诊断性试验的分析与评价,四川大学华西医院 实验医学科 秦 莉,2,一、定义,对疾病进行诊断的试验方法，即称为诊 断性试验。 诊断性试验不仅包括实验室检查，还包括病史、体检结果、影象学检查、各种公认的诊断标准等。,3,诊断性试验的应用,诊断疾病 筛检无症状病人 疾病的随访 判断疾病的严重性 估计疾病的临床过程极其预后 估计对治疗的反应 测定目前对治疗的实际反应,4,二、评价诊断性试验的条件,1.标准诊断： 疾病的诊断，必须有标准诊断（即金标准, gold standard，或参考标准，reference standard）。标准诊断是目前公认的诊断方法，如：活检、手术、尸检、特殊检查或长期随访的结果,5,二、评价诊断性试验的条件,2.诊断方法的对比： 评价新的诊断性试验，必须与标准诊断方法进行比较。 新的诊断性试验，应该具备方法更为简便、更为可靠或者减少危险、减少创伤、节约费用等优点，这样的诊断性试验才具有推广意义。,6,二、评价诊断性试验的条件,3.列出四格表,7,所评价的资料应能列出四格表，方法如下 用标准诊断方法，诊断的病例数为 a+c 在有病的受试者中，诊断性试验阳性者为 a，阴性者为 c 用标准诊断方法，判断无该病的例数为 b+d 无该病的受试者中，诊断性试验阳性例数为 b，阴性例数为 d 从评价的资料中，不能绘制四格表的诊断性试验，无法进行评价,8,三、评价诊断性试验的常用指标,1.评价指标 敏感度（sensitivity）：经金标准确诊有病的人中，诊断性试验阳性者所占的比例。 SEN = a /（ a+c） 特异度（specificity）：经金标准诊断确定为无该病的人中，诊断性试验阴性所占的比例。 SPE = d /（b+d）,9,准确性（accuracy）：经诊断性试验检查后真阳性与真阴性占总例数的比例。 ACC =（a+d）/（a+b+c+d） 阳性预测值（positive predictive value）：诊断性试验阳性的人中有病的人数所占的比例。（即诊断性试验阳性时，患病的可能性,即阳性结果的验后概率） +PV = a /（a+b） 阴性预测值（negative predictive value）：诊断性试验阴性的人中，无该病的人数所占的比例。（即诊断性试验阴性时，不患该病的可能性） -PV = d /（c+d）,10,患病率（prevalence）： PREV =（a+c）/（a+b+c+d） 阳性似然比（positive likelihood ratio）：有病者诊断性试验阳性的概率与无病者试验阳性的概率之比。 +LR = a /（a+c） / b /（b+d） = Sen/（1-Spe） 阴性似然比（negative likelihood ratio）：有病者试验阴性的概率和无病者试验阴性的概率之比。 -LR = c /（a+c） / d /（b+d） =（1-Sen）/ Spe,11,LR：有病者得出某一试验结果的概率与无病者得出该试验结果的概率之比。表示一个诊断试验结果出现在有病者和出现在无病者的可能性比值大小，代表了一个诊断性试验区分有病和无病的能力大小。LR越大，患病可能性越大,12,举例,An Oxfordshire (England) group 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 Table,13,Performance of B-type Natriuretic Peptide 18 pg/mL As a diagnostic test for left ventricular dysfunction,14,You can calculate the proportion of patients with LVD who also have elevated BNP. （敏感度） a/(a + c) = 35/40 = 0.88, or 88% “positivity in the presence of the target disorder” is Sensitivity. You can calculate the proportion of patients who are free of LVD who also have normal BNP. （特异度） d/(b + d) = 29/86 = 0.34, or 34% “negativity in the absence of the target disorder” is Specificity.,15,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（阳性结果验后概率） 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 negative result.（阴性结果验后概率）,16,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 any additional diagnostic information) as Prevalence, because it describes the prevailing rate of the target disorder in the patients who are undergoing the diagnostic test.,17,验前概率、验后概率、患病率,验前概率：患者没有进行诊断性试验时的患病概率 验后概率：根据患者诊断性试验结果，结合验前概率推测的患病概率 患病率=验前概率,18,You can calculate the odds that a patient has LVD before you ever measure their BNP. Pre-test odds（验前比）= Pre-test Probability (100% Pre-test Probability) = 32%/(100% 32%) = 32%/68% = 0.47 By convention, we refer to this as Pre-test Odds. And you can convert an odds back into a probability. Probability=odds/(odds + 1) = 0.47/1.47 = 0.32, or 32%,19,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% = 1.3 By convention, we refer to that as a Likelihood Ratio of a positive test (some prefer to call it a Positive Likelihood Ratio).,20,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% 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).,21,You can discover that if you multiply the Pre-test Odds（验前比）from the population studied by the LR of a positive test result and convert the resulting Post-test Odds（验后比） back to a probability, it is identical to the +PV. 验后比 = 验前比似然比（Pre-test odds x LR） = 0.47 x 1.3 = 0.61 and 验后概率 = 验后比/(1+验后比) =0.61/1.61 = 0.38, or 38% (the same as you calculated in no. 3 above).,22,10. 阴性似然比(-LR)验前比得到阴性结果的验后比，可用公式将此验后比转化为验后概率，即阴性结果的验后概率。 Pre-test odds（-LR） = 0.47 x 0.4 = 0.19 and 0.19/1.19 = 0.15, or 15% (阴性结果验后概率） and 100% 15% = 85%（阴性预测值） (the same as you calculated in no. 4 above). 阴性结果的验后概率=100% (-PV),23,You may have noticed th