Analysis of Reporting Adverse Drug Reactions in Paediatric Patients in a University Hospital in the Netherlands

Abstract

Aims The risk to develop adverse drug reactions (ADRs) is high for paediatric patients. This is, amongst other reasons, due to the inevitable use of off-label and unlicensed medicines. Moreover, there is limited knowledge on ADRs in children. Thus, adequate recognition may be challenging. The lack of dedicated studies and the voluntary nature of pharmacovigilance systems used to gain insight into the characteristics of ADRs contribute to this problem. The goal of this study is to identify whether ADRs in paediatric patients are adequately documented by the medical team and whether they are subsequently reported to the national pharmacovigilance system. Methods All patients admitted to the paediatric medium care of the Radboudumc Amalia Children's hospital during 1 month, and using one or more drugs, were included. Two researchers analysed retrospectively and independently the number of possible ADRs in the medical records. The ADRs were listed per paediatric subspecialty, to evaluate any differences in documentation and reporting of the ADRs. Subsequently, the causality, severity, and seriousness of the ADRs were assessed. The ADRs were categorised by system organ class and drug class. The national pharmacovigilance centre was consulted to check if there were any reports coming from our hospital and to collect the total number of reports. Results The medical records of 301 patients were analysed, 81 patients were suffering from one or more ADRs. In total 132 suspected ADRs were found, divided among 19 different paediatric subspecialties. Numbers were too small to investigate the differences in ADR documentation. Of these found ADRs, 55% were not explicitly noted as such in the medical records by the treating physician. None of the ADRs were reported to the national pharmacovigilance centre. Most ADRs scored 'possible' in the causality assessment, were mild or moderate, and a small number were serious. The ADRs occurred in 25 different organ systems. In total 25 different drug classes were involved. Conclusions The results of the present study show that a large number of ADRs are not registered in the medical records and are not reported to the national pharmacovigilance system. Furthermore, it is shown that the number of ADRs occurring at our centre is much higher than the number reported to the national pharmacovigilance centre. Only an average of 513 ADRs in paediatric patients are reported per year nationwide, suggesting that there is extensive underreporting.

Effects of the number of drugs used on the prevalence of adverse drug reactions in children

“…In the present study, the most common ADRs were "gastrointestinal disorders" followed by "skin and subcutaneous tissue disorders, " while in a previous study in the Netherlands, the most common ADRs were "gastrointestinal disorders" followed by "investigations" according to CTCAE classification 24 . Moreover, the most common ADRs affected "skin and appendages", followed by "gastrointestinal" in previous studies conducted in Saudi Arabia 16 and in India 25 .…”

“…Serious ADRs of grade ≥ 3 severity accounted for 18.5% of all ADRs. Serious ADRs was 12% in CTCAE classification in the previous study conducted in the Netherlands 24 . A meta-analysis of pediatric patients hospitalized for ADRs reported a rate of 39.3% (95% CI, 30.4–47.9) for serious ADRs 26 , but it is difficult to make a strict comparison because this study included not only hospitalizations but also outpatient visits.…”

“…This was followed by “respiratory system” and “antineoplastic and immunomodulating agents”. The suspected drugs were most commonly “cytostatics”, followed by “antibiotics” in the previous report from the Netherlands 24 . The suspected drugs were most commonly “anti-infective drugs” in the previous report from Saudi Arabia.…”

“…The causality of ADRs was 11.1% for “certain,” 22.2% for “probable/likely,” and 66.7% for “possible.” In a previous report on pediatric patients in a hospital in the Netherlands, the proportions were 25%, 24%, and 51%, respectively, based on the Causality Assessment System of WHO 24 . In another previous report on pediatric patients in a hospital in India, the proportions were 0%, 30%, and 70%, respectively, based on the Causality Assessment System of WHO 25 .…”

Global Perspective of Paediatric Pharmacovigilance and its Importance: Where Have We Reached?

“…Most participants recommended the implementation of educational programs and a series of continuing medical education (CME) programmes. Targeted outreach projects are obviously able to increase ADR reporting rates among doctor [31].…”