When conducting neonatal trials in pre-term and/or low-birth-weight infants, twins may represent 10-20% of the study sample. Frailty models and proportional hazards regression with a robust sandwich variance estimate are common approaches for handling correlated time-to-event data or duration outcomes that are subject to censoring. However, the operating characteristics of these methods for mixes of correlated and independent time-to-event data are not well established. Simulation studies were conducted to compare frailty models and proportional hazards regression models with a robust sandwich variance estimate to standard proportional hazards regression models to estimate the treatment effect in two-armed clinical trials. While overall frailty models showed the best performance, caution must be exercised as the interpretation of the parameters differs from the marginal models. Data from the National Institute of Child Health & Human Development sponsored PROPHET trial are used for illustration.