To gain a better understanding of the meaning of the primary outcome data of the trials, various supplementary analyses were conducted, using additional outcome parameters.
The first supplementary analysis focussed on the question whether or not the improvements in some patients in the experimental and control group occurred at the expensive of deteriorations in other patients. To this end, the group of non-responders was divided into (1) subjects who had improved 40% or more on at least one of the outcome domains, but had concurrently deteriorated on at least one of the other outcome domains, (2) subjects who had neither improved, nor deteriorated according to the criteria, and (3) subjects who had not shown improvement (of 40% or more) on any of the outcome domains, but who had deteriorated on at least one of the outcome domains.
The second supplementary analysis concerned the percentage of response at subsequent assessments in the course of the trials. To investigate this topic, the percentage responders in the intention-to-treat population was calculated for each assessment-point, using LOCF for each missing assessment during the trial.
The third analysis looked at the relative contribution of the outcome domains to response. To this end, the type(s) of outcome domains on which the patients responded in the course of the trial ("response profiles") were investigated. In addition, the number of response domains were investigated, distinguishing single-domain responders and multi-domain responders.
The fourth and fifth supplementary analyses focussed on two very conservative approaches of response. The fourth analysis pertained to the issue of stable or sustained response. Sustained responders were defined as patients who (1) became responder prior to the month 12 assessment, and (2) remained a responder during the course of the trial, once they became responder for the first time. The fifth analysis focussed on a definition of response in which patients were not allowed to meet any of the inclusion thresholds.
The sixth supplementary analysis concerned an investigation of the potential effect of differential underreporting of illegal drug use between the treatment groups in the inhalable heroin trial on the occurrence of response (see paragraph 3.2.8). To this end, illegal drug use (i.e. cocaine and amphetamines) was removed as component of the primary outcome measure. Thus, the percentage responders was calculated, regardless the occurrence of deterioration in the area of illegal drug use.