Fred Gebhart

Wayne Salverda, RPh, senior director of clinical services for National CooperativeRx, remembers visiting Eli Lilly and Company while in pharmacy school. “They had a crazy supercomputer working on drug design and that was 30 years ago,” he said. “About 1 in 10 drugs in development makes it to market, but companies like Vertex or Regeneron that have invested in and leveraged AI see 30% to 40% of their new molecular entities make it to market. It’s not a coincidence; it’s putting smart science and AI into drug development.” 

AI can be just as useful in medication management. Pharmacy benefit manager Prime Therapeutics worked with AI provider SAS to save clients $355 million over 18 months by consolidating and analyzing data from pharmacy, drug claims, and medical services to target fraud.

“We have gotten some good recoveries and great cost avoidances with AI,” Salverda said. “We will be able to leverage AI even more in the future to help make sure that individual patients are getting the most appropriate medications at the most appropriate dose by factoring in their specific genetics and health conditions. We’re going to see a lot of advances in pharmacogenomics with AI.”


AI is a concept, not a gadget like the robot Maria in the 1927 film Metropolis or R2-D2 in Star Wars 50 years later. “AI is nothing more than a means to an end, improving processes and improving outcomes,” said Codrin Arsene, chief marketing officer for Digital Authority Partners. “It’s just an automation of data, rules, and statistical processes that help people do their jobs more efficiently.”

When the American Society of Health-System Pharmacists (ASHP) and the American Medical Association discuss AI, they mean augmented intelligence: leveraging the strengths of computers and clinicians to improve outcomes for patients. “AI today is everywhere in pharmacy: drug discovery, drug design, drug development, trial design, participant selection, clinical decision support, drug response and risk prediction, personalized therapy, everywhere,” said Wei-Hsuan Lo-Ciganic, PhD, MS, MSPharm, associate professor in the Department of Pharmaceutical Outcomes and Policy at the University of Florida College of Pharmacy.


AI has come to pharmacy in 3 waves, noted Chenglong Li, PhD, a professor in the Medicinal Chemistry, Biochemistry, and Biophysics Department at the University of Florida College of Pharmacy (see Sidebar). Pharmacy management systems, IVR, and DUR screens are first-wave products. Second-wave AI powers some of the more advanced decision-support tools and systems that are starting to track fraud. Third-wave applications will change pharmacy in ways that are difficult to imagine, Li explained.

“AI is going to have the kind of impact we see with digital cameras,” Lo-Ciganic said. “When I was in school, people laughed at digital cameras. But when the iPhone came out, with its smart camera, the world changed. We are going to see the same kind of change in the world of pharmacy.” Lo-Ciganic is using AI to improve risk prediction for opioid misuse by linking Medicaid, human services, and criminal justice data. AI helped her identify 30 key predictors of opioid overdose.

“The methods used today can predict about 30% of opioid overdoses,” she said. “When we use our machine learning rule, we can improve to 70% to 90% accuracy for individuals who have an opioid overdose or misuse. That helps focus time and resources on the people at highest risk.”

Li’s lab modeled an enzyme that represses tumor suppressor genes and a native compound that blocks the enzyme, which allows suppressor genes to be expressed and kill the tumor. “We have a few collections of really potent compounds, maybe 10,000-fold more potent than the native compounds that work in cell culture,” Li said. “We are trying them in animal models to see if they are active in vivo.”

More changes in drug discovery are coming. In July 2021, DeepMind announced the latest version of its AlphaFold platform has identified the 3D structure of 98% of the entire human protein complement. More than 350,000 protein structures are available in a public database hosted by the European Molecular Biology Laboratory’s European Bioinformatics Institute.


AI isn’t making any of these advances on its own. AI needs human intervention as much as humans need AI.

“AI has the potential to help pharmacists improve their workflows.,” said Sophia Chhay, PharmD, assistant director of the ASHP Innovation Center. “Any pharmacist will tell you that ‘anything that gets me away from the computer and spending more time with patients is going to be an answer.”

Freeing up pharmacist time is key, said Ken Perez, vice president of healthcare policy and government a¡airs at Omnicell. The typical pharmacist spends 75% of working hours on nonclinical tasks.

“If you think about every medication as a node on a network, every drug has a journey, and where every dose goes is important,” he said. “Pharmacists spend too much time as de facto supply chain specialists, figuring out where drugs are [and] how to get them to the right patient at the right time. That time would be better spent with patients, not products. And that’s where AI can make a huge difference. The real prize of AI is helping pharmacists [to] practice at the top of their licenses, spending more time with the patients who need them the most.”


AI may shift pharmacist roles by giving them more hands-on time with patients, but don’t expect massive layoffs. “I don’t think any state board is at all comfortable with turning over critical decision-making to automation or AI,” said Lisa Schwartz, PharmD, senior director for professional a¡airs at the NCPA. “AI might make a recommendation, maybe a medication adjustment to avoid an interaction or adjusting the time of day a patient takes something, but it’s up to the pharmacist to decide what needs to be done.”


US clinicians, including pharmacists, are slow to adopt AI, Arsene noted. About 25% of European Union physicians are using voice assistants in daily practice. “For all the research that goes on, this is an industry that has a very low level of innovation and too much bureaucracy to change quickly,” he said. Arsene likened pharmacy to the financial services industry. It wasn’t until Credit Karma, Mint.intuit.com, and other new entrants began to affect customer preferences and banking profits that traditional providers moved to AI.

New entrants in pharmacy are presenting similar challenges. Kit Check uses AI to audit 100% of hospital-controlled substance use in less time than a conventional 5% random audit.

“Nobody can track controlled substances manually; there is just too much information,” said Doug Zurawski, PharmD, Kit Check’s senior vice president of clinical strategy. “We and our competitors can give you a dynamic picture of everything and everyone in your system relative to controlled substances.”

AI systems developed for the relatively closed universe of health systems can be expanded to ambulatory care and retail pharmacy, he added. On the dispensing side, InterLink-AI is expanding Rx verification by identifying every pill as it goes into a patient vial. Different versions of image-based verification can be adapted for a single pharmacy, telepharmacy, load sharing across multiple pharmacies.

“You have a clean record of the chain of custody from the raw materials used in a batch of medication through distribution of the stock bottle,” said Ram Subramanian, PhD, InterLink’s chief business officer. “But from the stock bottle on, there are questions. Verifying 100% of the pills that go into every vial optimizes the pharmacy workflow and frees up time for technicians and pharmacists. Improving the workflow puts the pharmacist in the driver’s seat regarding patient care.”

Articles

Artificial intelligence has been an integral part of pharmacy for decades. It is called the pharmacy management system: the collection of digital tools that houses patient utilization and drug data in virtually all pharmacy settings. 

Artificial Intelligence Has Come in Waves

Delivering clinical services doesn’t start with the patient walking into the pharmacy or talking with the pharmacist. Clinical care begins long before. Existing programs such as medication synchronization and Medicare Part D’s Medication Therapy Management (MTM) can help. Medication synchronization serves 2 purposes. Enrolling 30% to 50% of chronic patients in an appointment-based refill program frees up a significant amount of pharmacist time compared with walk-in refills, according to Cody Clifton, PharmD, director of clinical services at Duvall Family Drugs in Duvall, Washington, and director of practice transformation and clinical programs for Community Pharmacy Enhanced Services Network (CPESN).

Regular, scheduled follow-ups then pave the way for other clinical services. “Reaching out to patients 7 to 10 days in advance of every refill lets you take services to the next level by asking straightforward questions about medication changes, changes in health, vaccinations, testing, and all the other ways we can help,” Clifton said.

Many independent pharmacies use Outcomes MTM’s standalone Part D MTM program. The program boosts nondispensing cash flow and can help identify patients who need more than a compre- hensive medication review (CMR). “We sometimes use that CMR to identify patients [who] could benefit from other services,” said Tripp Logan, PharmD, vice president of SEMO Rx Pharmacies, which has pharmacies across 3 counties in southeast Missouri.“From a value standpoint, we don’t see a ton of clinical value in 1 visit because these patients are complex enough that they need more than 1 intervention a year. That CMR is an identify clinical needs. The payer or network can forward patient contacts or selection criteria directly.

“Our program identifies patients who are part of a certain health plan, have disease states within certain date ranges, or [have] other criteria,” explained Farah Madhat, PharmD, executive vice president at PrescribeWellness.“We try to empower community pharmacies to run their own clinical programs. And once you’ve identified that population through software, you can send out singular communications to only those select patients.”

Read the rest of the article on Totalpharmacy.com

Medication synchronization and Medicare Part D’s Medication Therapy Management (MTM) can help deliver clinical care to patients.

Synchronization, Communication, Staff Participation Boost Sales and Help Patients

COVID-19 has flooded media headlines and health care practices for the past year, but diabetes has not taken a pandemic holiday. Professional groups continue to publish and update practice guidelines and the FDA continues to work on new diabetes drug applications. During a virtual session titled 

New and Approved: Your Annual Diabetes Update

 at the American Pharmacists Association Annual Meeting and Exposition, which was held March 12-15, Jennifer D. Smith, PharmD, BCACP, BC-ADM, CDCES, a clinical pharmacy specialist for the US Department of Veterans Affairs, provided an update on treatment advances in the type 2 diabetes (T2D) space.

The FDA has approved continuous glucose monitoring (CGM) for ambulatory care, but pandemic pressures are spurring the use of CGM in all practice settings, especially inpatient.

“You are going to see more CGM in the hospital setting,” said Smith during her presentation.

The FDA has not approved CGM for inpatient use, Smith noted. But a growing number of institutions are using CGM to reduce patient contact and consumption of personal protective equipment during the pandemic. As health system practices and procedures increasingly promote CGM, pharmacists should remember that CGM is not appropriate for intensive care or other critically ill patients, Smith said. All CGM use should be supervised to ensure that appropriate adjustments to insulin doses can be made in a timely manner.

 The American Diabetes Association (ADA) guideline goal for CGM is to maintain patients within their target glucose range at least 70% of the time, she noted.

 It is also important to individualize glucose targets, according to Smith. The ADA’s global glycated hemoglobin (A1C) target is less than 7%. New 2021 guidelines target from less than 7% to less than 7.5% for healthy adults aged 55 years or older. Patients with complex cases might do better with an A1C target of less than 8%. However, in very complex cases, targeting A1C goals may not be helpful. 

“Instead, let’s keep our patients comfortable and avoid glycemic extremes,” Smith said. “The goal is to avoid all hypoglycemia and any symptomatic hyperglycemia.”

The Kidney Disease: Improving Global Outcomes Diabetes Work Group issued its first-ever practice guidelines for diabetes management in chronic kidney disease (CKD) in late 2020.

Angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blockade treatment should be initiated for patients with diabetes, hypertension, and albuminuria. Titrate medications to the highest tolerated dose.

A1C is the appropriate measure of glycemic control, but A1C accuracy and precision declines with advanced CKD, in dialysis, or when using erythropoietin-stimulating agents. Individualize A1C targets from less 6.5% to less 8.0% based on comorbidities. A glucose management indicator derived from CGM may be useful for glycemic assessment, especially in patients for whom A1C is not accurate because of declining kidney function, dialysis, or other treatment factors.

Metformin plus a sodium-glucose cotransporter 2 inhibitor (SGLT2i) can be used as a first-line treatment for T2D in CKD. Avoid SGLT2i treatment if the patient has an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73m2 and stop SGLT2i in dialysis. The preferred agents for patients with a low eGFR are a dipeptidyl peptidase 4 inhibitor, insulin, or a thiazolidinedione. The preferred add-on agent for all patients is a long acting glucagon-like peptide-1 (GLP-1) receptor agonist.

The ADA takes a different approach. For patients with CKD and no albuminuria, the ADA recommends a GLP-1 receptor agonist or SGLT2i with proven cardiovascular disease benefit. For patients with CKD and albuminuria, use a SGLT2i with a documented reduction in CKD progression. For patients who cannot use a SGLT2i, a GLP-1 receptor agonist is acceptable.

 The American Association of Endocrinology (AACE) and the American College of Endocrinology (ACE) published a new algorithm for the comprehensive management of dyslipidemia and prevention of cardiovascular disease in late 2020. Lifestyle changes remain the primary management tool, but treatment recommendations have been updated since AACE/ACE last addressed dyslipidemia in 2017.

The low-density lipoprotein cholesterol (LDL-C) goal for high-risk patients with diabetes and no other risk factors is 100 mg/dL. The triglycerides (TG) goal is less than 150 mg/dL. Recommended treatment is a moderate- to high-intensity statin as needed. Major risk factors include advancing age, elevated nonhigh-density lipoprotein cholesterol (HDL-C), elevated LDL-C, reduced HDL-C, diabetes, hypertension, CKD, cigarette use, or family history of atherosclerotic cardiovascular disease (ASCVD).

For very high-risk patients who have diabetes with 1 or more risk factors, the LDL-C goal is less than 70 mg/dL and the TG goal is less than 150 mg/dL. Add ezetimibe, a PCKS9 inhibitor, colesevelam, or bempedoic acid, depending on LDL needs.

For extreme risk patients with established clinical ASCVD and diabetes, the LDL-C goal is less than 55 mg/dL and the TG goal is less than 150 mg/dL. Add a PCKS9 inhibitor, ezetimibe, colesevelam, or bempedoic acid, depending on LDL needs. For patients with diabetes, 2 or more risk factors and TG 135-499 mg/dL, add icosapent ethyl.

 For patients with heart failure with reduced ejection fraction (HFrEF), left ventricle ejection fraction less than 45%, the ADA recommends a SGLT2i with proven heart failure benefits. Prescribers have multiple choices, according to Smith.

 Two agents, dapagliflozin and empagliflozin, have primary heart failure outcome data.

 Three agents––empagliflozin, canagliflozin, and dapagliflozin––have shown reduction in heart failure and reduction of 

CKD progression in cardiovascular outcome trials.

 The 2021 ADA guidelines introduced a new concept: overbasalization, which is characterized as an excessive basal dose of insulin. Too much basal insulin can overcorrect fasting glucose levels, which then rebound to excessive levels, Smith explained. Typical examples of overbasalization are an elevated bedtime-morning glucose differential, greater than 50 mg/dL, an elevated post-preprandial differential, hypoglycemia, and high glucose variability.

Guidelines noted overbasalization is a potential concern anytime the basal dose exceeds 0.5 units/kg/d, Smith said. Any indication of overbasalization should prompt reevaluation of insulin dosing to reduce glucose variability.

 High-dose glucocorticoids can increase the need for insulin. Patients with diabetes who start high-dose prednisone for an asthma flare, for example, need a corresponding increase in insulin. Neutral protamine Hagedorn insulin protocol is the standard approach for once daily or twice daily steroids, Smith said.

 Insulin formulation and dose should match the steroid. A long-acting steroid needs a long-acting insulin and increasing doses of steroids need increasing doses of basal, prandial, and correctional insulin. The ADA recommends an increase of 0.1 IU/kg of insulin for each 10 mg/d of prednisone to a maximum of 0.4 IU/kg for 40 mg or more of prednisone.

Jennifer D. Smith, PharmD, BCACP, BC-ADM, CDCES, a clinical pharmacy specialist for the US Department of Veterans Affairs, highlighted recent safety changes for diabetes treatments that pharmacists should know:

Canagliflozin has lost its black box warning for lower-limb amputation. However, an increased risk of lower-limb amputation remains in the label warning and precautions section.

An FDA safety communication recommends stopping canagliflozin, dapagliflozin, and empagliflozin at least 3 days prior to scheduled therapy. Ertugliflozin should be stopped at least 4 days before surgery. All 4 agents can be restarted after surgery.

New data also suggest stopping sodium-glucose cotransporter 2 inhibitor therapy before scheduled surgery to lessen the risk for ketoacidosis.

At least 4 new agents are in the pipeline, Smith reported.

, a once-weekly “twincretin” combination of a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide, showed solid phase 3 data in T2D. A cardiovascular outcomes trial is ongoing.

 a nonsteroidal selective mineralocorticoid receptor antagonist, reduced the risk of composite cardiovascular outcomes in patients with CKD and T2D in the FIDELIO-DKD trial (NCT02540993). The agent’s application has been submitted to the FDA, she said, and a decision is expected sometime this summer.

, a prefilled rescue pen for severe hypoglycemia, is under review by the FDA.

, a once-weekly basal insulin, showed efficacy and safety profiles similar to once-daily insulin glargine U100 in T2D.

“Even with all these changes, we cannot underscore more the benefits of lifestyle and nutrition management,” Smith said. “Whole-food, plant-based, Mediterranean, and DASH [dietary approaches to stop hypertension] diets remain the bedrock of therapy for diabetes and ASCVD risk reduction. Physical activity is key, and treatment must be tailored to the patient.”

Smith JD. New and approved: your annual diabetes update. Presented at: American Pharmacists Association 2021 Annual Meeting and Exposition; March 12-15, 2021; virtual. Accessed March 12, 2021. 

A session held during the American Pharmacists Association 2021 Annual Meeting and Exposition provided an update on diabetes practice changes and new treatments. 

Diabetes Treatment Guidelines, Practices Advance Despite COVID-19 Focus in Health Care

Telepharmacy turns 20 this year. Two decades after it emerged as a way of preserving and expanding pharmacy access across rural North Dakota, telepharmacy innovators are moving into sterile compounding, secure medication storage, primary care consults, and more.

 Telepharmacy has gone from a pilot project to accepted practice in 25 states, according to Jessica Adams, PharmD, director of regulatory affairs for Telepharm, an early telepharmacy provider acquired by Cardinal Health in 2016

. Many states who do not have telepharmacy rules in place today, are in some stage of approving telepharmacy as pharmacists and patients continue to push the need for access to pharmacy care. As pharmacists, providers, patients, payers, and regulators recognize the benefits that telehealth can bring to pharmacy, technology-based services will continue to expand.

At its simplest, telepharmacy allows a pharmacist to supervise a remote dispensing site via HIPAA-compliant, 2-way audio-visual technology. The pharmacist remotely supervises the telepharmacy technicians, verifies prescriptions, and counsels patients from their host pharmacy location. Newer iterations are combining remote oversight with other familiar technologies to expand the reach of pharmacy care.

 One of the newest expansions is using remote verification for sterile IV compounding at the University of North Carolina (UNC). Pharmacists saw the potential to balance workload across multiple pharmacies that were using BD Pyxis IV Prep to prepare sterile IV solutions, explained Lindsey B. Amerine, PharmD, MS, BCPS, director of pharmacy and associate professor of clinical education at the UNC Eshelman School of Pharmacy in Chapel Hill, North Carolina. She proposed a double arm, prospective study of remote versus onsite verification at 4 UNC pharmacies.

 The Pyxis system uses gravimetric-based technology to weigh and verify compounded products, Amerine explained. The system images the compounding process, which is typically managed by a technician and reviewed by a local pharmacist. Because the onsite pharmacist was using images generated by the system, there was no obvious difference between reviewing images in the next room or 25 miles away.

 Results of the 90-day trial demonstrated no difference in accuracy or safety for remote versus local oversight, and resulted in an annualized cost savings of nearly $24,800, according to Amerine. “When we did the study, the state had no rules around this kind of telepharmacy,” Amerine said, “so we designed the trial with remote plus onsite review of all compounded sterile products.” When the COVID-19 pandemic started, “we received a waiver from the [State] Board of Pharmacy 

to be able to do this remote sterile product check as long as the health emergency lasts,” she said.

“Our next initiative is to be able to use telepharmacy routinely in the long term to do more workload sharing across sites. There is also the advantage of having a pharmacist able to check product from anywhere in the hospital. Not being tied to the pharmacy frees you up to spend more time with patients.”

 Roger Rose, RPh, director of pharmacy services for Wickenburg Community Hospital, opened the first telepharmacy in Arizona in 2019. Wickenburg has long had a satellite clinic in the town of Congress, which is about 16 miles away

. With a population of 3500, Congress is too small to support an onsite pharmacist, Rose said. The drive to Wickenburg to fill prescriptions is not always practical for patients.

 “We were doing deliveries to the Congress clinic twice a day, but that didn’t always work, either,” Rose said. “Patients still had to go home after their clinic visit, then come back later, or maybe the next day. Too many prescriptions never got picked up.”

 When Arizona approved telepharmacy in 2018, Rose had a solution and 2 more problems. One was security. Most telepharmacy operations he visited had a single technician handling the entire operation.

 “You’ve got your front end, you’ve got prescriptions at the back, and just 1 person,” Rose said. “For any pharmacist who has been around for a while, that’s a stress.”

 The second problem was space. State telepharmacy regulations required at least 300 square feet. The only available space at the Congress clinic was 125 square feet.

 His solution was RxSafe, a secure medication storage unit that can hold about 1300 medication vials. The unit weighs every container coming out and going back into storage to verify the medication removed for each prescription.

 “Combining telepharmacy and RxSafe answered our questions,” Rose said. “We can stock just about everything our providers write in the limited space, and I know the location is safe for our tech. The technologies work well together.”

 Adam Chesler, PharmD, MBA, senior vice president for pharmacy integration at VillageMD, a network of primary care clinics, envisions a day when every patient in nearly 2000 primary care clinics can have a pharmacist consult. Some consults will likely come through an in-person Walgreens pharmacist. Walgreens is investing $1 billion to support up to 700 new Village Medical primary care clinics at its locations by 2025. Other consults will likely come via telepharmacy.

 “Having a pharmacist directly involved in care improves patient outcomes,” said Chesler. “By integrating a pharmacist into primary care, we have shown significant, sustained increases in medication adherence to treat cholesterol, diabetes, and hypertension. We can utilize telepharmacy and telehealth technology by taking an iPad or tablet into any exam room and having a conversation between the pharmacist, physician, and patient anywhere, anytime.”

 The telepharmacy technology already exists and VillageMD already has a focus on pharmacy integration. Patients with multiple chronic disease states or those who use multiple pharmacies have an elevated risk of therapy failure. These patients already receive in-person or telephonic pharmacy consults, as do discharged and homebound patients. Telepharmacy can further expand this reach. Pharmacists in these settings have full access to patient electronic medical records, a common communication platform with clinicians, and collaborative practice agreements with delegated prescribing authority.

 “We are taking full financial risk for many Medicare patients,” Chesler explained. “The physicians here understand that the best way, the only way, to successfully improve outcomes and reduce costs is by having pharmacists directly integrated into the care team. Having a pharmacist on the care team is integral to our success and telepharmacy can help make that integration happen.”

As telepharmacy evolves, regulators are playing catch-up. On a federal level, the COVID-19 pandemic called for loosened telehealth restrictions overall during the public health emergency. The Centers for Medicare and Medicaid Services (CMS) expanded the number of covered services that can be provided via telehealth. Many of these changes are noted as temporary during the COVID-19 emergency period. However, as telehealth benefits prove valuable, it is the hope that these changes will carry over post pandemic, enabling telepharmacy expansion. 

Many states already had telepharmacy laws in place prior to the pandemic. California’s Legislature authorized telepharmacy in 2018. It took 2 years to work out the regulatory details and open the state’s first telepharmacy. Arizona’s first telepharmacy was 6 years in the making.

 “When we first asked, the state pharmacy board told us they had no regulations and nothing in the practice act that would let them authorize telepharmacy for the hospital’s remote clinic,” said Rose. “Five years later, they had changes to the practice act, called us back for a hearing in July, and we were licensed the next April.”

 Outreach to the state board, showing up at board meetings, and providing public comments make the difference, said Adams. “ Each state is unique and has its own challenges, but access is an issue everywhere. Telepharmacy has been proven to work for 20 years, and is now permitted in 25 states. If pharmacists attend board of pharmacy meetings and explain how telepharmacy can reduce gaps in pharmacy care that their patients are experiencing, it can make a positive difference in getting telepharmacy moving,” she explained.

 Changing pharmacy regulation and legislation is a team sport, Adams continued. Arizona was slow to adopt telepharmacy in part because chain pharmacists feared remote oversight could lead to job losses. The Arizona Pharmacy Association demanded language in the practice act to safeguard pharmacist employment.

 Rural health associations can be solid partners, particularly for pharmacists seeking to bring telepharmacy to underserved rural areas. Federally qualified health centers, health systems, and physician practices that recognize the advantages of bringing pharmacy to the care team can help build support.

 “The basic message is telepharmacy safely provides greater access to pharmacist care,” Adams said. “Why are we not using a proven technology to help ensure that our patients are getting the best pharmacy care possible? The more stakeholders you bring to support your message, the more likely you are to get a positive response.”
