观察性研究方法设计及实例余运贤浙大医学院流行病学与统计学学科Tel ：88208191 Email ：yunxianyu@www.book118.com Induced First-Trimester Abortionand Risk of Mental Disorder Author: Munk-Olsen T, Laursen TM, Pedersen CB, Lidegaard , Mortensen PB. Journal: N Engl J Med. 2011;364(4):332-9. Published date: 2011 Jan 27 背景和目的Background ：Concern has been expressed about potential harm to women’s mental health in association with having an induced abortion ( 人工流产), but it remains unclear whether induced abortion is associated with an increased risk of subsequent psychiatric problems Aim: Assess the risk of a first psychiatric contact ( 精神症状) after first-trimester induced abortion, as compared with before the event; we also looked at the risk of a first psychiatric contact after, as compared with before, childbirth( 分娩). 研究设计(1) Study Population Data from the Danish Civil Registration System (CRS), which holds information on all Danish residents, was used to establish an underlying study population of all girls and women born in Denmark between 1962 and 1993 who were alive on their 15th birthday, for a total of 954,702 girls and women. The CRS was established in 1968, when data were recorded for all people alive and residing in Denmark. Among other variables, it includes each resident’s personal identification number (CRS number), which is assigned to all Danes ( 丹麦人) at birth or immigration, sex, date of birth, parents’CRS numbers, and daily updated information on vital status. 研究设计(2) Mental Disorders The Danish Psychiatric Central Register covers information on mental disorders in the girls and women in our study population and their parents. There are no private psychiatric hospitals in Denmark, and the register contains information of inpatient psychiatric contact (ICD-8) from 1969 and information about outpatient psychiatric contact(icd-10)from 1995. The girls and women in the study population, as well as their parents, were classified as having a mental disorder if they had records of inpatient or outpatient contact at psychiatric facilities in Denmark for any mental disorder. 研究设计(3) Induced Abortions The Danish National Register of Patients contains data on information on induced abortions of inpatients (from 1977) and outpatients (from 1995) in Denmark, except abortions performed by practicing specialists at private clinic since 2005 or later. From this register, we obtained the dates of first-trimester medical or surgical induced abortions. Girls and women with records of induced abortions before January 1, 1995, were excluded from the study to ensure that the sample included only girls and women with a first-ever abortion in the first trimester. To further ensure that all induced abortions in the study population were first-time abortions, we restricted the population to women and girls born in 1962 or later. 研究设计(4) Final Study Population and Study Design (1) Our final study population consisted of girls and women born in Denmark between 1962 and 1993 who were alive and had no history of a mental disorder, defined as inpatient psychiatric contact, 9 months before a first-ever first-trimester induced abortion or first childbirth. We excluded girls and women who were born outside Denmark and girls and women emigrating from Denmark (because of the lack of information on psychiatric admissions outside Denmark) and girls and women with records of psychiatric admission occurring before the 9-month period preceding the abortion or childbirth. Final Study Population and Study Design (2) The girls and women in the final study population were followed individually from 9 months before the first-time first-trimester induced abortion or birth of a live infant through 12 months after the event or until a psychiatric contact occurred for a first mental disorder, until death, until emigration, or until December 31, 2007 —whichever came first. We included only new psychiatric contacts, and we censored follow-up data on the date of the initial contact 问题该研究属于流行病学中的哪种研究设计类型？( 讨论) 流行病学总共有几大类科研设计方法? 观察性研究描述性研究研究特定时点或期间和特定范围内人群中的有关变量(因素)与疾病或健康状况的关系。又称描述性流行病学。指根据日常记录资料或通过特殊调查所得的资料，包括实验室检查结果。按不同地区、不同时间及不同人群特征分组，将一个社区人群疾病或健康状态分布情况进行简单描述，常常是流行病学调查的第一步，也是分析流行病学的基础。它主要描述分布的三大特征，即：地区特征、时间特征和人群特征。现况调查是一种常用的描述性研究现况研究定义：现况研究是流行病学研究方法中的一种基础性研究方法。它是按照事先设计的要求在某一人群中应用普查和抽样调查的方法收集特定时间内疾病的描述性资料，以描述疾病的分布及观察某些因素与疾病之间的关联。亦可称为横断面调查，或患病率调查。因所收集的有关因素与疾病或健康之间的资料既不是过去暴露史，又不是随访调查所得的结果，而是调查当时所获得的资料，故称它为现况研究。掌握目标群体中疾病的患病率及其分布状态。提供病因线索。利用普查或筛检可实现疾病的二级预防。确定高危人群。进行疾病监测、预防接种效果及其他资料质量的评价。现况研究的特点一般不设对照组关心的是某一特定时点或短时期内某一群体中暴露和疾病的状况或联系。不能确定暴露与疾病的因果关系。对固定的暴露因素可作因果推论。在现在暴露水平与既往变化不大或存在良好相关性；或已知其变化规律时，可用现在的暴露状态来代替或估计过去的暴露状态。定期重复可获得发病率资料现况研究的种类生态学研究定义：描述性研究的一种，从群体的水平上研究某种因素与疾病的关系，以群体为观察和分析单位，描述不同人群中某因素的暴露状况与疾病的频率，分析该暴露因素与疾病的关系。生态学研究类型：1 、比较生态学研究（ecological comparison study ）比较不同人群中某疾病或健康状态，他们的疾病率或死亡率的差别，以了解某疾病或健康状态在不同人群中分布有无异同点。从而探索该现象产生的原因，找到值得进一步深入研究的线索。2 、生态趋势研究（ecological trend study ）指连续观察不同人群中某疾病或健康状态的发生率或死亡率，了解其变动趋势。观察性研究一、基本原理以确诊患某种特定疾病的病人作为病例. 以不患该病但具有可比性的个体作为对照. 通过询问、实验室检查或复查病史，搜集既往危险因素暴露史. 测量并比较两组各因素的暴露比例，经统计学检验该因素与疾病之间是否存在统计学关联. 病例对照研究特点回顾性由果→因研究观察法不能验证病因巢式病例对照研究（1）基本原理按队列研究方式进行样本收集。选择一队列，收集基线资料，采集所研究的生物学标志的组织或体液标本储存备用；随访：随访到出现能满足病例对照研究样本量的病例数为止；巢式病例对照研究（2）匹配：按病例进入队列的时间、疾病出现时间与性别、年龄等匹配条件，从同一队列选择1个或数个非病例作对照，抽取病例与对照的基线资料并检测收集的标本资料处理：按匹配病例对照研究方法处理资料病例-队列研究基本原理研究开始时，在队列中随机选取一组样本作为对照组；观察结束时，队列中出现被研究疾病所有病例作病例组；与随机对照组进行比较；这种研究模式，可同时研究几种疾病，不同疾病有不同病例组，但对照组都是同一组随机样本病例-- 队列与巢式病例对照研究的区别对照是随机选取，不与病例进行匹配。随机对照组中成员如发生被研究疾病，既为对照，又同时为病例。1 个随机对照组可以同时和几个病例组比较分析。因果关系清楚(符合时间顺序) 资料可靠（实时记录数据）论证强度高（前瞻性队列研究设计）省时省力省钱（不需要收集典型cohort 研究那么多样本量）适合于分子流行病学研究背景：1994 年Piegorseh 、Begs 等提出遗传与环境的关系交互作用病例对照研究和队列研究的效率费用观察性研究队列研究研究对象是加入研究时未患所研究疾病的一群人，根据是否暴露于所研究的病因或暴露程度而划分为不同组别（队列），随访观察不同组别结局。暴露组的率>未暴露组的率，则可认为暴露与疾病存在联系，可能是因果联系。队列研究的类型根据研究对象进入队列的时间：固定队列动态队列根据研究设计的时间点：前瞻性队列研究(prospective cohort study) 历史性队列研究(historical cohort study ）双向性队列研究(ambispective cohort study) 主要特点观察法设立对照由因到果，符合时间顺序确证暴露和结局因果关系“Induced First-Trimester Abortion and Risk of Mental Disorder”是什么设计类型？Outcome of interest The outcome of interest was the first psychiatric contact (inpatient admission or outpatient visit) for any mental disorder. We compared the 12-month period after the abortion or childbirth with the 9-month period before the event, treating the period before the event as a separate category in analyses. For the main analyses of incidence-rate ratios, the reference category was the period from 9 to 0 months