This study aims to analyze the clinical use of ornidazole injection at the post-marketing stage by centralized hospital monitoring system method,and investigate its widespread use in patients,in order to regulate and ...This study aims to analyze the clinical use of ornidazole injection at the post-marketing stage by centralized hospital monitoring system method,and investigate its widespread use in patients,in order to regulate and guide the rational drug use,improve the drug specificity and provide a basis for drug therapy.The study adopts a prospective,multi-center,large sample size,centralized hospital monitoring system.We selected five leading hospitals in Hubei province,and observed the inpatients who received the ornidazole injection from July 1,2015 to October 31,2015.The basic information of patients was recorded,as well as the drug use and adverse events.The statistical analysis was performed based on these data.A total of 4396 individuals were enrolled in this study,most of them were middle-aged female patients and the ornidazole injection was mainly used as prophylactic prior to surgery to prevent the infections,and surgical treatment of anaerobic infections,abdominal infections and pelvic infections.The irrational drug use existed mainly in the prescribing and administration process,including unreasonable dosing frequency,rapid intravenous drip speed and extended duration of drug use.Eleven cases of adverse reactions were collected during the monitoring,incidence rate of adverse reactions was 2.5‰;adverse drug reactions occurred within 30 min.The study results fully reflected the usage of ornidazole injection in the real world.Based on the study,we calculated the adverse reaction incidence of ornidazole and identified the risk factors which may affect the safety of ornidazole injection.Study results strongly recommend that the manufacturers should publish standards for inpatient use and doctors should prescribe with caution accordingly.展开更多
OBJECTIVE:Toidentify the potential risk factors associated with Shenqifuzheng injection(SFI), a solution made of Dangshen(Radix Codonopsis) and Huangqi(Radix Astragali Mongolici), for the timely provision of informati...OBJECTIVE:Toidentify the potential risk factors associated with Shenqifuzheng injection(SFI), a solution made of Dangshen(Radix Codonopsis) and Huangqi(Radix Astragali Mongolici), for the timely provision of information to regulatory authorities.METHODS: A comprehensive analysis of the production process, quality standards, pharmacology,post-marketing clinical studies, and safety evaluation using the primary literature of adverse reactions(ADR), case analyses, and systematic reviews,intensive hospital safety monitoring of post-marketing drugs, and data provided by the hospital in-formationsystem(HIS).RESULTS: Sub-acute toxicity tests suggesting that a dose of 15 mL/kg(concentrated solution) had specific biological effects, whereas a smaller dose engendered no observable effects. Long-term toxicity testing in domestic rabbits showed that after SFI was administered for 90 days, the animals in each dosing group showed no chronic toxic reactions. Among 20 100 cases observed, the incidence of an ADR was 1.85‰. From March to November 2013,of the leading institutions and 22 sub-centers involved in the post-marketing clinical safety intensive hospital monitoring, 21 units completed 8484 cases of monitoring, and reported 23 cases of adverse reactions. No damage to renal function was found using SFI ata dosageanda treatment course larger and longer than that recommended for the adjuvant treatment of tumors. This could reduce the mortality rate of admitted patients based on the analysis of the data provided by the HIS. A total of 16 clinical case reports of adverse reactions related to SFI in 1999-2012 were obtained through literature retrieval. These reports contained information concerning 17 cases, with adverse reaction symptoms including thrombocytopenia, rash,chills,feeling cold,palpitation,dyspnea,edemaofa lower extremity, palpebral edema, and superficial vein in flammation,among others.CONCLUSION: This study introduces "get full access" to the flow of information on medicines regarding their ADR incidence rate and characteristics and factors.It supports the safety of SFI for clinical, research, and production uses based on objec-tive, reliable, and scientific information to provide safe medication.展开更多
The clinical efficacy and safety of proprietary Chinese medicine has become a more prevailing public health concern.The China Food and Drug Administration has pushed drug companies to conduct post-marketing reappraisa...The clinical efficacy and safety of proprietary Chinese medicine has become a more prevailing public health concern.The China Food and Drug Administration has pushed drug companies to conduct post-marketing reappraisal for proprietary Chinese medicine to provide additional evidence supporting the efficacy and safety of these medicine.In this paper,we propose a reappraisal protocol called“precise proprietary Chinese medicine”to precisely i)define the therapeutic aim;ii)design the protocol;iii)control the quality of proprietary Chinese medicine;iv)implement the protocol in the trial;v)study the mechanism-of-action of the proprietary Chinese medicine and vi)describe the indications of the proprietary Chinese medicine.We hope that these steps facilitate the post-marketing reappraisal of proprietary Chinese medicine.展开更多
Aims: In the Add-on Lantus®?to Oral Hypoglycaemic Agents 2 (ALOHA 2) Study in Japanese adults with type 2 diabetes mellitus (T2DM), data on the safety and efficacy of combination therapy with insulin glargine ...Aims: In the Add-on Lantus®?to Oral Hypoglycaemic Agents 2 (ALOHA 2) Study in Japanese adults with type 2 diabetes mellitus (T2DM), data on the safety and efficacy of combination therapy with insulin glargine (Lantus®) and oral anti-hyperglycaemic drugs (OADs) including dipeptidyl peptidase-4 (DPP-4) inhibitors in a real-life setting were collected and analyzed. Methods: This postmarketing surveillance was a prospective, observational, 24-week study that complied with the pharmaceutical affairs law and the ministerial ordinance of “Good Post-Marketing Study Practice (GPSP)” in Japan. Safety, efficacy and patient-reported outcomes (PROs);patients’ satisfaction with treatment (DTSQs and DTSQc) and patients’ self-reported health (EQ-5D and EQ-VAS) of combination therapy of insulin glargine and OADs were evaluated. Results: A total of 2,630 patients were enrolled. Of the 2,602 patients in the safety analysis population, 161 patients experienced 175 cases of adverse drug reactions, and the major adverse drug reaction was hypoglycaemia (140 patients, 5.38%). Out of those with hypoglycaemia, 11 patients (0.42%) had severe hypoglycaemia and the incidence rate (episodes per patient-year) was 0.019. Basal supported oral therapy (BOT) with insulin glargine substantially reduced the HbA1c, FPG and 2 hour-PPG levels for 24 weeks by -1.61%, -54.4 mg/dL and -74.5 mg/dL respectively. The mean weight was increased, however the change was +0.50 kg. In addition, the treatment satisfaction scores of DTSQs (mean treatment satisfaction score increased 3.6 from baseline to last observation) and DTSQc, EQ-5D index scores and EQ-VAS scores were significantly improved. Conclusion: Insulin glargine and OADs combination therapy was suggested to be effective and well tolerated. Patients’ satisfaction with treatment and their self-reported health improved in spite of the addition of injections to oral agents. The combination therapy of insulin glargine and OADs including DPP-4 inhibitors is likely to be considered an important therapeutic option in the diabetic patients.展开更多
This paper reviewed the situation of regulations and guidelines on post-marketing medicines in the developed countries and in China. The developed countries have accumulated a lot of empirical principles and technique...This paper reviewed the situation of regulations and guidelines on post-marketing medicines in the developed countries and in China. The developed countries have accumulated a lot of empirical principles and techniques on post- marketing surveillance （also named pharmacovigilance）, therefore, their regulation systems are nearly perfect. In China, the regulations on post-marketing re-evaluation and relative technical guidelines do not cover the whole aspects, even lack in some important aspects, and long-term risk management mechanisms have not been established. So it is urgent to establish new regulations and improve the regulatory system in China based on the existing regulations and guidelines, by learning from the ideas of foreign advanced regulations, then fully integrating them with China＇s actual conditions, and cooperating with multidisciplinary researchers.展开更多
Objective: To evaluate the efficacy and safety of Tongxiening Granules(痛泻宁颗粒, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea(IBS-D). Methods: A randomized, double-blind, double-dummy...Objective: To evaluate the efficacy and safety of Tongxiening Granules(痛泻宁颗粒, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea(IBS-D). Methods: A randomized, double-blind, double-dummy, and positive paral el control ed clinical trial was conducted from October 2014 to March 2016. Total y 342 patients from 13 clinical centers were enrolled and randomly assigned(at the ratio of 1:1) to a treatment group(171 cases) and a control group(171 cases) by a random coding table. The patients in the treatment group were administered oral y with TXNG(5 g per time) combined with pinaverium bromide Tablet simulator(50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator(5 g per time) combined with pinaverium bromide Tablets(50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score(IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief(AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire(IBS-QOL), Hamilton Anxiety Scale(HAMA), Hamilton Depression Scale(HAMD), and the recurrence rate at fol ow-ups. Safety indices including the adverse events(AEs) and related laboratory tests were evaluated. Results: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set(FAS) and per protocol set(PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group(147/171, 86.0%) was higher than the control group(143/171, 83.6%) by FAS(P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups(P>0.05). The recurrence rate at 8-week fol ow-up was 12.35%(10/18) in treatment group and 15.79%(12/76) in control group, respectivery(P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups(P>0.05). Conclusion: Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide.(No. ChiCTR-IPR-15006415)展开更多
ABSTRACT Evidence based medicine demands the highest form of scientific evidence to demonstrate the efficacy and clinical effectiveness for any therapeutic intervention in order to provide best care. It is however acc...ABSTRACT Evidence based medicine demands the highest form of scientific evidence to demonstrate the efficacy and clinical effectiveness for any therapeutic intervention in order to provide best care. It is however accepted that in the absence of scientific evidence, personal experience and expert opinion together with professional judgement are critical. Obtaining evidence for drug safety, post- marketing surveillance （PMS） has focussed on follow up of observational cohorts exposed to a particular drug in order to estimate the incidence of adverse drug reactions （ADRs）. Evidence on PMS of Chinese herbal products is still limited, in particular for herbal injections. The aim of this article is to suggest a new model of ascertaining the safety of Chinese medicine using a more comprehensive approach for collecting data. To collect safety data on the Chinese herbal injection, Kudiezi, a mixed methods approach is proposed using 18 hospital information systems to detectADRs in order to prospectively observe 30,000 patients over 3 years. Evidence will also be collected using a questionnaire survey and through a sample of semi structured interviews. This information based on the expert opinion and the experience of clinicians will produce additional data on the frequency and types of side effects in clinical practice. Furthermore semi structured interviews with a random sample of patients receiving the injection will be carried out to ascertain any potential side effects missed. It is hoped that this comprehensive approach to data collection will accumulate wider evidence based on individual traditional Chinese medicine care and treatment and provide important feedback to the national data collection system to ensure completeness of ADR data recording, monitoring and any potential wider effects through developing improved ADR guidelines.展开更多
戊型肝炎(简称“戊肝”)是一种由戊型肝炎病毒(Hepatitis E virus,简称“HEV”)引起的病毒性肝脏炎症,在孕妇、患有基础性肝病、免疫缺陷等人群中可导致严重疾病,卫生资源欠佳的地区常发生暴发流行。目前尚缺乏针对戊肝的特效治疗方法,...戊型肝炎(简称“戊肝”)是一种由戊型肝炎病毒(Hepatitis E virus,简称“HEV”)引起的病毒性肝脏炎症,在孕妇、患有基础性肝病、免疫缺陷等人群中可导致严重疾病,卫生资源欠佳的地区常发生暴发流行。目前尚缺乏针对戊肝的特效治疗方法,因此,接种戊肝疫苗成为戊肝防控的关键措施。全球唯一的戊肝疫苗HEV 239安全性良好,且具有可持续至少十年的高效保护性。2022年,HEV 239疫苗被无国界医生组织成功用于南苏丹的戊肝疫情控制,2024年该疫苗被纳入全球疫苗免疫联盟的战略储备,这均为戊肝疫苗未来更加广泛的真实世界应用奠定了基础。本文对HEV 239疫苗上市后的临床研究进展及真实世界应用情况进行综述。展开更多
文摘This study aims to analyze the clinical use of ornidazole injection at the post-marketing stage by centralized hospital monitoring system method,and investigate its widespread use in patients,in order to regulate and guide the rational drug use,improve the drug specificity and provide a basis for drug therapy.The study adopts a prospective,multi-center,large sample size,centralized hospital monitoring system.We selected five leading hospitals in Hubei province,and observed the inpatients who received the ornidazole injection from July 1,2015 to October 31,2015.The basic information of patients was recorded,as well as the drug use and adverse events.The statistical analysis was performed based on these data.A total of 4396 individuals were enrolled in this study,most of them were middle-aged female patients and the ornidazole injection was mainly used as prophylactic prior to surgery to prevent the infections,and surgical treatment of anaerobic infections,abdominal infections and pelvic infections.The irrational drug use existed mainly in the prescribing and administration process,including unreasonable dosing frequency,rapid intravenous drip speed and extended duration of drug use.Eleven cases of adverse reactions were collected during the monitoring,incidence rate of adverse reactions was 2.5‰;adverse drug reactions occurred within 30 min.The study results fully reflected the usage of ornidazole injection in the real world.Based on the study,we calculated the adverse reaction incidence of ornidazole and identified the risk factors which may affect the safety of ornidazole injection.Study results strongly recommend that the manufacturers should publish standards for inpatient use and doctors should prescribe with caution accordingly.
基金Supported by National Science and Technology Major Projects for "Major New Drugs Innovation and Development":Study on Key Technologies of Post-marketing Evaluation for Chinese Medicine(No.2009ZX09502-030)
文摘OBJECTIVE:Toidentify the potential risk factors associated with Shenqifuzheng injection(SFI), a solution made of Dangshen(Radix Codonopsis) and Huangqi(Radix Astragali Mongolici), for the timely provision of information to regulatory authorities.METHODS: A comprehensive analysis of the production process, quality standards, pharmacology,post-marketing clinical studies, and safety evaluation using the primary literature of adverse reactions(ADR), case analyses, and systematic reviews,intensive hospital safety monitoring of post-marketing drugs, and data provided by the hospital in-formationsystem(HIS).RESULTS: Sub-acute toxicity tests suggesting that a dose of 15 mL/kg(concentrated solution) had specific biological effects, whereas a smaller dose engendered no observable effects. Long-term toxicity testing in domestic rabbits showed that after SFI was administered for 90 days, the animals in each dosing group showed no chronic toxic reactions. Among 20 100 cases observed, the incidence of an ADR was 1.85‰. From March to November 2013,of the leading institutions and 22 sub-centers involved in the post-marketing clinical safety intensive hospital monitoring, 21 units completed 8484 cases of monitoring, and reported 23 cases of adverse reactions. No damage to renal function was found using SFI ata dosageanda treatment course larger and longer than that recommended for the adjuvant treatment of tumors. This could reduce the mortality rate of admitted patients based on the analysis of the data provided by the HIS. A total of 16 clinical case reports of adverse reactions related to SFI in 1999-2012 were obtained through literature retrieval. These reports contained information concerning 17 cases, with adverse reaction symptoms including thrombocytopenia, rash,chills,feeling cold,palpitation,dyspnea,edemaofa lower extremity, palpebral edema, and superficial vein in flammation,among others.CONCLUSION: This study introduces "get full access" to the flow of information on medicines regarding their ADR incidence rate and characteristics and factors.It supports the safety of SFI for clinical, research, and production uses based on objec-tive, reliable, and scientific information to provide safe medication.
文摘The clinical efficacy and safety of proprietary Chinese medicine has become a more prevailing public health concern.The China Food and Drug Administration has pushed drug companies to conduct post-marketing reappraisal for proprietary Chinese medicine to provide additional evidence supporting the efficacy and safety of these medicine.In this paper,we propose a reappraisal protocol called“precise proprietary Chinese medicine”to precisely i)define the therapeutic aim;ii)design the protocol;iii)control the quality of proprietary Chinese medicine;iv)implement the protocol in the trial;v)study the mechanism-of-action of the proprietary Chinese medicine and vi)describe the indications of the proprietary Chinese medicine.We hope that these steps facilitate the post-marketing reappraisal of proprietary Chinese medicine.
文摘Aims: In the Add-on Lantus®?to Oral Hypoglycaemic Agents 2 (ALOHA 2) Study in Japanese adults with type 2 diabetes mellitus (T2DM), data on the safety and efficacy of combination therapy with insulin glargine (Lantus®) and oral anti-hyperglycaemic drugs (OADs) including dipeptidyl peptidase-4 (DPP-4) inhibitors in a real-life setting were collected and analyzed. Methods: This postmarketing surveillance was a prospective, observational, 24-week study that complied with the pharmaceutical affairs law and the ministerial ordinance of “Good Post-Marketing Study Practice (GPSP)” in Japan. Safety, efficacy and patient-reported outcomes (PROs);patients’ satisfaction with treatment (DTSQs and DTSQc) and patients’ self-reported health (EQ-5D and EQ-VAS) of combination therapy of insulin glargine and OADs were evaluated. Results: A total of 2,630 patients were enrolled. Of the 2,602 patients in the safety analysis population, 161 patients experienced 175 cases of adverse drug reactions, and the major adverse drug reaction was hypoglycaemia (140 patients, 5.38%). Out of those with hypoglycaemia, 11 patients (0.42%) had severe hypoglycaemia and the incidence rate (episodes per patient-year) was 0.019. Basal supported oral therapy (BOT) with insulin glargine substantially reduced the HbA1c, FPG and 2 hour-PPG levels for 24 weeks by -1.61%, -54.4 mg/dL and -74.5 mg/dL respectively. The mean weight was increased, however the change was +0.50 kg. In addition, the treatment satisfaction scores of DTSQs (mean treatment satisfaction score increased 3.6 from baseline to last observation) and DTSQc, EQ-5D index scores and EQ-VAS scores were significantly improved. Conclusion: Insulin glargine and OADs combination therapy was suggested to be effective and well tolerated. Patients’ satisfaction with treatment and their self-reported health improved in spite of the addition of injections to oral agents. The combination therapy of insulin glargine and OADs including DPP-4 inhibitors is likely to be considered an important therapeutic option in the diabetic patients.
基金Supported by the Research on Key Techniques of Reevaluation of Post-marketing Chinese Medicines,the Ministry of Science and Technology(No.2009ZX09502-030)the Sixth-Science Foundation of Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences(No. Z0215)
文摘This paper reviewed the situation of regulations and guidelines on post-marketing medicines in the developed countries and in China. The developed countries have accumulated a lot of empirical principles and techniques on post- marketing surveillance （also named pharmacovigilance）, therefore, their regulation systems are nearly perfect. In China, the regulations on post-marketing re-evaluation and relative technical guidelines do not cover the whole aspects, even lack in some important aspects, and long-term risk management mechanisms have not been established. So it is urgent to establish new regulations and improve the regulatory system in China based on the existing regulations and guidelines, by learning from the ideas of foreign advanced regulations, then fully integrating them with China＇s actual conditions, and cooperating with multidisciplinary researchers.
文摘Objective: To evaluate the efficacy and safety of Tongxiening Granules(痛泻宁颗粒, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea(IBS-D). Methods: A randomized, double-blind, double-dummy, and positive paral el control ed clinical trial was conducted from October 2014 to March 2016. Total y 342 patients from 13 clinical centers were enrolled and randomly assigned(at the ratio of 1:1) to a treatment group(171 cases) and a control group(171 cases) by a random coding table. The patients in the treatment group were administered oral y with TXNG(5 g per time) combined with pinaverium bromide Tablet simulator(50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator(5 g per time) combined with pinaverium bromide Tablets(50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score(IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief(AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire(IBS-QOL), Hamilton Anxiety Scale(HAMA), Hamilton Depression Scale(HAMD), and the recurrence rate at fol ow-ups. Safety indices including the adverse events(AEs) and related laboratory tests were evaluated. Results: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set(FAS) and per protocol set(PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group(147/171, 86.0%) was higher than the control group(143/171, 83.6%) by FAS(P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups(P>0.05). The recurrence rate at 8-week fol ow-up was 12.35%(10/18) in treatment group and 15.79%(12/76) in control group, respectivery(P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups(P>0.05). Conclusion: Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide.(No. ChiCTR-IPR-15006415)
基金Supported by National Natural Science Foundation of China (General Program,No.81202776)the Sixth-Science Foundation of Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences(No.Z0215)
文摘ABSTRACT Evidence based medicine demands the highest form of scientific evidence to demonstrate the efficacy and clinical effectiveness for any therapeutic intervention in order to provide best care. It is however accepted that in the absence of scientific evidence, personal experience and expert opinion together with professional judgement are critical. Obtaining evidence for drug safety, post- marketing surveillance （PMS） has focussed on follow up of observational cohorts exposed to a particular drug in order to estimate the incidence of adverse drug reactions （ADRs）. Evidence on PMS of Chinese herbal products is still limited, in particular for herbal injections. The aim of this article is to suggest a new model of ascertaining the safety of Chinese medicine using a more comprehensive approach for collecting data. To collect safety data on the Chinese herbal injection, Kudiezi, a mixed methods approach is proposed using 18 hospital information systems to detectADRs in order to prospectively observe 30,000 patients over 3 years. Evidence will also be collected using a questionnaire survey and through a sample of semi structured interviews. This information based on the expert opinion and the experience of clinicians will produce additional data on the frequency and types of side effects in clinical practice. Furthermore semi structured interviews with a random sample of patients receiving the injection will be carried out to ascertain any potential side effects missed. It is hoped that this comprehensive approach to data collection will accumulate wider evidence based on individual traditional Chinese medicine care and treatment and provide important feedback to the national data collection system to ensure completeness of ADR data recording, monitoring and any potential wider effects through developing improved ADR guidelines.
