34 minute read
ISMP’s Michael Cohen: a career dedicated to medication safety
One Error, One Journal Article, One Movement Toward Medication Safety
By Marie Rosenthal
If you think it’s not possible to make a difference as one pharmacist, consider the story of Michael R. Cohen, RPh, MS, ScD (hon.), DPS (hon.), FASHP, who was “just” a hospital pharmacist when he wrote about one medication error and turned that article into a movement dedicated to improving medication safety for all patients.
Mr. Cohen is stepping back as the president of the Institute for Safe Medication Practices (ISMP), an organization that he founded almost 30 years ago. ISMP is now a leader in helping to prevent medication errors, not just in the United States but globally. Mr. Cohen and ISMP are called upon by hospitals, agencies like the FDA and even pharmaceutical and device companies to investigate medication errors or, more importantly, to provide solutions to prevent them.
ISMP’s Origin Story
It all began in 1974, when he and his first collaborator, Neil M. Davis, PharmD, heard about a patient who had died from an overdose of insulin at a local hospital. Both men were pharmacists at Temple University Hospital, in Philadelphia, and were discussing the incident, when Dr. Davis suggested Mr. Cohen write it up as a cautionary tale for the journal Hospital Pharmacy, which Dr. Davis edited at the time (1975;10[3]).
The positive response led to a column about errors, which was based on real cases. “When we published information those first few months, we heard from pharmacists from all over the country, and out of complete altruism, they were willing to share information,” Mr. Cohen said, as long as he did not identify the individuals or the organization involved. “In fact, we’ve never done that in all the years we’ve been doing this work.”
Withholding identities in the reports was important, because talking about medication errors in the 1970s was just not done, according to Mr. Cohen. Although the pharmacists and nurses appreciated the alerts, the C-suite would have preferred they remained silent.
“People were kind of upset with us at first, so we didn’t know what was going to happen as we moved along,” Mr. Cohen admitted. “Pharmacists certainly got it. They saw these things happening in their own practice, and I think a lot of nurses did, too, but those in some leadership circles were upset that we were talking about very serious harms that could come to patients from medical errors,” and they thought that could scare patients away from care, he said.
Dr. Cohen and his colleagues continued their efforts with a book, “Medication Errors: Causes and Preventions,” published in 1981 by G.F. Stickley Co. “It got a lot of publicity, and that brought us even more reports [of medication errors], and then Dr. Davis and I started getting requests to go to state pharmacy meetings and give talks. We were thrilled to be able to do that, to share our information.”
The FDA Takes Notice
People outside of pharmacy began to take notice, and by the late 1980s, the FDA asked to meet to discuss productrelated medication errors, and the agency formed the labeling and nomenclature committee.
Mr. Cohen and Dr. Davis realized that this “could be a full-time operation,” said Mr. Cohen, who was then an assistant director of pharmacy at Temple. They sought help and received it initially from USP, and established a national reporting program.
By the time ISMP was founded, Dr. Davis was retiring, and medication safety was becoming Mr. Cohen’s entire focus, but to call it a full-time job would be a gross understatement. For Mr. Cohen, it was a calling, a mission, a passion—one he is stepping away from, but not leaving completely, he told Pharmacy Practice News.
“Why did I decide to retire? Well, I am not retired completely,” he admitted. “I couldn’t do it. This work is just amazing. It’s enjoyable to be in a position to help colleagues around the country, and to work with the kind of staff that we have at ISMP.
“How can you just stop?” he asked, but admitted there were many activities he enjoyed outside of pharmacy that he wanted to start doing, including spending more time with his grandchildren.
“I’m in my upper 70s, I hate to say that, and it’s time that I tried to enjoy life a little, too, so I’m trying to get a nice mix,” he said. “But so far, it hasn’t quite worked out that way,” he joked, adding that he’s still working but finding time to grow orchids, play golf and travel as COVID-19 abates.
Dr. Davis retired as ISMP was kicking off, and Mr. Cohen put together a board of trustees with the help of Allen Vaida, PharmD, FASHP, who retired in 2021 as the executive vice president of ISMP.
At first, Mr. Cohen had no idea that those first couple of articles would be his life’s work, but by the time they were registered as a nonprofit in 1994, “I think we did have a premonition that this could turn into something big, and of course over time, with the help of organizations like ASHP that helped us get the word out, the Food and Drug Administration, USP and quite a few others, it really grew into something that has had a major impact on product- and practice-related issues.”
One program, the ISMP Medication Safety Self Assessments, is a shining example of how ISMP helps medical professionals. The self-assessments allow professionals in various healthcare settings to assess their practices and processes related to medication use. They are meant to be completed by an interdisciplinary team that includes front-line staff and management.
The first assessment evaluated acute care and was done with support from the American Hospital Association. It had almost 200 characteristics of a safe drug distribution system in hospitals, and was released about the same time that the former Institute of Medicine (IOM; now the National Academy of Medicine) issued its famous report “To
A Just Culture
One of the important tenets of the Institute for Safe Medication Practices (ISMP) is encouraging people to come forward and report errors. To do that, the focus needs to be on fixing and preventing the error from occurring again, rather than focusing on blame and punishment.
The idea is to form a just culture, explained Michael R. Cohen, RPh, MS, ScD (hon.), DPS (hon.), FASHP, the president emeritus of ISMP. “We subscribe to a just culture, and that isn’t necessary blame-free. There are some situations that cross over into reckless behavior.”
Reckless behavior “truly should never happen, because we know better,” like taking shortcuts even though you are well aware that behavior can sometimes lead to patient harm, Mr. Cohen explained. But once a behavior is noticed, the organization can work to correct and change that behavior, he said. ISMP, however, analyzes the systems that healthcare workers use to see whether there is a better way to encourage safety.
“Our work from the very start has been identifying the system-based causes of medication errors. We’ve never really focused blame on individuals when errors happen,” Mr. Cohen explained. “We are looking at the systems that literally set people up for making a medication error and identifying what they are.”
In many cases, it is product related, he said (products with similar names and dosing, labeling issues, etc.).
“So, those are the things that we focused on over the years and working with individuals, as well as organizations, hospitals, community, pharmacies, etc., and trying to work with drug companies and the Food and Drug Administration and regulators to make corrections that hopefully will not set people up for making errors.
“That’s what it’s been about for us, and from the very beginning, we were not focusing on blame,” he said. Michael R. Cohen, RPh, MS, FASHP (second from right), was invited to the White House to discuss medication safety issues with former President Bill Clinton around the time the famous IOM report, “To Err is Human,” was released.
Michael R. Cohen, RPh, MS, FASHP, still takes every medication error report seriously. Here he discusses labeling with an ISMP staff member.
—Rita Jew, PharmD, MBA, BCCPPS, FASHP
Err is Human,” about medical errors. In addition to being on a national call about the IOM report, Mr. Cohen and his colleagues were invited to the White House to meet former President Bill Clinton.
“President Clinton greeted us, and we had a roundtable in the cabinet room, and then went out to the Rose Garden and met with the press,” he said. “That was pretty thrilling for me, a hospital pharmacist.”
The self-assessments gave hospitals an opportunity to really look at their operations, and a guide to work on not only medication safety but also other patient safety issues and to compare themselves with other hospitals around the country.
The assessments are sponsored by agencies such as the FDA and the Agency for Healthcare Research and Quality or private foundations such as the Commonwealth Fund. Currently, ISMP is working on a perioperative medication safety assessment, which was sponsored by the FDA. Many of the assessments become guidance statements.
Technology Helps, But Not Foolproof
Many technological changes have greatly improved patient safety, Mr. Cohen said. For instance, electronic prescribing was really helpful because the old joke about a doctor’s poor handwriting was no joke. Some prescriptions were nearly impossible to read. However, just having electronic prescribing doesn’t preclude the occurrence of errors, he reminded. There are computer selection errors, similar drug names or dosing issues. “Without a doubt, electronic prescribing has been really helpful, but I do want to mention a caveat, and that is when we had handwriting problems, if you had trouble reading an order, you could call the doctor or the prescriber [and find out what should be dispensed],” he said.
“I think we’ve made great improvements, and it is largely due to getting the information out there and having individuals and organizations who take this seriously. We’ve set up safety committees. We’ve developed technologies. We have barcoding and electronic prescribing now that we didn’t have 20, 30 years ago.”
There have been improvements with labeling, such as tall man lettering, changes and standards set by USP and other accrediting bodies, and work in the FDA and other federal agencies that has improved patient safety. ISMP has been working alongside many of them, gathering information and disseminating it to others.
“We also take the opportunity to publicize [the issues] in our various columns and journals and newsletters. Pharmacy Practice News has been a tremendous [source of support] in helping us get the word out on so many of the major issues,” Mr. Cohen said.
“The culture of safety has changed dramatically. There are still problems out there, and there are still improvements to be made for sure,” he said. “But I believe there has been a vast improvement in patient safety over the years, thanks to medication safety.”
ECRI Helps ISMP Become A Global Presence
In 2019, ISMP became an affiliate of ECRI (formerly the ECRI Institute of Emergency Care Research Institute), which bolstered the ability for both organizations to make medication, medical devices and healthcare practice settings safer for patients. The affiliation made ISMP the largest nonprofit organization dedicated to patient safety in the world, a crowning achievement for a man who graduated with a Bachelor of Science degree in Pharmacy in 1968 from Temple University School of Pharmacy.
Mr. Cohen would go on to receive a Master of Science in Pharmacy, also from Temple, as well as honorary doctorates from Thomas Jefferson University, the University of the Sciences in Philadelphia, Long Island University and the University of Maryland. He also received the John M. Eisenberg Patient Safety and Quality Award from the National Quality Forum and the Joint Commission, the Harvey A.K. Whitney Award from ASHP, and was recognized as a MacArthur Fellow by the John D. and Catherine T. MacArthur Foundation.
But anyone who spends any time with Mr. Cohen quickly realizes that these honors have not gone to his head, that he is quick to list all the people who have helped him and his organization improve the safety of medical care, and that he is truly honored by the opportunity to help others and to share what he has learned with them.
“Mike Cohen is like the grandfather of medication safety. He created this field basically, and no one will ever be able to fill his shoes,” said Rita Jew, PharmD, MBA, BCCPPS, FASHP, who recently assumed the role as the president at ISMP.
And just like a grandfather, unsolicited, Mr. Cohen made a point of bragging about her qualifications: “I have great confidence in the person who’s following me, and that’s Dr. Rita Jew. She is sharp about technology. She is great management-wise, having graduated from the Wharton School with an MBA as well as a PharmD. She has a great background in patient safety.
“I’ve known Rita for years, and I think she’s going to do a fantastic job as president of ISMP.”
Dr. Jew said she is grateful for his confidence as well as humbled by the task ahead. “It will take me a long time to even get to the point where I can feel like I can represent some of what Mike has represented in the past.
“It will be a lot of on-the-job training,” she joked, adding that she was grateful he is still there to offer advice.
But the best advice she has received is watching him work and working alongside him. “He never directly sat down and said, ‘Hey, Rita, this is my advice for you.’ But over the year I’ve worked at ISMP ... it is really his example [that has inspired me], the way he handles things, that is really the advice I’ve taken in,” she said.
“Watching how he takes every single medication error that is reported seriously, and deliberates [the issues] —it’s just his passion,” Dr. Jew said. “I’ve learned a lot over the years from Mike, and I just continue to do so. Every single conversation I have had with him is sound advice that I can take on and keep doing this job.”
The sources reported no relevant fi nancial disclosures.
Test-to-Treat
continued from page 1
risky,” the group noted. The clinics “typically treat simple illnesses such as strep throat. Yet, COVID-19 is a complex disease and there are many issues to consider when prescribing COVID-19 antiviral medications. Leaving prescribing decisions this complex in the hands of people without knowledge of a patient’s medical history is dangerous in practice and precedent.”
Michael Ganio, PharmD, the senior director for pharmacy practice and quality at ASHP, disagreed with that characterization. “Pharmacists are the most qualified healthcare professionals to review DDIs [drug-drug interactions], make dose adjustments and navigate a patient’s medical history,” Dr. Ganio said. “That is literally what we do all day, collaborating regularly with an interdisciplinary team. In fact, our members are frequently being consulted by physicians who are not comfortable with managing all the DDIs associated with these antivirals, and that predates the test-to-treat program.”
The test-to-treat initiative, which launched in hundreds of pharmacy-based clinics across the United States during the week of March 7, 2022, offers immediate access to the COVID-19 antiviral pills nirmatrelvir plus ritonavir (Paxlovid, Pfizer) and molnupiravir (Merck/ Ridgeback) for people who test positive for the virus. The initial rollout focused on large retail chains that offer on-site healthcare services, such as CVS Minute Clinics. “I’m 100% confident that the skills and the training of the pharmacists in these clinics are well suited to manage these medications, identify drug-drug interactions and contraindications, and consult with a patient’s physician when appropriate,” Dr. Ganio said. He noted that additional sites, including ambulatory care and retail pharmacies affiliated with hospitals and health systems, will be added to the program in the coming weeks and months as supplies of the antivirals are made available from both federal and state resources.
“There’s a reason why brick-and-mortar pharmacies are the places that have done so much of the COVID-19 testing and vaccinations,” said Jeff Little, PharmD, the chair of ASHP’s Section of Pharmacy Practice Leaders. “It’s because pharmacists are the most accessible healthcare professionals, and we’re also the medication experts and the profession that is best suited to deal with complicated [DDIs].”
The AMA’s statement sparked controversy on social media, including comments from several doctors who disagreed with the organization’s stance. “It’s offensive that the AMA chose Biden’s Test-to-Treat COVID-19 plan as an opportunity to double down on their ‘scope creep’ messaging and to take a swipe at pharmacists, when in fact, it’s pharmacists that are *the* experts on drug-drug interactions,” tweeted emergency physician Uché Blackstock, MD, a former associate professor of emergency medicine at NYU Grossman School of Medicine, in New York City, and the founder and CEO of Advancing Health Equity. “I can’t even share the number of times that pharmacists have called the ER to tell us that one of our physicians had prescribed a medication that could have had a potentially dangerous interaction with another medication a patient was taking and helped us to find a substitute.”
“I trust PharmDs to manage routine Paxlovid drug interactions, & to get MDs involved for tough calls (?stop a med while taking Pax?),” tweeted Bob Wachter, MD, the chair of the Department of Medicine at the University of California, San Francisco School of Medicine. “Your plan (Rx by MDs only) will markedly limit/delay access to key Covid med.”
EUAs Getting in the Way?
Regulatory barriers already exist that prohibit pharmacists from taking a leading role in making test-to-treat a success, according to ASHP. Both nirmatrelvir plus ritonavir and molnupiravir currently are available under an emergency use authorization (EUA) that specifically limits prescribing authority to physicians, nurse practitioners (NPs) and physician assistants (PAs)—and excludes pharmacists, despite the fact that many states license pharmacists to order medications, either independently or in collaboration with a physician. Therefore,
Available when you need them most
Multi-source Injectable Products from Amneal
DEXAMETHASONE SODIUM PHOSPHATE INJECTION, USP
Our ever-expanding portfolio includes generic medicines that you can count on. At Amneal, we take pride in delivering vital medicines like Dexamethasone Sodium Phosphate Injection. Our goal is to get these important products into the hands of those who need them most...when they need them most. With over 250 generic pharmaceuticals, we provide customers and patients with value, accessibility, and quality. This is how we make healthy possible.
Dexamethasone Sodium Phosphate Injection, USP Pack NDC Dosage Strength Pack Size
70121-1399-05 10 mg/mL 25 x 1 mL Single-Dose Vials
Not made with natural rubber latex Preservative free
Order from your wholesaler/distributor or contact Amneal: 866.525.7270 or CustomerRelations@amneal.com
only pharmacies that have prescribing authorities on site can participate in the program. Leading pharmacy organizations are responding by calling for changes to the EUA to permit pharmacists to provide increased access to treatment in locations where access to physicians is limited.
In a March 9 letter to President Biden, ASHP and 13 other pharmacy groups called for the removal of these restrictions, noting that in September 2021, the Department of Health and Human Services authorized pharmacists in all 50 states to order oral treatments for COVID-19.
“Unfortunately, the FDA’s limitation undermines the intent of your announcement and patient access to pharmacies as a one-stop shop for COVID-19 testing and treatment with antivirals. This limitation is also inconsistent with FDA’s normally providerneutral prescriber directives in approval and EUA decisions,” the letter stated.
Cut Out of the Equation
When the Public Readiness and Emergency Preparedness Act was passed in September 2021, it specifically expanded the scope of authority for licensed pharmacists to order and administer oral, intramuscular and subcutaneous COVID-19 therapeutics. “But then, when the FDA issued the EUAs for these agents in December 2021 for molnupiravir, they disallowed pharmacists from being able to order them,” Dr. Little said.
Restricting oral antiviral prescribing to physicians, NPs and PAs will significantly limit the number of locations where patients can receive these drugs on the spot, the organizations noted, pointing out that many pharmacies do not have in-house non-pharmacist prescribers. This burden is likely to fall disproportionately on rural and underserved communities, the letter added.
“Approximately 90% of Americans live within five miles of a pharmacy, and that can’t be said with regard to primary care physicians or other healthcare providers,” said Monica Mahoney, PharmD, a clinical pharmacy specialist in infectious diseases at Beth Israel Deaconess Medical Center, in Boston, who noted that she spoke on her own behalf as a pharmacist and not as a representative of her institution. “If pharmacists were given the authorization to prescribe these antivirals, either as part of a collaborative practice agreement or in states where we are recognized as independent prescribers, that would vastly improve access to test-to-treat.”
Most independent pharmacies in small towns and rural areas are trusted members of their communities and have excellent relationships with their patients, which facilitates communication and encourages testing and treatment, Dr. Mahoney said. “But they often do not have a physician or NP/PA on site. Many pharmacies have been offering testing at their locations throughout the pandemic, and this is just a natural extension. If the test is positive, the next logical step is for the pharmacist to look up the patient profile, make sure there aren’t any DDIs or contraindications, and give the patient immediate access to the medication they need.”
Dr. Mahoney acknowledged that there are justified concerns from community pharmacists about understaffing issues, given the increased demand on pharmacies. “There were staffing issues even prior to the pandemic, and testing and dispensing takes time,” she said. “We need to make sure that there is adequate staffing to support these pharmacies and that whatever dispensing fee is available covers those costs, so that more of our community pharmacy colleagues can provide these therapies without unduly burdening them.”
Dr. Little echoed the workforce concerns. “The healthcare system has probably never been more strained than it is right now, and we need to do whatever we can do to get patients more access to these treatments—not less,” he said. “Pharmacists are very well positioned to provide these therapies to patients. In fact, in hospitals and health systems, we are usually the go-to people to manage medication order sets and therapy plans. Anything we can do as a healthcare system to increase access to care is something we need to do.”
Drs. Ganio and Little reported no relevant fi nancial disclosures. Dr. Mahoney reported a fi nancial relationship with Merck.
FUNGITELL FUNGITELL STAT STAT ® ®
Single Sample Format Single Sample Format (1 (1 3)3)- -- D-Glucan TestingD-Glucan Testing Better Turnaround Time For Better Turnaround Time For Better Patient Management! Better Patient Management!
Fungitell STAT ® is the first and only single sample format FDA-cleared and CE marked rapid in vitro diagnostic screening test for IFI (including Candida, Aspergillus and Pneumocystis) that detects (1 3)- -D-Glucan in serum.
SpecialtyPharmacyContinuum.com/ Registration
Get the latest news from the most widely read specialty pharmacy publication in the United States, including multimedia and web-only content, delivered directly to your inbox!
Serving managed care health-system and specialty pharmacy decision makers
Brought to you by the same team who publish
Navigating Biosimilars
continued from page 1
they did. In 2003, the Pediatric Research Equity Act required manufacturers to assess pediatric-specific dosage forms, dosing regimens, routes of administration and active ingredients when submitting a New Drug or Biologics Product Application, Dr. Jacob noted in a session at the 2021 annual meeting of the American College of Clinical Pharmacy (ACCP).
Nevertheless, “the data for biosimilars in pediatrics is still limited,” said Dr. Jacob, who is also a clinical pharmacy faculty member at the Mount Sinai Hospital, in New York City.
These limitations behoove pediatric pharmacists to “become experts on each of the medications and the biosimilars for use in their pediatric populations, and to serve as a source of knowledge for physician specialists, nurses and anybody else on the care team that is going to be involved in use of these medications,”
Table. Pediatric Biologics and Their Biosimilars
Medication Biosimilar
Adalimumab • Reference product (Humira, AbbVie) approved for JIA (age ≥2 years), pediatric Crohn’s disease (age ≥6 years), uveitis (age ≥2 years), hidradenitis suppurativa (age ≥12 years) and UC (age ≥5 years) • Six biosimilars available • Biosimilar pediatric approvals only for JIA (age ≥4 years); other indications under orphan drug exclusivity • Limited biosimilar pediatric literature, with one study revealing safety and efficacy in JIA Epoetin alfa • Pediatric approval for anemia due to CKD in patients on dialysis and not on dialysis (age 1 month to 16 years), anemia due to zidovudine in patients with HIV infection (age 8 months to 17 years), and anemia due to concomitant myelosuppressive chemotherapy • One biosimilar available, approved for these indications based on extrapolation of reference biologic (Epogen, Amgen) data • No pediatric studies of biosimilar Etanercept • Reference product (Enbrel, Amgen) and biosimilar approval for polyarticular JIA (age ≥2 years) and plaque psoriasis (age ≥4 years) • Two biosimilars approved • One study showed no difference in safety and efficacy in JIA Filgrastim • Reference product (Neupogen, Amgen) approved for PN, mobilization of autologous hematopoietic progenitor cell and HARS • Three biosimilars available, all approved for all indications, except HARS, which is under reference drug exclusivity • Minimal pediatric literature on biosimilars, but data showed safety and efficacy in mobilizing peripheral blood stem cells and for prophylaxis of CIN Infliximab • Four available biosimilars • All approved for pediatric IBD (age ≥6 years) • Pediatric infliximab biosimilar studies primarily in CT-P13a for IBD • No outcomes differences between reference product (Remicade, Janssen) and CT-P13 in IBD • No data on multiple switches among biosimilars and reference drug or various biosimilars in pediatric IBD patients Pegfilgrastim • Reference product (Neulasta, Amgen) approved for pediatric CIN and HARS • Three available biosimilars • HARS indication under orphan drug exclusivity until November 2022 • No biosimilar studies in pediatric patients Rituximab • Reference product (Rituxan, Genentech) approved for PGP and MP (age ≥2 years) • Three available biosimilars • Reference biologic has market exclusivity for pediatric indications until 2026
a CT-P13 is an investigational biosimilar; see bit.ly/35qSv0Q for more information. CIN, chemotherapy-induced neutropenia; CKD, chronic kidney disease; HARS, hematopoietic acute radiation syndrome; IBD, inflammatory bowel disease; JIA, juvenile idiopathic arthritis; MP, microscopic polyangiitis; PGP, pediatric granulomatosis with polyangiitis; PN, pediatric neutropenia; UC, ulcerative colitis Source: Elsen Jacob, PharmD. Adapted from presentation at the 2021 annual meeting of the American College of Clinical Pharmacy.
Sara Hovey, PharmD, a pediatric clinical pharmacy specialist at Rush University Medical Center, in Chicago, said during the ACCP meeting session.
When to Switch
When it comes to deciding whether to switch from a reference biologic to a biosimilar, it is critical to consider not only clinical data but logistical and operational angles as well, Dr. Hovey said. “For example, if there are differences between a biosimilar and its reference biologics in the approved indications, pulling data on your institution’s usage and seeing what indications you use the medication for most often can help determine which drug to add to your formulary.”
Adalimumab is one drug for which indications between the reference biologic and biosimilars differ, she noted. While adalimumab biosimilars have pediatric approvals only for juvenile idiopathic arthritis (ages ≥4 years), the reference biologic (Humira, AbbVie) has exclusive approval for a number of additional pediatric indications, including Crohn’s disease (Table). In this case, if the agent is used in a hospital primarily for pediatric patients with Crohn’s disease, staying with the reference product may make more sense, Dr. Hovey noted.
Other considerations may make a switch from a reference biologic to a biosimilar less straightforward, she said. For example, variations in dilution and stability between biosimilars and reference biologics can affect how they are prepared in the pharmacy. “Particularly in our pediatric population, a lot of the dilution and stability information comes from post-marketing studies of reference biologics,” Dr. Hovey said. “Because minor differences in the formulations and in the molecules between biologics and biosimilars could affect stability, those post-marketing biologics data may not always be applicable to biosimilars.”
In terms of the cost savings associated with a biosimilar implementation switch, institutions should consider a number of factors before concluding that direct savings on a drug makes a switch worthwhile. For example, pharmacists should consider how much work is needed to revise electronic order sets. “Think about how many different order sets include the drug and how many IT [information technology] and clinical pharmacist hours would be needed to make changes to these builds,” Dr. Hovey said. “Some changes might be simple, but some might be a lot more complex, and the cost of making these changes may outweigh any direct drug cost savings.”
A Case in Point: Infliximab
Dr. Hovey used a hypothetical example of infliximab use to illustrate how the above considerations can factor into the decision to switch to a biosimilar. In the pediatric population, both the originator biologic (Remicade, Janssen) and its biosimilars are approved for use in pediatric patients ages 6 years and older with inflammatory bowel disease (IBD). Although the agent is commonly used off-label for juvenile idiopathic arthritis, Kawasaki disease and Behcet’s disease, as well as several other conditions, because there are no differences in approved indications between the reference product and its biosimilars, an institution’s on- and off-label use of infliximab should not affect the decision to implement a biosimilar.
Originator infliximab and all three biosimilars are dispensed operationally as IV piggybacks in the inpatient setting, and all are available in the same format and formulation, with the same dilution, storage and stability requirements. If there is only one order set for infliximab, as Dr. Hovey said is the case at some institutions, it would be logistically straightforward to implement a biosimilar switch.
“In this case, because there aren’t many operational changes to make within the pharmacy, it might make sense to simply switch to the cheapest biosimilar available,” she said.
Another strategy is to look at the data. The literature, albeit limited, suggests that pediatric patients can fare well on both originator and biosimilar versions of biologic medications. One study included 384 patients with juvenile idiopathic arthritis who were started on the originator version of etanercept and 55 on a biosimilar version of the medication. Another 57 patients switched to the biosimilar during the course of therapy.
A significant decrease or a stable remission of disease activity was observed in both patient groups, according to the researchers (ACR Open Rheumatol 2021;3[11]:779-787). The safety profiles were comparable, and the frequencies and types of adverse events (AEs) and serious AEs were similar in patients starting therapy with the originator or a biosimilar. Only injection site reactions occurred slightly more frequently with biosimilar therapy, without having an impact on therapy adherence. In patients who switched therapy, the AE rate per 100 patient-years was comparable before (26.4) and after (32.1) the switch.
Patient Outreach
Once a decision on a biologic or biosimilar is made, pharmacists and providers should put aside time to speak with patients set to undergo a switch, according to Shubha Bhat, PharmD, an IBD clinical pharmacy specialist in the Digestive Disease and Surgery Institute at Cleveland Clinic, and Jacob Kurowski, MD, the medical director of pediatric IBD at Cleveland Clinic Children’s.
“Suggesting a switch to another medication, albeit with the same mechanism of action, can be anxiety-provoking for patients and their families, so it’s very important to educate them about biosimilars and reassure them of equivalent efficacy,” Drs. Bhat and Kurowski, who were not involved in the ACCP presentation, said in a joint email interview. “This can prevent a nocebo effect, which is when the perception that a medication is inferior potentially leads to worse outcomes.”
Ensuring Insurance Coverage
Managing insurer issues for pediatric patients can be an ongoing logistical hurdle, they said, noting that although many payors now include biosimilars on their formulary, it can take time to identify the specific biosimilar included, leading to potential delays in treatment.
“In addition, if a parent moves between employers and the biosimilar needs to change based on the new payor’s formulary, the patient might need to undergo multiple switches, which we do not have supporting data for in the pediatric population,” they said.
Drs. Bhat and Kurowski said they regularly appeal to insurers to keep patients on the same biosimilar, but those appeals are frequently denied and they reluctantly proceed with a switch. “In these cases, we closely monitor the patient to ensure medication efficacy and safety is not compromised despite multiple switching.”
The sources reported no relevant fi nancial disclosures.
HIV Rx Safety ARTists
continued from page 1
practice at Nova Southeastern University, in Fort Lauderdale, Fla., who helped launch her own institution’s program.
Inpatient medication errors related to ART or opportunistic infection (OI) treatments occur in up to 72% of hospitalized patients with HIV (Open Forum Infect Dis 2020;7[8]:ofaa073), making medication monitoring imperative in this population, Amber Ladak, PharmD, an HIV pharmacist in the Division of Infectious Disease at the Medical College of Georgia at Augusta University, said during a session on ARVSPs at the 2021 annual meeting of the American College of Clinical Pharmacy (ACCP).
“Hospitalized patients with HIV require careful medication review and management, both because of their complex antiretroviral regimens and because they are receiving increasingly more medications for non-HIV comorbidities,” Dr. Ladak said.
Part of the reason the error rate is so high is that many hospital physicians do not have expertise in HIV treatment and can make mistakes when initiating or modifying complex HIV regimens, Dr. Ladak said. “There are just so many different combinations of antiretrovirals that it’s quite easy for physicians to start a regimen without a booster, for example, or to prescribe a regimen that doesn’t match the patient’s outpatient treatment,” she explained.
The good news is that pharmacists can help reduce these errors by implementing simple ARVSP interventions. For example, adding clear instructions in computerized physician order entry (CPOE) systems can guide accurate dosing and prompt physicians to double-check the regimen they are prescribing, Dr. Ladak said.
Another low-cost measure that Dr. Ladak and her colleagues have found helpful in mitigating errors for ART orders has been to add brand names alongside single-tablet multidrug treatments in their CPOE system. “If someone is ordering quickly and looking only at the first couple of drugs of a regimen, they can easily confuse it for another regimen,” she said.
Reducing Mix-Ups
Although Dr. Ladak did not share details on the effectiveness of adding brand names to the CPOE system at her institution, she said it has reduced the number of mix-ups between ART treatments that share some of the same components. She also cited data showing CPOE-based tools such as this have reduced inpatient ART-related errors by more than 40% (Clin Infect Dis 2020;70[11]:2241-2246).
Other stewardship tools pharmacists can use include HIV-specific clinical checklists, Dr. Ladak said. Checklists can augment medication reviews at the time of admission and discharge and can be tailored to the specific institution. Common components in use by Dr. Ladak and her colleagues, and described in a 2020 study she co-authored, include patients’ outpatient and inpatient ART and non-ART medications, drug allergies, interactions with non-ART drugs, OI prophylaxis and a review of their most recent HIV viral loads, to verify treatment efficacy (J Int Assoc Provid AIDS Care 2020;19:2325958219898457).
In a separate study examining the impact of an ARVSP with a strong emphasis on medication reviews, investigators found that 17% of patients admitted with HIV had medication errors
prior to an ARVSP (Open Forum Infect
D Dis 2020;7[8]:ofaa073). These included omissions of OI treatment or ART, drug–drug interactions and incorrect therapy. After the program’s implementation, the error rate dropped to 6%, all errors were resolved prior to discharge and the 30-day all-cause readmission rate fell from 27% to 12% (P=0.03). To ensure they don’t miss any opportunity to conduct a thorough medication review and use their checklist, Dr. Ladak said she and her colleagues have set their electronic health record (EHR) to generate a daily list of patients admitted with HIV. They use the checklist at the time of admission and discharge, when they also educate patients on any new medications, document changes to their treatment regimens and contact patients’ outpatient providers to notify them of these changes.
Errors Slashed at Nova Southeastern University
Reviewing thrice-weekly EHRgenerated reports of inpatients receiving an ARV has had a profound effect on medication error rates at Nova Southeastern University, noted Dr. Sherman, who served as one of four pharmacists in the nation selected to author the ASHP Guidelines on Pharmacist Involvement in HIV Care (bit. ly/3vEb2kR). Her team implemented their ARVSP in January 2020 and found that the program significantly reduced the number of uncorrected ART errors. Six months before rollout, the error rate was 64% versus 31% six months after implementation (P<0.05) (J Am Pharm Assoc 2022;62[1]:264-269). Moreover, the proportion of patients with at least one medication error fell from 55.5% to 32.6%, reported Dr. Sherman, who was not part of the ACCP session.
Taking It Slow
Institutions interested in launching their own ARVSP can set themselves up for success by implementing the program gradually, Dr. Ladak advised. “Perform a baseline evaluation and identify areas with the greatest need, whether that’s improving medication reviews at the time of admission or
educating physicians,” she said. “Focus on one or two stewardship activities first, do them well and then add more activities as needed.”
It is also important to designate a program lead with expertise in HIV or other infectious diseases who can provide oversight, assume responsibility for the ARVSP, spearhead the development of policies and review the program’s results after implementation, Dr. Ladak said. In addition, one of the most important steps the ARVSP program lead can take is to provide prescriber education, she said.
“Sharing ART pearls, educating prescribers about the most common prescribing errors and drug interactions, and providing regular updates on available treatments can go a long way,” Dr. Ladak said.
Dr. Sherman echoed this sentiment, urging institutions that may not have the resources to implement a full ARVSP to focus on education as one way of improving ART use in hospitals. “Educating healthcare staff about clinical pearls and using medication errors as learning lessons, or even just having a dedicated person the staff can call with questions about ARV regimens, can be very helpful in preventing ARV medication errors.”
Table. ARVSP Initiatives
Clinical checklist—ART-specific medication review
• Conducted by HIV/ID specialist • What is patient’s most recent outpatient regimen?
Order entry
• Guided ordering instructions • Removal/alert of outdated ARV/inappropriate doses • Including brand names for combination products. Example: emtricitabine/ tenofovir disoproxil fumarate versus emtricitabine/tenofovir alafenamide
Leveraging EHR capabilities
• Generating patient lists of admitted people with HIV • Notification of ARV orders
Formulary management
• Ensure most commonly used products available • Restriction of ARV prescribing to ID team
Education
• Common ART pearls (incomplete regimens, drug interactions) • Who to reach for questions/consults
ARV, antiretroviral; ARVSP, antiretroviral stewardship program; EHR, electronic health record; ID, infectious disease Source: Amber Ladak, PharmD, based on material presented at the 2021 annual meeting of the American College of Clinical Pharmacy. ‘Hospitalized patients with HIV require careful medication review and management, both because of their complex antiretroviral regimens and because they are receiving increasingly more medications for non-HIV comorbidities.’
—Elizabeth Sherman, PharmD
