按CONSORT声明要求报告随机对照试验

按CONSORT声明要求报告随机对照试验,中华医学杂志英文版汪谋岳,何谓CONSORT声明,ConsolidatedstandardsofreportingtrialsCONSORT小组发布的写作指南专门针对两组的RCT1995年初次发布，2000年修订，随后有补充目前国际许多主流医学期刊使用,何谓CONSORT声明,CONSORT小组临床试验学家统计学家流行病学家生物医学编辑,CONSORT声明主要内容,一个流程图：介绍病例入组到进入分析各阶段的动态变化一个核查表：22个项目，从文题到讨论都有要求,CONSORT声明核查表,CONSORT声明核查表,CONSORT声明核查表,CONSORT声明,CONSORT声明的内容,文题和摘要如何把参加者分配到干预组（如：“随机分配”、“随机化”、“随机指定”）,文题举例,EfficacyandSafetyofBenazeprilforAdvancedChronicRenalInsufficiency(贝那普利)EfficacyandSafetyofBenazeprilforAdvancedChronicRenalInsufficiency：arandomized,double-blindstudy,文题举例,ActinomycinDVersusMethotrexate-FolinicAcidastheTreatmentofStageI,Low-RiskGestationalTrophoblasticNeoplasia:ARandomizedControlledTrialImmunogenicity,Reactogenicity,andSafetyofHumanPapillomavirus16/18AS04-AdjuvantedVaccineinJapaneseWomen:InterimAnalysisofaPhaseII,Double-blind,RandomizedControlledTrialatMonth7,摘要举例,BackgroundAngiotensin-convertingenzymeinhibitorsproviderenalprotectioninpatientswithmild-to-moderaterenalinsufficiency(serumcreatininelevel,3.0mgperdeciliterorless).Weassessedtheefficacyandsafetyofbenazeprilinpatientswithoutdiabeteswhohadadvancedrenalinsufficiency.,摘要举例,MethodsWeenrolled422patientsinarandomized,double-blindstudy.Afteraneight-weekrun-inperiod,104patientswithserumcreatininelevelsof1.5to3.0mgperdeciliter(group1)received20mgofbenazeprilperday,whereas224patientswithserumcreatininelevelsof3.1to5.0mgperdeciliter(group2)wererandomlyassignedtoreceive20mgofbenazeprilperday(112,摘要举例,patients)orplacebo(112patients)andthenfollowedforameanof3.4years.Allpatientsreceivedconventionalantihypertensivetherapy.Theprimaryoutcomewasthecompositeofadoublingoftheserumcreatininelevel,end-stagerenaldisease,ordeath.Secondaryendpointsincludedchangesinthelevelofproteinuriaandtherateofprogressionofrenaldisease.,摘要举例,ResultsOf102patientsingroup1,22(22percent)reachedtheprimaryendpoint,ascomparedwith44of108patientsgivenbenazeprilingroup2(41percent)and65of107patientsgivenplaceboingroup2(60percent).Ascomparedwithplacebo,benazeprilwasassociatedwitha43percentreductionintheriskoftheprimaryendpointingroup2(P=0.005).,摘要举例,Thisbenefitdidnotappeartobeattributabletobloodpressurecontrol.Benazepriltherapywasassociatedwitha52percentreductioninthelevelofproteinuriaandareductionof23percentintherateofdeclineinrenalfunction.Theoverallincidenceofmajoradverseeventsinthebenazeprilandplacebosubgroupsofgroup2wassimilar.,摘要举例,ConclusionsBenazeprilconferredsubstantialrenalbenefitsinpatientswithoutdiabeteswhohadadvancedrenalinsufficiency.(ClinicalTnumber,NCT00270426.),CONSORT声明的内容,引言科学背景和原理的解释,引言举例,Angiotensin-convertingenzyme(ACE)inhibitorsslowtheprogressionofchronickidneydiseaseinthepresenceorabsenceofdiabetes,particularlyinpatientswithmild-to-moderaterenalinsufficiency,asreflectedbyaserumcreatininelevelof1.5to3.0mgperdeciliter(133to265molperliter).1-3,引言举例,Data,however,havebeenlimitedtopatientswithserumcreatininelevelsof3.0mgperdeciliterorless.ManyphysiciansarereluctanttouseACEinhibitorsinpatientswithadvancedrenalinsufficiencybecauseofconcernthatserumcreatinineorpotassiumlevelswillrise.4,5,引言举例,Manyinferthattheuniquebenefitsofthesedrugsinpatientswithadvancedrenalfailuremightnotbesuperiortothoseaffordedbyblood-pressurecontrolalone.4Asaresult,patientswithadvancedchronickidneydiseasehavenotbeenincludedinprospective,large-scaleclinicaltrialsofACEinhibitors.1,6,引言举例,Consequently,therenaloutcomeandtheriskbenefitprofileofACEinhibitorsinthispopulationremainpoorlydefined.,引言举例,InChina,theprimarycauseofend-stagerenaldiseaseisnondiabeticchronickidneydisease.7,8In1999,41,000registeredpatientswerereceivingdialysis,accountingfor5percentofthetotalpopulationrequiringrenal-replacementtherapy.7,引言举例,Thus,therapythatcoulddelaytheprogressionofchronickidneydiseasetoend-stagerenaldiseaseisanessentialmanagementgoal.Ourpreviousopen-labelstudyinvolvingasmallnumberofpatientswithadvancedchronicrenaldisease,somewithandsomewithoutdiabetes,suggestedthatbenazepril,anonsulfhydryl-containingACEinhibitor,mayconferrenalbenefits.9,引言举例,Thepresentrandomized,double-blindstudywasdesignedtodeterminewhetherbenazeprilcouldslowtheprogressionofrenaldysfunctioninpatientswithoutdiabeteswhohadadvancedrenalinsufficiency.,CONSORT声明的内容,方法受试者参加者的合格标准；资料收集的环境和地点,受试者介绍举例,StudydesignThestudywasconductedattheNanfangHospitalRenalDivision,acenterofkidneydiseasecareinsouthernChina.ThecatchmentareaofthecenterincludeseightcitiesnearGuangzhouwithatotalpopulationof29.8millionasof2000.,受试者介绍举例,PatientsBetweenMay1999andMay2001,wescreenedconsecutivepatientswithchronickidneydiseasewhowere18to70yearsofage.AllthepatientswereChinese.EligiblepatientshadnotreceivedACEinhibitorsorangiotensinIIreceptorantagonistsforatleastsixweeksbeforescreening,受试者介绍举例,Andmetthefollowinginclusioncriteria:aserumcreatininelevelof1.5to5.0mgperdeciliter(133to442molperliter)andacreatinineclearance10of20to70mlperminuteper1.73m2,withvariationsoflessthan30percentinthethreemonthsbeforescreening;nondiabeticrenaldisease(asestablishedonthebasisoftheirhistoryandtheresultsofserumbiochemicaltestsandrenalbiopsy);,受试者介绍举例,andpersistentproteinuria(definedbyurinaryproteinexcretionofmorethan0.3gperdayforthreeormoremonthswithoutevidenceofurinarytractinfectionorovertheartfailureaNewYorkHeartAssociationclassofIIIorIV).,受试者介绍举例,Exclusioncriteriaincludedanimmediateneedfordialysis;currenttreatmentwithcorticosteroids,nonsteroidalantiinflammatorydrugs,orimmunosuppressivedrugs;renovasculardisease;myocardialinfarctionorcerebrovascularaccidentintheyearprecedingthetrial;connective-tissuedisease;andobstructiveuropathy.,CONSORT声明的内容,方法干预各组干预的准确详情，和如何及何时实施了这些干预,干预举例,TreatmentEligiblepatientsweredividedintotwogroupsaccordingtotheirserumcreatininelevels:group1consistedofpatientswithserumcreatininelevelsof1.5to3.0mgperdeciliter,andgroup2consistedofpatientswithserumcreatininelevelsof3.1to5.0mgperdeciliter(274to442molperliter).,Treatment,Allpatientsenteredaneight-weekrun-inphaseduringwhichtheyreceived10mgofbenazeprilperdayforfourweeksundercloseobservation,includingweeklymeasurementsofblood,Treatment,Aftertherun-inphase,benazeprilwasdiscontinuedforthreeweeksandalternativeantihypertensiveagents(asdescribedabove)wereadministeredasnecessarytomaintainblood-pressurecontrol.Afterthreeweeks,allpatientsingroup1received10mgofbenazepriltwicedaily,CONSORT声明的内容,方法目的特定的目的和假设,特定的目的和假设举例,Thepresentrandomized,double-blindstudywasdesignedtodeterminewhetherbenazeprilcouldslowtheprogressionofrenaldysfunctioninpatientswithoutdiabeteswhohadadvancedrenalinsufficiency.,CONSORT声明的内容,方法结局清楚地界定主要和次要结局指标，可能的话，描述任何用于增强测量质量的方法（如：多重观察，培训评估者）,结局举例,OutcomemeasuresTheprimaryefficacymeasurewasthetimetothefirsteventinthecompositeendpointofadoublingoftheserumreatininelevel,end-stagerenaldisease,ordeath.Secondaryendpointsincludedchangesintherateofurinaryproteinexcretionandtheprogressionofrenaldisease,CONSORT声明的内容,方法样本量样本量是如何确定的；可能的话解释中期分析情况和终止试验的规则,样本量举例,ThesamplesizewasestimatedbeforethestudywiththeuseofnQueryAdvisorsoftware.Ourpreliminarystudy9ofthetreatmentofpatientswithadvancedrenaldysfunctionshowedthatthetwoyearrateoftheprimaryendpointamongpatientswhowerenottakinganACEinhibitorwas60percent.ItwasestimatedthatACE-inhibitortreatmentwouldreducethisrateto40percent.Thus,theenrollmentof100patientspergroupwouldprovidethestudywithastatisticalpowerof80percentatatwosidedsignificancelevelof0.05.,CONSORT声明的内容,方法随机化顺序产生产生随机分配顺序的方法，包括任何限制措施（如：模块化，分层）,顺序产生举例,Acomputer-generatedlist,maintainedbyapartynotinvolvedintheconductofthestudy,wasusedforrandomization.,CONSORT声明的内容,方法随机化分配隐蔽实施随机分配顺序的方法（如：编号的容器或中心的电话），明确在实施干预前顺序是否封存,分配隐蔽举例,Patientsingroup2wererandomlyassignedtoAcomputer-generatedlist,maintainedbyapartynotinvolvedintheconductofthestudy,wasusedforrandomizationAphysicianwhowasunawareofthepatientstreatmentassignmentsexaminedeachpatienteverytwoweeksduringthefirstmonthandeverythreemonthsthereafter.,CONSORT声明的内容,方法随机化实施谁产生的分配顺序，谁登记的参加者，谁将参加者分配到各组中,随机化实施举例,Acomputer-generatedlist,maintainedbyapartynotinvolvedintheconductofthestudy,wasusedforrandomizationAphysicianwhowasunawareofthepatientstreatmentassignmentsexaminedeachpatienteverytwoweeksduringthefirstmonthandeverythreemonthsthereafter.,CONSORT声明的内容,方法随机化盲法（掩蔽）是否参加者、实施干预者和那些评估结局者对分组情况一无所知,盲法举例,Aphysicianwhowasunawareofthepatientstreatmentassignmentsexaminedeachpatienteverytwoweeksduringthefirstmonthandeverythreemonthsthereafter.,CONSORT声明的内容,方法统计学方法比较各组主要结局的统计学方法；额外分析如亚组分析和调整分析的方法,统计学方法举例,ThesamplesizewasestimatedbeforethestudywiththeuseofnQueryAdvisorsoftware.,统计学方法举例,Theprimaryandsecondaryendpointswereanalyzedaccordingtotheintention-to-treatprinciple.ACoxregressionmodelwasusedtodeterminethehazardratiofortheprimaryendpoint.Theriskreductionwascalculatedas100percent(1thehazardratio).EventcurvesarebasedonKaplanMeieranalysis,andsignificancewasassessedbymeansofthelog-ranktest.,统计学方法举例,Changesinthelevelofurinaryproteinexcretion,creatinineclearance,andbloodpressurewereanalyzedbyrepeated-measuresanalysisofvariance.Toidentifyinteractionsbetweenthetreatmentgroupsandbloodpressure,weusedproportional-hazardsregressionandthemostrecentmeasurementofmeanarterialpressureasatimevaryingcovariate.TherelationshipbetweenthereductioninproteinuriaandtherateofthedeclineinrenalfunctionwasanalyzedbyPearson,统计学方法举例,correlation.SPSSsoftwareforWindows(version12.0)wasusedforanalyses.,CONSORT声明的内容,结果受试者流动各阶段受试者的流动（极力推荐一种流程图）。特别是报告各组随机分配、接受治疗、参加者在不同阶段的流动情况（强烈推荐图示），特别是就各组而言，报告随机指定的参加者、接受预期的治疗、完成研究草案和分析主要结局的人数；描述与计划的研究草案的差别，及其原因,CONSORT声明的内容,结果招募用日期来明确招募和随访时间,招募举例,BetweenMay1999andMay2001,wescreenedconsecutivepatientswithchronickidneydiseasewhowere18to70yearsofage.,CONSORT声明的内容,结果基底资料各组的基线人口统计学资料和临床特征,基底资料举例,CONSORT声明的内容,结果分析的人数每次分析各组的参加者人数（分母），分析是否是“意向处理法”；可行的话，用绝对数描述结果（如：10/20，而非50%）,分析的人数举例,Theprimaryandsecondaryendpointswereanalyzedaccordingtotheintention-to-treatprinciple.72patientshadadrycough(17percent,30ingroup1and42ingroup2),CONSORT声明的内容,结果结局和评估总结各组的主要和次要结局结果，评估的效应大小及其精度（如：95%CI）,结局和评估举例,PrimaryoutcomesIngroup2,44patientsassignedtobenazeprilreachedtheprimaryendpoint,ascomparedwith65patientsassignedtoplacebo(41percentvs.60percent,P=0.004)(Fig.2).,结局和评估举例,SecondaryoutcomesIngroup2,therewasasignificantlygreaterreductioninthelevelofproteinuriaamongpatientsassignedtobenazeprilthanamongthoseassignedtoplacebo(52percentvs.20percent,P0.001),CONSORT声明的内容,结果辅助分析报告任何其他的分析结果来解决结果的多样性问题，包括亚组分析和调整分析，指出哪些是有待详细说明的，哪些是探索性的,CONSORT声明的内容,结果不良事件每个干预组的任何重要不良事件和副反应,不良事件举例,Therewerenosignificantdifferencesinthenumberofnonfatalcardiovasculareventsbetweenthetwogroupsorbetweenthetwosubgroupsingroup2(Table3).Theincidenceofotheradverseeventswasalsosimilarinthetwogroupsandinthetwosubgroupsofgroup2.,CONSORT声明的内容,讨论解释综合考虑研究假设、潜在偏倚或不精确的来源和分析及结局的多样性的危险，解释结果,解释举例,Ourfindingsindicatethatbenazepril,alongwithconventionalantihypertensivetreatment,asneeded,confersrenalprotectioninpatientswithoutdiabeteswhohaveadvancedrenalinsufficiency,CONSORT声明的内容,讨论可推广性试验结果的可推广性（外部有效性）,可推广性举例,Thesedatasuggestthattheadditionofbenazepriltoaconventionalregimenofantihypertensivetherapyisacceptable,eveninpatientswithserumcreatininelevelsexceeding3.0mgperdeciliter.,CONSORT声明的内容,讨论总的证据在现有证据的背景下，全面解释结果,伦理问题举例,ThestudyprotocolwasapprovedbytheNanfangEthicsCommittee,andallsubjectsprovidedwritteninformedconsent.,与他人结果雷同举例,Consistentwithpreviousfindings,16,17ourdatasuggestthattheresponsetoACEinhibitorswasindependentofthebaselineglomerularfiltrationrate.,总结举例,Insummary,benazepriltherapywasassocia