Handling drop‐out in longitudinal clinical trials: a comparison of the LOCF and MMRM approaches

Lane, P. W.

doi:10.1002/pst.267

Cited by 229 publications

(197 citation statements)

References 19 publications

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“…If their attrition rates had been low, the risk of bias would also be very low; however, their attrition rates were relatively high (17% and 16% respectively), therefore we also view their results with caution. Whilst LOCF is not the only method for the imputation of missing data, it is still the most widely used; however, given repeated warnings about the dangers of using the LOCF method it seems clear that its use as the sole form of analysis should be discontinued (Lane, 2008;Shapiro, 2001;Barnes, Mallinckrodt, Lindborg, & Carter, 2008;Streiner, 2002).…”

Section: Discussionmentioning

confidence: 99%

Assessing treatments used to reduce rumination and/or worry: A systematic review

Querstret

Cropley

2013

Clinical Psychology Review

196

112

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Perseverative cognitions such as rumination and worry are key components of mental illnesses such as depression and anxiety. Given the frequent comorbidity of conditions in which rumination and worry are present, it is possible they are underpinned by the same cognitive process. Furthermore, rumination and worry appear to be part of a causal chain that can lead to long-term health consequences, including cardiovascular disease and other chronic conditions. It is important therefore to understand what interventions may be useful in reducing their incidence. This systematic review aimed to assess treatments used to reduce worry and/or rumination. As we were interested in understanding the current treatment landscape, we limited our search from 2002-2012. Nineteen studies were included in the review and were assessed for methodological quality and treatment integrity. Results suggested that mindfulness-based and cognitive behavioural interventions may be effective in the reduction of both rumination and worry; with both Internet-delivered and face-to-face delivered formats useful. More broadly, it appears that treatments in which participants are encouraged to change their thinking style, or to disengage from emotional response to rumination and/or worry (e.g., through mindful techniques), could be helpful. Implications for treatment and avenues for future research are discussed.

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Section: Discussionmentioning

confidence: 99%

Assessing treatments used to reduce rumination and/or worry: A systematic review

Querstret

Cropley

2013

Clinical Psychology Review

196

112

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“…The mixed models account for the clustering of individuals within centers, allow use of all repeated measurements and provide unbiased estimates in the presence of dropout without imputation. 29,30 It has been repeatedly demonstrated that mixed models are preferable to end-point analyses with last-observation-carried-forward procedure. 29,30 All models included fixed effects of time (linear and quadratic), baseline depression severity, drug, age and sex, and random effects of individual and recruitment center.…”

Section: Discussionmentioning

confidence: 99%

Genetic predictors of response to antidepressants in the GENDEP project

et al. 2009

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The objective of the Genome-based Therapeutic Drugs for Depression study is to investigate the function of variations in genes encoding key proteins in serotonin, norepinephrine, neurotrophic and glucocorticoid signaling in determining the response to serotonin-reuptake-inhibiting and norepinephrine-reuptake-inhibiting antidepressants. A total of 116 single nucleotide polymorphisms in 10 candidate genes were genotyped in 760 adult patients with moderate-to-severe depression, treated with escitalopram (a serotonin reuptake inhibitor) or nortriptyline (a norepinephrine reuptake inhibitor) for 12 weeks in an open-label part-randomized multicenter study. The effect of genetic variants on change in depressive symptoms was evaluated using mixed linear models. Several variants in a serotonin receptor gene (HTR2A) predicted response to escitalopram with one marker (rs9316233) explaining 1.1% of variance (P ¼ 0.0016). Variants in the norepinephrine transporter gene (SLC6A2) predicted response to nortriptyline, and variants in the glucocorticoid receptor gene (NR3C1) predicted response to both antidepressants. Two HTR2A markers remained significant after hypothesis-wide correction for multiple testing. A false discovery rate of 0.106 for the three strongest associations indicated that the multiple findings are unlikely to be false positives. The pattern of associations indicated a degree of specificity with variants in genes encoding proteins in serotonin signaling influencing response to the serotonin-reuptake-inhibiting escitalopram, genes encoding proteins in norepinephrine signaling influencing response to the norepinephrine-reuptake-inhibiting nortriptyline and a common pathway gene influencing response to both antidepressants. The single marker associations explained only a small proportion of variance in response to antidepressants, indicating a need for a multivariate approach to prediction.

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“…Linear mixed effect modelling uses all available measurements, takes account of non-independence of repeated measurements within individuals and provides unbiased estimates in the presence of missing data under relatively unrestrictive assumptions (Mallinckrodt et al 2001 ;Gueorguieva & Krystal, 2004 ;Lane, 2008).…”

Section: Other Statistical Analysesmentioning

confidence: 99%

Trajectories of change in depression severity during treatment with antidepressants

et al. 2009

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Background. Response and remission defined by cut-off values on the last observed depression severity score are commonly used as outcome criteria in clinical trials, but ignore the time course of symptomatic change and may lead to inefficient analyses. We explore alternative categorization of outcome by naturally occurring trajectories of symptom change.Method. Growth mixture models were applied to repeated measurements of depression severity in 807 participants with major depression treated for 12 weeks with escitalopram or nortriptyline in the part-randomized Genome-based Therapeutic Drugs for Depression study. Latent trajectory classes were validated as outcomes in drug efficacy comparison and pharmacogenetic analyses.Results. The final two-piece growth mixture model categorized participants into a majority (75 %) following a gradual improvement trajectory and the remainder following a trajectory with rapid initial improvement. The rapid improvement trajectory was over-represented among nortriptyline-treated participants and showed an antidepressant-specific pattern of pharmacogenetic associations. In contrast, conventional response and remission favoured escitalopram and produced chance results in pharmacogenetic analyses. Controlling for drop-out reduced drug differences on response and remission but did not affect latent trajectory results.Conclusions. Latent trajectory mixture models capture heterogeneity in the development of clinical response after the initiation of antidepressants and provide an outcome that is distinct from traditional endpoint measures. It differentiates between antidepressants with different modes of action and is robust against bias due to differential discontinuation.

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Handling drop‐out in longitudinal clinical trials: a comparison of the LOCF and MMRM approaches

Cited by 229 publications

References 19 publications

Assessing treatments used to reduce rumination and/or worry: A systematic review

Assessing treatments used to reduce rumination and/or worry: A systematic review

Genetic predictors of response to antidepressants in the GENDEP project

Trajectories of change in depression severity during treatment with antidepressants

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