Missing Data in Longitudinal Trials - Part B, Analytic Issues.

Longitudinal designs in psychiatric research have many benefits, including the ability to measure the course of a disease over time. However, measuring participants repeatedly over time also leads to repeated opportunities for missing data, either through failure to answer certain items, missed assessments, or permanent withdrawal from the study. To avoid bias and loss of information, one should take missing values into account in the analysis. Several popular ways that are now being used to handle missing data, such as the last observation carried forward (LOCF), often lead to incorrect analyses. We discuss a number of these popular but unprincipled methods and describe modern approaches to classifying and analyzing data with missing values. We illustrate these approaches using data from the WECare study, a longitudinal randomized treatment study of low income women with depression.

[1]  S D Imber,et al.  Some conceptual and statistical issues in analysis of longitudinal psychiatric data. Application to the NIMH treatment of Depression Collaborative Research Program dataset. , 1993, Archives of general psychiatry.

[2]  D. Hedeker,et al.  Bias reduction with an adjustment for participants' intent to dropout of a randomized controlled clinical trial , 2007, Clinical trials.

[3]  Richard J Cook,et al.  Marginal Analysis of Incomplete Longitudinal Binary Data: A Cautionary Note on LOCF Imputation , 2004, Biometrics.

[4]  P W Lavori,et al.  Clinical trials in psychiatry: should protocol deviation censor patient data? , 1992, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[5]  D. Rubin Multiple Imputation After 18+ Years , 1996 .

[6]  Donald Hedeker,et al.  Longitudinal Data Analysis , 2006 .

[7]  Donald Hedeker,et al.  Application of random-efiects pattern-mixture models for miss-ing data in longitudinal studies , 1997 .

[8]  Roger A. Sugden,et al.  Multiple Imputation for Nonresponse in Surveys , 1988 .

[9]  Roderick J. A. Little,et al.  Statistical Analysis with Missing Data: Little/Statistical Analysis with Missing Data , 2002 .

[10]  R. Little,et al.  Pattern-mixture models for multivariate incomplete data with covariates. , 1996, Biometrics.

[11]  D. Rubin,et al.  Statistical Analysis with Missing Data. , 1989 .

[12]  Geert Molenberghs,et al.  Random Effects Models for Longitudinal Data , 2010 .

[13]  M. Liebowitz,et al.  Statistical choices can affect inferences about treatment efficacy: a case study from obsessive-compulsive disorder research. , 2008, Journal of psychiatric research.

[14]  Ken P Kleinman,et al.  Much Ado About Nothing , 2007, The American statistician.

[15]  C. Hendricks Brown,et al.  Power Calculations for Data Missing by Design: Applications to a Follow-Up Study of Lead Exposure and Attention , 2000 .

[16]  J. Ware,et al.  Random-effects models for longitudinal data. , 1982, Biometrics.

[17]  J. Graham,et al.  How Many Imputations are Really Needed? Some Practical Clarifications of Multiple Imputation Theory , 2007, Prevention Science.

[18]  John L.P. Thompson,et al.  Missing data , 2004, Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases.

[19]  D. Rubin INFERENCE AND MISSING DATA , 1975 .

[20]  D B Rubin,et al.  Multiple imputation in health-care databases: an overview and some applications. , 1991, Statistics in medicine.

[21]  N M Laird,et al.  Missing data in longitudinal studies. , 1988, Statistics in medicine.

[22]  Wei Wang,et al.  Methods for testing theory and evaluating impact in randomized field trials: intent-to-treat analyses for integrating the perspectives of person, place, and time. , 2008, Drug and alcohol dependence.

[23]  Roderick J. A. Little,et al.  Modeling the Drop-Out Mechanism in Repeated-Measures Studies , 1995 .

[24]  G. Molenberghs,et al.  Linear Mixed Models for Longitudinal Data , 2001 .

[25]  Roderick J. A. Little,et al.  A Class of Pattern-Mixture Models for Normal Incomplete Data , 1994 .

[26]  Joseph L Schafer,et al.  Analysis of Incomplete Multivariate Data , 1997 .

[27]  Juned Siddique,et al.  Treating depression in predominantly low-income young minority women: a randomized controlled trial. , 2003, JAMA.

[28]  P. Lane Handling drop‐out in longitudinal clinical trials: a comparison of the LOCF and MMRM approaches , 2008, Pharmaceutical statistics.

[29]  J. Schafer,et al.  A comparison of inclusive and restrictive strategies in modern missing data procedures. , 2001, Psychological methods.

[30]  Russell V. Lenth,et al.  Statistical Analysis With Missing Data (2nd ed.) (Book) , 2004 .

[31]  Naihua Duan,et al.  Missing Data in Longitudinal Clinical Trials Part A: Design and Conceptual Issues. , 2008, Psychiatric annals.