Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘Figure 4. Fitted visit-specific mean responses for four missing data scenarios and three analysis strategies.Dataset II: Available dataDataset III: Available dataDataset IV: Available dataMean response200180160140Group AGroup B1 2 3 42001801601401 2 3 42001801601401 2 3 4Dataset II: Completers onlyDataset III: Completers onlyDataset IV: Completers onlyMean response2001801601401 2 3 42001801601401 2 3 42001801601401 2 3 4Dataset II: LOCFDataset III: LOCFDataset IV: LOCFMean response2001801601401 2 3 42001801601401 2 3 42001801601401 2 3 4LOCF = last observation carried forward.Visit Visit VisitThere are a number of observations from these results. Firstly, for MCAR(Dataset II), the estimated treatment effects at the final visit are close to the truevalue for all three approaches, as expected. The standard error for the analysis ofall available data is smaller than that from the analysis of complete cases only,reflecting the fact that the complete case analysis discards informative data.Despite the LOCF analysis leading to an underestimation of the mean levels ineach group at all visits other than the first, the LOCF analysis does give anunbiased estimate of the treatment effect in this case.Turning to Dataset III (MAR), Figure 4 shows that only the analysis of allavailable data gives rise to fitted response curves that are similar to those for thefull dataset (Figure 2). Table 2 confirms that this is the only method that results inan unbiased estimate of the treatment effect at the final visit. It is important toemphasize that such unbiased estimates at a particular visit are only obtainedwhen the linear mixed model is used to simultaneously model the outcomes ateach follow-up visit.349