed concern that the AIDS Clinical Trials Group (ACTG) network may not be able to keep pace with the ever increasing requirements for expansion and modification of its focus and activities. We have given considerable thought to this evolutionary process, are constantly evaluating the program, and have taken several steps to ensure both flexibility and responsiveness to changing scientific priorities. Two of the most recent changes within the clinical trials program include the recompetition of the adult units of the ACTG, which will provide for performancebased funding for research grant recipients, and the implementation of the Division of AIDS "DAIDS Initiative" within the National Institute of Allergy and Infectious Diseases (NIAID), which will provide greater flexibility and more rapid evaluation of therapeutic agents and treatment approaches. The NIH intends to use the IOM report as a planning tool in its development of a long-range strategy for AIDS research activities. Like the panel, we believe that NIH AIDS research should continue to receive high scientific priority so that the challenges presented by AIDS can be met. The IOM report indicates several areas of research that require additional resources. These areas and the relevant recommendations include: basic research in such areas as immunology, virology, and molecular biology (Recommendation 3.1); vaccine research program (Recommendation 3.2); behavioral research, especially basic behavioral research (Recommendation 3.9); nursing research for the care of people with HIV-related illness (Recommendation 3.11); mechanism-of-action studies for anti-HIV agents as part of drug development efforts (Recommendation 3.13); basic and applied research in the area of opportunistic infections (OIs) (Recommendation 3.14); pre- and post-doctoral training programs in a wide range of AIDS-related disciplines including molecular biology, virology, cell biology, immunology, epidemiology, behavioral sciences, infectious diseases, and clinical medicine (Recommendation 3.27); and a program on the biology of rhesus monkeys as part of the research resources (Recommendation 3.28). In some of the research areas for which the IOM report indicates additional resources are needed, expansion has already been implemented as demonstrated by the increased budget for nursing studies of HIV-infected patients, expansion of clinical trials for OIs and expansion of several animal resources programs. As part of the ongoing evaluation of these programs, these research programs will be periodically reviewed for progress and level of funding by their sponsoring ICDs as recommended by the IOM panel. Significant progress has been made in AIDS-related research in the last several years with funding appropriated by Congress. Progress has been made in gaining an understanding of the epidemiology of AIDS through a number of large cohort natural history studies. Progress in basic research has provided a basic understanding of HIV and its pathogenesis, which has permitted the development of specific therapeutic agents directed toward the prevention, treatment and control of HIV infection. The NIH-funded clinical trials efforts have evaluated the safety and efficacy of numerous potential therapies for the treatment of HIV infection and the opportunistic infections (OIs) and malignancies associated with HIV. Efforts to develop a safe and immunogenic vaccine for the prevention of HIV are ongoing with substantial progress being achieved. A description of the activities in each of these areas is described further in the following sections. EPIDEMIOLOGY -- CHANGING PROFILE OF THE EPIDEMIC NIH-funded studies have demonstrated that the prevalence of AIDS continues to increase steadily in underserved populations at a rate that is disproportionate to the demographics of the U.S. population. Epidemiological studies indicate that HIV infection and AIDS are steadily increasing among several special populations that include minorities, intravenous drug users (IVDUs), and women and their offspring. Among women and children, AIDS is predominantly a disease of minorities. A brief listing of the major epidemiology and natural history studies funded by the NIH include: Multicenter AIDS Cohort Study (MACS)-behavioral correlates with disease transmission and progression, 6000 gay and bisexual men, started 1984. San Francisco Men's Health Study (SFMHS) Heterosexual AIDS Transmission (HATS)-includes minority women, children and IVDUS Women and Infant Transmission Study (WITS)-course of HIV in infected pregnant women and children, majority are IVDUS. Newark Perinatal Study - includes minority women, NICHD-NCI study on high level of anti-gp120 and low NCI SEER study showed increased incidence of non- NCI study showed decrease in expected incidence rate of NIAID-PAHO and Mexican Ministry of Health study on Recent activities reflecting the changing demographics indicated by natural history and epidemiological studies include: Supplemental funding provided to the AIDS Clinical Trials Units (ACTUs) to increase participation of racial and ethnic minorities, IVDUS and HIV-infected pregnant women. Opportunity for full participation of women in almost Committees in the ACTG and CPCRA have been established to focus on the specific needs of women. Awards made to Howard University (Washington, D.C.), the University of Puerto Rico, and the University of Hawaii to develop infrastructure in order to begin clinical trials and compete successfully for an ACTU. National Conference on Women and HIV Infection held on December 13-14, 1990, to draft recommendations for research on special problems associated with HIV infection in women. NICHD and NIAID clinical trials in infants, children and pregnant women. Twenty clinical trials are currently evaluating 19 therapeutic agents. Collaboration with the National Institute on Drug Abuse to encourage increased participation of HIV-infected IVDUs at ACTUS and with the Human Resource and Service Administration (HRSA) to provide ancillary services to increase participation of pediatric patients at specialized ACTUS and Pediatric Centers. BASIC RESEARCH Basic research investigations supported and performed by the NIH have led to rapid and significant increases in the understanding of HIV. Similarly, the scientific understanding of HIV infection and AIDS is making significant contributions to resolving other basic scientific issues in the fields of virology, immunology, microbiology, animal models and molecular biology with important applications to clinical medicine. The influence of basic research on the scientific response to the AIDS epidemic includes: Early research on retroviruses facilitated the Advances in molecular biology allowed elucidation of genetic function of HIV. Previous advances in immunology allowed more rapid Previous advances in microbiology provided the basis for recognition and understanding of opportunistic infections. o The molecular and behavioral aspects of transmission. The effects of AIDS research on non-AIDS areas includes: O Development of sophisticated technology such as polymerase chain reaction (PCR) and new animal models of viral disease. Understanding of central nervous system pathology. Understanding of the development of nervous and immune systems in children. |