Pansa, P; Hsia, Y; Bielicki, J; Lutsar, I; Walker, AS; Sharland, M; Folgori, L; (2018) Evaluating Safety Reporting in Paediatric Antibiotic Trials, 2000–2016: A Systematic Review and Meta-Analysis. Drugs , 78 (2) pp. 231-244. 10.1007/s40265-017-0850-x.

Preview	Text (Article) Walker_Manuscript_R1.pdf - Accepted Version Download (607kB) | Preview
Preview	Image (Figure 1) Fig 1.jpg - Accepted Version Download (89kB) | Preview
Preview	Image (Figure 2) Fig 2.jpg - Accepted Version Download (75kB) | Preview
Preview	Image (Figure 3) Fig 3.jpg - Accepted Version Download (136kB) | Preview
Preview	Text (Supplementary material 1) Walker_Electronic Supplementary figures_R1.pdf - Accepted Version Download (367kB) | Preview
Preview	Text (Supplementary material 2) Walker_Electronic Supplementary material_R1.pdf - Accepted Version Download (508kB) | Preview

Abstract

Background: There are very few options to treat multidrug-resistant bacterial infections in children. A major barrier is the duration and complexity of regulatory trials of new antibiotics. Extrapolation of safety data from adult trials could facilitate drug development for children. / Objective: We performed a systematic review on the safety of antibiotic clinical trials (CTs) in children (0–18 years) to evaluate the overall quality of safety trials conducted in children and to determine if age-specific adverse events (AEs) could be identified for specific antibiotic classes. / Data Sources: We searched the MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov electronic databases for trials conducted between 2000 and 2016. / Study Selection: All trials in which safety was declared a primary or secondary endpoint were included. Exclusion criteria were (1) topical or inhalational route of administration; (2) non-infectious conditions; (3) administration for prophylaxis rather than treatment; (4) selected population (i.e. cystic fibrosis, malignancies, HIV and tuberculosis); and (5) design other than randomized controlled trials. Trials reporting data on both adults and children were included only if paediatric results were reported separately. / Data Extraction and Synthesis: Two authors independently extracted the data. To assess the quality of published trials, the Extension for harms for Consolidated Standards of Reporting Trials (CONSORT) Statement 2004 was used. / Main Outcome and Measure: In order to quantitatively assess the rate of developing AEs by drug class, the numbers of overall and body-system-specific AEs were collected for each study arm, and then calculated per single drug class as median and interquartile range (IQR) of the proportions across CTs. The AEs most frequently reported were compared in the meta-analysis by selecting the CTs on the most represented drug classes. / Results: Eighty-three CTs were included, accounting for 27,693 children. Overall, 69.7% of CONSORT items were fully reported. The median proportion of children with any AE was 22.5%, but did not exceed 8% in any single body system. Serious drug-related AEs and drug-related discontinuations were very rare (median 0.3 and 0.9%, respectively). Limitations included the inability to stratify by age group, particularly neonates. / Conclusions and Relevance: Overall, AEs in paediatric antibiotic CTs were predictable and class-specific, and no unexpected (age-specific) side effects were identified. Smaller, open-label, dose-finding, high-quality, single-arm pharmacokinetic trials seem potentially sufficient for certain common antibiotic classes, extrapolating well-established safety profiles determined from large adult efficacy trials. This approach could reduce duration and enhance subsequent registration of urgently needed new antibiotics. This will need to be combined with enhanced methods of pharmacovigilance for monitoring of emerging AEs in routine clinical practice.

Download activity - last month

Export as JSONXMLCSV

Download activity - last 12 months

Export as XMLJSONCSV

Downloads by country - last 12 months

Export as CSVJSONXML

Archive Staff Only

View Item