臨床研究設(shè)計分析和文章寫作課件

ClinicalStudyDesign,Analysis,andPresentationYiqingSong,MD,ScDHarvardMedicalSchoolBoston,MA,USAJuly,2009臨床研究設(shè)計分析和文章寫作宋一青ClinicalStudyDesign,Analysi1StudyDesign(科研設(shè)計)Why

（為什么要做科研？）臨床體會，經(jīng)驗是否正確；興趣；等等。What

（做什么?）內(nèi)容包括完整提出自己的假說，新理論、新方法或新模型？或者只是來驗證別人的How

（怎么做？)方法的科學(xué)性和嚴格性StudyDesign(科研設(shè)計)Why（為什么要做科2OverviewClinicalStudy(definition):(定義）ClinicalStudyPurpose(臨床研究主要目的）Etiology(病因?qū)W）Prediction（疾病預(yù)測）Treatment（疾病治療）StudyDirection（側(cè)重方向）

Genetics（基因研究）Biomarkers（生物標(biāo)記物）Nutrition（營養(yǎng)）Pharmacologicalagentsorsurgery（藥物或外科手術(shù)）Psychosocialfactors（社會心理學(xué)）…(等等）OverviewClinicalStudy(defini3KeyissuesinstudyDesign

(研究設(shè)計的關(guān)鍵）Knowledgementinyourfield（本學(xué)科知識）Literaturesearch（文獻追蹤）KeyissuesinstudyDesign

(研4FundamentalStudyDesign

(基本研究設(shè)計類型）ObservationalStudy(觀察性臨床研究）EcologicalStudies(生態(tài)性研究）Casereport（病例報告）Cross-sectionalStudy（橫斷面研究）Case-ControlStudy（病例對照研究）ProspectiveCohortStudy(前瞻性定群研究）RetrospectiveCohortStudy(回顧性定群研究）InterventionTrial（臨床干預(yù)試驗）

OpenTrial（開放性研究）RandomizedTrial（隨機干預(yù)試驗）Randomizeddouble-blindTrial（隨機雙盲干預(yù)試驗）Randomizedsingle-blindTrial（隨機單盲干預(yù)試驗）Evidence-basedStudy（循證醫(yī)學(xué)研究）

SystemicReview（系統(tǒng)性文獻綜述）Meta-analysis(薈萃分析）FundamentalStudyDesign

(基本研究5AnyclinicalstudypublishedintheMedicalJournalsStudyDesign?Studypopulation?Studieshypothesisorquestionsoftesting?.TitleAbstractIntroductionHowtoreadtheliterature(如何有效地閱讀文獻）MainAnalysismethodsResults?研究問題？研究類型？研究人群？主要分析方法？研究結(jié)果？Anyclinicalstudypublishedi6大氣污染與糖尿病發(fā)生率的關(guān)系出生體重與成人II型糖尿病的關(guān)系糖尿病人合并HIV感染的特征分析Examples(實例分析）Casereportorcase-controlstudyEcologicalstudyCohortstudyorCase-controlstudy空腹血糖水平與發(fā)生腫瘤的關(guān)系Cohortstudy；case-controlstudy胰島素治療對糖尿病合并癥的效果Randomizedtrial；cohortstudy？新降糖藥的療效Randomizedtrial基因多態(tài)性與糖尿病的關(guān)系Case-controlstudy;cohortstudy;cross-sectionalstudy新檢測方法對糖尿病預(yù)測的改善Cohortstudy血中幾種檢測標(biāo)記物的相關(guān)性Cross-sectionalstudy大氣污染與糖尿病發(fā)生率的關(guān)系出生體重與成人II型糖尿病的關(guān)系7Summary（總結(jié)）StudyPopulation（研究人群的建立最為關(guān)鍵）Representative（代表性）SampleSize（數(shù)量）StudyDesign（研究設(shè)計類型）Prospective（前瞻性最優(yōu)，其次，病例對照或橫斷面）Longitudinal（續(xù)貫性）DataCollection(數(shù)據(jù)收集齊備）Basiccharacteristics(demographic,geographic,anthropometric,andlifestyleorpsychosocialfactors)Biologicalsamplecollection(blood,toenail,hair,andurine).Accurateoutcomeascertainment(疾病診斷準(zhǔn)確）StudyGroup（研究團隊）DifferentResearchAreas（不同側(cè)重點）Multidisciplinarycollaboration（多學(xué)科協(xié)作）Keeptrackofthelatestinformation(跟蹤最新文獻）Summary（總結(jié)）StudyPopulation8StudyPopulationTotalpopulationlivinginaspecificarea(一個范圍明確的地區(qū)的全體或其樣本）Highriskpopulation（高危人群）Specialpopulations（特殊人群）：e.g.HealthProfessionals,volunteers.StudyPopulationTotalpopulati9臨床資料充分人群特殊橫斷面研究但是人群代表性傳統(tǒng)方法陽性結(jié)果臨床資料充分人群特殊橫斷面研究但是人群代表性傳統(tǒng)方法陽性結(jié)果10臨床資料充分人群特殊同一人群傳統(tǒng)方法陽性結(jié)果臨床資料充分人群特殊同一人群傳統(tǒng)方法陽性結(jié)果11CommonvariantsinKCNQ1areassociatedwithtype2diabetesandimpairedfastingglucoseinaChineseHanpopulation.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.CommonvariantsinKCNQ1area12CommonDisease（常見病的研究）在有代表性的人群中從橫斷面研究做起，樣本要大，基線數(shù)據(jù)要齊備，生物樣本注意正確采取和妥善長期保存可包括前期疾病狀態(tài)資金及其它條件允許下，加入隊列定群研究，或加做隨機試驗RareDisease（臨床少見病的研究）建議做病例對照研究注意對照組病人的正確選擇3.數(shù)據(jù)收集要齊備，注意保存生物樣本CommonDisease在有代表性的人群中從橫斷面研究13小型病例對照研究小型病例對照研究14ALS（肌萎縮性脊髓側(cè)索硬化癥）合適病例對照研究ALS（肌萎縮性脊髓側(cè)索硬化癥）合適病例對照研究15RandomizedClinicalTrialDesign

(隨機臨床試驗設(shè)計）Studypopulation（研究人群）Randomization（隨機化）Blindmethod（盲法）Placebo（安慰劑使用）Dosage（治療劑量）Samplesizeandpowercalculation（樣本量計算）Duration（治療時間）Compliance（隨訪性）Safetymonitoring（安全性監(jiān)測）RandomizedClinicalTrialDesi16Timescited（累積引用次數(shù)）:Google:1,906ISI:1,048課題新穎；臨床意義大；隨機試驗；結(jié)果陽性。優(yōu)勢：小樣本；隨機效果是否達到預(yù)期；糖尿病的診斷是否一致不足處：Timescited（累積引用次數(shù)）:課題新穎；優(yōu)勢：小1720,000MenandWomenwillbeRandomizedintheVITALTrialVitaminD(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)20,000MenandWomenwillbeR188171WomenRandomizedintheWACSTrial(June1995-January31,2005)5442RandomizedintheWAFACSTrial(April1998-July31,2005)DailytakeofacombinationpilloffolicacidandvitaminsB6andB12(n=2,132freeofdiabetesatbaseline)Dailyintakeofaplacebopill(n=2,120freeofdiabetesatbaseline)245Incidentcases259IncidentcasesFigure1.FlowdiagramillustratingdiabetesoutcomesintherandomlyassignedtreatmentoffolicacidandvitaminsB6andB12oftheWomen’sAntioxidantandFolicAcidCardiovascularStudy(WAFACS).(Songetal.Diabetes,2009)8171WomenRandomizedintheW19LogranktestP=0.44YearsofFollow-upFolate/BvitaminsGroup21322044193518151738No.atRiskPlaceboGroup21202017190117891720Figure2.Cumulativeincidenceoftype2diabetesbyrandomizedtreatmentassignment(activetreatmentvs.placebo)intheWAFACS.RR=0.94(0.79-1.11)SimilarResultsaftercensoringnon-compliance(Songetal.Diabetes,2009)LogranktestP=0.44YearsofF2000.501.001.502.00RelativeRiskforType2DiabetesFigure3.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)0.900.9900.5021SCI-ScienceCitationIndex

（科學(xué)索引指數(shù)）ScienceCitationIndex(SCI)isacitationindexoriginallyproducedbytheInstituteforScientificInformation(ISI)in1960,whichisnowownedbyThomsonReuters.Thisdatabaseallowsaresearchertoidentifywhichlaterarticleshavecitedanyparticularearlierarticle,orcitedthearticlesofanyparticularauthor,ordeterminewhicharticleshavebeencitedmostfrequently.ThompsonISI論文檢索數(shù)據(jù)庫挑選世界上一批有影響的科學(xué)刊物，將其論文題目和作者及作者單位、文摘和引用論文進行檢索，建立數(shù)據(jù)庫，并向世界各地科研單位定期發(fā)行他們的檢索數(shù)據(jù)庫，為科學(xué)工作者提供便捷的論文檢索和引用統(tǒng)計服務(wù)。收錄在SCI中的雜志論文比較容易被科研人員檢索查閱。論文絕大多數(shù)是英文刊物

（10，000多種期刊，120，000個國際會議錄）SCI-ScienceCitationIndex

（科學(xué)22臨床研究設(shè)計分析和文章寫作課件23Impactfactor

（引用因子）TheImpactfactorwasdevisedbyEugeneGarfield,thefounderoftheInstituteforScientificInformation(ISI),nowpartofThomson,alargeworldwideUS-basedpublisher.ImpactfactorsarecalculatedeachyearbyThomsonScientificforthosejournalswhichitindexes,andthefactorsandindicesarepublishedinJournalCitationReports.引用因子是針對某一年的評價指標(biāo)：舉例來說，2008年的某一個雜志的IF值就是該雜志在2008前兩年（2006和2007）的文章在2008一年內(nèi)被引用的總次數(shù)除以這兩年發(fā)表的文章總數(shù)（包括編者按和給編輯的來信）。Impactfactor

（引用因子）TheImpact24臨床研究設(shè)計分析和文章寫作課件25臨床研究設(shè)計分析和文章寫作課件26臨床研究設(shè)計分析和文章寫作課件27ResearchResults

(研究結(jié)果）OriginalResearch:

即有原創(chuàng)性的成果。ReplicationResearch:

重復(fù)性成果。Comprehensive，SystematicReview（qualitativeandquantitative):較全面系統(tǒng)的文獻綜述。ResearchResults

(研究結(jié)果）Origina28ManuscriptPreparationOriginality(Novelty)(內(nèi)容原創(chuàng)性新穎性)NovelFindings(獨特的發(fā)現(xiàn))Goodwriting(可讀性方面)Clearthinking（思路清晰）Logic（邏輯性強）Concisesentence（語句通順）ClearTablesandFigures(表格圖表清晰，信息豐富)ManuscriptPreparationOriginal29研究論文的大致結(jié)構(gòu)Title（題目）AuthorsandAffiliation（作者和單位）Abstract（摘要）Introduction（引言）ResearchDesignandMethods(研究設(shè)計和方法）Results（結(jié)果）Discussion（討論和結(jié)論）Acknowledgement（致謝）References（參考文獻）TablesandFigures(表和圖)研究論文的大致結(jié)構(gòu)Title（題目）30臨床研究設(shè)計分析和文章寫作課件31Introduction（引言）提出研究動機和目的提出研究問題必須參考引證最新的相關(guān)研究文獻Introduction（引言）提出研究動機和目的32Discussion(討論）Summary(概括性總結(jié)）Comparison（與其它研究從理論、方法到結(jié)果的相同和不同點）Mechanisms（可能的機制討論）StrengthandLimitation（本研究優(yōu)缺點）Conclusions（結(jié)論和意義）Discussion(討論）Summary(概括性總結(jié)）33Reference（文獻引用）ENDNOTE（幫助軟件）Keynotepapers（關(guān)鍵的文獻）Originalpaper(原創(chuàng)論文為主）Keyreviewpaper(關(guān)鍵的綜述性文章）

Reference（文獻引用）ENDNOTE（幫助軟件）34CommonReasonsforPaperRejection（退稿的常見的原因）首先分析向SCI刊物投稿命中率低、退稿率高的原因。研究問題不新穎；2.實質(zhì)性內(nèi)容的原因;

-實驗設(shè)計缺陷；

-數(shù)據(jù)不全；

-分析方法；3.語言和寫法方面的原因;4.無新或重要的補充。僅是簡單重復(fù)他人工作。CommonReasonsforPaperRejec35Performanceevaluation(業(yè)績評估）Quality（研究質(zhì)量）Quantity（研究數(shù)量）ContinuousContribution（持續(xù)性研究）Researcherpotential（研究者潛質(zhì)）Passionate(熱情）Persistent(堅持）Patient(耐心）Performanceevaluation(業(yè)績評估）Q36AnIntegrativeParadigmforMedicineandPublicHealthintheNewMillennium

（臨床醫(yī)學(xué)和公共衛(wèi)生領(lǐng)域在下一世紀的融合發(fā)展）DNARNAProteinPathwaysNetworksCellsOrgansPersonsPopulationsGenomicsFunctional/expressionProteomicsMetabolomicsSystembiologyCellBiologyPhysiology/PathologyMedicinePublicHealthAdynamicintegrationthroughspaceandtimeAnIntegrativeParadigmforMe37RegulationofEnergyBalanceBrainNPYAGRPgalaninOrexin-AdynorphinStimulateα-MSHCRH/UCNGLP-ICARTNE5-HTInhibitCentralSignalsGlucoseCCK,GLP-1,

Apo-A-IV

VagalafferentsInsulinGhrelin

Leptin

CortisolPeripheralsignalsPeripheralorgans++Gastrointestinal

tractAdipose

tissueFood

IntakeAdrenalglandsExternalfactorsEmotionsFoodcharacteristicsLifestylebehaviorsEnvironmentalcuesSchwartzetal.Nature2000RegulationofEnergyBalanceBr38InterdisciplinaryNeedsStrongmultidisciplinaryteams（多學(xué)科協(xié)作）clinicalscientists（臨床大夫）populationscientists(人群研究人員）laboratoryscientists（實驗工作者）mathematicalscientists（數(shù)學(xué)或量化分析家）InterdisciplinaryNeedsStrong39“Knowingisnotenough;wemustapply.Willingisnotenough;wemustdo.”—Goethe知道和了解是遠遠不夠的；我們必須要在實際中應(yīng)用。僅懷有愿望是不夠的；我們必須要付出實際行動?！癒nowingisnotenough;wemus40Thankyou!Thankyou!41ClinicalStudyDesign,Analysis,andPresentationYiqingSong,MD,ScDHarvardMedicalSchoolBoston,MA,USAJuly,2009臨床研究設(shè)計分析和文章寫作宋一青ClinicalStudyDesign,Analysi42StudyDesign(科研設(shè)計)Why

（為什么要做科研？）臨床體會，經(jīng)驗是否正確；興趣；等等。What

（做什么?）內(nèi)容包括完整提出自己的假說，新理論、新方法或新模型？或者只是來驗證別人的How

（怎么做？)方法的科學(xué)性和嚴格性StudyDesign(科研設(shè)計)Why（為什么要做科43OverviewClinicalStudy(definition):(定義）ClinicalStudyPurpose(臨床研究主要目的）Etiology(病因?qū)W）Prediction（疾病預(yù)測）Treatment（疾病治療）StudyDirection（側(cè)重方向）

Genetics（基因研究）Biomarkers（生物標(biāo)記物）Nutrition（營養(yǎng)）Pharmacologicalagentsorsurgery（藥物或外科手術(shù)）Psychosocialfactors（社會心理學(xué)）…(等等）OverviewClinicalStudy(defini44KeyissuesinstudyDesign

(研究設(shè)計的關(guān)鍵）Knowledgementinyourfield（本學(xué)科知識）Literaturesearch（文獻追蹤）KeyissuesinstudyDesign

(研45FundamentalStudyDesign

(基本研究設(shè)計類型）ObservationalStudy(觀察性臨床研究）EcologicalStudies(生態(tài)性研究）Casereport（病例報告）Cross-sectionalStudy（橫斷面研究）Case-ControlStudy（病例對照研究）ProspectiveCohortStudy(前瞻性定群研究）RetrospectiveCohortStudy(回顧性定群研究）InterventionTrial（臨床干預(yù)試驗）

OpenTrial（開放性研究）RandomizedTrial（隨機干預(yù)試驗）Randomizeddouble-blindTrial（隨機雙盲干預(yù)試驗）Randomizedsingle-blindTrial（隨機單盲干預(yù)試驗）Evidence-basedStudy（循證醫(yī)學(xué)研究）

SystemicReview（系統(tǒng)性文獻綜述）Meta-analysis(薈萃分析）FundamentalStudyDesign

(基本研究46AnyclinicalstudypublishedintheMedicalJournalsStudyDesign?Studypopulation?Studieshypothesisorquestionsoftesting?.TitleAbstractIntroductionHowtoreadtheliterature(如何有效地閱讀文獻）MainAnalysismethodsResults?研究問題？研究類型？研究人群？主要分析方法？研究結(jié)果？Anyclinicalstudypublishedi47大氣污染與糖尿病發(fā)生率的關(guān)系出生體重與成人II型糖尿病的關(guān)系糖尿病人合并HIV感染的特征分析Examples(實例分析）Casereportorcase-controlstudyEcologicalstudyCohortstudyorCase-controlstudy空腹血糖水平與發(fā)生腫瘤的關(guān)系Cohortstudy；case-controlstudy胰島素治療對糖尿病合并癥的效果Randomizedtrial；cohortstudy？新降糖藥的療效Randomizedtrial基因多態(tài)性與糖尿病的關(guān)系Case-controlstudy;cohortstudy;cross-sectionalstudy新檢測方法對糖尿病預(yù)測的改善Cohortstudy血中幾種檢測標(biāo)記物的相關(guān)性Cross-sectionalstudy大氣污染與糖尿病發(fā)生率的關(guān)系出生體重與成人II型糖尿病的關(guān)系48Summary（總結(jié)）StudyPopulation（研究人群的建立最為關(guān)鍵）Representative（代表性）SampleSize（數(shù)量）StudyDesign（研究設(shè)計類型）Prospective（前瞻性最優(yōu)，其次，病例對照或橫斷面）Longitudinal（續(xù)貫性）DataCollection(數(shù)據(jù)收集齊備）Basiccharacteristics(demographic,geographic,anthropometric,andlifestyleorpsychosocialfactors)Biologicalsamplecollection(blood,toenail,hair,andurine).Accurateoutcomeascertainment(疾病診斷準(zhǔn)確）StudyGroup（研究團隊）DifferentResearchAreas（不同側(cè)重點）Multidisciplinarycollaboration（多學(xué)科協(xié)作）Keeptrackofthelatestinformation(跟蹤最新文獻）Summary（總結(jié)）StudyPopulation49StudyPopulationTotalpopulationlivinginaspecificarea(一個范圍明確的地區(qū)的全體或其樣本）Highriskpopulation（高危人群）Specialpopulations（特殊人群）：e.g.HealthProfessionals,volunteers.StudyPopulationTotalpopulati50臨床資料充分人群特殊橫斷面研究但是人群代表性傳統(tǒng)方法陽性結(jié)果臨床資料充分人群特殊橫斷面研究但是人群代表性傳統(tǒng)方法陽性結(jié)果51臨床資料充分人群特殊同一人群傳統(tǒng)方法陽性結(jié)果臨床資料充分人群特殊同一人群傳統(tǒng)方法陽性結(jié)果52CommonvariantsinKCNQ1areassociatedwithtype2diabetesandimpairedfastingglucoseinaChineseHanpopulation.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.CommonvariantsinKCNQ1area53CommonDisease（常見病的研究）在有代表性的人群中從橫斷面研究做起，樣本要大，基線數(shù)據(jù)要齊備，生物樣本注意正確采取和妥善長期保存可包括前期疾病狀態(tài)資金及其它條件允許下，加入隊列定群研究，或加做隨機試驗RareDisease（臨床少見病的研究）建議做病例對照研究注意對照組病人的正確選擇3.數(shù)據(jù)收集要齊備，注意保存生物樣本CommonDisease在有代表性的人群中從橫斷面研究54小型病例對照研究小型病例對照研究55ALS（肌萎縮性脊髓側(cè)索硬化癥）合適病例對照研究ALS（肌萎縮性脊髓側(cè)索硬化癥）合適病例對照研究56RandomizedClinicalTrialDesign

(隨機臨床試驗設(shè)計）Studypopulation（研究人群）Randomization（隨機化）Blindmethod（盲法）Placebo（安慰劑使用）Dosage（治療劑量）Samplesizeandpowercalculation（樣本量計算）Duration（治療時間）Compliance（隨訪性）Safetymonitoring（安全性監(jiān)測）RandomizedClinicalTrialDesi57Timescited（累積引用次數(shù)）:Google:1,906ISI:1,048課題新穎；臨床意義大；隨機試驗；結(jié)果陽性。優(yōu)勢：小樣本；隨機效果是否達到預(yù)期；糖尿病的診斷是否一致不足處：Timescited（累積引用次數(shù)）:課題新穎；優(yōu)勢：小5820,000MenandWomenwillbeRandomizedintheVITALTrialVitaminD(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)20,000MenandWomenwillbeR598171WomenRandomizedintheWACSTrial(June1995-January31,2005)5442RandomizedintheWAFACSTrial(April1998-July31,2005)DailytakeofacombinationpilloffolicacidandvitaminsB6andB12(n=2,132freeofdiabetesatbaseline)Dailyintakeofaplacebopill(n=2,120freeofdiabetesatbaseline)245Incidentcases259IncidentcasesFigure1.FlowdiagramillustratingdiabetesoutcomesintherandomlyassignedtreatmentoffolicacidandvitaminsB6andB12oftheWomen’sAntioxidantandFolicAcidCardiovascularStudy(WAFACS).(Songetal.Diabetes,2009)8171WomenRandomizedintheW60LogranktestP=0.44YearsofFollow-upFolate/BvitaminsGroup21322044193518151738No.atRiskPlaceboGroup21202017190117891720Figure2.Cumulativeincidenceoftype2diabetesbyrandomizedtreatmentassignment(activetreatmentvs.placebo)intheWAFACS.RR=0.94(0.79-1.11)SimilarResultsaftercensoringnon-compliance(Songetal.Diabetes,2009)LogranktestP=0.44YearsofF6100.501.001.502.00RelativeRiskforType2DiabetesFigure3.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)0.900.9900.5062SCI-ScienceCitationIndex

（科學(xué)索引指數(shù)）ScienceCitationIndex(SCI)isacitationindexoriginallyproducedbytheInstituteforScientificInformation(ISI)in1960,whichisnowownedbyThomsonReuters.Thisdatabaseallowsaresearchertoidentifywhichlaterarticleshavecitedanyparticularearlierarticle,orcitedthearticlesofanyparticularauthor,ordeterminewhicharticleshavebeencitedmostfrequently.ThompsonISI論文檢索數(shù)據(jù)庫挑選世界上一批有影響的科學(xué)刊物，將其論文題目和作者及作者單位、文摘和引用論文進行檢索，建立數(shù)據(jù)庫，并向世界各地科研單位定期發(fā)行他們的檢索數(shù)據(jù)庫，為科學(xué)工作者提供便捷的論文檢索和引用統(tǒng)計服務(wù)。收錄在SCI中的雜志論文比較容易被科研人員檢索查閱。論文絕大多數(shù)是英文刊物

（10，000多種期刊，120，000個國際會議錄）SCI-ScienceCitationIndex

（科學(xué)63臨床研究設(shè)計分析和文章寫作課件64Impactfactor

（引用因子）TheImpactfactorwasdevisedbyEugeneGarfield,thefounderoftheInstituteforScientificInformation(ISI),nowpartofThomson,alargeworldwideUS-basedpublisher.ImpactfactorsarecalculatedeachyearbyThomsonScientificforthosejournalswhichitindexes,andthefactorsandindicesarepublishedinJournalCitationReports.引用因子是針對某一年的評價指標(biāo)：舉例來說，2008年的某一個雜志的IF值就是該雜志在2008前兩年（2006和2007）的文章在2008一年內(nèi)被引用的總次數(shù)除以這兩年發(fā)表的文章總數(shù)（包括編者按和給編輯的來信）。Impactfactor

（引用因子）TheImpact65臨床研究設(shè)計分析和文章寫作課件66臨床研究設(shè)計分析和文章寫作課件67臨床研究設(shè)計分析和文章寫作課件68ResearchResults

(研究結(jié)果）OriginalResearch:

即有原創(chuàng)性的成果。ReplicationResearch:

重復(fù)性成果。Comprehensive，SystematicReview（qualitativeandquantitative):較全面系統(tǒng)的文獻綜述。ResearchResults

(研究結(jié)果）Origina69ManuscriptPreparationOriginality(No