Pediatric drug safety signal detection of non-chemotherapy drug-induced neutropenia and agranulocytosis using electronic healthcare records

ABSTRACT

Objectives: This study aimed to develop a procedure to explore the adverse drug reaction signals of drug-induced neutropenia (DIN) or drug-induced agranulocytosis (DIA) in children using an electronic health records (EHRs) database.

Methods: A two-stage design was presented. First, the suspected drugs to induce DIN or DIA were selected. Second, the associations were evaluated by a retrospective cohort study.

Results: Ten and five drugs were potentially identified to be associated with DIN and DIA, respectively. Finally, five (oseltamivir, chlorpheniramine, vancomycin, meropenem, and ganciclovir) and two (chlorpheniramine, and vancomycin) drugs were found to be associated with DIN and DIA, respectively. Of these, the association between oseltamivir and neutropenia (P = 9.83 × 10^–9; OR, 2.10; 95% CI, 1.62−2.69) was considered as a new signal for both adults and children. Chlorpheniramine-induced neutropenia (P = 3.01 × 10^–8; OR, 1.59; 95% CI, 1.35−1.87) and agranulocytosis (P = 3.16 × 10^–7; OR, 3.76; 95% CI, 2.25−6.26) were considered as new signals in children. Other drugs associated with DIN or DIA were confirmed by previous studies.

Conclusion: A method to detect signals for DIN and DIA has been described. Several pediatric drugs were found to be associated with DIN or DIA.

KEYWORDS:

• Electronic healthcare records
• drug safety
• signal detection
• drug-induced neutropenia
• drug-induced agranulocytosis
• children

Authors’ contributions

R Wei contributed to the data collection, data analysis, interpretation of data and drafting the article. ZG Zhao and XL Wang contributed to the conception and design of the study. LL Jia, YC Yu, ZY Song, DF Fan and YF Xie contributed to the data collection. YC Yu, XL Nie and XX Peng contributed to the data analysis. LL Jia and YC Yu contributed to drafting the article and offered important recommendations in terms of methodology.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the National Major Scientific and Technological Special Project for ‘Significant New Drugs Development’ during the 13th Five-year Plan Period (no. 2017ZX09304029) and the National Natural Science Foundation of China (81400766).