Time and Personnel Costs Associated with Adverse Event (AE) Management Among Patients with Chronic Lymphocytic Leukemia (CLL) Treated with Acalabrutinib, Ibrutinib, or Venetoclax
Authors: Patel Hetalkumari , Wahlstrom Svea K. , DerSarkissian Maral , Kunzweiler Colin , Castriota Felicia , Chang Rose , Cheung Hoi Ching , Gu Yuqian , Guo Helen , Duh Mei Sheng , Ryan Kellie J. 
Published: November 2021

Abstract
Introduction
Guidelines recommend chemoimmunotherapy and novel agents such as Bruton's tyrosine kinase inhibitors and B-cell lymphoma 2 inhibitors for the treatment of CLL. AE profiles differ across therapies, and management of AEs in patients with CLL treated with novel agents incurs burden on healthcare professionals (HCPs) and oncology practices. Time and personnel costs associated with AE management are not well understood for patients with CLL and are overlooked while assessing the value of oncology drugs. To assess practice burden, this study quantified HCP time and personnel costs related to AE management for patients with CLL who received a novel agent, either acalabrutinib, ibrutinib, or venetoclax.
Methods
HCPs (i.e., oncologists, pharmacists, physician assistants, nurse practitioners, and registered nurses) who actively treated ≥5 patients with CLL during the past year with &gt;1 patient receiving acalabrutinib, ibrutinib, or venetoclax in the past month were recruited through a physician panel vendor to participate in a longitudinal, observational, prospective survey. This study was conducted in two phases (November 2020-January 2021; April-June 2021). Over the 2-month data collection period, HCPs reported on a daily basis the time spent performing AE management activities for CLL patients receiving a novel agent, which included 1) interactions with patients in-person or via remote consultation (telephone, video, or email), 2) interactions with other HCPs, and 3) other management activities that did not include interactions with patients or other HCPs (e.g., recording notes in patient's charts, ordering lab tests). Mean time and personnel costs per AE management activity were summarized using descriptive statistics. Personnel costs (USD) were calculated by multiplying median wage information reported by the ureau of Labor Statistics Occupational Employment Statistics survey by HCP-reported time spent managing AEs.
Results
Among 49 HCPs enrolled in the survey, 36 (73%; Table 1) reported managing ≥1 AE during a total of 1,106 AE management activities (229 for acalabrutinib; 500 for ibrutinib; 377 for venetoclax) for 421 patients with CLL during the 2-month study period. Among all patients, 108 (26%), 186 (44%), and 129 (31%) received acalabrutinib, ibrutinib, or venetoclax in any line, respectively (Table 2). Anemia was the most frequently managed AE reported among all patients (19%), but differed by treatment: 11%, 19%, and 26% for patients treated with acalabrutinib, ibrutinib, and venetoclax, respectively (Table 2). Other AEs reported among ≥10% of patients with a reported AE management activity also differed by treatment. For acalabrutinib, this included only headache. For both ibrutinib and venetoclax patients, thrombocytopenia, diarrhea, and myalgia were managed in ≥10% of patients. For venetoclax patients, back pain and arthralgia were also managed in ≥10% of patients. Mean (standard deviation [SD]) time spent managing AEs per activity was 11.8 (7.7) minutes (min) overall, 12.1 (7.4) min for acalabrutinib, 11.6 (6.9) min for ibrutinib, and 11.8 (8.9) min for venetoclax (Table 3). Mean time per AE management activity was numerically similar across the three treatments overall and stratified by type of HCP, treatment duration, and line of therapy. We noted differences in the type of HCP managing AEs by treatment, with a lower proportion of oncologists managing acalabrutinib AEs compared to the other two therapies. Corresponding mean (SD) personnel costs per AE management activity were $16.0 ($10.6) overall, and $14.4 ($9.8) for acalabrutinib, $16.3 ($9.8) for ibrutinib, and $16.7 ($11.9) for venetoclax.
Conclusions
This study demonstrates the importance of accounting for time and labor costs related to AE management, as results suggest that the burden to HCPs related to AE management for patients with CLL treated with acalabrutinib, ibrutinib, and venetoclax is substantial. During the 2-month study period, almost three-quarters of HCPs reported managing ≥1 AEs and an average of 12 AE management days was observed across these HCPs. While mean time and personnel costs were similar, differences in types of AE and types of HCPs managing AEs were observed across treatments. Future research should confirm our observed differences in types of AE and types of HCPs managing AEs by treatment to comprehensively assess the burden of managing AEs for patients with CLL.
Figure 1 Figure 1.

Disclosures
Wahlstrom: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. DerSarkissian: Analysis Group, Inc.: Current Employment. Kunzweiler: Apellis: Other: Employee of Analysis Group, Inc., Research Funding. Castriota: Analysis Group, Inc.: Ended employment in the past 24 months. Chang: Analysis Group, Inc.: Current Employment. Cheung: Analysis Group, Inc.: Ended employment in the past 24 months. Gu: Analysis Group, Inc.: Current Employment. Guo: Analysis Group, Inc.: Current Employment. Duh: Novartis: Other: I am an employee of Analysis Group, a consulting company that received funding from Novartis for this research study.. Ryan: AstraZeneca: Current Employment, Current equity holder in publicly-traded company.