Recruiting young pre-symptomatic children for a clinical trial in type 1 diabetes: insights from the Fr1da insulin intervention study

Background: Although detection of children at high risk of developing type 1 diabetes and diagnosis of early stages is possible, up to now there exists no approved therapy to delay or prevent type 1 diabetes. Thus it is vital to develop evidence-based interventions. For this a sufficient number of trial participants is crucial but difficult to obtain especially in asymptomatic children. Aim: Identifying family characteristics that lead to or impede trial participation and analyze reasons stated by families for non-participation. Methods: Participants for the Fr1da Insulin Intervention study are recruited from the Fr1da study, a population based screening for early stage type 1 diabetes in Bavaria. Families with eligible children were invited to enroll. We analyzed sex and age of the child, distance of the family to the study center in Munich and the existence of a first degree family member with type 1 as possible influential factors for study participation. We also analyzed reasons stated by families who declined study participation in a phone interview. Results: Of 146 eligible children 77 (53%) were enrolled into the trial. None of the tested family characteristics differed significantly between the enrolling and the families not participating, but in general enrolling families lived closer to the study site than families not participating. This is also reflected in the reasons given by non-participating families. The most frequent reason stated were time restrictions. The second most frequent reason was the venous blood draw. Conclusion: The factors for non-participation identified in this project need be taken into account for the design of future trials in young children to ensure proper recruitment and thus to generate valid results for medical treatment of children. More research on the reason of participation and non-participation in clinical trials is needed. Keywords: Type 1 diabetes, Trial recruitment, Trial enrollment, Infants, Children, Asymptomati

Die Referenzeinholung durch Personalberater als Auswahlinstrument

Läßt sich durch das Einholen von Referenzen die Qualität der Personalauswahl verbessern? Wie kann der geeignete Referenzgeber ermittelt werden? Welche Wege werden bei der Referenzeinholung beschritten und wie kann ein Referenzgespräch gestaltet werden? Diese und eine Reihe anderer Fragen beantwortet eine Studie, die im Jahr 1994 an der Fachhochschule Offenburg durchgeführt wurde, und an der sich 238 von 1000 angeschriebenen Personalberatern beteiligten. Die wichtigsten Ergebnisse der Untersuchung werden im nachfolgenden Beitrag dargelegt

Common ground or mutual exclusion

xiii.226 hal.;21 c

Cetuximab Resistance in Head and Neck Cancer Is Mediated by EGFR-K 521 Polymorphism

Head and neck squamous cell carcinomas (HNSCC) exhibiting resistance to the EGFR-targeting drug cetuximab poses a challenge to their effective clinical management. Here, we report a specific mechanism of resistance in this setting based upon the presence of a single nucleotide polymorphism encoding EGFR-K-521 (K-allele), which is expressed in > 40% of HNSCC cases. Patients expressing the K-allele showed significantly shorter progressionfree survival upon palliative treatment with cetuximab plus chemotherapy or radiation. In several EGFR-mediated cancer models, cetuximab failed to inhibit downstream signaling or to kill cells harboring a high K-allele frequency. Cetuximab affinity for EGFR-K-521 was reduced slightly, but ligand-mediated EGFR acti-vation was intact. We found a lack of glycan sialyation on EGFR-K-521 that associated with reduced protein stability, suggesting a structural basis for reduced cetuximab efficacy. CetuGEX, an antibody with optimized Fc glycosylation targeting the same epitope as cetuximab, restored HNSCC sensitivity in a manner associated with antibody-dependent cellular cytotoxicity rather than EGFR pathway inhibition. Overall, our results highlight EGFR-K-521 expression as a key mechanism of cetuximab resistance to evaluate prospectively as a predictive biomarker in HNSCC patients. Further, they offer a preclinical rationale for the use of ADCC-optimized antibodies to treat tumors harboring this EGFR isoform