L. Paloma Rojas-Saunero MD, PhD
Postdoctoral scholar
Mayeda Research Group, Department of Epidemiology
Hill et al. Ethnicity and disease. 2015
www.express.co.uk, 2016
Medscape, 2019
Austin et al. Circulation.2016
Searching criteria
Original research published between Jan/2018 to Dec/2019
Dementia/AD & longitudinal/cohort & hazard/risk
Alzheimer’s and Dementia, Annals of Neurology, BMJ, Neurology, JAMA, Jama Neurology, Lancet, Lancet Neurology
Searching criteria
Original research published between Jan/2018 to Dec/2019
Dementia/AD & longitudinal/cohort & hazard/risk
Alzheimer’s and Dementia, Annals of Neurology, BMJ, Neurology, JAMA, Jama Neurology, Lancet, Lancet Neurology
Eligibility criteria
Time-to-dementia/AD as primary or co-primary outcome
With a clear exposure/intervention, and uses methods to handle confounding
Not a descriptive or predictive aim
Out of 57/209 papers included:
Out of 57/209 papers included:
Out of 57/209 papers included:
56% report death numbers, 18% death by exposure level
47% do not include any description about death in the methods section, 26% consider it a sensitivity example, 14% only mention it was treated as a censoring event
Out of 57/209 papers included:
56% report death numbers, 18% death by exposure level
47% do not include any description about death in the methods section, 26% consider it a sensitivity example, 14% only mention it was treated as a censoring event
87% use Cox PH models, 93% present hazard ratios
Out of 57/209 papers included:
56% report death numbers, 18% death by exposure level
47% do not include any description about death in the methods section, 26% consider it a sensitivity example, 14% only mention it was treated as a censoring event
87% use Cox PH models, 93% present hazard ratios
86% innacurate interpretations (e.g. "risks")
What is the risk of dementia at 20 years of follow-up had all individuals stopped smoking, compared to had all individuals continued smoking?
Pr[Ya=120]−Pr[Ya=020]
What is the risk of dementia at 20 years of follow-up had all individuals stopped smoking, compared to had all individuals continued smoking?
Pr[Ya=120]−Pr[Ya=020]
What is the risk of dementia at 20 years of follow-up had all individuals stopped smoking and not died throughout the study period, compared to had all individuals continued smoking in adulthood and not died throughout the study period?
Pr[Ya=1,d19=020]−Pr[Ya=0,d19=020]
What is the risk of dementia at 20 years of follow-up had all individuals stopped smoking and not died throughout the study period, compared to had all individuals continued smoking in adulthood and not died throughout the study period?
Pr[Ya=1,d19=020]−Pr[Ya=0,d19=020]
What is the risk of dementia at 20 years of follow-up had all individuals stopped smoking and not died throughout the study period, compared to had all individuals continued smoking in adulthood and not died throughout the study period?
Pr[Ya=1,d19=020]−Pr[Ya=0,d19=020]
Assumption | Total Effect | Controlled direct effect |
---|---|---|
Exchangeability assumption needed for death (competing events)? | Not needed | At each k + 1, conditional on the measured past, death is independent of future counterfactual outcomes had everyone followed A = a and death was eliminated. |
Assumption | Total Effect | Controlled direct effect |
---|---|---|
Exchangeability assumption needed for death (competing events)? | Not needed | At each k + 1, conditional on the measured past, death is independent of future counterfactual outcomes had everyone followed A = a and death was eliminated. |
Positivity assumption needed for death (competing events)? | Not needed | For any possibly observed level A = a and covariate history amongst those remaining uncensored (alive) and free of dementia diagnosis through k, some individuals continue to remain alive through _k + 1_. |
Assumption | Total Effect | Controlled direct effect |
---|---|---|
Exchangeability assumption needed for death (competing events)? | Not needed | At each k + 1, conditional on the measured past, death is independent of future counterfactual outcomes had everyone followed A = a and death was eliminated. |
Positivity assumption needed for death (competing events)? | Not needed | For any possibly observed level A = a and covariate history amongst those remaining uncensored (alive) and free of dementia diagnosis through k, some individuals continue to remain alive through _k + 1_. |
Consistency assumption needed for death (competing events) | Not needed | An intervention that “eliminates death (competing events)” is well-defined. |
Participants from Rotterdam Study I, recruited between 1990-1993 and with follow-up data
Current and former smokers
No prior history of dementia diagnosis
Complete information at baseline
Final sample size of 4179 participants
Mean age at baseline of 62 years
368 developed dementia and 1318 died
For confounding: Inverse probability weighting for treatment (IPTW)
Total effect: Cause-specific cumulative incidence / Aalen-Johansen estimator + IPTW
For confounding: Inverse probability weighting for treatment (IPTW)
Total effect: Cause-specific cumulative incidence / Aalen-Johansen estimator + IPTW
Controlled direct effect: Kaplan-Meier + Inverse probability censoring weights + IPTW
For confounding: Inverse probability weighting for treatment (IPTW)
Total effect: Cause-specific cumulative incidence / Aalen-Johansen estimator + IPTW
Controlled direct effect: Kaplan-Meier + Inverse probability censoring weights + IPTW
Bootstrapping for confidence intervals
Semi-parametric or parametric alternatives are also possible
Causal effect | Risk Difference (95%CI) | Risk Ratio (95%CI) |
---|---|---|
Total effect on dementia | 2.1 (-0.1, 4.2) | 1.21 (0.99, 1.50) |
Controlled direct effect on dementia (with IPCW for death) | -2.6 (-6.1, 0.8) | 0.86 (0.72, 1.05) |
Total effect on mortality | -17.4 (-20.5, -14.2) | 0.68, (0.63, 0.72) |
Assumption | Risk Difference (95%CI) | Risk Ratio (95%CI) |
---|---|---|
Evoking unconditional exchangeability assumption for censoring | -0.7 (-3.3, 2.2) | 0.96 (0.82, 1.16) |
Evoking conditional exchangeability assumption on baseline covariates for censoring | -1.5 (-4.6, 1.8) | 0.92 (0.78, 1.12) |
Evoking conditional exchangeability assumption on baseline and time-varying covariates for censoring | -2.7 (-6.1, 0.8) | 0.86 (0.7, 1.1) |
Survivors average causal effect: The risk of dementia on a subgroup of individuals who would never experience the competing event.
Separable effects: Effects of modified treatments motivated by the physical decomposition of the exposure assumed to operate on dementia and death through separate pathways.
Survivors average causal effect: The risk of dementia on a subgroup of individuals who would never experience the competing event.
Separable effects: Effects of modified treatments motivated by the physical decomposition of the exposure assumed to operate on dementia and death through separate pathways.
Composite outcome of dementia and death
When competing events are present there is more than one way to consider them as part of the primary research question.
Let the question guide the most appropiate methods and estimators.
When competing events are present there is more than one way to consider them as part of the primary research question.
Let the question guide the most appropiate methods and estimators.
For various reasons, risks and survival curves should be preferred over hazards.
When competing events are present there is more than one way to consider them as part of the primary research question.
Let the question guide the most appropiate methods and estimators.
For various reasons, risks and survival curves should be preferred over hazards.
Collaborative work between clinical researchers, epidemiologists and statisticians should narrow the gap between methods development and applied research.
Hill et al. Ethnicity and disease. 2015
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