key: cord-1024250-1tjmftst authors: Woltemate, Thomas J.; Wadas, Richard J.; McCreary, Erin K.; Bariola, Ryan; Minnier, Tami; Marroquin, Oscar C.; Schmidhofer, Mark; Albin, Debbie; Angus, Derek C.; Yealy, Donald M. title: Emergency department implementation of monoclonal antibody infusion for the treatment of coronavirus disease 2019: A template for rapid deployment date: 2021-09-17 journal: J Am Coll Emerg Physicians Open DOI: 10.1002/emp2.12550 sha: f945e078e00eccdec015ec912c1c434c8394cb13 doc_id: 1024250 cord_uid: 1tjmftst Monoclonal antibody (mAb) therapy can improve coronavirus disease 2019 outcomes when infused early in select patients. We sought to rapidly create and implement a program for emergency department (ED) mAb infusion to aid care. Using multiple strategies and actions—education, selection criteria, screening tools, rapid testing, compounding, and delivery—we infused 832 ED patients with a mAb. The screening tool identified 94.5% of these patients as potential candidates. Length of stay was nearly identical for patients who tested positive for coronavirus disease 2019 versus those requiring testing. Mild adverse reactions occurred in 2.3% of mAb infusions, and severe reactions occurred in 0.5% of infusions. We highlight a strategic approach for using the ED as a key coronavirus disease 2019 therapeutic site for this intervention and with high utility and low disruption. In late 2020, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the first monoclonal antibody (mAb) therapy available to patients with mild to moderate infections with the severe acute respiratory syndrome coronavirus 2 virus. Bariola et al 1 demonstrated that mAb therapy administered within 10 days of coronavirus disease 2019 symptom onset in patients with mild to moderate coronavirus disease 2019 improved outcomes at 28 days. The authors observed a 60% reduction in hospitalizations and deaths in patients treated with the singular mAb bamlanivimab compared with untreated patients. 1 The authors also noted that earlier therapy (within 4 days of symptom onset) may be more beneficial compared with mAb therapy later in the disease course (ie, 5-10 days after symptom onset). 1 Since that first mAb, newer mAb combinations (2 antibody prepara- demonstrate the efficacy of mAb therapy on hospitalization and mortality rates. Given these options and the public health benefit of therapy, expanding easy access to mAb infusions is important for public health. 3 We describe our experience with the implementation of an emergency department (ED)-based mAb infusion program across the 28 EDs in our 40-hospital health system. The University of Pittsburgh Medical Center (UPMC) is a large, inte- Developing a process for ED mAb therapy for the treatment of coronavirus disease 2019 involved many challenges-it required ED physician or APP, nurses, pharmacists, and leadership to quickly adopt an unfamiliar therapy for the treatment of an unfamiliar disease-and multiple potential barriers existed to initiating this therapy in the ED. First, mAbs are not currently a class of drug typically administered in the ED. This means that ED physician or APP lacked familiarity with this treatment option, notably the indications, exclusions, and adverse effects. Second, the logistics of ordering, compounding, and infusing a drug only available through an EUA in the ED is a new challenge. This task started with a glaring, but basic, gap-no preexisting mAb ordering process using the electronic health record (EHR) existed. Third, nursing staff also lacked familiarity with mAb infusions. Finally, concerns regarding competing priorities and potential increased ED length of stay (LOS) attributed to testing and infusion time were commonly cited as potential barriers to implementation. We share our approach to addressing these barriers and we share the steps taken to rapidly develop, implement, and grow a mAb infusion program for in-ED care, recognizing the need for prompt action to address the pandemic and to meet our goals of care and learning. F I G U R E 1 Flowchart depicting the workflow for ED mAb infusions from patient presentation to time of infusion. For clarification, MyApps is the UPMC homepage for accessing health care related applications (EHR for ED physician or APP, nursing, pharmacy, intranet, digital libraries). COVID-19, coronavirus disease 2019; ED, emergency department; EHR, electronic health record; mAb, monoclonal antibody; SARS Cov-2, severe acute respiratory syndrome coronavirus 2; UPMC, University of Pittsburgh Medical Center We describe our strategy for deployment from ED physician or APP and nursing education through screening and testing and, finally, to the infusion specifics. This process began with a multifaceted approach to educating ED physician or APP, leadership, and nursing staff. We collaboratedwith information technology specialists to develop appropriate EHR orders and ordersets as well as a screening tool. Finally, we developed, in conjunction with our pharmacy staff, a protocol for specific mAb formulation assignment and infusion. We summarize the workflow process of ED mAb infusion in Figure 1 and fully detail the process in the next sections. ED physicians, advanced practice PA/NP, and nursing staff lack familiarity with mAb infusions, as these are rarely given in this setting. We deployed multiple communication strategies to raise awareness and educate all staff. We targeted education detailing the EUA clinical criteria for eligibility, the common features of those who did not qualify, and the beneficial impact of therapy, including the most current data on outcomes and any effects of the infusion. We employed both ad hoc and regularly standing meetings with ED leadership and staff, and we added online electronic meeting forums for question-and-answer sessions. This effort required intense and prompt action-in days, not weeksand a dedicated multidisciplinary team of messengers and experts. As an ancillary tool, we update our system intranet page (called Infonet)the repository for all coronavirus disease 2019 policy and advice-daily with the latest information, education, and frequently asked questions. We promoted this site as the definitive, easy-access resource for staff that would allow an asynchronous and "just-in-time" place for staff seeking insights. We also sent individual emails from key leaders with harmonized content to all ED staff. Finally, ED leaders met with all staff to educate and respond to any concerns. We recognized the importance of timely identification of potential mAb candidates as vital to expediting testing and infusions while maintaining ED throughput. As part of the implementation process of our ED mAb infusion program, we implemented a series of screening questions as part of the patient intake on ED arrival. The goal is to identify potential mAb candidates from the onset of their visit to expedite their testing and treatment. This also serves as a reminder to ED physician or APP to consider mAb therapy for these patients. We created an icon adjacent to the patient's name on the computer-based ED tracking board that denotes a positive screen. The screening form triggering the icon is a series of 4 questions ( Figure 2 ) using a preexisting 30day interval, deployed for many threats and clinically relevant in coronavirus disease 2019. A "yes" reply to any of the first 3 questions triggers a positive screen. A "yes" to the fourth question about international travel triggers a follow-up question and, depending on the country of travel, will flag the screen as positive or negative. The travel screen is regularly updated. We did not implement nursing-driven testing protocols and allow the ED physician or APP to determine the need for testing. A positive screen is not a requisite for testing, and an ED physician or APP can test patients with atypical symptoms (eg, gastrointestinal symptoms) or a negative screen for whom the ED physician or APP holds a suspicion of coronavirus disease 2019. In the early 2020 months of the pandemic, the supply of rapid and reliable PCR testing for severe acute respiratory syndrome coronavirus 2 limited ED testing to those patients with more severe symptoms and who usually required higher levels of inpatient care. By the time of the first EUA for severe acute respiratory syndrome coronavirus 2-targeted mAb in November 2020, rapid PCR testing availability increased. By January 2021, system-wide demand for PCR testing declined, allowing PCR testing capabilities with a 1-hour turnaround time in our EDs. Given the use of nasopharyngeal sampling for other respiratory pathogens in the ED, adding this capability was not a challenge or unfamiliar to our teams. The EUA specifies eligibility criteria for patients to receive mAb therapy, starting with a known positive severe acute respiratory syndrome coronavirus 2 test (either obtained in the ED or from an outside facility), mild to moderate symptoms for ≤10 days, and A challenge with the EUA inclusion and exclusion criteria is that it is regularly revised and updated as more data and research become available. We used the UPMC Infonet (see section 2.1) and orderset updates to keep ED physician or APP abreast of the most up-to-date criteria and recommendations. Given the novelty of the coronavirus disease 2019 virus, our EHR lacked the orders needed for rapid testing and specimen prioritization as well as for the appropriate precautions these patients require. Therefore, we created ordersets using a multidisciplinary team of physicians, pharmacists, programmers, quality improvement specialists, and representatives from coding/billing. Two ordersets were integral to the process. The "ED Suspected COVID" orderset clearly identified patients under investigation to every other ED physician or APP involved in their care, from registration staff to all ancillary services. The "ED COVID Testing" orderset included a specific mAb subphase with the eligibility criteria within the order; the use of this orderset prioritized specimen collection and testing for the laboratory. Unlike many other medications dispensed in the ED, mAb infusions require compounding before delivery. All drug preparation occurs in a hospital pharmacy to minimize risk of errors and comply with compounding standards. We ensured prioritization of compounding and delivery by having a designated pharmacy professional assume responsibility for all requests. We targeted infusion times of ≤31 minutes depending on mAb product, allowing for better efficiency and less impact on overall ED care capabilities and throughput. We also monitored ED length of stay (LOS) and set a priori comparisons with other common ED evaluations and treatment times, such as abdominal pain or migraine headache. A unique challenge that arose with ED mAb infusion involved developing a method of assigning a mAb product to a patient that ensured efficient delivery and supply chain management, especially given that 2 Finally, our process allows for quick and efficient for adoption of new mAb drug combinations of the same class as they become available and as the landscape of the pandemic shifts, for example, the delta variant. Patients We learned that rapid action is possible, but it requires intense organization, strict schedules, and prompt evaluation/reevaluation/"honing as needed" actions. This contrasts with the much slower traditional approaches. We also learned that an intense effort had clear uptakebenefits when done as planned. This meant that our teams rapidly began using the training and tools, and the short feedback cycles helped us gain a quick foothold in care. We also learned that structured observations to inform care was possible with this frameworkand in the ED. The size and preexisting infrastructure of our health system allowed us to use our already robust network of EDs, ED staff, pharmacists, and our supply chain to implement this therapy. In addition, the ability to centralize and standardize the ED mAb program over our health system and the large catchment area it serves proved crucial to successful implementation and afforded us the ability to implement on a large scale. To our knowledge, no other health system is delivering ED mAbs on this scale. Although the coronavirus disease 2019 pandemic is unique, the lessons may apply to the next infectious threat and any time-sensitive therapy. We "learned by doing," identifying and addressing barriers quickly. Our program can serve as a template for other hospitals and health systems to build their ED approach, and we hope that our experiences, as well as those of others who implement similar programs, can be shared and further entrench the role of EDs in acute care opportunities. We share our template for rapid ED mAb deployment as part of an effort to deliver this transformative therapy in a timely, structured, patient-centered manner. Our insights can inform future efforts. We conclude that it is possible to act promptly and use the ED as a key coronavirus disease 2019 therapeutic site for this intervention and with high utility and low disruption. This approach may also serve well for future time-sensitive and new ED care opportunities. Impact of monoclonal antibody treatment on hospitalization and mortality among nonhospitalized adults with SARS-CoV-2 infection Bamlanivimab plus etesevimab in mild or moderate covid-19 Establishing a distribution network for COVID-19 monoclonal antibody therapy across a large health system during a global pandemic Optimizing the trade-off between learning and doing in a pandemic Emergency department implementation of monoclonal antibody infusion for the treatment of coronavirus disease 2019: A template for rapid deployment The authors declare no conflict of interest. Thomas J. Woltemate MD https://orcid.org/0000-0002-9640-3220