《医学统计学》课件

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,*,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,医学统计学课件,1,Chapter 13,Design of medical research,Chapter 13,2,医学统计学课件,3,医学统计学课件,4,医学统计学课件,5,The aim of research design:,To get a reliable result in the lowest cost of manpower, time and money;,To estimate the random error within,the observed data;,To promote the efficiency of the,research,There are two kinds of research:,Laboratory experiment and Clinical trial,Medical survey,The aim of research design:,6,13.1 Principles of research design,1. Control,2. Balance,3. Randomization,4. Replication,13.1 Principles of research d,7,1. Control,If there is no control, then there is no comparison.,Others,Effect of others,Effect of treatment,Treatment,Subject,Others,Control,Effect of control,Subject,Effect of others,1. ControlOthersEffect of o,8,Some forms of control:,(1) Empty control,(2) Placebo control,(for animal, Experimental control),(3) Mutual control,(4) Self control,(5) Standard control,(6) Historical control,Some forms of control:,9,(1) Empty control,Others,Effect of others,Effect of treatment,Treatment,Subject,A,Others,Subject,B,Effect of others,(1) Empty controlOthersEffect,10,(2) Placebo control,Others,Effect of others,Effect of treatment,Treatment,Subject,A,Others,Placebo,Effect of placebo,Subject,B,Effect of others,(2) Placebo controlOthersEffec,11,(3) Mutual control,Others,Effect of others,Effect of,Treatment A,Treatment I,Subject,A,Others,Treatment II,Effect of,Treatment B,Subject,B,Effect of others,(3) Mutual controlOthersEffe,12,(4) Self control,Others,Effect of others,Effect of treatment,Treatment,Subject,Others,Control,Effect of control,Subject,Effect of others,(4) Self controlOthersEffect,13,(5) Standard control,Others,Effect of others,Effect of treatment,Treatment,Subject,There is no control group,but compare with certain “standard”,(5) Standard controlOthersEffe,14,(6) Historical control,There is no control group,but compare with “historical result”,Others,Effect of others,Effect of treatment,Treatment,Subject,(6) Historical controlThere is,15,2. Balance: The,experimental group and control group are almost the same in all aspects except the treatment.,Others,Effect of others,Effect of treatment,Treatment,Subject,Others,Control,Effect of control,Subject,Effect of others,2. Balance: The experiment,16,3. Randomization,Many factors, we know that they may influence the results, but they are very difficult to deal with Randomization is the best choice!,Example To improve the homogeneity of subjects, collect a number of students with same age and gender; randomly arrange them into two groups to make them balance in height and weight.,3. Randomization,17,Randomization is the prerequisite of,statistical inference.,Randomization,Casual,Randomization means that all subjects in population have same probability to be sampled out for research.,Randomization is the prerequis,18,4. Replication,One meaning of replication :,The results can be reproduced in different labs and by different researchers.,Another meaning of replication :,The study should be performed in a big enough sample.,Altman & Dore checked 90 papers:,39% mentioned their sample size and why.,Sample sizes of 27% papers were too small to make a conclusion.,4. Replication,19,How to estimate sample size in the design stage?,Four parameters are needed:,(1),: the maximal probability of type,error is,allowed,(2),:,the maximal probability of type,I,error is,allowed,(3), :,the minimal difference between two means is,allowed,(4), : the standard deviation among subjects in the same group,How to estimate sample size,20,Check Table 13-2, or calculate by,Example 13-1 A pilot study shows, the sample mean and,standard deviation of pulse among male patients with lead,poisoning are 67/min and 5.97/min respectively. To test,whether the population mean of this kind of patients is,lower than the mean of normal males (one-side test), how,many cases are needed? Given , take,(Check Table 13-2,/, 0.85,n,=14),1. Comparison between the mean and a given number,Check Table 13-2, or calculat,21,Check Table 13-2, or calculate by,Example 13-2 Comparing mean reductions of blood sedimentation,between drug A and B. To test whether the effects of two drugs are,different (two-side), how many cases are needed? A pilot study,shows, .,Take , .,(Check Table 13-3,/ 0.60,n,=60),2. Comparison between two means of two independent samples,Check Table 13-2, or calculate,22,3. Comparison between two frequencies of twoindependent samples,Check Table 13-4, or calculate by,Example 13-3 Comparing two chemotherapies for,lymphoma, how many cases are needed? The pilot study,shows, the remission rates are .,Given . (Check Table 13-4,n,=35),3. Comparison between two freq,23,13.2 Experimental design,Why?,To plan and arrange subject selection, treatment,assignment, data collection and statistical analysis,To make sure validity, reproducible and economy.,2. Types of research,Experiment: animal experiment, clinical trial,community intervention trial,Survey,Both need well design !,13.2 Experimental designWhy?,24,Subject:,Subject could be: gene, protein, cell, tissue, animal, patient or healthy population.,Subject should be clearly defined, and homogeneous.,Eligible,subjects,Treatment,effects,Control,3. Three elements of experimental design,EligibleTreatmenteffectsContro,25,2) Treatment:,A measure used to intervene a life process.,Treatment factor: drug,Levels of treatment factor: dose A, dose B,Treatment factor and non-treatment factors should be identified.,Non-treatment factors: age, gender, disease status,weather, environment ,Treatment should be standardized:,3) Effect:,Change caused by treatment.,Effect measurement should be objective, accurate, precise, specific and sensitive.,2) Treatment:,26,医学统计学课件,27,医学统计学课件,28,医学统计学课件,29,医学统计学课件,30,(1) Completely random design,Randomly allocate the subjects into two or more groups,Independently sampling from two or more populations,Example 13-4 Randomly allocate 10 animals,into two groups. (Using Table 13-1, read 0-9 only),A: 1, 4, 6, 8, 9 B: 2, 3, 5, 7, 10,4.Commonly used experimental designs,(1) Completely random design4.,31,Example 13-5 Randomly allocate 15 animals,into three groups.,A: 4, 6, 8, 11, 15 B: 3, 5, 9, 12, 14,C: 1, 2, 7, 10, 13,Data analysis:,t,test; rank sum test,Advantage: Simple; stable,Disadvantage: If there are many confounders,they may not be balanced by randomization only,Example 13-5 Randomly allocate,32,(2) Paired design,Example 13-6 Randomly allocate 8 pairs of,subjects into two groups (read 0-7 only, odd for AB),A: 1-1, 2-2, 3-2, 4-1, 5-2, 6-1, 7-2, 8-1; B: the rest,Data analysis: Paired,t,test; signed rank sum test,Advantage: Well control the non-treatment factors,Save sample size,Disadvantage: Difficult to perform in practice,Used for short period studies,(2) Paired design,33,(3) Random block design,Example 13-7 Four groups of subjects; four,treatments: A, B, C, D.,(3) Random block design,34,Data analysis: Analysis of variance for random block design,Advantage: The individuals in same block are quite similar so that the comparison within block is more sensitive than that between completely randomized groups.,Disadvantage: if any one individual observation is missed, the data analysis in the block will be very difficult.,Data analysis: Analysis of var,35,(4) Cross-over design,1st period wash-out 2nd period,Group 1 A none B,Group 2 B none A,Example 13-8,If there are 16 patients, then randomly allocate them into group 1 and 2 (same as Completely randomized,design).,If there are 8 pairs of patients, then randomly,allocate two subjects within each pair into group 1 and,2 (same as paired design).,(4) Cross-over design,36,Data analysis: Analysis of variance for cross-over design,Advantage:,Well control the non-treatment factors, save sample size;,Everyone receives both treatments Equity,Disadvantage:,Assume the subjects keep the same in 1,st,period and 2,nd,period - it can only be used for chronic diseases;,Wash-out period is required the treatment should be stopped during wash-out period,Data analysis: Analysis of var,37,Blinding and Placebo,Necessary for clinical trial.,Blinding (Masking) - To reduce the bias caused by,psychological effect of knowing the treatment,Single blinding: Any patient does not know what,treatment is taken.,Double blinding: Both patient and physician do not,know the treatment.,Placebo To ensure blinding,Everything should be the same to the treatment group,except that it does not contain any effective components of,the treatment.,Special skills are needed for blinding and placebo.,Blinding and PlaceboNecessary,38,13.3 Survey design,1. Survey,Observe the existing process,Without intervention,Well design,Example for surveys:,Health condition survey,Epidemiological survey,Etiologic survey,Clinical follow up survey,Sanitary survey,.,13.3 Survey design1. Survey,39,2. Design,(1) The purpose of survey, clear,(2) The population concerned, well defined.,(3),Space, time and sample size, specified,(4) Observed unit, well decided individual? Family? Class?,(5) The questionnaire, well designed,Items, carefully chosen,Language, clear and specific,Possible answers, well coded in advance,2. Design (1) The purpose o,40,(6) Data collection,Direct observation,Measurement, observation, test, count ,Interview,Form filling,Group meeting,Telephone or internet ( the response rate ?),(6) Data collectionDirect obs,41,(1) Overall survey (Complete survey),Example: National Census,To get the population parameters directly,There is no sampling error, but non-sampling error is,relatively high,(2) Sampling survey,Sampling Observation Statistical inference ,knowledge about population,Advantage: Efficient,Disadvantage: Complicate in design, implementation and analysis,3.,Classification of survey,(1) Overall survey (Complete s,42,Simple random sampling,Every individual has same probability to be sampled.,Suitable for small population.,Systematic sampling,According to the sequence of individuals, to sample subjects in a fixed interval.,When population has a sequence number ( such as ID code), it is convenient to carry out.,Methods of random sampling,Simple random samplingMet,43,Stratified sampling,The population is stratified according some factors that may influence the results of study and then the individuals in strata were randomly sampled.,Some important confounding factors could be controlled by stratified sampling.,Cluster sampling,If the individuals belong to certain unit ( such as community, school, class, city, county), we may directly sample the unit other than individuals.,Stratified samp,44,Stratified sampling,Systematic sampling,Simple random sampling,Cluster sampling,Sampling error,Stratified sampling Sa,45,(3) Typical survey (case survey),Advantage: Only a few typical subjects are observed, who well reflect the main characteristics of same kind of subjects.,Disadvantage: There is no ground for any statistical inference.,医学统计学课件,46,(4) Case-control survey (retrospective study),Good for,rare diseases,:,Outcome Exposure (Cause?),“Case”,: Patients,“Control”,: Non patients, main confounders are similar to the patients,Comparing,the frequency (or intensity) of exposure,1:1 case-control; 1:m case-control,group group case control,(4) Case-control survey (retro,47,(5) Cohort survey,(Follow-up study, prospective study),Exposure,(,Cause?) Outcome,Different groups of exposure,Comparing the outcomes of different groups:,Does different condition of exposure leads to,different outcome?,(5) Cohort survey,48,Summary,1. Commonly used Experimental Designs,Completely random design,Paired design,Random block design,Cross-over design,Summary1. Commonly used Experi,49,2. Content of Survey Design,Purpose,Population concerned,Space, time and sample size,Observed unit,Questionnaire,Data collection,2. Content of Survey Design,50,3.Classification,of survey,Overall survey,Sampling survey,Sampling error,Stratified sampling,Systematic sampling,Simple random sampling,Cluster sampling,Typical survey,Case-control survey,Cohort survey,3.Classification of survey,51,医学统计学课件,52,医学统计学课件,53,更多精品文档，请点击：, 松下幸之助,人的一生，总是难免有浮沉。不会永远如旭日东升，,55,成功人生八大心态,成功人生八大心态,56,一、成功者的心态（老板的心态）,天生赢家,为成功而生,责任,老板的心态,一、成功者的心态（老板的心态）天生赢家,57,二、学习的心态,学习是通向未来的护照,空杯归零,低头,以身作则,盗版,学到，做到，教到,二、学习的心态学习是通向未来的护照,58,三、合作的心态,环境改变人,1+1 2,雁群飞翔-合作,天时-地利-人和,三、合作的心态环境改变人,59,四、付出的心态,四、付出的心态,60,五、积极 的心态,平常心,平等心,包容心,五、积极 的心态平常心,61,六、吃苦耐劳的心态,六、吃苦耐劳的心态,62,七、坚持的心态,七、坚持的心态,63,八、感恩的心态,感恩国家、社会、董事长、推荐人伙伴,父母,另一半,子女,八、感恩的心态感恩国家、社会、董事长、推荐人伙伴,64,