Lamp, Sophia J.

Abstract More than half of randomized phase 3 oncology trials fail to meet their primary endpoints, often despite favorable results from phase 1 and phase 2 trials. One potential reason for this high failure rate is effect size selection practices for powering these trials. In a systematic review of phase 3 oncology trials published in 10 top medical journals in 2023, we identified a pattern of effect size overestimation for survival endpoints, where the expected hazard ratios (average HR = 0.66) were stronger than those observed in the primary analyses (average HR = 0.72; 2-sided signed-rank test P = .0035). Across 111 trials, 82 of 143 (57.3%) observed hazard ratios for primary survival endpoints were weaker than expected; among 5 journals with 2023 impact factors between 9.9 and 56.7 (vs 58.7-98.4 for the top 5 journals), this ratio was 70.2% (59/84). These results suggest that phase 3 oncology trials are likely underpowered, contributing to the high failure rates in oncology research.

Abstract Background. Patients with migraine often have poor sleep quality between and during migraine attacks. Furthermore, extensive research has identified photophobia as the most common and most bothersome symptom in individuals with migraine, second only to headache. Seeking the comfort of darkness is a common strategy for managing pain during an attack and preventing its recurrence between episodes. Given the well-established effects of daily light exposure on circadian activity rhythms and sleep quality, this study aims to investigate the relationship between photophobia symptoms and sleep quality in a cohort of patients with migraine. Methods. A cross-sectional observational study was conducted using existing data extracted from the American Registry for Migraine Research (ARMR). Participants with a migraine diagnosis who had completed the baseline questionnaires (Photosensitivity Assessment Questionnaire (PAQ), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-2 (PHQ-2)), and selected questions of the ARMR Sleep questionnaire were included. Models were created to describe the relationship of photophobia and photophilia with various sleep facets, including sleep quality (SQ), sleep disturbance (SDis), sleep onset latency (SOL), and sleep-related impairments (SRI). Each model was controlled for age, sex, anxiety, and depression. Results. A total of 852 patients meeting the inclusion criteria were included in the analysis (mean age (SD) = 49.8 (13.9), 86.6% (n = 738) female). Those with photophobia exhibited significantly poorer sleep quality compared to patients without photophobia (p < 0.001). Photophobia scores were associated with SQ (p < 0.001), SDis (p < 0.001), SOL (p = 0.011), and SRI (p = 0.014), after controlling for age, sex, depression, and anxiety, signifying that higher levels of photophobia were associated with worse sleep-related outcomes. Conversely, photophilia scores were associated with better sleep-related outcomes for SQ (p < 0.001), SDis (p < 0.001), and SOL (p = 0.016). Conclusion. Results suggest that photophobia is a risk factor for sleep disorders in those with migraine. These results underscore the necessity for comprehensive and systematic investigations into the intricate interplay between photophobia and sleep to enhance our understanding and develop tailored solutions for individuals with migraine.