Some basic issues relevant for demonstration of superior efficacy are discussed with the case of the development of zoledronic acid 4 and 8 mg in hypercalcemia of malignancy. Topics such as number of studies, significance level, consistency of results across subgroups, and choice of primary efficacy variable are addressed. Two calibration studies using a comparison with a prespecified value as a criterion for efficacy are compared with one between-treatment pooled analysis. A further point is the switch from noninferiority to superiority. Some lessons for statistics can be drawn from the case study.
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Quebe-Fehling, E. A Case Study Demonstrating Superiority of a New Compound over the Gold Standard. Ther Innov Regul Sci 35, 1173–1178 (2001). https://doi.org/10.1177/009286150103500414
- Evidence of efficacy
- Calibration study
- One pivotal study
- Switching from noninferiority to superiority