In a quote that has been repeated so often that it has almost become cliché, Secretary of State Donald Rumsfeld once answered a question about weapons of mass destruction by saying, "There are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns – the ones we don't know we don't know."

The concepts of known knowns, known unknowns, and unknown unknowns apply not only to intelligence and politics, but to any discipline where the gathering of knowledge is paramount. So it was fitting that a workshop on the devastating opioid crisis began by invoking this quote from Rumsfeld.

The all-day event, called "Developing a Research Agenda for Addressing the Opioid Epidemic in NC," was held on May 16, 2018 at the Research Triangle Park (RTP) Conference Center in Durham. To kick off the discussion, Aaron McKethan, PhD, Chief Data Officer at the N.C. Department of Health and Human Services (NC DHHS), explained that the meeting was unconventional, by design.

"Most of the time when we come to meetings like this, we bring together a bunch of smart people to discuss the things we know," he said. "That is not what we are doing today. We are going to focus on the things that are known unknowns. What are the most important questions that we don't have answers for? Once we have that list, we can decide how best to devote our time and resources to collectively address this problem."

In the United States, someone dies from an opioid overdose every 12.5 minutes. In North Carolina, the number of deaths attributed to opioids grew by more than 900 percent between 1999 and 2016.

In April, the state posted N.C.'s Opioid Action Plan with the intention of identifying specific and achievable steps that will have the greatest impact on reducing the burden of death from the opioid epidemic. One of the steps on the plan recommends the "establishment of an opioid research consortium and a research agenda among state agencies and state institutions to inform future work and evaluate existing work."

For the May workshop, the NC DHHS joined forces with the UNC Injury Prevention Research Center (IPRC), the North Carolina Translational and Clinical Sciences (NC TraCS) Institute, the Duke-Margolis Center for Health Policy and the UNC Gillings School of Global Public Health to bring together more than 70 experts from state agencies, academic centers, and area businesses to help put the plan for a state opioid research consortium into action. After introductory remarks, the attendees broke up into groups to brainstorm a list of "known unknowns" pertinent to four topic areas: prevention, dynamic use/misuse, harm mitigation, and treatment.

The questions they generated ranged from routine to complex. For example, one participant asked if they could measure how many naloxone kits expire at different organizations before they get used. Naloxone is a medication that quickly reverses the effects of an overdose from opioids such as heroin, methadone, fentanyl and morphine. Another wondered how they could make a better case for harm reduction activities (like needle exchange programs) so that policy makers and the public will better understand the benefits of such programs and get behind them.

In between breakout sessions and talks, the attendees were joined by Governor Roy Cooper who provided encouragement and support for their efforts to address the opioid epidemic and to help North Carolinians become better educated, healthier, and more prosperous.

"It is great to be in a room of North Carolinians who are making a difference, and who together can change the world," said the Governor. "I say that in all seriousness because I am not sure any state in the country has the concentration of talent that North Carolina has; we are a state of minds."

Governor Cooper then heard three-minute lightning talks from some a panelist of the key scientists present, including Marisa Domino of the University of North Carolina at Chapel Hill Gillings School of Global Public Health, Larry Greenblatt, MD of Duke University, Philip Graham, DrPH of RTI International, and Emily Pfaff, MS, Administrative Director, Informatics & Data Management, of the North Carolina Translational and Clinical Sciences (NC TraCS) Institute at UNC-Chapel Hill. Pfaff led a team of UNC data scientists sent to Washington, DC, to participate in a Code-a-Thon, a 24-hour competition to develop data-driven solutions to the opioid epidemic. Her team created a new app called tHOR that can be used to help individuals identify their or their loved ones' risk of opioid addiction.

"I learned that we are not going to solve this opioid crisis with an algorithm," said Pfaff. "Data is messy, particularly when it has to do with people."

Data was a big theme throughout the entire conference. Many participants indicated that if they could come up with ways to access, share, and integrate data on the opioid epidemic, they could answer a lot of questions that were previously unanswerable.

Since this was an ideas-generating event, it was a great opportunity to get input from neighboring states about how data is being collected and used to address the opioid epidemic in other communities. Melissa McPheeters, PhD, MPH, Director, Office of Informatics and Analytics, Tennessee Department of Health and Jeffery Talbert, PhD, Professor, College of Pharmacy, University of Kentucky, presented information about promising models and approaches, including linking data from multiple sources to better monitor access to and use of health services and to help researchers and practitioners understand the many factors that contribute to health outcomes, particularly addiction and overdose. Dr. Talbert emphasized, "Most policy interventions have addressed the supply of opioid prescriptions (e.g., policies to reduce the number of prescriptions and the doses prescribed), but much more needs to be done on reducing the demand for opioids through increased access to Medication Assisted Treatment (buprenorphine, methadone, and naltrexone) and high quality behavioral health services." Dr. Talbert commended North Carolina for creating a space during the May workshop where these kinds of strategies can be explored. "I was particularly impressed with the collaborative team science approach across the UNC and Duke researchers, and the participation by North Carolina government officials. To have the Governor, state health officials, and university researchers discussing and debating strategies to address the opioid epidemic is a model for other states to consider as they face complex crisis and epidemics."

The questions generated at the event are currently being compiled into a report that will be sent to the Governor's Office. "The true value of today is going to come with what happens next," said Susan Kansagra, MD, MBA, Section Chief of the Chronic Disease and Injury Section at the NC DHHS. "I feel this sense of urgency to address what we can today, because otherwise we will be in a much worse position. North Carolina must be the leader in the nation in solving this problem, and the people in this room are the ones who are going to make that possible."

For more information on NC's Opioid Action Plan, visit: www.ncdhhs.gov/opioid-epidemic

NC TraCS is the integrated hub of the NIH Clinical and Translational Science Awards (CTSA) Program at the University of North Carolina at Chapel Hill. The CTSA program is led by the NIH's National Center for Advancing Translational Sciences (NCATS). NC TraCS combines the research strengths, resources and opportunities of the UNC-Chapel Hill campus, partner institution RTI International (RTI) in the Research Triangle Park (RTP), North Carolina Agricultural and Technical State University (N.C. A&T) in Greensboro, and North Carolina State University (NCSU) in Raleigh.

The University of North Carolina Injury Prevention Research Center (UNC IPRC) is supported by an Injury Control Research Center award (R49-CE002479) from the National Center for Injury Prevention and Control, Centers for Disease Control and Prevention. IPRC works to implement prevention solutions that reduce the impact of injury and violence in North Carolina and worldwide.