Hot flash clinical trial baseline measurements: how long is needed?

OBJECTIVES:Classically, hot flash studies included a baseline period of 1 week or longer. The objective of this study was to compare the accuracy of a 1-day baseline diary to a traditional 1-week diary. METHODS:Raw data from 5 pilot studies and 15 phase III randomised controlled trials (RCTs), all of which used a 1-week baseline period, were obtained. Descriptive statistics were used to describe day-by-day variations in hot flash frequencies and scores, during the baseline week. Additional analyses evaluated whether the conclusions from any of the individual pilot studies would have been changed if only a 1-day baseline period had been used. For the RCTs, p values were recalculated using mixed models, adjusting for the baseline value by including it as a covariate. RESULTS:A total of 2573 participants were included. On average, participants had 8.5 hot flashes per day on day 1. Mean hot flash frequencies and scores on subsequent days (days 2-7) were within 6% of day 1 values. When comparing a 1-day to a 1-week baseline period, there was an absolute difference of only 0.29 hot flashes per day (SD 2.25). Reanalysis for each pilot study revealed that no individual study conclusions would have been altered by a shorter baseline. For the RCTs, a shorter baseline period changed the results of only 1 of 24 comparisons from statistically significant to not significant, or vice versa. CONCLUSIONS:A 1-day hot flash diary appears to accurately reflect the true frequency and severity of baseline symptoms in appropriately sized cohorts.