临床科研设计方案PPT文档.ppt

单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,clinical study design for postgraduate 2003,*,单击此处编辑母版标题样式,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,临床科研设计方案PPT文档,临床科研设计方案PPT文档临床科研设计方案PPT文档前言,保证研究的真实性和可靠性，设计和实施同等重要。,没有哪种统计方法能挽救瑕疵设计的真实性和可靠性。2021/3/23clinical study design for postgraduate 2003,书籍能培养我们的道德情操，给我们巨大的精神力量，鼓舞我们前进,前言,保证研究的真实性和可靠性，设计和实施同等重要,。,没有哪种统计方法能挽救瑕疵设计的真实性和可靠性。,2026/10/17,clinical study design for postgraduate 2003,临床科研设计方案论证强度的影响因素,随机化,randomization,对照,control,时向,direction,盲法,blinding,2026/10/17,clinical study design for postgraduate 2003,随机,Randomization,每一参与者有,同等的机会,接受干预措施，使已知和未知的影响因素一致,减少,研究者和被研究者,的主观干扰,2026/10/17,clinical study design for postgraduate 2003,方法,简单随机,分层随机,区组随机,系统随机抽样,多级随机抽样,半随机,2026/10/17,clinical study design for postgraduate 2003,分层随机,选择影响治疗结果的因素作为分层变量,分层不宜过多,一层组数为4，两层组数为16,每组最好大于50例，精确性好,避免调整基线,2026/10/17,clinical study design for postgraduate 2003,分层随机与分层分析,2026/10/17,clinical study design for postgraduate 2003,区组随机法,对照组和治疗组比例相同,时间影响因素少,使用灵活-区组可大可小,2026/10/17,clinical study design for postgraduate 2003,随机的特点,基线一致性,避免选择性偏倚,等量原则,2026/10/17,clinical study design for postgraduate 2003,使用随机原则时应避免的几点,半随机,无隐匿（non-concealment）的方法，减少测量偏倚,自我管理分配程序,非正规的随机和无监督的分配方法,2026/10/17,clinical study design for postgraduate 2003,有关随机的错误概念,把“随意”当作“随机”,随机确保研究组的可比性,基线之间的差异是随机失败的标志,“随机”可以检验,非随机分配的治疗研究是不可靠的,2026/10/17,clinical study design for postgraduate 2003,临床科研设计方案论证强度的影响因素,随机化,randomization,对照,control,时向,direction,盲法,blinding,2026/10/17,clinical study design for postgraduate 2003,对照,比较组间的差异,类型：,-同期对照(,concurrent control),随机,非随机,-自身对照(,self control),同期,不同期,2026/10/17,clinical study design for postgraduate 2003,-历史对照(,historical control),非随机，非同期,偏倚多,-,配对对照（,matching）,2026/10/17,clinical study design for postgraduate 2003,临床科研设计方案论证强度的影响因素,随机化,randomization,对照,control,时向,direction,盲法,blinding,2026/10/17,clinical study design for postgraduate 2003,研究时向,前瞻性 Prospective study,时点 Point,回顾性Retrospective study,研究时点,2026/10/17,clinical study design for postgraduate 2003,临床科研设计方案论证强度的影响因素,随机化,randomization,对照,control,时向,direction,盲法,blinding,2026/10/17,clinical study design for postgraduate 2003,盲法,blinding,避免测量性偏倚（主观指标）,避免研究者和被研究者的影响,随机分配为盲法评定奠定基础,2026/10/17,clinical study design for postgraduate 2003,2026/10/17,clinical study design for postgraduate 2003,随机临床试验研究（,Randomized Clinical Trial）,开始,随机分配,研究人群,试验,对照,疾病/结果-,疾病/结果+,疾病/结果+,疾病/结果-,现在,测量对比结果,将来,R,研究指向,2026/10/17,clinical study design for postgraduate 2003,随机对照研究,结果指向,2026/10/17,clinical study design for postgraduate 2003,随机对照研究要考虑的问题！,研究人群的确定,效能和有效性（efficacy and effectiveness),终点指标的选择（end-points),观察期的确定（follow-up）,治疗意向分析（intention to treat analysis）而不是（explanatory analysis),医德问题,2026/10/17,clinical study design for postgraduate 2003,2026/10/17,clinical study design for postgraduate 2003,研究人群,General population,Experimental population (10.7%)Unwilling,Eligibility criteria,Study population (7.6%)Uneligible,Enrollment,Study sample (3.1%)Unwilling,Randomized,(2%)Death,Dropped out Completed Study,Ann Intern Med 1993;119:36-41,2026/10/17,clinical study design for postgraduate 2003,符合标准（纳入、诊断标准）,非典型病例,有合并症等,排除不愿意参加者,潜在的志愿者偏倚？,社会因素（特殊人群）,排除不合作者,重症？或其他原因,RCT,的研究人群是高度选择的人群,2026/10/17,clinical study design for postgraduate 2003,效能和有效性（efficacy and effectiveness),效能（,efficacy）,在“理想”环境中的效果，本身的效能,有效性（,effectiveness),在“实际”环境中的效果，受到各种因素的影响，如：病人的依从性、经济、实用性、副作用等等。,2026/10/17,clinical study design for postgraduate 2003,终点指标的选择（end-points),客观指标、终点指标,盲法判断,观察期的确定（,follow-up）,随访时间要合适。既要避免浪费人力物力,又要避免因观察时间过短的假阴性结果。,2026/10/17,clinical study design for postgraduate 2003,治疗意向分析（intention to treat analysis）,Sample,Sample,Drop out,Cross over,Drop out,Analysis according to treatment assigned,population,population,Drop out,Cross over,Drop out,Analysis according to treatment received,2026/10/17,clinical study design for postgraduate 2003,医德问题,2026/10/17,clinical study design for postgraduate 2003,RCT,的优缺点,1.因果关系中最强的研究,2.尽可能的限制混杂因素（知道和不知的因素）,3.内部真实性好,4.可以盲法,5.统计效率高,6.治疗性研究的标准设计方案,外部真实性差（纳入标准、,排除标准，严格的计划）,花费高,费时,研究问题窄,医德,实施及管理困难,志愿者偏倚,2026/10/17,clinical study design for postgraduate 2003,交叉试验,Crossover studies,开始,随机分配,A,B,结果-,结果+,结果+,结果-,洗脱期,R,研究人群,A,B,结果+,结果-,结果+,结果-,随机选择方案,研究指向,2026/10/17,clinical study design for postgraduate 2003,配对卡方,结果指向,2026/10/17,clinical study design for postgraduate 2003,Crossover Design,优点,样本量减少,自我对照减少偏倚,都治疗无医德问题,可随机，可盲法,缺点,疾病过程有变化,变量受限,洗脱期时间确定困难,(不能用于易治愈的疾病,),2026/10/17,clinical study design for postgraduate 2003,队列研究,Cohort study,开始,测量分类,研究人群,危险,因素+,危险,因素-,疾病/结果-,疾病/结果+,疾病/结果+,疾病/结果-,现在,已有病,无病,测量对比结果,将来,2026/10/17,clinical study design for postgraduate 2003,队列研究,Cohort Study,时向：,-前瞻性,Prospective,-,回顾性,Retrospective,-,回顾-前瞻,Longitudinal,队列类型,-固定的队列：,确定队列后不再有新成员加入,。,如急性心肌梗塞的病人；爆炸后的生存者；,HIV,感染母亲生产的孩子,-开放队列,：,允许队列中的个体进入或退出，动态人群,2026/10/17,clinical study design for postgraduate 2003,历史队列研究,开始,测量分类,研究人群,危险,因素+,危险,因素-,疾病/结果-,疾病/结果+,疾病/结果+,疾病/结果-,现在,已有病,无病,测量对比结果,2026/10/17,clinical study design for postgraduate 2003,Cohort Study DesignDirectionality,1990,2000,2010,Prospective,Retrospective,Retrospective,Cohort Study,Prospective,Cohort Study,Longitudinal,2026/10/17,clinical study design for postgraduate 2003,Deaths,Loss to follow-up,Fixed Cohort,Time,Open Cohort,In-,Migrations,Migrations,Out-,2026/10/17,clinical study design for postgraduate 2003,Relative Risk,No,Disease,Disease,Exposed,Unexposed,A,B,C,D,A+C,B+D,A+B,C+D,N,Incidence,exp,=A/A+B,Incidence,unexp,=C/C+D,2026/10/17,clinical study design for postgraduate 2003,COHORT STUDY EXAMPLE,口服避孕药与深静脉血栓,(DVT),形成的关系,.,OUTCOME(DVT),Yes No,Exposed(on oral contraceptive)41a 9996b 10037a+b,Not exposed(not on o.c.),7 c 10009d 10016c+d,RR=,a/a+b /c/c+d=,41/10037 /7/10016=5.8=6,*numbers to indicate the possibility of a real association between exposure and outcome.However,the possibility of,biases,very often arises.,2026/10/17,clinical study design for postgraduate 2003,Cohort Study DesignPotential Biases,检测偏倚,两组检测不一致，不能采用同样的方式，客观地在暴露和非暴露中测量暴露和结果,信息偏倚,两组获得信息不一致,无应答或失访，随访时间不足,不能控制对照组的混杂因素,2026/10/17,clinical study design for postgraduate 2003,Cohort Study,Strengths,暴露因素少的可得到结果,因-果时相关系清楚,单个暴露多种结果,可以发现短暂时间的结果,直接测量发病率,因果关系强,无医德问题,确定自然病程,可配对、标准统一，管理容易,Weaknesses,不宜用于少见病研究,花费高,要求随访率高,暴露存在混杂因素,对照难确定，,不能随机，盲法，,历史对照暴露和结果不可靠,2026/10/17,clinical study design for postgraduate 2003,随机对照与队列研究区别,前瞻,随机分配,几乎不能用于临床病因学研究,治疗性研究的标准设计方案,给予暴露（治疗）分析结果,前瞻或回顾等,不是随机分配而是自然形成的队列,病因学研究中论证强度较高的设计,观察暴露后的结果,2026/10/17,clinical study design for postgraduate 2003,前-后对照研究,before-after,studies,开始,A,结果+,结果-,洗脱期,研究人群,B,结果+,结果-,2026/10/17,clinical study design for postgraduate 2003,前-后对照研究（before-after study),两种措施在两个阶段进行,可以是同一个体或不同个体,前瞻或回顾-前瞻,2026/10/17,clinical study design for postgraduate 2003,不同个体前后研究历史性对照,A,结果+,结果-,结果+,结果-,过去,现在,B,将来,2026/10/17,clinical study design for postgraduate 2003,前-后对照研究优缺点,优点,每一病人同时治疗,样本量减少,自我对照减少偏倚,都治疗无医德问题,缺点,两阶段疾病的可比性有变化,洗脱期时间病情可能加重,2026/10/17,clinical study design for postgraduate 2003,交叉试验与前后研究区别,前瞻,随机分配,为两组同期对比,前瞻或其他,不是随机分配但可以随机选择方案,不同期前后对比（一组）,2026/10/17,clinical study design for postgraduate 2003,病例-对照研究,（,Case control study）,开始,测量对比,Case,有病/结果,危险因素+,过去,Control,无病/无结果,危险因素-,危险因素-,危险因素+,现在,回顾性,2026/10/17,clinical study design for postgraduate 2003,病例对照研究的基本要求,病例与对照的确定诊断手段一致、病例的确定应是确诊病人,病例与对照来源人群应同源,病例与对照的纳入及排除标准一致,2026/10/17,clinical study design for postgraduate 2003,Case-Control StudyInterpretation,Case,Control,Exposed,Unexposed,a,b,c,d,a+c,a+b,c+d,b+d,N,OR=,a,c,b,d,任何影响病例组和对照组的暴露比都将造成偏倚,.,2026/10/17,clinical study design for postgraduate 2003,CASE CONTROL EXAMPLE-SMOKING&LUNG CANCER,DISEASE,CasesControls,EXPOSURE Yes,a b,EXPOSURE No,c d,Odds Ratio=ad/bc(1=no association,1=possible association,1=protective effect),DISEASE,CasesControls,(lung cancer),EXPOSUREYes,56 230,(smoking)No 7 246,The odds ratio would therefore be,56 x 246 =13776,=8.6.,7 x 230 1610,2026/10/17,clinical study design for postgraduate 2003,优点,研究稀少病种和潜伏期长的疾病的暴露与结果间关系最合适的研究方案，确定潜在因果关系,不需要随访，,结果已很好的定义,适用于潜伏期长的疾病,病例数需要的少，（比横断面研究）,省钱，省时,提出假说,无医德问题,同时研究多个危险因素，有几个假说,2026/10/17,clinical study design for postgraduate 2003,缺点,病例的选择容易出现偏倚,对照与病例的人群来源不一致。暴露可能与生存率有关而不是疾病的发生,不能计算患病率、发病率、相对危险度，因果关系不清,短暂的关系很难确定,存在生存率偏倚、样本偏倚，以及各种测量偏倚，共75种,2026/10/17,clinical study design for postgraduate 2003,病例对照研究的偏倚举例,不易明确的确定对照组,有时不能采用同样的方式，客观地在病例组和对照组测量暴露和结果,回忆偏倚等,2026/10/17,clinical study design for postgraduate 2003,减少样本偏倚,配对,Matching,人群样本,人群登记选择对照,随机拨号,邻居对照,多个对照病例和对照的发病率最好与一般人群中相似,2026/10/17,clinical study design for postgraduate 2003,减少测量偏倚,盲询问者,Case/Control Status,Risk Factors,盲病人和对照,Case/Control Status:,2026/10/17,clinical study design for postgraduate 2003,病例对照研究与回顾性队列研究区别,不能确定因果关系,首先确定结果（病例）,因果关系时向清楚,首先确定暴露（病因）,？,？,暴露,疾病,？,？,开始,开始,疾病,暴露,病例对照研究,回顾性队列研究,2026/10/17,clinical study design for postgraduate 2003,横断面研究,cross-sectional survey,开始,测量,研究人群,无病,有病,危险因素-,危险因素+,危险因素+,危险因素-,时点,2026/10/17,clinical study design for postgraduate 2003,横断面,随机选择、适宜,应答率,真实性和重复性,2026/10/17,clinical study design for postgraduate 2003,横断面研究,Cross-Sectional study,测量：,在同一时间内，检查结果与危险因素等暴露因素的关系,得到患病率（,Prevalence）,容易、快捷、便宜、无医德问题,不能说明因果关系，只能表明联系,回忆偏倚，混杂因素分布不均匀、样本不等,形成假说,2026/10/17,clinical study design for postgraduate 2003,优点,无随访时间（时点）,是唯一可得到患病率的研究类型,假说的形成,前瞻性队列研究的开始,prospective cohort study,2026/10/17,clinical study design for postgraduate 2003,缺点,只能建立因果联系,时相关系不清楚,不使用于发病率低的疾病,2026/10/17,clinical study design for postgraduate 2003,叙述性研究（,descriptive study）,结果,病因+,病因-,研究方向,2026/10/17,clinical study design for postgraduate 2003,叙述性研究（,descriptive study）,措施/病因,结果+,结果-,研究方向,2026/10/17,clinical study design for postgraduate 2003,叙述性研究（,descriptive study）,个案报道或病历报道（,case report or case series),详细描述单个病例或多个病例的特点,目的：用于少见病例、新发现、教学等,新治疗方案的尝试、预试验等,不是研究,无对照,一般不能说明因果关系,2026/10/17,clinical study design for postgraduate 2003,病历报道有时可以提示病因联系或提供强的证据,结果很少并且具有特点,暴露因素去除，情况改善，再暴露，再出现,脱发与乙肝疫苗,基因治疗,持久的媒介,媒介的结果和靶器官的毒性作用,.,基因治疗,明显改善预后,如AIDS病治疗,2026/10/17,clinical study design for postgraduate 2003,2026/10/17,clinical study design for postgraduate 2003,2026/10/17,clinical study design for postgraduate 2003,2026/10/17,clinical study design for postgraduate 2003,强,弱,2026/10/17,clinical study design for postgraduate 2003,研究目的与研究设计的选择,2026/10/17,clinical study design for postgraduate 2003,研究课题的设计,临床观察,视力差和戴眼镜似乎与缺乏胡萝卜素有关,科学理论,视紫质的形成需要胡萝卜素，视黄醛与夜间视力有关,假说,视力的好坏与进食胡萝卜的量有关,2026/10/17,clinical study design for postgraduate 2003,病例-对照研究,开始,测量对比,Case,视力差组,食胡萝卜多,过去,Control,视力好组,食胡萝卜少,食胡萝卜少,食胡萝卜多,现在,2026/10/17,clinical study design for postgraduate 2003,横断面研究,开始,测量,选定人群,视力好,视力差,胡萝卜多膳食,时点,胡萝卜少膳食,胡萝卜多膳食,胡萝卜少膳食,2026/10/17,clinical study design for postgraduate 2003,队列研究,开始,测量分类,研究人群,食多胡萝卜,食少胡萝卜,视力差,视力好,视力好,视力差,现在,视力差,测量对比结果,将来,2026/10/17,clinical study design for postgraduate 2003,随机对照,开始,随机分配,研究人群,食多胡萝卜,食少胡萝卜,视力差,视力好,视力好,视力差,现在,视力差,测量对比结果,将来,2026/10/17,clinical study design for postgraduate 2003,几点说明,所有的设计都有优缺点,选择最适合研究问题的设计,尽量避免劣势,最大限度的保证真实性和可靠性,严格地计划每一细节过程,设计,Overlap,2026/10/17,clinical study design for postgraduate 2003,References,Robert H.Fletcher ect,Clinical Epidemiology.,The essentials,RCT:,1.Pocock,S.J.,Statistical Aspects of Clinical Trial Design.The Statistican,31:1-18,1982.,2.Yusuf,S.Collins,Why do we need some large,simple randomized trial?,2026/10/17,clinical study design for postgraduate 2003,汇报结束,谢谢大家,!,请各位批评指正,