A Bayesian natural cubic B-spline varying coefficient method for non-ignorable dropout

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(2020) 20:250

RESEARCH ARTICLE

Open Access

A Bayesian natural cubic B-spline varying coefficient method for non-ignorable dropout Camille M. Moore1,2*

, Samantha MaWhinney2 , Nichole E. Carlson2 and Sarah Kreidler3

Abstract Background: Dropout is a common problem in longitudinal clinical trials and cohort studies, and is of particular concern when dropout occurs for reasons that may be related to the outcome of interest. This paper reviews common parametric models to account for dropout and introduces a Bayesian semi-parametric varying coefficient model for exponential family longitudinal data with non-ignorable dropout. Methods: To demonstrate these methods, we present results from a simulation study and estimate the impact of drug use on longitudinal CD4+ T cell count and viral load suppression in the Women’s Interagency HIV Study. Sensitivity analyses are performed to consider the impact of model assumptions on inference. We compare results between our semi-parametric method and parametric models to account for dropout, including the conditional linear model and a parametric frailty model. We also compare results to analyses that fail to account for dropout. Results: In simulation studies, we show that semi-parametric methods reduce bias and mean squared error when parametric model assumptions are violated. In analyses of the Women’s Interagency HIV Study data, we find important differences in estimates of changes in CD4+ T cell count over time in untreated subjects that report drug use between different models used to account for dropout. We find steeper declines over time using our semi-parametric model, which makes fewer assumptions, compared to parametric models. Failing to account for dropout or to meet parametric assumptions of models to account for dropout could lead to underestimation of the impact of hard drug use on CD4+ cell count decline in untreated subjects. In analyses of subjects that initiated highly active anti-retroviral treatment, we find that the estimated probability of viral load suppression is lower in models that account for dropout. Conclusions: Non-ignorable dropout is an important consideration when analyzing data from longitudinal clinical trials and cohort studies. While methods that account for non-ignorable dropout must make some unavoidable assumptions that cannot be verified from the observed data, many methods make additional parametric assumptions. If these assumptions are not met, inferences can be biased, making more flexible methods with minimal assumptions important. Keywords: Reversible jump Markov chain Monte Carlo, Missing data, Dropout, Varying coefficient model, HIV

*Correspondence: [email protected] Center for Genes, Environment and Health, National Jewish Health, 1400 Jackson St., 80206 Denver, CO, USA 2 Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, 17th Pl., Mail Stop B119, 80045 Aurora, CO, USA Full list of author information is available at the end of the article 1

© The Author(s). 2020 Ope