-
摘要:
目的 介绍处理时依性混杂的G方法,并对不同G方法进行探讨和比较。 方法 通过4个情境的模拟试验验证不同G方法在不同情境下对时依性混杂的处理效果,并应用英国生物样本库(UK Biobank)的数据集进行实例分析。 结果 模拟试验和实例分析结果均显示G方法能有效处理时依性混杂。模拟试验显示3种方法效果类似,G-computation易受G-null paradox的影响。随着时依性混杂因素数量增加,相比于G-computation和G-estimation,逆概率加权法(inverse probability of treatment weighting, IPTW)的效果波动较大。 结论 不同G方法都能适当地处理时依性混杂,降低统计分析过程中的偏倚大小。 Abstract:Objective To introduce and compare different G-methods which can deal with time varying confounding. Methods The simulation experiments of four scenarios were carried out to verify the effects of different G-methods on time varying confounding in different situations. Dataset from UK Biobank was then analyzed using different G-methods. Results All three G methods can effectively deal with time varying confounding with similar performance, while G-computation was vulnerable to G-null paradox. However, with the increasing number of time varying confounders, the estimated effects of inverse probability of treatment weighting (IPTW) were more variable. Conclusion All of the three G-methods can remove the bias resulted from time varying confounding appropriately. -
Key words:
- Time varying confounding /
- Collider bias /
- G-methods
-
表 1 模拟试验情境一结果
Table 1. Results of the first scenario of simulation
样本量 方法 偏倚 MSE 95% CI覆盖率(%) 检验效能(%) 400 调整 0.140 8 0.029 7 0.00 100.00 未调整 -0.000 3 0.039 7 95.80 100.00 G-computation -0.000 6 0.039 6 94.90 100.00 IPTW 0.105 1 1.138 2 100.00 67.60 G-estimation a -0.066 3 90.70 99.30 1 000 调整 0.140 6 0.029 9 0.00 100.00 未调整 -0.000 4 0.039 8 93.40 100.00 G-computation 0.000 3 0.039 8 94.60 100.00 IPTW 0.146 1 1.151 8 100.00 97.30 G-estimation a -0.063 1 86.50 100.00 2 000 调整 0.140 8 0.030 0 0.00 100.00 未调整 -0.000 1 0.040 0 94.20 100.00 G-computation 0.000 0 0.040 0 94.80 100.00 IPTW 0.143 9 1.153 3 100.00 100.00 G-estimation a -0.062 4 78.30 100.00 注:a此情境下,G-estimation无法得到预测值,因此无法估计MSE。 表 2 模拟试验情境三结果
Table 2. Results of the third scenario of simulation
效应 方法 结果1 a 结果2 b 结果3 c 偏倚 MSE 95% CI覆盖率(%) Ⅰ类错误率(%) 偏倚 MSE 95% CI覆盖率(%) Ⅰ类错误率(%) 偏倚 MSE 95% CI覆盖率(%) Ⅰ类错误率(%) A0 调整 0.000 8 0.262 6 96.60 4.80 -0.108 0 0.263 2 48.90 51.10 -0.106 0 0.860 2 84.20 15.80 未调整 0.131 9 0.275 2 35.50 24.60 0.078 4 0.274 5 64.60 35.40 0.080 4 0.872 1 84.30 15.70 G-computation d 0.000 3 93.40 6.60 -0.000 2 94.00 6.00 -0.002 6 94.60 5.40 IPTW 0.000 3 0.278 9 93.30 6.70 -0.000 2 0.279 7 94.70 5.30 -0.002 6 0.879 9 94.80 5.30 G-estimation d 0.000 0 94.30 5.70 0.003 9 94.80 5.20 0.005 4 94.70 5.20 A1 调整 -0.002 4 0.262 6 94.10 5.60 -0.007 2 0.263 2 93.00 7.00 -0.008 7 0.860 2 94.90 5.10 未调整 -0.065 8 0.275 2 74.30 13.10 -0.061 9 0.274 5 75.20 24.80 -0.064 3 0.872 1 87.10 12.90 G-computation d -0.002 6 93.10 6.90 -0.000 7 95.40 4.60 0.001 6 94.50 5.50 IPTW -0.002 6 0.278 9 94.40 5.60 -0.000 7 0.279 4 97.00 3.00 0.001 6 0.879 9 94.60 5.40 G-estimation d -0.000 8 95.00 5.00 0.001 7 95.40 4.60 0.000 5 94.40 5.40 注:a结果1:A0对L的效应为0;b结果2:A0对L的效应为0.3,标准差为0.2;c结果3:A0对L的效应为0.3,标准差为0.8。d此情境下,G-computation和G-estimation无法得到预测值,因此无法估计MSE。 表 3 实例分析结果
Table 3. Results of real data analysis
方法 第一阶段BMI 第二阶段BMI β值 OR值 β值 OR值 调整 0.513 1.670 -0.195 0.823 未调整 0.534 1.706 -0.171 0.843 G-computation 0.599 1.820 -0.028 0.972 IPTW 0.765 2.149 0.325 1.384 G-estimation 0.108 1.114 0.282 1.326 -
[1] Robins JM, Hernán MA, Brumback B. Marginal structural models and causal inference in epidemiology[J]. Epidemiology, 2000, 11(5): 550-560. DOI: 10.1097/00001648-200009000-00011. [2] Fewell Z, Hernán MA, Wolfe F, et al. Controlling for time-dependent confounding using marginal structural models[J]. Stata Journal, 2004, 4(4): 402-420. DOI: 10.1177/1536867X0400400403. [3] Schisterman EF, Cole SR, Platt RW. Overadjustment bias and unnecessary adjustment in epidemiologic studies[J]. Epidemiology, 2009, 20(4): 488-495. DOI: 10.1097/EDE.0b013e3181a819a1. [4] Greenland S. Quantifying biases in causal models: classical confounding vs collider-stratification bias[J]. Epidemiology, 2003, 14(3): 300-306. DOI: 10.1088/0256-307X/25/1/054. [5] Mansournia MA, Etminan M, Danaei G, et al. Handling time varying confounding in observational research[J]. BMJ, 2017, 359: j4587. DOI: 10.1136/bmj.j4587. [6] Hernán MA, Brumback B, Robins JM. Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men[J]. Epidemiology, 2000, 11(5): 561-570. DOI: 10.1097/00001648-200009000-00012. [7] Daniel RM, Cousens SN, De Stavola BL, et al. Methods for dealing with time-dependent confounding[J]. Stat Med, 2013, 32(9): 1584-1618. DOI: 10.1002/sim.5686. [8] Robins JM. A new approach to causal inference in mortality studies with a sustained exposure period-application to control of the healthy worker survivor effect[J]. Mathematical Modelling, 1986, 7(9-12): 1393-1512. DOI: 10.1016/0270-0255(86)90088-6. [9] Robins JM, Blevins D, Ritter G, et al. G-estimation of the effect of prophylaxis therapy for pneumocystis carinii pneumonia on the survival of AIDS patients[J]. Epidemiology, 1992, 3(4): 319-336. DOI: 10.1097/00001648-199207000-00007. [10] Austin PC. The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments[J]. Stat Med, 2014, 33(7). DOI: 10.1002/sim.5984. [11] Cole SR, Hernán MA. Adjusted survival curves with inverse probability weights[J]. Comput Methods Programs Biomed, 2004, 75(1): 45-49. DOI: 10.1016/j.cmpb.2003.10.004. [12] Hernan MA, Robins JM. Estimating causal effects from epidemiological data[J]. J Epidemio Community Health, 2006, 60(7): 578-586. DOI: 10.1136/jech.2004.029496. [13] Whitcomb BW, Schisterman EF, Perkins NJ, et al. Quantification of collider-stratification bias and the birthweight paradox[J]. Paediatr Perinat Epidemiol, 2009, 23(5): 394-402. DOI: 10.1111/j.1365-3016.2009.01053.x. [14] Hernán M, Robins J. Causal inference: what if[M]. Boca Raton: Chapman & Hall/CRC, 2020. [15] National Institutes of Health. Clinical guidelines on the identification, evaluation and treatment of overweight and obesity in adults-the evidence report[J]. Obes Res, 1998, 6(6): 464. http://ci.nii.ac.jp/naid/10018714807 [16] Obesity S. Obesity: preventing and managing the global epidemic. Report of a WHO consultation[J]. World Health Organ Tech Rep Ser, 2000, 894(1): 18-30. DOI: 10.1002/jps.3080150106. [17] Xu S, Ross C, Raebel MA, et al. Use of stabilized inverse propensity scores as weights to directly estimate relative risk and its confidence intervals[J]. Value Health, 2010, 13(2): 273-277. DOI: 10.1111/j.1524-4733.2009.00671.x. [18] Funk MJ, Westreich D, Wiesen C, et al. Doubly robust estimation of causal effects[J]. Am J Epidemiol, 2011, 173(7): 761-767. DOI: 10.1093/aje/kwq439.