The Armed Forces Institute of Regenerative Medicine: a collaborative approach to Department of Defense-relevant research

The wars in Iraq and Afghanistan are different from previous conflicts in numerous ways, but most relevant to the field of regenerative medicine is the shift in casualties from fatalities to catastrophic trauma. As of 30 June 2011, almost 44,000 service members had been wounded in Operation Iraqi Freedom and Operation Enduring Freedom since the start of those conflicts in 2001 [101]. Improvised explosive devices account for as many as 78% of combat injuries, which represents the highest proportion of such injuries seen in any large-scale conflict [1]. As a result of significant improvements in personal protective equipment and combat casualty care, soldiers in these conflicts are surviving injuries that would have killed them in previous wars; the case–fatality rate for Operation Enduring Freedom and Operation Iraqi Freedom (8.8%) is significantly lower than for either Vietnam (16.5%) or WWII (22.8%) [2]. Unfortunately, survival does not equate with full recovery. Some injuries are so severe as to outstrip the ability of current medical treatments to repair them, despite the best efforts of medical staff. These critical gaps in injury management were the impetus for a collaborative project between the Department of Defense (DoD) and the best academic biomedical researchers in the USA: the Armed Forces Institute of Regenerative Medicine (AFIRM).

The AFIRM was established in 2008. It is managed and funded through the US Army Medical Research and Materiel Command with additional funding from the US Air Force, Office of the Surgeon General, the US Navy, Office of Naval Research, the National Institutes of Health, the Veterans Affairs Administration, and the DoD, Health Affairs. The mission of the AFIRM is to accelerate the development of new products and therapies to treat severe injuries suffered by US service members. The desperate need to deliver new technologies quickly was the motivation to try a new approach to funding and collaboration. Traditional means of research funding unintentionally support ‘isolationist’ development of products and technologies by virtue of funding individual projects. Those who envisioned the AFIRM understood that combining substantial intellectual resources could lead to exponential, rather than linear, scientific discovery. Fostering the development of ideas and products in a collaborative environment of thought-leaders with vastly different perspectives could encourage novel approaches to problems with very difficult solutions. To that end, the AFIRM was conceived as a consortium, with many leading researchers and institutions working in concert and combining resources – intellectual, material and, at times, financial – to work toward one goal: helping the wounded warrior (Figure 1).

Current status

The AFIRM consists of two consortia – the Wake Forest Pittsburgh Consortium, led by Anthony Atala, MD, and the Rutgers Cleveland Clinic Consortium, led by Joachim Kohn, PhD – leveraging collaboration and healthy competition to drive efficient technology development. Each consortium is a multidisciplinary, net-centric, internally managed organization of top academic researchers and clinicians throughout the country. Approximately 31 institutions are involved in total, and over 80 projects are funded within the five research program areas: Limb and Digit Salvage, Craniofacial Reconstruction, Scarless Wound Healing, Burn Repair and Compartment Syndrome.

The consortia are using biomaterials, stem cells, growth factors, immunomodulation, bioreactors, novel peptides and cutting-edge surgical techniques, either alone or in combination, to address the challenges before them. An overview of current research projects is listed in Box 1.

Funding for the AFIRM from US government sources totals $100 million for the 5-year period of the cooperative agreement. State governments, universities and industry have contributed $80 million, and $109 million of pre-existing research support directly related to AFIRM deliverables has been leveraged. Thus, total funding for the 5-year period of the AFIRM is close to $300 million [102].

As both the AFIRM and its funded research projects have matured, the focus of the collaboration has evolved. While the beginning of the 5-year program was primarily a science and technology effort, 3 years into the funding period there has been a marked maturation of projects. The goal of the AFIRM at the outset was to treat one patient with one product in one clinical trial by the end of 5 years. That goal was far surpassed in just the first 3 years. Within 3 years, 12 projects moved into advanced development, with over 30 patients already enrolled and treated in clinical trials. But this overwhelming success brought challenges of its own. Owing to funding constraints, the AFIRM could not support later stages of clinical development and collaboration with industry partners was essential to the continued progress and success of product development. Of necessity, the AFIRM collaboration shifted as products matured, from provision of early science and technology support (primarily funding) to enhanced regulatory, product development, and early-stage clinical trial guidance, in an effort to position the product for commercial engagement.

Partnership with industry provides necessary capital for investigators to proceed with development, but it also provides indirect feedback on program direction. The private sector is unlikely to invest in products with substantial regulatory, manufacturing, reimbursement or scientific challenges. Likewise, those with little potential for widespread application, rapid adoption and commercial success will struggle to engage industry partners. Consequently, agreements and investment by commercial partners provide a surrogate measure of the potential utility and success of a developing product. At the close of Program Year 2 (June 2010), 13 commercial partnerships were formalized with AFIRM investigators and six more investigators were in discussions with potential partners (Figure 2).

DoD collaboration extends beyond simply funding projects, however. The AFIRM provides ample opportunities and a ready community for military clinicians to offer their experience and expertise in battlefield trauma to the researchers developing products. Product development is shaped both by the critical needs of wounded warriors, and by the experience of military clinicians who know what is necessary, and what is possible, in delivering care at each echelon.

The final element of collaboration within the AFIRM occurs with clinical trials. As stated previously, the AFIRM cannot fully fund late-stage clinical trials, but Military Treatment Facilities offer opportunities for collaboration as potential clinical trial sites. At present, the primary Military Treatment Facility identified to conduct regulated clinical trials for the AFIRM is the US Army Institute for Surgical Research, but the possibility of involvement by other facilities is burgeoning. This gives researchers varied options for testing their products, and in particular, it offers potential access to the population for which the product was originally intended.

Conclusion

The AFIRM was envisioned as a rapid incubator for regenerative medicine technology desperately needed to treat severely wounded warriors. In just 3 years of program funding, the collaborations forged with and between the military, academic researchers and corporate partners has proven far more effective and successful than even its most hopeful proponents imagined. The next 2 years of funding will deliver additional products to clinical trials, and will prepare the program for what is hoped will be a second, more mature phase of funding.

Future perspective

The AFIRM is at the end of Program Year 3, with 2 more years to follow. While the federal budget crisis makes all predictions of future funding hazardous, hopes are that the Program will continue through 2018 in a second round of funding. An additional 5 years of funding would allow the maturation of some promising basic science technologies, and would see the ‘graduation’ to industry and commercialization of several current advanced development technologies: new options for treating severe burns that will accelerate wound closure and significantly reduce skin graft donor site morbidity; new ways to treat and prevent severe scarring; novel solutions to devastating avulsion injuries with the ability to regenerate bone, muscle and nerves; ways to reduce the progression of burn injury; and strategies for transplanting composite tissue that do not trade form, function and identity for the lifelong risks of immunosuppression. Given 5 more years of funding, it is very possible we would see the first AFIRM incubated-and-developed product complete its lifecycle and reach a wounded warrior as a commercially available technology, the ultimate goal of the AFIRM endeavor.

▪ Further information

Please see the publications listed in the AFIRM Annual Report 2010, Appendix B (www.afirm.mil/assets/documents/annual_report.pdf, pages B1-B11) for further information regarding funded projects.