key: cord-0721895-5ioq2uzl authors: Lambrou, A. S.; Redd, J. T.; Stewart, M. A.; Rainwater-Lovett, K.; Thornhill, J. K.; Hayes, L.; Smith, G.; Thorp, G. M.; Tomaszewski, C.; Edward, A.; Elias Calles, N.; Amox, M.; Merta, S.; Pfundt, T.; Callahan, V.; Tewell, A.; Scharf-Bell, H.; Imbriale, S.; Freeman, J. D.; Anderson, M.; Kadlec, R. P. title: Implementation of SARS-CoV-2 monoclonal antibody infusion sites at three medical centers in the United States: Strengths and challenges assessment to inform COVID-19 pandemic and future public health emergency use date: 2021-04-06 journal: nan DOI: 10.1101/2021.04.05.21254707 sha: 98feb2a00d40e64ba4fcf1d80effdc967992af4e doc_id: 721895 cord_uid: 5ioq2uzl Background: The COVID-19 pandemic caught the globe unprepared without targeted medical countermeasures, such as therapeutics, to target the emerging SARS-CoV-2 virus. However, in recent months multiple monoclonal antibody therapeutics to treat COVID-19 have been authorized by the U.S. Food and Drug Administration (FDA) under Emergency Use Authorization (EUA). Despite these authorizations and promising clinical trial efficacy results, monoclonal antibody therapies are currently underutilized as a treatment for COVID-19 across the U.S. Many barriers exist when deploying a new infused therapeutic during an ongoing pandemic with limited resources and staffing, and it is critical to better understand the process and site requirements of incorporating monoclonal antibody infusions into pandemic response activities. Methods: We examined the monoclonal antibody infusion site process components, resources, and requirements during the COVID-19 pandemic using data from three initial infusion sites at medical centers in the U.S. supported by the National Disaster Medical System. A descriptive analysis was conducted using process assessment metrics to inform recommendations to strengthen monoclonal antibody infusion site implementation. Results: The monoclonal antibody infusion sites varied in physical environment and staffing models due to state polices, infection control mechanisms, and underlying medical system structure, but exhibited a common process workflow. Sites operationalized an infusion process staffing model with at least two nurses per ten infusion patients. Monoclonal antibody implementation success factors included tailoring the infusion process to the patient community, strong engagement with local medical providers, batch preparing the therapy before patient arrival, placing the infusion center in proximity to emergency services, and creating procedures resilient to EUA changes. Infusion process challenges stemmed from confirming patient SARS-CoV-2 positivity, strained staff, scheduling needs, and coordination with the pharmacy for therapy preparation. Conclusions: Infusion site processes are most effective when integrated into the pre-existing pandemic response ecosystems and can be implemented with limited staff and physical resources. As the pandemic and policy tools such as EUAs evolve, monoclonal antibody infusion processes must also remain adaptable, as practice changes directly affect resources, staffing, timing, and workflows. Future use may be aided by incorporating innovative emergency deployment techniques, such as vehicle and home-based therapy administration, and by developing drug delivery mechanisms that alleviate the need for observed intravenous infusions by medically-accredited staff. Data were collected from three medical centers in the United States (U.S.), El Centro Regional Medical and all three medical sites also deemed this work non-human subjects research exempt from institution CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. ; https://doi.org/10.1101/2021.04.05.21254707 doi: medRxiv preprint Data were collected through three mechanisms to inform the monoclonal antibody infusion process 146 assessment, model, and recommendations: 1) key informant interviews, 2) onsite observations, and 3) 147 infusion records. A process assessment framework informed the seven key metrics on which data were 148 collected to ensure standard data collection at each site ( Figure 1 ): logistics, timing, staffing, physical 149 environment, resources, monitoring and resilience, and engagement (SI Table 2 ). The seven framework Timing Engagement Staffing Resources Physical Environment Community engagement, patient identification, timing, resources, processes and procedures Implementation Challenges Implementation Strengths . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. ; https://doi.org/10.1101/2021.04.05.21254707 doi: medRxiv preprint process workflow. Each step in the infusion process was timed for multiple patients and the staff, 169 resources, and information needed for the step were recorded. The onsite observations also facilitated 170 validating data from the key informant interviews. Descriptive analysis of the monoclonal antibody infusion process was conducted to examine the timing, examined from patient engagement through the infusion appointment and discharge from the infusion 176 site. The physical environment of each infusion site was also mapped to analyze resource and 177 implementation needs for this new therapy option. Data on each process metric from the process 178 assessment framework was synthesized and compiled for each site. A descriptive analysis of three medical center monoclonal antibody infusion sites was conducted using a 183 process assessment to inform recommendations to strengthen infusion site implementation during 184 current pandemic response efforts. This investigation evaluated the process of monoclonal antibody 185 infusion and staffing equipment, physical space, and resource requirements during the COVID-19 186 pandemic. A general monoclonal antibody infusion site workflow process (Figure 2 ) was developed to 187 integrate the data from the three data collection sites. It is important to note that there was not a single 188 standard monoclonal antibody infusion site process workflow. Each site exhibited common process 189 components, staffing models, and resources, yet adapted the system to address local policies, patient 190 populations, and medical center characteristics. An effective monoclonal antibody infusion site 191 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 6, 2021. The sites exhibited two major medical center mechanisms of implementing a monoclonal 208 antibody infusion site: 1) an outpatient infusion clinic model, and 2) an Emergency Department (ED) 209 medication visit model (Table 1) . Site 1 employed a model tied to ED operations, while Sites 2 and 3 210 operated as outpatient infusion sites co-located with a medical center. The infusion sites also presented 211 two appointment types: 24/7 walk-up and scheduled appointments during business hours. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 6, 2021. timing. Scheduling-based infusion site pharmacies were equipped with data to enable pre-preparation 237 of monoclonal antibody doses in batches before patients arrive. The three infusion sites emphasized 238 that coordination with the pharmacy is difficult due to physical proximity and the need to conserve any 239 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 6, 2021. prepared doses. Monoclonal antibody infusion process workflows were strongly shaped by EUA 240 requirements regarding drug preparation, storage, timing, and delivery. Monday-Friday • 9:00am-5:00pm . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. ; https://doi.org/10.1101/2021.04.05.21254707 doi: medRxiv preprint Similar to the infusion process components, the infusion site staffing metrics varied between sites. The 248 different staffing models relied on the same underlying requirements to ensure monoclonal antibody 249 referral, prescription, preparation, and administration (Table 2) . Staffing models differed due to state Informed by initial implementation experience, sites recommended developing a process workflow split 257 into two staffing components with one RN completing pre-infusion and intake processes such as patient 258 initial vitals, data collection, and consent. All sites also recommended integrating paramedics, to start 259 IVs and monitor patients, into the staffing model to alleviate stress on constrained medical center 260 nursing staff. One site leveraged a local medical volunteer organization to support staffing the infusion 261 site during the ongoing pandemic to reduce stress on the medical center's pandemic response staffing. Each of the three sites also strongly recommended initiating a multidisciplinary staffing meeting 263 between the medical center's leadership, pharmacy, infection control, ED, nursing, information 264 technology, and security to coordinate the implementation process and medical center staffing 265 allocation. These representatives were not needed for the day-to-day operations of the monoclonal 266 antibody infusion site, but their expertise and support were for developing the initial workflow and 267 staffing models at the three sites. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. ; https://doi.org/10.1101/2021.04.05.21254707 doi: medRxiv preprint This building was only being used by monoclonal antibody patients and the therapy was transferred by a 284 driving courier from the pharmacy in the main medical center campus to the site. The sites differed in the total number of patients who could be infused at one point in time. While the indoor site allocated six rooms for infusion, the two tent sites had 10 and 30 infusion chairs. Medical and technological infusion site resources were needed to perform the infusion process, record 288 patient data, and ensure an infection-controlled environment. The resources did not vary greatly 289 between the three infusion sites; however, some sites improved the overall monoclonal antibody 290 infusion process by using a mobile, miniature refrigeration unit to store batches of the monoclonal 291 antibody and scanners to rapidly send prescription and paperwork (Table 3 ). The temporary tent sites 292 required more infrastructure resources such as electricity sources, power strips, lights, HVAC systems, 293 and generators to remain self-sufficient while adjacent to the medical center. At the current stage in the 294 pandemic, the three infusion sites did not report any supply chain barriers related to the physical 295 environment and infusion-related resources. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. ; https://doi.org/10.1101/2021.04.05.21254707 doi: medRxiv preprint In these three Assistant Secretary for Preparedness and Response-supported monoclonal antibody infusion sites, our primary finding was that existing processes do not need to be reinvented to the therapy to be prepared at bedside and this preparation mechanism may be more effective at refrigerator. Scheduling monoclonal antibody infusion appointments was time-and staff-intensive; 391 however, scheduling enabled more efficient workflows and monoclonal antibody preparation. Confirming patient test positivity and scheduling individuals within 10 days of their symptom 393 onset was another barrier to optimal monoclonal antibody infusions. Rigorous and timely testing and is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. ; https://doi.org/10.1101/2021.04.05.21254707 doi: medRxiv preprint The monoclonal antibody infusion site process description and assessment has informed general 413 recommendations for the current implementation and future use of these therapies to tackle public 414 health emergencies (Table 5) CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. ; https://doi.org/10.1101/2021.04.05.21254707 doi: medRxiv preprint subcutaneous delivery. 15 There is evidence that current monoclonal antibody therapies may show reduced neutralization and potential effectiveness against novel SARS-CoV-2 virus variants to which the 437 drugs were not optimized. 16 However, a strength of monoclonal antibodies is rooted in their adaptability 438 and rapid production. Monoclonal antibody therapies can act as a platform biologic that can be updated 439 as emerging infectious diseases evolve and evade targeting. Integrate into existing health system processes such existing outpatient infusion processes and ED/Urgent Care med visits . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 6, 2021. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 6, 2021. ; https://doi.org/10.1101/2021.04.05.21254707 doi: medRxiv preprint Antibodies for Prevention and 3. FDA. Drug and Biological Therapeutic Products SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19 REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-494 19 Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab Real-world Effect of Monoclonal Antibody Treatment in COVID-19 Impact of monoclonal antibody treatment on hospitalization and mortality 501 among non-hospitalized adults with SARS-CoV-2 infection Real-World Effectiveness and Tolerability of Monoclonal Antibodies for Expanded Access Programs, compassionate drug use AAMC Discusses Monoclonal Antibody Therapeutics for SARS-CoV-2 Infection Pandemic 514 Preparedness: Developing Vaccines and Therapeutic Antibodies For COVID-19 The Equitable Distribution of COVID-19 Therapeutics 517 and Vaccines Fruitful Neutralizing Antibody Pipeline Brings Hope To Defeat SARS-Cov-2 Emerging SARS-CoV-2 variants reduce neutralization sensitivity to convalescent sera The authors acknowledge the significant efforts of the members of the Disaster Medical Assistance 461 Teams (DMAT) who coordinated the monoclonal antibody infusion site set-up, initiation, and integration