版权说明:本文档由用户提供并上传,收益归属内容提供方,若内容存在侵权,请进行举报或认领
文档简介
Lecture4ClinicalResearchrelapsebiomarkerfollow-upinformedconsentendpointsubjectblindingprotocolbiasretrospectivetestnewtreatmentsormedicaldevicesinpeopleitisshowntobesafeinpeopleandworkswell20to100participantswithorwithoutthedisease Learnaboutsafety,howthetreatmentworksinthehumanbody,andthebestamounttotake Lessthanayear About300participantswiththedisease Learnmoreaboutsafetybylookingatsideeffectsandotherproblems Afewmonthsto2years Hundredsorthousandsofparticipantswiththedisease Seehowwellthetreatmentworksandlearnmoreaboutsideeffects 1–3years Thousandsofparticipantswiththedisease Continuetolookatthetreatment’sbenefitforpeople Manyyears protectthesafetyof
participants1.Whatisblindinginclinicaltrials?Blindingisaprocedureinwhichoneormorepartiesinatrialarekeptunawareoftreatmentarmallocationofparticipants.2.Whocanbeblindedinclinicaltrials?Dependingonthetypeofthetrialthefollowingcanbeblinded,participantsbeingtreated,clinicalstafforinvestigatoradministeringtreatment,teamcollectingoutcomedataordataanalysts.3.Whatisanopen-labeltrial?Andwhenisitused?Allthepeopleinvolvedinthetrialwillbeawareofthetreatmentgroupassignmentofstudyparticipants.Itisusedwhenethicalconsiderationsdonotpermitblindingandifnocontrolgroupcanbeused.4.Whatisasingle-blindedtrial?Andwhenisitused?Usuallythesubjectreceivingtheinterventionisblinded.Itisusedwhendoubleblindingisnotpossible,andwhentheexperimentalmedicineandcontrolcannotbemanufacturedidentically.5.Whatisadoubleblindedtrial?Andwhenisitused?Usually,theinvestigatorsaswellasthestudyparticipantsareblindedtothetreatmentallocation.Doubleblindingshouldbeusedwheneverpossiblebecauseitisthebestcontroltrialdesignwithdecreasedtenseofobservationalbias.6.Whatisatripleblindedtrial?Andwhatareitsadvantages?Usually,thesubjects,theinvestigators,andtheoutcomeassessorsareblinded.Tripleblindingincreasestheaccuracyandobjectivityofclinicaloutcomes.Ithelpstoavoidbiasintheanalysisofresults.TFTFTTTFTFTFFF1.HowwasthephaseIclinicalstudyofBMS-986393designed?Thephase1studywasamulti-center,open-labelstudywiththetraditionaldoseescalation.Patientswithrelapserefractorymyelomaandreceivingatleast3priorlinesoftherapy,includingaPI,anIMiD,andantibody-CD38,wereselected.Thestartingdosewas25×106CART-cells,thenwentupto75,150,300and450.TheprimaryobjectivesweretoassesssafetyandtolerabilityandtodetermineMTD/RP2D.2.WhatisthetargetofBMS-986393CART-cells,andwhyisthistargetselected?ItisaGPRC5DtargetedchimericantigenreceptorT-celltherapy.BCMAdirectedCART-celltherapieshavedemonstratedunprecedenteddepthanddurationofresponseinthetreatmentofrelapsed/refractorymultiplemyeloma.However,mostpatientsrelapseandadditionaltargetsforCARTT-celltherapyareneeded.3.WhatisthetoxicityprofileofBMS-986393?MostpatientsexperiencedtreatmentemergentAEsandmostofthemwereGrade3or4.IntermsofhematologicTEATs,mostpatientsexperiencedneutropeniaofanygradeandmostwereGrade3or4;40%ofthepatientshadthrombocytopenia,with20Grade3or4.Intermsofnon-hematologicTEATs,cytokinereleasesyndromeisthemostcommontypeandexperiencedby64%ofthepatients,butmostwereGrade1–2,only6%ofthepatientswereatGrade3or4;fatiguepyrexiawasthesecondmostcommontoxicities.Therewasadose-limitingtoxicityofprolongedGrade4neutropeniareportedintwopatientsat25and75CAR-TsbuttheMTDhadnotbeenexceeded.Nodeathrelatedtothestudyhadbeenreported.IntermsofthemostcommonTEAEcytokinereleasesyndrome:-CRSwasseeninalldoselevels;themajorityoftheCRSwasstillGrade1–2,anddidnotseemtoincreasewithincreasingcelldose.Othertoxicities:neurotoxicitywasrarelyseen;cerebraltoxicityhadnotbeenreportedtothetimeofcutoff.dysgeusiaandtastedisorders,aswellasskintoxicityandnailtoxicityhavebeenseen,butwereatverylowlevelsandverytransient.4.WhatistheefficacyprofileofBMS-986393?Intermsofresponserate:theoverallresponserateis89.5%,
withacompleteresponserateof
47.4%;everydoselevelhadresponses;patientswithoutpriorBCMAtherapyhadanoverallresponserateof100%withacompleteresponserateof50%,whereaspatientswithpriorBCMAtherapyhadanoverallresponserateof77.8%andacompleteresponserateof44.4%.Intermsofresponseovertime:Intermsofpharmacodynamicanalyses:5.DothereportedresultswarrantfurtherdevelopmentofBMS-986393?Whyorwhynot?Accordingtotheresultsofphase1study:BMS-986393hasasafetyprofilethatiscomparablewithpriorautologousCAR-Tcelltherapieswithnonewunexpectedtoxicities;Thedose-escalationisongoingandthemaximumtolerateddoseh
温馨提示
- 1. 本站所有资源如无特殊说明,都需要本地电脑安装OFFICE2007和PDF阅读器。图纸软件为CAD,CAXA,PROE,UG,SolidWorks等.压缩文件请下载最新的WinRAR软件解压。
- 2. 本站的文档不包含任何第三方提供的附件图纸等,如果需要附件,请联系上传者。文件的所有权益归上传用户所有。
- 3. 本站RAR压缩包中若带图纸,网页内容里面会有图纸预览,若没有图纸预览就没有图纸。
- 4. 未经权益所有人同意不得将文件中的内容挪作商业或盈利用途。
- 5. 人人文库网仅提供信息存储空间,仅对用户上传内容的表现方式做保护处理,对用户上传分享的文档内容本身不做任何修改或编辑,并不能对任何下载内容负责。
- 6. 下载文件中如有侵权或不适当内容,请与我们联系,我们立即纠正。
- 7. 本站不保证下载资源的准确性、安全性和完整性, 同时也不承担用户因使用这些下载资源对自己和他人造成任何形式的伤害或损失。
最新文档
- 报表系统设计方案v2
- 学生网上选课管理系统(uml)
- 国家开放大学(河南)《信息技术与信息管理》作业练习1-3参考答案
- 2023年西藏教师资格证《小学综合素质》科目真题冲刺卷
- 2022年广西教师资格证《小学综合素质》科目真题冲刺卷
- 第三单元练习卷 (提高练习)2024-2025学年三年级上册语文统编版
- 北师大版小学三年级下册语文全本教案
- +初+中数学一元二次方程根与系数的关系++课件+湘教版数学九年级上册
- 第九章 恒定电流-2025版高考物理真题选练
- 《2024年 《珠宝概念与工艺》(1-2章)英汉翻译实践报告》范文
- 员工关怀与心理支持管理制度
- 水土保持监理合同范本
- DL-T5434-2021电力建设工程监理规范
- 2024年北京市房山区九年级(初三)二模语文试卷及答案
- 2023年国家公务员考试行测真题及答案(完整版)-三套真题
- 2024-2030年中国直流微型电机行业运营态势与盈利前景预测报告
- 应收账款管理总结
- 供应链协调与沟通技巧
- 新部编版一年级语文上册:(教案2)3-b-p-m-f-教案
- 工伤保险中心关于工伤保险工作自查报告
- 企业安全文化手册
评论
0/150
提交评论