Dataset Information

Finding vulnerable subpopulations in the Seychelles Child Development Study: effect modification with latent groups.

ABSTRACT: The Seychelles Child Development Study is a research project with the objective of examining associations between prenatal exposure to low doses of methylmercury from maternal fish consumption and children's developmental outcomes. Whether methylmercury has neurotoxic effects at low doses remains unclear and recommendations for pregnant women and children to reduce fish intake may prevent a substantial number of people from receiving sufficient nutrients that are abundant in fish. The primary findings of the Seychelles Child Development Study are inconsistent with adverse associations between methylmercury from fish consumption and neurodevelopmental outcomes. However, whether there are subpopulations of children who are particularly sensitive to this diet is an open question. Secondary analysis from this study found significant interactions between prenatal methylmercury levels and both caregiver IQ and income on 19-month IQ. These results are sensitive to the categories chosen for these covariates and are difficult to interpret collectively. In this paper, we estimate effect modification of the association between prenatal methylmercury exposure and 19-month IQ using a general formulation of mixture regression. Our mixture regression model creates a latent categorical group membership variable which interacts with methylmercury in predicting the outcome. We also fit the same outcome model when in addition the latent variable is assumed to be a parametric function of three distinct socioeconomic measures. Bayesian methods allow group membership and the regression coefficients to be estimated simultaneously and our approach yields a principled choice of the number of distinct subpopulations. The results show three groups with different response patterns between prenatal methylmercury exposure and 19-month IQ in this population.

SUBMITTER: Love TM

PROVIDER: S-EPMC4577466 | biostudies-other | 2017 Apr

REPOSITORIES: biostudies-other

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Finding vulnerable subpopulations in the Seychelles Child Development Study: effect modification with latent groups.

Love Tanzy Mt TM Thurston Sally W SW Davidson Philip W PW

Statistical methods in medical research 20141214 2

The Seychelles Child Development Study is a research project with the objective of examining associations between prenatal exposure to low doses of methylmercury from maternal fish consumption and children's developmental outcomes. Whether methylmercury has neurotoxic effects at low doses remains unclear and recommendations for pregnant women and children to reduce fish intake may prevent a substantial number of people from receiving sufficient nutrients that are abundant in fish. The primary fi ...[more]

PMID: 25512145

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Project description:BackgroundLimited options are available for dose-finding clinical trials requiring group-specific dose selection. While conducting parallel trials for groups is an accessible approach to group-specific dose selection, this approach allows for maximum tolerated dose selection that does not align with clinically meaningful group order information.MethodsThe two-stage continual reassessment method is developed for dose-finding in studies involving three or more groups where group frailty order is known between some but not all groups, creating a partial order. This is an extension of the existing continual reassessment method shift model for two ordered groups. This method allows for dose selection by group, where maximum tolerated dose selection follows the known frailty order among groups. For example, if a group is known to be the most frail, the recommended maximum tolerated dose for this group should not exceed the maximum tolerated dose recommended for any other group.ResultsWith limited alternatives for dose-finding in partially ordered groups, this method is compared to two alternatives: (1) an existing method for dose-finding in partially ordered groups which is less computationally accessible and (2) independent trials for each group using the two-stage continual reassessment method. Simulation studies show that when ignoring information on group frailty, using independent continual reassessment method trials by group, 30% of simulations would result in maximum tolerated dose selection that is out of order between groups. In addition, the two-stage continual reassessment method for partially ordered groups selects the maximum tolerated dose more often and assigns more patients to the maximum tolerated dose compared to using independent continual reassessment method trials within each group. Simulation results for the proposed method and the less computationally accessible approach are similar.ConclusionThe proposed continual reassessment method for partially ordered groups ensures appropriate maximum tolerated dose order and improves accuracy of maximum tolerated dose selection, while allowing for trial implementation that is computationally accessible.

Dataset Information

Finding vulnerable subpopulations in the Seychelles Child Development Study: effect modification with latent groups.

Publications

Finding vulnerable subpopulations in the Seychelles Child Development Study: effect modification with latent groups.

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