Testosterone-induced singing in songbirds is thought to involve testosterone-dependent morphological changes that include angiogenesis and neuronal recruitment into the HVC, a central part of the song control circuit. Previous work showed that testosterone induces the production of vascular endothelial growth factor (VEGF) and its receptor (VEGFR2 tyrosine kinase), which in turn leads to an upregulation of brain-derived neurotrophic factor (BDNF) production in HVC endothelial cells. Here we report for the first time that systemic inhibition of the VEGFR2 tyrosine kinase is sufficient to block testosterone-induced song in adult female canaries, despite sustained androgen exposure and the persistence of the effects of testosterone on HVC morphology. Expression of exogenous BDNF in HVC, induced locally by in situ transfection, reversed the VEGFR2 inhibition-mediated blockade of song development, thereby restoring the behavioral phenotype associated with androgen-induced song. The VEGFR2-inhibited, BDNF-treated females developed elaborate male-like song that included large syllable repertoires and high syllable repetition rates, features known to attract females. Importantly, although functionally competent new neurons were recruited to HVC after testosterone treatment, the time course of neuronal addition appeared to follow BDNF-induced song development. These findings indicate that testosterone-associated VEGFR2 activity is required for androgen-induced song in adult songbirds and that the behavioral effects of VEGFR2 inhibition can be rescued by BDNF within the adult HVC.

There is currently a heightened need for transparency in pharmaceutical sectors. The inclusion of real-world (RW) evidence, in addition to clinical trial evidence, in decision-making processes, was an important step forward toward a more inclusive established value proposition. This advance has introduced new transparency challenges. Increasing transparency is a critical step toward accelerating improvement in type, quality, and access to data, regardless of whether these originate from clinical trials or from RW studies. However, so far, advances in transparency have been relatively restricted to clinical trials, and there remains a lack of similar expectations or standards of transparency concerning the generation and reporting of RW data. This perspective paper aims to highlight the need for transparency concerning RW studies, data, and evidence across health care sectors, to identify areas for improvement, and provide concrete recommendations and practices for the future. Specific issues are discussed from different stakeholder perspectives, culminating in recommended actions, from individual stakeholder perspectives, for improved RW study, data, and evidence transparency. Furthermore, a list of potential guidelines for consideration by stakeholders is proposed. While recommendations from different stakeholder perspectives are made, true transparency in the processes involved in the generation, reporting, and use of RW evidence will require a concerted effort from all stakeholders across health care sectors.

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proposed to identify respondents who might not understand the DCE tasks, and these questions also teach respondents how to interpret text and graphics and reinforce important survey elements. We reviewed 11 DCE surveys to assess the performance of a comprehension question. Methods: We reviewed data from 13 DCE surveys that used a common risk grid comprehension question. The percent of respondents who failed the comprehension question was calculated and summarized by recruiting source and respondent type. Results: The failure rate on the risk grid comprehension question ranged from 5% to 36%. The failure rates by recruitment source were: 11%-36% online panel (n=6), 5%-15% patient group (n=4), 5%-13% clinical site (n=3). In all 13 surveys, the analysis of the preference weights using the full sample yielded intuitive results. Across respondent types, failure rates were: patients 5% to 15% (n=8), caregivers 13% to 36% (n=4), general population 17% (n=1). In several studies, we compared the results with and without including respondents who failed the risk grid comprehension question and found that the results were qualitatively similar. Conclusions: We provide a summary of failure rates for a comprehension question across multiple studies against which other researchers can compare their studies. Datasets with failure rates as high as 36% still produced reasonable estimates of preference weights (no extreme disordering or large confidence intervals). Our experience suggests that comprehension questions help respondents learn and provide a check on respondent understanding. Very high failure rates may be helpful in signaling the presence of data quality problems like attributes that are very difficult to understand or inattentive respondents.

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