Jennifer Hatzfeld
Fort Detrick, Maryland, United States

Disclaimer: The views expressed in the article are those of the author, and do not reflect the official policy or position of the United States Air Force, Department of Defense, or the U.S. Government.

It was a short walk back to the research office, down a relatively clean, well-lit hallway from the Emergency Room at Craig Joint Theater Hospital at Bagram Airfield, Afghanistan. I knew that any trauma patient arriving with Cardio Pulmonary Resuscitation (CPR) in progress had less than a one percent chance of survival.¹ Still, having watched the staff unsuccessfully try to save the life of another service member, my thoughts went out to his family, his unit, the staff in the emergency room, and all the others affected by his passing. It was made all the more tragic to hear that his fatal wounds were likely self-inflicted. Mainly, my heart ached that I couldn’t do more. I was in Afghanistan as part of the Joint Combat Casualty Research Team in the role of  “senior scientist.” Inside, though, I was still a clinician. I longed to jump in and help place a line, push a drug, hang some blood, and maybe even save a life.

One day a week I set aside my normal twelve-hour work day to work alongside the nurses in the Intermediate Care Ward. I liked to think that it helped the nursing staff and that I could make a difference in the lives of individual patients. In the end, I think I got the most benefit. I had the distinct honor of caring for our wounded warriors—injured enough to need definitive care away from Afghanistan, but desperate to get back in the fight and worried about their “guys” left behind. I also had the opportunity to care for innocent children injured by a war that had surrounded them for their entire lives; kids the same age as my daughters but almost half their size and with a shadow under their eyes. And I even found myself privileged to care for enemy combatants wounded by our own service members, who then selflessly (and often at great risk) called for life-saving care to aid the wounded enemy. Those busy days inspired me to continue the less glamorous work of navigating future research protocols through the regulatory process, collecting blood samples and data for research protocols, and providing oversight and guidance for a host of other projects owned by busy researchers who had since returned home.

It was my second deployment as a researcher, the first was to Kandahar two years before, and then to Bagram. I never intended to return, but God (and the Air Force) had another plan. The injuries, the fog and friction of war, and the occasional anguish of the hospital staff hadn’t changed much in those intervening years.

But after watching what felt like a completely unnecessary death, I was suddenly overwhelmed by the burden of regulatory requirements needed to accomplish research during a deployment. Our small research team was there to help exactly this type of person—to prevent the suffering that can lead to considering suicide, or finding even better ways to put a life back together if (or when) the unthinkable happens. These research regulations were put in place to satisfy a human protections standard designed for academic institutions with teams of dedicated researchers in stable, peacetime settings where concerned family members are available to provide informed consent for their injured loved one. The problem? That really doesn’t exist in combat.

Human protection programs and Institutional Review Boards are an essential element of research. Even the most well intended scientific process benefits from the outside review of other scientists, peers, and members of the community to ensure it meets the principles of beneficence, justice, and respect for persons. Sometimes it’s easy to lose sight of the big picture, and that’s what a human protections program does best.

Since the first researchers were deployed to Iraq in 2006, a formal US CENTCOM Human Protections Program was developed to outline the approval process for all research conducted in Iraq, Afghanistan, and Kuwait. The existence of this program was essential, especially given the special vulnerability of deployed service members from many different countries and local nationals that find themselves at one of the many military medical facilities throughout Afghanistan. Another important motivator was the media coverage of in-theater research studies with questionable outcomes or that appeared to cause more harm than good. A classic example was the scathing report on the use of Factor VII, which was used as a last resort to help manage persistent bleeding in severely injured trauma patients.² It was recommended for massive bleeding in Europe at the time,³ but only approved by the US Food and Drug Administration (FDA) for hemophilia. Data collected by diligent military physicians found that its use might actually be associated with deadly blood clots. But then again, those patients weren’t exactly healthy to start with.

For a research protocol to be approved for data collection in the combat zone, it required three different levels of critical review before being considered by the Institutional Review Board, a standard well above the Code of Federal Regulations and Department of Defense Instruction governing human subjects’ research in the military.⁴ These reviews were required for all protocols, regardless of the level of risk or whether they met the criteria for exemption. Depending on the level of critique by the reviewers, each phase could require complete revisions to the protocol before being permitted to continue to the next phase. In some cases, the approval process took only four months. Then again, one protocol intended to help patients handle anxiety after a traumatic event required multiple revisions over two years and was never able to start enrolling patients as willing study team members returned home from their deployments. Other studies were turned away because FDA requirements could not be met (like regular audit visits), or it was determined by a three-member panel to be either not feasible or not necessary to be done in theater. In the end, most of all prospective research projects were never approved, usually because the investigator withdrew the protocol or was unable to adequately address the required revisions.⁵

Combat medicine is hard. Combat medical research can be even harder, and sometimes those regulatory rules harm the very people they were designed to protect; people like that broken soldier that didn’t survive beyond the Emergency Room. He, and all of the other patients—the ones that we fly to Germany and then back home to recover and manage their own personal demons, deserve to have their injuries contribute to the science of combat medicine in order to inform the absolute best practice for the next person that comes through the door. In the military, there are well-established processes in place to develop and oversee dozens of clinical practice guidelines. The Joint Theater Trauma System collects data on all trauma patients to provide invaluable knowledge on the injury patterns, treatments, and outcomes from the moment of injury through their rehabilitation.⁶ The problem is that in many cases we just do not have any scientific evidence from past research studies to guide this unique type of medical care.

Parsimony is a concept used in statistics to choose the best statistical model to describe the interactions among multiple variables for a data set. According to the dictionary, parsimony means “frugal” or “stinginess”.⁷ But parsimony could also be seen as the perfect balance between doing too much and doing too little. In the small world of research in the combat zone, the perfect balance between the need to protect human subjects in the conduct of research and the need to generate as much new knowledge as possible to treat our combat casualties is a an imperative pursuit.

The research program in CENTCOM was closed in 2014 and all research protocols ended with no path to start any new research in that theater. But at some point in the future there will be a need to develop another human protections program within a combatant command. Perhaps parsimony will be one of the guiding principles to identify exactly what is required to conduct research in combat that can also quickly adjust to emerging clinical needs. That would be a noble legacy for a lonely suicide victim and a team of discouraged Emergency Room clinicians who slowly cleaned the trauma bay to make room for the next soldier to arrive.

References

1. Stockinger ZT, McSwain NE Jr. Additional evidence in support of withholding or terminating cardiopulmonary resuscitation for trauma patients in the field. Journal of the American College of Surgeons. 2004;198:227-231.
2. Little R. Dangerous Remedy. Baltimore Sun Times.  November 19, 2006. Available at: http://www.baltimoresun.com/news/nation-world/bal-factor7part1,0,1091401.story. Accessed on February 4, 2016.
3. Vincent J. Rossaint R, Riou B, et al. Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding – a European Perspective. Critical Care. 2006; 10: R120
4. Office of the Under Secretary of Defense for Acquisition, Technology, and Logistics. Department of Defense Instruction 3216.02, Protection of Human Subjects and Adherence to Ethical Standards in DoD-Supported Research. November 8, 2011. Available at: http://www.dtic.mil/whs/directives/corres/pdf/321602p.pdf Accessed on February 4, 2016.
5. Eastridge BJ, Wade CE, Spott MA, et al. Utilizing a trauma systems approach to benchmark and improve combat casualty care. The Journal of Trauma and Acute Care Surgery. 2010 Jul;69 Suppl 1:S5-9.
6. Dukes S, Tourtillott B, Bryant D, Carter K, McNair S. Finishing What Was Started: An Analysis of Theater Research Conducted From 2010 to 2012. Military Medicine. 2015 Mar; 180 Suppl:8-13.
7. Parsimony definition. Available at: http://dictionary.reference.com/browse/parsimony?s=t  Accessed on February 4, 2016.