Activation of Human Auditory Cortex in Retrieval Experiments: An fMRI Study

In a previous functional magnetic resonance (fMRI) study, a subdivision of the human auditory cortex into four distinct territories was achieved. One territory (T1a) exhibited functional specialization in terms of a foreground-background decomposition task involving matching-to-sample monitoring on tone sequences. The present study more specifically determined whether memory-guided analysis of tone sequences is part of the T1a specialization. During the encoding periods, an arbitrary and unfamiliar four-tone-sequence (melody) played by one instrument was presented. The melody-instrument-combination was different in each period. During subsequent retrieval periods, learned and additional combinations were presented, and the tasks were either to detect the target melodies (experiment I) or the target instruments (experiment II). T1a showed larger activation during the melody retrieval. The results generally suggest that (1) activation of T1a during retrieval is determined less by the sound material than by the executed task, and (2) more specifically, that memory-guided sequential analysis in T1a is dominant over recognition of characteristic complex sounds

Embracing model-based designs for dose-finding trials

Background: Dose-finding trials are essential to drug development as they establish recommended doses for later-phase testing. We aim to motivate wider use of model-based designs for dose finding, such as the continual reassessment method (CRM). Methods: We carried out a literature review of dose-finding designs and conducted a survey to identify perceived barriers to their implementation. Results: We describe the benefits of model-based designs (flexibility, superior operating characteristics, extended scope), their current uptake, and existing resources. The most prominent barriers to implementation of a model-based design were lack of suitable training, chief investigators’ preference for algorithm-based designs (e.g., 3 þ 3), and limited resources for study design before funding. We use a real-world example to illustrate how these barriers can be overcome. Conclusions: There is overwhelming evidence for the benefits of CRM. Many leading pharmaceutical companies routinely implement model-based designs. Our analysis identified barriers for academic statisticians and clinical academics in mirroring the progress industry has made in trial design. Unified support from funders, regulators, and journal editors could result in more accurate doses for later-phase testing, and increase the efficiency and success of clinical drug development. We give recommendations for increasing the uptake of model-based designs for dose-finding trials in academia

Analysis of patient-reported outcomes from the LUME-Lung 1 trial: A randomised, double-blind, placebo-controlled, Phase III study of second-line nintedanib in patients with advanced non-small cell lung cancer

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