There was about a 10-minute cross-over period of uncertainty, but it was really not that bad". A slight laugh.
To avoid a carry-over effect, only the first randomized cross-over period was considered for analysis.
For each cross-over period, the mean [least-square (LS) mean] and 95% CI of individual proportions of heroin-positive urine samples were calculated.
For each patient the extent of heroin use was defined as proportions and calculated by dividing the number of the patient's heroin-positive urine samples by the number of their weekly urine samples selected for urinalysis per cross-over period.
Kaplan-Meier curves showed a crossover time point, an indication that the proportional hazards assumption might be violated; thus, time to event was analyzed separately before the cross-over period in each analysis.
Further, the extent of self-reported use of heroin, cocaine, alcohol, cannabis and benzodiazepines per period was assessed by calculating the average number of days of reported consumption during the cross-over period.
For the cluster RCT, we estimated a cluster size of 40 from Figure 1 of the publication [ 13] (that is, approximately 20 patients per cross-over period per ICU) and an ICC of 0.01 (actual ICC not reported), which gives a design effect of 1.39.
The trial was to be conducted over a 10-month period consisting of three phases: (1) a 2-month baseline period where all participants would receive the 'self-serve' evidence service; (2) a 6-month intervention period where the intervention group would receive the 'full-serve' evidence service; and (3) a 2-month cross-over period where all participants would receive the 'full-serve' evidence.
This was followed by two 8 month cross-over periods, with one month follow up of study patients at the end of the final period.
In the PP population 12 (8%) patients received prescribed benzodiazepines, but 75 (47.7%) patients used non-prescribed benzodiazepines in both cross-over periods, according to urinalyses.
Following the first fMRI session, all participants received a further 7 days of placebo and then either naproxen or placebo (crossed over from period 1) as their second period of dosing.
