Tweel Ingeborg van der, Schipper Maria
Centre for Biostatistics, Utrecht University, Padualaan 14, 3584 CH Utrecht, The Netherlands.
Stat Med. 2004 Dec 30;23(24):3755-71. doi: 10.1002/sim.2071.
The sample size necessary to detect a significant gene x environment interaction in an observational study can be large. For reasons of cost-effectiveness and efficient use of available biological samples we investigated the properties of sequential designs in matched case-control studies to test for both non-hierarchical and hierarchical interactions. We derived the test statistics Z and V and their characteristics when applied in a two-sided triangular test. Results of simulations show good agreement with theoretical values for V and the type I error. Power values were larger than their theoretical values for very large sample sizes. Median gain in efficiency was about 27 per cent. For a 'rare' phenotype gain in efficiency was larger when the alternative hypothesis was true than under the null hypothesis. Sequential designs lead to substantial efficiency gains in tests for interaction in matched case-control studies.
在观察性研究中，检测显著的基因与环境相互作用所需的样本量可能很大。出于成本效益和有效利用现有生物样本的考虑，我们研究了匹配病例对照研究中序贯设计的特性，以检验非分层和分层相互作用。我们推导了检验统计量Z和V及其在双侧三角检验中的特性。模拟结果表明，V值和I型错误与理论值吻合良好。对于非常大的样本量，功效值大于其理论值。效率的中位数提高约为27%。对于“罕见”表型，当备择假设为真时，效率提高比在原假设下更大。序贯设计在匹配病例对照研究的相互作用检验中可显著提高效率。
