临床研究设计分析和文章写作

ClinicalStudyDesign,Analysis,andPresentationYiqingSong,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OverviewClinicalStudy(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）AnyclinicalstudypublishedintheMedicalJournalsStudyDesign?Studypopulation?Studieshypothesisorquestionsoftesting?.TitleAbstractIntroductionHowtoreadtheliterature(如何有效地阅读文献）MainAnalysismethodsResults?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-controlstudyEcologicalstudyCohortstudyorCase-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-sectionalstudySummary（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）StudyPopulationTotalpopulationlivinginaspecificarea(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.

Clin

Endocrinol(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.JClin

Endocrinol

Metab.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：20,000MenandWomenwillbeRandomizedintheVITALTrialVitaminD(1,600IU)N=10,000PlacebovitaminDN=10,000DHA/EPA(1g/day)N=5,000FishOilPlaceboN=5,000Flowdiagramillustratingthe22

randomlyassignedtreatmentcomponentsoftheVITaminDandOmegaA-3TriaL(VITAL),whichwillstartinJanuary2010.DHA/EPA(1g/day)N=5,000FishOilPlaceboN=5,000TheVITaminDandOmegaA-3TriaL(VITAL)8171WomenRandomizedintheWACSTrial(June1995-January31,2005)5442RandomizedintheWAFACSTrial(April1998-July31,2005)DailytakeofacombinationpilloffolicacidandvitaminsB6andB12(n=2,132freeofdiabetesatbaseline)Dailyintakeofaplacebopill(n=2,120freeofdiabetesatbaseline)245Incidentcases259IncidentcasesFigure1.FlowdiagramillustratingdiabetesoutcomesintherandomlyassignedtreatmentoffolicacidandvitaminsB6andB12oftheWomen’sAntioxidantandFolicAcidCardiovascularStudy(WAFACS).(Songetal.Diabetes,2009)LogranktestP=0.44YearsofFollow-upFolate/BvitaminsGroup21322044193518151738No.atRiskPlaceboGroup21202017190117891720Figure2.Cumulativeincidenceoftype2diabetesbyrandomizedtreatmentassignment(activetreatmentvs.placebo)intheWAFACS.RR=0.94(0.79-1.11)SimilarResultsaftercensoringnon-compliance(Songetal.Diabetes,2009)00.501.001.502.00RelativeRiskforType2DiabetesFigure3.SubgroupFolicAcid/BVitaminActiveGroupPlaceboGroupPvalueforInteractionAge45-54yr57(0.13)80(0.17)No.ofcases(%)55-64yr94(0.12)95(0.13)

65yr94(0.10)84(0.09)<25.08(0.01)19(0.04)25.0-29.962(0.10)52(0.08)

30.0175(0.19)188(0.20)BMIHigh,>1000kcal/wk74(0.09)80(0.10)Low,1000kcal/wk171(0.13)179(0.13)PhysicalActivity0.360.850.60Current29(0.11)39(0.15)Past106(0.12)113(0.12)Never110(0.11)107(0.12)CigaretteSmoking0.61Yes110(0.15)140(0.19)No123(0.09)113(0.09)FamilyHistoryofdiabetes0.060.71Tertile1(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)0.900.99SCI-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,thefounderoftheInstit