Co-authored by Hugh Auchincloss, M.D., NIAID Deputy Director and Carole Heilman, Ph.D., Director of NIAID’s Division of Microbiology and Infectious Diseases

So far all of the postings on this blog series have been about HIV/AIDS research or about diseases that are major comorbidities. This is appropriate since we have been discussing the upcoming re-competition of a clinical trials infrastructure that until now has been funded entirely with AIDS-appropriated funds.  However, several times over the past year, NIAID Director Dr. Anthony S. Fauci has said publicly that we are exploring the possibility of using this infrastructure for research on a broader range of infectious diseases. In this posting we will discuss our current thinking about how this might be accomplished, and how non-AIDS infectious diseases clinical researchers can participate.

The first consideration that is important to understand is that funding for NIAID comes in three separate categories: 1) AIDS and AIDS-related, 2) Biodefense, and 3) Immunology and Infectious Diseases (IID). AIDS funds can be used for critical AIDS comorbidities such as TB and infectious hepatitis, whether or not those diseases are studied in HIV-infected patients. That is why the AIDS research agenda that has been described in previous postings by Carl Dieffenbach, director of NIAID’s Division of AIDS (DAIDS), has included TB and infectious hepatitis as high priorities. The inclusion of these two co-infections represents a great opportunity for infectious diseases investigators with expertise in TB and hepatitis to develop and execute cutting-edge clinical trials on these infections. Biodefense funding can be used for a broad range of emerging and re-emerging infectious diseases and conditions. For example, research on both antimicrobial resistance and influenza can be funded with Biodefense dollars. However, many other infectious diseases must be funded by IID dollars. Given these constraints, expanding the scope of the research conducted in our DAIDS-sponsored clinical trials networks obviously requires that we introduce new sources of funding from non-AIDS appropriated funds. Since NIAID funding has been nearly flat for several years, this can only be accomplished incrementally. Clearly, our goal is to maximize the value of these non-AIDS dollars by avoiding duplicating many elements of the clinical trials infrastructure that already exist.

The second consideration that is important to understand is that the existing clinical trials networks are basically funded in three ways: 1) core funding for “leadership groups”, which are formed to develop and implement a research agenda based on priorities established by NIAID with input from the scientific community; 2) core funding for Clinical Trial Units (CTUs) which are basically the headquarters for a larger number of Clinical Research Sites (CRSs) where studies are actually conducted; and 3) protocol implementation funds, which are the incremental dollars needed to enroll patients in research studies.  The postings on this blog so far have described the key research priorities identified by DAIDS. These will form the basis for reviewing the applications of potential leadership groups during the next competition of the clinical trials networks that will be funded by AIDS dollars.  A future posting on this blog will describe how we envision the structure and function of the CTUs, which will be competed after the “leadership groups”. Another future posting will describe how we will develop a governance structure that will allow us to prioritize the implementation of research protocols based on the available funding.

Based on these considerations, our plan to broaden the scope of the research conducted in what used to be called the “DAIDS” clinical trials networks requires three elements: 1) a description of non-AIDS infectious disease research priorities that can form the basis for “leadership group” applications that are targeted at non-AIDS infectious diseases; 2) the structuring of the CTUs and their CRSs so that they have the capacity to perform research on more than just AIDS and its related co-infections and conditions; and 3) the introduction of funding from non-AIDS dollars (a mix of Biodefense and IID funding). NIAID plans to implement each of these elements during the re-competition of the “DAIDS” clinical trial networks, which will be referred to from now on as the “NIAID HIV/AIDS and Infectious Diseases Clinical Trials Networks”. These non-AIDS infectious diseases leadership groups and CTUs represent a major opportunity for infectious diseases investigators to identify and implement a critical research agenda in priority areas. 

1. Leadership Groups:  Some of the research priorities that will form the basis for a non-AIDS infectious diseases leadership group application include the following:  1) anti-microbial resistance, 2) influenza, 3) other emerging and re-emerging infectious diseases (including ones we do not yet know about), 4) malaria, and 5) gram negative infections. This list is not meant to be comprehensive, and indeed part of the function of a “leadership group” is to respond to shifting priorities and opportunities as they emerge. Furthermore, we are looking forward to discussing this list of priorities during the Town Hall meeting on October 26, 2010.
   
   How many non-AIDS infectious diseases leadership groups will emerge from the next round of competition? Obviously that depends to some extent on the number of applications and their quality.  However, given that each leadership group absorbs a certain amount of core funding that is then not available for research protocols, and given that the non-AIDS resources available for this research are limited, it will be surprising if NIAID is able to fund more than a single non-AIDS infectious diseases leadership group at this time. How can a single “leadership group” address such a broad research agenda in infectious diseases? The answer to that question requires that one understand the profound difference between a “leadership group” and a traditional Principal Investigator. An effective leadership group should be made up of a group of widely-respected infectious diseases experts, none of whom is participating solely in order to implement their own personal research agenda, but rather have as their goal the implementation of a robust clinical research portfolio in non-AIDS associated infectious diseases.
2. CTUs and CRSs:  The second part of broadening the scope of the clinical trials networks will be the expansion of the charge to the CTUs regarding their research capacity. In the past, CTUs have been evaluated entirely on the basis of their capacity to perform different types of AIDS-related research.  In the next round of competition, CTUs will be evaluated on one of two criteria: 1) their ability to do AIDS research alone or 2) their ability to do AIDS and non-AIDS research. Now that multiple-PIs are allowed on NIH grant applications, we would expect that many successful CTU applications in the future will come from some combination of AIDS and non-AIDS investigators.
   
3. Funding From Non-AIDS Dollars: The third part of broadening the scope of the clinical trials networks is the introduction of non-AIDS funding. Obviously, the implication is that funding for the non-AIDS infectious diseases research will come from NIAID’s Division of Microbiology and Infectious Diseases (DMID) rather than from DAIDS.  DMID will therefore be responsible for the oversight of the infectious diseases “leadership group(s)”, the CRSs that perform non-AIDS research, and the implementation of the infectious diseases research protocols. Oversight of the CTUs will require cooperation between DAIDS and DMID.

Finally, as we consider our effort to broaden the scope of our HIV/AIDS and Infectious Diseases Clinical Trials Networks, it is important to keep the size of this effort in perspective. First, the non-AIDS infectious diseases research conducted in the new networks will by no means represent all of the clinical research supported by DMID.

The VTEUs, for example, will continue to play a vital role, and numerous other clinical research projects will be part of the DMID portfolio, including investigator-initiated clinical trials.  Second, the initiative we are describing will not create a brand new infectious disease clinical trials network. Rather, the broadening of the existing networks is designed to leverage the enormous investment by DAIDS for the benefit of non-AIDS research. However, initially it is unlikely that the non-AIDS research will amount to more than 10% of that funded by AIDS dollars.  Nonetheless, we believe that this is an extraordinary opportunity to expand infectious disease research using a clinical trials infrastructure not previously available to non-AIDS investigators. The success of this effort will require exceptional cooperation within the community of infectious disease investigators to develop a highly creative research agenda addressing the most pressing issues in the field.