Analysis of the Results of Phase III Controlled Clinical Trials with Recombinant Human Thyrotropin: Developing a Clinical Guide

Abstract

To review two phase III clinical trials with recombinant human thyrotropin (rhTSH) in patients with treated thyroid cancer, which led to its approval by the Food and Drug Administration. The trial designs, the results of radioiodine scanning, and the findings with use of both scanning and thyroglobulin (Tg) response are described. In the overall study design, the findings on whole-body radioiodine scanning were compared after use of two techniques--administration of rhTSH and withdrawal of thyroid hormone therapy. In the first phase III trial, two independent reviewers assessed 127 scan pairs and found 21 scan pairs to be discordant. In 18 of these cases, the scan after thyroid hormone withdrawal was judged as better than the scan after rhTSH administration. Subsequent analysis, however, revealed some problems with the protocol, and adjustments and standardizations were implemented for the second phase III trial, for which multiple blood samples were also obtained for serum Tg determinations. In this second study, 195 of 220 scan pairs were concordant, and only 25 pairs were discordant--17 were better after thyroid hormone withdrawal and 8 were better after rhTSH administration (P<0.1). The Tg response to rhTSH was not sufficiently reliable independently but was useful in combination with whole-body scanning (detection rate of 85 to 90%). The data indicate that rhTSH will be useful for investigation and long-term follow-up of patients with treated thyroid cancer.