Since 2002 some of the world's largest disease management programs have been launched in Germany--initially for type II diabetes and coronary heart disease--with approximately 5 million eligible insured persons and (in 2005) 2.04 million registered participants. The programs were not piloted prior to their start, and the prescribed statutory evaluation cannot be expected to result in an effectiveness validation. The article describes the development of a study protocol for a randomized controlled trial. It also discusses methodological problems, in particular the definition of primary target criteria, the guarantee of a 'naturalistic' intensity of intervention, and the creation of a control group during nation-wide implementation. Due to lacking support from the stakeholders the proposed randomized trial could not be implemented. Its design, however, allows the required standards for the program evaluation to be specified.