秒速赛车控制器

當前位置: 首頁 > 政策法規 > 綜合 > 行政管理
行政管理
NASH治療藥物臨床試驗技術指導原則(試行)
發布時間: 2019-12-23     來源: 新浪醫藥

12 YUE 20 RI,WEIZHIDAOHEGUIFANFEIJIUJINGXINGZHIFANGXINGGANYANZHILIAOYAOWULINCHUANGSHIYAN,GUOJIAYAOPINJIANDUGUANLIJUZUZHIZHIDINGLE《FEIJIUJINGXINGZHIFANGXINGGANYANZHILIAOYAOWULINCHUANGSHIYANZHIDAOYUANZE(SHIXING)》,XIANYUFABU。

YIXIAWEIQUANWEN:

 

 

一、適用范圍

BENZHIDAOYUANZEYOUYAOPINJIANDUGUANLIBUMENYULINCHUANGYANJIUZHEGONGTONGTAOLUNZHIDING,WEIFEIJIUJINGXINGZHIFANGXINGGANYAN(NonalcoholicSteatohepatitis,NASH)ZHILIAOYAOWUDEYANFATIGONGJISHUJIANYI。BENZHIDAOYUANZEZHIZHENDUINASHBANYOUXIANZHUGANXIANWEIHUA(F2~F4)(BAOKUODAICHANGQIGANYINGHUA)DECHENGRENHUANZHE,BUSHEJISHIDAICHANGQIGANYINGHUAHUOERTONGHUANZHE。

BENZHIDAOYUANZESHIYONGYUHUAXUEYAOPINHEZHILIAOYONGSHENGWUZHIPINDEYAOWUYANFA,JINZUOWEITUIJIANXINGJIANYI。ZAIYINGYONGBENZHIDAOYUANZESHI,HUANYINGTONGSHICANKAOGUOJIRENYONGYAOPINZHUCEJISHUXIEDIAOHUI(The InternationalCouncil for Harmonization of Technical Requirements for Pharmaceuticals forHuman Use,ICH)HEQITAGUONEIWAIYIFABUDEXIANGGUANJISHUZHIDAOYUANZE。

BENZHIDAOYUANZEJIANGJIYUKEXUEYANJIUJINZHANJINYIBUGENGXIN。JIANYUNASHZHILIAOYAOWULINCHUANGYANFAZHONGGUANJIANYAOSUDEJINZHANHEGENGXINXUNSU,BENZHIDAOYUANZEJINDAIBIAODANGQIANJIANYI。

二、概述

BENZHIDAOYUANZEZHUYAOTAOLUNNASHZHILIAOYAOWUYANFAZHONGLINCHUANGSHIYANSHEJIDEZHONGDIANGUANZHUNEIRONG。GUANYULINCHUANGSHIYANSHEJIHUOTONGJIXUEFENXIDEYIBANXINGWENTIKECANKAOQITAXIANGGUANZHIDAOYUANZE。

(YI)DINGYI

秒速赛车控制器FEIJIUJINGXINGZHIFANGXINGGANBING(NonalcoholicFatty Liver Disease,NAFLD)SHIYIZHONGYUYIDAOSUDIKANGHEYICHUANYIGANMIQIEXIANGGUANDEDAIXIEYINGJIXINGGANZANGSUNSHANG,JIBINGPUBAOKUOFEIJIUJINGXINGGANZHIFANGBIAN(NonalcoholicHepatic Steatosis)(DENGTONGFEIJIUJINGXINGZHIFANGGANNAFL〔Nonalcoholicfatty liver〕)、FEIJIUJINGXINGZHIFANGXINGGANYAN(NonalcoholicSteatohepatitis,NASH)JINASHXIANGGUANGANYINGHUAHEGANXIBAOAI。NASHBIAOXIANWEI5%YISHANGDEGANXIBAOZHIFANGBIANHEBINGXIAOXIENEIYANZHENGHEGANXIBAOQIQIUYANGBIANXING。

(ER)LIUXINGBINGXUE

NAFLDSHIQUANQIULIUXINGDEZHUYAOGANZANGJIBINGZHIYI,YOUWENXIANBAODAO,QUANQIUHUANBINGLVWEI25.24%(95% CI :22.10-28.65),QIEHUANBINGLVZHUNIANZENGJIA。LAIZISHANGHAI、BEIJINGDENGDIQUDELIUXINGBINGXUEDIAOCHAJIEGUOXIANSHI,PUTONGCHENGRENBXINGCHAOSHENGZHENDUANDENAFLDHUANBINGLV10NIANQIJIANCONG15%ZENGJIADAO31%YISHANG。NASHZAIHEBINGDAIXIEZONGHEZHENG、2XINGTANGNIAOBINGDENAFLDHUANZHEZHONGJIANCHULVGAO。NASHSHIDAOZHIGANYINGHUADEZHUYAOYUANYINZHIYI,NASHHUANZHE10~15NIANNEIGANYINGHUAFASHENGLVGAODA15%~25%。XINXUEGUANJIBING、EXINGZHONGLIUHEGANYINGHUASHIDAICHANGSHIYINQINASHHUANZHESIWANGDECHANGJIANYUANYIN。

(SAN)ZHILIAOYAOWU

ZHILIAOMUBIAO:ZUIZHONGMUDESHIYANHUAN、ZUZHI、NIZHUANNASHDEJINZHAN,GAISHANLINCHUANGJIEJU,BAOKUOJIANGDIGANYINGHUAJIQIBINGFAZHENGDEFASHENG,JIANGDIGANYIZHIDEXUQIU,TIGAOCUNHUOLV,GAISHANSHENGHUOZHILIANGDENG。

ZHILIAOYAOWU:MUQIANSHANGWUTONGGUOSUIJIDUIZHAOLINCHUANGSHIYANQUEZHENGYOUXIAOXINGHEANQUANXINGDEZHILIAOYAOWUSHANGSHI。

三、臨床試驗設計

(YI)ZONGTIKAOLV

YAOWUYANFALINCHUANGSHIYANDESHEJIJIYULINCHUANGSHIYANMUDEERDING。GENJUZHILIAONASHYAOWUBADIANBUTONG,ZHIDINGLINCHUANGSHIYANFANGAN。

1.SHOUSHIZHE

NASHZHENDUAN:JINGUANGANZUZHIXUEJIANCHACUNZAIYOUCHUANGXING、QUYANGHEPINGJIAWUCHADENGJUXIANXING,DANRENGRANSHIMUQIANNASHZHENDUANDE“JINBIAOZHUN”。ZAINASH YAOWUYANFAZHONG,GANZUZHIBINGLIXUESHIQUEZHENGXINGLINCHUANGSHIYANZHONGSHOUSHIZHEZHENDUANJIZHUYAOZHONGDIANDEPINGJIAZHIBIAO。NAFLD/NASHDEZUZHIXUEPINGJIAXITONGZHUYAOBAOKUO BruntXITONG、MEIGUONASHLINCHUANGYANJIUWANGLUOPINGFENXITONG(NASH-CRN)、OUZHOUZHIFANGGANJINZHANZUDUANZUZHIXUEPINGFENXITONG(FattyLiver Inhibition of Progression,FLIP-SAF)DENG。

GULITANSUOWUCHUANGBIAOZHIWUZUOWEIZAOQICHUBUSHAIXUANNASHSHOUSHIZHEDEFANGFA,QIZHONGBAOKUOALTDENGXUEQINGSHENGHUAZHIBIAOHEFUBUCHAOSHENG、HECIGONGZHENCHENGXIANGDENGYINGXIANGXUEZHIBIAO。

2.ZHONGDIANZHIBIAOPINGJIA

YOUXIAOXINGPINGJIAZHONGDIANBAOKUOLINCHUANGJIEJUZHONGDIANHEGANZUZHIXUETIDAIZHONGDIAN,YIJIXUEQINGSHENGHUAJIANCHA、YINGXIANGXUEJIANCHADENGQITATANSUOXINGZHONGDIAN。

(1)LINCHUANGJIEJUPINGJIA

DUIYUNASHWUGANYINGHUADEHUANZHE,LINCHUANGZHONGDIANBAOKUOJINZHANZHIGANYINGHUA、CHUXIANSHIDAICHANGSHIJIAN(FUSHUI、SHIGUANWEIDIJINGMOQUZHANGCHUXUEHUOGANXINGNAOBINGDENG)、GANYIZHI、GANXIBAOAIHUOGANBINGXIANGGUANSIWANG/QUANYINSIWANGDENGSHIJIAN。

DUIYUNASHGANYINGHUADAICHANGQIDEHUANZHE,LINCHUANGZHONGDIANBAOKUOCHUXIANSHIDAICHANGSHIJIAN、GANYIZHI、GANXIBAOAIHUOGANBINGXIANGGUANSIWANG/QUANYINSIWANGDENGSHIJIAN。

秒速赛车控制器(2)GANZUZHIBINGLIXUEPINGJIA

秒速赛车控制器GANZUZHIBINGLIXUEPINGJIAZHIBIAOBAOKUOZHIFANGXINGGANYAN、XIANWEIHUADEGAISHAN。

ZUZHIBINGLIXUEPINGJIAZHILIANGSHOUDUOZHONGYINSUYINGXIANG,BAOKUOHUOJIANFANGSHI、HUOJIANLEIXING(CUZHENCHUANCI/XIEXINGHUOJIAN)、CHUANCIBUWEI、CHUANCIZHENGUIGEYIJIBINGLIXUEZHUANJIAPINGGUDENG。WEIBAOZHENGZUZHIXUEYANGBENDECHULIZHILIANG,YAOQIUYANGEZUNXUNBINGLIYANGBENSOP(StandardOperation Procedure)。WEIJIANSHAOZUZHIBINGLIXUEPINGJIADECHAYI,BINGLIDUPIANYINGCAIYONGZHONGXINYUEPIAN,JIANYIYOULIANGMINGJIYISHANGGANZANGBINGLIZHUANJIAJINXINGSHUANGMANGDUPIAN。GANZUZHIBINGLIXUEYANGBENSOPKECANKAOXIANGGUANZHIDAOYUANZE,RU:《GANXIANWEIHUAZHENDUANJIZHILIAOGONGSHI》DENG。

(3)YINGXIANGXUEPINGJIA

秒速赛车控制器CIGONGZHENZHIZIMIDUZHIFANGFENSHU(MagneticResonance Imaging–derived Proton Density Fat Fraction,MRI-PDFF)KEDINGLIANGPINGJIAGANZANGZHIFANGHANLIANG。ZAIPEIXUNHELIANGHAOZHIKONGDEQIANTIXIA,KEYIYONGMRI-PDFFGAIBIANDEJUEDUIZHIHUOZHEXIANGDUIBAIFENBIPINGJIAYIGANZHIFANGBIANWEIZHILIAOBADIANDEYAOWU。

CIGONGZHENDANXINGCHENGXIANG(MagneticResonance Elastography,MRE)HESHUNSHIDANXINGCHENGXIANG(TransientElastography,TE)DENGWUCHUANGJISHUKEYIYONGYUPINGJIAGANXIANWEIHUAGAIBIAN。QIZHONGTETONGSHILIANHEJIANCEKONGZHISHUAIJIANCANSHU(ControlledAttenuation Parameter,CAP)KEYIXIEZHUPINGJIAGANZHIFANGBIAN。DANSHIYOUYUSHOUDAOGANZANGYANZHENG、DANZHIYUJI、CAOZUOGUIFANDENGYINSUYINGXIANG,ZAIZHENDUANNASHXIANWEIHUACHENGDUHEPANDUANZHILIAOQIANHOULIAOXIAOFANGMIAN,RENGBUNENGTIDAIZUZHIBINGLIXUEPINGJIA。

(4)XUEQINGXUEPINGJIA

秒速赛车控制器WUCHUANGZHIBIAOZHONG,YUPINGJIATANGZHIDAIXIEXIANGGUANDEYOUTIZHONG、TIZHILIANGZHISHU(BMI)、YAOTUNBI、KONGFUXUETANG、TANGHUAXUEHONGDANBAI、YIDAOSUDIKANG(RUHOMA-IR)、XUEZHIDENG。YUGANZANGYANZHENG/SUNSHANGXIANGGUANDEYOUALT、AST、CK18PIANDUANDENG。YUPINGJIAGANXIANWEIHUAXIANGGUANDEYOUFibroTest、ELF(Enhanced LiverFibrosis)、NAFLDXIANWEIHUAPINGFEN(NAFLDFibrosis Score,NFS)、Pro-C3、FIB-4、ASTYUPLTBIZHIZHISHU(AST/PLT RatioIndex,APRI)DENG。

(5)QITA

YONGYUPINGJIAGANYINGHUALINCHUANGJIEJUDEZHIBIAOBAOKUOGANJINGMOYALITIDU(HepaticVenous Pressure Gradient,HVPG)HEGANGONGNENGChild-PughPINGFEN、ZHONGMOQIGANBINGMOXING(Model forEnd-stage Liver Disease,MELD)PINGFENDEBIANHUA。

3.FANGFAXUEKAOLV

JIJIESHOUCHUANTONGDELINCHUANGYANFASHEJI,YEJIESHOUXINYINGSHEJI,RU:SHIYINGXINGSHEJIDENG,DANYINGZAIFANGANZHONGSHIXIANSHUOMING。RUCAIYONGXINYINGSHEJI,JIANYIYUYAOPINJIANDUGUANLIBUMENSHIXIANGOUTONG。

SUIJIFENZUSHIKEYIKAOLVCAIYONGFENCENGSUIJIHUADEFANGFA,RU:KAOLVTANGNIAOBINGDENGBINGCUNJIBINGYINSU。

秒速赛车控制器YINGGAITIGONGMINGQUEZHENGJUZHENGMINGHUANZHEZAISUIJIRUZUQIAN6~8ZHOUTIZHONGHEDAIXIECANSHUBAOCHIWENDING。WENDINGDETIZHONGDINGYIWEIBIANHUABUCHAOGUO5%。

JIANYIBIMIANSHIYONGKENENGYINGXIANGLIAOXIAOPINGJIADEHEBINGYONGYAO,RUGUOSHIYONG,JIANYIZHISHAOYOU3GEYUEDEWENDINGJILIANG。

秒速赛车控制器RUYANJIUZHONGSHEJIDUOGEYAOWUDUOBADIANLIANHEZHILIAOHUOGUDINGJILIANGFUFANGZHIJI,XUYAOTIGONGLIANHEYONGYAODECHONGFENYIJU。

RUYANJIUZHONGSHEJIHEBINGYONGYAO,BAOKUOZHONGYAODENG,XUYAOZAIYANJIUFANGANZHONGMINGQUEGUIDING,BINGXIANGXIJILUXIANGGUANXINXI。

秒速赛车控制器ZAIGUOJIDUOZHONGXINLINCHUANGSHIYANZHONG,YINNASHYUYINSHIDENGSHENGHUOFANGSHIJIYICHUANDAIXIEYINSUXIANGGUAN,YINGGUANZHUZHONGZUCHAYI(BAOKUOLINCHUANGYAOLIXUEHELINCHUANGSHIJIANFANGMIANDECHAYI)。JIANYIZAIZAOQIJIEDUANJIARUQUANQIUYANFA,YIBAOZHENGSHOUSHIZHENENGGOUCHONGFENDAIBIAOZHONGGUORENQUN。

秒速赛车控制器(ER)BUTONGYANFAJIEDUANJUTIKAOLV

1.LINCHUANGYAOLIXUEYANJIU

秒速赛车控制器TONGCHANG,LINCHUANGYAOLIXUEYANJIUBAOKUORENTINAISHOUXINGSHIYAN、RENTIYAODAIDONGLIXUEHEYAODONGXUE/YAOXIAOXUESHIYAN。

YOUYUZHILIAONASHDEYAOWUDUOXUJIAOCHANGSHIJIANGEIYAO,YINCI,CHUFEISHOUYAOWUDEDUXINGHUOYAOLIZUOYONGSUOJINJI,ZAIDUOCIGEIYAONAISHOUXINGSHIYANZHONGGEIYAODESHIJIANYINGZUGOUCHANG。

DUIYUKENENGSHEJIDAOGANZANGDAIXIEDEYAOWU,ZAIZAOQIYANFAJIEDUANYINGKAIZHANGANGONGNENGSUNHAIDUIYAOWUYAODAIDONGLIXUEDEYINGXIANGYANJIU,WEIHOUXULINCHUANGSHIYANZHONGHELIDEGEIYAOFANGANJIJILIANGDIAOZHENGTIGONGZHICHI。

ZAIYAOWUDEZAOQIYANFAJIEDUAN,KEYIKAOLVYIYINGXIANGXUE、XUEQINGXUE、NASHGANXIANWEIHUAWUCHUANGPANBIEMOXINGDENGZUOWEIYAOXIAOXUEZHIBIAO,JINXINGXIAOYANGBEN、DUANLIAOCHENGDEYAODONGXUE/YAOXIAOXUEPINGGU,QUANMIANLEJIEYAOWUDEBAOLU/XIAOYINGZUOYONGTEDIAN,WEIHOUXULINCHUANGSHIYANTIGONGZHIDAO。

ZAOQIYANFAJIEDUANYINGZHENDUIYAOWUTINEICHUZHIGUOCHENGGUANJIANHUANJIE,RUGUANJIANDAIXIEMEIHUOZHUANYUNTIDEDIWU、YOUDAOJIHUOYIZHIJIDENG,KAIZHANYAOWUXIANGHUZUOYONGYANJIU。NASHHUANZHECHANGTONGSHIHEBINGTANGNIAOBING、GAOXUEYA、GAOZHIXUEZHENG、TONGFENGDENGDAIXIEXIANGGUANJIBING,ERQIE,CILEIHUANZHEDEXINNAOXUEGUANSHIJIANFENGXIANZENGJIA。YINGZHONGDIANGUANZHUYUYISHANGJIBINGCHANGYONGYAOWUHEBINGYONGYAODEYAOWUXIANGHUZUOYONG。JIYUQUNTIYAODAIDONGLIXUEFENXIYEYOUZHUYUMIAOSHUYIZHIHUOXINQUEDINGXIANGHUZUOYONGDELINCHUANGYINGXIANG,BINGTIGONGJILIANGDIAOZHENGDEJIANYI。

2.TANSUOXINGLINCHUANGSHIYAN

(1)ZAOQIGAINIANYANZHENG

NASHYAOWUDEZAOQIGAINIANYANZHENGYINGFUHEGAIQIDEYIBANYUANZE。TIGONGCHUBUDEZHENGJUZHICHIHOUXUDELINCHUANGSHIYAN,BAOKUORUZUBIAOZHUN、LINCHUANGSHIYANDEZHOUQIYIJIZHONGDIANDESHEZHI。

SHOUSHIZHEDERUXUANKECAIYONGXUEQINGSHENGHUAJIANCHAHUOYINGXIANGXUEFANGFA。

ZHUYAOLIAOXIAOZHIBIAOKECAIYONGWUCHUANGXINGBIAOZHIWU,BAOKUOMRI-PDFF、MREDENGYINGXIANGXUEGAIBIAN,YIJIGANZANGJIBINGTEYIXINGDEXUEQINGSHENGHUAZHIBIAODEBIANHUADENG,YEKEJIEHEZUZHIBINGLIXUE、YINGXIANGXUEHEXUEQINGSHENGHUAJIANCHADENGWUCHUANGBIAOZHIWUDEBIANHUAGONGTONGPINGJIAGANZANGZHIFANGHANLIANG、YANZHENGHEXIANWEIHUA。

GEIYAOJILIANGHEZHILIAOCHIXUSHIJIANYAOGENJUZUOYONGJIZHIJIDUIYUSUOXUANLIAOXIAOZHIBIAODEYUQIZUOYONGLAISHEJI,YINGYOUZUGOUCHANGDEZHONGDIANGUANCHASHIJIAN。JIANYIGAIJIEDUANTANSUODUOGEJILIANGZUOWEIHOUXUSHEJIDEXUANZE。

(2)HOUQITANSUO

秒速赛车控制器SHEJI:ANWEIJIDUIZHAO、SUIJI、SHUANGMANGSHEJI。

SHOUSHIZHE:RUXUANXUKAOLVNIANLING、XINGBIE、ZHENDUANBIAOZHUN、JIBINGYANZHONGCHENGDU、HEBINGJIBINGDENG。JIANYINARUJINGGANZUZHIBINGLIXUEQUEZHENDENASHHUANZHE,GANZUZHIHUOJIANZHIRUZUDESHIJIANCHUANGYIBANBUCHAOGUO6GEYUE,ZAIGAISHIJIANCHUANGNEIXUZHUYIHUANZHESHIFOUJIESHOUKENENGYINGXIANGGANZUZHIXUEBIANHUADEGANYU。DUIYUNASHWUGANYINGHUADEHUANZHE,MUQIANJIANYIDEZHUYAORUZUBIAOZHUN:NASPINGFEN≥4FEN,QIZHONGYANZHENGHEQIQIUYANGBIANGEZHISHAO1FEN;TONGSHI,F2≤CRNXIANWEIHUA<F4。DUIYUNASHGANYINGHUADAICHANGQIDEHUANZHE,ZAIGANZUZHIBINGLIXUEQUEZHENNASHDEJICHUSHANG,HUANYINGYOUGANYINGHUADEZUZHIBINGLIXUEZHENGJU。ZHUYAOPAICHUBIAOZHUN:ALTHEASTSHENGGAOCHAOGUOZHENGCHANGSHANGXIAN(ULN)DE5BEI,DANHONGSUSHENGGAOCHAOGUO1.5BEIULN,MELDPINGFEN>12FEN,CTPPINGFEN>6FEN,HEBINGQITAGANZANGJIBINGDENASH。

ZHUYAOLIAOXIAOZHIBIAO:

秒速赛车控制器YIZUZHIXUEGAISHANWEIZHUYAOLIAOXIAOZHIBIAOSHI,TUIJIAN:①NASHGAISHAN,TONGSHIXIANWEIHUAWUEHUA;HUOZHE,②GANZUZHIXIANWEIHUAGAISHAN1FENJIYISHANG,TONGSHINASHWUEHUA;HUOZHE,③NASHGAISHANTONGSHIGANZUZHIXIANWEIHUAGAISHAN1FENJIYISHANG。NASHGAISHANDINGYIWEINASPINGFENZHISHAOJIANGDI2FEN,QIZHONGQIQIUYANGBIANZHISHAOJIANGDI1FEN,ZHIFANGBIANPINGFENBUZENGJIA。NASHWUEHUADINGYIWEIZAINASPINGFENZHONGDEYANZHENG、QIQIUYANGBIANHEZHIFANGBIANPINGFENJUNBUZENGJIA。

DUIYUNASHGANYINGHUADAICHANGQIDEHUANZHE,YEKEYIXUANZELINCHUANGJIEJUZHONGDIANZUOWEIZHUYAOLIAOXIAOZHIBIAO。

GEIYAOJILIANGHEZHILIAOCHIXUSHIJIAN:KESHEZHIDUOGEJILIANGZU,PINGJIAYAOWUDELIANGXIAOGUANXI。YINGBAOZHENGZUGOUCHANGDEYANJIUSHIJIANYIGUANCHAZUZHIXUEGAISHAN,ZHISHAOYAODADAO12~18YUE。

3.QUEZHENGXINGLINCHUANGSHIYAN

秒速赛车控制器SHEJI:ANWEIJIDUIZHAO、SUIJI、SHUANGMANGSHEJI。

SHOUSHIZHE、GEIYAOJILIANGHEZHILIAOCHIXUSHIJIANTONGHOUQITANSUOXINGLINCHUANGSHIYAN。

ZHUYAOLIAOXIAOZHIBIAO:

DUIYUNASHWUGANYINGHUADEHUANZHE,MUQIANKEJIESHOUDEGANZUZHIBINGLIXUETIDAIZHONGDIANBAOKUOZHIFANGXINGGANYANHE/HUOXIANWEIHUADEGAISHAN。

DUIYUNASHGANYINGHUADAICHANGQIDEHUANZHE,RUGUOXUANZEGANZUZHIBINGLIXUEZUOWEITIDAIZHONGDIAN,YINGYOUCHONGFENDEKEXUEYIJU,BINGSHIXIANYUYAOPINJIANDUGUANLIBUMENJINXINGGOUTONG。

YIZUZHIXUEGAISHANWEIZHUYAOLIAOXIAOZHIBIAOSHI,TUIJIAN:①NASHHUANJIETONGSHI,XIANWEIHUAWUEHUA;HUOZHE,②GANZUZHIXIANWEIHUAGAISHAN1FENJIYISHANG,TONGSHINASHWUEHUA;HUOZHE,③NASHHUANJIETONGSHIGANZUZHIXIANWEIHUAGAISHAN1FENJIYISHANG。NASHHUANJIEDINGYIWEINASPINGFENZHONGYANZHENGPINGFENWEI0-1FEN,QIQIUYANGBIANPINGFENWEI0FEN,ZHIFANGBIANPINGFENBUZENGJIA。NASHWUEHUADINGYIWEIZAINASPINGFENZHONGDEYANZHENG、QIQIUYANGBIANHEZHIFANGBIANPINGFENJUNBUZENGJIA。

秒速赛车控制器YOUYUNASHDEZHILIAOKENENGXUYAOCHANGQIFUYAO,YINGKAOLVTINGYAOHOUSUIFANG。

秒速赛车控制器ZAIQUEZHENGXINGLINCHUANGSHIYANTONGSHIKEJINXINGQUNTIYAODAIDONGLIXUEYANJIU、YAOWUJIYINZUXUEYANJIUDENG。

4.QUEZHENGLINCHUANGHUOYIDESHIYAN

秒速赛车控制器JIANYUZUZHIXUEGAISHANDETIDAIZHONGDIANYULINCHUANGJIEJUDEXIANGGUANXINGSHANGWEIQUELI,YINGJINXINGLINCHUANGSHIYANQUEZHENGLINCHUANGJIEJUDEHUOYI。

TUIJIANYIXIAFUHEZHONGDIAN:CHUXIANSHIDAICHANGSHIJIAN(FUSHUI、SHIGUANWEIDIJINGMOQUZHANGCHUXUEHUOGANXINGNAOBING)、GANYIZHI、MELDPINGFEN≥15、GANXIBAOAI、QUANYINSIWANG。DUIYUNASHWUGANYINGHUADEHUANZHE,HUANBAOKUOJINZHANZHIGANYINGHUA。

(SAN)ANQUANXINGPINGJIA

YOUYUNASHXUYAOCHANGSHIJIANDELIANXUFUYAO,YINCIXUYAOYOUZUGOUDEBAOLULIANGHEBAOLUSHIJIANJINXINGANQUANXINGGUANCHA。JIANYIZAICHANGQISHIYANZHONGSHELIDULIDEKEXUEWEIYUANHUI。

秒速赛车控制器NASHLINCHUANGSHIYANZHONGYINGTEBIEGUANZHUYIXIAKENENGDEBULIANGSHIJIAN:

秒速赛车控制器1.GANZANGBULIANGSHIJIAN:YOUYUNASHHUANZHEDUIYAOWUSUOZHIDEGANSUNSHANGMINGANXINGZENGJIA,YOUSHIYAOWUKENENGYOUFAGANSUNSHANGJIAZHONG,SHEJILINCHUANGSHIYANSHIYINGJIANGZHEYIKENENGXINGKAOLVZAINEI。YINGJINLIANGQUEDINGGANSUNSHANGJIAZHONGDEYUANYIN,HUANYINGTEBIEGUANZHUTINGYAOHOUFANTIAOXINGGANGONGNENGYICHANG。DUIYUYOUQIANZAIGANZANGDUXINGDEYAOWU,YINGZAILINCHUANGSHIYANZHONGSHELIJIANCEJIHUA。

秒速赛车控制器2.SHENZANGBULIANGSHIJIAN:YOUYUNASHBENSHENHUIZENGJIAMANXINGSHENZANGJIBINGDEFENGXIAN,ZAISHIYANQIANHESHIYANGUOCHENGZHONGYAOQUANMIANPINGGUHEJIANCESHOUSHIZHEDESHENZANGGONGNENG。

3.XINXUEGUANBULIANGSHIJIAN:XINXUEGUANSHIJIANSHINASHHUANZHEDEZHUYAOSIYIN,YINGGENJUYAOWUDETEDIAN,JIANCEYAOWUDUIXINXUEGUANXITONGDEYINGXIANG。

秒速赛车控制器4.DAIXIEHENEIFENMIBULIANGSHIJIAN:NASHCHANGHEBINGDAIXIEZONGHEZHENG,YINGGENJUYAOWUDETEDIAN,JIANCEDUITIZHONG、XUETANGDENGDAIXIEZHIBIAODEYINGXIANG。

SI、CANKAOWENXIAN

1.FEIJIUJINGXINGZHIFANGXINGGANBINGZHENLIAOFANGZHIZHINAN(2018GENGXINBAN).ZHONGHUAGANZANGBINGZAZHI,2018,26(3):195-203.

秒速赛车控制器2.GANXIANWEIHUAZHENDUANJIZHILIAOGONGSHI(2019NIAN).LINCHUANGGANDANBINGZAZHI,2019,35(10):2163-2172.

3.NMPA.YAOWULINCHUANGSHIYANDEYIBANKAOLVZHIDAOYUANZE.2017NIAN1YUE

4.Sanyal AJ, Friedman SL, McCullough AJ, etal. Challenges and opportunities in drug and biomarker development fornonalcoholic steatohepatitis: findings and recommendations from an AmericanAssociation for the Study of Liver Diseases–U.S. Food and Drug Administration JointWorkshop [J]. Hepatology, 2015,61(4):1392-1405.

5.Angulo P, Kleiner DE, Dam-Larsen S,et al.Liver fibrosis, but no other histologic features, is associated with long-termoutcomes of patients with nonalcoholic fatty liver disease [J]. Gastroenterology,2015,149:389–397.

秒速赛车控制器6.Younossi ZM,Koenig AB,AbdelatifD,et al. Global epidemiology of nonalcoholic fatty liverdisease—meta-analytic assessment of prevalence,incidence,andoutcome [J].Hepatology,2016,64(1):73-84.

秒速赛车控制器7.Sanyal AJ,Miller V.Regulatory science and drug approval for alcoholic and nonalcoholicsteatohepatitis [J]. Gastroenterology, 2016,150(8):1723–1727.

8.Hannah WN, Torres DM, Harrison SA.Nonalcoholic steatohepatitis and endpoints in clinical trials [J].Gastroenterology & Hepatology,2016,12(12):756-763.

9.Patel YA, Imperial JC, Muir AJ,et al.Baseline parameters in clinical trials for nonalcoholic steatohepatitis :Recommendations from the Liver Forum [J]. Gastroenterology, 2017,153:621–625.

秒速赛车控制器10.Siddiqui M S, Harrison S A, AbdelmalekMF, et al. Case definitions for inclusion and analysis of endpoints in clinicaltrials for nonalcoholic steatohepatitis through the lens of regulatory science[J]. Hepatology, 2018,67(5):2001-2012.

秒速赛车控制器11.Cheung A, Neuschwander‐Tetri BA,Kleiner DE, et al. Defining improvement in nonalcoholic steatohepatitis fortreatment trial endpoints: Recommendations from the Liver Forum [J].Hepatology, 2019,70(5):1841-1855.