Table 2.
Methodological Characteristics of Mediation Analyses Performed Based on Observational Epidemiologic Studies Published Between 2015 and 2019
| Methodological characteristics | Overall (n = 174) | Causal steps, change-in-coefficient, and joint significance (n = 28) | Traditional mediation analysis (n = 123) | Causal mediation analysis (n = 23) |
|---|---|---|---|---|
| Year published, n (%)a | ||||
| 2015 | 21 (12.1) | 4 (14.3) | 16 (13.0) | 1 (4.3) |
| 2016 | 29 (16.7) | 8 (28.6) | 16 (13.0) | 5 (21.7) |
| 2017 | 27 (15.5) | 2 (7.1) | 21 (17.1) | 4 (17.4) |
| 2018 | 47 (27.0) | 6 (21.4) | 34 (27.6) | 7 (30.4) |
| 2019 | 50 (28.7) | 8 (28.6) | 36 (29.3) | 6 (26.1) |
| Study design, n (%)a | ||||
| Cross-sectional | 84 (48.3) | 15 (53.6) | 64 (52.0) | 5 (21.7) |
| Case-control | 7 (4.0) | 1 (3.6) | 3 (2.4) | 3 (13.0) |
| Prospective cohort | 78 (44.8) | 12 (42.9) | 53 (43.1) | 13 (56.5) |
| Retrospective cohort | 5 (2.9) | 0 (0.0) | 3 (2.4) | 2 (8.7) |
| Analytical sample size, median (IQR) | 428.5 (157.5–2026.0) | 443.5 (146.5–1442.3) | 326.0 (147.0–935.0) | 2249.0 (703.0–9484.0) |
| Software program used, n (%)a | ||||
| SAS | 21 (12.1) | 4 (14.3) | 9 (7.3) | 8 (34.8) |
| Stata | 27 (15.5) | 5 (17.9) | 18 (14.6) | 4 (17.4) |
| SPSS | 67 (38.5) | 13 (46.4) | 54 (43.9) | 0 (0.0) |
| Mplus | 26 (14.9) | 1 (3.6) | 25 (20.3) | 0 (0.0) |
| R | 14 (8.0) | 0 (0.0) | 5 (4.1) | 9 (39.1) |
| LISREL | 1 (0.6) | 0 (0.0) | 1 (0.8) | 0 (0.0) |
| Unclear, multiple programs used | 5 (2.9) | 1 (3.6) | 4 (3.3) | 0 (0.0) |
| Not mentioned | 13 (7.5) | 4 (14.3) | 7 (5.7) | 2 (8.7) |
| Number of exposures, n (%)a | ||||
| 1 | 116 (66.7) | 19 (67.9) | 81 (65.9) | 16 (69.6) |
| 2 | 35 (20.1) | 3 (10.7) | 26 (21.1) | 6 (26.1) |
| 3 or more (max. 14) | 23 (13.2) | 6 (21.4) | 16 (13.0) | 1 (4.3) |
| Type of exposure, n (% of studies)b | ||||
| Continuous | 105 (60.3) | 15 (53.6) | 84 (68.3) | 6 (26.1) |
| Binary | 51 (29.3) | 8 (28.6) | 28 (22.8) | 15 (65.2) |
| Categorical | 20 (11.5) | 5 (17.9) | 11 (8.9) | 4 (17.4) |
| Latent | 10 (5.7) | 2 (7.1) | 8 (34.8) | 0 (0.0) |
| Number of mediators, n (%)a | ||||
| 1 | 86 (49.4) | 14 (50.0) | 59 (48.0) | 13 (56.5) |
| 2 | 35 (20.1) | 5 (17.9) | 28 (22.8) | 2 (8.7) |
| 3 or more (max. 19) | 53 (30.5) | 9 (32.1) | 36 (29.3) | 8 (34.8) |
| Type of mediator, n (% of studies)b | ||||
| Continuous | 136 (78.2) | 19 (67.9) | 103 (83.7) | 14 (60.9) |
| Binary | 31 (17.8) | 10 (35.7) | 13 (10.6) | 8 (34.8) |
| Categorical | 9 (5.2) | 3 (10.7) | 3 (2.4) | 3 (13.0) |
| Count | 1 (0.6) | 0 (0.0) | 0 (0.0) | 1 (4.3) |
| Time-to-event | 2 (1.1) | 0 (0.0) | 2 (1.6) | 0 (0.0) |
| Latent | 10 (5.7) | 3 (10.7) | 7 (5.7) | 0 (0.0) |
| Number of outcomes, n (%)a | ||||
| 1 | 126 (72.4) | 22 (78.6) | 88 (71.5) | 16 (69.6) |
| 2 | 26 (15.0) | 2 (7.1) | 22 (17.9) | 2 (8.7) |
| 3 or more (max. 8) | 22 (12.6) | 4 (14.3) | 13 (10.6) | 5 (21.6) |
| Type of outcome, n (% of studies)b | ||||
| Continuous | 110 (63.2) | 18 (64.3) | 86 (69.9) | 6 (26.1) |
| Binary | 47 (27.0) | 6 (21.4) | 27 (22.0) | 14 (60.9) |
| Categorical | 6 (3.4) | 2 (7.1) | 3 (2.4) | 1 (4.3) |
| Count | 4 (2.3) | 0 (0.0) | 2 (1.6) | 2 (8.7) |
| Time-to-event | 8 (4.6) | 3 (10.7) | 3 (2.4) | 2 (8.7) |
| Latent | 10 (5.7) | 3 (10.7) | 7 (5.7) | 0 (0.0) |
| Diagram of model included, n (%)a | ||||
| Yes | 130 (74.7) | 14 (50.0) | 106 (86.2) | 10 (43.5) |
| No | 44 (25.3) | 14 (50.0) | 17 (13.8) | 13 (56.5) |
| Repeated measurements, n (%)a | ||||
| Yes | 41 (23.6) | 6 (21.4) | 28 (22.8) | 7 (30.4) |
| No | 132 (75.9) | 22 (78.6) | 94 (76.4) | 16 (69.6) |
| Unclear | 1 (0.6) | 0 (0.0) | 1 (0.8) | 0 (0.0) |
| Type of mediation model, n (%)a | ||||
| Single mediator | 114 (65.5) | 20 (71.4) | 74 (60.2) | 20 (87.0) |
| Multiple mediator | 41 (23.6) | 5 (17.9) | 34 (27.6) | 2 (8.7) |
| Both single and multiple mediator | 16 (9.2) | 3 (10.7) | 12 (9.8) | 1 (4.3) |
| Unclear | 3 (1.7) | 0 (0.0) | 3 (2.4) | 0 (0.0) |
| Regression for the mediator equation, n (% of studies)b | ||||
| Linear | 122 (70.1) | 14 (50.0) | 98 (79.7) | 10 (43.4) |
| Logistic | 15 (8.6) | 2 (7.1) | 7 (5.7) | 6 (26.1) |
| Poisson | 1 (0.6) | 0 (0.0) | 0 (0.0) | 1 (4.3) |
| Cox proportional hazards | 2 (1.1) | 0 (0.0) | 2 (1.6) | 0 (0.0) |
| Multilevel linear | 7 (4.0) | 0 (0.0) | 7 (5.7) | 0 (0.0) |
| Multilevel logistic | 1 (0.6) | 1 (3.6) | 0 (0.0) | 0 (0.0) |
| Unclear | 16 (9.2) | 2 (7.1) | 8 (6.5) | 6 (26.1) |
| Not estimated | 12 (6.9) | 9 (32.1) | 3 (2.4) | 0 (0.0) |
| Regression for the outcome equation, n (% of studies)b | ||||
| Linear | 109 (62.6) | 17 (60.7) | 87 (70.7) | 5 (21.7) |
| Logistic | 39 (22.4) | 5 (17.9) | 23 (18.7) | 11 (47.8) |
| Probit | 1 (0.6) | 0 (0.0) | 1 (0.8) | 0 (0.0) |
| Log-linear | 1 (0.6) | 0 (0.0) | 0 (0.0) | 1 (4.3) |
| Multinomial logistic | 1 (0.6) | 1 (3.6) | 2 (1.6) | 0 (0.0) |
| Poisson | 3 (1.7) | 0 (0.0) | 0 (0.0) | 3 (13.0) |
| Negative binomial | 3 (1.7) | 0 (0.0) | 1 (0.8) | 2 (8.7) |
| Cox proportional hazards | 10 (5.7) | 4 (14.3) | 4 (3.3) | 1 (4.3) |
| Additive hazards model | 1 (0.6) | 0 (0.0) | 0 (0.0) | 1 (4.3) |
| Multilevel linear | 9 (5.2) | 2 (7.1) | 7 (5.7) | 0 (0.0) |
| Multilevel logistic | 1 (0.6) | 0 (0.0) | 1 (0.8) | 0 (0.0) |
| Multilevel log-linear | 1 (0.6) | 0 (0.0) | 1 (0.8) | 0 (0.0) |
| Unclear | 3 (1.7) | 1 (3.6) | 1 (0.8) | 1 (4.3) |
| Type of confidence interval for the indirect effect, n (%)a | ||||
| Normal-based | 7 (4.0) | 0 (0.0) | 6 (4.9) | 1 (4.3) |
| Percentile bootstrap | 7 (4.0) | 0 (0.0) | 5 (4.1) | 2 (8.7) |
| Bias-corrected bootstrap | 35 (20.1) | 0 (0.0) | 35 (28.5) | 0 (0.0) |
| Bias-corrected and accelerated bootstrap | 2 (1.1) | 0 (0.0) | 2 (1.6) | 0 (0.0) |
| Percentile and bias-corrected and accelerated bootstrap | 1 (0.6) | 0 (0.0) | 1 (0.8) | 0 (0.0) |
| Bootstrap, not specified | 36 (20.7) | 1 (3.6) | 28 (22.8) | 7 (30.4) |
| Distribution of the product | 3 (1.7) | 0 (0.0) | 3 (2.4) | 0 (0.0) |
| Monte Carlo | 2 (1.1) | 0 (0.0) | 2 (1.6) | 0 (0.0) |
| Bayesian credible intervals | 3 (1.7) | 0 (0.0) | 3 (2.4) | 0 (0.0) |
| Unclear | 18 (10.3) | 0 (0.0) | 8 (6.5) | 10 (43.5) |
| Not reported | 60 (34.5) | 27 (96.4) | 30 (24.4) | 3 (13.0) |
| Standard error for indirect effect, n (%)a | ||||
| Yes | 37 (21.3) | 0 (0.0) | 35 (28.5) | 2 (8.7) |
| No | 137 (78.7) | 28 (100.0) | 88 (71.5) | 21 (91.3) |
| Statistical test for indirect effect, n (%)a | ||||
| Yes | 62 (35.6) | 7 (25.0) | 46 (37.4) | 9 (39.1) |
| No | 112 (64.4) | 21 (75.0) | 77 (62.6) | 14 (58.3) |
| Effect size measure, n (%)a | ||||
| Proportion mediated | 65 (37.4) | 3 (10.7) | 43 (35.0) | 19 (82.6) |
| Standardized effect | 6 (3.4) | 0 (0.0) | 6 (4.9) | 0 (0.0) |
| No effect size measure | 103 (59.2) | 25 (89.3) | 74 (60.2) | 4 (17.4) |
| Inclusion of confounders, n (%)a | ||||
| Yes | 125 (71.8) | 19 (67.9) | 88 (71.5) | 18 (78.3) |
| No | 41 (23.6) | 8 (28.6) | 31 (25.2) | 2 (8.7) |
| Unclear | 8 (4.6) | 1 (3.6) | 4 (3.3) | 3 (13.0) |
| Sensitivity analyses for unmeasured confounders, n (%)a | ||||
| Yes | 3 (1.7) | 0 (0.0) | 0 (0.0) | 3 (13.0) |
| No | 170 (97.7) | 28 (100.0) | 123 (0.0) | 19 (82.6) |
| No, but discussed as unnecessary | 1 (0.6) | 0 (0.0) | 0 (0.0) | 1 (4.3) |
| Effect modifiers considered, n (%)a | ||||
| Yes, a priori stratification | 10 (5.7) | 3 (10.7) | 5 (4.1) | 2 (8.7) |
| Yes, through an interaction term | 28 (16.1) | 6 (21.4) | 19 (15.4) | 3 (13.0) |
| No | 136 (78.2) | 19 (67.9) | 99 (80.5) | 18 (78.3) |
| Assessment of exposure-mediator interaction, n (%)a | ||||
| Yes | 17 (9.8) | 3 (10.7) | 5 (4.1) | 9 (39.1) |
| No | 157 (90.2) | 25 (89.3) | 118 (95.9) | 14 (60.9) |
a The percentages are computed based on the column frequencies
b Because some studies considered multiple exposure, mediator, and outcome variables, the total number is higher than the number of studies. The percentages reflect the percentages of the total number of studies, e.g., 60.3% of the studies included analyses with a continuous exposure variable versus 39.7% which did not include analyses with a continuous exposure variable