流行病學課件：第7章 篩檢

1、 篩檢ScreeningStage of susceptibilityStage of Subclinical DiseaseStage of Clinical Disease Stage of Recovery,Disability, or DeathExposurePathological ChangesOnset ofSymptomsUsual Time of Diagnosis疾病自然史（Natural History of Disease）目 錄 概述 篩檢試驗的評價 篩檢效果的評價Introduction Evaluation of screening testEvaluation

2、 of effectivenessOutline篩檢是運用快速、簡便的試驗、檢查或其他方法，將健康人群中那些可能有病或缺陷，但表面健康的人、同那些可能無病者鑒別開來 Screening is defined as the use of quick and simple testing procedures to identify and separate persons who are apparently well, but who may be at risk of a disease, from those who probably do not have the disease.第一節(jié)

3、 概述IntroductionApparently Well Population to be TestedScreening TestDiagnostic TestDisease or Risk Factor PresentDisease or Risk Factor AbsentNegatives (Normal) (Persons presumed to be free of disease)Negative on screeningPositive on screen, no disease Positive on screen, disease presentPositives (a

4、bnormal)presumed tohave diseaseTreatment Intervention篩檢試驗流程圖 Flow diagram of screening test篩查方法的評價與選擇程序 Procedures of evaluation and selection for screening test 金標準 (gold standard)目標人群Targetpopulation病人Patient非病人Non-patient待評價篩查方法Screening to be evaluated評價指標Evaluation indicator篩檢試驗Screening test 識

5、別健康人群中未被發(fā)現(xiàn)的某病患者或可疑患者，或高危個體Screening is the detection of patients, suspected patient and high risk of the disease in healthy population篩檢試驗Screening test 問卷、常規(guī)體格檢查、物理學檢查、實驗室檢驗、分子生物學技術(shù)Questionnaire, routine physical examination, physical examination, laboratory tests, molecular biology techniques根據(jù)所用的

6、篩檢方法的數(shù)量多少單項篩檢多項篩選篩檢的分類Categories of screeningBased on the on the quantity of screening methodsSingle screening Multiple screening根據(jù)篩檢對象的范圍不同人群篩檢 目標篩檢篩檢的分類Categories of screeningBased on the scope of screening subjects Mass screening Targeted screening 簡單性 廉價性 快速性 安全性 可接受性篩檢試驗應具備五個特征Five characterist

7、ics that screening test should have Simple Cheap Quick Safe Acceptable一級預防 二級預防疾病的自然史流行病學檢測 篩檢的目的 Primary prevention Secondary prevention Natural history of disease Epidemiological surveillance Purposes of screening篩檢的疾病是當?shù)匾粋€重大的公共衛(wèi)生問題具備有效的治療或預防方法應用篩檢的原則 Principles for the application of screeningThe

8、 disease being screened should be a major problemAcceptable treatment or prevention methods should be available for individuals with diseases discovered in the screening process. 有進一步確診的方法與條件該病的自然史明確A suitable and effective test or examination for the disease should be available The natural history

9、of the disease should be adequately understood應用篩檢的原則 Principles for the application of screening該病具有較長的潛伏期或領(lǐng)先時間預期有良好的篩檢效益The disease should have a recognizable course, with early and latent states of the disease being identifiableExpected good efficiency of screening should be available應用篩檢的原則 Prin

10、ciples for the application of screening倫理學問題Ethical Issues 尊重個人意愿 Respect for persons will 有益無害 Useful and harmless 公正 Fairness一、篩檢試驗的評價方法 （Evaluation methods）確定金標準 (Determine Gold Standard)選擇研究對象 (Chose Study Subjects)樣本量的估計 (Estimate Sample Size) 整理評價結(jié)果 (Sort out evaluation result)第二節(jié) 篩檢試驗的評價Evalu

11、ation of Screening test金 標 準所謂“金標準”是指當前臨床醫(yī)學界公認的診斷疾病的最可靠方法Gold StandardThe best available test that is universally recognized by clinical medical circles is called the GOLD STANDARD . 病例組 納入各種類型的病人 對照組 最好選擇需要與研究疾病鑒別的其他病人，即所選擇的對照組與病例組具有許多相似的條件研究對象 Study Subjects Case group Include appropriate spectrum

12、 of patients Control group Need to be distinguished to the disease studied, that is the control has co-morbid conditions with case樣 本 量 Sample Size 影響樣本量的因素待評價篩檢試驗的靈敏度待評價篩檢試驗的特異度顯著性水平（）允許誤差（d） Factors determine sample sizeSensitivity of screening to be evaluated Specificity of screening to be evalua

13、ted Significance level（）Allowable error（d）當待評價篩檢試驗的靈敏度和特異度均接近50Both sensitivity and specificity of screening to be evaluated approach 50%n: the number of abnormal (diseased) or normal (healthy) patients in the study.: admissible error. P: the estimation of sensitivity and specificity for testing. ua

14、 : the u value for the cumulative probability equal to a/2. 當待評價篩檢試驗的靈敏度和特異度小于20%或大于80%Both sensitivity and specificity of screening to be evaluated less than 20% or greater than 80%本來有病，被篩檢為陽性本來有病，被篩檢為陰性本來無病，被篩檢為陽性本來無病，被篩檢為陰性評價結(jié)果 Evaluation Results評價結(jié)果 Evaluation ResultsDisease Status (Gold Standar

15、d)+-TestResult+Have disease,test positivea (TP)Free of disease, test positiveb (FP)TestPositive-Have disease, test negativec (FN)Free of disease, test negatived (TN)TestNegativeHave diseaseFree of disease 真實性（validity） 可靠性（reliability） 預測值（predictive value）二、篩檢試驗的評價指標Evaluation Index靈敏度（sensitivity）

16、假陰性率（false negative rate）篩檢試驗(screening)金標準(gold standard)合計(total)患者(patient)非患者(non-patient)陽性(positive)真陽性(TP) A假陽性(FP) BR1陰性(negative)假陰性(FN) C真陰性(TN) DR2合計(total)C1C2N真實性（validity）False Negative Rate Likelihood of a negative result when patient actually has diseaseFalse NegativesSensitivityFals

17、e NegativesSensitivity Likelihood of a negative result when patient actually has diseaseFalse Negative Rate False negative rate increases with decreased sensitivitySensitivityFalse NegativesFalse Negative Rate Likelihood of a negative result when patient actually has disease特異度（specificity）假陽性率（fals

18、e positive rate）篩檢試驗(screening)金標準(gold standard)合計(total)患者(patient)非患者(non-patient)陽性(positive)真陽性(TP) A假陽性(FP) BR1陰性(negative)假陰性(FN) C真陰性(TN) DR2合計(total)C1C2N真實性（validity）False Positive Rate Likelihood of a positive result when patient does not have the diseaseFalse PositivesSpecificityFalse Po

19、sitive Rate Likelihood of a positive result when patient does not have the diseaseFalse PositivesSpecificityFalse Positive Rate Likelihood of a positive result when patient does not have the disease False positive rate increases with decreased specificitySpecificityFalse Positives正確指數(shù)（Youdens index）

20、 （特異度靈敏度）1 1（假陽性率假陰性率）真實性（validity）篩檢試驗(screening)金標準(gold standard)合計(total)患者(patient)非患者(non-patient)陽性(positive)真陽性(TP) A假陽性(FP) BR1陰性(negative)假陰性(FN) C真陰性(TN) DR2合計(total)C1C2N陽性似然比(positive likelihood ratio，LR）陰性似然比(negative likelihood ratio，LR） 真實性（validity）篩檢試驗(screening)金標準(gold standard)合

21、計(total)患者(patient)非患者(non-patient)陽性(positive)真陽性(TP) A假陽性(FP) BR1陰性(negative)假陰性(FN) C真陰性(TN) DR2合計(total)C1C2N真實性（validity）篩檢試驗(screening)金標準(gold standard)合計(total)患者(patient)非患者(non-patient)陽性(positive)真陽性(TP) A假陽性(FP) BR1陰性(negative)假陰性(FN) C真陰性(TN) DR2合計(total)C1C2N 一致率（agreement rate），符合率一致率

22、真實性（validity）篩檢試驗(screening)金標準(gold standard)合計(total)患者(patient)非患者(non-patient)陽性(positive)真陽性(TP) A假陽性(FP) BR1陰性(negative)假陰性(FN) C真陰性(TN) DR2合計(total)C1C2N取值范圍：-1和1之間Range: between -1 and +1 Kappa值判斷標準Kappa值一致性強度0弱00.2輕0.210.40尚好0.410.60中度0.610.80高度0.811最強Kappa值 = 實際一致性/非機遇一致性觀察一致性(Observation

23、consistency) 機遇一致性(Opportunity consistency) 非機遇一致性(Non-opportunity consistency)實際一致性(Actral consistency)真實性（validity）篩檢試驗(screening)金標準(gold standard)合計(total)患者(patient)非患者(non-patient)陽性(positive)真陽性(TP) A假陽性(FP) BR1陰性(negative)假陰性(FN) C真陰性(TN) DR2合計(total)C1C2N標準差與變異系數(shù) coefficient of variance，CV符

24、合率（agreement rate）Agreement rateScreening test 2Screening test 1TotalPositiveNegativePositiveABR1NegativeCDR2TotalC1C2N可靠性（reliability） 影響可靠性的因素 Determinants of reliability Biological variations of subjectsVariations in different observersVariations in different lab condition受試對象生物學變異觀察變異實驗室條件陽性預測值(

25、positive predictive value) 陰性預測值(negative predictive value) Screening testGold standardTotalPatientNon-patientPositiveTrue Positive AFalse Positive BR1Negative False Negative CTrue Negative DR2TotalC1C2N預測值（predictive value）靈敏度、特異度、患病率與預測值的關(guān)系Relationship between sensitivity, specificity, prevalence

26、and predict value sensitivity and specificity in different blood sugar level blood sugar SN SP blood sugar SN SP（mg/100ml） （） （） （mg/100ml） （） （ ） 80 100.0 1.2 150 64.3 96.1 90 98.6 7.3 160 55.7 98.6 100 97.1 25.3 170 52.9 99.6 110 92.9 48.4 180 50.0 99.8 120 88.6 68.2 190 44.3 99.8 130 81.4 82.4 20

27、0 37.1 100.0 140 74.3 91.2Relationship between sensitivity and specificity靈敏度與特異度的關(guān)系非病人病人某項診斷標準的數(shù)值截斷點Threshold三、篩檢試驗截斷值的確定Determination of screening cut-off point 理想情況Ideal situation人數(shù)NumberNormalDisease非病人Normal病人Abnormal某項診斷標準的數(shù)值Cut-off三、篩檢試驗截斷值的確定Determination of screening cut-off point 實際情況Actua

28、l situation人數(shù)PopulationNumber of personsMeasurementScreening tests use an arbitrary cut-off to separate two populations (normal vs. abnormal)Normal AbnormalacbdNormal acdbNumberMeasurementWhere cut-off is placed determines sensitivity and specificityScreening tests use an arbitrary cut-off to separa

29、te two populations (normal vs. abnormal)NumberMeasurementWhere cut-off is placed determines sensitivity and specificityNormalAbnormalFew False NegativesHigh Sensitivity- result+ resultScreening tests use an arbitrary cut-off to separate two populations (normal vs. abnormal)NumberMeasurementWhere cut

30、-off is placed determines sensitivity and specificityNormalAbnormalFew False PositivesHigh Specificity- result+ resultScreening tests use an arbitrary cut-off to separate two populations (normal vs. abnormal)NumberMeasurementWhere cut-off is placed determines sensitivity and specificityNormalAbnorma

31、lTrade off between False and False +- result+ resultScreening tests use an arbitrary cut-off to separate two populations (normal vs. abnormal)NumberMeasurementTest with High SensitivityNormalAbnormalA negative result allows you to rule-out whatever you are testing - result+ resultSnNoutScreening tes

32、ts use an arbitrary cut-off to separate two populations (normal vs. abnormal)NumberMeasurementTest with High SpecificityNormalAbnormalA positive result allows you to rule-in whatever you are testing - result+ resultSpPinScreening tests use an arbitrary cut-off to separate two populations (normal vs.

33、 abnormal)用真陽性率和假陽性率作圖得出的曲線，可用于確定篩檢試驗的截斷值。A receiver operating characteristic (ROC), or simply ROC curve, is a graphical is a graphical plot of the sensitivity, or true positives, vs. (1 specificity), or false positives, for a binary classifier system as its discrimination threshold is varied. 受試者工作

34、特性曲線 Receiver operator characteristic curve, ROC特異度血糖測定診斷糖尿病的ROC曲線截斷點Cutoff pointROC curve for diagnosis of diabetes using blood glucose第三節(jié) 篩檢效果評價 Evaluation of effectiveness一、收益選擇患病率高的人群選用高靈敏度的篩檢試驗采用聯(lián)合試驗串聯(lián)并聯(lián)YieldTo select the population with high prevalence rate To select the test with high sensitivity To design a combine test Series testParallel test二、篩檢的生物學效果評價Biological effectiveness evaluation病死率、死亡率、生存率篩檢組Screened group未篩檢組Unscreened group比較Fatality rate、mortality rate、survival rate三、篩檢的衛(wèi)生經(jīng)濟學效果評價Health-economic effectiveness evaluation 成本效果分析 Cost-effectiveness analysis 成本效益分析