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The simultaneous integration of knowledge acquisition and development of clinical reasoning in preclinical medical education remains a challenge. To help address this challenge, the authors developed and implemented the Student-Generated Reasoning Tool (SGRT)—a tool asking students to propose and justify pathophysiological hypotheses, generate findings, and critically appraise information. In 2019, students in a first-year preclinical course ( n  = 171; SGRT group) were assigned to one of 20 teams. Students used the SGRT individually, then in teams, and faculty provided feedback. The control group ( n  = 168) consisted of students from 2018 who did not use SGRT. Outcomes included academic performance, effectiveness of collaborative environments using the SGRT, and student feedback. Students were five times more likely to get questions correct if they were in the SGRT group versus control group. Accuracy of pathophysiological hypotheses was significantly lower for individuals than teams. Qualitative analysis indicated students benefited from generating their own data, justifying their reasoning, and working individually as well as in teams. This study introduces the SGRT as a potentially engaging, case-based, and collaborative learning method that may help preclinical medical students become aware of their knowledge gaps and integrate their knowledge in basic and clinical sciences in the context of clinical reasoning.

The Student-Generated Reasoning Tool (SGRT): Linking medical knowledge and clinical reasoning in preclinical education