Like all these methods using spline functions, it requires the number and placement of the knots to be specified. By increasing the number of knots, we increase the flexibility of the spline function, but this also increases the variance associated with each coefficient.

The practical experience of most of the authors suggests that we can limit the search between 3 and 5 knots. So, we decided to a priori restrict the number of knots to three in order to keeping the number of knots for minimum.

For the placement of knots, two approaches have been general employed based either on event times or on all follow-up times both censored and un-censored. We have used here the two approaches, using the 5th and the 95th percentiles of the distribution.