臨床研究設(shè)計分析和文章寫作

ClinicalStudyDesign,Analysis,andPresentationYiqingSong,MD,ScDHarvardMedicalSchoolBoston,MA,USAJuly,2021臨床研究設(shè)計分析和文章寫作宋一青StudyDesign(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(yán)格性O(shè)verviewClinicalStudy(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〕KeyissuesinstudyDesign

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

(根本研究設(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(回憶性定群研究〕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〕AnyclinicalstudypublishedintheMedicalJournalsStudyDesign?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？StudyPopulationTotalpopulationlivinginaspecificarea(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.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同一人群傳統(tǒng)方法陽性結(jié)果CommonvariantsinKCNQ1areassociatedwithtype2diabetesandimpairedfastingglucoseinaChineseHanpopulation.HumMolGenet.2021Plasma25-hydroxyvitaminDconcentrationandmetabolicsyndromeamongmiddle-agedandelderlyChineseindividuals.DiabetesCare.2021Jul;32(7):1278-83.RBP4variantsaresignificantlyassociatedwithplasmaRBP4levelsandhypertriglyceridemiariskinChineseHans.JLipidRes.2021Jul;50(7):1479-86.AssociationofGCKRrs780094,aloneorincombinationwithGCKrs1799884,withtype2diabetesandrelatedtraitsinaHanChinesepopulation.Diabetologia.2021May;52(5):834-43.Associationsofinflammatoryfactorswithglycaemicstatusamongmiddle-agedandolderChinesepeople.ClinEndocrinol(Oxf).2021Jun;70(6):854-62.Epub2021Sep2.Associationsofresistinwithinflammatoryandfibrinolyticmarkers,insulinresistance,andmetabolicsyndromeinmiddle-agedandolderChinese.EurJEndocrinol.2021Nov;159(5):585-93.CommonvariantsinCDKAL1,CDKN2A/B,IGF2BP2,SLC30A8,andHHEX/IDEgenesareassociatedwithtype2diabetesandimpairedfastingglucoseinaChineseHanpopulation.Diabetes.2021Oct;57(10):2834-42.Variantsinthefatmass-andobesity-associated(FTO)genearenotassociatedwithobesityinaChineseHanpopulation.Diabetes.2021Jan;57(1):264-8.Elevatedretinol-bindingprotein4levelsareassociatedwithmetabolicsyndromeinChinesepeople.JClinEndocrinolMetab.2007Dec;92(12):4827-34.CommonDisease〔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，參加隊列定群研究，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，注意保存生物樣本小型病例對照研究ALS〔肌萎縮性脊髓側(cè)索硬化癥〕適宜病例對照研究RandomizedClinicalTrialDesign

(隨機臨床試驗設(shè)計〕Studypopulation〔研究人群〕Randomization〔隨機化〕Blindmethod〔盲法〕Placebo〔撫慰劑使用〕Dosage〔治療劑量〕Samplesizeandpowercalculation〔樣本量計算〕Duration〔治療時間〕Compliance〔隨訪性〕Safetymonitoring〔平安性監(jiān)測〕Timescited〔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；隨機效果是否到達預(yù)期；糖尿病的診斷是否一致缺乏處：20,000MenandWomenwillbeRandomizedintheVITALTrialVitaminD(1,600IU)N=10,000PlacebovitaminDN=10,000DHA/EPA(1g/day)N=5,000FishOilPlaceboN=5,000Flowdiagramillustratingthe22randomlyassignedtreatmentcomponentsoftheVITaminDandOmegaA-3TriaL(VITAL),whichwillstartinJanuary2021.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,2021)LogranktestP=0.44YearsofFollow-upFolate/BvitaminsGroup21322044193518151738No.atRiskPlaceboGroup21202021190117891720Figure2.Cumulativeincidenceoftype2diabetesbyrandomizedtreatmentassignment(activetreatmentvs.placebo)intheWAFACS.RR=0.94(0.79-1.11)SimilarResultsaftercensoringnon-compliance(Songetal.Diabetes,2021)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)計效勞。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〕Impactfactor

〔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，2021年的某一個雜志的IF值就是該雜志在2021前兩年〔2006和2007〕的文章在2021一年內(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〕。ResearchResults

(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。ManuscriptPreparationOriginality(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)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)Introduction〔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Discussion(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〕Reference〔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〕

CommonReasonsforPaperRejection〔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。Performanceevaluation(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〕AnIntegrativeParadigmforMedicineandPubli