Study Limitations
RECRUITMENT
Our study has several limitations. First, caution is needed when interpreting the results. The primary outcome, the achievement of therapeutic serum lithium concentrations, was not statistically significant, but the OR of 2.14 was somewhat in favor of the EHR-nested alerts. However, more patients in the usual care group were lost to follow-up, mainly because of moving to another hospital, and these patients were regarded as not having achieved the primary outcome. Multiple imputation analyses showed a consistent, but more conservative, effect than primary analysis. Second, this study randomized individual patients rather than physicians. Physicians may have learned how often they should monitor serum lithium levels, and this would tend to bias the results toward the null that the alerts did not improve the primary outcome. However, this would have worked toward decreasing the difference, but in our study, the monitoring of serum lithium was significantly and clearly more frequent in the reminder group. Third, the study may have lacked the statistical power to detect the small effect of the alert system. Our planned sample size was 120; however, recruitment was stopped at 110 because the eligible patient pool at Toyooka Hospital was exhausted. Fourth, adherence in our study, which was measured by PPDC and reached nearly 100% in both groups, was quite higher than in the previous reports, which reported that the median adherence was 50% to 60% [