Statistical Center for HIV/AIDS Prevention and Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Stat Med. 2012 Dec 10;31(28):3748-59. doi: 10.1002/sim.5446. Epub 2012 Jul 5.
In biomedical research such as the development of vaccines for infectious diseases or cancer, study outcomes measured by an assay or device are often collected from multiple sources or laboratories. Measurement error that may vary between laboratories needs to be adjusted for when combining samples across data sources. We incorporate such adjustment in the main study by comparing and combining independent samples from different laboratories via integration of external data, collected on paired samples from the same two laboratories. We propose the following: (i) normalization of individual-level data from two laboratories to the same scale via the expectation of true measurements conditioning on the observed; (ii) comparison of mean assay values between two independent samples in the main study accounting for inter-source measurement error; and (iii) sample size calculations of the paired-sample study so that hypothesis testing error rates are appropriately controlled in the main study comparison. Because the goal is not to estimate the true underlying measurements but to combine data on the same scale, our proposed methods do not require that the true values for the error-prone measurements are known in the external data. Simulation results under a variety of scenarios demonstrate satisfactory finite sample performance of our proposed methods when measurement errors vary. We illustrate our methods using real enzyme-linked immunosorbent spot assay data generated by two HIV vaccine laboratories.
在生物医学研究中,例如开发传染病或癌症疫苗,通常从多个来源或实验室收集通过测定或设备测量的研究结果。当跨数据源组合样本时,需要调整可能在实验室之间变化的测量误差。我们通过整合来自同一两个实验室的配对样本的外部数据,在主要研究中比较和组合来自不同实验室的独立样本,从而进行这种调整。我们提出以下方法:(i)通过根据观察结果对真实测量值进行条件化来将两个实验室的个体水平数据归一化为相同的尺度;(ii)在主要研究中,对两个独立样本的测定值平均值进行比较,以考虑跨源测量误差;以及(iii)配对样本研究的样本量计算,以使主要研究比较中的假设检验错误率得到适当控制。因为我们的目标不是估计真实的基础测量值,而是在同一尺度上组合数据,所以我们提出的方法不需要在外部数据中知道易出错测量值的真实值。在各种情况下的模拟结果表明,当测量误差变化时,我们提出的方法在有限样本中的表现令人满意。我们使用由两个 HIV 疫苗实验室生成的真实酶联免疫斑点测定数据来说明我们的方法。