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tice in EMS have been found harmful to patients. Military anti-shock trousers (MAST) are a prime example. Adopted by EMS in the 1970s under the premise that they temporarily reversed hypotension in trauma patients, they were removed from most ambulances after research in the late 1990s showed they did not improve patient outcomes and may even have increased mortality. 6 More recently, research on endotracheal intubation in the prehospital setting has generated intense debate in EMS regard- ing the potential harm from perform- ing advanced airway management in the field. 7,8 Even oxygen administration—long the mainstay of prehospital care for a vari- ety of medical conditions—has fallen under suspicion due to the potential harm from free radicals and hyperoxia. 9 A recent study found high-dose oxygen may harm some patients presenting with ST-elevation MI. 10 This study echoes previous research that questioned the benefit of oxygen adminis- tration for patients suffering from myocar- dial infarction. 11 Even if not harmful themselves, clinical interventions that lack proven efficacy in EMS may still lead to suboptimal care for patients by distracting from or delaying the application of other therapies that actually confer benefit. The evolution of prehospital CHF treatment over the past decade provides a good example of how evidence-based inter- ventions have come to supplant traditional, but unproven, therapies. Lasix, which has never been proven effective in the prehospital setting, has gradually fallen out of favor. 12 In its place, the prehospital application of continuous positive airway pressure (CPAP) and aggressive nitroglycerin administration have been proven to reduce mortality and intubation rates. 13,14 EMS research has thus already played an important role in ensuring better outcomes for patients suffering from acute CHF exacerbation. Prehospital Research Challenges Research in the prehospital setting faces several challenges. Researchers have rela- tively little control over patient recruitment, as EMS patients call 9-1-1 at a time and place of their choosing. As a result it is more dif- ficult, if not impossible, for EMS research- ers to craft an ideal study sample. Frequent EMS users in particular tend to overrepre- sent certain segments of the population. 16 EMS research also presents ethical bar- riers not always present in other contexts. For example, obtaining informed consent from patients in the prehospital setting may not be possible. Consequently—and despite the lack of evidence for much of the EMS "standard of care"—deviating from accepted interventions under an exception from informed consent can present a dif- ficult ethical quandary. 17 In the past year, media attention surrounding a clinical trial to examine the efficacy of epinephrine in cardiac arrest has questioned whether with- holding the medication (obviously without a patient's permission) would cause harm. 18 A recent study, however, found that patients themselves may be highly accepting of exceptions from informed consent. 19 The same cannot be said for prehospital provid- ers, as only 30% in one survey agreed with enrolling patients in a study without their informed consent. 20 These ethical issues make it more difficult for EMS researchers to perform well-con- structed clinical studies in the field. They also often add to the expense and length of research trials. As an example, agencies in Denver, Pittsburgh and Richmond (VA) are currently participating in a study funded by the Department of Defense to examine the prehospital use of blood plasma in trauma patients. To conduct the study under an exception from informed consent, it was necessary for the researchers and EMS agen- cies to spend several months reaching out to community members through the media and conducting public information sessions. These outreach efforts were required in order to give members of the community an opportunity to opt out of the study. Adequately controlling for extrane- ous variables is also problematic in EMS research. EMS patients often present with a variety of concomitant health issues, each of which may contribute differently to, or even supersede in terms of clinical importance, the patient's primary complaint. Even if a patient's underlying health problem can be Areas for Research Airway management—The safety and efficacy of advanced airway manage- ment by EMS remains under question, while the administration of high-flow oxy- gen is becoming increasingly suspect for certain conditions. Additional research in the prehospital setting will be necessary to inform any changes to existing indications for these interventions. Cardiac arrest—In the context of out-of-hospital cardiac arrest, important EMS research questions abound. Recently the effectiveness of mechanical CPR devices has been the subject of much debate. Several research studies have found the devices improve end-organ perfusion and increase return of spontane- ous circulation. 29 Large clinical trials, however, have concluded the devices do not provide a benefit in terms of survival to discharge and neurologic outcome. 30–32 Similarly, researchers are still searching for evidence of increased survival from the administration of cardiac medications during cardiac arrest. 33,34 The same is true for the use of impedance threshold devices, though researchers have recent- ly presented evidence that ITDs may improve survival to discharge if high-quality CPR is performed. 35,36 More study will likely be required to confirm their findings. TXA—Research in the prehospital setting is also needed to support the new- est clinical interventions in EMS, such as the administration of tranexamic acid (TXA) to control major traumatic hemorrhage. While TXA has been demonstrated to improve survival in the military setting, the evidence for its use in civilian trauma is very limited. 37 No published research has examined the use of TXA in a civilian EMS system. EMSWORLD.com | JUNE 2015 33