Suitability of external controls for drug evaluation in Duchenne muscular dystrophy

OBJECTIVE: To evaluate the suitability of real-world data (RWD) and natural history data (NHD) for use as external controls in drug evaluations for ambulatory Duchenne muscular dystrophy (DMD). METHODS: The consistency of changes in the 6-minute walk distance (Δ6MWD) was assessed across multiple clinical trial placebo arms and sources of NHD/RWD. Six placebo arms reporting 48-week Δ6MWD were identified via literature review and represented 4 sets of inclusion/exclusion criteria (n = 383 patients in total). Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total). Mean Δ6MWD was compared between each placebo arm and RWD/NHD source after subjecting the latter to the inclusion/exclusion criteria of the trial for baseline age, ambulatory function, and steroid use. Baseline covariate adjustment was investigated in a subset of patients with available data. RESULTS: Analyses included ∼1,200 patient-years of follow-up. Differences in mean Δ6MWD between trial placebo arms and RWD/NHD cohorts ranged from -19.4 m (i.e., better outcomes in RWD/NHD) to 19.5 m (i.e., worse outcomes in RWD/NHD) and were not statistically significant before or after covariate adjustment. CONCLUSIONS: We found that Δ6MWD was consistent between placebo arms and RWD/NHD subjected to equivalent inclusion/exclusion criteria. No evidence for systematic bias was detected. These findings are encouraging for the use of RWD/NHD to augment, or possibly replace, placebo controls in DMD trials. Multi-institution collaboration through the Collaborative Trajectory Analysis Project rendered this study feasible

Analysis of Oppositional Frames in Evaluating Movement Success: National and Local Debates Over Sex Education Programming

This thesis attempts to add to framing theory by identifying a cleavage in the types of framing strategies employed by social movement actors. A thorough analysis of the framing literature reveals that social movement actors either engage in proactive or reactive framing. Proactive framing involves creating new, previously unused frames, while reactive framing is the process through which social movement actors recycle frames. In order to fully understand these different framing strategies, I argue that scholars have to look at oppositional movements in conversation with each other. To further explore this idea, I pull two recent case studies from the contemporary sex education debate—one which explores funding legislation at the federal level, and other which analyzes a debate over curriculum content in Montgomery County, MD

How do “earworms” start? : classifying the everyday circumstances of Involuntary Musical Imagery

Involuntary Musical Imagery (INMI) or “earworms” describes the experience whereby a tune comes into the mind and repeats without conscious control. The present article uses an inductive, generative, grounded theory-based qualitative analysis to classify reports of everyday INMI circumstances, and creates graphical models that determine their relative frequency within two population samples; listeners to the BBC radio station 6 Music and an online survey. Within the two models, four abstract categories were defined that described the characteristics of the circumstances surrounding the onset of INMI episodes; Music exposure, Memory triggers, Affective states, and Low attention states respectively. We also note the variety of musical media by which exposure to a tune results in an INMI episode and discuss the impact of musical engagement on INMI experiences. The findings of the present study are considered within a framework of involuntary retrieval theory from both the autobiographical and semantic memory literatures. In addition, the results highlight the potential facilitative effects of varying affective and attentional states on INMI episodes