Current state-of-the-art and gaps in platform trials: 10 things you should know, insights from EU-PEARL.

Platform trials bring the promise of making clinical research more efficient and more patient centric. While their use has become more widespread, including their prominent role during the COVID-19 pandemic response, broader adoption of platform trials has been limited by the lack of experience and tools to navigate the critical upfront planning required to launch such collaborative studies. The European Union-Patient-cEntric clinicAl tRial pLatform (EU-PEARL) initiative has produced new methodologies to expand the use of platform trials with an overarching infrastructure and services embedded into Integrated Research Platforms (IRPs), in collaboration with patient representatives and through consultation with U.S. Food and Drug Administration and European Medicines Agency stakeholders. In this narrative review, we discuss the outlook for platform trials in Europe, including challenges related to infrastructure, design, adaptations, data sharing and regulation. Documents derived from the EU-PEARL project, alongside a literature search including PubMed and relevant grey literature (e.g., guidance from regulatory agencies and health technology agencies) were used as sources for a multi-stage collaborative process through which the 10 more important points based on lessons drawn from the EU-PEARL project were developed and summarised as guidance for the setup of platform trials. We conclude that early involvement of critical stakeholder such as regulatory agencies or patients are critical steps in the implementation and later acceptance of platform trials. Addressing these gaps will be critical for attaining the full potential of platform trials for patients. Funding: Innovative Medicines Initiative 2 Joint Undertaking with support from the European Union's Horizon 2020 research and innovation programme and EFPIA.

Decision-Making in Suicidal Behavior: The Protective Role of Loss Aversion.

BACKGROUND: Loss aversion is a central and well operationalized trait behavior that describes the tendency for humans to strongly prefer avoiding losses to making equivalent gains. Human decision-making is thus biased toward safer choices. AIM: The aim of this study was to explore the relationship between loss aversion and suicidal behavior in a large cohort of adolescents recruited in 30 schools of seven European countries for a longitudinal study (Current Controlled Trials ISRCTN65120704). We hypothesized that individuals with higher loss aversion would be less likely to attempt suicide. METHODS: A mixed monetary gamble task was used to generate loss aversion scores for each participant. Logistic regression was used to estimate the cross-sectional association between loss aversion and life-time suicide attempts in the baseline sample (N = 2,158; 156 attempters), and incident attempts were predicted in a 4-month prospective model (N = 1,763; 75 attempters). Multiple regression was used to estimate the association between loss aversion and suicidal ideation. RESULTS: Loss aversion was a significant predictor of attempted suicide in both the cross-sectional (OR = 0.79; P = 0.005) and prospective analysis (OR = 0.81; P = 0.040), adjusting for depression, anxiety, stress, and sex. The correlation between pre and post measures of loss aversion was r = 0.52 (P < 0.001). Interestingly, although depression, anxiety, and stress were associated with suicidal ideation, loss aversion was not (cross-sectional model: P = 0.092; Prospective model: P = 0.390). This suggests that the concept of loss aversion may be useful in understanding the transition from suicidal thoughts to attempts. CONCLUSION: This and previous studies suggest that altered decision-making is involved in suicide attempts. In our study, we show the involvement of loss aversion in particular, and propose that individuals high in loss aversion are discouraged from carrying out the suicide attempt because of a greater focus on the negative consequences of the decision.

Are Mental Health Effects of Internet Use Attributable to the Web-Based Content or Perceived Consequences of Usage? A Longitudinal Study of European Adolescents.

BACKGROUND: Adolescents and young adults are among the most frequent Internet users, and accumulating evidence suggests that their Internet behaviors might affect their mental health. Internet use may impact mental health because certain Web-based content could be distressing. It is also possible that excessive use, regardless of content, produces negative consequences, such as neglect of protective offline activities. OBJECTIVE: The objective of this study was to assess how mental health is associated with (1) the time spent on the Internet, (2) the time spent on different Web-based activities (social media use, gaming, gambling, pornography use, school work, newsreading, and targeted information searches), and (3) the perceived consequences of engaging in those activities. METHODS: A random sample of 2286 adolescents was recruited from state schools in Estonia, Hungary, Italy, Lithuania, Spain, Sweden, and the United Kingdom. Questionnaire data comprising Internet behaviors and mental health variables were collected and analyzed cross-sectionally and were followed up after 4 months. RESULTS: Cross-sectionally, both the time spent on the Internet and the relative time spent on various activities predicted mental health (P<.001), explaining 1.4% and 2.8% variance, respectively. However, the consequences of engaging in those activities were more important predictors, explaining 11.1% variance. Only Web-based gaming, gambling, and targeted searches had mental health effects that were not fully accounted for by perceived consequences. The longitudinal analyses showed that sleep loss due to Internet use (ß=.12, 95% CI=0.05-0.19, P=.001) and withdrawal (negative mood) when Internet could not be accessed (ß=.09, 95% CI=0.03-0.16, P<.01) were the only consequences that had a direct effect on mental health in the long term. Perceived positive consequences of Internet use did not seem to be associated with mental health at all. CONCLUSIONS: The magnitude of Internet use is negatively associated with mental health in general, but specific Web-based activities differ in how consistently, how much, and in what direction they affect mental health. Consequences of Internet use (especially sleep loss and withdrawal when Internet cannot be accessed) seem to predict mental health outcomes to a greater extent than the specific activities themselves. Interventions aimed at reducing the negative mental health effects of Internet use could target its negative consequences instead of the Internet use itself. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 65120704; http://www.isrctn.com/ISRCTN65120704?q=&filters=recruitmentCountry:Lithuania&sort=&offset= 5&totalResults=32&page=1&pageSize=10&searchType=basic-search (Archived by WebCite at http://www.webcitation/abcdefg).

Foreign travel and the risk of harm.

Systematic data on the risk of fatal and non-fatal injury from external causes to those who travel abroad for purposes of business or pleasure are seldom recorded and are consequently hard to come by. In this paper, the risk of fatal injuries to foreign travellers using historical and newly acquired data from national databases is estimated. Overall, it appears from these data that the risk of fatal injury to foreign travellers lies in the range of 20 to 90 per 100 000 person-years of exposure for many destinations worldwide, although different rates may pertain in selected situations where special conditions apply, for example, where there is heavy participation in risky sports or increased driving. This level of fatal injury risk is not noticeably different from that of staying in one's home country if one lives in a Western-style industrial country, although the types of hazards responsible may vary in type and proportion. With increasing levels of travel, and the growing popularity of more adventurous pursuits, it is possible that risks could be increasing in this sector.