Frameworks for estimating causal effects in observational settings: comparing confounder adjustment and instrumental variables

BMC Medical Research Methodology

Review

Joshua D. Grill¹  Roy S. Zawadzki²  Daniel L. Gillen² 

[1] Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, USA;Department of Neurobiology and Behavior, University of California, Irvine, Irvine, USA;Department of Statistics, University of California, Irvine, Irvine, USA;

关键词: Causal inference;    Observational studies;    Instrumental variables;    Adjustment;    Propensity scores;   

DOI  :  10.1186/s12874-023-01936-2

 received in 2022-10-24, accepted in 2023-04-25,  发布年份 2023

来源: Springer

【 摘 要 】

To estimate causal effects, analysts performing observational studies in health settings utilize several strategies to mitigate bias due to confounding by indication. There are two broad classes of approaches for these purposes: use of confounders and instrumental variables (IVs). Because such approaches are largely characterized by untestable assumptions, analysts must operate under an indefinite paradigm that these methods will work imperfectly. In this tutorial, we formalize a set of general principles and heuristics for estimating causal effects in the two approaches when the assumptions are potentially violated. This crucially requires reframing the process of observational studies as hypothesizing potential scenarios where the estimates from one approach are less inconsistent than the other. While most of our discussion of methodology centers around the linear setting, we touch upon complexities in non-linear settings and flexible procedures such as target minimum loss-based estimation and double machine learning. To demonstrate the application of our principles, we investigate the use of donepezil off-label for mild cognitive impairment. We compare and contrast results from confounder and IV methods, traditional and flexible, within our analysis and to a similar observational study and clinical trial.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

40517_2023_256_Article_IEq34.gif

Fig. 1

40517_2023_256_Article_IEq33.gif

Fig. 2

40517_2023_258_Article_IEq68.gif

40517_2023_258_Article_IEq138.gif

40517_2023_258_Article_IEq137.gif

Fig. 8

40517_2023_258_Article_IEq135.gif

Fig. 1

40517_2023_258_Article_IEq133.gif

40517_2023_258_Article_IEq132.gif

40517_2023_258_Article_IEq131.gif

40517_2023_258_Article_IEq130.gif

40517_2023_258_Article_IEq129.gif

40517_2023_258_Article_IEq128.gif

40517_2023_258_Article_IEq127.gif

40517_2023_258_Article_IEq126.gif

40517_2023_258_Article_IEq125.gif

Fig. 2

Fig. 1

Fig. 1

40517_2023_258_Article_IEq122.gif

40517_2023_258_Article_IEq121.gif

40517_2023_258_Article_IEq119.gif

Fig. 1

40517_2023_258_Article_IEq115.gif

40517_2023_258_Article_IEq114.gif

40517_2023_258_Article_IEq113.gif

Fig. 1

Fig. 1

40517_2023_256_Article_IEq14.gif

Fig. 8

Fig. 6

Fig. 7

40517_2023_256_Article_IEq11.gif

Fig. 5

40517_2023_256_Article_IEq5.gif

40517_2023_256_Article_IEq4.gif

41116_2023_36_Article_IEq117.gif

Fig. 2

41116_2023_36_Article_IEq116.gif

41116_2023_36_Article_IEq115.gif

41116_2023_36_Article_IEq818.gif

41116_2023_36_Article_IEq817.gif

41116_2023_36_Article_IEq816.gif

41116_2023_36_Article_IEq815.gif

41116_2023_36_Article_IEq813.gif

41116_2023_36_Article_IEq811.gif

41116_2023_36_Article_IEq809.gif

40517_2023_258_Article_IEq102.gif

41116_2023_36_Article_IEq806.gif

41116_2023_36_Article_IEq805.gif

41116_2023_36_Article_IEq803.gif

41116_2023_36_Article_IEq801.gif

41116_2023_36_Article_IEq799.gif

41116_2023_36_Article_IEq797.gif

41116_2023_36_Article_IEq795.gif

Fig. 1

41116_2023_36_Article_IEq793.gif

41116_2023_36_Article_IEq791.gif

41116_2023_36_Article_IEq789.gif

41116_2023_36_Article_IEq786.gif

41116_2023_36_Article_IEq785.gif

41116_2023_36_Article_IEq781.gif

41116_2023_36_Article_IEq778.gif

41116_2023_36_Article_IEq777.gif

41116_2023_36_Article_IEq774.gif

Fig. 2

Fig. 2

41116_2023_36_Article_IEq768.gif

41116_2023_36_Article_IEq767.gif

41116_2023_36_Article_IEq765.gif

41116_2023_36_Article_IEq763.gif

41116_2023_36_Article_IEq761.gif

41116_2023_36_Article_IEq759.gif

41116_2023_36_Article_IEq757.gif

41116_2023_36_Article_IEq754.gif

41116_2023_36_Article_IEq753.gif

41116_2023_36_Article_IEq749.gif

41116_2023_36_Article_IEq748.gif

41116_2023_36_Article_IEq747.gif

41116_2023_36_Article_IEq744.gif

41116_2023_36_Article_IEq737.gif

Fig. 1

41116_2023_36_Article_IEq734.gif

41116_2023_36_Article_IEq733.gif

41116_2023_36_Article_IEq731.gif

40517_2023_258_Article_IEq58.gif

Fig. 3

Fig. 1

41116_2023_36_Article_IEq726.gif

41116_2023_36_Article_IEq724.gif

Fig. 6

41116_2023_36_Article_IEq722.gif

41116_2023_36_Article_IEq720.gif

40517_2023_258_Article_IEq51.gif

41116_2023_36_Article_IEq718.gif

41116_2023_36_Article_IEq716.gif

41116_2023_36_Article_IEq714.gif

Fig. 2

40517_2023_258_Article_IEq46.gif

41116_2023_36_Article_IEq710.gif

41116_2023_36_Article_IEq708.gif

41116_2023_36_Article_IEq706.gif

41116_2023_36_Article_IEq701.gif

40517_2023_258_Article_IEq40.gif

41116_2023_36_Article_IEq700.gif

41116_2023_36_Article_IEq699.gif

41116_2023_36_Article_IEq698.gif

41116_2023_36_Article_IEq696.gif

40517_2023_258_Article_IEq34.gif

41116_2023_36_Article_IEq692.gif

41116_2023_36_Article_IEq689.gif

41116_2023_36_Article_IEq688.gif

41116_2023_36_Article_IEq686.gif

41116_2023_36_Article_IEq682.gif

41116_2023_36_Article_IEq680.gif

Fig. 1

Fig. 1

40517_2023_258_Article_IEq25.gif

41116_2023_36_Article_IEq675.gif

41116_2023_36_Article_IEq674.gif

41116_2023_36_Article_IEq672.gif

41116_2023_36_Article_IEq670.gif

41116_2023_36_Article_IEq667.gif

41116_2023_36_Article_IEq664.gif

41116_2023_36_Article_IEq663.gif

41116_2023_36_Article_IEq658.gif

41116_2023_36_Article_IEq657.gif

41116_2023_36_Article_IEq656.gif

41116_2023_36_Article_IEq655.gif

41116_2023_36_Article_IEq653.gif

41116_2023_36_Article_IEq649.gif

41116_2023_36_Article_IEq644.gif

Fig. 2

41116_2023_36_Article_IEq639.gif

Fig. 1

41116_2023_36_Article_IEq633.gif

41116_2023_36_Article_IEq631.gif

41116_2023_36_Article_IEq627.gif

41116_2023_36_Article_IEq623.gif

41116_2023_36_Article_IEq619.gif

41116_2023_36_Article_IEq616.gif

Fig. 1

40517_2023_258_Article_IEq11.gif

Fig. 1

40517_2023_258_Article_IEq8.gif

40517_2023_258_Article_IEq7.gif

Fig. 1

41116_2023_36_Article_IEq500.gif

41116_2023_36_Article_IEq499.gif

41116_2023_36_Article_IEq498.gif

41116_2023_36_Article_IEq497.gif

41116_2023_36_Article_IEq496.gif

Fig. 1

41116_2023_36_Article_IEq493.gif

12888_2023_4776_Article_IEq1.gif

41116_2023_36_Article_IEq489.gif

41116_2023_36_Article_IEq486.gif

41116_2023_36_Article_IEq483.gif

41116_2023_36_Article_IEq465.gif

41116_2023_36_Article_IEq456.gif

41116_2023_36_Article_IEq454.gif

41116_2023_36_Article_IEq446.gif

41116_2023_36_Article_IEq416.gif