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Adverse Drug Reactions in Children — International Surveillance and Evaluation (ADVISE)

A Multicentre Cohort Study

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Abstract

Background: A previous meta-analysis reported that 9.5% of hospitalized children suffered from an adverse drug reaction (ADR); however, reported incidences among studies varied.

Objective: To enhance the knowledge of ADRs in paediatric hospitalized patients at a global level we investigated the incidence and characteristics of ADRs in hospitalized children in European and non-European countries.

Methods: A prospective observational cohort study was conducted in academic and non-academic hospitals in five countries: Australia, Germany, Hong Kong, Malaysia and the UK. Children aged 0–18 years admitted during a 3-month period (between 1 October 2008 and 31 December 2009) were recruited. The main outcome measures were incidence, causality and outcome of ADRs.

Results: A total of 1278 patients (1340 admissions) were included [Australia n = 146 (149 admissions), Germany n = 376 (407), Hong Kong n = 143 (149), Malaysia n = 300 (314) and the UK n = 313 (321)]. The median age was 2 years (interquartile range [IQR] 0–7). Patients received a total of 5367 drugs (median 3; IQR 2–5) and median length of hospital stay was 4 days (IQR 3–7). A total of 380 ADRs were identified in 211 patients. The resultant ADR incidence of 16.5% (95% CI 14.5, 18.7) varied significantly between countries (p < 0.001). The highest incidences were observed in Malaysia and the UK. 65.3%(n = 248) of ADRs were found to be probable, and 24% of the ADRs were serious, with one being fatal.

Conclusions: By comparing data from five countries in Europe, Asia and Australia we have shown that the incidence of ADRs in hospitalized children is at least as high as incidences published in adults. However, the variation between countries was mainly due to different populations and treatment strategies. Particular attention should be given to opioid use in hospitalized children.

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Acknowledgements

The authors wish to thank the paediatric medical ward staff in the hospitals in the five countries that participated in this study. In addition, we wish to thank Professor Stephen Evans for his statistical advice, Ann-Kathrin Schramm (Germany), Dr Norrashidah Bt Abdul Wahab (Malaysia), Dr Valerie Sung (Australia) and Tsui Ha Chan (Hong Kong) for their help with the data collection, Dr Lynda Wilton for reviewing the manuscript and Ben Cross for developing the database.

Antje Neubert and Ian C.K. Wong created the idea of the study. Ian C.K. Wong revised the methodology and supervised the study. Antje Neubert was the chief investigator of the study and supervised the analysis and data collection. Asia N. Rashed was responsible for the management and analysis of the data from all sites, data collection in the UK and input the data into the database. Noel Cranswick, Wolfgang Rascher, Stephen Tomlin, Kenneth Lee and Siew Siang Chua were responsible for study implementation and data collection in their sites. Asia N. Rashed, Barbara Hefele, John Jackman, Kam-Lun Hon, Jeffrey Ong, Maisoon Ghaleb, Noel Cranswick, Wolfgang Rascher, Stephen Tomlin, Kenneth Lee, Tea Ming Hui and Siew Siang Chua were responsible for data assessment. Asia N. Rashed produced the first draft of the manuscript and all authors approved the final draft.

Asia N. Rashed was funded by the Yamani Cultural and Charitable Foundation, London, UK. The study in Germany was funded in part by the ELAN (Erlanger Leistungsbezogene Anschubfinanzierung und Nachwuchsförderung) funds of the Medical Faculty of the Friedrich Alexander University, Erlangen-Nuremberg, Germany. Kam-Lun Hon has received travel support from Pfizer, Wyeth, GlaxoSmithKline and Leo Pharma. All other authors have declared that they have no financial interests that may be relevant to the submitted work.

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Authors and Affiliations

  1. Centre for Paediatric Pharmacy Research, UCL School of Pharmacy, London, UK

    Asia N. Rashed, Ian C. K. Wong &  Antje Neubert

  2. Pharmacology Research Unit, Royal Children Hospital, Parkville, Victoria, Australia

    Noel Cranswick & Jeffrey Ong

  3. Department of Paediatric and Adolescent Medicine, University Hospital Erlangen, Loschgestr. 15, 91054, Erlangen, Germany

    Barbara Hefele, Wolfgang Rascher &  Antje Neubert

  4. Evelina Children’s Hospital, Guy’s & St Thomas’ NHS Foundation Trust, London, UK

    Stephen Tomlin & John Jackman

  5. School of Pharmacy, The Chinese University of Hong Kong, Hong Kong

    Kenneth Lee

  6. Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong

    Kam-Lun E. Hon

  7. Department of Practice and Policy, School of Pharmacy, University of Hertfordshire, Hatfield, UK

    Maisoon Ghaleb

  8. Department of Pharmacy, University of Malaya, Kuala Lumpur, Malaysia

    Siew Siang Chua & Tea Ming Hui

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  1. Asia N. Rashed
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Correspondence to Antje Neubert.

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Rashed, A.N., Wong, I.C.K., Cranswick, N. et al. Adverse Drug Reactions in Children — International Surveillance and Evaluation (ADVISE). Drug Saf 35, 481–494 (2012). https://doi.org/10.2165/11597920-000000000-00000

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