Minimum trial duration to reasonably assess long-term efficacy of nonhormonal hot flash therapies.
BACKGROUND
Because hot flashes usually persist for years after menopause, a clinically meaningful hot flash therapy needs to have long-term efficacy; however, it is unclear for how long a therapy needs to be compared with a placebo before long-term efficacy can be reasonably deduced. The Food and Drug Administration (FDA) requires a 12-week treatment period for industry-initiated hot flash trials, whereas most academic-initiated trials have ranged from 4 to 12 weeks. We have focused on reviewing nonhormonal hot flash trials to identify inadequate trial durations as a guide toward deducing adequate trial duration to reasonably assess for long-term efficacy.


METHODS
An electronic database search of MEDLINE, Web of Science, and PsycINFO was performed from 1966 to May 2009 to identify target studies showing a nonhormonal hot flash therapy to be effective at early time points only to become ineffective at later time points (i.e., showing short-term but not long-term efficacy) in a randomized controlled trial (RCT). The longest early time point of efficacy from the target studies plus 1 additional week would be considered the minimum treatment duration necessary to assess for long-term efficacy.


RESULTS
Of 2518 citations, 54 RCTs met our inclusion criteria, from which 3 target studies were identified. These 3 target studies evaluated Bellergal Retard (Sandoz, East Hanover, NJ), soy, and venlafaxine and showed times of 2, 6, and 7 weeks, respectively, when the nonhormonal compound last demonstrated efficacy before subsequently losing efficacy in a single RCT.


CONCLUSIONS
This analysis supports a hot flash RCT duration of at least 8 weeks to reasonably assess a nonhormonal compound's long-term efficacy.
Guttuso
Thomas
T
University at Buffalo , Buffalo, New York 14214, USA.
Evans
Michele
M
D004967:Estrogens / Q000627:therapeutic use; D005260:Female; D019584:Hot Flashes / Q000628:therapy*; D006801:Humans; D017064:Process Assessment, Health Care / Q000706:statistics & numerical data* / Q000639:trends; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016387:Women's Health
D004967:Estrogens