The Infectious Disease Clinical Research Program: Overview

The Infectious Disease Clinical Research Program (IDCRP) was founded in 2005 through an Interagency Agreement between the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH) and the Uniformed Services University of the Health Sciences (USU), through a cooperative agreement with The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF), with the primary objectives of developing and executing clinical research to address priority clinical concerns related to military-relevant infectious disease (ID) threats. The IDCRP also serves as an important bridge between military public health surveillance recognizing emergent and high-impact threats and Department of Defense (DoD) research and development efforts working toward materiel solutions, such as vaccines, drugs, and diagnostics. The overall mission of the IDCRP is to conduct ID clinical research of importance to the military through a unique, adaptive, and collaborative network to inform military health policy and clinical practice.

The foundation of the IDCRP was built upon the long-standing U.S. Military HIV Natural History Study (NHS) initially based at the Walter Reed Army Institute of Research Military HIV Research Program. The HIV NHS, highlighted in detail in the accompanying supplement, had successfully linked several military medical centers into a multisite study with standardized processes and distributed staffing, as well as a protocol-specific centralized regulatory review and approval approach. The framework established by the HIV NHS served as an effective launching point for which to build a much broader program. Within the United States, there existed disease-specific multisite networks, such as the AIDS Clinical Trials Group or the Mycoses Study Group; however, there was no broader clinical research network that could address a wide range of priority IDs. The vision from NIAID and USU leadership recognized this as a critical gap in the DoD, but also more broadly a need within the United States. A program such as IDCRP would need to develop sustainable capacity to move critical areas of research forward, while at the same time, to be responsive to emergent infection threats.

An early priority of the IDCRP was to build effective partnerships across TriService clinical research groups, military public health/surveillance organizations, and ID military research and development programs. This effort occurred not only at the ground-level but also through the establishment of an Operational Steering Committee for the Program with senior ID consultants to each Service Surgeon General (Army, Navy, and Air Force), Directors of the Military Infectious Diseases Research Program and the Armed Forces Health Surveillance Branch, and senior leadership from USU and NIAID. In addition, this oversight body has also gained participation of Veterans Health Administration ID representation. This committee meets monthly and provides input for program direction, as well as outward advocacy and engagement within the DoD and the U.S. interagency.

In addition to early and continued engagement with key stakeholders, the IDCRP team worked toward establishing structure and processes that nurture and develop new research ideas, so they may move forward to executable protocols, leading to impactful scientific findings disseminated through presentation and peer-reviewed publication. High-impact research is a highly collaborative venture and frequently requires multiple institutions to participate. The DoD, as in most governmental and academic research enterprises, was often stymied by extremely long delays related to numerous duplicative scientific and ethical reviews prior to approval to proceed. Early on, the IDCRP pioneered an effort (in 2008) to establish a single DoD Institutional Review Board review, predating the now expected and mandated DoD instruction. A streamlined review process was successfully developed under the auspices of a broad Memorandum of Understanding across all relevant parties within the DoD, establishing a single DoD Institutional Review Board of record, based at USU, but also consolidated to a single scientific review board and a Headquarters-level administrative review based at Health Affairs in coordination with each DoD Service Headquarters Human Research Protection Office. This was the first successful effort within the DoD to create a comprehensive framework for centralized research development and approval process, while also assuring local site considerations and institutional command and control at participating sites.

Of high importance to the program’s success has been the development of forward-looking Scientific Strategic Plans (SSP) with well-articulated major aims and explicit objectives for each research area within the program. The SSPs provide a scientific roadmap for a period of 5 years, which are reviewed annually and updated as needed with specific focus on key milestones and targeted deliverables. The research area SSP is also set in a framework around the program strategic plan. The IDCRP strategic aims are:

Aim 1: Plan, execute, and disseminate clinical ID research of relevance and impact for the U.S. military

Aim 2: Establish, maintain, and augment appropriate collaborative relationships with relevant partner DoD and Interagency organizations

Aim 3: Align and support clinical research along with investigator education and training within DoD

Aim 4: Develop and sustain a robust military clinical research network, with capability to execute U.S. Food and Drug Administration-regulated clinical trials

The research portfolio of the IDCRP has evolved based on the changing priority needs of the Military Health System (MHS) often in response to a new threat impacting U.S. military forces. In 2006, as the program was just beginning, a priority-setting meeting among DoD and NIH stakeholders was held at the national ID conference. At that time, the United States was engaged in wars in Afghanistan and Iraq. The advances in combat casualty care had begun to witness major improvements in survivability, which led to wounded personnel with extensive injuries being seen through U.S. military hospitals. Also, as was being reported throughout many areas of the world, increasing rates of multidrug-resistant organisms, most notably multidrug-resistant Acinetobacter baumannii, were increasingly challenging clinicians to find effective treatment approaches. Not surprisingly, the IDCRP initial priority-setting exercise led to the formation of the Trauma-Related Infections Research Area. In the United States and Europe, at the time there were also major increases in community-acquired methicillin-resistant Staphylococcus aureus infections. The U.S. military was increasingly observing very high rates of skin and soft-tissue infections (SSTI) during recruit training. The SSTI Research Area was also prioritized with specific focus on developing prevention strategies and interventional clinical trials.

In the field of ID, you do not need to wait long for another emergent threat. For IDCRP, this presented itself as the 2009 pandemic H1N1 influenza outbreak. The IDCRP, in close collaboration with the NIAID, the Global Emerging Infection Surveillance program, and partners across the MHS developed the Acute Respiratory Infections Research Area. Well known to military leaders, ID threats rising from endemic infections in overseas, often developing regions, as well as community-based threats in garrison leading to shortfalls in readiness during both peacetime and combat operations. These threats include food- and waterborne (such as travelers’ diarrhea and Norovirus), vectorborne (such as malaria and dengue), respiratory pathogens (as mentioned above), and sexually-transmitted infections (STI). In response to these diverse concerns, the IDCRP has developed Deployment and Travel-Related Infections, Emerging Infectious Diseases and Antimicrobial Resistance, and STI Research Areas. In all these areas, collaborations have evolved to include stakeholders and strategic partners from academia, industry, and the government.

Supporting the development and training of the next generation of clinical researchers in ID and related public health disciplines in the Armed Forces is another priority of the IDCRP. Graduate Medical Education efforts include opportunities for medical and graduate students, residents, and ID fellows to conduct research with IDCRP mentors or participate in analyses led by IDCRP investigators. These experiences provide the trainees with an opportunity to obtain valuable research skills that are not always learned within a classroom and have resulted in presentations at annual conferences, publications, awards, and degrees.

Since the IDCRP was established over a decade ago, the program continues to provide innovative leadership in military multisite clinical ID research to inform and improve the care of the Warfighter. Notable high-impact military accomplishments are presented in brief in Table I. Within this supplement are articles providing a detailed review of each of the research areas, as well as a discussion of the IDCRP support of Graduate Medical Education. The IDCRP has focused on coordinating studies that involve multiple, geographically diverse partners, as well as leading the way in advanced, collaborative, impactful research. The sustained success of the IDCRP can be attributed to the robust partnership between the USU, our DoD colleagues in the MHS and biomedical Research and Development commands, NIAID, collaborators from the Department of Veterans Affairs, and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. Over the years, the IDCRP has produced high-quality evidence for the MHS, contributing substantially to improving the health of service members, as well as DoD beneficiaries and civilian populations. Overall, the IDCRP remains a model for multicenter clinical research in the MHS.

Table I.

IDCRP Impact on Military Clinical Practice and Policy

Polytrauma-associated wound infections
Findings have supported refinement of Joint Trauma System clinical practice guidelines (CPG) and contributed to antibiotic stewardship
Invasive fungal wound infection outbreak
Provided recommendations for evaluation and management, which supported the development of the first Joint Trauma System CPG for invasive fungal wound infections
HIV
The DoD HIV cohort was cited by the Institute of Medicine for new Social Security HIV disability ratings
SSTI
Randomized-control prevention trial resulted in a change in prevention policy to de-emphasize chlorhexidine-based prevention strategies
Travelers’ diarrhea
Convened expert panel and published first DoD CPG for the prevention and management of acute travelers’ diarrhea in deployed personnel
STI
IDCRP designated the Central Coordinating Center for the newly established DoD Gonococcal Reference Laboratory and Repository at USU

The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Uniformed Services University of the Health Sciences, Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., National Institutes of Health or the Department of Health and Human Services, the Departments of the Air Force, Navy, or the Army, the Department of Defense, or the U.S. Government.