Lee S McDaniel1, Menggang Yu2, Rick Chappell3. 1. Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA lmcda4@lsuhsc.edu. 2. Department of Biostatistics & Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA. 3. Department of Biostatistics & Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA Department of Statistics, University of Wisconsin-Madison, Madison, WI, USA.
Abstract
BACKGROUND: The additive hazards model can be easier to interpret and in some cases fits better than the proportional hazards model. However, sample size formulas for clinical trials with time to event outcomes are currently based on either the proportional hazards assumption or an assumption of constant hazards. AIMS: The goal is to provide sample size formulas for superiority and non-inferiority trials assuming an additive hazards model but no specific distribution, along with evaluations of the performance of the formulas. METHODS: Formulas are presented that determine the required sample size for a given scenario under the additive hazards model. Simulations are conducted to ensure that the formulas attain the desired power. For illustration, the non-inferiority sample size formula is applied to the calculations in the SPORTIF III trial of stroke prevention in atrial fibrillation. CONCLUSION: Simulation results show that the sample size calculations lead to the correct power. Sample size is easily calculated using a tool that is available on the web at http://leemcdaniel.github.io/samplesize.html.
BACKGROUND: The additive hazards model can be easier to interpret and in some cases fits better than the proportional hazards model. However, sample size formulas for clinical trials with time to event outcomes are currently based on either the proportional hazards assumption or an assumption of constant hazards. AIMS: The goal is to provide sample size formulas for superiority and non-inferiority trials assuming an additive hazards model but no specific distribution, along with evaluations of the performance of the formulas. METHODS: Formulas are presented that determine the required sample size for a given scenario under the additive hazards model. Simulations are conducted to ensure that the formulas attain the desired power. For illustration, the non-inferiority sample size formula is applied to the calculations in the SPORTIF III trial of stroke prevention in atrial fibrillation. CONCLUSION: Simulation results show that the sample size calculations lead to the correct power. Sample size is easily calculated using a tool that is available on the web at http://leemcdaniel.github.io/samplesize.html.