ON THE DEVELOPMENT OF THE MEDICAL-RESEARCH-COUNCIL TRIAL OF ALPHA-INTERFERON IN METASTATIC RENAL-CARCINOMA

This paper describes the steps taken by the British Medical Research C ouncil (MRC) in developing the MRC REO1 trial, a randomized clinical t rial for patients with metastatic renal cancer; we discuss the reasons for adopting a triangular sequential design and the impact that this has upon the monitoring of the trial. It had been suggested to the MRC that a trial of biological agents for metastatic renal carcinoma shou ld be initiated. The Cancer Therapy Committee (CTC) of the MRC, throug h its associated site specific working parties, is responsible for des igning and co-ordinating randomized trials of alternative treatments i n cancer in solid tumours. Since no MRC working party for renal carcin oma existed at that time, development began by the formation of an ad hoc group set up under the auspices of the CTC. They assessed, by mean s of a postal questionnaire, U.K. interest in the trials of, and modal ities utilized for, treatment of renal cancer. The responses focused a ttention on the important questions to ask and indicated the level of potential collaboration. These responses and related clinical and stat istical issues suggested a protocol to compare medroxy-progesterone ac etate (MPA) against alpha-interferon (alpha-IFN). In view of the speci al problems of comparing an expensive and potentially toxic therapy wi th an inexpensive and non-toxic standard, a sequential design was used rather than a fixed sample size design. Statistical issues raised and solutions provided are described. The method of establishing the tria l data monitoring committee and a brief review of mortality from renal carcinoma in England and Wales are also included. The trial opened to patient recruitment on 1 January 1992. The formal statements regardin g statistical issues that appear in the formal trial protocol (REO1) a re set out in the Appendix.