Impact of drug treatment history on comparative effectiveness research in schizophrenia.

Objectives: Randomized clinical trials frequently attract volunteer patients who were either non-compliant or seeking to switch therapies. Patients on active therapies often undergo a washout period after which a single medication is initiated. Observational research has the potential to compare alternative treatments under a wider range of clinical situations if care is taken to document each patient's treatment history.

Methods: This study used paid claims data from a large commercial insurer to investigate drug therapy outcomes in schizophrenia. Episodes of drug therapy were defined each time a patient initiated or restarted drug therapy using an antipsychotic, antidepressant or mood stabilizing medication. Episode definitions were based on calculations of continuous drug therapy using a 15-day gap definition. A total of 21,570 episodes of drug therapy were included in the analysis, some of which used two drugs as initial therapy.

Results: Most episodes were initiated using a mood stabilizing drug (27%) or an antidepressant (38%). Over 62% of all episodes were augmentation therapy in which a psychotropic drug was added to an existing psychotropic medication, followed by switching episodes (22%) and restart episodes (16%). Patient outcomes measured by either duration of uninterrupted therapy or one-year post-treatment cost varied significantly with patient treatment history, especially episode type. The comparative effectiveness of alternative therapies is sensitive to the extent to which treatment history is taken into account.

Conclusions: Observational comparative effectiveness research should capture and evaluate patient outcomes across a wide range of patients taking into account the patient's treatment history.