[Design and Evaluation of a Clinical Investigator Training for Student-lead Prospective Multicentre Clinical Trials: a CHIR-Net SIGMA Research-based Learning Project]. / Design und Evaluation eines Prüf-Studierenden-Kurses für studentische prospektive Multicenterstudien ­ ein CHIR-Net-SIGMA-Projekt zum forschenden Lernen.

BACKGROUND: Scientific skills are not sufficiently taught during medical training, neither in medical school nor during postgraduate education. This results in a lack of clinician scientists. In order to counter this problem, the surgical study network (CHIR-Net) founded SIGMA (Student-initiated German Medical Audit). This paper describes the development, performance and evaluation of a Clinical Investigator Training (CIT) aiming to qualify students to autonomously conduct clinical trials. MATERIAL AND METHODS: Based on the Kern cycle, a curriculum was developed, composed of three parts: online tutorials, a workshop and a follow-up period. The educational objectives were defined according to Bloom's taxonomy of knowledge. The learning objectives were based on the requirements of the "Network of Coordinating Centers for Clinical Trials" and the German Medical Association as well as content relevant to clinical studies. A wide range of educational instruments and assessments were used. By including all relevant professional groups involved in clinical trials, an interconnected working environment for students was generated. The increase in knowledge was assessed by a multiple-choice pre/post exam. The satisfaction of participants was analysed by a 5-point Likert scale, on which 5 indicated full approval. RESULTS: The first SIGMA CIT was realised in 2018; the workshop took place in Heidelberg in February. Thirty-two medical students from thirteen different centres participated. On average, 53.8 ± 8.3% of questions were answered correctly in the pre-test, compared with 71.2 ± 7.2% in the post-test (p < 0.0001). The maximal individual improvement was 30%; the lowest difference compared to the pre-test was 5%. Subjective evaluation results were positive with an average result of 4.63 ± 0.34 on a 5-point Likert scale. CONCLUSION: It is feasible to teach medical students the fundamentals of clinical trials. A compact Clinical Investigator Training using modern principles of teaching is able to prepare students for an autonomous performance of clinical trials.

Transcriptome-based identification of tumor-reactive and bystander CD8+ T cell receptor clonotypes in human pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is generally refractory to immune checkpoint blockade, although patients with genetically unstable tumors can show modest therapeutic benefit. We previously demonstrated the presence of tumor-reactive CD8+ T cells in PDAC samples. Here, we charted the tumor-infiltrating T cell repertoire in PDAC by combining single-cell transcriptomics with functional testing of T cell receptors (TCRs) for reactivity against autologous tumor cells. On the basis of a comprehensive dataset including 93 tumor-reactive and 65 bystander TCR clonotypes, we delineated a gene signature that effectively distinguishes between these T cell subsets in PDAC, as well as in other tumor indications. This revealed a high frequency of tumor-reactive TCR clonotypes in three genetically unstable samples. In contrast, the T cell repertoire in six genetically stable PDAC tumors was largely dominated by bystander T cells. Nevertheless, multiple tumor-reactive TCRs were successfully identified in each of these samples, thereby providing a perspective for personalized immunotherapy in this treatment-resistant indication.

Postoperative complications and mobilisation following major abdominal surgery with vs. without fitness tracker-based feedback (EXPELLIARMUS): study protocol for a student-led multicentre randomised controlled trial (CHIR-Net SIGMA study group).

BACKGROUND: Postoperative complications following major abdominal surgery are frequent despite progress in surgical technique and perioperative care. Early and enhanced postoperative mobilisation has been advocated to reduce postoperative complications, but it is still unknown whether it can independently improve outcomes after major surgery. Fitness trackers (FTs) are a promising tool to improve postoperative mobilisation, but their effect on postoperative complications and recovery has not been investigated in clinical trials. METHODS: This is a multicentre randomised controlled trial with two parallel study groups evaluating the efficacy of an enhanced and early mobilisation protocol in combination with FT-based feedback in patients undergoing elective major abdominal surgery. Participants are randomly assigned (1:1) to either the experimental group, which receives daily step goals and a FT giving feedback about daily steps, or the control group, which is mobilised according to hospital standards. The control group also receives a FT, however with a blackened screen; thus no FT-based feedback is possible. Randomisation will be stratified by type of surgery (laparoscopic vs. open). The primary endpoint of the study is postoperative morbidity within 30 days measured via the Comprehensive Complication Index. Secondary endpoints include number of steps as well as a set of functional, morbidity and safety parameters. A total of 348 patients will be recruited in 15 German centres. The study will be conducted and organised by the student-led German Clinical Trial Network SIGMA. DISCUSSION: Our study aims at investigating whether the implementation of a simple mobilisation protocol in combination with FT-based feedback can reduce postoperative morbidity in patients undergoing major abdominal surgery. If so, FTs would offer a cost-effective intervention to enhance postoperative mobilisation and improve patient outcomes. TRIAL REGISTRATION: Deutsches Register Klinischer Studien (DRKS, German Clinical Trials Register): DRKS00016755, UTN U1111-1228-3320. Registered on 06.03.2019.