Administration of therapy is inconsistent with usual practice

The administration of the study medicine in trials (for example, dose, dose titration/escalation, frequency, route of administration, monitoring) may differ from the schedule that is likely to be used in clinical practice. This is perhaps more likely if the new therapy is added to current usual care, or if the treatment itself may be intentionally misused by patients if its administration is not under strict control (for example, opioids in pain relief). In some cases the clinical background and skill level of the administering clinicians may be important.