III. Detecting treatment effects in clinical trials with different indices of pain intensity derived from ecological momentary assessment

Repeated measures ANOVA models were used to estimate the standardized group differences in change for each pain index, contrasting each of the two doses (100 or 200 mg per day) to the placebo control group. Because each trial involved multiple weeks of stable dose treatment (24 weeks in study 1 and 26 weeks in study 2), it was possible to obtain multiple repeated treatment ES estimates per trial. Rather than testing a separate ANOVA model for each treatment week, we fitted combined models for all treatment weeks simultaneously, whereby the (repeated) changes from baseline were predicted from treatment group, effect-coded treatment week, and the group × week interaction terms. Using effect coding for the categories of treatment week, a main effect for treatment group on standardized change in a given pain index is interpreted as the ES of the treatment averaged over all the treatment weeks, and the week × treatment group interaction effects represent deviations from the average treatment effect for a given week. This allowed us to obtain the pooled average ES, as well as the week-to-week variance in treatment effects, for each pain index. Whereas the pooled average ES represents our best estimate of the overall effect of the intervention on a given pain index, the week-to-week variance in effect size is a potentially useful measure to evaluate the consistency of the treatment effects over time. Initial ANOVAs were conducted for each index separately. To investigate the differences in ES estimates comparing the Average Pain index and each of the alternative indices, we fitted a multivariate extension of the repeated-measures ANOVA models, in which two indices (i.e., Average Pain and one of the alternatives) were treated as correlated outcomes. ES differences between the indices for each week (as well as pooled average ES differences across weeks, treatment doses, and trials) were obtained using the delta method.