Aalen Odd O, Valberg Morten, Grotmol Tom, Tretli Steinar
Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway and Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway
Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway and.
Int J Epidemiol. 2015 Aug;44(4):1408-21. doi: 10.1093/ije/dyu192. Epub 2014 Dec 12.
The concept of frailty plays a major role in the statistical field of survival analysis. Frailty variation refers to differences in risk between individuals which go beyond known or measured risk factors. In other words, frailty variation is unobserved heterogeneity. Although understanding frailty is of interest in its own right, the literature on survival analysis has demonstrated that existence of frailty variation can lead to surprising artefacts in statistical estimation that are important to examine. We present literature that demonstrates the presence and significance of frailty variation between individuals. We discuss the practical content of frailty variation, and show the link between frailty and biological concepts like (epi)genetics and heterogeneity in disease risk. There are numerous suggestions in the literature that a good deal of this variation may be due to randomness, in addition to genetic and/or environmental factors. Heterogeneity often manifests itself as clustering of cases in families more than would be expected by chance. We emphasize that apparently moderate familial relative risks can only be explained by strong underlying variation in disease risk between families and individuals. Finally, we highlight the potential impact of frailty variation in the interpretation of standard epidemiological measures such as hazard and incidence rates.
虚弱的概念在生存分析的统计领域中起着重要作用。虚弱变异是指个体之间风险的差异，这种差异超出了已知或测量的风险因素。换句话说，虚弱变异是未观察到的异质性。尽管对虚弱的理解本身就很有意义，但生存分析的文献表明，虚弱变异的存在会导致统计估计中出现令人惊讶的假象，而这些假象对于研究来说很重要。我们展示了一些文献，这些文献证明了个体之间虚弱变异的存在及其重要性。我们讨论了虚弱变异的实际内容，并展示了虚弱与生物学概念（如（表观）遗传学和疾病风险异质性）之间的联系。文献中有许多建议表明，除了遗传和/或环境因素外，这种变异的很大一部分可能是由于随机性。异质性通常表现为家庭中病例的聚集，其程度超过了偶然预期。我们强调，表面上适度的家族相对风险只能通过家庭和个体之间疾病风险的强烈潜在变异来解释。最后，我们强调了虚弱变异在解释标准流行病学指标（如风险率和发病率）方面的潜在影响。
