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注册号: Registration number: |
ChiCTR2600126424 |
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最近更新日期: Date of Last Refreshed on: |
2026-06-09 10:43:12 |
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注册时间: Date of Registration: |
2026-06-09 00:00:00 |
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注册号状态: |
预注册 |
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Registration Status: |
Prospective registration |
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注册题目: |
III期不可切除非小细胞肺癌的转化治疗:一项前瞻性、开放标签、随机对照、多中心II期临床试验 |
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Public title: |
Conversion Therapy for Stage III Unresectable Non-Small Cell Lung Cancer: A Prospective, Open-Label, Randomized Controlled, Multicenter Phase II Trial |
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注册题目简写: |
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English Acronym: |
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研究课题的正式科学名称: |
III期不可切除非小细胞肺癌的转化治疗:一项前瞻性、开放标签、随机对照、多中心II期临床试验 |
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Scientific title: |
Conversion Therapy for Stage III Unresectable Non-Small Cell Lung Cancer: A Prospective, Open-Label, Randomized Controlled, Multicenter Phase II Trial |
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研究课题代号(代码): Study subject ID: |
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在二级注册机构或其它机构的注册号: The registration number of the Partner Registry or other register: |
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申请注册联系人: |
陈飏 |
研究负责人: |
方文涛 |
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Applicant: |
Yang Chen |
Study leader: |
Wentao Fang |
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申请注册联系人电话: Applicant telephone: |
+86 189 6484 6272 |
研究负责人电话:
Study leader's |
+86 199 2127 0909 |
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申请注册联系人传真 : Applicant Fax: |
研究负责人传真: Study leader's fax: |
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申请注册联系人电子邮件: Applicant E-mail: |
cyang0952@163.com |
研究负责人电子邮件: Study leader's E-mail: |
vwtfang@hotmail.com |
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申请单位网址(自愿提供): Applicant website(voluntary supply): |
研究负责人网址(自愿提供): Study leader's website(voluntary supply): |
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申请注册联系人通讯地址: |
上海市浦东新区即墨路150号 |
研究负责人通讯地址: |
150 Jimo Road, Pudong New Area, Shanghai, China |
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Applicant address: |
150 Jimo Road, Pudong New Area, Shanghai, China |
Study leader's address: |
150 Jimo Road, Shanghai, China |
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申请注册联系人邮政编码: Applicant postcode: |
200120 |
研究负责人邮政编码: Study leader's postcode: |
200120 |
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申请人所在单位: |
上海市东方医院 |
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Applicant's institution: |
Shanghai East Hospital |
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研究负责人所在单位: |
上海市东方医院 |
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Affiliation of the Leader: |
Shanghai East Hospital |
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是否获伦理委员会批准: |
是 |
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Approved by ethic committee: |
Yes |
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伦理委员会批件文号: Approved No. of ethic committee: |
[2026]研审第(105)号 |
伦理委员会批件附件: Approved file of Ethical Committee: |
查看附件View |
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批准本研究的伦理委员会名称: |
上海市东方医院医学伦理委员会 |
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Name of the ethic committee: |
Medical Ethics Committee of Shanghai East Hospital |
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伦理委员会批准日期: Date of approved by ethic committee: |
2026-04-23 00:00:00 | ||
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伦理委员会联系人: |
周斐 |
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Contact Name of the ethic committee: |
Zhou Fei |
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伦理委员会联系地址: |
上海市浦东新区云台路1800号 |
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Contact Address of the ethic committee: |
1800 Yuntai Road, Pudong New Area, Shanghai |
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伦理委员会联系人电话: Contact phone of the ethic committee: |
+86 138 0175 1704 |
伦理委员会联系人邮箱: Contact email of the ethic committee: |
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研究实施负责(组长)单位: |
上海市东方医院 |
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Primary sponsor: |
Shanghai East Hospital |
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研究实施负责(组长)单位地址: |
上海市浦东新区即墨路150号 |
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Primary sponsor's address: |
150 Jimo Road, Pudong New Area, Shanghai, China |
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试验主办单位(项目批准或申办者): Secondary sponsor: |
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经费或物资来源: |
转化诱导期研究药物:特瑞普利单抗由君实生物提供 |
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Source(s) of funding: |
During the conversion induction phase, the investigational drug Toripalimab is provided by Junshi Biosciences. |
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研究疾病: |
非小细胞肺癌 |
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Target disease: |
non small cell lung cancer |
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研究疾病代码: |
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Target disease code: |
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研究类型: |
干预性研究 |
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Study type: |
Interventional study |
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研究所处阶段: |
II期临床试验 | ||||||||||||||||||||||
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Study phase: |
2 |
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研究设计: |
随机平行对照 |
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Study design: |
Parallel |
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研究目的: |
1. 主要目的: 在多学科会诊指导下, 评估为III期肿瘤学不可切除的NSCLC患者经免疫-联合化疗诱导治疗后,评估接受根治性手术对比标准根治性放疗对患者2y无事件生存率(EFS)的提升; 2. 次要目的: (1)评价III期不可切除NSCLC患者在药物诱导治疗下的手术率、淋巴结降期率及手术人群的围术期外科结果; (2)评价III期不可切除NSCLC患者在药物诱导治疗后ORR以及手术患者的pCR、MPR; (3)评价III期不可切除NSCLC患者接受药物诱导治疗的安全性; 3. 探索性目的: 评价肿瘤相关生物标志物的变化以其与临床疗效、预后的相关性。 |
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Objectives of Study: |
1. Primary Objective: To evaluate, under the guidance of multidisciplinary team (MDT) consultation, the improvement in 2-year event-free survival (EFS) in patients with stage III oncologically unresectable non-small cell lung cancer (NSCLC) receiving radical surgery compared to those receiving standard radical radiotherapy after induction immunochemotherapy. 2. Secondary Objectives: (1) To evaluate the surgical conversion rate, lymph node downstaging rate, and perioperative surgical outcomes in patients with stage III unresectable NSCLC following induction therapy. (2) To evaluate the objective response rate (ORR) after induction therapy, as well as the pathological complete response (pCR) and major pathological response (MPR) rates in patients undergoing surgery. (3) To evaluate the safety of induction therapy in patients with stage III unresectable NSCLC. 3. Exploratory Objective: To evaluate changes in tumor-related biomarkers and their correlation with clinical efficacy and prognosis. |
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药物成份或治疗方案详述: |
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Description for medicine or protocol of treatment in detail: |
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纳入标准: |
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Inclusion criteria |
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排除标准: |
1.侵犯主动脉、食管、心脏和/或其他器官、组织的 T4 肿瘤,或同侧不同叶肺转移的无法行根治性手术T4肿瘤;融合或多站淋巴结包绕或侵犯主动脉、肺动脉、气管、食管、心脏等,MDT评估无法根治性切除; 2.根据第九版分期,排除III期可切除患者,即: (1) cT2N2a (IIIA期)非肿块和非浸润的单站N2 (2) cT3-4N0-1(IIIA期); (3) cT3-4N2 (IIIB期)非肿块和非浸润的单站N2的患者; 3.混合小细胞肺癌的患者; 4.既往接受过 PD-1/PD-L1药物的治疗或作用于另一种靶向T细胞受体的药物(例如CTLA-4 、OX-40等)的治疗; 5.对其他单克隆抗体发生过重度过敏反应; 6.对培美曲塞、紫杉醇或多西紫杉醇、顺铂、卡铂或其预防用药等有严重过敏史; 7. 5 年内患有除 NSCLC 以外的其他恶性肿瘤的患者,以下情况除外:接受过治愈性治疗且在试验用药品首次给药前≥2 年无已知的活动性疾病且复发潜在风险较低的恶性肿瘤;充分治疗的非黑色素瘤皮肤癌或雀斑样痣恶性肿瘤且无疾病证据;充分治疗的原位癌且无疾病证据; 8.任何不稳定的全身性疾病,包括活动性感染、不受控制的高血压(收缩压≥140 mmHg 或者舒张压≥90 mmHg,尽管进行了最佳药物治疗)、不稳定型心绞痛、近 3 个月内心绞痛发作、需要药物治疗的肝脏疾病、肾脏疾病或代谢疾病; 9.心脏功能和疾病符合下述情况之一: (1) 研究者认为具有临床意义,明显异常而不适合入组本试验的心律失常,包括但不限于完全性左束支传导异常,Ⅱ度房室传导阻滞; (2) 导联心电图(ECG)测量,QTc 间期男性≥450ms、女性≥470ms; (3) 美国纽约心脏学会(NYHA)分级≥3 级心功能不全或心脏彩超检查:左室射血分数(LVEF)<50%;筛选前 1 年内发生过心肌梗死; 10.首次给药前 1 年内存在需要糖皮质激素治疗的非感染性肺炎病史或当前存在间质性肺疾病; 11.确认人类免疫缺陷病毒(HIV)感染; 12.未经治疗的活动性乙型肝炎; 注:符合下列标准的乙肝受试者也可不排除: a.首次给药前 HBV 病毒载量必须<500 IU/ml 或<1000 拷贝/ml,研究者可根据受试者的情况决定研究期间是否给予抗 HBV 治疗; b.对于抗 HBc(+)、HBsAg(-)、抗 HBs(-)和 HBV 病毒载量(-)的受试者,不需要接受预防性抗 HBV 治疗,但是需要密切监测病毒再激活; 13.活动性的 HCV 感染受试者(HCV 抗体阳性且 HCV-RNA 水平高于检测下限); 14.已知的药物过敏(按照所对应分题研究确认相应药物过敏情况); 15.首次给药前 2 个月内发生重大手术或严重损伤的患者; 16.首次给药前 1 个月内出现过临床显著意义的出血症状或者具有明显出血倾向,如:消化道出血、胃溃疡出血或患有脉管炎等; 17.妊娠或哺乳期妇女; 18.接受过实体脏器或血液系统移植; 19.研究者认为患者不适合入组,如神经或代谢紊乱、体格检查或实验室检查怀疑患者有可能的疾病或有研究药物使用禁忌症,或治疗相关并发症风险高。 20.首次给药前 2 年内发生过需要全身性治疗(例如使用缓解疾病药物、皮质类固醇或免疫抑制剂)的活动性自身性免疫疾病。允许间歇使用吸入性类固醇或局部注射类固醇。替代疗法(例如甲状腺素、胰岛素或者用于肾上腺或垂体机能不全的生理性皮质类固醇等)不视为全身性治疗; 21.诊断为免疫缺陷或研究首次给药前 7 天内正在接受与肿瘤治疗非直接相关的全身性糖皮质激素治疗或任何其他形式的免疫抑制疗法;允许使用生理剂量的糖皮质激素(≤10 mg/天的强的松或等效药物); 22.首次用药前 4 周内发生过严重感染(CTCAE≥3 级)的受试者,包括但不局限于需要住院治疗的感染并发症、菌血症、重症肺炎等; 首次用药前 30 天内接种过活/减毒疫苗的受试者。 |
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Exclusion criteria: |
1. T4 tumors invading the aorta, esophagus, heart, and/or other organs or tissues, or T4 tumors with intrapulmonary metastases in a different ipsilateral lobe that cannot undergo radical surgery; confluent or multi-station lymph nodes encasing or invading the aorta, pulmonary artery, trachea, esophagus, heart, etc., assessed by MDT as not amenable to radical resection. 2. Exclusion of patients with resectable stage III disease according to the 9th edition staging, specifically: (1) cT2N2a (stage IIIA) with non-bulky, non-infiltrative single-station N2. (2) cT3-4N0-1 (stage IIIA). (3) cT3-4N2 (stage IIIB) with non-bulky, non-infiltrative single-station N2. 3. Patients with mixed small cell lung cancer. 4. Prior treatment with PD-1/PD-L1 inhibitors or agents targeting another T-cell receptor (e.g., CTLA-4, OX-40, etc.). 5. History of severe allergic reactions to other monoclonal antibodies. 6. History of severe allergy to pemetrexed, paclitaxel or docetaxel, cisplatin, carboplatin, or their prophylactic medications. 7. Patients with other malignancies within the past 5 years, except for: malignancies that have received curative treatment with no known active disease >=2 years prior to the first dose of investigational product and have a low potential risk of recurrence; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease. 8. Any unstable systemic disease, including active infection, uncontrolled hypertension (systolic blood pressure >=140 mmHg or diastolic blood pressure >=90 mmHg despite optimal medical therapy), unstable angina, angina pectoris within the last 3 months, liver disease requiring medication, kidney disease, or metabolic disease. 9. Cardiac function and disease meeting any of the following criteria: (1) Clinically significant arrhythmias deemed inappropriate for enrollment by the investigator, including but not limited to complete left bundle branch block, second-degree atrioventricular block. (2) QTc interval measured by 12-lead ECG >=450 ms in males or >=470 ms in females. (3) New York Heart Association (NYHA) class >= 3 cardiac insufficiency or echocardiogram: Left Ventricular Ejection Fraction (LVEF) <50%. Myocardial infarction occurred within 1 year prior to screening. 10. History of non-infectious pneumonia requiring glucocorticoid treatment within 1 year prior to first dose, or current presence of interstitial lung disease. 11. Confirmed human immunodeficiency virus (HIV) infection. 12. Untreated active hepatitis B. Note: Hepatitis B subjects meeting the following criteria may also not be excluded: (1) HBV viral load must be < 500 IU/mL or <1000 copies/mL prior to the first dose. The investigator may decide whether to administer anti-HBV therapy during the study based on the subject's condition. (2) Subjects who are anti-HBc (+), HBsAg (-), anti-HBs (-), and have undetectable HBV viral load do not require prophylactic anti-HBV treatment but require close monitoring for viral reactivation. 13. Subjects with active HCV infection (HCV antibody positive and HCV-RNA level above the lower limit of detection). 14. Known drug allergies (allergies to corresponding drugs confirmed according to the respective substudy). 15. Patients who have undergone major surgery or experienced severe trauma within 2 months prior to the first dose. 16. Clinically significant bleeding symptoms or a clear bleeding tendency within 1 month prior to the first dose, such as gastrointestinal bleeding, gastric ulcer bleeding, or vasculitis. 17. Pregnant or lactating women. 18. Recipients of solid organ or hematopoietic system transplants. 19. Patients deemed unsuitable for enrollment by the investigator, such as those with neurological or metabolic disorders, physical examination or laboratory findings suggesting a possible disease or contraindication to the study drug, or a high risk of treatment-related complications. 20. Active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within the past 2 years prior to the first dose. Intermittent use of inhaled steroids or local steroid injections is permitted. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal or pituitary insufficiency) is not considered systemic treatment. 21. Diagnosis of immunodeficiency or receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy not directly related to tumor treatment within 7 days prior to the first dose; physiologic doses of glucocorticoids (<=10 mg/day prednisone or equivalent) are permitted. 22. Subjects who experienced a severe infection (CTCAE grade >= 3) within 4 weeks prior to the first dose, including but not limited to infectious complications requiring hospitalization, bacteremia, severe pneumonia, etc. |
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研究实施时间: Study execute time: |
从 From 2026-06-15 00:00:00至 To 2031-06-30 00:00:00 |
征募观察对象时间: Recruiting time: |
从 From 2026-06-16 00:00:00 至 To 2028-06-16 00:00:00 |
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干预措施: Interventions: |
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研究实施地点: Countries of recruitment and research settings: |
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测量指标: Outcomes: |
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采集人体标本:
Collecting sample(s)
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征募研究对象情况: Recruiting status: |
尚未开始 Not yet recruiting |
年龄范围: Participant age: |
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性别: |
男女均可 |
Gender: |
Both |
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随机方法(请说明由何人用什么方法产生随机序列): |
中央随机分配至手术组和放疗组 |
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Randomization Procedure (please state who generates the random number sequence and by what method): |
Centrally randomized to the surgery group or the radiotherapy group |
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是否公开试验完成后的统计结果: Calculated Results after the Study Completed public access: |
公开/Public |
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盲法: |
开放 |
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Blinding: |
Open label |
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试验完成后的统计结果(上传文件): |
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Calculated Results after
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是否共享原始数据: IPD sharing |
是Yes |
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共享原始数据的方式(说明:请填入公开原始数据日期和方式,如采用网络平台,需填该网络平台名称和网址): |
本研究将在研究结束并完成主要结果分析后,或研究结果发表后 6 个月内,公开去标识化原始数据。共享内容包括经脱敏处理的病例报告表关键数据和研究方案,不包括任何可识别受试者个人隐私的信息。数据将通过临床试验公共管理平台 ResMan(www.medresman.org)进行共享;如需下载或进一步使用数据,研究者须向主要研究者提出合理申请,经牵头单位、主要研究者及伦理委员会审核批准后提供。涉及分中心数据使用时,将同时遵守各参加中心伦理审批意见及多中心数据共享协议。 |
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The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url): |
The de-identified raw data will be shared after completion of the study and primary data analysis, or within 6 months after publication of the study results. The shared data will include de-identified key case report form data and the study protocol, and will not include any information that could identify individual participants. The data will be shared through the public clinical trial data management platform ResMan ([www.medresman.org](http://www.medresman.org)). Researchers who wish to download or further use the data should submit a reasonable request to the principal investigator, and data access will be subject to approval by the leading institution, the principal investigator, and the ethics committee. For data from participating centers, data use will also comply with the ethical approvals and multicenter data-sharing agreements of the relevant participating centers. |
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数据采集和管理(说明:数据采集和管理由两部分组成,一为病例记录表(Case Record Form, CRF),二为电子采集和管理系统(Electronic Data Capture, EDC),如ResMan即为一种基于互联网的EDC: |
病例记录表 |
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Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture: |
Case Record Form |
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数据与安全监察委员会: Data and Safety Monitoring Committee: |
暂未确定/Not yet |