Driving Innovation
Written by Mark Adams Ph.D., and Kevin Vigilante, M.D., M.P.H.
MMT 2010 Volume: 14 Issue: 7 (October)
Advancing Military Medicine
Through Collaborative Research.
Research is the engine of innovation that brings new treatments to warriors, promotes the health of the force and contributes to national security. However, one of the most difficult management challenges in science is maximizing the return on investment in basic research. Often, inputs do not generate predictable outputs; investments not necessarily produce desired results. For example, the investment in cancer research has risen geometrically over the last 40 years; however, the number of new cancer compounds submitted to the FDA each year has not increased.
Some believe this is merely the nature of discovery. It is impossible to tell in advance which basic science investments will pay off—or when. Some “failures” turn out to be breakthroughs decades later, serving other unanticipated needs. Consequently, the scientific endeavor is often likened to an artistic enterprise: Attempts to manage it will likely quash creativity and retard scientific progress.
While there may be some truth to this view, we see mounting evidence that new models of collaborative research can dramatically improve the chances of scientific productivity, especially in research that may require significant investment, involve large numbers of investigators, and address urgent issues. In particular, we believe that a collaborative approach can have specific applications in military medicine, the care of wounded warriors, and targeted areas of chemical, biological, radiological, nuclear and high-yield explosives research.
COLLABORATIVE SCIENCE AT WORK
Competition, rather than collaboration, more aptly describes the culture of health and life sciences research. Researchers often compete with peers to publish results and gain promotions, tenure and recognition. Competition often leads to great discoveries, as occurred in the race to map the human genome. However, there is evidence that coordinated efforts and greater collaboration can bring synergies and accelerate progress.
The Manhattan Project and Apollo Program are two such examples. While both were engineering projects rather than basic science and translational research efforts, they involved significant scientific challenges that were tackled in a coordinated and collaborative model. Today, the collaborative model is gaining early traction in the National Institutes of Health (NIH) through a number of programs. One is the Cancer Biomedical Informatics Grid (caBIG).
The National Cancer Institute (NCI) launched caBIG in 2004 with the goal of accelerating the pace of discovery and enhancing the value of scientific investment by eliminating competitive silos and promoting information sharing across more than 60 academic cancer centers. When Booz Allen partnered with the NCI six years ago to develop and launch caBIG, skeptics asserted that entrenched attitudes and incentives would doom it to failure. Many thought the program would be lucky to recruit 10 centers to participate.
Today, more than 50 NCI-designated cancer centers and more than 30 community cancer centers are actively engaged in the program. As a result, a large research community is thriving across industry, government and academia, a robust governance structure has been created, intellectual property, privacy and research ethics issues are proactively addressed, common taxonomies and interoperability standards have been embraced, and scientific information and research tools are being shared. Data aggregation will become possible on a scale not previously imagined, opening the door for additional pathways to discovery through data mining and modeling.
One measure of the impact of collaboration is the number of papers produced because of collaborative efforts, as described in Figure 1. The majority of these papers, especially those published over the last couple of years, result from basic and clinical science researchers relying on the caBIG infrastructure to support their efforts to collaborate within and across disciplines and institutions. There is increasing interest by the scientific and medical research communities around translational research, adaptive clinical trials and other efforts which require both cross-disciplinary and inter-institutional collaboration. These needs can be served by collaborative research platforms. In one example, a groundbreaking large-scale adaptive clinical trial design was led by UCSF, in which caBIG infrastructure enabled the rapid evaluation of neoadjuvant chemotherapy.
APPLYING COLLABORATIVE SCIENCE IN MILITARY MEDICINE
There are many ways to apply a collaborative science approach in military medicine. We will offer two examples that are particularly relevant to the health of U.S. military forces and national security— treating traumatic brain injury (TBI) and developing countermeasures to genetically engineered resistant organisms. The urgency of these objectives requires a scientific enterprise that is actively managed to produce outcomes as quickly as possible.
Speeding TBI Treatment: The prevalence of TBI among our troops has pushed it to the top of the national research agenda. Nevertheless, despite aggressive federal funding, progress has been slow; the scientific and methodological challenges are significant. However, the funding mechanisms have also followed conventional approaches. Awards, which are not coordinated among different federal funding agencies, have gone to a broad spectrum of accomplished researchers who do high-quality research, but who also operate in scientific silos.
While there is an active community developing common data elements for TBI, we recommend creating a more formal and robust collaborative science program to help accelerate the pace of discovery and translation. Such an initiative would include an infrastructure to convene and sustain the scientific community and provide it with an appropriate governance model. Research priorities across major funding agencies would be established and a balanced portfolio of research created. Funding for individuals and investigators would incent behaviors that promote early sharing of pre-publication data. Data and data sources across multiple federal agencies (e.g., the Department of Veterans Affairs, NIH, National Intrepid Center of Excellence, Defense Centers for Psychological Health and Traumatic Brain Injury, Defense and Veterans Brain Injury Center, Armed Services and academia) would be made available to more investigators with fewer administrative barriers.
In turn, this data would be aggregated so that the broader community could mine it more effectively. Common taxonomies and informatics standards would be embraced to promote semantic and technical interoperability. While the cultural and bureaucratic barriers should not be underestimated, this is a matter of national urgency that requires alternative approaches— such as collaborative science—to hasten development of effective patient treatments.
Bioweapon Research: Given the pace at which genetic engineering capabilities are proliferating, we must anticipate that a genetically engineered bioweapon may be used in a future attack. This means, for example, that an “enhanced” anthrax, yersinia or tularensis bioweapon may be introduced that is not sensitive to current countermeasures, leaving the population completely exposed. While this nightmare scenario makes intelligence and prevention even more critical as components of the biosecurity life cycle, the response component must also be addressed. Once the organism is released, its genome must be rapidly sequenced, and countermeasures must be identified or created. Then an accelerated process of testing, approval, manufacturing and distribution must be pursued. In such a scenario, the health of our troops is imperative for national security.
To enable investigators to respond with maximum speed, we recommend creating a pre-established network of tier-one labs and institutions linked by a collaborative but secure informatics network. It would be important to establish this community well in advance of such an event and connect its members on an appropriate network. However, given that such an event would be rare, we recommend establishing a dual use for such an infectious disease network so that it is not used only in times of national emergency. As we have learned in other preparedness scenarios, functions that are not used routinely rarely perform optimally when they are needed.
ATTRIBUTES OF A COLLABORATIVE SCIENCE NETWORK
The examples offered above are two very different examples of how a collaborative science infrastructure may accelerate discovery and translation into practice. The intent is not to eliminate the healthy competition that is often the engine of discovery, but rather to balance it with collaborative structures that are necessary to address the complexity and urgency of certain research problems. In creating a collaborative science model, the most important component is the creation of a scientific community with an appropriate governance structure. Often this requires what we call a megacommunity that includes the three key social sectors—government, the commercial sector and the nonprofit sector (e.g. academic research institutions). That community is charged with a broad range of activities to promote collaboration, but they include at the very least:
- Agree upon common scientific/medical taxonomies, ontologies and standard vocabularies so that semantic interoperability can be achieved.
- Create a culture of information sharing in which the benefits are clearly articulated and an appropriate incentive structure for information sharing is created—this may include collaborative criteria for grant award, promotion or tenure.
- Create a technical infrastructure that permits digital information sharing across investigator teams and institutions.
This provides the foundation for a collaborative research environment. Though the nature of the network will vary depending on the nature of the disciplines included and scope of the problem being addressed.
CONCLUSION
Managing science is challenging. It is even more challenging when the scientific enterprise extends across multiple institutions in multiple sectors—academia, government and the commercial environment. In matters of national urgency, a collaborative approach that coordinates the scientific enterprise can improve efficiencies, minimize redundancies, fill gaps and, most importantly, speed the discovery and deployment of effective patient treatments and outcomes. Although collaborative science is more common in the physical sciences and large-scale engineering challenges, it is proving extremely effective in the caBIG cancer research program. It would be useful to apply a similar collaborative approach to specific scientific problems in military medical research, such as TBI and bioweapon response. While the cultural and bureaucratic barriers to collaborative science models are not trivial—particularly in the academic environment—it is, in many ways, more consistent with the military ethos in which team work and a focus on the mission are paramount. ♦
Mark Adams Ph.D., is a principal at Booz Allen Hamilton. Kevin Vigilante, M.D., M.P.H., is a vice president at Booz Allen Hamilton.