Krummenauer F, Kauczor H U
Institut für Medizinische Biometrie, Epidemiologie und Informatik der Universität Mainz, Germany.
Rofo. 2002 Nov;174(11):1438-44. doi: 10.1055/s-2002-35346.
A tutorial illustration of a flexible approach to determine the sample size in reference-controlled diagnostic trials.
Assuming the usual setting of a new diagnostic method to be compared with a reference method, the emphasis is on the sensitivity of the new method in comparison with the reference method, using a binary outcome (positive versus negative) for both methods. Based on the confidence interval of the sensitivity, a simple but flexible procedure for determining the sample size is described, which incorporates clinically interpretable information. The procedure is illustrated by the fictitious planning of a trial to assess the diagnostic value of MRI versus arthroscopy as a reference, in the detection of meniscal ruptures.
The principal investigator merely has to propose the range for the sensitivity in which the new method is considered equal to the reference method. Furthermore, it must be decided in advance how accurate the study outcome should determine the sensitivity of the new method, i.e., how wide its maximum confidence interval may become. The minimum sample size necessary for the trial can be directly derived from this outlined strategy, which can easily be extended by simultaneous consideration of sensitivity and specificity of the new method being tested.
The flexible approach to planning by means of the confidence interval of the sensitivity controls the desired confidence of the outcome of the diagnostic trial. It allows a priori evaluation of study budget, study duration, number of study centers and, above all, any ethical limitations. It provides arguments for the investigator to proceed with the comparison and a rationale for the decision to conduct the comparison as mono- or multicentric trial
介绍一种灵活的方法来确定参考对照诊断试验中的样本量。
假设将一种新的诊断方法与参考方法进行比较的常见情况，重点是新方法相对于参考方法的敏感性，两种方法均采用二元结果（阳性与阴性）。基于敏感性的置信区间，描述了一种简单但灵活的确定样本量的程序，该程序纳入了临床可解释的信息。通过虚构一项评估MRI与作为参考的关节镜检查在检测半月板撕裂中的诊断价值的试验计划来说明该程序。
主要研究者只需提出新方法被认为与参考方法相当的敏感性范围。此外，必须预先确定研究结果应多准确地确定新方法的敏感性，即其最大置信区间可能有多宽。试验所需的最小样本量可直接从该概述策略得出，通过同时考虑所测试新方法的敏感性和特异性，该策略可轻松扩展。
通过敏感性置信区间进行灵活的计划方法可控制诊断试验结果所需的置信度。它允许对研究预算、研究持续时间、研究中心数量进行先验评估，最重要的是，可评估任何伦理限制。它为研究者进行比较提供了依据，也为决定进行单中心或多中心试验提供了理由。
