临床研究设计分析和文章写作.ppt

ClinicalStudyDesign,Analysis,andPresentation,YiqingSong,MD,ScDHarvardMedicalSchoolBoston,MA,USAJuly,2009,临床研究设计分析和文章写作,宋一青,StudyDesign(科研设计),Why（为什么要做科研？）临床体会，经验是否正确；兴趣；等等。What（做什么?）内容包括完整提出自己的假说，新理论、新方法或新模型？或者只是来验证别人的How（怎么做？)方法的科学性和严格性,Overview,ClinicalStudy(definition):(定义）ClinicalStudyPurpose(临床研究主要目的）Etiology(病因学）Prediction（疾病预测）Treatment（疾病治疗）StudyDirection（侧重方向）Genetics（基因研究）Biomarkers（生物标记物）Nutrition（营养）Pharmacologicalagentsorsurgery（药物或外科手术）Psychosocialfactors（社会心理学）(等等）,KeyissuesinstudyDesign(研究设计的关键）,Knowledgementinyourfield（本学科知识）Literaturesearch（文献追踪）,FundamentalStudyDesign(基本研究设计类型）,ObservationalStudy(观察性临床研究）EcologicalStudies(生态性研究）Casereport（病例报告）Cross-sectionalStudy（横断面研究）Case-ControlStudy（病例对照研究）ProspectiveCohortStudy(前瞻性定群研究）RetrospectiveCohortStudy(回顾性定群研究）InterventionTrial（临床干预试验）OpenTrial（开放性研究）RandomizedTrial（随机干预试验）Randomizeddouble-blindTrial（随机双盲干预试验）Randomizedsingle-blindTrial（随机单盲干预试验）Evidence-basedStudy（循证医学研究）SystemicReview（系统性文献综述）Meta-analysis(荟萃分析）,AnyclinicalstudypublishedintheMedicalJournals,StudyDesign?,Studypopulation?,Studieshypothesisorquestionsoftesting?.TitleAbstractIntroduction,Howtoreadtheliterature(如何有效地阅读文献）,MainAnalysismethods,Results?,研究问题？,研究类型？,研究人群？,主要分析方法？,研究结果？,大气污染与糖尿病发生率的关系,出生体重与成人II型糖尿病的关系,糖尿病人合并HIV感染的特征分析,Examples(实例分析）,Casereportorcase-controlstudy,Ecologicalstudy,CohortstudyorCase-controlstudy,空腹血糖水平与发生肿瘤的关系,Cohortstudy；case-controlstudy,胰岛素治疗对糖尿病合并症的效果,Randomizedtrial；cohortstudy？,新降糖药的疗效,Randomizedtrial,基因多态性与糖尿病的关系,Case-controlstudy;cohortstudy;cross-sectionalstudy,新检测方法对糖尿病预测的改善,Cohortstudy,血中几种检测标记物的相关性,Cross-sectionalstudy,Summary（总结）,StudyPopulation（研究人群的建立最为关键）Representative（代表性）SampleSize（数量）StudyDesign（研究设计类型）Prospective（前瞻性最优，其次，病例对照或横断面）Longitudinal（续贯性）DataCollection(数据收集齐备）Basiccharacteristics(demographic,geographic,anthropometric,andlifestyleorpsychosocialfactors)Biologicalsamplecollection(blood,toenail,hair,andurine).Accurateoutcomeascertainment(疾病诊断准确）StudyGroup（研究团队）DifferentResearchAreas（不同侧重点）Multidisciplinarycollaboration（多学科协作）Keeptrackofthelatestinformation(跟踪最新文献）,StudyPopulation,Totalpopulationlivinginaspecificarea(一个范围明确的地区的全体或其样本）Highriskpopulation（高危人群）Specialpopulations（特殊人群）：e.g.HealthProfessionals,volunteers.,临床资料充分,人群特殊,横断面研究但是人群代表性,传统方法,阳性结果,临床资料充分,人群特殊,同一人群,传统方法,阳性结果,CommonvariantsinKCNQ1areassociatedwithtype2diabetesandimpairedfastingglucoseinaChineseHanpopulation.HumMolGenet.2009Plasma25-hydroxyvitaminDconcentrationandmetabolicsyndromeamongmiddle-agedandelderlyChineseindividuals.DiabetesCare.2009Jul;32(7):1278-83.RBP4variantsaresignificantlyassociatedwithplasmaRBP4levelsandhypertriglyceridemiariskinChineseHans.JLipidRes.2009Jul;50(7):1479-86.AssociationofGCKRrs780094,aloneorincombinationwithGCKrs1799884,withtype2diabetesandrelatedtraitsinaHanChinesepopulation.Diabetologia.2009May;52(5):834-43.Associationsofinflammatoryfactorswithglycaemicstatusamongmiddle-agedandolderChinesepeople.ClinEndocrinol(Oxf).2009Jun;70(6):854-62.Epub2008Sep2.Associationsofresistinwithinflammatoryandfibrinolyticmarkers,insulinresistance,andmetabolicsyndromeinmiddle-agedandolderChinese.EurJEndocrinol.2008Nov;159(5):585-93.CommonvariantsinCDKAL1,CDKN2A/B,IGF2BP2,SLC30A8,andHHEX/IDEgenesareassociatedwithtype2diabetesandimpairedfastingglucoseinaChineseHanpopulation.Diabetes.2008Oct;57(10):2834-42.Variantsinthefatmass-andobesity-associated(FTO)genearenotassociatedwithobesityinaChineseHanpopulation.Diabetes.2008Jan;57(1):264-8.Elevatedretinol-bindingprotein4levelsareassociatedwithmetabolicsyndromeinChinesepeople.JClinEndocrinolMetab.2007Dec;92(12):4827-34.,CommonDisease（常见病的研究）,在有代表性的人群中从横断面研究做起，样本要大，基线数据要齐备，生物样本注意正确采取和妥善长期保存可包括前期疾病状态资金及其它条件允许下，加入队列定群研究，或加做随机试验,RareDisease（临床少见病的研究）,建议做病例对照研究注意对照组病人的正确选择3.数据收集要齐备，注意保存生物样本,小型病例对照研究,ALS（肌萎缩性脊髓侧索硬化症）,合适病例对照研究,RandomizedClinicalTrialDesign(随机临床试验设计）,Studypopulation（研究人群）Randomization（随机化）Blindmethod（盲法）Placebo（安慰剂使用）Dosage（治疗剂量）Samplesizeandpowercalculation（样本量计算）Duration（治疗时间）Compliance（随访性）Safetymonitoring（安全性监测）,Timescited（累积引用次数）:Google:1,906ISI:1,048,课题新颖；临床意义大；随机试验；结果阳性。,优势：,小样本；随机效果是否达到预期；糖尿病的诊断是否一致,不足处：,20,000MenandWomenwillbeRandomizedintheVITALTrial,VitaminD(1,600IU)N=10,000,PlacebovitaminDN=10,000,DHA/EPA(1g/day)N=5,000,FishOilPlaceboN=5,000,Flowdiagramillustratingthe22randomlyassignedtreatmentcomponentsoftheVITaminDandOmegaA-3TriaL(VITAL),whichwillstartinJanuary2010.,DHA/EPA(1g/day)N=5,000,FishOilPlaceboN=5,000,TheVITaminDandOmegaA-3TriaL(VITAL),8171WomenRandomizedintheWACSTrial(June1995-January31,2005),5442RandomizedintheWAFACSTrial(April1998-July31,2005),DailytakeofacombinationpilloffolicacidandvitaminsB6andB12(n=2,132freeofdiabetesatbaseline),Dailyintakeofaplacebopill(n=2,120freeofdiabetesatbaseline),245Incidentcases,259Incidentcases,Figure1.FlowdiagramillustratingdiabetesoutcomesintherandomlyassignedtreatmentoffolicacidandvitaminsB6andB12oftheWomensAntioxidantandFolicAcidCardiovascularStudy(WAFACS).(Songetal.Diabetes,2009),LogranktestP=0.44,YearsofFollow-up,Folate/BvitaminsGroup21322044193518151738,No.atRisk,PlaceboGroup21202017190117891720,Figure2.Cumulativeincidenceoftype2diabetesbyrandomizedtreatmentassignment(activetreatmentvs.placebo)intheWAFACS.,RR=0.94(0.79-1.11),SimilarResultsaftercensoringnon-compliance,(Songetal.Diabetes,2009),00.501.001.502.00,RelativeRiskforType2Diabetes,Figure3.,Subgroup,FolicAcid/BVitaminActiveGroup,PlaceboGroup,PvalueforInteraction,Age,45-54yr57(0.13)80(0.17),No.ofcases(%),55-64yr94(0.12)95(0.13),65yr94(0.10)84(0.09),1000kcal/wk74(0.09)80(0.10),Low,1000kcal/wk171(0.13)179(0.13),PhysicalActivity,0.36,0.85,0.60,Current29(0.11)39(0.15),Past106(0.12)113(0.12),Never110(0.11)107(0.12),CigaretteSmoking,0.61,Yes110(0.15)140(0.19),No123(0.09)113(0.09),FamilyHistoryofdiabetes,0.06,0.71,Tertile1(1.82-9.75)78(0.11)75(0.11),Tertile2(9.76-43.7)81(0.12)87(0.13),BaselinevitaminB12intake(mcg/d),Tertile3(43.8-899)72(0.11)81(0.12),Tertile1(1.82-9.75)76(0.11)77(0.12),Tertile2(9.76-43.7)83(0.12)87(0.13),BaselinevitaminB6intake(mg/d),Tertile3(43.8-899)72(0.11)79(0.11),Tertile1(1.82-9.75)78(0.11)82(0.12),Tertile2(9.76-43.7)82(0.12)82(0.12),Baselinefolateintake(mg/d),Tertile3(43.8-899)71(0.11)79(0.12),0.90,0.99,SCI-ScienceCitationIndex（科学索引指数）,ScienceCitationIndex(SCI)isacitationindexoriginallyproducedbytheInstituteforScientificInformation(ISI)in1960,whichisnowownedbyThomsonReuters.Thisdatabaseallowsaresearchertoidentifywhichlaterarticleshavecitedanyparticularearlierarticle,orcitedthearticlesofanyparticularauthor,ordeterminewhicharticleshavebeencitedmostfrequently.ThompsonISI论文检索数据库挑选世界上一批有影响的科学刊物，将其论文题目和作者及作者单位、文摘和引用论文进行检索，建立数据库，并向世界各地科研单位定期发行他们的检索数据库，为科学工作者提供便捷的论文检索和引用统计服务。收录在SCI中的杂志论文比较容易被科研人员检索查阅。论文绝大多数是英文刊物（10，000多种期刊，120，000个国际会议录）,Impactfactor（引用因子）,TheImpactfactorwasdevisedbyEugeneGarfield,thefounderoftheInstituteforScientificInformation(ISI),nowpartofThomson,alargeworldwideUS-basedpublisher.ImpactfactorsarecalculatedeachyearbyThomsonScientificforthosejournalswhichitindexes,andthefactorsandindicesarepublishedinJournalCitationReports.引用因子是针对某一年的评价指标：举例来说，2008年的某一个杂志的IF值就是该杂志在2008前两年（2006和2007）的文章在2008一年内被引用的总次数除以这两年发表的文章总数（包括编者按和给编辑的来信）。,ResearchResults(研究结果）,OriginalResearch:即有原创性的成果。ReplicationResearch:重复性成果。Comprehensive，SystematicReview（qualitativeandquantitative):较全面系统的文献综述。,ManuscriptPreparation,Originality(Novelty)(内容原创性新颖性)NovelFindings(独特的发现)Goodwriting(可读性方面)Clearthinking（思路清晰）Logic（逻辑性强）Concisesentence（语句通顺）ClearTablesandFigures(表格图表清晰，信息丰富),研究论文的大致结构,Title（题目）AuthorsandAffiliation（作者和单位）Abstract（摘要）Introduction（引言）ResearchDesignandMethods(研究设计和方法）Results（结果）Discussion（讨论和结论）Acknowledgement（致谢）References（参考文献）TablesandFigures(表和图),Introduction（引言）,提出研究动机和目的提出研究问题必须参考引证最新的相关研究文献,Discussion(讨论）,Summary(概括性总结）Comparison（与其它研究从理论、方法到结果的相同和不同点）Mechanisms（可能的机制讨论）StrengthandLimitation（本研究优缺点）Conclusions（结论和意义）,Reference（文献引用）,ENDNOTE（帮助软件）Keynotepapers（关键的文献）Originalpaper(原创论文为主）Keyreviewpaper(关键的综述性文章）,CommonReasonsforPaperRejection（退稿的常见的原因）,首先分析向SCI刊物投稿命中率低、退稿率高的原因。研究问题不新颖；2.实质性内容的原因;-实验设计缺陷；-数据不全；-分析方法；3.语言和写法方面的原因;4.无新或重要的补充。仅是简单重复他人工作。,Performanceevaluation(业绩评估）,Quality（研究质量）Quantity（研究数量）ContinuousContribution（持续性研究）,Researcherpotential（研究者潜质）,Passionate(热情）Persistent(坚持）Patient(耐心）,An