The second in a three-part series exploring how School of Pharmacy faculty are curbing the opioid epidemic

By Katie Gerhards

Between 2016 and 2017, the Centers for Disease Control (CDC) reported a nearly 10 percent increase in drug overdose deaths — and opioids are responsible for more than two-thirds of those fatalities.

“The opioid epidemic continues to be the public health crisis of our time,” says Robert Redfield, CDC director.

Research institutions around the nation are targeting opioid misuse, including the University of Wisconsin–Madison School of Pharmacy, which has a broad range of projects underway that approach the issue from each end of the spectrum.

In part one of this series devoted to rounding up all of research happening within the School to curb the opioid crisis, we covered a project to give pharmacists the tools they need to become more involved in treating opioid misuse disorder, especially in the state’s rural areas that lack formal treatment facilities, as well as the groundwork going into a vaccine-based approach to treating opioid misuse.

In part two, we’ll introduce you to a breadth of projects that stretch from helping health care providers make appropriate opioid prescriptions to leveraging and empowering pharmacists to increase naloxone dispensing.  

Appropriate prescribing

Like any other medication, opioids have safe and unsafe dosages. The risks for opioids are calculated through a morphine milligram equivalent (MME), which considers the full number of pills included in the prescription. The CDC has assigned different advised MME thresholds to reflect different variables, such as acute versus chronic pain and patient history.

“There is good evidence that when patients reach a certain MME threshold, they are more likely to get addicted,” says Associate Professor Michelle Chui, director of the School of Pharmacy’s Sonderegger Research Center for Improved Medication Outcomes (SRC). Additionally, patients with prescriptions for a higher MME are more likely to have an accidental overdose.

In partnership with the Pharmacy Society of Wisconsin (PSW) and Fort HealthCare in Fort Atkinson, Chui and other researchers in the SRC are testing a new clinical decision support module designed to help physicians double-check their opioid prescriptions against MME recommendations.

“Our main goals are to make sure that when opioids are indicated, we’re being cautious about how we’re using them without impacting the quality of care for patients who need these medications.” –David Mott

The project is part of a five-state collaborative — funded by Cardinal Health with support from the American Association of Colleges of Pharmacy and the National Alliance of State Pharmacy Associations — designed to develop interventions to reduce opioid misuse. Throughout the course of the two-year grant, stakeholders from each of the five funded state projects, each led by a partnership between a state pharmacy organization and a pharmacy school, will meet twice a year to share ideas, barriers, and what they’re learning along the way.

The clinical decision support module is part of an opioid toolkit developed by Cerner, Fort HealthCare’s electronic health records (EHR) provider.

“Because physicians today work heavily within EHRs, it makes sense to incorporate this quality improvement program directly into the EHR, which sets it up for more sustainability in the future,” says Professor David Mott (BS ’88, MS ’92, PhD ’95), chair of the Social and Administrative Sciences Division.

The new toolkit will utilize information available in the EHR about patients’ past use of opioids, as well as consider the drug, strength, and directions for use to calculate an MME. If the MME is beyond the recommended threshold set by the CDC, the prescription will get flagged for the provider’s review.

“For example, if someone needs opioids, a prescription of 15 pills might be more appropriate than 30,” says Chui. “We can refill a prescription if necessary, but if we send patients home with 30 pills and they only need 10, the remaining 20 are sitting in their medicine cabinet, posing a risk of diversion or overdose.”

Mott and Chui are working with Fort HealthCare’s Pharmacy Director Sarah Pagenkopf (PharmD ’07) and Executive Director of Population Health Chris Barron (BS ’97) and others to extract data from the EHR both before and after the rollout of the tool to evaluate whether the toolkit is effective in improving opioid prescriptions. The data will be evaluated according to metrics from the Pharmacy Quality Alliance, including monitoring the doses of extended-release opioids and how many daily doses are prescribed at a time.

The evaluation will last 12 to 18 months, and every three months, the research team will evaluate their data, meet with prescribers, and investigate what’s working well and what should be improved to make the implementation as effective as possible.

“Our main goals are to make sure that when opioids are indicated, we’re being cautious about how we’re using them without impacting the quality of care for patients who need these medications for long-term pain management,” says Mott.

Raising naloxone awareness

The School’s research project with Fort HealthCare will also tackle another issue that’s crucial to reducing opioid-related deaths: naloxone.

Naloxone can reverse the effects of opioid overdose, and if it’s delivered early enough, it can save lives. It’s such an important tool in the fight against opioid deaths that since 2016, Wisconsin pharmacists have had a standing order to dispense naloxone without a prescription to any patient at risk of an overdose or to anyone in a position to assist someone in the event of an overdose. Forty-one other states have similar standing orders.

“If pharmacists are trained to play a bigger role, it meets an unmet need for our country in terms of finding ways to expand access to naloxone.” 
–Kevin Look

Despite its effectiveness and availability, data from the U.S. Department of Health and Human Services shows that fewer than 1 percent of at-risk patients receive naloxone with their opioid prescription.

“Naloxone is a really important drug from a public health safety standpoint, but there’s just not a lot of good information out there about it,” says Mott.

In addition to flagging prescriptions with high MMEs, the new tool debuting at Fort HealthCare will also trigger prescribers to encourage patients to discuss naloxone with their pharmacist. To enhance the impact of the conversation, the research team is also partnering with community pharmacists in Jefferson County, recruited through the PearlRx practice-based research network, who will receive training about having the naloxone conversation with patients.

“Pharmacists are great access points for dispensing naloxone to patients, but there’s research that shows patients might need to be primed by their physicians to discuss the drug with their pharmacist,” says Mott, which could be due to the stigma of naloxone being tied to illegal drug use. Even among patients who have been legally using prescription opioids long-term, there is always a risk for an overdose, whether it’s because of momentary confusion or someone else in the household accidentally ingesting the drugs.

“It’s very easy to make a mistake,” says Mott. “We’re hoping to see an increase in naloxone dispensing among those pharmacies we’re partnering with.”

Overcoming communication barriers

One of the challenges pharmacists face in discussing naloxone with patients is knowing how to most effectively communicate about what can be a difficult topic.

“Pharmacists can be hesitant to start these conversations because we don’t want to assume anything negative about patients, but we also know there are risks to the use and misuse of these drugs,” says Assistant Professor Kevin Look. “Pharmacists think patients don’t want to hear this information, but they really do want to know about these risks and how to handle them.”

The trainings currently available for pharmacists often contain mixed messages or are incomplete or difficult to understand, says Look, who assisted in a review of naloxone continuing education courses available to pharmacists in states with standing orders. He worked on the review with Delesha Carpenter, a faculty member at the University of North Carolina Chapel Hill, who he’s now collaborating with on a new National Institute on Drug Abuse-funded project to solve that problem.

By conducting a series of interviews with pharmacists, patients, and caregivers in Wisconsin, North Carolina, Iowa, and Alabama, Look and his collaborators will collect insights that will be used to create an online training module for pharmacists to learn how and what to communicate about naloxone.

“Opioid overdoses, as well as misuse, are particularly a problem in rural areas,” says Look. “If pharmacists are trained to play a bigger role, it meets an unmet need for our country in terms of finding ways to expand access to naloxone.”

As Wisconsin’s representative in the project, Look is working with PearlRx administrator Kate Rotzenberg (PharmD ’07) and partnering with Hometown Pharmacies to identify potentially eligible individuals for interviewing.

When the training module is complete, it will move into a randomized controlled trial in North Carolina, to measure how it impacts pharmacist-patient communications.

“We’ll be looking at patient perceptions, such as if they feel like they have more confidence in using naloxone,” says Look. “From the pharmacist perspective, we want to know if they feel more comfortable and confident in discussing these difficult issues.”

Follow-up interviews will also examine whether pharmacists are touching on vital points, such as safety, administration, and storage, as well as what to do if someone has a certain side effect or reaction to the naloxone.

“The needs in Wisconsin, North Carolina, and each of these states might be slightly different, but by having multiple states involved, we can get a clearer picture of what’s going on in our country to address this at a larger level,” says Look. “If no one talks about naloxone and opioids in a way that people everywhere understand, we’re not helping to address this problem.”

International reach

While most projects within the School are designed to decrease opioid misuse and keep prescriptions as low as possible, another is working to increase the usage of opioids — while ensuring stable and effective regulations are followed.

Through a collaborative R21 through the National Institutes of Health’s Fogarty International Center, the SRC is helping Nepal establish and disseminate guidelines for cancer pain management, including the appropriate use of opioid medications.

Nepal is on nearly the opposite end of the opioid spectrum: The country has historically had few available, even on alternative markets, and providers just gained consistent access to oral morphine in 2009, thanks to the efforts of Bishnu Dutta Paudel, an oncologist at Bir Hospital in Nepal.

“He worked with local manufacturers and convinced them to start producing oral morphine, which is the gold standard for end-of-life and cancer pain,” says Martha Maurer, associate scientist in the School’s SRC. Maurer is collaborating with Paudel and Virginia Townsend Lebaron at the University of Virginia on the R21 grant to build a mobile app to help oncologists follow pain management guidelines.

As the country expands its access to opioids and other modalities of cancer pain management, it’s increasingly important for practitioners to be aware of and to follow the guidelines.

“We want to promote the appropriate use of these medications, while ensuring that there are proper laws and regulations, as well as institutional policies at health care facilities that will help ensure diversion and abuse don’t occur,” says Maurer.

Maurer first connected with both Paudel and Lebaron at UW–Madison, through her previous work at the Carbone Cancer Center (CCC). Lebaron completed an internship with Maurer’s group at the CCC, and Paudel earned an International Pain Policy Fellowship through the CCC’s UW Pain and Policy Studies Group.

With guidance from his fellowship, Paudel worked with the Nepalese Association of Palliative Care to release the country’s first cancer pain management guidelines, which serve as the basis for the app the team is creating to expand the dissemination of the guidelines so that providers in other health care facilities and other areas of the country have access to the information.

“The idea is to develop it in a way such that with modification, it would be relevant to many other countries who are in a similar situation in terms of cancer pain management development and opioid access,” says Maurer. “It’s exciting to think about how this app will open up information for providers and give them tools to use at the point of care.”

Read Breaking the Opioid Cycle: Part 1 to learn more about a toolkit for pharmacist involvement in treating opioid misuse disorder and an opioid vaccine.

Read Breaking the Opioid Cycle: Part 3 to learn about initiatives to educate pharmacists and teens and about opioid safety and research into treating misuse with psilocybin.