Academic leaders all over the world are encouraging the use of active methodologies in teaching, especially in higher education. The reason for this is that social changes are happening at an ever-increasing rate, and they require students and teachers to develop digital skills. This is especially significant for health sciences degrees, in which future graduates must have effective problem-solving skills. To respond to this challenge, the use of a project-based learning (PBL) methodology, together with various monitoring techniques based on the use of Educational Data Mining (EDM) and mixed methods, will provide teachers with information about the effectiveness of the methodology and guide the implementation of personalized educational responses. This study provides a protocol for the application of the PBL methodology in e-Learning and blended-Learning (b-Learning) teaching modalities for health sciences students studying occupational therapy in higher education. In addition, statistical techniques for the analysis of covariance and unsupervised learning allow differences to be detected between the two teaching modalities, thus specifying their effectiveness in terms of a range of variables related to behavioral patterns, performance, and satisfaction. Data visualization also helps in understanding the qualitative aspects of the learning process. These data will help teachers to produce more effective proposals for the implementation of the PBL methodology based on the based on the context of the teaching-learning process. Therefore, this protocol offers many resources and materials to help teachers implement the PBL methodology in e-Learning and b-Learning teaching methods.