Core Curriculum

The didactic curriculum was designed with our overall aims in mind: to provide both depth and breadth of multidisciplinary research exposure; to provide practical skills for conducting rigorous, integrative clinical research; and to provide a supportive environment that creates excitement about clinical research. The typical K12 core curriculum listed below may be modified to fit the particular interests, needs, and previous experience of individual scholars, but the breadth of topics should be maintained.

Typical Core curriculum

Descriptions of selected items, Year 1

• Clinical Research Methods Mini Course: An introduction to research design originally developed for the Robert Wood Johnson Clinical Scholars Program. Recent fellows present and comment on the challenges of research designs they have used. Each Clinical Research Scholar will present a design for a potential research study. (3 class hours/week)



• Biomedical Research Integrity Series: Three lectures and panel discussions sponsored by the Dept. of Medical History and Ethics; conflicts of interest, publication practices and responsible authorship, issues in data management, evolution of ethics in research, and the challenges of collaborative research. Each is followed by a small-group discussion. (total 5 hours of classroom time)



• Critical Reading Sessions with the Program Directors: A 6-hour journal club-style series in which the Scholars will choose and critique the methodology of articles from the research literature dealing with diagnostic tests, therapy, disease etiology, and prognosis. The JAMA book on User’s Guides to the Medical Literature will be the text for this seminar.



• Applied Biostatistics: This 2 quarter series will cover principles and methods of data description, graphics, point and confidence interval estimation, hypothesis testing, relative risk, odds ratio, Mantel-Haenszel, chi square test, multiple regression; correlation; residual analysis; dummy variables; analysis of co-variance; 1-, 2-way analysis of variance; randomized blocks; fixed, random effects (repeated measure, factorial designs); and multiple comparisons.



• Design of Medical Studies: Emphasizes randomized controlled trials. Eliminating bias, need for randomization, intention-to-treat principles, eligibility criteria, stratification, use of blinding, factorial designs, role of surrogate markers, non-inferiority trials, subset analyses, role of DSMBs, ethical issues. Students draft a clinical trial protocol for presentation to peers, who critique it as a mock study section.



• Epidemiologic Methods: This year-long series will cover the principles and methods of epidemiology, aimed at future researchers. Topics will include measures of disease frequency, measures of effect, causal inferences, descriptive epidemiology, study types, misclassification, effect modification, design of epidemiologic studies to maximize etiologic inferences, confounding, randomized trials, cohort studies, and case control studies.



• Research Operations and Team Leadership: The pragmatic aspects of personnel management, data collection, subject recruitment and retention, data management, quality control, monitoring a project, and budgeting. (2 class hours/week)



• Writing for Publication and Grant Writing: A series of seminars on the organization of manuscripts and grant proposals; presentation of data in tables and figures; and fundamentals of clear and concise prose composition. It will take advantage of the faculty who have been editors and those serving on study sections. (1 hour/week)

Descriptions of selected items, Year 2

• Research Ethics: Topics include landmark cases in evolution of research ethics; federal regulations and international guidelines; the application of ethical principles to research review; investigator-IRB relations; privacy, confidentiality, and HIPAA regulations. Scholars will complete an IRB application, including a draft consent form to UW standards and will attend two meetings of a relevant IRB. (2 hours/week)



• Medical Informatics: Covers a full range of computer applications, from genomics and proteomics to electronic medical records, with an emphasis on the use of informatics for clinical research. (3 hours/week)



• Cost and Outcomes in Health and Medicine: Introduction to the concepts and methods for evaluating cost and outcomes in medical interventions, including the development and evaluation of outcome measures (e.g. quality of life, satisfaction, health state preferences) and cost-effectiveness analysis, resource allocation, and medical decision-making. (3 hours/week)



• Methods and Issues and Using Biological Measurements in Epidemiologic Research: Introduction to use of measurements from biological specimens in epidemiologic studies, preparation for interdisciplinary human studies. Evaluation of biomarkers, preliminary studies, methodological issues, quality control; brief review of molecular biology; applications in current literature discussed. (4 class hours/week)



• Biomedical Regulatory Affairs: An introduction to the relationships among researchers, government, and private industry; organization and jurisdiction of the FDA; classifications for drugs, biotechnology, devices; product approval process; good laboratory and clinical practices, good manufacturing practices; FDA inspection process and post-market issues; legal concerns relating to intellectual property, patents, technology transfer, clinical trials, and product liability; writing an IND or IDE; and an understanding of the dynamic nature of the regulatory environment. (3 hours/week)



• Seminar in Literature Synthesis and Meta-Analysis for Clinical Researchers: A short course developed for the K-30 program; conceptual understanding of quantitative methods for synthesizing evidence from independent studies; methods for pooling evidence, pooling binary and continuous outcomes, differences between fixed and random effects models, and guidelines for appraising systematic reviews or meta- analyses. (3 hours)

Throughout the First 2 Years

K12 Seminar and Work-in-Progress Sessions: The Clinical Research Scholars will apply newly learned concepts by participating in mentored research with ongoing faculty projects, and will also be encouraged to begin developing their own research project ideas early. To facilitate this, weekly work-in-progress multidisciplinary seminars will be held with all Scholars, key program and division directors, and individual mentors. These interactive seminars will allow Scholars to present their ideas and work to a group of peers for thoughtful review and critique. They will begin by describing the status of a project or idea and focusing group attention on certain issues. Vigorous discussion about the feasibility and merits of various study designs and likely project impact will follow. Such peer learning has become a centerpiece of other training programs at this institution, such as the Robert Wood Johnson Clinical Scholars Program and NRSA programs, and is analogous to laboratory meetings in laboratory-based research. The variety of specialties and personal backgrounds of the Scholars will assure diverse strengths, knowledge and experience to share with fellow Scholars.

These sessions are a stimulus to consolidate thoughts into a coherent presentation and a forum in which projects are sculpted. Developing research ideas in a group setting is also preparation for future collaborative projects, providing experience in both giving and receiving constructive feedback. Each Scholar will present a work-in-progress session at least twice a year during the first two years. Late in the first year, each Scholar will be expected to devote one session to presenting a formal research project proposal. This will include preparation of a written protocol, an expected budget, and a formal critique by a third, fourth, or fifth year Scholar. This is designed to emulate the process of an NIH study section, with a primary reviewer and scrutiny by a larger committee. Scholars in the third and later years will also be expected to present at work-in-progress sessions, but because of the number of Scholars, these will take the form of 10-minute presentations as at scientific meetings, with ensuing discussion. Each of the third, fourth, and fifth year Scholars would present at least once a year during the work-in-progress session.

Special Activities within the three K12 Divisions

Scholars may elect courses in the Schools of Medicine, Nursing, Pharmacy, Dentistry or Public Health in their particular fields. Examples would include basic and advanced immunology and cancer biology courses. Those interested in translational research would also chose 2-3 laboratory techniques to explore in detail. This strategy will allow them to learn more about how to interpret data, in some cases generated by others. The Scholars would spend 2-3 days shadowing scientists in the core laboratories. The experience would be rounded out by formal lectures from translational faculty describing clinical research projects that use these techniques. Scholars will also be encouraged to attend selected research seminars in the relevant departments to reinforce the application of the techniques they are learning.

Scholars would have access to a broad array of advanced courses in biostatistics and epidemiology relevant to the conduct of clinical trials. There are advanced biostatistics courses covering survival data analysis, categorical data analysis, statistical genetics, and sample survey techniques. Advanced course offerings in epidemiology include a series of courses in the epidemiology of genetic diseases, cardiovascular disease, infectious diseases, maternal and child health problems, injuries, cancer, AIDS, and emerging infections. Each of these courses covers issues in application of clinical trials and observational research designs in a particular disease area. Several courses in the School of Nursing are particularly relevant to the design and measurement of treatment effects in behavioral trials and community-based intervention trials.

Advanced Clinical Trials Topics: This will be an elective seminar for the second year and beyond. It will meet one quarter per year on a weekly basis for 2 hours. Key articles on trial design or final results with unique examples of design, analytical, or outcome measurement issues will be identified. The discussion will be co-led by one of the faculty and a fellow. Dr. Probstfield will lead this activity, but other mentors with relevant disease or methodological expertise will also participate. A Scholar emphasizing clinical trials may choose to participate in this course repeatedly in the third, fourth and fifth years.

Clinical Trials Center Practicum: Observation and work in a clinical trials center where patients are actively enrolled and data collected. This would be required for Scholars contemplating long term and specialized training in clinical trials or outcomes research. Translational research Scholars might divide their experience between a Trials Center and GCRC protocols. Examples of practicum sites include Dr. Probstfield’s Clinical Trials Service Unit and coordinating center experiences with Drs. Kronmal, Hallstrom. Fleming, Probstfield, Crowley , Ramsey, Corey, or Yusuf (McMaster). Other optional practicum experiences for Scholars with a particular interest in clinical trials would include more extended rotations with the appropriate IRB committee; the GCRC administration; local pharmaceutical or device companies; or even the FDA.

A wide range of potential course work is available in the Departments of Epidemiology, Pharmacy, Nursing, and Health Services. These include Advanced Epidemiologic Methods, Clinical Epidemiology, Pharmacoepidemiology, and Exposure Measurement. Other specialized courses that are appropriate in this division include economic studies of health care, applications of vital and health statistics, qualitative research methods, community-based research methods, health promotion and disease prevention, health behavior change, and advanced biostatistical methods. Nursing courses in questionnaire development and testing, observational research methods, and clinical outcomes research offer further options.

Many Scholars emphasizing this division will want to take the full two-quarter sequence in cost and outcomes during the second year. This covers the concepts and methods for evaluating cost and outcomes in medical interventions, with focused evaluation of outcome measures (e.g. quality of life, satisfaction, health state preferences) and cost-effectiveness analysis, resource allocation, and medical decision-making. These courses require that clinical research projects be proposed (design and analysis plan) or completed with a manuscript as the final outcome. Scholars taking this sequence of courses receive direct mentorship from the course faculty (Sean Sullivan and Donald Patrick).