药品不良反应监测中的序贯概率比检验方法

中国药物警戒 ›› 2018, Vol. 15 ›› Issue (4): 221-225.

药品不良反应监测中的序贯概率比检验方法

张新佶, 郭晓晶, 叶小飞, 彭旭娇, 贺佳^*

海军军医大学卫勤系,上海 200433

收稿日期:2018-05-29 修回日期:2018-05-29 出版日期:2018-04-20 发布日期:2018-05-29
通讯作者: 贺佳,女,教授·博导,药物流行病学及新药评价的统计分析。E-mail:hejia63@yeah.net
作者简介:张新佶,女,副教授,药物流行病学。
基金资助:
国家自然科学基金(81502895)：上市后药品不良反应信号检测中双稳健方法的构建; 国家自然科学基金(81703296)：药品不良反应监测中多重性检验和低频数膨胀问题的研究; 上海市自然科学基金（18ZR1449500)：疾病风险评分模型研究及在药品不良反应主动监测中的应用; 上海市第四轮公共卫生三年行动计划重点学科建设项目(15GWZK0901)：循证公共卫生与卫生经济学

Sequential Probability Ratio Analysis in Post-market Drug Safety Surveillance

ZHANG Xin-ji, GUO Xiao-jing, YE Xiao-fei, PENG Xu-jiao, HE Jia^*

Faculty of Health Services, Naval Military Medical University, Shanghai 200433, China

Received:2018-05-29 Revised:2018-05-29 Online:2018-04-20 Published:2018-05-29

摘要/Abstract

摘要： 目的序贯概率比检验方法在美国已被用于多种疫苗上市后实时安全性监测,也是目前药品不良反应信号检测的研究热点。然而,该方法的应用在我国少见报道,本研究对这类方法进行概述。方法通过文献检索,对连续性和成组序贯概率比检验方法的原理进行综述,并比较二者的优缺点,总结该类方法的应用现状,并对该类研究的进一步探索方向进行了展望。结果现有研究表明序贯概率比方法在药品安全性监测过程中有助于信号提炼,目前连续性序贯概率比检验应用较多,但成组序贯概率比方法有很大的发展空间。结论序贯概率比检验方法是一种实时监测药品安全性的可行方法,但仍有许多问题值得进一步探索。

关键词: 序贯概率比检验, 药品不良反应, 实时监测

Abstract: Objective To review currently used sequential probability ratio analysis methods in medical product safety surveillance. Methods The principles of continuous and group sequential probability ratio analysis methods were reviewed. The key features of these two kinds of sequential methods were compared, and the application status was summarized. Meanwhile, we discussed the areas needed further development. Results The use of sequential probability ratio analysis for post-market drug safety surveillance was quickly emerging. Continuous sequential methods were the preferred approach, but group sequential methods were also promising. ConclusionSequential probability ratio analysis is a feasible method to monitor the drug safety in real time, but methodological development is needed to improve success.

Key words: sequential probability ratio test, adverse drug reaction, near real-time surveillance

中图分类号:

R994.11

张新佶, 郭晓晶, 叶小飞, 彭旭娇, 贺佳. 药品不良反应监测中的序贯概率比检验方法[J]. 中国药物警戒, 2018, 15(4): 221-225.

ZHANG Xin-ji, GUO Xiao-jing, YE Xiao-fei, PENG Xu-jiao, HE Jia. Sequential Probability Ratio Analysis in Post-market Drug Safety Surveillance[J]. Chinese Journal of Pharmacovigilance, 2018, 15(4): 221-225.

参考文献

[1] Nelson J C, Cook A J, Yu O, et al.Methods for observational post-licensure medical product safety surveillance[J]. Statistical Methods in Medical Research, 2015, 24(2):177-193.
[2] Wald A.Sequential Tests of Statistical Hypotheses[J]. Annals of Mathematical Statistics, 1945, 16(2):117-186.
[3] Kulldorff M, Davis R, Kolczakâ M, et al. A Maximized Sequential Probability Ratio Test for Drug and Vaccine Safety Surveillance[J].Communications in Statistics Part C Sequential Analysis, 2011, 30(1):58-78.
[4] Li L, Kulldorff M.A conditional maximized sequential probability ratio test for pharmacovigilance[J]. Statistics in Medicine, 2010, 29(2):284-295.
[5] Nelson J C, Cook A J, Yu O, et al.Challenges in the design and analysis of sequentially monitored postmarket safety surveillance evaluations using electronic observational health care data[J]. Pharmacoepidemiology & Drug Safety, 2012, 21(S1):62-71.
[6] Zhao S, Cook A, Jackson L, et al.Statistical performance of group sequential methods for observational post-licensure medical product safety surveillance: A simulation study[J]. Statistics & Its Interface, 2012, 5(4):381-390.
[7] Lai T L, Shih M C.Power, sample size and adaptation considerations in the design of group sequential clinical trials[J]. Biometrika, 2004, 91(3):507-528.
[8] Brown J S, Kulldorff M, Chan K A, et al.Early detection of adverse drug events within population-based health networks: application of sequential testing methods[J]. Pharmacoepidemiology & Drug Safety, 2010, 16(12):1275-1284.
[9] Nelson J C, Yu O, Dominguezislas C P, et al.Adapting Group Sequential Methods to Observational Postlicensure Vaccine Safety Surveillance: Results of a Pentavalent Combination DTaP-IPV-Hib Vaccine Safety Study[J]. American Journal of Epidemiology, 2013, 177(2):131-41.
[10] Silva I R, Kulldorff M.Continuous versus group sequential analysis for post market drug and vaccine safety surveillance[J]. Biometrics, 2015, 71(3):851-858.
[11] 李婵娟. 药品不良反应信号检测方法理论及应用研究[D]. 第四军医大学, 2008.
[12] 邹元平, 林宇, 邢珂, 等. 中药不良反应信号检测系统的建立[J]. 中国药房, 2012(27):2584-2587.
[13] 林宇, 邢珂, 邹元平, 等. 中药注射剂不良反应信号检测研究[J]. 中药新药与临床药理, 2012, 23(3):357-360.
[14] Chan C L, Rudrappa S, Ang P S, et al.Detecting Signals of Disproportionate Reporting from Singapore's Spontaneous Adverse Event Reporting System: An Application of the Sequential Probability Ratio Test[J]. Drug Safety, 2017, 40(1):1-11.
[15] Davis R L, Kolczak M E, Nordin J, et al.Active surveillance of vaccine safety: a system to detect early signs of adverse events[J]. Epidemiology, 2005, 16(3):336-341.
[16] Yih W K, Nordin J D, Kulldorff M, et al.An assessment of the safety of adolescent and adult tetanus-diphtheria-acellular pertussis (Tdap) vaccine, using active surveillance for adverse events in the Vaccine Safety Datalink[J]. Vaccine, 2009, 27(32):4257-4262.
[17] Belongia E A, Irving S A, Shui I M, et al.Real-time surveillance to assess risk of intussusception and other adverse events after pentavalent, bovine-derived rotavirus vaccine[J]. Pediatric Infectious Disease Journal, 2010, 29(1):1-5.
[18] Klein N P, Fireman B, Yih W K, et al.Measles-Mumps-Rubella-Varicella Combination Vaccine and the Risk of Febrile Seizures[J]. Pediatrics, 2010, 126(1):1-8.
[19] Weintraub E S, Baggs J, Duffy J, et al.Risk of intussusception after monovalent rotavirus vaccination[J]. New England Journal of Medicine, 2014, 40(3):453-454.
[20] Kawai A T, Li L, Kulldorff M, et al.Absence of associations between influenza vaccines and increased risks of seizures, Guillain-Barre syndrome, encephalitis, or anaphylaxis in the 2012-2013 season[J]. Pharmacoepidemiology & Drug Safety, 2014, 23(5):548-553.
[21] Leite A, Andrews N J, Thomas S L.Near real-time vaccine safety surveillance using electronic health records-a systematic review of the application of statistical methods[J]. Pharmacoepidemiol Drug Saf, 2016, 25(3):225-237.
[22] Kulldorff M, Silva I R. Continuous Post-Market Sequential Safety Surveillance with Minimum Events to Signal [EB/OL]. (2015-03-06) [2018-03-24]. http://arxiv.org/abs/1503.01978.
[23] Stratton K G, Cook A J, Jackson L A, et al.Simulation study comparing exposure matching with regression adjustment in an observational safety setting with group sequential monitoring[J]. Statistics in Medicine, 2015, 34(7):1117-1133.
[24] Li L, Kulldorff M, Nelson J C, et al.A Propensity Score-Enhanced Sequential Analytic Method for Comparative Drug Safety Surveillance[J]. Statistics in Biosciences, 2011, 3(1):45-62.
[25] Yih W K, Kulldorff M, Fireman B H, et al.Active Surveillance for Adverse Events: The Experience of the Vaccine Safety Datalink Project[J]. Pediatrics, 2011, 127(S1): 54-64.
[26] Mcclure D L, Raebel M A, Yih W K, et al.Mini-Sentinel methods:framework for assessment of positive results from signal refinement[J]. Pharmacoepidemiology & Drug Safety, 2014, 23(1):3-8.
[27] Schneeweiss S.A basic study design for expedited safety signal evaluation based on electronic healthcare data[J]. Pharmacoepide-miology & Drug Safety, 2010, 19(8):858-868.