http://www.ncbi.nlm.nih.gov/pubmed/23493134

Ann Oncol. 2013 Mar 13. [Epub ahead of print]

Non-inferiority cancer clinical trials: scope and purposes underlying their design.

Riechelmann RP, Alex A, Cruz L, Bariani GM, Hoff PM.

Source

Discipline of Radiology and Oncology, Universidade de Sao Paulo, Instituto do Câncer de Estado de São Paulo, Sao Paulo, Brazil.

Abstract

Background

Non-inferiority clinical trials (NIFCTs) aim to demonstrate that the experimental therapy has advantages over the standard of care, with acceptable loss of efficacy. We evaluated the purposes underlying the selection of a non-inferiority design in oncology and the size of their non-inferiority margins (NIFm's).

Patients and methods

All NIFCTs of cancer-directed therapies and supportive care agents published in a 10-year period were eligible. Two investigators extracted the data and independently classified the trials by their purpose to choose a non-inferiority design.

Results

Seventy-five were included: 43% received funds from industry, overall survival was the most common primary end point and 73% reported positive results. The most frequent purposes underlying the selection of a non-inferiority design were to test more conveniently administered schedules and/or less toxic treatments. In 13 (17%) trials, a clear purpose was not identified. Among the trials that reported a pre-specified NIFm, the median value was 12.5% (range 4%-25%) for trials with binary primary end points and Hazard Ratio of 1.25 (range 1.10-1.50) for trials that used time-to-event primary outcomes.

Conclusion

Cancer NIFCT harbor serious methodological and ethical issues. Many use large NIFm and nearly one-fifth did not state a clear purpose for selecting a non-inferiority design.