Do children and adolescents with type 1 diabetes suffer from a lack of resources in France? Results from a benchmark study in the New Aquitaine region.

BACKGROUND: A benchmark study was conducted in the southwest of France, in the New Aquitaine region, to investigate metabolic outcomes and availability of resources in pediatric diabetes units. We assessed whether the level of care was in accordance with the International Society for Pediatric and Adolescent Diabetes recommendations. METHODS: Demographic and clinical data were collected, as were all HbA1c tests for the 2017 calendar year. Pediatricians specialized in diabetes care were invited to complete an online survey concerning means allocated to the management of type 1 diabetes in their centers. RESULTS: Sixteen centers provided data for 1277 patients and 3873 clinical visits. A total of 1115 children suffering from diabetes for more than 1 year were studied. Median HbA1c was 8% (7.4-8.6) for the whole region. Only 29.2% of children had good metabolic control in accordance with the <7.5% target. We identified slight but significant variation in glycemic control among centers (P=0.029). The use of an insulin pump varied greatly among centers but did not explain HbA1c differences. We did not identify a correlation between medical or paramedical time dedicated to the follow-up of diabetic patients and the mean HbA1c of each center. For 100 diabetic patients, follow-up was provided by 0.42 physicians (0.23-1.50), 0.15 nurses (0-0.56), 0.12 dietitians (0-0.48), and 0.07 psychologists (0-0.30). CONCLUSION: This study demonstrates a lack of human resources allocated to the management of type 1 diabetes in the region that is far below international recommendations. The proportion of children achieving the international glycemic target is low. There is a clear need to improve glycemic control in children, which will only be possible with improved professional practices, encouraged by benchmark studies, and by increasing the size of our multidisciplinary teams.

PhRMA survey of pharmacogenomic and pharmacodynamic evaluations: what next?

Interindividual variation in pharmacodynamic (PD) response to drugs is an ongoing area of research for drugs in clinical development, pre- and postapproval. To characterize how pharmacogenomic (PG ) variations can serves a predictor of differences in PD outcomes, the pharmaceutical industry has incorporated PG /PD analysis into clinical drug development. The Pharmaceutical Research and Manufacturers of America (PhRMA ) and the Industry Pharmacogenomics Working Group (I-PWG) conducted a survey of 16 pharmaceutical companies to ascertain to what extent PG/PD research is being incorporated into drug development. The survey results showed that, while the industry has made some attempt to incorporate PG/PD studies into drug development, application has been inconsistent. Nevertheless, several valid PG/PD markers have since emerged in drug labels. The I-PWG considers PG/PD research an important approach to improving success rates in drug development. This article reports the results of the survey and proposes steps toward increasing the use of PG/PD research by the industry.

Current practices for DNA sample collection and storage in the pharmaceutical industry, and potential areas for harmonization: perspective of the I-PWG.

Collection and storage of DNA samples in clinical drug development programs are an important investment for the pharmaceutical industry to allow efficient evaluation of observed variability in drug response. To enable collection and future use of samples, individual companies must define (i) processes to collect specimens worldwide, (ii) whether collection is optional or mandatory, (iii) conditions and duration of sample storage, (iv) whether research data can be returned to subjects, and (v) other logistical aspects. To determine current industry practices for collection and storage of these samples, the Industry Pharmacogenomics Working Group (I-PWG) conducted a survey of the industry (21 respondents) to identify areas of commonality and divergence. On the basis of the survey results, the I-PWG details areas of focus for harmonization of the industry's sample collection practices. A more unified approach would facilitate DNA sample collection, thereby contributing to the advancement of personalized medicine and more efficient development of safe and effective drugs.

Coding of DNA samples and data in the pharmaceutical industry: current practices and future directions--perspective of the I-PWG.

DNA samples collected in clinical trials and stored for future research are valuable to pharmaceutical drug development. Given the perceived higher risk associated with genetic research, industry has implemented complex coding methods for DNA. Following years of experience with these methods and with addressing questions from institutional review boards (IRBs), ethics committees (ECs) and health authorities, the industry has started reexamining the extent of the added value offered by these methods. With the goal of harmonization, the Industry Pharmacogenomics Working Group (I-PWG) conducted a survey to gain an understanding of company practices for DNA coding and to solicit opinions on their effectiveness at protecting privacy. The results of the survey and the limitations of the coding methods are described. The I-PWG recommends dialogue with key stakeholders regarding coding practices such that equal standards are applied to DNA and non-DNA samples. The I-PWG believes that industry standards for privacy protection should provide adequate safeguards for DNA and non-DNA samples/data and suggests a need for more universal standards for samples stored for future research.

Challenges in obtaining adequate genetic sample sets in clinical trials: the perspective of the industry pharmacogenomics working group.

Collection of DNA samples from subjects participating in clinical trials is vital to understanding variability in drug response. The purpose of this study was to assess pharmacogenetic sample-collection practices in the industry and to gather information on issues affecting collection. A survey questionnaire was developed and distributed to 20 pharmaceutical companies; 15 provided responses. Assessments included rate of DNA sample collection, reasons for low collection rates, reasons for rejection by health authorities (HAs) and institutional review boards/ethics committees (IRBs/ECs), and country-specific hurdles to sample collection. The results indicated that, although DNA samples are frequently collected, sample-acquisition rates remain lower than expected. Overall, the companies' experience has been that restrictions on sample usage are not consistently applied by regulatory bodies. This may reflect changing opinions/interpretations of HAs/IRBs/ECs. Collection of DNA samples in industry trials is still a challenge. Harmonization of sample-collection practices may facilitate the process.

Comparison of intra-oral and study cast measurements in the assessment of malocclusion.

Malocclusion assessment methods are based on registrations and measurements made on study casts, which requires that impressions be taken. In addition to being costly and time-consuming, this process can be unpleasant for very young children. Therefore, the aim of this study was to evaluate the reliability of intra-oral measurements that compute a malocclusion index score to determine malocclusion severity in the mixed dentition. The research was part of a longitudinal study in Slovenia on a sample of 530 3-year-old children. At 8 years of age (mean 8.5 years, standard deviation 0.2), a cohort of 101 children (44 boys, 57 girls) was randomly selected in a cross-sectional study. Quantitative registrations of space and occlusal anomalies were performed intra-orally as well as on study casts. Kappa (kappa) statistics were used to evaluate the agreement between clinical and study cast malocclusion assessments. Systematic bias of measurements was tested using Wilcoxon's signed rank test. The results showed complete agreement between the two measurements for anterior crossbite, anterior open bite and overjet scores (kappa = 1); excellent reliability for the buccal segment relationship (kappa = 0.93), transverse occlusion of posterior teeth (kappa = 0.87); and substantial agreement for overbite (kappa = 0.79) and midline deviation (kappa = 0.71). For the remainder of the traits the agreement was moderate: rotation of incisors (kappa = 0.58), crowding of upper incisors (kappa = 0.51), axial inclination of teeth (kappa = 0.44) and lower incisor crowding (kappa = 0.41). Intra-orally small, but statistically significant scoring of lower incisor rotation and crowding was identified. On the study casts the most favourable axial inclination was found for buccal segment occlusion. Overall classification into severity grades, based on the total malocclusion score, showed excellent agreement between the two methods (kappa = 0.89), without statistically significant bias. Malocclusion assessment, recorded and measured intra-orally, is as reliable as assessment on study casts. The proposed method can be used in screening, in epidemiological studies and in clinical orthodontic assessment.