目前臨床研究協調員（CRC）在完成高質量的臨床試驗中所扮演的角色越來越受到國內藥物臨床試驗機構及藥物申辦者的廣泛關注。作為臨床試驗過程中重要的一員，CRC承擔著協調及管理臨床試驗項目的任務，具有“項目管理助手、后勤保障支持”的特點。四川大學華西醫院國家藥物臨床試驗機構在中醫專業新藥臨床試驗過程中，嘗試配備CRC并在實際工作中取得了一定成效，同時也積累了實踐經驗。現就該機構中醫專業新藥臨床試驗過程中，CRC的運行機制和具體工作職責進行簡要介紹，為各藥物臨床試驗機構的建設和管理、藥物臨床試驗的質量和整體水平的提高提供參考。
Objective To evaluate the effectiveness and safety of Lianpu granule (LPG) in the treatment of common cold (Feng-Re syndrome). Methods The clinical trials were conducted by good clinical practice (GCP). In the phaseⅡ, a double-blind controlled trial involving 48 patients with common cold (Feng-Re syndrome) allocated by a random number table to receive LPG (n=24) or compound oral liquid of Shuanghuanglian (SHL) (n=24) as conducted; the other 80 patients included in the phase Ⅲ, multi-center randomized and controlled trial were divided into the LPG group (n=60) and SHL group (n=20) by a random number table. We didn’t evaluate the allocation concealment. LPG was administered as a dose of 8 g, three times a day, and SHL, as a dose of 10 ml, three times a day. The treatment duration for both groups was 3 days. All data were analyzed by using stata 7.0 for per-protocol population. Results In the Lianpu granule group, the good improvement rates were 90.00% (18/20) and 85.00% (51/60), and the improvement rates were 95.00% (19/20) and 98.33% (59/60); the good improvement rates for traditional Chinese medicine syndromes were 85.00% (17/20) and 85.00% (51/60), and the improvement rates were 95.00% (19/20) and 98.33% (59/60); the good improvement rates for fever were 85.00% (17/20) and 86.05% (37/43), and the improvement rates were 95.00% (19/20) and 95.35% (41/43) in the phase Ⅱ and Ⅲ respectively. Meanwhile for the compound oral liquid of SHL group, the good improvement rates were 85.71% (18/21) and 80.00% (16/20), and the improvement rates were 95.24% (20/21) and 95.00% (19/20); the good improvement rates for traditional Chinese medicine syndromes were 85.71% (18/21) and 80.00% (16/20), and the improvement rates were 95.24% (20/21) and 95.00% (19/20); the good improvement rates for fever were 85.71% (18/21) and 80.00% (12/15), and the improvement rates were 90.48% (19/21) and 93.33% (14/15) in the phase Ⅱ and Ⅲ respectively. No significant differences were seen between LPG and SHL groups on treatment duration, clinical effect and improvement rate for fever (all P ＞0.05). No adverse effects were seen in this study. Conclusion LPG has showed a definite clinical effect on common cold (Feng-Re syndrome) with no observed adverse effects.
Objective To evaluate the effectiveness and safety of traditional Chinese medicine (TCM) plus transcatheter arterial chemoembolization (TACE) compared with TACE alone, in the treatment of unresectable hepatocellular carcinoma (HCC). Methods The Cochrane Library, MEDLINE, EMBASE, CANCERLIT, CBM, CNKI and VIP were searched electronically. Relevant journals and conference proceedings were also handsearched. The quality of included studies was assessed according to the criteria recommended by the Cochrane Handbook for Systematic Reviews of Interventions, and meta-analyses were performed for homogeneous studies using The Cochrane Collaboration’s RevMan 4.2.10 software. Subgroup analyses by frequency of TACE (lt;3 or ≥3 times) were also performed. Results Thirty seven trials, all published in China, involving 2 653 participants were included. The quality of 2 studies was graded B (medium) and that of the other 35 was graded C (low). Meta-analyses showed that TCM plus TACE, compared with TACE alone, could significantly improve survival, tumor response (complete and partial), quality of life and clinical symptoms, and was also associated with a lower incidence of adverse reactions. Subgroup analyses indicated that, patients with less than three TACE had more significant improvement in survival and clinical symptoms, while patients with three or more TACE had more significant improvement in tumor response and quality of life. The incidence of adverse reactions was similar between these two different frequencies of TACE. Conclusions The treatment regimen of TCM plus TACE is superior to TACE alone in patients with unresectable HCC. As the existing data have a high risk of bias, the current evidence is insufficient to define the efficacy of the combination treatment, and further large-scale, high-quality randomized controlled trials are needed.
【摘要】 目的 評價中藥復方（益氣養陰、清熱活血方Yiqi Yangyin Qingre Huoxue decoction，YYQHD）聯合放射療法治療鼻咽癌在減毒增效方面的療效。 方法 采用Cochrane系統評價方法，電子檢索Cochrane圖書館臨床對照試驗資料庫（Cochrane Central Register of Controlled Trials，CENTRAL）、PubMed、EMBASE、中國生物醫學文獻數據庫（CBM）、中文科技期刊全文數據庫（CNKI）和中國期刊全文數據庫（VIP）以及萬方數據庫等數據庫2010年3月前所發表的相關文獻。同時互聯網檢索Current Controlled Trial、Clinical Trials和中國臨床試驗注冊網。手工檢索部分腫瘤類核心期刊。采用Cochrane協作網推薦的 “偏倚風險評估”工具，評估納入研究的質量，使用RevMan 5.0.23.0軟件對納入的研究進行定量系統評價。 結果 最終納入符合標準的中文文獻9篇共795例患者。定量分析結果顯示:與單純常規放射治療相比較，中藥復方（YYQHD）聯合常規放射治療能顯著提高腫瘤近期療效、生存率，并且能顯著減少放射治療常見毒副反應的發生，從而提高放射治療按時完成率確保放射治療療效、改善患者生存質量。 結論 雖現有研究尚不能得出可以將中藥復方（YYQHD）作為標準治療手段輔助放射治療的結論，但提示益氣養陰、清熱活血類中藥聯合放射治療治療鼻咽癌是值得繼續探索的研究方向，期待設計科學合理、高質量的多中心、大樣本、雙盲、隨機對照臨床試驗以進一步驗證其療效。【Abstract】 Objective To compare the efficacy of traditional Chinese medicine (TCM) plus radiotherapy (RT) with RT alone on nasopharyngeal carcinoma (NPC) by Yiqi Yangyin Qingre Huoxue decoction (YYQHD) through a meta-analysis of all available randomized controlled trials. Methods Literature retrieval was conducted using the Cochrane Library, PubMed, EMBASE, CBMdisk, CNKI, VIP, and Wanfang Database electronically. Relevant journals and conference proceedings were also hand-searched until March 31, 2010. The quality of included studies was assessed according to the criteria recommended by the Cochrane handbook, and the Meta-analysis was performed for homogeneous studies using RevMan 5.0.23.0 Software. Results Basing on our search criteria, we found nine trials (795 patients) which all published in Chinese. Our results showed that TCM (YYQHD) plus RT compared with RT alone, improved immediate tumor response, survival, completion rate of RT, quality of life, and alleviation of adverse effect of patients with NPC. Conclusions Considering the limitations related to this Meta-analysis, it nevertheless presents credible evidence that TCM (YYQHD) plus RT is worthy of additional study. Therefore, further large-scale, muti-center, randomized, and double-blind trials are warranted.
【摘要】 目的 評價九味柔肝顆粒治療慢性乙肝肝纖維化的療效和安全性。 方法 根據納入與排除標準，選取2007年2-8月入院的慢性乙肝肝纖維化（氣滯血瘀兼濕熱未凈證）患者96例，按3∶1隨機分為兩組進行隨機雙盲雙模擬對照試驗。試驗組72例，口服九味柔肝顆粒， 2次/d，每次10 g；陽性對照藥鱉甲軟肝片組（對照組）24例，口服鱉甲軟肝片，4片/次，3次/d；兩組療程均為6個月。 結果 試驗組完成治療66例，對照組完成21例。符合方案數據分析（PPS）結果顯示，試驗組治療后中醫證侯積分及B超積分分別下降了0.50±1.04和8.61±3.62，對照組分別下降了0.32±1.01和8.63±3.15，均較治療前顯著下降（Plt;0.05），兩組比較無統計學意義（Pgt;0.05）。在血清肝纖維化四項指標方面，試驗組除LN外，其余指標治療后均較治療前明顯下降（Plt;0.05），對照組中僅PⅢP有顯著下降（Plt;0.05），其余指標下降不明顯，兩組比較無統計學意義（Pgt;0.05）。兩組患者治療期間均未觀察到明顯不良反應，不良反應發生率分別為5.56%和4.17%。 結論 九味柔肝顆粒能明顯改善慢性肝炎肝纖維化患者的癥狀和部分肝纖維化指標，其療效與鱉甲軟肝片相當，安全性良好。【Abstract】 Objective To assess the safety and therapeutic effect of Jiuweirougan grandule on chronic hepatitis B with hepatic fibrosis. Methods A double-blind, double dummy and randomized controlled method was adopted. Ninety-six patients from February to August 2007 selected by including and excluding criteria were distributed randomly in accordance with the 3∶1 ratio into the test group (n=72, treated with Jiuweirougan 10 g, two times per day) and the control group (n=24, treated with Biejiaruangan 4 tablets, three times per day). The period of treatment for both groups lasted for half a year. Results A total of 66 cases in the test group and 21 cases in the control group completed the experiment. The results of per-protocol population (PPS) suggested that the accumulated score of B ultrasound and symptom decreased 0.50±1.04 and 8.61±3.62 in the test group and 0.32±1.01 and 8.63±3.15 in the control group, respectively. The score decreased remarkably compared with pre-treatment(Plt;0.05). There was no significant difference between the two groups (Pgt;0.05). For serum liver fibrotic parameters, all parameters except laminin (LN) in the test group decreased remarkably compared with pre-treatment(Plt;0.05). But in the control group, besides type Ⅲ procollagen (PCⅢ) decreased remarkably(Plt;0.05), other parameters showed no obvious changes. There was no significant difference between the two groups (Pgt;0.05). At the same time, no obvious adverse effect was found in the two groups. The incidence of adverse reactions was 5.56% and 4.17% respectively. Conclusion Jiuweirougan granule may improve the syndrome and part of fibrotic index of chronic hepatitis B with fibrosis, and the effect is equal to that of Biejiaruangan with good security.
Objective To evaluate the efficacy and safety of Tongxiening granule （TXNG） in the treatment of diarrhea-predominant irritable bowel syndrome （IBS） （stagnation of the liver-qi attacking the spleen）. Methods In a prospective, randomized, placebo-controlled, double-blind clinical trial, 60 patients with diarrhea-predominant IBS were randomly divided into the TXNG group （TXNG, 5.0g, 3 times daily; n =30） and the placebo group （placebo, 5. 0g, 3 times daily; n =30）. The treatment was administered for 3 weeks, and the follow-up was conducted for 4 weeks.Results （1）Abdominal pain： The cure rates were 57. 7% vs. 16. 0% （ by per-protocol analysis, PP） and 31.0% vs. 7.1% （ by intention-to-treat analysis （ITT） ; and the overall improvement rates were 92.3% vs. 44.0% （PP） and 82.7% vs. 39.3% （ITT） in the TXNG and the placebo groups respectively （ P 〈0. 05）. （2） Diarrhea ： the cure rates were 46. 2% vs. 20. 0% （PP） and 41.4% vs. 17. 9% （ITT） , and the overall improvement rates were 96. 2% vs 48. 0% （PP） and 86. 2% vs 42.9% （ITT） in the two groups respectively （P 〈0.05）. （3）Traditional Chinese medicine symptoms： the cure rates were 30.8% vs. 4.0% （PP） and 27.6% vs. 3.6% （ITT） ; and the overall improevment rates were 92.3% vs. 48.0% （PP） and 82.7% vs 42.9% （ITT） in the two groups respectively （P 〈0. 05）. The pain duration after treatment in the TXNG group was significantly shortened compared with the placebo group （7.6 ±4. 6d vs 14. 4 ±4. 3d, P =0. 0125）. After 4-week follow-up, it suggested that the recrudescent duration in symptoms related to IBS in the TXNG group was longer than that in the placebo group （11.5 ±5.3 d vs 6.2 ±6.9 d, P = 0. 019）. No adverse effects were found in the TXNG group. Conclusion It was demonstrated that TXNG is effective and safe in the treatment of diarrhea-predominant ms （stagnation of the liver-qi attacking the spleen）.
Objective To assess the effect and safety of Dalitong Granule in the treatment of the Piman syndrome (functional dyspepsia). Method The double-blind, double-dummy and randomized controlled method was adopted. 120 patients were randomized to the treatment group (n=90, Dalitong Granule 6 g, tid) and the control group (n=30, treated with cisapride 5 mg, tid). The therapeutic course for both groups was 2 weeks. Results All the results were analyzed on the basis of intention-to-treat and per-protocol population. In the treatment group, the markedly effective rates were 62.37% and 64.45% respectively. The effective rates were 99.55% and 96-67% respectively. In the control group, the markedly effective rates were 58-08% and 60.00% respectively. The effective rates were 90.33% and 93.33% respectively. There was no significant difference between two groups (Pgt;0.05). For effects on Piman syndrome, in the treatment group, the markedly effective rates were 53.76% and 55.56% respectively. The effective rates were 86.02% and 88.89% respectively. In the control group, the markedly effective rates were 48.38% and 50.00% respectively. The effective rates were 80.64% and 83.33% respectively. The results showed no statistical significance difference between two groups (Pgt;0.05). For effects on gastric emptying function (PP population), in the treatment group, the markedly effective rate and effective rate were 72.42% and 79.32%. In the control group those were 64.28% and 64.28%. There was no significant difference between the two groups (Pgt;0.05). ITT and PP analysis revealed similar results. No adverse effect was found in the observation. Conclusions Dalitong granule has the same clinical effect as cisapride with no obvious toxic-adverse effects.
Objective To assess the effectiveness and safety of Jiuweirougan granule in the treatment of chronic hepatitis with hepatic fibrosis. Methods A double-blind, double dummy and randomized controlled method was adopted. Forty-six patients were selected by using the inclusion and exclusion criteria and were randomizedly allocated to the treatment group (n=23, Jiuweirougan 10 g, twice a day) and the control group (n=23, treated with Biejiaruangan 4 pills, three times a day). The duration of treatment for both groups lasted for 6 months. Results Two patients in the treatment group dropped out halfway through the study, while one patient in the control group was withdrawal for irregular treatment. Analysis according to intention-to-treat (ITT) and per-protocol (PP) was conducted. In the treatment group, the effective rates of TCM (Traditional Chinese Medicine) on the syndrome were 82.61% (19/23) (ITT) and 90.48% (19/21) (PP), while in the control group, there were 86.96% (20/23) (ITT) and 86.36% (19/20) (PP). There was no significant difference between the two groups (P＞0.05). The improvement rate of serum parameters in the treatment group such as hyaluronic acid (HA), type Ⅲ procollagen (PCⅢ), type Ⅳ collagewn (CⅣ) and laminin (LN) were 28.57% (6/21), 23.81% (5/21), 28.57% (6/21) and 4.76% (1/21), respectively, while in control group, the rates were 36.37% (8/22),13.64% (3/22), 36.37% (8/22) and 9.09% (2/22), respectively. No significant difference was seen between the two groups (P＞0.05). ITT and PP analysis revealed similar results. No obvious adverse effects were noted. Conclusion Jiuweirougan granule may improve chronic hepatitis with fibrosis, and its effect is equal to that of Biejiaruangan. No obvious toxic-adverse effects were seen.
【摘要】 目的 觀察利膽清微丸治療慢性膽囊炎濕熱蘊結兼血瘀證患者的療效及安全性，進一步為臨床研究提供依據。 方法 2001年4—7月，采用雙盲、雙模擬、隨機平行對照臨床試驗，將40例患者隨機分為試驗組（20例）及對照組（20例）。試驗組服用利膽清微丸3.5 g/次，3次/d，同時服用膽寧片模擬劑；對照組服用膽寧片3片/次，3次/d，同時服用利膽清微丸模擬劑。 結果 試驗組痊愈1例，顯效12例，有效5例，無效2例，顯效率65%，有效率90%；對照組痊愈2例，顯效10例，有效7例，無效1例，顯效率60%，有效率95%，兩組療效比較差異無統計學意義（Pgt;0.05）。試驗過程中未發現明顯不良反應。 結論 利膽清微丸對于治療慢性膽囊炎濕熱蘊結兼血瘀證有良好效果，是一種安全有效的藥物。【Abstract】 Objective To observe the safety and efficacy of Lidanqing pellet on chronic cholecystitis with damp and hot accumulate knot including blood stasis, and to provide a basis for further clinical trials. Methods A double-blind, double dummy, randomized, and controlled clinic trial was undertaken between April and July 2001. A total of 40 patients were randomly divided into trail group and control group. The trial group was given Lidanqin pellet 3.5 g per time, and three times per day; simultaneously taking Danning tablet simulation agent. The control group was given 3 tablets of Danning tablet per time and three times per day; simultaneously taking taking Lidanqing pellets simulation agent. Results In the trail group, one patient was cured, the therapeutic effect was obvious in 12, basically effective in five and invalid in two (with the rate of obvious effect of 65.00% and rate of basic effect of 90.00%). In the control group, two patients was cured, the therapeutic effect was obvious in 12, basically effective in 10, effective in seven and invalid in one (with the rate of basic effect of 60.00% and the rate of obvious effect of 95.00%). The difference between the two groups was significant (Pgt;0.05). Adverse reaction was not found in the trial group. Conclusion Lidanqing pellet, a safe medication, is effective on chronic cholecystitis with damp and hot accumulate knot including blood stasis.
Background To prove the effect of Jinyebaidu Granule (JYBDG) in treating the Disease of Wind-heat Attacking the Lung (type of heat pathogen invading the defensive Qi of the lung) and objectively evaluate its safety. Methods The muti-center,double-blinded, double-dummy and randomized controlled method was adopted to observe 200 patients who were divided into the treatment group (n=100, treated with JYBDG 10 g, three times a day) and the control group (n=100, treated with Shuanghuanglian Granule 5 g, three times a day). The therapeutic course for both groups was 5 days. Results According to ITT (intention-to-treat) and PP (per-protocol population), In the treatment group, the markedly effective rate was 72.64% and 75.00% respectively, and effective rate was 94.00% and 96.00% respectively, while in the control group the markedly effective rate was 68.63% and 68.00% respectively, and effective rate was 90.20% and 90.00% respectively, no significant difference was found between the two groups (Pgt;0.05). For therapeutic effects on TCM syndromes, In the treatment group, the markedly effective rate was 71.70% and 74.00% respectively, and effective rate was 93.45% and 96.00 % respectively, while in the control group the markedly effective rate was 66.67% and 68.00% respectively, and effective rate was 89.22% and 90.00% respectively, also showed insignificantly difference (Pgt;0.05). No adverse effect was found in the observation. Conclusion JYBDG shows a definite clinical effect with no obvious toxic-adverse effects.