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A method to detect residual confounding in spatial and other observational studies.

ABSTRACT: Residual confounding is challenging to detect. Recently, we described a method for detecting confounding and justified it primarily for time-series studies. The method depends on an indicator with 2 key characteristics: (1) it is conditionally independent (given measured exposures and covariates) of the outcome, in the absence of confounding, misspecification, and measurement errors; and (2) like the exposure, it is associated with confounders, possibly unmeasured. We proposed using future exposure levels as the indicator to detect residual confounding. This choice seems natural for time-series studies because future exposure cannot have caused the event, yet they could be spuriously related to it. A related question addressed here is whether an analogous indicator can be used to identify residual confounding in a study based on spatial, rather than temporal, contrasts.Using directed acyclic graphs, we show that future air pollution levels may have the characteristics appropriate for an indicator of residual confounding in spatial studies of environmental exposures. We empirically evaluate performance for spatial studies using simulations.In simulations based on a spatial study of ambient air pollution levels and birth weight in Atlanta, and using ambient air pollution 1 year after conception as the indicator, we were able to detect residual confounding. The discriminatory ability approached 100% for some factors intentionally omitted from the model, but was very weak for others.The simulations illustrate that an indicator based on future exposures can have excellent ability to detect residual confounding in spatial studies, although performance varied by situation.

SUBMITTER: Flanders WD

PROVIDER: S-EPMC3233361 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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A method to detect residual confounding in spatial and other observational studies.

Flanders W Dana WD Klein Mitchel M Darrow Lyndsey A LA Strickland Matthew J MJ Sarnat Stefanie E SE Sarnat Jeremy A JA Waller Lance A LA Winquist Andrea A Tolbert Paige E PE

Epidemiology (Cambridge, Mass.) 20111101 6

<h4>Background</h4>Residual confounding is challenging to detect. Recently, we described a method for detecting confounding and justified it primarily for time-series studies. The method depends on an indicator with 2 key characteristics: (1) it is conditionally independent (given measured exposures and covariates) of the outcome, in the absence of confounding, misspecification, and measurement errors; and (2) like the exposure, it is associated with confounders, possibly unmeasured. We proposed ...[more]

PMID: 21968772

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Project description:Numerous observational studies suggest that bisphosphonates reduce mortality. This study showed that bisphosphonate use is associated with lower mortality within days of treatment, although the association was not significant until the second week. Such an early association is consistent with confounding, although an early treatment effect cannot be ruled out.IntroductionThe purpose of this study was to examine whether confounding explains why numerous observational studies show that bisphosphonate use is associated with lower mortality. To this end, we examined how soon after treatment initiation a lower mortality rate can be observed. We hypothesized that, due to confounding, the association would be observed immediately.MethodsThis was a retrospective cohort study of hip fracture patients discharged from Swedish hospitals between 1 July 2006 and 31 December 2015. The data covered 260,574 hip fracture patients and were obtained from the Swedish Hip Fracture Register and national registers. Of the 260,574 patients, 49,765 met all eligibility criteria and 10,178 were pair matched (bisphosphonate users to controls) using time-dependent propensity scores. The matching variables were age, sex, diagnoses, prescription medications, type of hip fracture, type of surgical procedure, known or suspected dementia, and physical functioning status.ResultsOver a median follow-up of 2.8 years, 2922 of the 10,178 matched patients died. The mortality rate was 7.9 deaths per 100 person-years in bisphosphonate users and 9.4 deaths in controls, which corresponded to a 15% lower mortality rate in bisphosphonate users (hazard ratio 0.85, 95% confidence interval 0.79-0.91). The risk of death was lower in bisphosphonate users from day 6 of treatment, although the association was not significant until the second week.ConclusionBisphosphonate use was associated with lower mortality within days of treatment initiation. This finding is consistent with confounding, although an early treatment effect cannot be ruled out.

Project description:ObjectivesTo estimate the association between childhood vaccination and subsequent morbidity and mortality by adjusting for environmental and host factors. Further, to examine the degree of residual confounding in such observational studies.DesignRegister-based cohort study including 1 122 929 Danish children.ParticipantsAll children born in Denmark in the period 1999-2016 who survived until 16 months of age without prior migration followed from 16 months until the first of the following: event of interest, migration, 5 years of age or 31 December 2016.Main outcome measuresAdjusted HRs (aHRs) and absolute risks were calculated for the three outcomes: mortality, hospitalisation for infection and asthma using register data on deaths, specific hospital contacts and dispensed prescribed medication. The exposure was the combination of the routine vaccines against diphteria-tetanus-pertussis-polio-Haemophilus influenzae type b and measles-mumps-rubella (DTP and MMR in short) administered in early childhood. Hospitalisation due to accidents was analysed as a negative control outcome to examine residual confounding.ResultsChildren with 3DTP+MMR had a lower hazard of mortality than the reference group with 3DTP, adjusted HR (aHR)=0.45 (95% CI: 0.35 to 0.57), whereas the children with 1 or 2 DTP had higher hazards of dying, aHR=1.55 (95% CI: 1.14 to 2.13) and aHR=1.96 (95% CI: 1.34 to 2.89). The vaccination group 3DTP+MMR was associated with a reduced hazard of asthma aHR=0.94 (95% CI: 0.92 to 0.96). Also, the vaccination group 3DTP+MMR was associated with a reduced hazard of hospitalisation due to accidents, aHR=0.83 (0.80 to 0.85) compared with the reference group with 3 DTP.ConclusionsThe results suggested a beneficial impact of MMR on under-five mortality but did not support the hypothesis that DTP is detrimental, since the group of children with fewer DTP vaccinations experienced increased mortality. The results of the study may to some degree be prone to residual confounding since an unexpected association between MMR vaccination and hospitalisation for accidents was observed.

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A method to detect residual confounding in spatial and other observational studies.

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A method to detect residual confounding in spatial and other observational studies.

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