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Confounding in longitudinal studies in addiction treatment research.

ABSTRACT: Background: The effectiveness of treatment for people with substance use disorders is usually examined using longitudinal cohorts. In these studies, treatment is often considered as a time-varying exposure. The aim of this commentary is to examine confounding in this context, when the confounding variable is time-invariant and when it is time-varying. Method: Types of confounding are described with examples and illustrated using path diagrams. Simulations are used to demonstrate the direction of confounding bias and the extent that it is accounted for using standard regression adjustment techniques. Results: When the confounding variable is time invariant or time varying and not influenced by prior treatment, then standard adjustment techniques are adequate to control for confounding bias, provided that in the latter scenario the time-varying form of the variable is used. When the confounder is time varying and affected by prior treatment status (i.e. it is a mediator of treatment), then standard methods of adjustment result in inconsistency. Conclusions: In longitudinal cohorts where treatment exposure is time varying, confounding is an issue which should be considered, even if treatment exposure is initially randomized. In these studies, standard methods of adjustment may result be inadequate, even when all confounders have been identified. This occurs when the confounder is also a mediator of treatment. This is a likely scenario in many studies in addiction.

SUBMITTER: Pierce M

PROVIDER: S-EPMC5360166 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Confounding in longitudinal studies in addiction treatment research.

Pierce Matthias M Dunn Graham G Millar Tim T

Addiction research & theory 20161222 3

<b>Background:</b> The effectiveness of treatment for people with substance use disorders is usually examined using longitudinal cohorts. In these studies, treatment is often considered as a time-varying exposure. The aim of this commentary is to examine confounding in this context, when the confounding variable is time-invariant and when it is time-varying. <b>Method:</b> Types of confounding are described with examples and illustrated using path diagrams. Simulations are used to demonstrate th ...[more]

PMID: 28392755

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Project description:ObjectivesTo adjust for confounding in observational data, researchers use propensity score matching (PSM), but more advanced methods might be required when dealing with longitudinal data and time-varying treatments as PSM might not include possible changes that occurred over time. This study aims to explore which confounding adjustment methods have been used in longitudinal observational data to estimate a treatment effect and identify potential inappropriate use of PSM.DesignMapping review.Data sourcesWe searched PubMed, from inception up to January 2021, for studies in which a treatment was evaluated using longitudinal observational data.Eligibility criteriaMethodological, non-medical and cost-effectiveness papers were excluded, as were non-English studies and studies that did not study a treatment effect.Data extraction and synthesisStudies were categorised based on time of treatment: at baseline (interventions performed at start of follow-up) or time-varying (interventions received asynchronously during follow-up) and sorted based on publication year, time of treatment and confounding adjustment method. Cumulative time series plots were used to investigate the use of different methods over time. No risk-of-bias assessment was performed as it was not applicable.ResultsIn total, 764 studies were included that met the eligibility criteria. PSM (165/201, 82%) and inverse probability weighting (IPW; 154/502, 31%) were most common for studies with a treatment at baseline (n=201) and time-varying treatment (n=502), respectively. Of the 502 studies with a time-varying treatment, 123 (25%) used PSM with baseline covariates, which might be inappropriate. In the past 5 years, the proportion of studies with a time-varying treatment that used PSM over IPW increased.ConclusionsPSM is the most frequently used method to correct for confounding in longitudinal observational data. In studies with a time-varying treatment, PSM was potentially inappropriately used in 25% of studies. Confounding adjustment methods designed to deal with a time-varying treatment and time-varying confounding are available, but were only used in 45% of the studies with a time-varying treatment.

Project description:IntroductionGiven the severity and impact of the current Zika virus (ZIKV) outbreak in the Americas, numerous countries have rushed to develop research studies to assess ZIKV and its potential health consequences. In an effort to ensure that studies are comprehensive, both internally and externally valid, and with reliable results, the World Health Organization, the Pan American Health Organization, Institut Pasteur, the networks of Fiocruz, the Consortia for the Standardization of Influenza Seroepidemiology (CONSISE) and the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) have generated six standardized clinical and epidemiological research protocols and questionnaires to address key public health questions on ZIKV.MethodsWe conducted a systematic search of ongoing study protocols related to ZIKV research. We analyzed the content of protocols of 32 cohort studies and 13 case control studies for systematic bias that could produce erroneous results. Additionally we aimed to characterize the risks of bias and confounding in observational studies related to ZIKV and to propose ways to minimize them, including the use of six newly standardized research protocols.ResultsObservational studies of ZIKV face an array of challenges, including measurement of exposure and outcomes (microcephaly and Guillain-Barré Syndrome). Potential confounders need to be measured where known and controlled for in the analysis. Selection bias due to non-random selection is a significant issue, particularly in the case-control design, and losses to follow-up is equally important for the cohort design.ConclusionObservational research seeking to answer key questions on the ZIKV should consider these restrictions and take precautions to minimize bias in an effort to provide reliable and valid results. Utilization of the standardized research protocols developed by the WHO, PAHO, Institut Pasteur, and CONSISE will harmonize the key methodological aspects of each study design to minimize bias at different stages of the study. Biases need to be considered by researchers implementing the standardized protocols as well as by users of observational epidemiological studies of ZIKV.

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.

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Confounding in longitudinal studies in addiction treatment research.

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Confounding in longitudinal studies in addiction treatment research.

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