Study design and protocol development process

As part of its public mental health care treatment initiative the US National Institute of Mental Health (NIMH) in 1998 issued a request for proposals (RFP) for a research program to evaluate the comparative effectiveness of antipsychotic drugs in schizophrenia, Alzheimer's disease, and depression with psychotic features. The RFP specified that the research protocols should focus on the newer (atypical or second-generation) antipsychotic drugs and should follow a public health model. In particular, the RFP stated that the trials should include the following features: focus on effectiveness and other outcome measures broader than efficacy alone; examine cost-effectiveness and the impact of external factors on treatment delivery, adherence, and outcomes; enhance generalizability by being as inclusive as possible, without exclusions for co-morbid psychiatric disorder, drug abuse, or medical illness; place a premium on demographic and geographic diversity; use multiple types of treatment settings that generally represent the systems of care in which patients with schizophrenia are treated; and generate results that inform community clinical practice. In addition, the RFP called for the program to develop a network of sites and investigators able to respond to future needs for effectiveness research and to serve as a platform for ancillary clinical investigations. Because additional new antipsychotics were expected to be introduced soon, the RFP also specified that proposals should include a mechanism for adding new medications. After an extended competitive bidding process, the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) program was funded through a contract with the University of North Carolina (UNC).