临床研究设计分析和文写作.ppt

Clinical Study Design,Analysis,and PresentationYiqing Song,MD,ScDHarvard Medical School Boston,MA,USAJuly,2009临床研究设计分析和文章写作宋一青1.Study Design(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2.OverviewClinical Study(definition):(定义）Clinical Study Purpose(临床研究主要目的）Etiology(病因学）Prediction（疾病预测）Treatment（疾病治疗）Study Direction（侧重方向）Genetics（基因研究）Biomarkers（生物标记物）Nutrition（营养）Pharmacological agents or surgery（药物或外科手术）Psychosocial factors（社会心理学）(等等）3.Key issues in study Design(研究设计的关键）Knowledgement in your field（本学科知识）Literature search（文献追踪）4.Fundamental Study Design(基本研究设计类型）Observational Study (观察性临床研究）Ecological Studies (生态性研究）Case report（病例报告）Cross-sectional Study（横断面研究）Case-Control Study（病例对照研究）Prospective Cohort Study(前瞻性定群研究）Retrospective Cohort Study(回顾性定群研究）Intervention Trial（临床干预试验）Open Trial（开放性研究）Randomized Trial（随机干预试验）Randomized double-blind Trial（随机双盲干预试验）Randomized single-blind Trial（随机单盲干预试验）Evidence-based Study（循证医学研究）Systemic Review（系统性文献综述）Meta-analysis(荟萃分析）5.Any clinical study published in the Medical Journals Study Design?Study population?Studies hypothesis or questions of testing?.Title Abstract Introduction How to read the literature(如何有效地阅读文献）Main Analysis methodsResults?研究问题？研究类型？研究人群？主要分析方法？研究结果？6.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）Case report or case-control studyEcological studyCohort study or Case-control study空腹血糖水平与发生肿瘤的关系Cohort study；case-control study胰岛素治疗对糖尿病合并症的效果Randomized trial；cohort study？新降糖药的疗效Randomized trial基因多态性与糖尿病的关系Case-control study;cohort study;cross-sectional study新检测方法对糖尿病预测的改善Cohort study血中几种检测标记物的相关性Cross-sectional study7.Summary（总结）Study Population（研究人群的建立最为关键）Representative（代表性）Sample Size（数量）Study Design（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）Data Collection(数据收集齐备）Basic characteristics(demographic,geographic,anthropometric,and lifestyle or psychosocial factors)Biological sample collection(blood,toenail,hair,and urine).Accurate outcome ascertainment(疾病诊断准确）Study Group（研究团队）Different Research Areas（不同侧重点）Multidisciplinary collaboration（多学科协作）Keep track of the latest information(跟踪最新文献）8.Study PopulationTotal population living in a specific area(一个范围明确的地区的全体或其样本）High risk population（高危人群）Special populations（特殊人群）：e.g.Health Professionals,volunteers.9.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10.临床资料充分人群特殊同一人群传统方法阳性结果11.1.Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population.Hum Mol Genet.20092.Plasma 25-hydroxyvitamin D concentration and metabolic syndrome among middle-aged and elderly Chinese individuals.Diabetes Care.2009 Jul;32(7):1278-83.3.RBP4 variants are significantly associated with plasma RBP4 levels and hypertriglyceridemia risk in Chinese Hans.J Lipid Res.2009 Jul;50(7):1479-86.4.Association of GCKR rs780094,alone or in combination with GCK rs1799884,with type 2 diabetes and related traits in a Han Chinese population.Diabetologia.2009 May;52(5):834-43.5.Associations of inflammatory factors with glycaemic status among middle-aged and older Chinese people.Clin Endocrinol(Oxf).2009 Jun;70(6):854-62.Epub 2008 Sep 2.6.Associations of resistin with inflammatory and fibrinolytic markers,insulin resistance,and metabolic syndrome in middle-aged and older Chinese.Eur J Endocrinol.2008 Nov;159(5):585-93.7.Common variants in CDKAL1,CDKN2A/B,IGF2BP2,SLC30A8,and HHEX/IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population.Diabetes.2008 Oct;57(10):2834-42.8.Variants in the fat mass-and obesity-associated(FTO)gene are not associated with obesity in a Chinese Han population.Diabetes.2008 Jan;57(1):264-8.9.Elevated retinol-binding protein 4 levels are associated with metabolic syndrome in Chinese people.J Clin Endocrinol Metab.2007 Dec;92(12):4827-34.12.Common Disease（常见病的研究）1.在有代表性的人群中从横断面研究做起，2.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3.可包括前期疾病状态4.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Rare Disease（临床少见病的研究）1.建议做病例对照研究2.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13.小型病例对照研究14.ALS（肌萎缩性脊髓侧索硬化症）合适病例对照研究15.Randomized Clinical Trial Design(随机临床试验设计）Study population（研究人群）Randomization（随机化）Blind method（盲法）Placebo（安慰剂使用）Dosage（治疗剂量）Sample size and power calculation（样本量计算）Duration（治疗时间）Compliance（随访性）Safety monitoring（安全性监测）16.Times cited（累积引用次数）:Google:1,906ISI:1,048 1.课题新颖；2.临床意义大；3.随机试验；4.结果阳性。优势：1.小样本；2.随机效果是否达到预期；3.糖尿病的诊断是否一致不足处：17.20,000 Men and Women will be Randomized in the VITAL TrialVitamin D(1,600IU)N=10,000Placebo vitamin DN=10,000DHA/EPA(1g/day)N=5,000Fish Oil PlaceboN=5,000Flow diagram illustrating the 22 randomly assigned treatment components of the VITamin D and OmegaA-3 TriaL(VITAL),which will start in January 2010.DHA/EPA(1g/day)N=5,000Fish Oil PlaceboN=5,000The VITamin D and OmegaA-3 TriaL(VITAL)18.8171 Women Randomized in the WACS Trial(June 1995-January 31,2005)5442 Randomized in the WAFACS Trial(April 1998-July 31,2005)Daily take of a combination pill of folic acid and vitamins B6 and B12(n=2,132 free of diabetes at baseline)Daily intake of a placebo pill(n=2,120 free of diabetes at baseline)245 Incident cases259 Incident casesFigure 1.Flow diagram illustrating diabetes outcomes in the randomly assigned treatment of folic acid and vitamins B6 and B12 of the Womens Antioxidant and Folic Acid Cardiovascular Study(WAFACS).(Song et al.Diabetes,2009)19.Log rank test P=0.44Years of Follow-up Folate/B vitamins Group 2132 2044 1935 1815 1738No.at Risk Placebo Group 2120 2017 1901 1789 1720Figure 2.Cumulative incidence of type 2 diabetes by randomized treatment assignment(active treatment vs.placebo)in the WAFACS.RR=0.94(0.79-1.11)Similar Results after censoring non-compliance(Song et al.Diabetes,2009)20.0 0.50 1.00 1.50 2.00Relative Risk for Type 2 DiabetesFigure 3.SubgroupFolic Acid/B Vitamin Active GroupPlacebo GroupP value for InteractionAge45-54 yr 57(0.13)80(0.17)No.of cases(%)55-64 yr 94(0.12)95(0.13)65 yr 94(0.10)84(0.09)1000kcal/wk 74(0.09)80(0.10)Low,1000kcal/wk 171(0.13)179(0.13)Physical Activity0.360.850.60Current 29(0.11)39(0.15)Past 106(0.12)113(0.12)Never 110(0.11)107(0.12)Cigarette Smoking 0.61Yes 110(0.15)140(0.19)No 123(0.09)113(0.09)Family History of diabetes 0.060.71Tertile 1(1.82-9.75)78(0.11)75(0.11)Tertile 2(9.76-43.7)81(0.12)87(0.13)Baseline vitamin B12 intake(mcg/d)Tertile 3(43.8-899)72(0.11)81(0.12)Tertile 1(1.82-9.75)76(0.11)77(0.12)Tertile 2(9.76-43.7)83(0.12)87(0.13)Baseline vitaminB6 intake(mg/d)Tertile 3(43.8-899)72(0.11)79(0.11)Tertile 1(1.82-9.75)78(0.11)82(0.12)Tertile 2(9.76-43.7)82(0.12)82(0.12)Baseline folate intake(mg/d)Tertile 3(43.8-899)71(0.11)79(0.12)0.900.9921.SCI-Science Citation Index（科学索引指数）Science Citation Index(SCI)is a citation index originally produced by the Institute for Scientific Information(ISI)in 1960,which is now owned by Thomson Reuters.This database allows a researcher to identify which later articles have cited any particular earlier article,or cited the articles of any particular author,or determine which articles have been cited most frequently.Thompson ISI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）22.23.Impact factor（引用因子）The Impact factor was devised by Eugene Garfield,the founder of the Institute for Scientific Information(ISI),now part of Thomson,a large worldwide US-based publisher.Impact factors are calculated each year by Thomson Scientific for those journals which it indexes,and the factors and indices are published in Journal Citation Reports.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）。24.25.26.27.Research Results(研究结果）Original Research:即有原创性的成果。Replication Research:重复性成果。Comprehensive，Systematic Review（qualitative and quantitative):较全面系统的文献综述。28.Manuscript PreparationOriginality(Novelty)(内容原创性新颖性)Novel Findings(独特的发现)Good writing(可读性方面)Clear thinking（思路清晰）Logic（逻辑性强）Concise sentence（语句通顺）Clear Tables and Figures(表格图表清晰，信息丰富)29.研究论文的大致结构Title（题目）Authors and Affiliation（作者和单位）Abstract（摘要）Introduction（引言）Research Design and Methods(研究设计和方法）Results（结果）Discussion（讨论和结论）Acknowledgement（致谢）References（参考文献）Tables and Figures(表和图)30.31.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32.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）Strength and Limitation（本研究优缺点）Conclusions（结论和意义）33.Reference（文献引用）ENDNOTE（帮助软件）Keynote papers（关键的文献）Original paper(原创论文为主）Key review paper(关键的综述性文章）34.Common Reasons for Paper Rejection（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。1.研究问题不新颖；2.2.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。35.Performance evaluation(业绩评估）Quality（研究质量）Quantity（研究数量）Continuous Contribution（持续性研究）Researcher potential（研究者潜质）Passionate(热情）Persistent(坚持）Patient(耐心）36.An Integrative Paradigm for Medicine and Public Health in the New Millennium（临床医学和公共卫生领域在下一世纪的融合发展）DNARNAProteinPathwaysNetworksCellsOrgansPersonsPopulationsGenomicsFunctional/expressionProteomicsMetabolomicsSystem biologyCell BiologyPhysiology/PathologyMedicinePublic HealthA dynamic integration through space and time37.Regulation of Energy BalanceBrainBrainNPYAGRPgalaninOrexin-AdynorphinStimulateStimulate-MSHCRH/UCNGLP-ICARTNE5-HTInhibitInhibitCentral SignalsCentral SignalsGlucoseCCK,GLP-1,Apo-A-IVVagal afferentsInsulinGhrelinLeptinCortisolPeripheral signalsPeripheral signalsPeripheral organsPeripheral organs+GastrointestinaltractAdiposetissueFoodIntakeAdrenal glandsExternal factorsEmotionsFood characteristicsLifestyle behaviorsEnvironmental cuesSchwartz et al.Nature 200038.Interdisciplinary NeedsStrong multidisciplinary teams（多学科协作）clinical scientists（临床大夫）population scientists(人群研究人员）laboratory scientists（实验工作者）mathematical scientists（数学或量化分析家）39.“Knowing is not enough;we must apply.Willing is not enough;we must do.”Goethe知道和了解是远远不够的；我们必须要在实际中应用。仅怀有愿望是不够的；我们必须要付出实际行动。40.Thank you!41.