To investigate the safety issues, including adverse events (AEs), adverse events related to SMDS (ADEs), and adverse drug reactions (ADRs) of the SMDS in the real world clinical practice
General Information of Study
Name Post-Marketing Safety Surveillance of the Salvia Miltiorrhiza Depside Salt for Infusion Project Number CCC2018111901 Website NA Investigators Institutions Department of Pharmacy, Peking University Third Hospital Contacts Funding State Administration of Traditional Chinese Medicine of the People’s Republic of China (2013ZX03) Objectives To investigate the safety issues, including adverse events (AEs), adverse events related to SMDS (ADEs), and adverse drug reactions (ADRs) of the SMDS in the real world clinical practice Start Date Mar 19, 2012. End Date Jan 8, 2015
Number of Participants 30180 Age Range 2~100 Geographic Distribution Nine province: Beijing，Xinjiang, Hubei, Shannxi, Heibei, Shanghai, Anhui, Sichuan, Jiangsu General Information of Study Design and Sample Methods None Inclusion Criteria Patients who were prescribed SMDS (Shanghai Green Valley Pharmaceutical Co, Ltd) during APR 2012 to JAN 2015, including inpatients, patients in the emergency, and outpatients with safety information, were all included in each site. Considering the t1/2 of SMDS is only 2.87h, patients were followed up until discharged or 14 days after SMDS discontinued Exclusion Criteria None
Key Achievements Thirty six hospitals were participated in the study and 30180 consecutive inpatients were included. The median age was 62 (interquartile range [IQR], 50–73) years, and male was 17384 (57.60%) among the 30180 patients. The incidences of the AEs, ADEs and ADRs were 6.40%, 1.57% and 0.79%, respectively. There were 9 kinds of new ADEs which were not on the approved label found in the present study, including rash, pruritus, erythemas, palpitations, fecal occult blood positive,
international normalised ratio increased, blood bilirubin increased, blood creatinine increased and platelet count abnormal. According to the multivariate analysis, male (RR = 1.381, P = 0.009, 95%CI [1.085~1.759]), more concomitant medications (RR = 1.049, P<0.001, 95%CI [1.041~1.057]), longer duration of SMDS therapy (RR = 1.027, P<0.001, 95%CI [1.013~1.041]), higher drug concentration (RR = 1.003, P = 0.014, 95%CI [1.001~1.006]), and resolvent unapproved (RR = 1.900, P = 0.002, 95%CI [1.260~2.866]) were the independent risk factors of the ADEs. Moreover, following the approved indication (RR = 0.655, P<0.001, 95%CI [0.532~0.807]) was associated with lower incidence of ADEs. It is recommended to follow the instructions when prescribing and administrating SMDS in the real world clinical practice.
Marker Papers Yan Y-Y, Yang Y-H, Wang W-W, Pan Y-T, Zhan S-Y, Sun M-Y, et al. (2017) Post-Marketing Safety Surveillance of the Salvia Miltiorrhiza Depside Salt for Infusion: A Real World Study. PLoS ONE 12(1): e0170182. doi:10.1371/journal. pone.0170182 Strength There are several other strengths in this study.
One is the representative of the sample. This pharmacist-led and large sample size design could avoid the selection bias maximum likelihood. Although the hospital is conducted mainly by physician, Wuhan Asia Heart Hospital is a cardiology specialized hospital which only has 2 clinical departments and could follow the protocol. Selection bias from 2 aspects would be avoided in drug safety study led by pharmacists. Firstly, without pharmacy data from the whole hospital, physicians might only focus on their own specialties which led to miss patients meeting the eligibility criteria. Then, there might be selective prescribing behavior by physicians in the observational study. In addition, we selected diverse hospital representatives in different levels and types.
Secondly, this cohort study is similar to products registry. With comprehensive data elements and data collection, the clinical prescribing pattern of SMDS in real world setting, including rational and irrational drug use, could be firstly assessed, and the risk of different clinical practice could be evaluated.
Thirdly, the present study is the first study to illustrate the safety issue and the risk factors of SMDS.
Weakness There are also some limitations of this study.
Very few outpatients were included in the study because of feasible difficulties. Since the electronic medical record system are quite different among each hospital in mainland China, follow-up information of outpatients was not available that led to many exclusion because of lacking full safety information.
Then, it is a challenge to evaluate effectiveness of SMDS with a single arm study design. However, with relatively full information collected, including the combined medications and outcomes of the disease, this study could provide the effectiveness of other medications indirectly when group them differently despite of the bias.
Thirdly, the long-term safety is difficult to investigate because of the relatively short follow-up. However, with the comprehensive study on the pharmacokinetics when compared with other TCM injection, adverse events may explained by its PK profile. Considering the pharmacokinetics parameters (t1/2 of SMDS is 2.87h; t1/2 of the metabolites are all 0.49–0.63h; SMDS could be rapidly metabolized; and SMDS excreted into bile rapidly mostly as methylated metabolites), our follow up duration could cover the progress of the metabolism and excretion to some extent.
General Information of Baseline Investigation
Variables of Baseline Investigation
General Information of Follow-up Investigation
Variables of Follow-up Investigation