Biomarker-guided drug development provides value for patients, payers and drug developers: lessons learned from 25 years in the biomarker industry.

INTRODUCTION: There is an urgent, persistent, need for better biomarkers in clinical drug development. More informative biomarkers can increase the likelihood of drug advancement or approval, and implementing biomarkers increases the success rate in drug development. Biomarkers may guide decisions and allow resources to be directed to the projects most likely to succeed. However, biomarkers that are validated to high standards are needed, reflecting biological and pathological processes accurately. Such biomarkers are needed to develop treatments faster, and to improve and guide clinical trial design by selecting and de-selecting patients. METHODS: In this review based on the authors' previous published experience and interaction with pharmaceutical- and biomarker stakeholders, we highlight the use and value of biomarkers in clinical development according to the BEST guidelines. We highlight the value of 3 types of biomarkers that may provide optimal value to stakeholders: diagnostic, prognostic and pharmacodynamic biomarkers. RESULTS: A more appropriate clinical trial design, increasing the ratio between benefits and side effects, may come from a more tailored biomarker-approach identifying suitable molecular endotypes of patients to treat. DISCUSSION: Biomarkers may guide drug developers in selecting the optimal projects to progress, when designing clinical studies and development paths. Biomarkers may aid in the diagnosis and prognostic assessment of patients and assist in matching the molecular endotype to the selected treatment, which improves the success rate of clinical development progression. The aim of this paper is to provide a comprehensive ideation framework for how to utilize biomarkers in clinical development, with a focus on utility for patients, payers and drug developers.

Problematic usage of the internet among Hungarian elementary school children: a cross-sectional study.

INTRODUCTION: Problematic usage of the internet (PUI) is perhaps one of the most frequently studied phenomena of the 21st century receiving increasing attention in both scientific literature and the media. Despite intensive research there have been relatively few meaningful studies among elementary school students in Hungary and worldwide, who may be considered as a high-risk population with regard to problematic internet use. The aim of our study was to carry out a complex research focusing on the prevalence and risk factors of PUI among elementary school children aged 10-15 years (Grade 5-8). METHODS: Demographics included were gender, age, place of stay, type of residence, family type, parental education, start of internet use, used devices, daily internet use, purpose of internet use, internet accounts, ways of keeping in touch with friends and sporting activities. PUI was evaluated using the paper-based version of the Potentially Problematic Use of the Internet Questionnaire. RESULTS: Overall, 2000 paper-based questionnaires were successfully delivered and the final analysis included 1168 responses (overall response rate 58.4%). Mean age was 12.55 ± 1.24 years. Female gender (OR = 2.760, p = 0,006, CI 95% 0.065 to 0.384), younger age (11-12 years) (OR = 3.812, p < 0.001, 95% CI: 1.747-4.731), early exposure to the internet (OR = 3.466, p = 0.001, 95% CI 1.535-5.446), living in a small village (OR = 1.081, p = 0.002, 95% CI 1.041-1.186) urgency to answer online (OR = 4.677, p < 0.001, 95% CI: 2.714-6.639), decreased frequency of personal contact with friends (OR = 2.897, p = 0.004, 95% CI: 1.037-1.681), spending more than 6 h online (OR = 12.913, p < 0.001, 95% CI: 10.798-14.892), morning and nighttime internet use (OR = 3.846, p < 0.001, CI 95% 1.886-5.810) and never doing any sports (OR = 2.016, p = 0.044, 95% CI: 1.050-3.354) were independently associated with problematic internet use. CONCLUSIONS: Based on the results of our questionnaire survey more than 10% seemed to be problematic users in our study population, which is a relatively high rate. Early exposure to the internet as well as younger age were strongly related to this phenomenon. Duration of being online as well as daily time interval of internet use are important predisposing factors. Scarcely studied social factors such as being online at the expense of personal relationships and the lack of physical activity should be payed more attention to prevent the development of PUI.

The association of problematic usage of the internet with burnout, depression, insomnia, and quality of life among Hungarian high school students.

Introduction: The extensive availability of the internet has led to the recognition of problematic usage of the internet (PUI) or so called internet addiction (IA), probably mostly involving adolescents. Aim: Here we present a study focusing on the incidence and consequences (including burnout, which is relatively rarely studied) of internet addiction among high school students using a questionnaire-based non-random sampling cross-sectional survey. Included questionnaires were the Problematic Internet Use Questionnaire, the Maslach Burnout Inventory General Survey for Students MBI-GS (S), the 9-item short version of Beck Depression Inventory (BDI-SF), the Athens Insomnia Questionnaire and the EQ-5D (quality of life) questionnaire. Data were evaluated the exertion of Student's t-test, chi square test and Pearson's rank-order correlation. Logistic regression analysis was used to determine the significance of the different parameters as independently associated with PUI. Results: Overall 3,000 paper-based questionnaires were successfully delivered and 2,540 responses received (response rate of 84.6%). 1,309 males (mean age 17.6 ± 1.43 years) (51.5%) and 1,231 females (mean age 17.5 ± 1.4 years) (48.5%) took part in our study. Problematic usage of the internet was detected in 486 (19.1%) students (232 males, mean age 17.6 ± 1.35 years and 254 females, mean age 17.34 ± 1.37 years). In a logistic regression analysis sleep disturbance (OR: 1.84, 95% CI: 1.83-2.03), depression (OR: 1.97, 95% CI: 1.77-2.02) and burnout (OR: 1.8, 95% CI: 1.16-1.94) were significantly associated with PUI. Conclusion: Nearly one fifth of our study population suffered from PUI, which was strongly associated with school burnout, insomnia and depression, which underlines the importance of this phenomenon.

The Association of Internet Addiction with Burnout, Depression, Insomnia, and Quality of Life among Hungarian High School Teachers.

The extensive availability of Internet has led to the recognition of problematic Internet use (so called Internet addiction, IA) mostly involving adolescents. There are limited data about the prevalence and consequences of IA in adults especially among high school teachers. Here, we present a cross-sectional prospective study focusing on the association of Internet addiction with burnout, depression, insomnia, and lower quality of life among high school teachers taking many co-variates into account. Overall, 623 males (34.3%) and 1194 females (65.7%) participated in our study. Internet addiction was detected in 5.2% (95/1817) based on the Problematic Internet Use Questionnaire. Internet addiction was associated with severe burnout (10.5 vs. 2.7%, p < 0.001), moderate (36.8 vs. 1.7%, p < 0.001), and severe (6.3 vs. 0.1%, p < 0.001) depression, insomnia (23.1 vs. 11.4%, p < 0.001), and severe sleep disturbance (severe insomnia, 27.4 vs. 3.8%, p < 0.001) and lower quality of life in all domains (p < 0.001). There was also a significant correlation of the severity of the above-mentioned parameters and the severity of IA (overall scores, p < 0.001 in all cases). In a multivariate analysis including demographic criteria, risk factors medical conditions and the above-mentioned parameters as co-variates internet addiction was significantly associated with depression (OR = 3.836, CI: 2.92-5.44, p = 0.03), and insomnia (OR: 3.932, CI: 3.6-5.69, p = 0.002). This is the first study from Hungary and is one of the first studies showing the association of IA with mental issues, burnout, and lower quality of life among adults. It underlines the clinical importance of problematic Internet use among adults.