A proposal for a new PhD level curriculum on quantitative methods for drug development

This paper provides an overview of “Improving Design, Evaluation and Analysis of early drug development Studies” (IDEAS), a European Commission–funded network bringing together leading academic institutions and small‐ to large‐sized pharmaceutical companies to train a cohort of graduate‐level medical statisticians. The network is composed of a diverse mix of public and private sector partners spread across Europe, which will host 14 early‐stage researchers for 36 months. IDEAS training activities are composed of a well‐rounded mixture of specialist methodological components and generic transferable skills. Particular attention is paid to fostering collaborations between researchers and supervisors, which span academia and the private sector. Within this paper, we review existing medical statistics programmes (MSc and PhD) and highlight the training they provide on skills relevant to drug development. Motivated by this review and our experiences with the IDEAS project, we propose a concept for a joint, harmonised European PhD programme to train statisticians in quantitative methods for drug development

Preoperative imaging for hyperparathyroidism often takes upper parathyroid adenomas for lower adenomas

Abstract We retrospectively evaluated how accurately preoperative imaging localizes parathyroid adenoma in superior versus inferior parathyroids. Over 6 years, 104 patients with primary hyperparathyroidism underwent parathyroid surgery in a single centre. Of these, 103 underwent ultrasound, 97 [99mTc]pertechnetate/MIBI SPECT/CT and 30 [18F]fluorocholine (FCH) PET/CT. One patient with a unilateral double adenoma was excluded from the analysis. Surgical findings with histopathologic confirmation of adenoma were used as the standard. Ultrasound misjudged 5 of 48 detected lower adenomas as upper, but 14 of 29 upper adenomas as lower (error rate 10 vs 48%, p = 0.0002). The corresponding error rates for [99mTc]pertechnetate/MIBI SPECT/CT were 3 versus 55% (p = 0.000014), and for [18F]FCH PET/CT 17 versus 36% (p = 0.26). Our results suggest that about half of the superior parathyroid adenomas which are detected, are erroneously assigned to the inferior position by both ultrasound and SPECT/CT imaging whereas the opposite mistake is significantly less frequent with ultrasound and SPECT/CT

Structural coronary artery remodelling in the rabbit fetus as a result of intrauterine growth restriction

Intrauterine growth restriction (IUGR) is a fetal condition that affects up to 10% of all pregnancies and is associated with cardiovascular structural and functional remodelling that persists postnatally. Some studies have reported an increase in myocardial coronary blood flow in severe IUGR fetuses which has been directly associated to the dilatation of the coronary arteries. However, a direct measurement of the coronaries’ lumen diameter in IUGR has not been reported before. The aim of this paper is to perform, for the first time, a quantitative analysis of the effects of IUGR in cardiac geometry and coronary vessel size in a well-known rabbit model of IUGR using synchrotron-based X-ray Phase Contrast Tomography Imaging (X-PCI). Eight rabbit fetal hearts were imaged non-destructively with X-PCI. 3D reconstructions of the coronary arterial tree were obtained after semi-automatic image segmentation. Different morphometric features including vessel lumen diameter of the three main coronaries were automatically quantified. IUGR fetuses had more globular hearts and dilated coronary arteries as compared to controls. We have quantitatively shown that IUGR leads to structural coronary vascular tree remodelling and enlargement as an adaptation mechanism in response to an adverse environment of restricted oxygen and nutrients and increased perfusion pressure.This study was partially supported by the Spanish Ministry of Economy and Competitiveness (grant TIN2014-52923-R to BB; Maria de Maeztu Units of Excellence Programme - MDM-2015-0502); la Caixa Foundation (Spain); Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (2014 SGR grant nº 928, 2016FI_B01184); Instituto de Salud Carlos III (PI14/00226 to FC, PI15/00130 to EG and INT16/00168 to FC) as part of the Plan Nacional de I+D+I and co-funded by ISCIII-Subdirección General de Evaluación; the Fondo Europeo de Desarrollo Regional (FEDER) “Otra manera de hacer Europa” (Spain)