Termination of a randomized controlled trial of two vasectomy techniques.
Family Health International (FHI) and EngenderHealth conducted a multicenter, randomized controlled trial to evaluate a fascial interposition (FI) component of a vas occlusion procedure for male sterilization. A data monitoring committee (DMC) was established to provide independent review of the interim report. The DMC met to review the interim report after enrollment of 552 men. As planned, an estimate of the hazard ratio (HR) for successful vasectomy for the FI group versus the no-FI group controlling for age of the participant and level of experience of the surgeon was obtained for the interim report using Cox's proportional hazards regression. The main analysis comparing time to vasectomy success, defined as two consecutive azoospermic semen samples, was highly significant and met the prespecified level for stopping enrollment (HR=1.54, p<0.01). However, a troublesome age by vasectomy technique interaction became apparent in the analysis. FI was clearly beneficial for younger males. However, the trend for older men was not as clear. The DMC recommended continuing the trial to better study this interaction and obtain more data to clarify the effect of FI for older men. After consulting further with the DMC, the study statisticians presented the interim report to senior management at FHI. A meeting between FHI senior management and the DMC followed. After much deliberation, trial enrollment was terminated. Follow-up of participants already enrolled in the study continued as planned. This paper presents the issues involved in the decision to terminate the study.
Chen-Mok
Mario
M
Family Health International, Durham, NC, USA. mchen@fhi.org
Bangdiwala
Shrikant I
SI
Dominik
Rosalie
R
Hays
Melissa
M
Irsula
Belinda
B
Sokal
David C
DC
D000367:Age Factors; D026661:Clinical Trials Data Monitoring Committees; D003627:Data Interpretation, Statistical; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic / Q000592:standards / Q000706:statistics & numerical data*; D012107:Research Design; D036302:Therapeutic Human Experimentation / Q000941:ethics; D014481:United States; D014659:Vasectomy / Q000009:adverse effects* / Q000379:methods*