中药新药临床试验不良反应及其相关影响因素的学术探讨(1)
[摘要]收集2002—2012年11年间经国家食品药品监督管理局认定的56个临床试验机构主持及参与的临床试验项目，对项目总结/统计报告中不良反应进行汇总，分析中药新药临床试验的不良反应发生率及其相关影响因素，提高对中药新药安全性的认识。收录14个专业209个项目共73050个病例，其中中药新药组49689个病例，中药新药导致的不良反应共271例，不良反应发生率为0.55%。3个月<中长疗程≤6个月的不良反应发生率最高，为1.04%，短疗程≤半个月的不良反应发生率最低，为0.48%。外用药不良反应发生率1.28%>注射给药0.63%>口服给药0.50%。仅使用试验药时，贴剂不良反应发生率最高，为2.68%，气雾剂、栓剂不良反应发生率最低，为0。试验药合并使用模拟剂时，外用试验贴剂+胶囊不良反应发生率最高，为3.38%，胶囊剂+口服液、丸剂+颗粒、片剂+口服液、片剂+丸剂、片剂+胶囊剂不良反应发生率最低，为0。单用试验药时不良反应发生率为0.47%，合并模拟剂(用药体积增加)时不良反应发生率为0.74%。不同用药剂量所致不良反应发生率有所不同，全疗程使用剂量在1100～1200g时不良反应发生率最高，为3.36%，在500～600，900～1000，1400～1500，1600～1700，1800～1900g时不良反应发生率最低，为0。综上，中药新药导致的不良反应发生率仍较高为0.55%，11年间不良反应的发生率为0.47%～0.72%，各年度无明显的差异性;不良反应发生率与疗程、给药途径、剂型、用药体积关系密切，与疗程内用药剂量的多少无明显相关性，不良反应发生率随着试验疗程的增加而增加，随着用药体积的增加而增加;单用试验药时，外用剂型、注射剂的不良反应发生率大于口服给药剂型。应对中药新药临床试验中疗程长、用药体积大、注射剂及外用贴剂的不良反应予以高度重视。
, 百拇医药
[关键词]中药新药;临床试验;不良反应
Academic discussion of adverse reaction of clinical trials of new traditional
Chinese medicines and relevant influencing factors
WANG Wen-ping 1， YU Ming 1， WANG Li 2， JIANG Xi-ren 2， LI Xiao-bin 1，WANG Hua-wei 1， CAO Ying 2， LIU Kai2， HUANG Lu-qi 3 *
(1. Affiliated Hospital of Liaoning University of Traditional Chinese Medicine， Shenyang 110032， China;
, 百拇医药
2. Liaoning University of Traditional Chinese Medicine， Shenyang 110847， China;
3. State Key Labratory of Dao-di Herbs， National Resouce Center of
Chinese Materia Medica， China Academy of Chinese Medicinal Sciences， Beijing 100700， China)
[Abstract]Data of clinical trial projects involved by clinical trial institutions certified by the State Food and Drug Administration from 2002 to November 2012 were collected to summarize adverse reactions in project summary/statistical reports， analyze the rate of adverse reactions of clinical trials of new traditional Chinese medicines and relevant influencing factors， and increase the awareness of the safety of new traditional Chinese medicines. A total of 73 050 cases in 209 projects of 14 specialties were collected， including 49 689 cases in the new traditional Chinese medicine group and 271 adverse reaction cases， with an incidence rate of adverse reactions at 0.55%. The adverse reaction rate in 3 months﹤middle long course ≤ 6 months was the highest (1.04%)， whereas that in short course ≤ half a month was the lowest (0.48%). The adverse reaction was closely related with the route of administration， 1.28% for topical > 0.63% for injection > 0.50% for oral. In the administration of only the test drug， the adverse reaction rate of patches was the highest (2.68%)， whereas that of aerosols and suppositories was lowest (0). In the combined administration of the test drug and the simulation agent， the adverse reaction rate of external test patch + capsule was the highest (3.38%)， whereas that of capsule+oral liquid， pills+granules， tablets+oral liquid， tablets +pills， tablet + capsule was the lowest (0). In the administration of only the test drug， the adverse reaction rate was 0.47%; In the combined administration with simulation agent (drug volume increase)， the adverse reaction rate was 0.74%. Different doses caused adverse reaction different rates; The adverse reaction rate of drugs with whole-course dose between 1 100-1 200 g was the highest (3.36%)， that for whole-course doses of 500-600， 900-1 000， 1 400-1 500， 1 600-1 700， 1 800-1 900 g was the lowest (0). In conclusion， the adverse reaction rate of new traditional Chinese medicines was still up to 0.55%， with the adverse reaction rate between 0.47% and 0.72% over the 11 years， without significant difference in each year. The adverse reaction rate was closely related to course of treatment， approach of administration， dosage form and medication dosage， with no significant correlation with medication dosage during the course of treatment. The adverse reaction rate increased with the rise in trial duration and drug volume. In the administration of only the test drug， the adverse reaction rates of external formulations and injections were higher than that of oral dosage forms. It is suggested to give more attention to the adverse reactions of drugs with long course of treatment and large volumes， injections and external patches in clinical trials of new traditional Chinese medicines., http://www.100md.com(王文萍 喻明 王丽 姜希仁 李晓斌 王华伟 曹莹 刘凯 黄璐琦)
, 百拇医药
[关键词]中药新药;临床试验;不良反应
Academic discussion of adverse reaction of clinical trials of new traditional
Chinese medicines and relevant influencing factors
WANG Wen-ping 1， YU Ming 1， WANG Li 2， JIANG Xi-ren 2， LI Xiao-bin 1，WANG Hua-wei 1， CAO Ying 2， LIU Kai2， HUANG Lu-qi 3 *
(1. Affiliated Hospital of Liaoning University of Traditional Chinese Medicine， Shenyang 110032， China;
, 百拇医药
2. Liaoning University of Traditional Chinese Medicine， Shenyang 110847， China;
3. State Key Labratory of Dao-di Herbs， National Resouce Center of
Chinese Materia Medica， China Academy of Chinese Medicinal Sciences， Beijing 100700， China)
[Abstract]Data of clinical trial projects involved by clinical trial institutions certified by the State Food and Drug Administration from 2002 to November 2012 were collected to summarize adverse reactions in project summary/statistical reports， analyze the rate of adverse reactions of clinical trials of new traditional Chinese medicines and relevant influencing factors， and increase the awareness of the safety of new traditional Chinese medicines. A total of 73 050 cases in 209 projects of 14 specialties were collected， including 49 689 cases in the new traditional Chinese medicine group and 271 adverse reaction cases， with an incidence rate of adverse reactions at 0.55%. The adverse reaction rate in 3 months﹤middle long course ≤ 6 months was the highest (1.04%)， whereas that in short course ≤ half a month was the lowest (0.48%). The adverse reaction was closely related with the route of administration， 1.28% for topical > 0.63% for injection > 0.50% for oral. In the administration of only the test drug， the adverse reaction rate of patches was the highest (2.68%)， whereas that of aerosols and suppositories was lowest (0). In the combined administration of the test drug and the simulation agent， the adverse reaction rate of external test patch + capsule was the highest (3.38%)， whereas that of capsule+oral liquid， pills+granules， tablets+oral liquid， tablets +pills， tablet + capsule was the lowest (0). In the administration of only the test drug， the adverse reaction rate was 0.47%; In the combined administration with simulation agent (drug volume increase)， the adverse reaction rate was 0.74%. Different doses caused adverse reaction different rates; The adverse reaction rate of drugs with whole-course dose between 1 100-1 200 g was the highest (3.36%)， that for whole-course doses of 500-600， 900-1 000， 1 400-1 500， 1 600-1 700， 1 800-1 900 g was the lowest (0). In conclusion， the adverse reaction rate of new traditional Chinese medicines was still up to 0.55%， with the adverse reaction rate between 0.47% and 0.72% over the 11 years， without significant difference in each year. The adverse reaction rate was closely related to course of treatment， approach of administration， dosage form and medication dosage， with no significant correlation with medication dosage during the course of treatment. The adverse reaction rate increased with the rise in trial duration and drug volume. In the administration of only the test drug， the adverse reaction rates of external formulations and injections were higher than that of oral dosage forms. It is suggested to give more attention to the adverse reactions of drugs with long course of treatment and large volumes， injections and external patches in clinical trials of new traditional Chinese medicines., http://www.100md.com(王文萍 喻明 王丽 姜希仁 李晓斌 王华伟 曹莹 刘凯 黄璐琦)