McGee Emma E, Hernán Miguel A, Giovannucci Edward, Mucci Lorelei A, Chiu Yu-Han, Eliassen A Heather, Dickerman Barbra A
From the CAUSALab, Harvard T.H. Chan School of Public Health, Boston, MA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
Epidemiology. 2025 Sep 1;36(5):705-718. doi: 10.1097/EDE.0000000000001889. Epub 2025 Jun 3.
Many organizations recommend lifestyle modifications for cancer survivors. Effect estimates for these interventions are often based on observational data and are challenging to interpret due to vaguely defined causal questions, design-induced biases, and lack of comparability between individuals.
We outlined a three-step procedure to address these challenges: target trial specification, emulation, and modification to explore lack of comparability due to unmeasured confounding or positivity violations. We illustrated this procedure by specifying the protocols of two target trials that estimate the effects of adhering to seven physical activity and dietary recommendations and abstaining from alcohol on 20-year mortality among adults with breast or prostate cancer. We emulated these target trials using data from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study.
In the main analysis, we included 9,107 adults (5,840 with breast cancer, 3,267 with prostate cancer) and 1,791 deaths occurred. After we modified the target trials, mortality risk differences (95% confidence intervals) comparing the physical activity and dietary intervention versus no intervention ranged from -4.8% (-7.5%, -2.3%) to -13.0% (-15.8%, -9.8%) for breast cancer and from -3.0% (-7.4%, 0.9%) to -12.8% (-17.6%, -7.6%) for prostate cancer. Risk differences comparing no alcohol consumption versus no intervention ranged from 1.3% (0.1%, 2.4%) to 3.6% (2.5%, 4.9%) for breast cancer and from -1.7% (-4.3%, 1.0%) to 6.4% (4.0%, 9.0%) for prostate cancer.
We described a three-step procedure that improves the interpretability of observational estimates of the effects of lifestyle interventions and showed how estimates varied under different modifications.
许多组织建议癌症幸存者改变生活方式。这些干预措施的效果估计通常基于观察性数据，由于因果问题定义模糊、设计导致的偏差以及个体之间缺乏可比性，因此难以解释。
我们概述了一个三步程序来应对这些挑战：目标试验规范、模拟以及修改以探索由于未测量的混杂因素或阳性违反导致的缺乏可比性。我们通过指定两项目标试验的方案来说明这个程序，这两项试验估计了遵守七项体育活动和饮食建议以及戒酒对成年乳腺癌或前列腺癌患者20年死亡率的影响。我们使用护士健康研究、护士健康研究II和卫生专业人员随访研究的数据模拟了这些目标试验。
在主要分析中，我们纳入了9107名成年人（5840名乳腺癌患者，3267名前列腺癌患者），发生了1791例死亡。在我们修改目标试验后，比较体育活动和饮食干预与不干预的死亡率风险差异（95%置信区间），乳腺癌患者为-4.8%（-7.5%，-2.3%）至-13.0%（-15.8%，-9.8%），前列腺癌患者为-3.0%（-7.4%，0.9%）至-12.8%（-17.6%，-7.6%）。比较不饮酒与不干预的风险差异，乳腺癌患者为1.3%（0.1%，2.4%）至3.6%（2.5%，4.9%），前列腺癌患者为-1.7%（-4.3%，1.0%）至6.4%（4.0%，9.0%）。
我们描述了一个三步程序，该程序提高了生活方式干预效果观察性估计的可解释性，并展示了在不同修改下估计值如何变化。
