診斷性試驗的設(shè)計與評價研究生-3節(jié)課

1、診斷性試驗的分診斷性試驗的分析與評價析與評價四川大學(xué)華西醫(yī)院四川大學(xué)華西醫(yī)院實驗醫(yī)學(xué)科實驗醫(yī)學(xué)科秦秦 莉莉2一、定義一、定義v對疾病進(jìn)行診斷的試驗方法，即稱為診對疾病進(jìn)行診斷的試驗方法，即稱為診斷性試驗。斷性試驗。診斷性試驗不僅包括實驗室檢查，還包括病診斷性試驗不僅包括實驗室檢查，還包括病史、體檢結(jié)果、影象學(xué)檢查、各種公認(rèn)的診史、體檢結(jié)果、影象學(xué)檢查、各種公認(rèn)的診斷標(biāo)準(zhǔn)等。斷標(biāo)準(zhǔn)等。3診斷性試驗的應(yīng)用診斷性試驗的應(yīng)用1.1.診斷疾病診斷疾病2.2.篩檢無癥狀病人篩檢無癥狀病人3.3.疾病的隨訪疾病的隨訪4.4.判斷疾病的嚴(yán)重性判斷疾病的嚴(yán)重性5.5.估計疾病的臨床過程極其預(yù)后估計疾病的臨床過程

2、極其預(yù)后6.6.估計對治療的反應(yīng)估計對治療的反應(yīng)7.7.測定目前對治療的實際反應(yīng)測定目前對治療的實際反應(yīng)4二、評價診斷性試驗的條件二、評價診斷性試驗的條件v1.1.標(biāo)準(zhǔn)診斷：標(biāo)準(zhǔn)診斷： 疾病的診斷，必須有標(biāo)準(zhǔn)診斷（即金標(biāo)準(zhǔn)疾病的診斷，必須有標(biāo)準(zhǔn)診斷（即金標(biāo)準(zhǔn), , gold standardgold standard，或參考標(biāo)準(zhǔn)，或參考標(biāo)準(zhǔn)，reference reference standardstandard）。標(biāo)準(zhǔn)診斷是目前公認(rèn)的診斷方）。標(biāo)準(zhǔn)診斷是目前公認(rèn)的診斷方法，如：活檢、手術(shù)、尸檢、特殊檢查或長法，如：活檢、手術(shù)、尸檢、特殊檢查或長期隨訪的結(jié)果期隨訪的結(jié)果5二、評價診斷性試驗的條

3、件二、評價診斷性試驗的條件v2.2.診斷方法的對比：診斷方法的對比：評價新的診斷性試驗，必須與標(biāo)準(zhǔn)診斷方法進(jìn)行評價新的診斷性試驗，必須與標(biāo)準(zhǔn)診斷方法進(jìn)行比較。比較。新的診斷性試驗，應(yīng)該具備方法更為簡便、更為新的診斷性試驗，應(yīng)該具備方法更為簡便、更為可靠或者減少危險、減少創(chuàng)傷、節(jié)約費(fèi)用等優(yōu)點，可靠或者減少危險、減少創(chuàng)傷、節(jié)約費(fèi)用等優(yōu)點，這樣的診斷性試驗才具有推廣意義。這樣的診斷性試驗才具有推廣意義。6二、評價診斷性試驗的條件二、評價診斷性試驗的條件v3.3.列出四格表列出四格表標(biāo)準(zhǔn)診斷標(biāo)準(zhǔn)診斷有病有病無病無病診斷性試驗診斷性試驗+ +a a( (真陽性真陽性) )b b( (假陽性假陽性) )-

4、 -c c( (假陰性假陰性) )d d( (真陰性真陰性) )7所評價的資料應(yīng)能列出四格表，方法如下所評價的資料應(yīng)能列出四格表，方法如下用標(biāo)準(zhǔn)診斷方法，診斷的病例數(shù)為用標(biāo)準(zhǔn)診斷方法，診斷的病例數(shù)為 a+ca+c在有病的受試者中，診斷性試驗陽性者為在有病的受試者中，診斷性試驗陽性者為 a a，陰性者為陰性者為 c c用標(biāo)準(zhǔn)診斷方法，判斷無該病的例數(shù)為用標(biāo)準(zhǔn)診斷方法，判斷無該病的例數(shù)為 b+db+d無該病的受試者中，診斷性試驗陽性例數(shù)為無該病的受試者中，診斷性試驗陽性例數(shù)為 b b，陰性例數(shù)為，陰性例數(shù)為 d d 從評價的資料中，不能繪制四格表的診斷性試從評價的資料中，不能繪制四格表的診斷性試驗

5、，無法進(jìn)行評價驗，無法進(jìn)行評價8三、評價診斷性試驗的常用指標(biāo)三、評價診斷性試驗的常用指標(biāo)v1.1.評價指標(biāo)評價指標(biāo)1)1)敏感度（敏感度（sensitivitysensitivity）：經(jīng)金標(biāo)準(zhǔn)確診有病的）：經(jīng)金標(biāo)準(zhǔn)確診有病的人中，診斷性試驗陽性者所占的比例。人中，診斷性試驗陽性者所占的比例。 SEN = a /SEN = a /（ a+ca+c）2)2)特異度（特異度（specificityspecificity）：經(jīng)金標(biāo)準(zhǔn)診斷確定為）：經(jīng)金標(biāo)準(zhǔn)診斷確定為無該病的人中，診斷性試驗陰性所占的比例。無該病的人中，診斷性試驗陰性所占的比例。 SPE = d /SPE = d /（b+db+d）93

6、)3)準(zhǔn)確性（準(zhǔn)確性（accuracyaccuracy）：經(jīng)診斷性試驗檢查后）：經(jīng)診斷性試驗檢查后真陽性與真陰性占總例數(shù)的比例。真陽性與真陰性占總例數(shù)的比例。 ACC =ACC =（a+da+d）/ /（a+b+c+da+b+c+d）4)4)陽性預(yù)測值（陽性預(yù)測值（positive predictive positive predictive valuevalue）：診斷性試驗陽性的人中有病的人）：診斷性試驗陽性的人中有病的人數(shù)所占的比例。（即診斷性試驗陽性時，患數(shù)所占的比例。（即診斷性試驗陽性時，患病的可能性病的可能性, ,即陽性結(jié)果的即陽性結(jié)果的驗后概率驗后概率） +PV = a /+PV

7、 = a /（a+ba+b）5)5)陰性預(yù)測值（陰性預(yù)測值（negative predictive negative predictive valuevalue）：診斷性試驗陰性的人中，無該?。涸\斷性試驗陰性的人中，無該病的人數(shù)所占的比例。（即診斷性試驗陰性時，的人數(shù)所占的比例。（即診斷性試驗陰性時，不患該病的可能性）不患該病的可能性） -PV = d /-PV = d /（c+dc+d）106)6)患病率（患病率（prevalenceprevalence）：）： PREV =PREV =（a+ca+c）/ /（a+b+c+da+b+c+d）7)7)陽性似然比（陽性似然比（positive

8、likelihood ratiopositive likelihood ratio）：有）：有病者診斷性試驗陽性的概率與無病者試驗陽性的病者診斷性試驗陽性的概率與無病者試驗陽性的概率之比。概率之比。 +LR = a /+LR = a /（a+ca+c） / b / / b /（b+db+d） = =SenSen/ /（1-Spe1-Spe）8)8)陰性似然比（陰性似然比（negative likelihood rationegative likelihood ratio）：有）：有病者試驗陰性的概率和無病者試驗陰性的概率之病者試驗陰性的概率和無病者試驗陰性的概率之比。比。-LR = c /-L

9、R = c /（a+ca+c） / d / / d /（b+db+d） = =（1-Sen1-Sen）/ Spe/ Spe11LRLR：有病者得出某一試驗結(jié)果的概率與無病者得出該試驗結(jié)果的：有病者得出某一試驗結(jié)果的概率與無病者得出該試驗結(jié)果的概率之比。表示一個診斷試驗結(jié)果出現(xiàn)在有病者和出現(xiàn)在無病概率之比。表示一個診斷試驗結(jié)果出現(xiàn)在有病者和出現(xiàn)在無病者的可能性比值大小，代表了一個診斷性試驗區(qū)分有病和無病者的可能性比值大小，代表了一個診斷性試驗區(qū)分有病和無病的能力大小。的能力大小。LRLR越大，患病可能性越大越大，患病可能性越大12舉例舉例An Oxfordshire (England) grou

10、p of clinical investigators invited general practitioners in their area “to refer patients with suspected heart failure to our clinic.” Once there, these 126 patients underwent independent, blind BNP measurements and echocardiography. The first set of results from that study is shown in Table13Perfo

11、rmance of B-type Natriuretic Peptide 18 pg/mLPerformance of B-type Natriuretic Peptide 18 pg/mL As a As a diagnostic test for left ventricular dysfunctiondiagnostic test for left ventricular dysfunction141.You can calculate the proportion of patients with LVD who also have elevated BNP. （敏感度）（敏感度）a/

12、(a + c) = 35/40 = 0.88, or 88%“positivity in the presence of the target disorder” is Sensitivity.2.You can calculate the proportion of patients who are free of LVD who also have normal BNP. （特異度）（特異度）d/(b + d) = 29/86 = 0.34, or 34% “negativity in the absence of the target disorder” is Specificity.1

13、53.You can calculate the proportion of patients with elevated BNP who also have LVD. a/(a + b) = 35/92 = 0.38, or 38% “presence of the target disorder among positives” is Positive Predictive Value (PPV).Another term to express this value is the Post-test Likelihood given a Positive Test Result（陽性結(jié)果驗

14、后概率）（陽性結(jié)果驗后概率）4.You can calculate the proportion of patients with normal BNP who also are free of LVD. d/(c + d) = 29/34 = 0.85, or 85% “absence of the target disorder among negatives” as Negative Predictive Value (NPV).Clinicians more commonly think in terms of the post-test likelihood given a nega

15、tive result.（陰性結(jié)果驗后概率）（陰性結(jié)果驗后概率） 165.You can calculate the proportion of patients with LVD before you even measure their BNP. (a + c)/(a + b + c + d) = 40/126 = 0.32, or 32%By convention, we refer to that “pre-test probability of the target disorder” in the total population at risk (not considering

16、any additional diagnostic information) as PrevalencePrevalence, because it describes the prevailing rate of the target disorder in the patients who are undergoing the diagnostic test. 17驗前概率、驗后概率、患病率驗前概率、驗后概率、患病率v驗前概率：患者沒有進(jìn)行診斷性試驗時的患驗前概率：患者沒有進(jìn)行診斷性試驗時的患病概率病概率v驗后概率：根據(jù)患者診斷性試驗結(jié)果，結(jié)合驗后概率：根據(jù)患者診斷性試驗結(jié)果，結(jié)合驗前概率

17、推測的患病概率驗前概率推測的患病概率v患病率患病率= =驗前概率驗前概率186.You can calculate the odds that a patient has LVD before you ever measure their BNP. Pre-test odds（驗前比）（驗前比）= Pre-test Probability (100% Pre-test Probability) = 32%/(100% 32%)= 32%/68%= 0.47By convention, we refer to this as Pre-test Odds.And you can convert a

18、n odds back into a probability. Probability=odds/(odds + 1) = 0.47/1.47 = 0.32, or 32%197.You can calculate the likelihood that an elevated BNP is found in patients with, as opposed to patients without, LVD. a/(a + c)/b/(b + d) = Sensitivity/(100% Specificity)= 88%/(100% 34%)= 88%/66%= 1.3By convent

19、ion, we refer to that as a Likelihood Ratio of a positive test (some prefer to call it a Positive Likelihood Ratio).208.You can calculate the likelihood that a normal BNP is found in patients with, as opposed to patients without, LVD. c / (a + c) / d / (b + d) = (100% Sensitivity)/Specificity= (100%

20、 88%)/34%= 12%/34%= 0.4.By convention, we refer to that as a Likelihood Ratio of a negative test (some prefer to call it a Negative Likelihood Ratio).219.You can discover that if you multiply the Pre-test Odds（驗前比）（驗前比）from the population studied by the LR of a positive test result and convert the r

21、esulting Post-test Odds（驗后比）（驗后比） back to a probability, it is identical to the +PV. 驗后比驗后比 = 驗前比驗前比似然比（似然比（Pre-test odds x LR） = 0.47 x 1.3= 0.61and驗后概率驗后概率 = 驗后比驗后比/(1+驗后比驗后比) =0.61/1.61 = 0.38, or 38%(the same as you calculated in no. 3 above).2210. 陰性似然比陰性似然比(-LR)驗前比得到陰性結(jié)果的驗后比，可用公驗前比得到陰性結(jié)果的驗后比，可

22、用公式將此驗后比轉(zhuǎn)化為驗后概率，即陰性結(jié)果的驗后概率。式將此驗后比轉(zhuǎn)化為驗后概率，即陰性結(jié)果的驗后概率。Pre-test odds（-LR） = 0.47 x 0.4 = 0.19and0.19/1.19 = 0.15, or 15% (陰性結(jié)果驗后概率）陰性結(jié)果驗后概率）and100% 15% = 85%（陰性預(yù)測值）（陰性預(yù)測值）(the same as you calculated in no. 4 above).陰性結(jié)果的驗后概率陰性結(jié)果的驗后概率=100% (-PV)23You may have noticed that we havent introduced the terms

23、“true-positive rate” and “false-positive rate.” This is because weve found inconsistencies in their construction. Sure, the obvious numerator in a “false-positive” rate is cell b of Table 81, but what should we use for its denominator? Weve encountered three different denominators. Some folks insert

24、 (b+d) for its denominator, creating a number equal to (1-specificity); others use (a+b), creating a number equal to (1-PPV); and weve even encountered folks using (a+b+c+d) for its denominator, telling us the percentage of false-positive results in the entire study population. These are ambiguous t

25、erms and we wont use them here.24真陽性率、真陰性率、假陽性率、假陰性率真陽性率、真陰性率、假陽性率、假陰性率盡管臨流學(xué)家不提倡用上述說法，但很多盡管臨流學(xué)家不提倡用上述說法，但很多文獻(xiàn)仍然使用上述說法，目前公認(rèn)的定義如文獻(xiàn)仍然使用上述說法，目前公認(rèn)的定義如下：下：真陽性率真陽性率= =敏感度敏感度真陰性率真陰性率= =特異度特異度假陽性率假陽性率=1=1特異度特異度假陰性率假陰性率=1=1敏感度敏感度25vIf you apply these rules-of-thumb to BNP and LVD, youd conclude that this diag

26、nostic test had a good sensitivity (88%) and -PV (85%), but that its poor specificity (34%) dragged down its +PV (38%) and its +LR (1.3), and led to an -LR (0.4) that was almost as useless as the +LR. In fact, its +PV or post-test probability (38%) was only slightly higher than its pre-test probabil

27、ity or prevalence (34%). And thats the way it was reported. These investigators concluded, “introducing routine measurement (of BNP) would be unlikely to improve the diagnosis of symptomatic (LVD) in the community.”26vHowever, their report also documented the effect of two other cut-points for BNP.

28、This led both to a counter claim on the usefulness of BNP in the subsequent letters to the editor and to an opportunity for us to describe some alternative ways of presenting information about the accuracy of a diagnostic test. When we applied a higher cut-point for a positive BNP test (75 rather th

29、an 18 in the original report) we could construct the following table27SenSen=26/40=0.65=26/40=0.65SpeSpe=75/86=0.87=75/86=0.87+LR=5.08+LR=5.0828vMultilevel Likelihood Ratios（多水平似然比）（多水平似然比）Because the authors of the BNP study presented their results for two other cutoffs (10 pg/mL and 76 pg/mL), you

30、 can divide their test results into three groups ( 75). Although you cant any longer describe these results with binary measures like sensitivity and specificity, you can make great use of “multilevel” LRs. That is, you can describe, for any level of the test result, the likelihood that that level w

31、ould be observed in a patient with, as opposed to one without, the target disorder. 2930You can easily apply the LR for a test result to any prevalence (pre-test odds) of the target disorder. Suppose a patient has a pre-test probability of 50% (a pre-test odds of 1:1). You can simply multiply that p

32、atients pre-test odds (say, 1:1) by the LR for that patients test result (say, 80 pg/mL, with an LR of 5.1). This generates a post-test odds of 5.1, which you can convert into a post-test probability by solving 5.1/(1+5.1). This yields a posttest probability of 84%, which is much higher than you wou

33、ld generate with the cutoff of 10 pg per mL. For the latter case, you multiply 11.3 and get a post-test probability of LVD of only 1.3/2.3=0.56 or 56%31v2.2.診斷性試驗指標(biāo)的臨床意義診斷性試驗指標(biāo)的臨床意義穩(wěn)定的指標(biāo)：敏感性、特異性、穩(wěn)定的指標(biāo)：敏感性、特異性、LRLR、LRLR（是最重要的指標(biāo)）（是最重要的指標(biāo)） 相對穩(wěn)定的指標(biāo)：準(zhǔn)確性相對穩(wěn)定的指標(biāo)：準(zhǔn)確性不穩(wěn)定的指標(biāo)：陽性預(yù)測值、陰性預(yù)測值、不穩(wěn)定的指標(biāo)：陽性預(yù)測值、陰性預(yù)測值、患病率

34、患病率 32不穩(wěn)定指標(biāo)及其影響因素不穩(wěn)定指標(biāo)及其影響因素 現(xiàn)舉例說明不穩(wěn)定指標(biāo)及其影響因素：某地運(yùn)動現(xiàn)舉例說明不穩(wěn)定指標(biāo)及其影響因素：某地運(yùn)動員有胸前區(qū)疼痛史者例，分別作運(yùn)動心員有胸前區(qū)疼痛史者例，分別作運(yùn)動心電圖及冠狀動脈造影，結(jié)果如下：電圖及冠狀動脈造影，結(jié)果如下： 冠狀動脈狹窄冠狀動脈狹窄75%75%（金標(biāo)準(zhǔn)）（金標(biāo)準(zhǔn)） 是是 否否運(yùn)動心電圖運(yùn)動心電圖 + 55+ 55（a a） 7 7（b b） 6262 - 49 - 49（c c） 8484（d d） 133133 104 91 195 104 91 19533vSEN=a/(a+c)=55/104=53%SEN=a/(a+c)=5

35、5/104=53%vSPE=d/(b+d)=84/91=92%SPE=d/(b+d)=84/91=92%vACC=(a+d)/(a+b+c+d)=55+84/195=71%ACC=(a+d)/(a+b+c+d)=55+84/195=71%v+PV=a/(a+b)=55/62=89%+PV=a/(a+b)=55/62=89%v-PV=d/(c+d)=84/133=63%-PV=d/(c+d)=84/133=63%vPREVPREV（冠狀動脈狹窄）（冠狀動脈狹窄）=(a+c)/(a+b+c+d)=104/195=53%=(a+c)/(a+b+c+d)=104/195=53%v+LR=SEN/(1-

36、SPE)=0.53/+LR=SEN/(1-SPE)=0.53/（1-0.921-0.92）=6.6=6.6v-LR=(1-SEN)/SPE=(1-0.53)/0.92=0.51-LR=(1-SEN)/SPE=(1-0.53)/0.92=0.51v陽性率陽性率=(a+b)/(a+b+c+d)=62/195=31%=(a+b)/(a+b+c+d)=62/195=31%34如果擴(kuò)大檢查范圍，將該地全體運(yùn)動員均如果擴(kuò)大檢查范圍，將該地全體運(yùn)動員均作上述檢查，結(jié)果如下：作上述檢查，結(jié)果如下： 冠狀動脈狹窄冠狀動脈狹窄 是是 否否運(yùn)動心電圖運(yùn)動心電圖 55(a) 42(b) 55(a) 42(b) 979

37、7 49(c)49(c)478(d)478(d)527527 104104520520 624624 35vSEN=55/104=53%SEN=55/104=53%（不變）（不變）vSPE=478/520=92%SPE=478/520=92%（不變）（不變）vACC=(55+478)/624=85%ACC=(55+478)/624=85%（增加，個百（增加，個百分點）分點）v+PV=55/97=57%+PV=55/97=57%（下降，個百分點）（下降，個百分點）v-PV=478/527=91%-PV=478/527=91%（增加，個百分點）（增加，個百分點）vPREV=104/624=17%P

38、REV=104/624=17%（原為）（原為）v+LR=0.53/+LR=0.53/（1-0.921-0.92）=6.6=6.6（不變）（不變）v-LR=-LR=（1-0.531-0.53）/0.92=0.51/0.92=0.51（不變）（不變）v陽性率陽性率=97/624=15%=97/624=15%（下降，個百分點）（下降，個百分點）36結(jié)果解釋結(jié)果解釋PREV 的下降是由于擴(kuò)大了檢查范圍，被的下降是由于擴(kuò)大了檢查范圍，被檢人群中，患病者例數(shù)減少所致。檢人群中，患病者例數(shù)減少所致。隨著隨著PREV的下降，、的下降，、，而，而、陽性率、陽性率。SEN、SPE、LR、LR、穩(wěn)定不變。、穩(wěn)定不變

39、。v在評價診斷性試驗中，一般不用陽性率，因陽在評價診斷性試驗中，一般不用陽性率，因陽性病例數(shù)并未說明是真陽性或假陽性。性病例數(shù)并未說明是真陽性或假陽性。37 從以上組數(shù)據(jù)可以看出從以上組數(shù)據(jù)可以看出： v當(dāng)患病率變化后，當(dāng)患病率變化后，SENSEN、SPESPE、LRLR及及-LR-LR都很穩(wěn)定，都很穩(wěn)定，兩組數(shù)字相同，而兩組數(shù)字相同，而PVPV隨隨PREVPREV不同有很大變化，不同有很大變化，PVPV隨患病率增高而增加。因此，隨患病率增高而增加。因此，PVPV不能看做試驗本身不能看做試驗本身的特性。敏感度越高，則假陰性越低，假陰性率等的特性。敏感度越高，則假陰性越低，假陰性率等于漏診率。因

40、此，高敏感度的試驗，用于臨床診斷于漏診率。因此，高敏感度的試驗，用于臨床診斷時漏診率低。通常用高敏感度試驗，陰性結(jié)果排除時漏診率低。通常用高敏感度試驗，陰性結(jié)果排除診斷，又稱為診斷，又稱為SnNoutSnNout。v高敏感度試驗用于：高敏感度試驗用于：疾病漏診可能造成嚴(yán)重后果；疾病漏診可能造成嚴(yán)重后果；用于排除疾?。挥糜谂懦膊?；用于篩選無癥狀且發(fā)病率又比較低的疾病。用于篩選無癥狀且發(fā)病率又比較低的疾病。38v特異性越高，則假陽性率越低，假陽性率等于誤特異性越高，則假陽性率越低，假陽性率等于誤診率。因此，特異性高的試驗，用于臨床時誤診診率。因此，特異性高的試驗，用于臨床時誤診機(jī)會少。高特異性試

41、驗，用于肯定診斷、確診疾機(jī)會少。高特異性試驗，用于肯定診斷、確診疾病。當(dāng)試驗結(jié)果陽性時，臨床確診價值最大。病。當(dāng)試驗結(jié)果陽性時，臨床確診價值最大。v用高特異性試驗，陽性結(jié)果肯定診斷，又稱為用高特異性試驗，陽性結(jié)果肯定診斷，又稱為SpPinsSpPins。v特異性高的試驗適用于：特異性高的試驗適用于：肯定疾病診斷；肯定疾病診斷；凡假陽性結(jié)果會導(dǎo)致病人精神負(fù)擔(dān)，或不當(dāng)防凡假陽性結(jié)果會導(dǎo)致病人精神負(fù)擔(dān)，或不當(dāng)防治措施會給病人帶來嚴(yán)重危害。治措施會給病人帶來嚴(yán)重危害。39四、診斷性試驗的樣本大小的計算四、診斷性試驗的樣本大小的計算v計算時，先查閱文獻(xiàn)或作預(yù)試估計計算時，先查閱文獻(xiàn)或作預(yù)試估計SENSE

42、N、SPESPEv病例組（）：用該試驗敏感性估計病例組（）：用該試驗敏感性估計= =（）（）v對照組（）：用該試驗特異性估計對照組（）：用該試驗特異性估計 P P= =（）（）v用估計總體率的樣本公式分別計算用估計總體率的樣本公式分別計算vm ma a2 2（）（）2 2vm ma a2 2（）（）2 2顯著性水平顯著性水平a a取取. . . .（雙側(cè)檢驗）（雙側(cè)檢驗）診斷性試驗的允許誤差診斷性試驗的允許誤差一般定在一般定在0.05-0.100.05-0.1040五、似然比的臨床應(yīng)用五、似然比的臨床應(yīng)用 v可用于臨床計算患病的概率，便于更準(zhǔn)確地對患者作出可用于臨床計算患病的概率，便于更準(zhǔn)確地

43、對患者作出診斷。診斷。 例如：對懷疑急性心肌梗塞患者，作肌酸磷酸激酶例如：對懷疑急性心肌梗塞患者，作肌酸磷酸激酶（CPKCPK）測定，根據(jù)其結(jié)果可計算似然比。愛丁堡皇家）測定，根據(jù)其結(jié)果可計算似然比。愛丁堡皇家醫(yī)院將懷疑心肌梗死者醫(yī)院將懷疑心肌梗死者360360例收入病房例收入病房, ,檢測檢測CPKCPK，由一，由一位不知位不知CPKCPK結(jié)果的醫(yī)生根據(jù)心電圖和尸檢結(jié)果判斷有心結(jié)果的醫(yī)生根據(jù)心電圖和尸檢結(jié)果判斷有心肌梗死者肌梗死者230230例，無心梗者例，無心梗者130130例，測定值如下：例，測定值如下： 2-39 40-79 80-119 120-159 160-199 200-239

44、 240-279 280-319 320-359 360-399 400-439 440-4792-39 40-79 80-119 120-159 160-199 200-239 240-279 280-319 320-359 360-399 400-439 440-479 =480 =480AMI AMI + 2 13 30 30 21 19 18 13 19 15 7 8 35+ 2 13 30 30 21 19 18 13 19 15 7 8 35 - 88 26 8 5 0 1 1 1 0 0 0 0 0 - 88 26 8 5 0 1 1 1 0 0 0 0 0 41如將如將CPK

45、80CPK 80單位作為診斷心肌梗死的臨界值，列出四格單位作為診斷心肌梗死的臨界值，列出四格表表 急性心肌梗塞急性心肌梗塞 是是 否否 80u 215 1680u 215 16 CPK CPK 80u 15 11480u 15 114 230 130 230 130 SEN=a/ SEN=a/（a+ca+c）=215/230=0.93=215/230=0.93 SPE=d/ SPE=d/（b+db+d）=114/130=0.88=114/130=0.88 +LR=SEN/ +LR=SEN/（1-SPE1-SPE）=0.93/=0.93/（1-0.881-0.88） =7.75=7.7542再一

46、步分析，則可計算不同水平的似然比：再一步分析，則可計算不同水平的似然比：CPK AMICPK AMI（+ +） AMIAMI（- -） LRLR n n 比例比例 n n 比例比例 280 97 97/230=0.42 1 1/130=0.01 0.42/0.01=42 280 97 97/230=0.42 1 1/130=0.01 0.42/0.01=42 80279 118 118/230=0.51 15 15/130=0.12 0.51/0.12=4.2 80279 118 118/230=0.51 15 15/130=0.12 0.51/0.12=4.2 4079 13 13/230=

47、0.06 26 26/130=0.02 0.06/0.02=0.34079 13 13/230=0.06 26 26/130=0.02 0.06/0.02=0.3139 2 2/230=0.01 88 88/130=0.67 0.01/0.67=0.01139 2 2/230=0.01 88 88/130=0.67 0.01/0.67=0.01合計合計 230 130230 13043v似然比的應(yīng)用：似然比的應(yīng)用：驗前比（驗前比（Pretest OddsPretest Odds）= =驗前概率驗前概率/ /（1-1-驗前概率）驗前概率）驗后比（驗后比（Post-test OddsPost-te

48、st Odds）= =驗前比驗前比似似然比然比驗后概率（驗后概率（Post-test ProbabilityPost-test Probability）= =驗驗后比后比/ /（1+1+驗后比）驗后比）44例：某患者活動后即感胸前區(qū)疼痛，在醫(yī)院檢查例：某患者活動后即感胸前區(qū)疼痛，在醫(yī)院檢查CPKCPK為為7272單位，試問患單位，試問患AMIAMI的可能性有多大？的可能性有多大？解：（解：（1 1） 估計患估計患AMIAMI的可能性有的可能性有50%50%（試驗前概（試驗前概率）率） （2 2） 按前表中按前表中CPKCPK為為72U72U的的 LR=0.30LR=0.30 （3 3） 計算：

49、計算： 驗前比驗前比=0.50/=0.50/（1-0.501-0.50）=1=1 驗后比驗后比=1=10.30=0.300.30=0.30 驗后概率驗后概率=0.3/=0.3/（1+0.31+0.3）=0.23=0.23 答：該病例患答：該病例患AMIAMI的機(jī)會只有的機(jī)會只有23%23%。4546部份常見病、診斷性試驗結(jié)果的陽性似然比部份常見病、診斷性試驗結(jié)果的陽性似然比病名病名金標(biāo)準(zhǔn)金標(biāo)準(zhǔn)診斷性試驗診斷性試驗陽性似然比陽性似然比冠心病冠心病冠狀動脈造影，狹窄冠狀動脈造影，狹窄75%75%典型心絞痛發(fā)作典型心絞痛發(fā)作115115冠心病冠心病冠狀動脈狹窄（血管造冠狀動脈狹窄（血管造影）影）不典

50、型心絞痛，有陽性病史不典型心絞痛，有陽性病史1414心肌梗塞心肌梗塞心電圖或尸檢心電圖或尸檢肌酸激酶肌酸激酶80u80u7.757.75深靜脈血栓形成深靜脈血栓形成靜脈造影靜脈造影深靜脈血栓形成癥狀（疼痛、皮深靜脈血栓形成癥狀（疼痛、皮膚顏色改變、局部發(fā)熱、壓痛、膚顏色改變、局部發(fā)熱、壓痛、周徑增大周徑增大3cm3cm）全部體征伴周徑）全部體征伴周徑增大增大2.62.6深靜脈血栓形成深靜脈血栓形成靜脈造影靜脈造影以上體征以上體征4 4項，且無周徑改變項，且無周徑改變0.150.15深靜脈血栓形成深靜脈血栓形成靜脈彩色多普勒靜脈彩色多普勒血漿血漿D-dimerD-dimer1292 ng1292

51、 ng/ml/ml2.02.03.13.1冠心病冠心病冠狀動脈狹窄（血管造冠狀動脈狹窄（血管造影）影）心電圖運(yùn)動試驗心電圖運(yùn)動試驗 STST下抑下抑2.5mm2.5mm393922.4922.4911111.51.991.51.994.24.21.01.491.01.492.12.10.05-0.990.05-0.990.920.9247六、六、ROCROC曲線曲線v“Receiver” or “Response” Operating Characteristic (ROC) curves，受試者工作特性曲線，受試者工作特性曲線，a helpful way of distinguishing

52、real signals for false noises in the early days of radar.vIf you plot the SEN versus (1-SPE) or “false alarms” that result from selecting different cutoffs for the diagnostic test results, you generate a useful picture of the tests accuracy that is called an “ROC curve.” ROC curves nicely display th

53、e trade-offs of using one or more cutoffs for the test. 4849vAn ROC curve has some useful properties:It illustrates the performance of a dichotomous diagnostic test when you select different cut-points to distinguish “normal” from “abnormal” results.It demonstrates the fact that any increase in sens

54、itivity will be accompanied by a decrease in specificity, and vice versa. The closer the curve gets to the upper left corner of the display, the more the overall accuracy of the test. That is, choosing the point labelled “BNP 76” correctly identifies 26 affected and 75 normal patients out of the tot

55、al of 126, or 80% overall accuracy. However, choosing the point labelled “BNP18 ” correctly identifies 35 affected but only 29 normal patients from the total of 126, which is only 51% overall accuracy. 50The closer the curve comes to the 45-degree diagonal of the ROC space, the less accurate the tes

56、t. At 45 degrees, the test adds no diagnostic information at all. Getting a bit fancier, the slope of the tangent at a cut-point gives the LR for that value of the test. Notice how much steeper the tangent is for the cutoff of 76 than it is for the cutoff of 18. The area under the curve provides an

57、overall measure of a tests accuracy. This property can help decide which of two competing tests for the same target disorder is the better one. 51ROCROC：描述診斷性試驗優(yōu)劣描述診斷性試驗優(yōu)劣確定確定cut-offcut-off值值比較不同診斷性試驗比較不同診斷性試驗52七、提高診斷性試驗效率的方法：七、提高診斷性試驗效率的方法：聯(lián)合試驗聯(lián)合試驗1.1.平行試驗：同時做幾個試驗，只要有一個陽性，即平行試驗：同時做幾個試驗，只要有一個陽性，即可認(rèn)為

58、有患病證據(jù)。平行試驗提高了可認(rèn)為有患病證據(jù)。平行試驗提高了敏感度和陰性敏感度和陰性預(yù)測值預(yù)測值，但降低了特異度及陽性預(yù)測值。，但降低了特異度及陽性預(yù)測值。SenSen=Sen1 + Sen2 - Sen1 X Sen2=Sen1 + Sen2 - Sen1 X Sen2SpeSpe=Spe1 X Spe2=Spe1 X Spe2驗后比驗后比= =驗前比驗前比 X LR1 X LR2X LR1 X LR253聯(lián)合試驗聯(lián)合試驗2.2.序列試驗：依次相繼的試驗，要所有的試驗陽性序列試驗：依次相繼的試驗，要所有的試驗陽性才能做出診斷。序列試驗提高了才能做出診斷。序列試驗提高了特異度及陽性預(yù)特異度及陽性

59、預(yù)測值測值。但降低了敏感度及陰性預(yù)測值。但降低了敏感度及陰性預(yù)測值。例如：診斷心肌梗死的例如：診斷心肌梗死的CPKCPK、ASTAST、LDHLDH，沒有一，沒有一種試驗是很特異的，如采用序列試驗，即三項均種試驗是很特異的，如采用序列試驗，即三項均陽性才能診斷，這樣可提高診斷心肌梗死的特異陽性才能診斷，這樣可提高診斷心肌梗死的特異度。度。SEN = SEN1 X SEN2SEN = SEN1 X SEN2SPE = SPE1 +SPE2 - SPE1 X SPE2SPE = SPE1 +SPE2 - SPE1 X SPE254七、診斷性試驗的評價原則七、診斷性試驗的評價原則v新的診斷性試驗用于

60、臨床之前或雜志上有關(guān)新的診斷性試驗用于臨床之前或雜志上有關(guān)診斷性試驗的結(jié)論，均須經(jīng)過科學(xué)的評價。診斷性試驗的結(jié)論，均須經(jīng)過科學(xué)的評價。1.1.是否采用盲目法將診斷性試驗與標(biāo)準(zhǔn)診斷法是否采用盲目法將診斷性試驗與標(biāo)準(zhǔn)診斷法（金標(biāo)準(zhǔn)）作過對比研究？（金標(biāo)準(zhǔn)）作過對比研究？J診斷性試驗必須與金標(biāo)準(zhǔn)比較，才能確定是診斷性試驗必須與金標(biāo)準(zhǔn)比較，才能確定是否可靠。否可靠。J盲法對比，更為科學(xué)。盲法對比，更為科學(xué)。J列出四格表進(jìn)行分析對比，計算各項指標(biāo)，列出四格表進(jìn)行分析對比，計算各項指標(biāo)，根據(jù)根據(jù)ACCACC、SENSEN、SPESPE確定診斷性試驗有無應(yīng)用確定診斷性試驗有無應(yīng)用價值。價值。552.2.被檢