Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘In MCAR, the probability that a response is missing is completely unrelated toboth the observed information and the hypothetical response value that wouldhave been observed were it not missing. In MAR, the probability that a responseis missing depends on some or all of the observed variables and responses.However conditional on the observed data, this probability is unrelated to thehypothetical value that would have been observed were the data not missing.A process that is neither MCAR nor MAR is termed MNAR.In practice, it might not be possible to state with confidence whether a particularmissing data mechanism is MCAR, MAR, or MNAR. However, this classificationis useful and if we can decide which assumption is most plausible then it providesa good guide to the type of analysis that should be adopted to account for themissing data.What are the potential effects of missing data?Three types of concern typically arise in the analysis of missing data [6]:• loss of efficiency• complications in data handling and analysis• introduction of biasThe importance of each of these is determined by the missing data mechanism(MCAR, MAR, or MNAR) and the way in which the data are analyzed. Forexample, if the missing data mechanism is MCAR then an analysis that excludesparticipants with incomplete data will not introduce bias, but will not necessarilybe efficient. An analysis in which missing values are replaced with ‘plausible’values (eg, by carrying forward the last observed measurement) might increaseprecision, but might also introduce bias if the method for choosing the plausiblevalues is inappropriate.When the missingness is not MCAR, however, a simple analysis restricted toparticipants with no missing values (completers), or even to all available data,can introduce serious bias – eg, if data were missing due to the side-effects ofa drug causing participants to drop out. Indeed, with MAR and MNAR processes,it is necessary to consider an analysis strategy that takes account of the influenceof missingness process.341