Erratum : The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men (Clinical Trials (2014) 11 (362-375) DOI: 10.1177/1740774514524032)

CLINICAL TRIALS DESIGN Clinical Trials 2014; 11: 362–375 The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men Peter J Snyder a , Susan S Ellenberg b , Glenn R Cunningham c , Alvin M Matsumoto d , Shalender Bhasin e , Elizabeth Barrett-Connor f , Thomas M Gill g , John T Farrar h , David Cella i , Raymond C Rosen j , Susan M Resnick k , Ronald S Swerdloff l , Jane A Cauley m , Denise Cifelli h , Laura Fluharty h , Marco Pahor n , Kristine E Ensrud o , Cora E Lewis p , Mark E Molitch q , Jill P Crandall r , Christina Wang l , Matthew J Budoff s , Nanette K Wenger t , Emile R Mohler 3rd u , Diane E Bild v , Nakela L Cook w , Tony M Keaveny x , David L Kopperdahl y , David Lee y , Ann V Schwartz z , Thomas W Storer ab , William B Ershler ac , Cindy N Roy ad , Leslie J Raffel ae , Sergei Romashkan af and Evan Hadley af Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of tes- tosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and to determine definitively whether testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objec- tive measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this set of trials. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concen- trations and symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Func- tion Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive func- tion (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, common approaches to treatment and monitoring, and the ability to pool safety data. The logistical advantages were a sin- gle steering committee, data coordinating center and data and safety monitoring board, the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in participant selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone defi- cient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary outcomes for each trial were identifying those of the highest clinical importance and identifying the minimum clini- cally important differences between treatment arms for sample size estimation. Please refer to the Appendix at the end of this paper for individual affiliation details. Author for correspondence: Peter J Snyder, Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadel- phia, PA 19104-5160, USA. Email: pjs@mail.med.upenn.edu O The Author(s), 2014 Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav Downloaded from ctj.sagepub.com at AMGEN, INC. on May 22, 2015