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藥物臨床試驗(yàn)數(shù)據(jù)現(xiàn)場核查要點(diǎn)
一、Ⅱ、Ⅲ期臨床試驗(yàn)、人體生物等效性(BE)/ 人體藥代動(dòng)力學(xué)(PK)試驗(yàn)、疫苗臨床試驗(yàn)數(shù)據(jù)現(xiàn)場核查要點(diǎn)——通用內(nèi)容
1、臨床試驗(yàn)條件與合規(guī)性（含各方在臨床試驗(yàn)項(xiàng)目中職責(zé)落實(shí)）
1.1、機(jī)構(gòu)承擔(dān)臨床試驗(yàn)的條件和合規(guī)性
1.1.1、是否具備臨床試驗(yàn)資格的醫(yī)院進(jìn)行（臨床試驗(yàn)批件或備案），確認(rèn)是否包含本專業(yè)；（2004年（藥物臨床試驗(yàn)機(jī)構(gòu)認(rèn)定辦法），專業(yè)認(rèn)定有效期為3年，根據(jù)《中華人民共和國許可法》在有效期前6個(gè)月進(jìn)行資格復(fù)審，NMPA復(fù)查前有效。2018年《關(guān)于調(diào)整藥物臨床試驗(yàn)機(jī)審評(píng)審批程序的公告》如實(shí)施備案管理，專業(yè)、主要研究者需要在系統(tǒng)中進(jìn)行備案，支持文件《臨床試驗(yàn)機(jī)構(gòu)資格證書》《受理通知書》）
1.1.2、具有合法的《臨床試驗(yàn)批件》或默認(rèn)許可制度；（根據(jù)2007年、2020年《藥品注冊管理辦法》藥物臨床試驗(yàn)應(yīng)該在批準(zhǔn)后3年內(nèi)實(shí)施，根據(jù)2018年《關(guān)于調(diào)整藥物臨床試驗(yàn)審評(píng)審批程序的公告》需要《臨床試驗(yàn)通知書》，核查文件《藥物臨床試驗(yàn)批件》、《臨床試驗(yàn)通知書》，首例簽署ICF）
1.1.3、項(xiàng)目實(shí)施時(shí)間與《臨床試驗(yàn)批件》的有效期是否合規(guī)；第一例受試者入組時(shí)間。（根據(jù)2018年《醫(yī)療器械臨床試驗(yàn)檢查要點(diǎn)及判定原則》試驗(yàn)開始的定義為篩選受試者。）
1.2、倫理審查批件及記錄的原始性和完整性
1.2.1、有出席倫理委員會(huì)的簽到表和委員討論的記錄；（根據(jù)2010年《藥物臨床試驗(yàn)倫理審查指導(dǎo)原則》附件2要求，審查投票單、會(huì)議記錄。根據(jù)第五條及《藥物臨床試驗(yàn)機(jī)構(gòu)資格認(rèn)定檢查細(xì)則（試行）》審查倫理委員會(huì)的組成是否符合要求。根據(jù)《關(guān)于調(diào)整藥物臨床試驗(yàn)審評(píng)審批程序的公告》需要考慮區(qū)域倫理委員會(huì)及項(xiàng)目中心倫理委員會(huì)使用，即備案和溝通程序）
1.2.2、委員表決票及審查結(jié)論保存完整與倫理批件保存一致；（根據(jù)2010年《藥物臨床試驗(yàn)倫理審查指導(dǎo)原則》第二十條、二十五條、二十六條等審查投票與批件的一致性。）
1.3、臨床試驗(yàn)合同經(jīng)費(fèi)必須覆蓋臨床試驗(yàn)全部開支（檢查費(fèi)、受試者補(bǔ)貼、研究者觀察費(fèi)等）（可參考《藥物臨床試驗(yàn)合同管理· 廣東共識(shí)（2014年版）》）
1.4、申辦方/CRO按照GCP、方案及合同承擔(dān)相應(yīng)的職責(zé)，保存文件和記錄等。（核查文件《申辦方委托函》《藥物臨床試驗(yàn)協(xié)議》）
2、臨床試驗(yàn)部分（以研究數(shù)據(jù)的真實(shí)完整性為關(guān)注點(diǎn)）
2.1、受試者篩選/入組的相關(guān)數(shù)據(jù)鏈的完整性
2.1.1、總結(jié)報(bào)告與受試者篩選入選表、分中心小結(jié)及實(shí)際進(jìn)行臨床試驗(yàn)的例數(shù)保存一致
2.1.2、方案規(guī)定的入排選標(biāo)準(zhǔn)。（HIS溯源確認(rèn)受試者的入排選標(biāo)準(zhǔn)、操作是否符合要求并記錄完整，入選的受試者是否符合入排標(biāo)準(zhǔn)。）
2.1.3、受試者的鑒認(rèn)代碼表、體檢等記錄包含受試者的鑒別信息（身份照、住院號(hào)、聯(lián)系地址等），由此核查受試者身份的真實(shí)信息。
2.1.4、對(duì)受試者的相關(guān)醫(yī)學(xué)判斷和處理必須由本機(jī)構(gòu)具有執(zhí)業(yè)資格的醫(yī)護(hù)人員執(zhí)行并記錄，核查執(zhí)業(yè)許可證及參與臨床試驗(yàn)的實(shí)際情況。（研究者授權(quán)、簡歷、培訓(xùn)、執(zhí)業(yè)證書等，檢驗(yàn)報(bào)告的判斷及AE報(bào)告等信息是否由研究者進(jìn)行簽署）（核查進(jìn)行醫(yī)學(xué)判斷研究者的執(zhí)業(yè)地點(diǎn)及范圍，現(xiàn)在有多點(diǎn)執(zhí)業(yè)，需要特別關(guān)注，特別是上海，不進(jìn)行醫(yī)學(xué)判斷的實(shí)習(xí)生、規(guī)培醫(yī)生亦可以作為研究者）
2.1.5、受試者不得在方案規(guī)定的時(shí)間內(nèi)重復(fù)參加臨床試驗(yàn)。（HIS溯源，北京可以溯源到前50天內(nèi)的數(shù)據(jù)。BE試驗(yàn)需要核驗(yàn)（受試者數(shù)據(jù)庫）北京和南京庫）
2.2、知情同意書的簽署及過程真實(shí)完整
2.2.1、已簽署ICF的數(shù)量和總結(jié)報(bào)告中的篩選入組病例數(shù)一致（核查物資運(yùn)輸記錄，防止簽署后銷毀，中心打印版除外）
2.2.2、所有ICF簽署的內(nèi)容完整、規(guī)范（含研究者的電話、日期）（根據(jù)2016年版器械GCP-知情同意模版要求）
2.2.3、ICF簽署的時(shí)間不得早于倫理批準(zhǔn)時(shí)間，記錄違規(guī)病例數(shù)（根據(jù)200年版第十條規(guī)定）
2.2.4、知情同意書由本人或法定代理人簽署（必要時(shí)經(jīng)過多方核實(shí)確認(rèn)受試者參加本試驗(yàn)的實(shí)際情況）（根據(jù)1987年和2017年（中華人民共和國民法通則）中確定法定代理人，1987年規(guī)定10歲以下兒童，2017年規(guī)定8歲以下，根據(jù)2016年器械GCP和2013年疫苗GCP對(duì)見證人的要求，2020年GCP）
2.3、臨床試驗(yàn)過程記錄及臨床檢查、化驗(yàn)單的溯源
2.3.1、臨床試驗(yàn)的原始記錄，如方案、CRF、采血記錄、接種記錄、觀察記錄、受試者日記卡等保存完整，核查任意一個(gè)不完整、不真實(shí)的數(shù)據(jù)。（重點(diǎn)關(guān)注試驗(yàn)的“主要療效指標(biāo)”和“安全性指標(biāo)”）（根據(jù)2016年《臨床試驗(yàn)的電子數(shù)據(jù)采集技術(shù)指導(dǎo)原則》及2020年版GCP的數(shù)據(jù)質(zhì)量完整性-ALCOACCEA原則）
2.3.2、核查CRF中記錄的臨床試驗(yàn)過程（如訪視時(shí)間點(diǎn)、接種時(shí)間、采血點(diǎn)、觀察時(shí)間）與執(zhí)行方案一致（查看PD中的列表與實(shí)際PD是否一致）
2.3.3、核查CRF中的檢查數(shù)據(jù)與溯源的檢驗(yàn)科、影像科、心電圖等檢查數(shù)據(jù)一致（床邊心電圖熱敏紙打印，經(jīng)研究者簽字后，屬于核正副本）
2.3.4、核查CRF中數(shù)據(jù)和信息與住院病歷中入組、知情同意、用藥醫(yī)囑、病情記錄等關(guān)聯(lián)性。
2.3.5、核查門診受試者的CRF中入組、訪視、病情記錄等信息與門診病歷（住院病歷）的關(guān)聯(lián)性；（根據(jù)2020年《電子病歷基本規(guī)范》《》）
2.3.6、受試者用藥應(yīng)有原始記錄、如受試者日記卡、醫(yī)囑或原始病歷（住院病歷、門診病歷）等
2.3.7、CRF中的數(shù)據(jù)與總結(jié)報(bào)告中一致。
2.3.8、核查CRF中AE的判斷和記錄與原始記錄/總結(jié)報(bào)告一致。
2.4、CRF中違背方案和SAE等關(guān)鍵數(shù)據(jù)
2.4.1、核查CRF中的CM與門診/住院記錄是否一致，記錄漏記的CM數(shù)量
2.4.2、核查CRF中合并禁用藥的記錄與門診/住院病歷是否一致，核實(shí)漏記合并禁用藥的的例數(shù)；
2.4.3、CRF中偏離和違背方案的記錄和處理與實(shí)際發(fā)生（門診/住院病歷）及總結(jié)報(bào)告是否一致。
2.4.4、CRF中發(fā)生SAE處理與報(bào)告，與原始病歷（住院/門診病歷）總結(jié)報(bào)告一致。
2.5、試驗(yàn)用藥的管理過程和記錄
2.5.1、來源和藥檢具有合法性（參比制劑的合法來源、藥檢報(bào)告）（臨床用藥生產(chǎn)，應(yīng)符合2018年《臨床試驗(yàn)用藥生產(chǎn)質(zhì)量管理規(guī)范》，根據(jù)2016年《對(duì)照藥品一次性進(jìn)口》公告，需要有《一致性進(jìn)口批件》。生物制品參考2008年《生物制品參照藥品一次性進(jìn)口》）
2.5.2、試驗(yàn)用藥物的接收、保存、發(fā)放、使用和回收有原始記錄
2.5.3、試驗(yàn)用藥物的接收、保存、發(fā)放、使用和回收的數(shù)量一致。
2.5.4、試驗(yàn)用藥品的運(yùn)輸和儲(chǔ)存過程溫度符合要求（根據(jù)2017年《疫苗儲(chǔ)存和運(yùn)輸管理規(guī)范》要求，記錄儲(chǔ)存溫度，比如每天兩次書寫記錄溫度，間隔需要大于6小時(shí)）
2.5.5、試驗(yàn)用藥物批號(hào)和藥檢報(bào)告、總結(jié)報(bào)告保持一致
2.6、生物樣本的采集、保存、運(yùn)送和交接記錄
2.6.1、生物樣本采集、預(yù)處理、保存、轉(zhuǎn)運(yùn)過程的各環(huán)節(jié)均有原始記錄；追溯各環(huán)節(jié)記錄的完整性和原始性。
2.6.2、血樣采集時(shí)間與計(jì)劃時(shí)間和總結(jié)報(bào)告一致
2.6.3、需要進(jìn)行特殊處理的生物樣本采集、預(yù)處理、應(yīng)在方案中進(jìn)行規(guī)定
3、委托研究
其他部門或單位進(jìn)行的研究、檢測等工作，是否有委托證明材料。委托證明材料反映的委托單位、時(shí)間、項(xiàng)目及方案等是否與申報(bào)資料記載一致。被委托機(jī)構(gòu)出具的報(bào)告書或圖譜是否為加蓋其公章的原件。對(duì)被委托機(jī)構(gòu)進(jìn)行現(xiàn)場核查，以確證其研究條件和研究情況。
4、出現(xiàn)下列情況，視為拒絕或逃避檢查
4.1、拖延、限制、拒絕檢查人員進(jìn)入被檢查場所或者區(qū)域的，或者限制檢查時(shí)間的；
4.2、無正當(dāng)理由不提供或者規(guī)定時(shí)間內(nèi)未提供與檢查相關(guān)的文件、記錄、票據(jù)、憑證、電子數(shù)據(jù)等材料的
4.3、以聲稱相關(guān)人員不在, 故意停止經(jīng)營等方式欺騙、誤導(dǎo)、逃避檢查的；
4.4、拒絕或者限制拍攝、復(fù)印、抽樣等取證工作。
二、人體生物等效性(BE)/ 人體藥代動(dòng)力學(xué)(PK)試驗(yàn)數(shù)據(jù)現(xiàn)場核查要點(diǎn)——專有內(nèi)容
5、BE、PK生物樣本檢測部分（檢測數(shù)據(jù)的真實(shí)完整性為重點(diǎn)）
5.1、具備與試驗(yàn)相適應(yīng)的實(shí)驗(yàn)室檢查設(shè)備設(shè)施與條件
5.1.1、分析測試的關(guān)鍵設(shè)備、儀器有相關(guān)的維護(hù)記錄
5.1.2、遵循《藥物I 期臨床試驗(yàn)管理指導(dǎo)原則》( 試行), 2011 年12 月2 日以后的試驗(yàn)項(xiàng)目須開啟源計(jì)算機(jī)（采集原始數(shù)據(jù)的計(jì)算機(jī)）和工作站的稽查系統(tǒng)。
5.2、生物樣本檢測試驗(yàn)股過程記錄的真實(shí)完整性
5.2.1、生物樣本檢測實(shí)驗(yàn)須有完整的原始記錄（包括實(shí)驗(yàn)單位、人員、日期、條件及實(shí)驗(yàn)結(jié)果等）；核實(shí)記錄的完整和原始性。
5.2.2、生物樣本分析方法學(xué)確證的原始數(shù)據(jù)與總結(jié)報(bào)告一致。
5.2.3、 核查血藥濃度數(shù)據(jù)與對(duì)應(yīng)標(biāo)準(zhǔn)曲線計(jì)算的一致性；現(xiàn)場重新計(jì)算用以核實(shí)試驗(yàn)數(shù)據(jù)的真實(shí)性。
5.3、生物樣本你的管理可溯源
5.3.1、生物樣本有接收、入庫、存放的原始記錄，且記錄完整（含樣本標(biāo)識(shí)、數(shù)量、來源、轉(zhuǎn)運(yùn)方式和條件、到達(dá)日期和到達(dá)時(shí)樣本狀態(tài)等信息）
5.3.2 貯存的生物樣本有領(lǐng)取、存入的原始記錄。
5.3.3 在規(guī)定期限內(nèi)，該項(xiàng)目保存的生物樣本留樣及其原始記錄；核查留存生物樣本的實(shí)際數(shù)量及記錄的原始性。
5.4、分析測試圖譜的可溯源性
5.4.1、圖譜上的文件編碼/ 測試樣本編碼與受試者生物樣本編碼的對(duì)應(yīng)關(guān)系能夠追溯；
5.4.2 所有紙質(zhì)圖譜包含完整的信息（進(jìn)樣時(shí)間、峰高/ 峰面積、血藥濃度等）；
5.4.3、核查未知樣本、方法學(xué)驗(yàn)證樣本及隨行標(biāo)準(zhǔn)曲線、QC樣本的圖譜，并在源計(jì)算機(jī)溯源，核對(duì)其與工作站電子圖譜的一致性；
5.4.4、核查未知樣本、隨行標(biāo)曲、QC樣本圖譜其進(jìn)樣/ 采集時(shí)間與文件編碼順序、試驗(yàn)時(shí)間順序的對(duì)應(yīng)一致性。
5.4.5、紙質(zhì)圖譜數(shù)據(jù)與總結(jié)報(bào)告一致性。
5.5、核查并記錄影響Cmax、AUC等BE評(píng)價(jià)數(shù)據(jù)手動(dòng)積分
5.6、復(fù)測生物樣本應(yīng)有復(fù)測數(shù)量、復(fù)測原因、采用數(shù)據(jù)的說明
5.7、血藥濃度/ 藥代動(dòng)力學(xué)/ 生物等效性的分析計(jì)算數(shù)據(jù)及結(jié)果在相應(yīng)的軟件上可重現(xiàn)，且與總結(jié)報(bào)告一致。
三、Ⅱ、Ⅲ期臨床試驗(yàn)數(shù)據(jù)和疫苗臨床試驗(yàn)數(shù)據(jù)現(xiàn)場核查要點(diǎn)——專有內(nèi)容
6. Ⅱ、Ⅲ期臨床試驗(yàn)/ 疫苗臨床試驗(yàn)部分
6.1、核查原始數(shù)據(jù)、統(tǒng)計(jì)分析和總結(jié)報(bào)告與鎖定的數(shù)據(jù)庫一致性：
6.1.1、數(shù)據(jù)庫鎖定后是否有修改及修改說明；核實(shí)和記錄無說明擅自修改的數(shù)據(jù)。
6.1.2、鎖定數(shù)據(jù)庫的入組、完成例數(shù)與實(shí)際發(fā)生的入組、完成例數(shù)對(duì)應(yīng)一致
6.1.3、核查鎖定數(shù)據(jù)庫與CRF和原始病歷記錄的主要療效指標(biāo)及安全性指標(biāo)一致性
6.1.4、核對(duì)統(tǒng)計(jì)報(bào)告例數(shù)與鎖定數(shù)據(jù)庫的一致性
6.1.5、核對(duì)總結(jié)報(bào)告例數(shù)與鎖定數(shù)據(jù)庫的一致性
以下為中英文對(duì)照版：
藥物臨床試驗(yàn)數(shù)據(jù)現(xiàn)場核查要點(diǎn)
Key Points for On-siteVerification of Drug Clinical Trial Data
一、Ⅱ、Ⅲ期臨床試驗(yàn)、人體生物等效性(BE)/人體藥代動(dòng)力學(xué)(PK)試驗(yàn)、疫苗臨床試驗(yàn)數(shù)據(jù)現(xiàn)場核查要點(diǎn)——通用內(nèi)容
I. Key points for on-site verification of thedata in phase II and III clinical trials, human bioequivalence (BE)trials/human pharmacokinetics (PK) trials and vaccine clinical trials – generalcontents
1. 臨床試驗(yàn)條件與合規(guī)性（含各方在臨床試驗(yàn)項(xiàng)目中職責(zé)落實(shí)）
1.Conditions and compliance of clinical trials (including responsibilitiesassumed by all parties in the clinical trial project)
1.1* 臨床試驗(yàn)單位承擔(dān)藥物臨床試驗(yàn)的條件與合規(guī)性：
1.1* Conditions and compliance of clinicaltrials conducted by the clinical trial institutions:
1.1.1 臨床試驗(yàn)須在具有藥物臨床試驗(yàn)機(jī)構(gòu)資格的醫(yī)院內(nèi)進(jìn)行（含具有一次性臨床試驗(yàn)機(jī)構(gòu)資格認(rèn)定的批件），落實(shí)臨床試驗(yàn)條件是否支持試驗(yàn)項(xiàng)目實(shí)際的實(shí)施過程。
1.1.1 Clinical trials must be conducted inthe hospitals with the qualification of drug clinical trials (including theapproval documents for one-time qualification of clinical trial institutions)and after confirming whether the clinical test conditions support the actualimplementation processes of the trial project.
1.1.2 具有合法的《藥物臨床試驗(yàn)批件》。
1.1.2 The clinical trial institution hasobtained the legitimate Approval Letter for Drug Clinical Trial.
1.1.3 核對(duì)項(xiàng)目開始實(shí)施時(shí)間與國家食品藥品監(jiān)督管理總局《藥物臨床試驗(yàn)批件》時(shí)間相符性。
1.1.3 The clinical trial institution checkswhether the project initiation time is consistent with the time of ApprovalLetter for Drug Clinical Trial issued by the CFDA.
1.2 倫理審查批件及記錄的原始性及完整性：
1.2 Originality and integrity of approvalletter for ethical review and records:
1.2.1 有出席倫理審查會(huì)議的簽到表和委員討論的原始記錄。
1.2.1 Sign-in table of attending theethical review meeting and original record of member discussion
1.2.2 委員表決票及審查結(jié)論保存完整且與倫理審批件一致。
1.2.2 Members’votes and review conclusionshould be kept intact and consistent with the approval letter for ethicalreview.
1.3 臨床試驗(yàn)合同經(jīng)費(fèi)必須覆蓋臨床試驗(yàn)所有開支（含檢測、受試者營養(yǎng)/交通費(fèi)補(bǔ)貼、研究者觀察費(fèi)等）。
1.3 Clinical trial contract funds mustcover all the clinical trial expenses (including examination cost,nutrition/transportation subsidies of the subject, observation cost of theinvestigator, etc.).
1.4 申辦者/合同研究組織（CRO）按照藥物臨床試驗(yàn)管理規(guī)范（GCP）原則、 方案及合同承擔(dān)相應(yīng)職責(zé)的文件和記錄（如合同或方案中規(guī)定的項(xiàng)目質(zhì)量管理責(zé)任及監(jiān)查、稽查相關(guān)記錄等）。
1.4 Documents and records of the sponsor/contract research organization (CRO) who assumes corresponding responsibilityin accordance with the Good Clinical Practice (GCP) principles, protocol andcontract (such as records related to project quality management responsibility,monitoring and audit stipulated in the contract or protocol)
2. 臨床試驗(yàn)部分（以研究數(shù)據(jù)的真實(shí)完整性為關(guān)注點(diǎn)）
2. Clinical trials (with the authenticity andintegrity of the research data as the focus)
2.1 受試者的篩選/入組相關(guān)數(shù)據(jù)鏈的完整性：
2.1 Integrity of the data chain related tosubject screening/inclusion
2.1.1* 申報(bào)資料的總結(jié)報(bào)告中篩選、入選和完成臨床試驗(yàn)的例數(shù)與分中心小結(jié)表及實(shí)際臨床試驗(yàn)例數(shù)一致，若不一致須追查例數(shù)修改的環(huán)節(jié)。
2.1.1* The number of cases screened,enrolled and completing the clinical trial in the summary report of theapplication dossiers should be consistent with the number of cases recorded inthe summary table of the sub-center and actually participating in the clinicaltrial. If not, the processes of modifying the number of cases should betracked.
2.1.2* 方案執(zhí)行的入選、排除標(biāo)準(zhǔn)符合技術(shù)規(guī)范（如實(shí)記錄體檢、血尿常規(guī)、血生化、心電圖等詳細(xì)內(nèi)容），其篩選成功率為多少？（含有證據(jù)的初篩受試者例數(shù)）。
2.1.2* If the inclusion and exclusioncriteria for implementing the protocol are consistent with the technicalspecifications (faithfully record the detailed contents of physicalexamination, blood routine test, urine routine test, blood biochemical test andECG), what is the success rate of screening? (The evidenced number of subjectsinitially screened is included.)
2.1.3* 受試者代碼鑒認(rèn)表或篩選、體檢等原始記錄涵蓋受試者身份鑒別信息（如姓名、住院號(hào)/門診就診號(hào)、身份證號(hào)、聯(lián)系地址和聯(lián)系方式等），由此核查參加臨床試驗(yàn)受試者的真實(shí)性。
2.1.3* Because the subject codeidentification table or screening record, physical examination record and otheroriginal records cover the subject identification information (such as thename, admission number/outpatient number, ID number, contact address andcontact number, etc.), the authenticity of the subject participating in theclinical trial can be verified upon these information.
2.1.4 對(duì)受試者的相關(guān)醫(yī)學(xué)判斷和處理必須由本機(jī)構(gòu)具有執(zhí)業(yè)資格的醫(yī)護(hù)人員執(zhí)行并記錄，核查醫(yī)護(hù)人員執(zhí)業(yè)許可證及其參與臨床試驗(yàn)的實(shí)際情況。
2.1.4 Medical judgment and treatmentrelated to the subjects must be performed and recorded by qualified medicalstaff in the institution, and the practice license of medical staff and theiractual situations of participating in the clinical trial must be verified.
2.1.5 受試者在方案規(guī)定的時(shí)間內(nèi)不得重復(fù)參加臨床試驗(yàn)。
2.1.5 Subjects should not participate inthe clinical trial repeatedly within the time specified in the protocol.
2.2 知情同意書的簽署與試驗(yàn)過程的真實(shí)完整性：
2.2 Signing the informed consent form andthe authenticity and integrity of the trial process:
2.2.1 已簽署的知情同意書數(shù)量與總結(jié)報(bào)告中的篩選和入選病例數(shù)一致。
2.2.1The number of signed ICF should beconsistent with the number of screened and enrolled cases in the summaryreport.
2.2.2 所有知情同意書簽署的內(nèi)容完整、規(guī)范（含研究者電話號(hào)碼，簽署日期等）。
2.2.2 The contents of all the ICFs signedshould be intact and standardized (containing the phone number and signaturedate of the investigator).
2.2.3 知情同意簽署時(shí)間不得早于倫理批準(zhǔn)時(shí)間，記錄違規(guī)例數(shù)。
2.2.3 The time of signing the ICF shouldnot be earlier than the time of ethical approval, and the number of casesviolating the rules should be recorded.
2.2.4* 知情同意書按規(guī)定由受試者本人或其法定代理人簽署（必要時(shí)，多方核實(shí)受試者參加該項(xiàng)試驗(yàn)的實(shí)際情況）。
2.2.4* The ICFs should be signed uponregulations by the subjects themselves or their legal agents. (When necessary,their actual conditions of participating in the clinical trial should beverified by multiple parties.)
2.3 臨床試驗(yàn)過程記錄及臨床檢查、化驗(yàn)等數(shù)據(jù)的溯源：
2.3 Recording of the clinical trial processand tracing the data of clinical examinations and laboratory tests:
2.3.1 臨床試驗(yàn)的原始記錄，如執(zhí)行方案、病例報(bào)告表（CRF）、采血記錄、接種記錄、觀察記錄、受試者日記卡等保存完整；核查任何一項(xiàng)不完整、不真實(shí)的數(shù)據(jù)。
2.3.1 The original records of clinicaltrials, such as the implementation protocol, case report form (CRF), bloodcollection records, vaccination records, observation records and subjects’diary cards, should be kept intact, and any one of incomplete and unreal datashould be checked.
2.3.2 核查CRF記錄的臨床試驗(yàn)過程（如訪視點(diǎn)、接種時(shí)間、采血點(diǎn)、觀察時(shí)間等）與執(zhí)行方案的一致性；核查任何一項(xiàng)不一致、不真實(shí)的數(shù)據(jù)。
2.3.2 The consistency of the clinical trialprocess recorded in the CRF (such as the visiting points, vaccination points,blood collection points, observation time points, etc.) with the implementationprotocol and any one of incomplete and unreal data should be checked.
2.3.3*核查CRF中的檢查數(shù)據(jù)與檢驗(yàn)科、影像科、心電圖室、內(nèi)鏡室（LIS、PACS等信息系統(tǒng)）/等檢查數(shù)據(jù)一致；核實(shí)任何一項(xiàng)不一致/不能溯源的數(shù)據(jù)。
2.3.3* The consistency of the test data inthe CRF with the test data of the clinical laboratory, imaging department, ECGroom and endoscopy room (LIS, PACS and other information systems) and any oneof inconsistent/untraceable data should be checked.
2.3.4 核查CRF中的數(shù)據(jù)和信息與住院病歷（HIS）中入組、知情同意、用藥醫(yī)囑、訪視、病情記錄等關(guān)聯(lián)性記錄；核實(shí)完全不能關(guān)聯(lián)的受試者臨床試驗(yàn)的實(shí)際過程。
2.3.4 The consistency of the data andinformation in the CRF with the relevant data of the enrollment, informedconsent, medical instructions, visiting and medical history records and theactual clinical trial process of the completely irrelevant subjects should bechecked.
2.3.5 核查門診受試者的CRF中入組、訪視、病情記錄等信息與門診病歷（研究病歷）的關(guān)聯(lián)性（必要時(shí)，可通過醫(yī)院HIS系統(tǒng)核查門診就診信息）。
2.3.5 The correlation of the enrollment,visiting, medical records and other information of the outpatient subjects inthe CRF with the outpatient medical records should be checked. (When necessary,the outpatient consultation information can be checked via the HIS system ofthe hospital.)
2.3.6 受試者用藥應(yīng)有原始記錄，如受試者日記卡或醫(yī)囑或原始病歷（住院/門診 /研究病歷）等；核查記錄的完整性（用藥時(shí)間、用藥量等）及其原始性。
2.3.6 The subjects should have the originalrecords before medication, such as their diary cards or medical instructions ororiginal medical records (admission/ outpatient/medical records). The integrity(medication time and doses) and originality of the records should be checked.
2.3.7* CRF/研究病歷中的臨床檢查數(shù)據(jù)與總結(jié)報(bào)告一致（2.3.3款繼續(xù)核查）； 落實(shí)任何一項(xiàng)不一致數(shù)據(jù)發(fā)生的原由。
2.3.7* The consistency of the clinicaltrial data in the CRF/medical records with the summary report should be checked(with Item 2.3.3 continuously), and the reasons for any one of inconsistentdata should be determined.
2.3.8 核查CRF的不良事件(AE)的記錄及判斷與原始病歷/總結(jié)報(bào)告一致，核實(shí)并記錄漏填的AE例數(shù)。
2.3.8 The consistency of the records andjudgments of adverse events (AEs) in the CRF with the original medical records/summary report and the number of cases with AE who missed filling in the tableshould be checked.
2.4 CRF中違背方案和嚴(yán)重不良事件（SAE）例數(shù)等關(guān)鍵數(shù)據(jù)：
2.4 Key data such as the number of casesviolating the protocol and the number of cases with severe adverse events (SAE)in the CRF:
2.4.1核查CRF中合并用藥記錄與門診/住院病歷記載是否一致，核實(shí)并記錄漏填的合并用藥例數(shù)；若一致則核實(shí)其與總結(jié)報(bào)告是否一致。
2.4.1 The consistency of the records ofcombined medication in the CRF with the outpatient/admission medical records aswell as the number of cases who are missed out and receive combined medicationshould be checked and recorded. If consistent, their consistency with thesummary report should be checked.
2.4.2 核查CRF中違背方案的合并禁用藥的記錄與門診/住院病歷記載是否一致，核實(shí)并記錄漏填合并方案禁用藥的例數(shù)；若一致則核實(shí)其與總結(jié)報(bào)告是否一致。
2.4.2 The consistency of the records ofcombined contraindicated medication violating the protocol in the CRF with theoutpatient/admission medical records as well as the number of cases who aremissed out and receive combined contraindicated medication should be checkedand recorded. If consistent, their consistency with the summary report shouldbe checked.
2.4.3 CRF中偏離和/或違背方案相關(guān)記錄和處理與實(shí)際發(fā)生例數(shù)（門診/住院病 歷）及總結(jié)報(bào)告一致；核實(shí)并記錄漏填的例數(shù)。
2.4.3 The consistency of the relevant recordsand handling of deviating and/or violating the protocol in the CRF with theactual number of cases (outpatient/admission medical records) and summaryreport as well as the number of cases with AE who are missed out should bechecked and recorded.
2.4.4* CRF中發(fā)生的SAE處理和報(bào)告記錄，與原始病歷（住院病歷、門診/研究病 歷）、總結(jié)報(bào)告一致；核實(shí)并記錄瞞填的例數(shù)。
2.4.4* The consistency of SAE handling andreport records in the CRF with the original medical records(admission/outpatient/ medical records) and summary report as well as thenumber of cases with AE who are falsely reported should be checked andrecorded.
2.5 試驗(yàn)用藥品/疫苗的管理過程與記錄：
2.5 Management processes and records ofinvestigational drugs/vaccines:
2.5.1* 試驗(yàn)用藥品/疫苗的來源和藥檢具有合法性（參比制劑的合法來源證明為藥檢報(bào)告、藥品說明書等）。
2.5.1*The sources and testing ofinvestigational drugs/vaccines should be legitimate. (The legitimate sources ofthe reference products should be proved by the CoA and package inserts of thedrug, etc.)
2.5.2* 試驗(yàn)用藥品/疫苗的接收、保存、發(fā)放、使用和回收有原始記錄；核實(shí)原始記錄各環(huán)節(jié)的完整性和原始性。
2.5.2* There should be the original recordsfor the reception, storage, distribution, use and recovery of investigationaldrugs/ vaccines. The integrity and originality of all processes in the originalrecords should be checked.
2.5.3* 試驗(yàn)用藥品/疫苗接收、保存、發(fā)放、使用、回收原始記錄的數(shù)量一致， 核實(shí)并記錄各環(huán)節(jié)數(shù)量的誤差。
2.5.3* The number of investigational drugs/vaccines received, stored, distributed, used and recovered should be consistentin the original records. The errors in the number of all processes should bechecked and recorded.
2.5.4試驗(yàn)用藥品/疫苗運(yùn)輸和儲(chǔ)存過程中的溫度均符合要求。
2.5.4 The temperatures of investigational drugs/vaccinesduring transportation and storage should meet the requirements.
2.5.5 試驗(yàn)用藥品/疫苗批號(hào)與藥檢報(bào)告、總結(jié)報(bào)告等資料一致。
2.5.5 The batch numbers of investigationaldrugs/vaccines should be consistent with the data such as CoA and summaryreport.
2.6 臨床試驗(yàn)的生物樣本采集、保存、運(yùn)送與交接記錄：
2.6 Collection, storage, delivery andreception records of biological samples in the clinical trial:
2.6.1* 生物樣本采集、預(yù)處理、保存、轉(zhuǎn)運(yùn)過程的各環(huán)節(jié)均有原始記錄；追溯各環(huán)節(jié)記錄的完整性和原始性。
2.6.1* There should be the original recordsfor the collection, pretreatment, storage and transportation of biologicalsamples. The integrity and originality of all processes in the original recordsshould be tracked.
2.6.2 血樣采集時(shí)間與計(jì)劃時(shí)間的變化與總結(jié)報(bào)告一致。
2.6.2 The blood sample collection time andchanges of planned time should be consistent with those in the summary report.
2.6.3 根據(jù)化學(xué)藥品性質(zhì)需進(jìn)行特殊處理的生物樣本采集、預(yù)處理應(yīng)在方案中有規(guī)定，且原始記錄與方案要求一致。
2.6.3 The collection and pretreatment ofbiological samples that should be specially treated according their chemicalproperties should be prescribed in the protocol, and the original recordsshould meet the requirements of the protocol.
3. 委托研究
3.Entrusted research
3.1 其他部門或單位進(jìn)行的研究、檢測 等工作，是否有委托證明材料。委托證明材料反映的委托單位、時(shí)間、項(xiàng)目及方案 等是否與申報(bào)資料記載一致。被委托機(jī)構(gòu) 出具的報(bào)告書或圖譜是否為加蓋其公章的 原件。對(duì)被委托機(jī)構(gòu)進(jìn)行現(xiàn)場核查，以確 證其研究條件和研究情況。
3.1 Whether other departments orinstitutions responsible for the research and testing have the entrustingcertificates, whether the entrusted institution, time, project and protocolreflected in the entrusting certificate are consistent with those recorded inthe application dossiers and whether the report or map issued by the entrustedinstitution is the original document affixed with the official seal should bechecked. The entrusted institution is inspected on site to confirm its researchconditions and research state.
4. 其他
Others
4.1* 出現(xiàn)下列情況，視為拒絕或逃避檢查：
4.1* Any one of the conditions will beconsidered as refusing or evading from inspection:
4.1.1拖延、限制、拒絕檢查人員進(jìn)入被檢查場所或者區(qū)域的，或者限制檢查時(shí)間的；
4.1.1 The inspectors are withheld,restricted and refused to enter the inspected places or areas, or theinspection time is limited.
4.1.2 無正當(dāng)理由不提供或者規(guī)定時(shí)間內(nèi)未提供與檢查相關(guān)的文件、記錄、票據(jù)、憑證、電子數(shù)據(jù)等材料的；
4.1.2 The documents, records, bills,vouchers, electronic data and other materials related to inspection are notprovided with justified reasons or within the specified period.
4.1.3 以聲稱相關(guān)人員不在,故意停止經(jīng)營等方式欺騙、誤導(dǎo)、逃避檢查的；
4.1.3 Inspectors are deceived, mislead andevaded by claiming the absence of related personnel and arbitrarydiscontinuation of the operation.
4.1.4 拒絕或者限制拍攝、復(fù)印、抽樣 等取證工作的；
4.1.4 Photographing, photocopying, samplingand other evidencing works are refused or limited.
4.1.5 其他不配合檢查的情形。
4.1.5 Other conditions of beingincooperative with the inspection
二、人體生物等效性（PK）/人體藥代 動(dòng)力學(xué)（PK）試驗(yàn)數(shù)據(jù)現(xiàn)場核查要點(diǎn)—— 專有內(nèi)容
II.Key points for on-site verification of the data in the human bioequivalence(BE) trials/human pharmacokinetics (PK) trials – proprietary contents
5.BE、PK生物樣本檢測部分（檢測數(shù)據(jù)的真實(shí)完整性為重點(diǎn)）
5.Detection of BE and PK biological samples (with the authenticity and integrityof the test data as the focus)
5.1 具備與試驗(yàn)項(xiàng)目相適應(yīng)實(shí)驗(yàn)室檢測設(shè)備與條件：
5.1 Has the laboratory test instruments andconditions suited to test items:
5.1.1 分析測試的關(guān)鍵實(shí)驗(yàn)設(shè)備、儀器應(yīng)有相關(guān)維護(hù)記錄。
5.1.1 There should be related maintenancerecords of key laboratory equipment and instrument for analysis and testing.
5.1.2* 遵循《藥物I期臨床試驗(yàn)管理指導(dǎo)原則》(試行), 2011年12月2日以后的試驗(yàn)項(xiàng)目須開啟源計(jì)算機(jī)（采集原始數(shù)據(jù)的計(jì)算機(jī)）和工作站的稽查系統(tǒng)。
5.1.2* Guidelines for Phase I Drug ClinicalTrial Management (Interim) should be followed. For test projects initiatedafter December 2, 2011, the audit system of the source computer (computercollecting the original data) and work station must be started.
5.2 生物樣本檢測實(shí)驗(yàn)過程記錄的真實(shí)完整性：
5.2 Authenticity and integrity of therecords of biological sample detection process:
5.2.1 生物樣本檢測實(shí)驗(yàn)須有完整的原始記錄（包括實(shí)驗(yàn)單位、人員、日期、條件及實(shí)驗(yàn)結(jié)果等）；核實(shí)記錄的完整和原始性。
5.2.1 There should be complete originalrecords of testing the biological samples (including the testing institution,personnel, date, conditions and results). The completeness and originality ofthe records should be checked.
5.2.2* 生物樣本分析方法學(xué)確證的原始數(shù)據(jù)與總結(jié)報(bào)告一致。
5.2.2* The original data validated by theanalytical method of biological samples should be consistent with those in thesummary report.
5.2.3* 核查血藥濃度數(shù)據(jù)與對(duì)應(yīng)標(biāo)準(zhǔn)曲線計(jì)算的一致性；現(xiàn)場重新計(jì)算用以核實(shí)試驗(yàn)數(shù)據(jù)的真實(shí)性。
5.2.3* The consistency of blood drugconcentrations with the calculated corresponding standard curves should bechecked. The authenticity of the test data should be checked by on-siterecalculation.
5.3 生物樣本的管理軌跡可溯源：
5.3 Traceability of management trails ofbiological samples:
5.3.1* 生物樣本有接收、入庫、存放的原始記錄，且記錄完整（含樣本標(biāo)識(shí)、數(shù)量、來源、轉(zhuǎn)運(yùn)方式和條件、到達(dá)日期和到達(dá)時(shí)樣本狀態(tài)等信息）
5.3.1* There should be the original recordsof receiving, warehousing and storing biological samples and the records shouldbe intact (contain the information like the labels, number, sources,transportation mode and conditions, arrival date and status of the samples).
5.3.2 貯存的生物樣本有領(lǐng)取、存入的原始記錄。
5.3.2 There should be the original recordsof receiving and storing biological samples.
5.3.3 在規(guī)定期限內(nèi)，該項(xiàng)目保存的生 物樣本留樣及其原始記錄；核查留存生物樣本的實(shí)際數(shù)量及記錄的原始性。
5.3.3 The retention of stored biologicalsamples and their original records of the project within the specified periodas well as the actual number of reserved biological samples and the originalityof the records should be checked.
5.4 分析測試圖譜的可溯源性：
5.4 Traceability of the map for analysisand testing:
5.4.1* 圖譜上的文件編碼/測試樣本編碼與受試者生物樣本編碼的對(duì)應(yīng)關(guān)系能夠追溯；核實(shí)和記錄不可追溯的環(huán)節(jié)。
5.4.1* The corresponding relationshipbetween document codes/test sample codes on the map and biological sample codesof the subjects can be traced back. Untraceable processes should be checked andrecorded.
5.4.2 所有紙質(zhì)圖譜包含完整的信息（進(jìn)樣時(shí)間、峰高/峰面積、血藥濃度等）；核實(shí)和記錄不完整的信息。
5.4.2 All the hard-copy maps containcomplete information (injection time, peak height/area, blood drugconcentration, etc.). Incomplete information should be checked and recorded. 5.4.3*核查未知樣本、方法學(xué)驗(yàn)證樣本及隨行標(biāo)準(zhǔn)曲線、QC樣本的圖譜，并在源計(jì)算機(jī)溯源，核對(duì)其與工作站電子圖譜的一致性；記錄檢查數(shù)量以及不一致和不可溯源的數(shù)量。
5.4.3* The maps of unknown samples, samplesfor method validation, accompanying standard curves and QC samples should bechecked and traced on the source computer. The consistency of the maps withelectronic maps of the work stations should be checked. The testing,inconsistent and untraceable number should be recorded.
5.4.4* 核查未知樣本、隨行標(biāo)曲、QC樣本圖譜其進(jìn)樣/采集時(shí)間與文件編碼順序、試驗(yàn)時(shí)間順序的對(duì)應(yīng)一致性；追蹤和記錄所有不一致的數(shù)據(jù)。
5.4.4* The corresponding consistency of themaps of unknown samples, accompanying standard curves and QC samples and theirinjection/collection time with the document coding order and test time sequenceshould be checked. All the inconsistent data should be tracked and recorded.
5.4.5* 紙質(zhì)圖譜數(shù)據(jù)與總結(jié)報(bào)告一致性，記錄不一致數(shù)量。
5.4.5* The hard-copy map data should beconsistent with those in the summary report. The inconsistent number should berecorded.
5.5* 核查并記錄影響Cmax、AUC等BE評(píng)價(jià)數(shù)據(jù)手動(dòng)積分。
5.5* Check and record the manual integralsaffecting Cmax, AUC and other BE evaluation data.
5.6 復(fù)測生物樣本應(yīng)有復(fù)測數(shù)量、復(fù)測原因、采用數(shù)據(jù)的說明。
5.6 There should be instructions forretesting number, retesting reasons and adopted data of retested biologicalsamples.
5.7* 血藥濃度/藥代動(dòng)力學(xué)/生物等效性的分析計(jì)算數(shù)據(jù)及結(jié)果在相應(yīng)的軟件上可重現(xiàn)，且與總結(jié)報(bào)告一致。
5.7* The data and results of analyzing andcalculating blood drug concentration/ pharmacokinetics/bioequivalence can bereproduced in the corresponding software, and are consistent with the summaryreport.
三、Ⅱ、Ⅲ期臨床試驗(yàn)數(shù)據(jù)和疫苗臨 床試驗(yàn)數(shù)據(jù)現(xiàn)場核查要點(diǎn)——專有內(nèi)容
III.Key points for on-site verification of the data in phase II and III clinicaltrials and vaccine clinical trials – proprietary contents
6.Ⅱ、Ⅲ期臨床試驗(yàn)/疫苗臨床試驗(yàn)部分（以數(shù)據(jù)庫的真實(shí)性為重點(diǎn)）
6.Phase II and III clinical trials and vaccine clinical trials (with theauthenticity of the database as the focus)
6.1 核查原始數(shù)據(jù)、統(tǒng)計(jì)分析和總結(jié)報(bào)告與鎖定的數(shù)據(jù)庫一致性：
6.1 Check the consistency of original data,statistical analysis and summary report with locked database:
6.1.1* 數(shù)據(jù)庫鎖定后是否有修改及修改說明；核實(shí)和記錄無說明擅自修改的數(shù)據(jù)。
6.1.1* Whether there are modifications andinstructions for modifications after locking the database should be checked.The nonarbitrarily modified data should be checked and recorded.
6.1.2* 鎖定數(shù)據(jù)庫的入組、完成例數(shù)與實(shí)際發(fā)生的入組、完成例數(shù)對(duì)應(yīng)一致；核實(shí)和記錄不一致的例數(shù)。
6.1.2* The number of cases who are enrolledand complete the study in the locked database should be corresponding to andconsistent with the actual number of cases. The inconsistent number of casesshould be checked and recorded.
6.1.3* 核查鎖定數(shù)據(jù)庫與CRF和原始病歷記錄的主要療效指標(biāo)及安全性指標(biāo)一致性(如有修改需進(jìn)一步核查疑問表的修改記錄)；記錄檢查例數(shù)和擅自修改的數(shù)據(jù)。
6.1.3* The consistency of the lockeddatabase with the primary efficacy indicator and safety indicator recorded inthe CRF and original medical records should be checked. (If modified, themodified records of the questioning table should be further checked.) The casenumber and arbitrarily modified data should be recorded.
6.1.4 核對(duì)統(tǒng)計(jì)報(bào)告例數(shù)與鎖定數(shù)據(jù)庫的一致性。
6.1.4 The clinical trial institution checkswhether the case number in the statistical report is consistent with that inthe locked database.
6.1.5 核對(duì)總結(jié)報(bào)告例數(shù)與鎖定數(shù)據(jù)庫的一致性。
6.1.5 The clinical trial institution checkswhether the case number in the summary report is consistent with that in thelocked database.
（2015-11-10）/(November10, 2015)
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