Randomized Trials with Repeatedly Measured Outcomes: Handling Irregular and Potentially Informative Assessment Times.

Randomized trials are often designed to collect outcomes at fixed points in time after randomization. In practice, the number and timing of outcome assessments can vary among participants. (i.e., irregular). In fact, the timing of assessments may be associated with the outcome of interest (i.e., informative). For example, in a trial evaluating the effectiveness of treatments for major depressive disorder, not only did the timings of outcome assessments vary among participants, but symptom scores were associated with assessment frequency. This type of informative observation requires appropriate statistical analysis. While analytic methods have been developed, they are rarely used. The purpose of this paper is to review the literature on irregular assessments with a view toward developing recommendations for analyzing trials with irregular and potentially informative assessment times. We show how the choice of analytic approach hinges on assumptions about the relationship between the assessment and outcome processes. We argue that irregular assessment should be treated with the same care as missing data, and propose that trialists: adopt strategies to minimize the extent of irregularity; describe the extent of irregularity in assessment times; make their assumptions about the relationships between assessment times and outcomes explicit; adopt analytic techniques that are appropriate to their assumptions; assess sensitivity of trial results to their assumptions.