儿科患者的标签外用药：基于全国常规处方数据的对比分析。

Department of Pediatrics, Haydarpasa Numune Training and Research Hospital, İstanbul, Turkey.

Department of Medical Pharmacology, Marmara University Faculty of Medicine, İstanbul, Turkey.

Turk J Pediatr. 2020;62(6):949-961. doi: 10.24953/turkjped.2020.06.006.

BACKGROUND

Children constitute a special population for off-label drug use (OLDU), yet limited drug-focused data exist regarding pediatric OLDU in clinical practice. This study aimed to investigate pediatric OLDU practice and compare it with pediatric drug utilization patterns of routine prescribing data.

METHODS

This cross-sectional study examined all approved pediatric OLDU applications, compared with electronic prescription data on national Prescription Information System of Turkish Medicines and Medical Devices Agency in 2015. OLDU applications and prescriptions were analyzed for demographic characteristics, healthcare/socioeconomic indices as well as details of drugs and diagnoses.

RESULTS

We found 7,896 OLDU applications and 7,029,512 prescriptions for the pediatric population in 2015. OLDU applications and prescriptions were mostly practiced for 2-11-year-old children (52.7% vs. 63.4%, respectively; p < 0.01). OLDU applications and prescriptions were detected to have a positive correlation with socio-economic development index (r = 0.45, p < 0.0001 and r: 0.40, p = 0.0002; respectively) and the physician density (r = 0.66, p < 0.0001 and r: 0.43, p < 0.0001; respectively). In addition, OLDU was also positively correlated with the number of hospital beds per province (r = 0.39, p = 0.0003). Antineoplastic/immunomodulating agents were the most commonly applied drug category in OLDU (47.0%), compared with respiratory system drugs (36.6%) in routine prescribing. Eculizumab (6.5%), mycophenolate (5.6%), and canakinumab (4.4%) were the top drugs used as off-label. OLDU applications and routine prescription data revealed the most frequent diagnosis as I27-other pulmonary heart diseases (7.4%) and J06-acute upper respiratory infections (12.6%), respectively.

CONCLUSIONS

This is the first nationwide study to show indication- and drug-centered aspects of pediatric OLDU and prescribing practice. Though OLDU applications is overall consistent with routine clinical practice in terms of demographics and institutional capacity, substantial variations exist regarding main drug classes and diseases. Our findings are expected to shed light on interventions focused on improving indicated pediatric use of drugs currently applied as off-label.

背景

儿童是超说明书用药（OFF-LABEL DRUG USE，OLDU）的特殊群体，但目前临床实践中针对儿科 OLDU 的药物相关数据有限。本研究旨在调查儿科 OLDU 实践情况，并将其与常规处方数据中的儿科药物利用模式进行比较。

方法

本横断面研究分析了所有获批的儿科 OLDU 申请，并与 2015 年土耳其药品和医疗器械管理局国家处方信息系统的电子处方数据进行比较。对 OLDU 申请和处方的人口统计学特征、医疗/社会经济指标以及药物和诊断详细信息进行了分析。

结果

2015 年，我们共发现 7896 例儿科 OLDU 申请和 7029512 例儿科处方。52.7%（7896 例）的 OLDU 申请和 63.4%（7029512 例）的处方适用于“2-11 岁”儿童（p<0.01）。OLDU 申请和处方与社会经济发展指数呈正相关（r=0.45，p<0.0001 和 r：0.40，p=0.0002；分别），与医生密度呈正相关（r=0.66，p<0.0001 和 r：0.43，p<0.0001；分别）。此外，OLDU 与每省的医院床位数也呈正相关（r=0.39，p=0.0003）。在 OLDU 中，最常用的药物类别是抗肿瘤/免疫调节剂（47.0%），而在常规处方中最常用的是呼吸系统药物（36.6%）。依库珠单抗（6.5%）、霉酚酸酯（5.6%）和卡那单抗（4.4%）是最常作为 OLDU 使用的药物。OLDU 申请和常规处方数据显示，最常见的诊断分别为“I27-其他肺心病”（7.4%）和“J06-急性上呼吸道感染”（12.6%）。

结论

这是第一项针对儿科 OLDU 和处方实践的全国性研究，展示了以适应证和药物为中心的方面。尽管 OLDU 申请在人口统计学特征和机构能力方面与常规临床实践总体一致，但在主要药物类别和疾病方面存在很大差异。我们的研究结果有望为目前作为 OFF-LABEL 使用的药物的“适应证”儿科使用提供干预措施提供参考。