A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

SAEs within 28 days after any dose of CYD-TDV vaccine or placebo in participants aged 9–60 years.

<p>None of the preferred term events affected ≥0.1% of the participants; n = number of participants with ≥1 of each SAE.</p

Safety Overview of a Recombinant Live-Attenuated Tetravalent Dengue Vaccine: Pooled Analysis of Data from 18 Clinical Trials

<div><p>A recombinant live attenuated tetravalent dengue vaccine (CYD-TDV) has been shown to be efficacious in preventing virologically-confirmed dengue disease, severe dengue disease and dengue hospitalization in children aged 2–16 years in Asia and Latin America. We analyzed pooled safety data from 18 phase I, II and III clinical trials in which the dengue vaccine was administered to participants aged 2–60 years, including long-term safety follow-up in three efficacy trials. The participants were analyzed according to their age at enrollment. The percentage of participants aged 2–60 years reporting ≥1 solicited injection-site or systemic reactions was slightly higher in the CYD-TDV group than in the placebo group. The most common solicited injection-site reactions were pain. Headache and malaise were the most common solicited systemic reactions. In both groups 0.3% of participants discontinued for safety reasons. The most common unsolicited adverse events were injection-site reactions, gastrointestinal disorders, and infections. Reactogenicity did not increase with successive doses of CYD-TDV. The frequency and nature of SAEs occurring within 28 days of any dose were similar in the CYD-TDV and placebo groups and were common medical conditions that could be expected as a function of age. Baseline dengue virus serostatus did not appear to influence the safety profile. No vaccine-related anaphylactic reactions, neurotropic events or viscerotropic events were reported. In year 3 after dose 1, an imbalance for dengue hospitalization, including for severe dengue, observed in participants aged <9 years in the CYD-TDV group compared with the placebo group was not observed for participants aged ≥9 years. In Year 4, this imbalance in participants aged <9 years was less marked, giving an overall lower risk of dengue hospitalization or severe dengue from dose 1 to Year 4 in the CYD-TDV group. These results have contributed to the definition of the target population for vaccination (≥9 years old) for which CYD-TDV has a satisfactory safety profile. Long-term safety will continue to be monitored in the ongoing follow-up of efficacy trials. Safety and effectiveness in real-life settings will be assessed through post-licensure studies.</p></div

Number of CYD-TDV (final formulation) injections received overall and by age group in main trials (CYD-TDV at D0 M6 and M12), and all trials (including those who received three doses of CYD-TDV at D0 M3.5/4 and M12) and number of placebo and active control injections.

<p>Number of CYD-TDV (final formulation) injections received overall and by age group in main trials (CYD-TDV at D0 M6 and M12), and all trials (including those who received three doses of CYD-TDV at D0 M3.5/4 and M12) and number of placebo and active control injections.</p

Summary of the characteristics of clinical trials included in the analysis.

<p>Summary of the characteristics of clinical trials included in the analysis.</p

Long-term immunogenicity and safety of tetravalent dengue vaccine (CYD-TDV) in healthy populations in Singapore and Vietnam: 4-year follow-up of randomized, controlled, Phase II trials

10.1080/21645515.2019.1578595Human Vaccines & Immunotherapeutics15102315-232

Relative risk (solid line) and 95% confidence interval (dotted lines) against hospitalized or severe dengue due to any serotype by age at enrollment.

<p>The Epanechnikov kernel method (with h = 2.0) was used to provide a smooth curve. Data were combined from post-dose 1 up to year 3 in the phase III trial in Latin America and up to year 4 in the phase IIb and phase III trial in Asia.</p

Unsolicited non-serious adverse reactions affecting ≥0.1% of participants aged 9–60 years in the CYD-TDV and placebo groups.

<p>n = number of participants with ≥1 of each SAE.</p

Definitions and severity scales for solicited injection site and systemic reactions.

<p>Definitions and severity scales for solicited injection site and systemic reactions.</p

Overall safety profile of CYD-TDV and placebo.

<p>Percentages and 95% confidence intervals for participants those who received at least one dose of CYD-TDV (left) or placebo (right) reporting solicited injection-site reactions within 7 days of any dose, solicited systemic reactions within 14 days of any dose, unsolicited AEs and SAEs within 28 days of any dose, by age group.</p