Characterization of a Real-World Response Variable and Comparison with RECIST-Based Response Rates from Clinical Trials in Advanced NSCLC.

INTRODUCTION: Effectiveness metrics for real-word research, analogous to clinical trial ones, are needed. This study aimed to develop a real-world response (rwR) variable applicable to solid tumors and to evaluate its clinical relevance and meaningfulness. METHODS: This retrospective study used patient cohorts with advanced non-small cell lung cancer from a nationwide, de-identified electronic health record (EHR)-derived database. Disease burden information abstracted manually was classified into response categories anchored to discrete therapy lines (per patient-line). In part 1, we quantified the feasibility and reliability of data capture, and estimated the association between rwR status and real-world progression-free survival (rwPFS) and real-world overall survival (rwOS). In part 2, we investigated the correlation between published clinical trial overall response rates (ORRs) and real-world response rates (rwRRs) from corresponding real-world patient cohorts. RESULTS: In part 1, 85.4% of patients (N = 3248) had at least one radiographic assessment documented. Median abstraction time per patient-line was 15.0 min (IQR 7.8-28.1). Inter-abstractor agreement on presence/absence of at least one assessment was 0.94 (95% CI 0.92-0.96; n = 503 patient-lines abstracted in duplicate); inter-abstractor agreement on best confirmed response category was 0.82 (95% CI 0.78-0.86; n = 384 with at least one captured assessment). Confirmed responders at a 3-month landmark showed significantly lower risk of death and progression in rwOS and rwPFS analyses across all line settings. In part 2, rwRRs (from 12 rw cohorts) showed a high correlation with trial ORRs (Spearman's ρ = 0.99). CONCLUSIONS: We developed a rwR variable generated from clinician assessments documented in EHRs following radiographic evaluations. This variable provides clinically meaningful information and may provide a real-world measure of treatment effectiveness.

Evaluating probe techniques and a situated theory of situation awareness.

Probe techniques for measuring situation awareness (SA) vary in whether scenarios are paused and displays visible while questions are presented. We examined which technique is least intrusive on workload and performance in air traffic control, and which is most sensitive at capturing differences in SA when automation varies. We also tested predictions from the situated SA theory, which holds that operators offload specific and low-priority information onto displays to limit internal processing. To accomplish these goals, Experiments 1 and 2 manipulated whether radar displays were visible and scenarios paused during queries. Experiment 2 also manipulated the amount of automation by varying the percentage of aircraft equipped with NextGen tools. We found all probe techniques were equally sensitive at capturing SA differences for different levels of equipage, but those that paused scenarios were least intrusive. Moreover, consistent with situated SA, blanking displays impaired ability to answer questions about specific but not general information. Experiment 3 recorded eye gaze frequency and duration during queries when scenarios were visible and not paused and, as predicted by situated SA, found participants were more likely to look at radar displays while answering specific and low-priority questions than general and high-priority questions. (PsycINFO Database Record

Acute postnatal exposure to the pentaBDE commercial mixture DE-71 at 5 or 15 mg/kg/day does not produce learning or attention deficits in rats.

Polybrominated diphenyl ethers (PBDEs), flame retardant chemicals added to polymer products, have become ubiquitous in the environment, and they are bioaccumulating in humans and wildlife. Therefore, understanding their biological effects is important for public health. We have previously observed learning deficits in rats exposed to DE-71, a commercial PBDE mixture consisting primarily of pentabrominated diphenyl ethers, at a dose of 30 mg/kg/day from postnatal day (PND) 6 to 12. The purpose of the current study was to determine if this effect could be seen with lower doses of DE-71. Long-Evans rats were administered daily oral doses of corn oil alone or DE-71, 5 or 15 mg/kg/day, dissolved in corn oil, from PND 6 to 12. As young adults, the rats were administered a series of five-choice visual learning and attention tasks. No effects of DE-71 were found on learning, attention, or inhibitory control. Given that developmental DE-71 exposure at similar doses and for shorter time periods has been shown in other laboratories to affect locomotion and hyperactivity, the current results suggest that cognitive functions may not be as sensitive as neuromotor functions to the effects of acute DE-71 exposure.