The use of adaptive methods in clinical development has become very popular in recent years due to its flexibility in modifying trial procedures and/or statistical procedures of on-going clinical trials. Modifications to trial procedures are usually documented by protocol amendments. However, the actual patient population after protocol amendments could deviate from the originally targeted patient population. In addition, protocol amendments made based on accrued data of the on-going trial may distort the sampling distribution of the statistic designed for the case of no protocol change. In this article, we model the population deviations due to protocol amendments using some covariates and study how to develop a valid statistical inference procedure. An example concerning an asthma trial is presented for illustration.