Dataset Information

Standardising neonatal and paediatric antibiotic clinical trial design and conduct: the PENTA-ID network view.

ABSTRACT: Antimicrobial development for children remains challenging due to multiple barriers to conducting randomised clinical trials (CTs). There is currently considerable heterogeneity in the design and conduct of paediatric antibiotic studies, hampering comparison and meta-analytic approaches. The board of the European networks for paediatric research at the European Medicines Agency (EMA), in collaboration with the Paediatric European Network for Treatments of AIDS-Infectious Diseases network (www.penta-id.org), recently developed a Working Group on paediatric antibiotic CT design, involving academic, regulatory and industry representatives. The evidence base for any specific criteria for the design and conduct of efficacy and safety antibiotic trials for children is very limited and will evolve over time as further studies are conducted. The suggestions being put forward here are based on the adult EMA guidance, adapted for neonates and children. In particular, this document provides suggested guidance on the general principles of harmonisation between regulatory and strategic trials, including (1) standardised key inclusion/exclusion criteria and widely applicable outcome measures for specific clinical infectious syndromes (CIS) to be used in CTs on efficacy of antibiotic in children; (2) key components of safety that should be reported in paediatric antibiotic CTs; (3) standardised sample sizes for safety studies. Summarising views from a range of key stakeholders, specific criteria for the design and conduct of efficacy and safety antibiotic trials in specific CIS for children have been suggested. The recommended criteria are intended to be applicable to both regulatory and clinical investigator-led strategic trials and could be the basis for harmonisation in the design and conduct of CTs on antibiotics in children. The next step is further discussion internationally with investigators, paediatric CTs networks and regulators.

SUBMITTER: Folgori L

PROVIDER: S-EPMC6955510 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Standardising neonatal and paediatric antibiotic clinical trial design and conduct: the PENTA-ID network view.

Folgori Laura L Lutsar Irja I Standing Joseph F JF Walker A Sarah AS Roilides Emmanuel E Zaoutis Theoklis E TE Jafri Hasan H Giaquinto Carlo C Turner Mark A MA Sharland Mike M

BMJ open 20191231 12

Antimicrobial development for children remains challenging due to multiple barriers to conducting randomised clinical trials (CTs). There is currently considerable heterogeneity in the design and conduct of paediatric antibiotic studies, hampering comparison and meta-analytic approaches. The board of the European networks for paediatric research at the European Medicines Agency (EMA), in collaboration with the Paediatric European Network for Treatments of AIDS-Infectious Diseases network (www.pe ...[more]

PMID: 31892658

Similar Datasets

Project description:Reproducibility in animal research is alarmingly low, and a lack of scientific rigor has been proposed as a major cause. Systematic reviews found low reporting rates of measures against risks of bias (e.g., randomization, blinding), and a correlation between low reporting rates and overstated treatment effects. Reporting rates of measures against bias are thus used as a proxy measure for scientific rigor, and reporting guidelines (e.g., ARRIVE) have become a major weapon in the fight against risks of bias in animal research. Surprisingly, animal scientists have never been asked about their use of measures against risks of bias and how they report these in publications. Whether poor reporting reflects poor use of such measures, and whether reporting guidelines may effectively reduce risks of bias has therefore remained elusive. To address these questions, we asked in vivo researchers about their use and reporting of measures against risks of bias and examined how self-reports relate to reporting rates obtained through systematic reviews. An online survey was sent out to all registered in vivo researchers in Switzerland (N = 1891) and was complemented by personal interviews with five representative in vivo researchers to facilitate interpretation of the survey results. Return rate was 28% (N = 530), of which 302 participants (16%) returned fully completed questionnaires that were used for further analysis. According to the researchers' self-report, they use measures against risks of bias to a much greater extent than suggested by reporting rates obtained through systematic reviews. However, the researchers' self-reports are likely biased to some extent. Thus, although they claimed to be reporting measures against risks of bias at much lower rates than they claimed to be using these measures, the self-reported reporting rates were considerably higher than reporting rates found by systematic reviews. Furthermore, participants performed rather poorly when asked to choose effective over ineffective measures against six different biases. Our results further indicate that knowledge of the ARRIVE guidelines had a positive effect on scientific rigor. However, the ARRIVE guidelines were known by less than half of the participants (43.7%); and among those whose latest paper was published in a journal that had endorsed the ARRIVE guidelines, more than half (51%) had never heard of these guidelines. Our results suggest that whereas reporting rates may underestimate the true use of measures against risks of bias, self-reports may overestimate it. To a large extent, this discrepancy can be explained by the researchers' ignorance and lack of knowledge of risks of bias and measures to prevent them. Our analysis thus adds significant new evidence to the assessment of research integrity in animal research. Our findings further question the confidence that the authorities have in scientific rigor, which is taken for granted in the harm-benefit analyses on which approval of animal experiments is based. Furthermore, they suggest that better education on scientific integrity and good research practice is needed. However, they also question reliance on reporting rates as indicators of scientific rigor and highlight a need for more reliable predictors.

Dataset Information

Standardising neonatal and paediatric antibiotic clinical trial design and conduct: the PENTA-ID network view.

Publications

Standardising neonatal and paediatric antibiotic clinical trial design and conduct: the PENTA-ID network view.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets