Population-based analysis of non-steroidal anti-inflammatory drug use among children in four European countries in the SOS project: what size of data platforms and which study designs do we need to assess safety issues?

BMC Pediatrics

Miriam CJM Sturkenboom⁹  Ernst J Kuipers³  Marco Villa⁵  Huub Straatman¹  Tania Schink⁶  Gino Picelli⁷  Silvia Lucchi⁵  Ron Herings¹  Edeltraut Garbe⁶  Andrea Arfe⁸  Martijn J Schuemie²  Silvana Romio⁸  Geert W ‘t Jong⁴  René Schade²  Vera E Valkhoff³ 

[1] PHARMO Institute, Van Deventerlaan, Utrecht, The Netherlands;Department of Medical Informatics, Erasmus University Medical Center, Dr. Molewaterplein, Rotterdam, The Netherlands;Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Dr. Molewaterplein, Rotterdam, The Netherlands;Division of Clinical Pharmacology & Toxicology, Hospital for Sick Children, University Avenue, Toronto, ON, Canada;Local Health Authority ASL Cremona, Via San Sebastiano, Cremona, Italy;Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology-BIPS, Bremen, Germany;International Pharmacoepidemiology and Pharmacoeconomics Research Center, Desio 20033, Italy;Division of Biostatistics and Public Health, Department of Quantitative Methods, University of Milano-Bicocca, Via Bicocca degli Arcimboldi, Milan, Italy;Department of Epidemiology, Erasmus University Medical Center, Dr. Molewaterplein, Rotterdam, The Netherlands

关键词: Case-crossover design;    Self-controlled case series design;    Asthma exacerbation;    Sample size;    Drug safety;    Health resource utilization;    Drug utilization;    Database;    Pharmacoepidemiology;   

Others  :  1144239
DOI  :  10.1186/1471-2431-13-192

 received in 2013-07-04, accepted in 2013-11-14,  发布年份 2013

【 摘 要 】

Background

Data on utilization patterns and safety of non-steroidal anti-inflammatory drugs (NSAIDs) in children are scarce. The purpose of this study was to investigate the utilization of NSAIDs among children in four European countries as part of the Safety Of non-Steroidal anti-inflammatory drugs (SOS) project.

Methods

We used longitudinal patient data from seven databases (GePaRD, IPCI, OSSIFF, Pedianet, PHARMO, SISR, and THIN) to calculate prevalence rates of NSAID use among children (0–18 years of age) from Germany, Italy, Netherlands, and United Kingdom. All databases contained a representative population sample and recorded demographics, diagnoses, and drug prescriptions. Prevalence rates of NSAID use were stratified by age, sex, and calendar time. The person-time of NSAID exposure was calculated by using the duration of the prescription supply. We calculated incidence rates for serious adverse events of interest. For these adverse events of interest, sample size calculations were conducted (alpha = 0.05; 1-beta = 0.8) to determine the amount of NSAID exposure time that would be required for safety studies in children.

Results

The source population comprised 7.7 million children with a total of 29.6 million person-years of observation. Of those, 1.3 million children were exposed to at least one of 45 NSAIDs during observation time. Overall prevalence rates of NSAID use in children differed across countries, ranging from 4.4 (Italy) to 197 (Germany) per 1000 person-years in 2007. For Germany, United Kingdom, and Italian pediatricians, we observed high rates of NSAID use among children aged one to four years. For all four countries, NSAID use increased with older age categories for children older than 11. In this analysis, only for ibuprofen (the most frequently used NSAID), enough exposure was available to detect a weak association (relative risk of 2) between exposure and asthma exacerbation (the most common serious adverse event of interest).

Conclusions

Patterns of NSAID use in children were heterogeneous across four European countries. The SOS project platform captures data on more than 1.3 million children who were exposed to NSAIDs. Even larger data platforms and the use of advanced versions of case-only study designs may be needed to conclusively assess the safety of these drugs in children.

【 授权许可】

   
2013 Valkhoff et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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