<p><strong>OBJECTIVE: </strong>Adverse event (AE) reporting is crucial for determining safety of trials. Adverse events are captured manually by clinical research associates (CRAs) and research nurses (RNs), and prior studies show underreporting. It is necessary to understand AE reporting training, processes, and institution-level differences to improve AE capture.</p>

<p><strong>METHODS: </strong>A 26-item questionnaire regarding AE reporting training, identification, tracking, and challenges was distributed to all Children's Oncology Group (COG) CRAs and RNs from February 15 to March 11, 2019, regardless of if they report AEs based on limitations of COG rosters. Results were tabulated. Institutions were grouped by self-reported full-time equivalents and compared using χ2 tests.</p>

<p><strong>RESULTS: </strong>Of 1315 CRAs and 2703 RNs surveyed, 509 (12.7%) responded. Of those, 369 (64.9%) representing 71.8% of COG institutions report AEs. Only data from respondents who report AEs were collected and analyzed. There was a range in AE training; COG training modules were most common (79.7%). There was wide variability in AE ascertainment; only 51.2% use standardized approaches at their site. There was no standard AE tracking method; larger sites more commonly use spreadsheets (P = 0.002) and smaller sites more commonly use paper (P = 0.028). The greatest AE reporting challenges were differences between protocols (70%) and between AE definitions and documentation (53%). Half of the respondents endorsed 6 of 13 proposed tools for improving reporting including online AE reporting modules (75.3%), tip sheets for interpreting Common Terminology Criteria for Adverse Events definitions (67.5%), and standardized AE tracking forms (66.9%). Only half of the respondents reported that all colleagues at their site followed the same AE reporting practices, and there was no dominant AE tracking approach across the respondents.</p>

<p><strong>DISCUSSION: </strong>There is wide variability in AE reporting training and practices. Numerous challenges exist, including differences between trials, challenges in interpreting AE definitions, and engaging clinicians.</p>

<p><strong>CONCLUSIONS: </strong>Respondents are eager for additional central resources. These results provide a roadmap for areas of potential improvement.</p>

<p><strong>Importance: </strong>Bacteremia causes considerable morbidity among children with acute leukemia and those undergoing hematopoietic stem cell transplantation (HSCT). There are limited data on the effect of antibiotic prophylaxis in children.</p>

<p><strong>Objective: </strong>To determine the efficacy and risks of levofloxacin prophylaxis in children receiving intensive chemotherapy for acute leukemia or undergoing HSCT.</p>

<p><strong>Design, Setting, and Participants: </strong>In this multicenter, open-label, randomized trial, patients (6 months-21 years) receiving intensive chemotherapy were enrolled (September 2011-April 2016) in 2 separate groups-acute leukemia, consisting of acute myeloid leukemia or relapsed acute lymphoblastic leukemia, and HSCT recipients-at 76 centers in the United States and Canada, with follow-up completed September 2017.</p>

<p><strong>Interventions: </strong>Patients with acute leukemia were randomized to receive levofloxacin prophylaxis for 2 consecutive cycles of chemotherapy (n = 100) or no prophylaxis (n = 100). Those undergoing HSCT were randomized to receive levofloxacin prophylaxis during 1 HSCT procedure (n = 210) or no prophylaxis (n = 214).</p>

<p><strong>Main Outcomes and Measures: </strong>The primary outcome was the occurrence of bacteremia during 2 chemotherapy cycles (acute leukemia) or 1 transplant procedure (HSCT). Secondary outcomes included fever and neutropenia, severe infection, invasive fungal disease, Clostridium difficile-associated diarrhea, and musculoskeletal toxic effects.</p>

<p><strong>Results: </strong>A total of 624 patients, 200 with acute leukemia (median [interquartile range {IQR}] age, 11 years [6-15 years]; 46% female) and 424 undergoing HSCT (median [IQR] age, 7 years [3-14]; 38% female), were enrolled. Among 195 patients with acute leukemia, the likelihood of bacteremia was significantly lower in the levofloxacin prophylaxis group than in the control group (21.9% vs 43.4%; risk difference, 21.6%; 95% CI, 8.8%-34.4%, P = .001), whereas among 418 patients undergoing HSCT, the risk of bacteremia was not significantly lower in the levofloxacin prophylaxis group (11.0% vs 17.3%; risk difference, 6.3%; 95% CI, 0.3%-13.0%; P = .06). Fever and neutropenia were less common in the levofloxacin group (71.2% vs 82.1%; risk difference, 10.8%; 95% CI, 4.2%-17.5%; P = .002). There were no significant differences in severe infection (3.6% vs 5.9%; risk difference, 2.3%; 95% CI, -1.1% to 5.6%; P = .20), invasive fungal disease (2.9% vs 2.0%; risk difference, -1.0%; 95% CI, -3.4% to 1.5%, P = .41), C difficile-associated diarrhea (2.3% vs 5.2%; risk difference, 2.9%; 95% CI, -0.1% to 5.9%; P = .07), or musculoskeletal toxic effects at 2 months (11.4% vs 16.3%; risk difference, 4.8%; 95% CI, -1.6% to 11.2%; P = .15) or at 12 months (10.1% vs 14.4%; risk difference, 4.3%; 95% CI, -3.4% to 12.0%; P = .28) between the levofloxacin and control groups.</p>

<p><strong>Conclusions and Relevance: </strong>Among children with acute leukemia receiving intensive chemotherapy, receipt of levofloxacin prophylaxis compared with no prophylaxis resulted in a significant reduction in bacteremia. However, there was no significant reduction in bacteremia for levofloxacin prophylaxis among children undergoing HSCT.</p>