SY 02-1 DESIGNING HYPERTENSION TREATMENT TRIALS.

Results of outcome trials form the basis for treatment guidelines in hypertension. Further outcome trials are needed wherever there are gaps in knowledge. Thus, rationale for setting up and performing and outcome trial with investment of large resources is based on a strong hypothesis.Second, an outcome trial must be done with sufficient statistical power. Power is calculated from the risk level of the people to be investigated and the event rate, the expected benefit of the agent to be investigated and the number of treatment years (number of participants involved and years in the study). The agent and comparators are selected in line with the hypothesis and detailed attention is given to dosing, format, timing etc.Inclusion criteria should be harmonized with the hypothesis and need for power, and exclusion criteria are mostly standard. A pilot study or exploratory assessment whether the potential participants exist in the population and can be recruited within reasonable time is needed. The organization with various committees must be set up according to international standard and financial support secured. Patient report forms must be carefully developed in order to catch all details and be supported by a study manual with instructions to investigators.Measurements of blood pressure in and out of office need special attention. Selection of the primary endpoint is crucial for the success, and secondary endpoint should be identified at the outset. Important sub-studies should be designed already at this stage and included into written informed consent for approval by regulatory agents before study start. The protocol should include statements regarding interims analyses, usually at one and two thirds of accumulated primary endpoints, and a protocol may benefit from being endpoint driven and no futility stopping.