本文關(guān)鍵詞：中藥臨床試驗(yàn)肝腎功能指標(biāo)異常值的分析與評(píng)價(jià)，由筆耕文化傳播整理發(fā)布。

        目的：建立藥物臨床試驗(yàn)肝腎功能指標(biāo)異常值不良反應(yīng)數(shù)據(jù)庫(kù)，通過(guò)對(duì)中藥臨床試驗(yàn)肝腎功能指標(biāo)異常值的分析與評(píng)價(jià)，研究中藥新藥臨床試驗(yàn)中指標(biāo)異常意義的判定與解釋存在的問(wèn)題及肝腎功能異常與藥物的相關(guān)性。方法：通過(guò)查詢、收集2005-2010年遼寧省中醫(yī)院國(guó)家藥物臨床試驗(yàn)機(jī)構(gòu)保存的72項(xiàng)新藥臨床試驗(yàn)總結(jié)報(bào)告，收錄報(bào)告中安全性評(píng)價(jià)內(nèi)容中肝腎指標(biāo)異常的試驗(yàn)病例，建立包含錄入、查詢等功能的藥物臨床試驗(yàn)不良反應(yīng)數(shù)據(jù)庫(kù)，對(duì)異常狀態(tài)判定與進(jìn)行回顧性研究與統(tǒng)計(jì)分析。結(jié)果：1.不良反應(yīng)數(shù)據(jù)庫(kù)收錄臨床試驗(yàn)項(xiàng)目的基本情況數(shù)據(jù)庫(kù)中共收錄新藥臨床試驗(yàn)項(xiàng)目涉及48個(gè)國(guó)家食品藥品監(jiān)督管理局藥物臨床試驗(yàn)機(jī)構(gòu)，430個(gè)次臨床試驗(yàn)參加單位，總病例24535例，異常肝腎功能病例有2051例。不良反應(yīng)數(shù)據(jù)庫(kù)收錄的項(xiàng)目涉及9大系統(tǒng)72個(gè)項(xiàng)目，包含神經(jīng)精神系統(tǒng)疾病、心血管系統(tǒng)疾病、內(nèi)分泌系統(tǒng)疾病、婦科系統(tǒng)疾病、泌尿系統(tǒng)疾病、骨科疾病、呼吸系統(tǒng)疾病、五官系統(tǒng)疾病、風(fēng)濕免疫系統(tǒng)疾病等，數(shù)據(jù)庫(kù)收錄項(xiàng)目的用藥主要包括口服給藥、注射給藥及局部用藥三大類，收錄劑型最多的為膠囊劑、顆粒劑、片劑和注射液。2.臨床試驗(yàn)肝腎功能異常值臨床意義判定情況通過(guò)查詢肝腎功能指標(biāo)異常值數(shù)據(jù)庫(kù)，臨床試驗(yàn)療前肝腎功能異常值中有141例臨床判定為有意義，占療前異常病例總數(shù)的26.9%，而383例臨床判定為無(wú)意義，占療前異常病例總數(shù)的73.1%，在療后肝腎功能異常值中有349例臨床判定為有意義，占療后異常病例總數(shù)的22.9%，而1178例臨床判定為無(wú)意義，占療后異常病例總數(shù)的77.1%。在肝功能指標(biāo)異常值數(shù)據(jù)庫(kù)中，ALT異常數(shù)據(jù)總計(jì)1050例，治療前ALT在40-60U/L、60-80U/L范圍內(nèi)判定為有臨床意義的病例數(shù)為18例、17例，分別占ALT異常病例總數(shù)的1.7%、1.6%，治療后ALT在40-60U/L、60-80U/L范圍內(nèi)判定為有臨床意義的病例數(shù)為34例、25例，分別占ALT異常病例總數(shù)的3.2%、2.4%，ALT在40-60U/L、60-80U/L范圍內(nèi)判定為有臨床意義的病例分別占ALT異常病例總數(shù)的4.9%和4.0%；治療前ALT在40-60U/L、60-80U/L范圍內(nèi)判定為無(wú)臨床意義的病例數(shù)為158例、57例，分別占ALT異常病例總數(shù)的15.0%、5.4%，治療后ALT在40-60U/L、60-80U/L范圍內(nèi)判定為無(wú)臨床意義的病例數(shù)為452例、133例，分別占ALT異常病例總數(shù)的43.0%、12.7%，ALT在40-60U/L、60-80U/L范圍內(nèi)判定為無(wú)臨床意義的病例分別占ALT異常病例總數(shù)的58%和17.7%。在肝功能指標(biāo)異常值數(shù)據(jù)庫(kù)中，AST異常數(shù)據(jù)總計(jì)207例，治療前AST在40-60U/L、60-80U/L范圍內(nèi)判定為有臨床意義的病例數(shù)為4例、1例，分別占AST異常病例總數(shù)的1.9%、0.4%，治療后AST在40-60U/L、60-80U/L范圍內(nèi)判定為有臨床意義的病例數(shù)為16例、11例，分別占AST異常病例總數(shù)的7.7%、5.3%，AST在40-60U/L、60-80U/L范圍內(nèi)判定為有臨床意義的病例分別占AST異常病例總數(shù)的9.6%和5.7%；治療前AST在40-60U/L、60-80U/L范圍內(nèi)判定為無(wú)臨床意義的病例數(shù)為30例、5例，分別占AST異常病例總數(shù)的14.5%、2.4%，治療后AST在40-60U/L、60-80U/L范圍內(nèi)判定為無(wú)臨床意義的病例數(shù)為106例、19例，分別占AST異常病例總數(shù)的51.2%、9.2%，AST在40-60U/L、60-80U/L范圍內(nèi)判定為無(wú)臨床意義的病例分別占AST異常病例總數(shù)的65.7%和11.6%。在腎功能BUN異常值數(shù)據(jù)庫(kù)中，BUN異常病例總計(jì)811例，治療前BUN在6.4-10.5mmol/L、10.5-21mmol/L范圍內(nèi)判定為有臨床意義的病例數(shù)為13例、5例，分別占BUN異常病例總數(shù)的1.6%、0.6%，治療后BUN在6.4-10.5mmol/L范圍內(nèi)判定為有臨床意義的病例數(shù)為21例、8例，分別占BUN異常病例總數(shù)的2.6%，0.9%，BUN在6.4-10.5mmol/L、10.5-21mmol/L范圍內(nèi)判定為有臨床意義的病例分別占BUN異常病例總數(shù)的4.2%和1.5%；治療前BUN在6.4-10.5mmol/L、10.5-21mmol/L范圍內(nèi)判定為無(wú)臨床意義的病例數(shù)為66例、8例，分別占BUN異常病例總數(shù)的8.1%、1.0%，治療后BUN在6.4-10.5mmol/L范圍內(nèi)判定為無(wú)臨床意義的病例數(shù)為360例，分別占BUN異常病例總數(shù)的44.4%，BUN在6.4-10.5mmol/L、10.5-21mmol/L范圍內(nèi)判定為無(wú)臨床意義的病例分別占BUN異常病例總數(shù)的52.5%和1.0%。在腎功能CR異常值數(shù)據(jù)庫(kù)中，CR異常病例共計(jì)188例，治療前CR在110-140umol/l、140-180umol/l范圍內(nèi)判定為有臨床意義的病例數(shù)為13例、8例，分別占CR異常病例總數(shù)的6.9%、4.2%，治療后CR在110-140umol/l、140-180umol/l范圍內(nèi)判定為有臨床意義的病例數(shù)為25例、12例，分別占CR異常病例總數(shù)的13.3%、6.4%，而治療前CR在110-140umol/l、140-180umol/l范圍內(nèi)判定為無(wú)臨床意義的病例數(shù)分別為4例、13例，分別占CR異常病例總數(shù)的2.1%、6.9%，治療后CR在110-140umol/l、140-180umol/l范圍內(nèi)判定為無(wú)臨床意義的病例分別為4例、13例，分別占CR異常病例總數(shù)的2.1%、6.9%。（1）臨床試驗(yàn)中療前及療后肝功能異常病例原因解釋臨床試驗(yàn)肝功能ALT異常有臨床意義病例解釋中，肝功能數(shù)值在40-60U/L范圍內(nèi)共計(jì)54例，異常原因判定為脂肪肝的為33例，合并用藥者2例，飲酒或飲食1例，其他原因8例，未判定原因者5例，分別占該異常值范圍病例的61.1%、3.7%、1.9%、14.8%、9.3%；肝功能數(shù)值在60-80U/L范圍內(nèi)共計(jì)46例，異常原因判定為脂肪肝或酗酒的為25例，其他原因3例，合并用藥者1例，未判定原因者17例，分別占該異常值范圍病例的54.3%、6.5%、2.2%、37.0%；肝功能數(shù)值在80-120U/L范圍內(nèi)共計(jì)42例，異常原因判定為脂肪肝的為10例，合并用藥及飲酒者8例，其他原因7例，未判定原因者17例，分別占該異常值范圍病例的23.8%、19.0%、16.7%、40.5%。臨床試驗(yàn)肝功能ALT異常無(wú)臨床意義病例解釋中，肝功能數(shù)值在40-60U/L范圍內(nèi)共計(jì)611例，異常原因判定為脂肪肝等為151例，飲酒或飲食等14例，未判定原因者446例，分別占該異常值范圍病例的24.7%、2.3%、73.0%；肝功能數(shù)值在60-80U/L范圍內(nèi)共計(jì)192例，異常原因判定為脂肪肝的為69例，飲酒或飲食等6例，未判定原因者117例，分別占該異常值范圍病例的35.9%、3.1%、60.9%；肝功能數(shù)值在80-120U/L范圍內(nèi)共計(jì)32例，異常原因判定為脂肪肝或酒精肝為17例，飲酒者3例，未判定原因者13例，分別占該異常值范圍病例的53.1%、9.3%、40.6%。臨床試驗(yàn)肝功能AST異常有臨床意義病例解釋中，全部肝功能異常數(shù)值均進(jìn)行了異常原因解釋，臨床試驗(yàn)療后肝功能AST異常有臨床意義病例解釋中，肝功能數(shù)值在40-60U/L范圍內(nèi)共計(jì)16例，異常原因判定為脂肪肝的為6例，未判定原因者10例，分別占該異常值范圍病例的37.5%、62.5%；肝功能數(shù)值在60-80U/L范圍內(nèi)共計(jì)11例，異常原因判定為脂肪肝的為6例，未判定原因者5例，分別占該異常值范圍病例的54.5%、45.4%。臨床試驗(yàn)肝功能AST異常無(wú)臨床意義病例解釋中，肝功能數(shù)值在40-60U/L范圍內(nèi)共計(jì)136例，異常原因判定為脂肪肝及飲酒為22例，未判定原因者114例，分別占該異常值范圍病例的16.2%、83.8%；肝功能數(shù)值在60-80U/L范圍內(nèi)共計(jì)24例，其中8例進(jìn)行了異常原因判定，其余16例未判定原因，分別占該異常值范圍病例的33.3%、66.7%。（2）臨床試驗(yàn)中療前及療后腎功能異常病例原因解釋臨床試驗(yàn)?zāi)I功能BUN異常有臨床意義病例解釋中，BUN數(shù)值在6.4-10.5mmol/L范圍內(nèi)共計(jì)34例，異常原因判定為痛風(fēng)性腎病等為7例，未判定原因者25例，分別占該異常值范圍病例的20.6%、73.5%；BUN數(shù)值在10.5-21mmol/L范圍內(nèi)共計(jì)13例，異常原因判定為痛風(fēng)性腎病等為6例，未判定原因者7例，分別占該異常值范圍病例的46.2%、53.8%。臨床試驗(yàn)?zāi)I功能BUN異常無(wú)臨床意義病例解釋中，BUN數(shù)值在6.4-10.5mmol/L范圍內(nèi)共計(jì)378例，異常原因判定為飲食等為80例，未判定原因者298例，分別占該異常值范圍病例的21.2%、78.8%；BUN數(shù)值在10.5-21mmol/L范圍內(nèi)共計(jì)8例，異常原因判定為糖尿病腎病等為1例，其余7例未判定原因。臨床試驗(yàn)療前腎功能CR異常有臨床意義病例解釋中，CR數(shù)值在70-110umol/l范圍內(nèi)共計(jì)7例，異常原因判定為痛風(fēng)性腎病、慢性腎功能不全為2例，未判定原因者5例；CR數(shù)值在110-140umol/l范圍內(nèi)共計(jì)37例，異常原因判定為痛風(fēng)性腎病等為19例，未判定原因者19例；CR數(shù)值在140-180umol/l范圍內(nèi)共計(jì)12例，異常原因判定為痛風(fēng)性腎病等為3例，未判定原因者9例；CR數(shù)值在≥180umol/l范圍內(nèi)共計(jì)4例，有3例進(jìn)行了異常原因解釋。臨床試驗(yàn)療后腎功能CR異常無(wú)臨床意義病例解釋中，CR數(shù)值在70-110umol/l范圍內(nèi)共計(jì)54例，異常原因判定為糖尿病腎病等為8例，未判定原因者46例，分別占該異常值范圍總病例的14.8%、85.2%；CR數(shù)值在110-140umol/l范圍內(nèi)共計(jì)15例，異常原因判定為痛風(fēng)性腎病等為3例，未判定原因者12例，分別占該異常值范圍總病例的20%、80%；CR數(shù)值在140-180umol/l范圍內(nèi)共計(jì)1例，，異常原因判定未判定。3.臨床試驗(yàn)肝腎功能異常原因分析及與試驗(yàn)藥物相關(guān)性判斷通過(guò)對(duì)肝腎功能指標(biāo)異常值數(shù)據(jù)庫(kù)中的數(shù)據(jù)分析，引起肝腎功能異常最常見的原因依次為飲酒、脂肪肝、飲食，而使各臨床試驗(yàn)中肝腎功指標(biāo)結(jié)果影響最主要的原因依次為脂肪肝、其它疾病、飲酒、飲食及合用它藥。在肝腎功能指標(biāo)異常值數(shù)據(jù)庫(kù)中，療后肝腎功能異常值與藥物關(guān)系判定為可能有關(guān)的為3例，可疑26例，占全部療后異常病例的1.5%，其余異常病例均判斷為與試驗(yàn)藥物無(wú)關(guān)。結(jié)論：1、臨床試驗(yàn)中研究人員對(duì)于安全性評(píng)價(jià)指標(biāo)異常數(shù)值的評(píng)價(jià)存在疏漏，對(duì)新藥臨床試驗(yàn)藥物安全性的警戒意識(shí)和專業(yè)知識(shí)欠缺。關(guān)于臨床試驗(yàn)肝腎功指標(biāo)異常值數(shù)據(jù)庫(kù)中的數(shù)據(jù)，對(duì)于治療前數(shù)據(jù)多數(shù)研究者能給予足夠的重視，而對(duì)于藥物治療結(jié)束出組時(shí)的安全性評(píng)價(jià)指標(biāo)異常值研究者對(duì)異常原因未進(jìn)行充分的解釋和評(píng)價(jià)，無(wú)法（難以）正確評(píng)價(jià)試驗(yàn)藥物的用藥安全性。2、臨床試驗(yàn)中對(duì)安全性評(píng)價(jià)重視不夠。對(duì)Ⅱ/Ⅲ期臨床試驗(yàn)安全性的觀察和總結(jié)重視不夠,包括不良事件的描述不詳細(xì)、臨床意義判定得出的結(jié)論缺乏正確的分析,甚至是“不良事件與藥物無(wú)關(guān)”的結(jié)論,影響了對(duì)新藥安全性的全面評(píng)價(jià)和認(rèn)識(shí)。3、研究者對(duì)于肝腎功能異常無(wú)臨床意義的判定缺少可靠依據(jù)。存在肝腎功能異常無(wú)臨床意義者解釋原因的缺失比例要遠(yuǎn)大于肝腎功能異常有臨床意義者，一是說(shuō)明研究者對(duì)于這部分無(wú)臨床意義數(shù)值的判定存在一定的困惑，缺少可靠的判定依據(jù)，另一方面可能是研究者對(duì)于肝功能異常無(wú)臨床意義病例未給予足夠的重視，忽視其在新藥臨床安全性評(píng)價(jià)中的重要作用，這些判定的差異性嚴(yán)重影響著臨床試驗(yàn)質(zhì)量的控制，影響了研究結(jié)果的可靠性，不能真實(shí)反映臨床試驗(yàn)?zāi)康摹?/p>

    Objective:To establish a database of clinical trials of drug liver and kidney functionindicators outliers adverse reactions, analysis and evaluation of the value ofChinese medicine clinical trials liver and kidney function abnormalities, studyChinese medicine clinical trials indicators unusual significance determinationand interpretation problems in liver renal dysfunction drug relevance.Methods：By querying and collecting72clinical trials of new drugs summary reportsof Liaoning Provincial Hospital of national clinical trial from2005to2010,included in the safety evaluation report content indicators of liver and kidneyabnormalities test cases to establish entry containing the query functions indrug clinical trial database of adverse reactions, undertakeing retrospectivestudies and statistical analysis of the abnormal state.Results:First the basic situation of the clinical trial program,in the adversereaction database.Database were included in clinical trials of new drugs project involves48countries of the Food and Drug Administration for clinical test,430clinicaltrial participants in total cases,24,535cases,2051cases of abnormal liverand kidney function. The adverse reactions Indexed project involves nine system 72projects, including neuropsychiatric diseases, diseases of thecardiovascular system, endocrine system diseases, gynecological diseases,urinary system diseases, orthopedic diseases, respiratory diseases, facialsystem diseases, rheumatological The system diseases Indexed medicationincluding oral administration, injection and topical application threecategories, RECORDING formulations Maximum capsules, granules, tablets andinjection.Second, the whole situation of clinical significance of dysfunction liverand kidney value in clinical trialsOutliers database by querying the indicators of liver and kidney function,liver and kidney function abnormal values in clinical trials before treatmentin141cases judged meaningful, accounting for26.9%of the total number ofabnormal cases before treatment, and383cases determined to be meaningless,accounting treatment73.1%of the total number of abnormal cases,349casesjudged to be meaningful, accounting for22.9%of the total number of abnormalcases after treatment in the treatment of liver and kidney function abnormalvalues, and1178cases of clinical judgment as meaningless, accounting for thetreatment of abnormal cases77.1%of the total.Abnormal liver function values database, ALT abnormal data a total of1050cases, treatment of ALT in40-60U/L,60-80U/L range judged to be clinicallysignificant number of cases to18cases,17cases, accounting for ALT abnormalcases the total number of1.7%,1.6%, ALT determined within the range of40-60U /L,60-80U/L after treatment for clinically significant number of cases,34cases,25cases, respectively, of the total number of cases of abnormal ALT3.2%,2.4%, ALT clinically significant cases accounted for4.9%and4.0%of the totalnumber of cases of abnormal ALT determined within the range of40-60U/L,60-80U/L; pretreatment ALT in40-60U/L60-80U/L range determination is notclinically significant number of cases to158cases,57cases, accounting for15.0%of the total number of cases of abnormal ALT,5.4%, after treatment ALT40-60U/L,60-80U/L, determine the number of cases of no clinical significanceof452cases,133cases, accounting for the the abnormal ALT total number ofcases of43.0%,12.7%, ALT within the range of40-60U/L,60-80U/L judgedas clinical The significance of the cases accounted for58%and17.7%of thetotal number of cases of abnormal ALT.Abnormal liver function values database, AST abnormal data a total of207cases, treatment the former AST in40-60U/L,60-80U/L range judged to beclinically significant number of cases in4cases,1case, respectively, of ASTabnormal cases the total number of1.9%,0.4%, AST within the range of40-60U/L,60-80U/L after treatment determine the clinical significance of the numberof cases to16cases,11cases, respectively, of the total number of cases ofabnormal AST7.7%,5.3%, AST clinically significant cases accounted for9.6%and5.7%of the total number of cases of abnormal AST is determined within therange of40-60U/L,60-80U/L; pre-treatment AST40-60U/L60-80U/L rangedetermination is not clinically significant number of cases,30cases,5cases, accounting for14.5%of the total number of cases of abnormal AST,2.4%, ASTafter treatment in the40-60U/L,60-80U/L within the judgment is not clinicallysignificant number of cases to106cases,19cases, respectively, of the totalnumber of cases of abnormal AST51.2%,9.2%, AST within the range of40-60U/L,60-80U/L judged as clinical The significance of the cases accounted for65.7%and11.6%of the total number of cases of abnormal AST.In renal BUN outliers database, BUN abnormal cases totaled811cases,6.4-10.5mmol/L,10.5-21mmol/L within the pre-treatment BUN judged to beclinically significant number of cases to13cases,5cases, respectively.accounted for1.6%of the total number of cases of abnormal BUN,0.6%, treatmentBUN6.4-10.5mmol/L range judged to be clinically significant number of cases,21cases,8cases, accounting for2.6%of the total number of cases of BUN abnormal,0.9%, BUN6.4-10.5mmol/L,10.5-21mmol/L range judged to be clinicallysignificant cases accounted for4.2%and1.5%of the total number of BUN abnormalcases; pre-treatment BUN6.4-10.5mmol/L,10.5-21mmol/L range judged to benot clinically significant number of cases,66cases,8cases, accounting for8.1%of the total number of BUN abnormal cases,1.0%, after treatment BUN judgedas6.4-10.5mmol/L within the clinical The significance of the number of casesto360cases, accounting for BUN of44.4%of the total number of cases of abnormalBUN6.4-10.5mmol/L,10.5-21mmol/L within the range determined to be noclinically significant cases accounted for52.5%of the total number of casesof BUN abnormal and1.0%, respectively. Renal CR outliers database CR abnormal cases amounted to188cases, thetreatment of former CR in the the110-140umol/l,140-180umol/l range judgedto be clinically significant number of cases to13cases,8cases, respectively,of CR abnormal cases the total number of6.9%,4.2%, after treatment CR in thethe110-140umol/l,140-180umol/l within the scope determined to be clinicallysignificant number of cases to25cases,12cases, respectively, of the totalnumber of cases of CR abnormal13.3%,6.4%, and treatment before the CR in the110-140umol/l,140-180umol/l range judged to be not clinically significantnumber of cases were4cases,13cases, accounting for2.1%of the total numberof cases of CR abnormal,6.9%, CR is determined within the range of110-140umol/l,140-180umol/l after treatment for cases of no clinical significance were4cases,13cases, accounting for2.1%of the CR exception of the total cases,6.9%.(1) explanations of abnormal liver function cases in clinical trials beforetreatment and after treatment.Clinical trials liver function abnormal ALT interpretation of clinicalsignificance cases, liver function values in the range of40-60U/L, total54cases, the reason for the exception determination of fatty liver in33cases,combination therapy in2cases, drinking or eating one cases,8cases of otherreasons, did not determine the cause of five cases, respectively accounting for61.1%of the cases of abnormal values range,3.7%,1.9%,14.8%,9.3%; liverfunction values in the range of60-80U/L total of46cases, the reason for the exception is determined as fatty liver or alcohol for25cases,3cases ofother reasons, combination therapy, not determine reasons in17cases,accounting for54.3%of the cases the exception value range,6.5%,2.2%,37.0%; liver function values in the range of80-120U/L, a total of42cases, thereason for the exception determination of fatty liver for10cases, concomitantmedications and drinker eight cases, seven cases of other reasons, did notdetermine the cause in17cases, accounting for the range of values of theexception cases23.8%,19.0%,16.7%,40.5%.Interpretation of clinical trials liver function abnormal ALT cases ofclinical significance, liver function values in the range of40-60U/L, a totalof611cases, the reason for the exception is determined that the fatty liverand other151cases, drinking or eating14cases, did not determine the cause446cases, accounting for24.7%of the cases of the outliers range,2.3%,73.0%;liver function values in the range of60-80U/L, a total of192cases, the reasonfor the exception determination of fatty liver was69cases, drinking or eating6cases, did not determine the reason for117cases, respectively accountingfor35.9%of the cases the outliers range,3.1%,60.9%; liver function valuesin the range of80-120U/L, a total of32cases, the reason for the exceptionis determined that fatty liver or alcohol liver in17cases, three cases of thedrinker, did not determine the cause in13cases, accounting for53.1%of thecases of abnormal values range,9.3%,40.6%.Clinical trials liver function abnormal AST interpretation of clinical significance cases, abnormal liver function values are abnormal reasons toexplain the clinical trials after treatment cases the interpretation of theclinical significance of abnormal liver function AST, liver function valuesin40-60U/L range within a total of16cases, the reason for the exceptionjudged to fatty liver in6cases, did not determine the cause in10cases,accounting for37.5%of the cases of abnormal values range,62.5%; liver functionvalues in the range of60-80U/L11For example, the reason for the exceptiondetermination for fatty liver in6cases, not determined the reasons in5patients,respectively, accounted for54.5%of the cases of abnormal values range45.4%.A total of136cases, the reason for the exception judged to fatty liverand drinking22cases,114cases not determined by reason, interpretation ofclinical trials liver function abnormal AST case of no clinical significance,liver function values in the range of40-60U/L respectively of the totaloutliers range of cases16.2%,83.8%; liver function values in the range of60-80U/L total of24cases,8cases determine the reason for the exception, theremaining16patients did not determine the cause of the abnormal cases of therange of values33.3%,66.7%.(2) clinical trials before treatment and after treatment of renaldysfunction cases explanationsAbnormal clinical trials of renal BUN interpretation of cases of clinicalsignificance, BUN values in the6.4-10.5mmol/L within the total34cases, thereason for the exception determination gouty nephropathy7cases not determine the reason there were25cases respectively of the total outliers range of20.6%of the cases,73.5%; BUN value in the10.5-21mmol/L range, a total of13cases,the reason for the exception is determined to gouty nephropathy in6cases, didnot determine the cause in7cases, accounting for the outliers range46.2%ofthe cases,53.8%.Abnormal clinical trials of renal BUN no cases of clinical significanceinterpretation, BUN values in the6.4-10.5mmol/L within the scope of a totalof378cases, the reason for the exception is determined that diet and other80cases not determine the reason there were298cases, accounting for theoutliers cases in the range of21.2%,78.8%; the BUN value1.05-21mmol/L withinthe scope of a total of eight cases, the reason for the exception determinationdiabetic nephropathy in1case, the remaining seven patients did not determinethe cause.Clinical trials before treatment cases the interpretation of the clinicalsignificance of the CR value in the the70-110umol/l within the total of7cases, the reason for the exception determination gouty nephropathy, chronicrenal insufficiency in2cases, did not determine the cause abnormal renal CRcases; CR value in the the110-140umol/l within the total37cases, abnormaldetermine the reason for the gouty nephropathy in19cases, not determine thereason there were19cases; CR values the140-180umol/l within the scope ofa total of12cases, abnormal judged to gouty nephropathy as3cases, did notdetermine the cause in9cases; CR values of≥180umol/l within the scope of a total of4cases,3cases explain the cause of the exception.Clinical trials after treatment, abnormal renal function CR no clinicalsignificance in the case explained the CR value in the the70-110umol/l withinthe total54cases, the reason for the exception determination as diabeticnephropathy and other8cases, did not determine the cause in46casesrespectively of the total the total cases of abnormal values range14.8%,85.2%;CR value in the range of the110-140umol/l, a total of15cases, the reasonfor the exception is determined to gouty nephropathy in3cases, did not determinethe cause in12cases, accounting for the outliers range of20%of the cases,80%; CR value in the the140-180umol/l within the total cases, the reason forthe exception determination not determined.Third，clinical trials, liver and kidney dysfunction reason analysis andcorrelation with the test drug judgmentThe data in the database of liver and kidney function abnormalities value,causing liver and kidney dysfunction the most common causes were drinking, fattyliver, diet, leaving the indicators of liver and kidney function results inclinical trials of the main reason is as follows fatty liver, other diseases,alcohol consumption, diet and combination drug.In liver and kidney function indicators outliers database, liver and kidneydysfunction after treatment with the drug judged as may be relevant for the3cases, suspicious in26cases, accounting for1.5%of all after treatment ofabnormal cases, the rest of the abnormal cases were judged independent of the test drug.Conclusions:Firstly, clinical trials researchers are omissions in the evaluation of thesafety evaluation indicators of abnormal values, lack of awareness andexpertise of clinical trials of new drugs drug safety alertion. The data in thedatabase of clinical trials and kidney function indicators outliers, for thepre-treatment data most researchers can give adequate attention, but forsecurity evaluation for the end of the drug treatment researchers is not in fullinterpretation and evaluation can not be correctly evaluated for drug safetyof the test drug.Secondly, insufficient attention should be paid to the safety evaluationof clinical trials. safety observation and summary of clinical trials of PhaseII/III was given inadequate attention, including a description of the adverseevents detailed clinical significance determination concluded lack of properanalysis, even "adverse events has nothing to do with drugs," the conclusion,affecting a comprehensive evaluation of new drug safety and awareness.Thirdly, researchers lack of reliable basis for liver and kidney dysfunctionwithout clinical significance of determination. Explanation of loss ratio ofdysfunction of liver and kidney without clinical significance is much greaterthan the liver and kidney dysfunction which has clinical implications, on onehand the researcher has certain confusion for those parts which has no clinicalsignificance value judgement, on the other hand researchers might not give enough attention for the cases of abnormal liver function without clinical significance,neglecting its important role in new drug clinical safety evaluation, theseseriously affected the quality control of clinical trial, for the results can’treflect the real clinical trial purpose.

中藥臨床試驗(yàn)肝腎功能指標(biāo)異常值的分析與評(píng)價(jià)

摘要4-9Abstract9-19前言20-22文獻(xiàn)綜述22-361. 資料與方法362. 結(jié)果與分析36-68分析討論68-78結(jié)論78-79參考文獻(xiàn)79-84致謝84-85個(gè)人簡(jiǎn)歷85

  本文關(guān)鍵詞：中藥臨床試驗(yàn)肝腎功能指標(biāo)異常值的分析與評(píng)價(jià)，由筆耕文化傳播整理發(fā)布。