A plausible explanation for a negative trial is still a hypothesis. If counseling intensity was identical across medication groups, the trial cannot establish what would have happened with less counseling.
Three doses, a common counseling program
Johnson and colleagues’ 2008 report described 150 adults in an eight-week, double-blind, placebo-controlled methamphetamine-dependence trial. Oral ondansetron doses were 0.25, 1 or 4 mg twice daily. Every group was offered 90-minute cognitive behavioral therapy sessions three times weekly.
No dose outperformed placebo on the primary methamphetamine-use measures, including urine outcomes, reported nonuse days and sustained abstinence. Craving changes also did not differ significantly (p=0.63). The urine classification used a 300 ng/mL boundary. Across groups, 44.19% of urine samples were missing; a methamphetamine-free week required the available samples to be negative.
What does the counseling explanation actually show?
The authors proposed that less intensive counseling might have made a medication effect easier to detect. Counseling intensity was not randomized. The report also identified limited sample size, short duration and loss to follow-up as interpretive limitations.
The randomized comparison estimates the added effect of ondansetron in the tested treatment setting. Because counseling was common to the arms, its presence is part of that setting. It does not invalidate the comparison. A different setting could produce a different result, but establishing that possibility requires another comparison rather than a revised description of this one.
There is also no demonstrated interaction between medication efficacy and counseling intensity here. To establish such an interaction, investigators would need evidence that the medication’s relative effect changed across counseling conditions. Offering the same counseling program to everyone leaves that question unanswered.
How missing urine samples change the reading
A week classified using available specimens should not be described as continuous biologically verified abstinence. The strength of the claim depends on the observation schedule and the handling of absent observations. A negative collected specimen and an uncollected specimen supply different information.
That distinction works in both directions. Missing samples should not automatically be called evidence of use unless that was an explicitly defined analytical rule, and they should not be silently counted as evidence of nonuse. The appropriate report identifies the rule and separates the recorded classification from the larger claim it might be used to support.
This historical trial does not support an ondansetron benefit under its tested conditions. It leaves room for further research into other conditions, without establishing efficacy in those untested settings or providing a current treatment recommendation.
Source
Johnson BA, et al. A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of methamphetamine dependence. Int J Neuropsychopharmacol. 2008;11:1–14. doi:10.1017/S1461145707007778. Publisher full text.