实验设计和调查设计.ppt

Chapter 13 Design of medical research,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,13.1 Principles of research design,1.Control 2.Balance 3.Randomization 4.Replication,1.ControlIf there is no control,then there is no comparison.,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,(1)Empty control,(2)Placebo control,(3)Mutual control,(4)Self control,(5)Standard control,There is no control group,but compare with certain“standard”,(6)Historical control,There is no control group,but compare with“historical result”,2.Balance:The experimental group and control group are almost the same in all aspects except the treatment.,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.,Randomization is the prerequisite of statistical inference.Randomization CasualRandomization means that all subjects in population have same probability to be sampled out for research.,4.ReplicationOne 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.,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,Check Table 13-2,or calculate byExample 13-1 A pilot study shows,the sample mean andstandard deviation of pulse among male patients with leadpoisoning are 67/min and 5.97/min respectively.To testwhether the population mean of this kind of patients islower than the mean of normal males(one-side test),howmany 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 calculate byExample 13-2 Comparing mean reductions of blood sedimentationbetween drug A and B.To test whether the effects of two drugs aredifferent(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,3.Comparison between two frequencies of twoindependent samples,Check Table 13-4,or calculate byExample 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),13.2 Experimental design,Why?To plan and arrange subject selection,treatmentassignment,data collection and statistical analysis To make sure validity,reproducible and economy.2.Types of researchExperiment:animal experiment,clinical trial,community intervention trial Survey Both need well design!,Subject:Subject could be:gene,protein,cell,tissue,animal,patient or healthy population.Subject should be clearly defined,and homogeneous.,Eligiblesubjects,Treatment,effects,Control,3.Three elements of experimental design,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.,(1)Completely random designRandomly allocate the subjects into two or more groupsIndependently sampling from two or more populationsExample 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,Example 13-5 Randomly allocate 15 animals into three groups.A:4,6,8,11,15 B:3,5,9,12,14 C:1,2,7,10,13Data analysis:t test;rank sum testAdvantage:Simple;stableDisadvantage:If there are many confounders,they may not be balanced by randomization only,(2)Paired designExample 13-6 Randomly allocate 8 pairs ofsubjects 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 restData 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,(3)Random block designExample 13-7 Four groups of subjects;fourtreatments:A,B,C,D.,Data analysis:Analysis of variance for random block designAdvantage: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.,(4)Cross-over design,1st period wash-out 2nd periodGroup 1 A none BGroup 2 B none AExample 13-8 If there are 16 patients,then randomly allocate them into group 1 and 2(same as Completely randomizeddesign).If there are 8 pairs of patients,then randomly allocate two subjects within each pair into group 1 and 2(same as paired design).,Data analysis:Analysis of variance for cross-over designAdvantage:Well control the non-treatment factors,save sample size;Everyone receives both treatments EquityDisadvantage:Assume the subjects keep the same in 1st period and 2nd period-it can only be used for chronic diseases;Wash-out period is required the treatment should be stopped during wash-out period,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.,13.3 Survey design,1.Survey Observe the existing process Without intervention Well designExample for surveys:Health condition survey Epidemiological survey Etiologic survey Clinical follow up survey Sanitary survey.,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,(6)Data collection,Direct observation Measurement,observation,test,count Interview Form filling Group meeting Telephone or internet(the response rate?),(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,Simple random samplingEvery individual has same probability to be sampled.Suitable for small population.Systematic samplingAccording 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,Stratified samplingThe 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 samplingIf the individuals belong to certain unit(such as community,school,class,city,county),we may directly sample the unit other than individuals.,Stratified sampling Systematic sampling Simple random sampling Cluster sampling,Sampling error,(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.,(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,(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?,Summary,1.Commonly used Experimental Designs Completely random design Paired design Random block design Cross-over design,2.Content of Survey Design Purpose Population concerned Space,time and sample size Observed unit Questionnaire Data collection,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,