1. Course Proposal: Foundations of Clinical and Translational Research Design Team: Chris Rees, Geoff Noble, Cynthia Hahn, Jon Lurie (course director), Todd MacKenzie (course director), Alexander Thorngren

2. A Brief History At present, MD-PhD candidates are required to take two courses (MEDI545 and PHARM602) during their final year of medical school. MEDI545: “Clinical and Translational Research Project” (4 weeks) PHARM602: “Clinical Investigation” (12 hours)

3. Proposed Change To integrate, re-sequence, and strengthen the MD/PhD-specific curriculum by creating a new course, “Fundamentals of Clinical and Translational Research”, consisting of: (1) a two-week, non-clinical elective covering the design, conduct and analysis of clinical/translational research, (2) a four-week clinical/translational research experience, (3) small group discussions focused on the physician-scientist career

4. Course Structure Phase I (2 weeks, full-time): Focuses on the fundamental designs and data analysis methods used in clinical or translational research studies. Students will gain familiarity with: observational data designs, including cross-sectional, case-controls, and cohort studies, and experimental data designs including phase I, phase II, parallel, and cross-over studies. Important concepts will include: bias, confounding, randomization, blinding, and measures of risk and association.

5. Course Structure Phase II (4 weeks, full-time): Features full-time work on a clinical or translational research project being conducted at Dartmouth Hitchcock Medical Center, under the guidance of a physician-scientist. Students will be expected to gain clinical exposure by interacting with patients, as well as other members of the health care team that are involved in conducting clinical or translational research studies. Students will be expected to collect and analyze data, and present their findings to a group consisting of their peers and physician-scientists.

6. Course Structure Phase III (3-5 lunch hour sessions): Overlaps with the fourth-year HSP course. Sessions will take place during lunch, and as such, students will not be exempt from any elements of the standard HSP curriculum. These sessions will focus on career development, including funding opportunities for early-career investigators. Christopher Dant (affiliated with NCCC) has offered to lead at least two sessions on K-awards and grantsmanship.

7. Grading Scheme Fundamentals of Clinical and Translational Research will be graded using the “Pass/Fail” system, with the cutoff for a passing grade set at 70%. For each element associated with narrative feedback, a grading rubric will be made available to both students and faculty so that expectations are clearly defined at the outset of the course.

8. Grading Scheme Phase I30% Biostatistics/epidemiology problem sets (2 at 5% each)10% Written summaries of case studies 10% Preparedness and participation in weekly meetings*10% Phase II60% Oral presentation of research*20% Assessment of research performance by physician-scientist mentor*40% Phase III10% Attendance and participation at lunch sessions*10% *Element involves narrative feedback

9. Course Registration Because Phase I and III are largely non-clinical and Phase II is mainly clinical, different course numbers will be associated with each phase. We propose to use the same system used by On Doctoring and ICE, which involves “marking” the three phases such that a grade is awarded only after the completion of all three phases.

10. Sample Schedule: Phase I

11. Course Objectives 1. Describe common study designs used in both clinical and translational research studies, including experimental as well as observational methods (1b). 2. Describe common biostatistical and epidemiological techniques used in the analysis of clinical and translational research data (1b). 3. Describe the rationale for the use of various study designs and biostatistical methods, including methods of controlling confounding and other bias in the analysis of clinical and translational research data (1b). 4. Perform basic biostatistical analyses relevant to translational research, including determination of study size and power, and the use of secondary data for meta-analysis (1b). 5. Define important terms and equations used in the study of epidemiology, and apply the use of these terms and equations to clinical and translational research data (1b).

12. Course Objectives 6. Critically evaluate the use of commonly used study design and biostatistical techniques in the scientific, peer-reviewed, literature (1b, 5a,b). 7. Describe the translational research continuum (T1 through T4), as well as the research methods and biostatistical approaches utilized at each phase of translational research (1b). 8. Describe the possible career trajectories available to MD-PhD program graduates, as well as funding mechanisms available for early career investigators (1b). 9. Describe essential elements of a research grant, specifically pertaining to the development and structuring of specific aims as well as one's research strategy (1b). 10. Describe the process by which grants are reviewed by the National Institutes of Health as well as other important funding agencies (1b).

13. Course Objectives 11. Describe ethical issues that may arise during the process of conducting clinical or translational research, and the roles of the IACUC, CPHS, COIC, and Ethics Committee in relation to these issues (1b,e). 12. Critique translational and clinical research studies published in peer-reviewed scientific journals, with specific attention to study design and potential for confounding variables (1b, 5a,b). 13. Analyze data pertaining to a clinical or translational research project under the guidance of a physician scientist (1b,c, 2a,e,f,g,h, 4h). 14. Interact with patients and other health care personnel involved in a clinical or translational research study (1b,c,f, 2a,e,f,g, 3a,b,e,f,g, 4a,b,g,h). 15. Present a synopsis of findings and experiences associated with a clinical or translational research endeavor (1b,d, 3e,f,g, 4a,b,g).