Rodgers A, MacMahon S
Department of Medicine, University of Auckland, New Zealand.
Thromb Haemost. 1995 Feb;73(2):167-71.
Many clinical trials that have assessed strategies for the prevention of deep vein thrombosis have employed diagnostic tests that are less accurate than venography. The correct interpretation of these trials has been the subject of considerable debate. This paper attempts to quantify the likely effects of the use of inaccurate diagnostic tests (in particular fibrinogen scanning) on the validity and precision of estimates of treatment effects. It is shown that, if there is no difference in the rate of misclassification of deep vein thrombosis between study and control groups, then treatment effects will tend to be systematically underestimated in trials that only use inaccurate diagnostic tests. However, for trials in which there are no false positive diagnoses, such as those employing venography, the estimate of relative treatment effects will be unbiased. This phenomenon is demonstrated empirically by data from randomised trials of antiplatelet therapy. The implications of these findings are two-fold. First, so long as the accuracy of the test is the same in study and control groups, positive trial results cannot be ascribed to diagnostic test inaccuracy. Second, unbiased estimates of relative treatment effects can be obtained by using cheap, practicable and non-invasive screening tests that are supplemented by venographic assessment of positive test results. This would facilitate the conduct of much larger randomised trials than has generally been possible when mandatory venography was used; if future trials randomised some thousands of patients and employed confirmatory venography then they would provide both unbiased and precise estimates of relative treatment effects.
许多评估深静脉血栓形成预防策略的临床试验所采用的诊断测试，其准确性低于静脉造影。对这些试验的正确解读一直是相当多争论的主题。本文试图量化使用不准确的诊断测试（特别是纤维蛋白原扫描）对治疗效果估计的有效性和精确性可能产生的影响。结果表明，如果研究组和对照组之间深静脉血栓形成的错误分类率没有差异，那么在仅使用不准确诊断测试的试验中，治疗效果往往会被系统性低估。然而，对于没有假阳性诊断的试验，如那些采用静脉造影的试验，相对治疗效果的估计将是无偏的。抗血小板治疗随机试验的数据通过实证证明了这一现象。这些发现的影响有两方面。首先，只要测试在研究组和对照组中的准确性相同，试验的阳性结果就不能归因于诊断测试的不准确。其次，通过使用廉价、可行且非侵入性的筛查测试，并对阳性测试结果进行静脉造影评估，可以获得相对治疗效果的无偏估计。这将有助于开展比使用强制静脉造影时通常可能进行的规模大得多的随机试验；如果未来的试验将数千名患者随机分组并采用确认性静脉造影，那么它们将提供相对治疗效果的无偏且精确的估计。
