Impact of psychotic relapse definitions in assessing drug efficacy and costs: comparison of quetiapine XR, olanzapine and paliperidone ER

Objective: The objective of this study was to illustrate the implications of using standardised psychotic relapse definitions by comparing published clinical trial relapse and drop-out rates for patients with schizophrenia. Methods: Relapse definitions from three published placebo-controlled clinical trials were standardised to facilitate pair-wise retrospective comparison of relapse outcomes in patients with schizophrenia receiving extended-release quetiapine fumarate (quetiapine XR), paliperidone extended release (paliperidone ER) and olanzapine. Relapse definitions were based on changes in the Positive and Negative Syndrome Scale score, Clinical Global Impression-Severity score and predefined Brief Psychiatric Rating Scale positive items. Economic implications of relapse outcomes were also calculated. A limitation of this study is that this was not a head-to-head comparison. In addition, patient-level data were lacking for the paliperidone ER and olanzapine studies. Results: When the relapse definition from the paliperidone study was applied to the quetiapine XR clinical trial data, 14 quetiapine XR patients (15%) relapsed compared with 23 (22%) in the paliperidone ER study. According to the olanzapine relapse definition, three quetiapine XR patients (3.2%) experienced a relapse compared with nine patients (4.0%) in the olanzapine study. An illustrative calculation of potential economic impact associated with these standardised relapse rates implied incremental expenditures ranging from £74.8 million to £373.9 million (£2006) for paliperidone ER versus quetiapine XR treatment and no material difference with olanzapine. Conclusion: The results show that the definition of relapse has a significant impact on relapse outcomes, and associated economic implications, and that relative drug efficacy can only be considered when results are based on standardised relapse criteria