As we look toward the opening of our new Pavilion for Advanced Care (PAC) and the transition of our trauma center from the Hospital of the University of Pennsylvania to Penn Presbyterian Medical Center, throughout the month of January, the News Blog is highlighting some of the latest news and stories from across the areas of Penn Medicine that will find new homes in the PAC.
Researchers here at Penn Medicine are among the country’s leaders in the effort to gain a better understanding of traumatic brain injury (TBI), including concussion, how it can be prevented and the best treatments for the most optimal outcomes for patients. But physicians must move swiftly to ensure the best chance at a good outcome, and conducting neurotrauma research in those early minutes and hours after injury can be very challenging, says James Schuster, MD, PhD, director of Penn’s Neurotrauma program and associate professor of Neurosurgery.
One of the biggest hurdles, explains Schuster, when conducting medical research, as with any medical procedure, you need to get the patient’s consent before you provide care. Though informed consent of patients is a crucial requirement for enrollment in clinical trials, the patients who suffer TBIs often arrive to the hospital in some state of unconsciousness, making obtaining consent to participate in studies near impossible. Conducting research in this patient population has been hampered by these hurdles, even as the incidence of TBI has surged – It is one of the most common “invisible injuries” of war—with TBI resulting from blast exposures, motor vehicle crashes, falls, flying debris or being physically thrown against the ground or other hard surface, placing veterans and non-veterans with severe TBI at greater risk for long-term complications. According to the Brain Trauma Foundation, at least 5.3 million Americans, 2 percent of the U.S. population, are currently living with disabilities resulting from TBI.
“We need the research data so that we can determine the best path of care for these patients,” says Schuster.
These challenges are not unique to physicians who conduct research on TBI. In fact, there are commonalities across all time-sensitive illnesses and injuries, including cardiac arrest, stroke and a range of other complex traumatic and orthopedic injuries. Schuster, Josh Levine, MD, co-director of the Neurocritical Care program and associate professor of Neurology and Anesthesiology and Critical Care, and colleagues across several departments are looking forward to practicing in the new Pavilion for Advanced Care, a building whose design unites researchers with seemingly disparate expertise and interests in new and exciting ways.
“Our goal is to improve access and outcomes for trauma patients,” says Schuster. “This state of the art facility will allow a more focused, multidisciplinary approach to comprehensive trauma care through standardization of care, patient registries, as well as clinical and basic science research, in order to build on our reputation as the premiere trauma center in the region.”
“The good news here is that we are able to conduct this type of research under the FDA-allowed exception from informed consent, which allows for patients in these situations to be exempt from consenting to their care in the name of advancing medical research and getting them the best care in the most expedited manner,” says Schuster. But conducting studies through these guidelines require an often time-consuming community consultation process and more hurdles to clear with obtaining approval for studies that are slated to take place on in the “pre-hospital” setting, such as on board ambulances.
One recent example of a national TBI treatment study conducted under these guidelines was led by Jill Baren, MD, MBE, professor and chair of Emergency Medicine and a national expert in exception from informed consent research. The researchers, along with Dr. Schuster, looked at whether administration of the hormone progesterone provided any benefit to patients with TBI. The study involved 882 patients; some of whom received an infusion of progesterone within four hours of injury and for four days following acute brain trauma, and some of whom were given a placebo.
The rationale for the study grew, in part, out of the observation that women tend to respond to treatment and recover better than men after TBI. Unfortunately, researchers found that progesterone provided no significant benefit to patients; survival and favorable outcomes were not significantly different in the progesterone-treated group than in the placebo-treated group.
“We were disappointed in the results,” says Schuster, “as animal studies did show a neuroprotective effect.”
But the location and extent of injuries to the brain, time elapsed before reaching the hospital, doctors’ management and the patient’s underlying health and resilience can all affect outcomes and obscure the effects of a proposed neuroprotective agent.
These large, multicenter studies are crucial as they allow enrollment of substantial numbers of patients, which are necessary to evaluate novel therapies. Physicians who conduct clinical research say the PAC holds fresh promise to promote closer collaboration across the many departments who conduct this type of research, with the aim of designing new studies and increasing patient enrollment – and saving more lives -- in these most time-sensitive trials.