临床研究方案设计protocol-writing

HOWTOWRITEASTUDYPROTOCOL北京大学临床研究所王燕芳2014.3.1WhatIsResearchProtocol?Aresearchprotocolisadetailedsetofinstructionswrittenbyscientificresearchersthatoutlinetheproceduresforconductingtheexperimentandcollectingdata.Grantapplicationsandethicsboardapprovalrequireresearchprotocolsubmission.Anyresearchersusinghumansubjectsmustcreatearesearchprotocol,althoughthesedocumentsarealsousedbyscientistsinotherfields.3/24/20142InitialConsiderationsBeforewritingaresearchprotocol,anauthormustconsider：themainresearchquestionandhaveaclearquestionandspecifichypothesesabouttheresultsofthestudy.Shethendeterminesthemethodsusedtoanswerthequestion.Itisessentialthatthemethodologybecleartoreadersandprovideananswertotheresearchquestion.Thespecificresearchmethodsandproceduresmustbesafeandappropriateforbothresearchsubjectsandlaboratoryworkers.3/24/20143MisconceptionsManyscientiststhinkthatafteraresearchprotocolissubmitteditiscomplete.Infact,researchprotocolsareconstantlychangingdocuments.Ifanychangetoastudyprocedureismade,itmustbeapprovedbyanethicsboard(IRB)ifhumansubjectsareused.Scientistsamendresearchprotocolstoincludeup-to-dateinformationaboutproceduresandtechniques.Theyalsoincludeanyrevisionstoinformedconsentformsandotherdocumentsusedduringthestudy.Keepingallrecordscurrentisessentialtoappropriateandethicalcompletionofaresearchstudy.3/24/20144Studyprotocol:What?DescribeseverystepofastudyidentificationoftheproblemapplicationoftheresultsAnswersrelevantquestionsSignificance：Publichealthproblem:Important?Studyquestion:relevanttotheproblem?Objectives:consistentwiththestudyquestion?Studydesign:achievesobjectives?Powerofthestudy:sufficient?Publichealthimpactofthefindings?3/24/20145StudyProtocol:Why?TocheckiftheobjectivescanbeachievedTocheckthefeasibilityofthestudyPreventsfailuretocollectcrucialinformationLaysdowntherulesforallpartnersToobtainapprovalofethicalcommittee(s)ApplicationforfundsMakesitmucheasiertowritearticle3/24/20146StudyProtocol:howtostart?GetgoodexamplesGetideasfromsimilarpublishedstudiesUseachecklistofitemstoincludeGettherequestedformat(NIHgrantapplication)Shareideaswithcolleagues3/24/20147ProtocolOutline1.Presentation2.Backgroundandjustifications3.Objectivesandresearchquestions4.Methods5.Ethicalconsiderations6.Projectmanagement7.Timetable8.Resources9.References10.Appendices3/24/20148OutlineoftheStudyProtocolElementPurposeResearchQuestionsWhatquestionswillthestudyaddress?Significance(background)Whyarethesequestionsimportant?DesignTimeFrameEpidemiologicapproachSubjectsSelectioncriteriaSamplingdesignWhoarethesubjectsandhowwilltheybeselected?VariablesPredictorvariablesConfoundingvariableOutcomevariableWhatmeasurementswillbemade?StatisticalissuesHypothesesSamplesizeAnalyticapproachHowlargeisthestudyandhowwillitbeanalyzed?3/24/201491.PresentationTitleInvestigatorsMaincentres(Steeringcommittee)SummaryoftheprotocolTitle•清楚•明确（descriptive,informative,specific）•通常研究方案首页清楚表明•作者•版本与日期（最新版本）3/24/2014102.BackgroundandJustificationStatementoftheproblem,studyjustificationDiscussimportanceofsubjectareaDescribewhystudyisnecessaryDescribetheprincipalquestionstobeaddressedDescribehowstudyresultswillbeusedReviewrelevantliteratureandcurrentknowledge3/24/2014113.ObjectivesandResearchQuestionsSpecific-not“focuson….”Tomeasuresomething(prevalence,incidence,riskincrease…)Actionoriented–“inorderto….”RelevantTimespecifiedMainobjectiveMustbeachievedDictatesdesignandmethodsSecondaryobjectivesOfinterest,butnotessentialSpecificresearchquestions3/24/2014123.ObjectivesandresearchquestionsObjective:Theoverallobjectiveofthetrialistostudytheeffectsofsodiumintakewithintwodietarypat-ternsthathavebeenshownbythepreviousDASHtrialtohavemarkedlycontrastingeffectsonbloodpressureResearchquestions:Researchquestionistheobjectiveofthestudy,theuncertaintythattheinvestigatorwantstoresolve.e.g.,Shouldwomentakehormonesaftermenopause?Morespecific:howcommonlywomentakeestrogenaftermenopause?Aretherebenefitsandharmsofestrogentreatment?3/24/201413研究问题与假设本研究需要探讨的问题是值得研究的问题(pass“sowhat“test)可以用“是/否”或数字来回答的问题用来产生研究假设和研究目的研究假设•最佳猜测（bestguess）•可以用统计方法来检验3/24/201414目的什么样的“目的”是一个好的研究目的？现实vs.理想具体vs.普遍清楚vs.不清楚3/24/201415研究目的：描述中国人**病的临床和生物学特征，应用Affymetrix6.0对800名中国患者和2400名对照者进行全基因组扫描研究（GWAS）。Example1.Nostudyhypothesis163/24/2014研究目的：将无心跳死亡供体器官捐献用于临床实践，探讨其可行性及运行中的问题，提高北京大学在我国器官移植事业中的地位，为我国器官移植的健康发展作出贡献。Example2.Notresearchablequestions173/24/2014研究题目：**肿瘤的外科治疗研究研究目的：本项目拟解决**肿瘤外科技术中的疑难问题；通过循证医学的方法建立**肿瘤治疗的指导性临床路径和治疗常规。研究设计：六种不同肿瘤六种不同研究设计Example3.Unclear,toobroaderaims183/24/2014ResearchQuestionmaybestatedasObjectivesOverallobjectsareanindicationofthecontributiontobemadetobiomedicalknowledge/theoryandpublichealthSpecificobjectivesareintheformofanswerablequestions,eitheryes/nooranumberSpecificobjectivesareoftendividedintoprimaryandSecondary3/24/201419PartII：DASH减钠研究EffectsonBloodPressureofReducedDietarySodiumandtheDietaryApproachestoStopHypertension(DASH)DietSacks,F.M.,etal.NewEnglandJournalofMedicine.Jan4,20013/24/201420Run-in:11-14day