MPTX 517/Nursing 540: Structure and Management of Clinical Research

Instructors:
Anne-Caroline Dupont, M.Eng., PhD, Alfred E Mann Institute forBiomedical Engineering
FJR Richmond, PhD, RN, USC School of Pharmacy
Peggy Kalowes, MN, RN, Department of Nursing, USC
Linda Lillington, DNSc, RN, Harbor-UCLA Medical Center
Maryalice Jordan-Marsh, PhD, RN, Department of Nursing, USC

Course weight: 4 Units
Placement: Distance learning modules are sent out 6 weeks previous to start of class. Assignments should be completed before the first day of class.

Introduction and Purposes:

Well-structured and managed clinical trials are an important cornerstone in the development of medical products. The development and execution of such trials requires a knowledge of scientific principles and statistical methods, complemented by a solid grounding in bioethical principles underlying the protection of human research subjects. It also requires training in the logistics of Good Clinical Practices, documentation, and project management. The present course is designed for students with a strong background in biomedical science, pharmacy or the allied health professions, including students who will be enrolled in the Master’s of Regulatory Science program. It will provide a learning environment in which students will analyze the current policies and guidelines under which clinical projects are organized and regulated. In this course students will explore the trends in policy development relating to human research. Students will be expected by the end of the course to understand similarities and differences in regulatory requirements for studies conducted in the US, Canada, Europe and other international constituencies. Differences in the structure of clinical trials for different types of medical products (e.g pharmaceutical products, devices, food s and additives) will be evaluated. Project planning and clinical auditing skills will be enhanced by practice sessions, workshops and case studies. The course will be given as a blend of distance and classroom components. As part of a novel strategy to meet the needs of part-time as well as full-time students, students will be taught in the classroom with two intensive periods of full-day sessions. These sessions will be supplemented by the use of materials developed in a distance learning format on CD-ROM. These learning modules will eventually account for about 40% of the programmatic content. The learning modules will be available at the pace of the student as he/she completes individual components. Students will expand this new knowledge by writing short research papers on issues of policy or project management related to a clinical trial. Topics will be assigned in advance by the instructor.

Course Objectives:

Students graduating from this course will have a sound understanding of the organization and conduct of clinical trials. They will be able to explain and compare the types of testing that will be required to introduce a new drug or device onto market, and describe the relationship of statistical design and hypothesis development to the validity of the trial and the formulation of claims. They will be able to identify criteria for accepting a study site, for budgeting, and managing a group of sites, and reporting data appropriately. Students will articulate and give examples of applying psychosocial concepts in recruiting and retaining subjects and project staff. They will articulate the differences between Good Clinical Practices in different countries and the implications of these differences for the structure and conduct of trials. Students will demonstrate awareness of the new requirements in place for the protection of human subjects in the US, and provide rationales for those requirements. Within this new base of knowledge, students will be able to identify, demonstrate, and critique examples of the documentation required to submit clinical trial results to regulatory authorities, to conduct post-marketing studies and to document and act on adverse events.

Course Outline:

Course content is provided by classroom instruction and seminar discussion that is complemented by newly developed distance-learning modules. During classroom experiences, core material presented by the instructors will be complemented by 1-2 hour sessions featuring outside speakers from industry or government. These experts in the field will highlight key points, provide opportunities for questions and guide the analysis of case studies to consolidate and expand upon the knowledge gained by the students in materials covered in the “distance” modules. Students will engage in seminar type discussion and exercises to promote application of knowledge.

Module 1: Protection of Human Subjects

- History and rationale for regulatory rules and guidelines
- Videos—History of Human Research Guidelines, Belmont report.
- Contemporary examples of human subjects violations
- Strategies for minimizing risks and ensuring informed consent
- New initiatives related to recent problems with genetic testing
- Where are we now?

Module 2: Beginning a trial…

- Introduction to the various players: sponsors, IRBs, site researchers, government
- The role of the IRB in human protection
- Film: “Balancing Society’s Mandates”
- Submissions to the IRB
- Informed consent processes and rules
- Role of previous and concurrent studies

Module 3: Planning of clinical trials for regulatory submission

- Stages of clinical trials in drug development
- Differences in clinical trials for the device arena
- Goals and planning of phase I safety trials
- Considerations when planning testing protocols
- Goals and planning of pivotal trials

Module 4: Managing clinical trials

- Selecting sites and investigators for clinical research
- Preinitiation meetings and activities through the eyes of the clinical monitor
- Preinitiation meetings and activities through the eyes of site investigators
- Building in evaluation and monitoring: compliance/adherence of subjects, data collectors, investigators
- Strategies for building buy-in from all stakeholders
- Budgets and time-lines
- Good Clinical Practices

Module 5: Identifying and Reporting Adverse Events

- Evaluating seriousness and unexpectedness
- Reporting structures and time-lines in the US
- Reporting structures and time-lines internationally
- Communication at the clinical site level
- Human subjects implications
- The product recall
- Unexpected trial terminations

Module 6: Recruitment Issues

- Rules governing recruitment
- Advertising
- Challenges surrounding recruitment and patient management
- Implications for trial design
- Retention strategies

Module 7: Documentation of Clinical Data

- Organizing and auditing clinical report forms
- Monitoring a trial--how often and how?
- Archiving data: timing and back up
- Storing records, guarding access
- Documenting clinical supplies
- Filing and configuration management
- Quality assurance

Module 8: Clinical test materials

- When are drugs and devices ready for use in humans?
- Labeling and transporting test articles
- Partnerships at the clinical site: circle of stakeholders
- Site arrangements to prevent adulteration and mixups
- Use of investigational devices and drugs beyond a specified trial

Module 9: Clinical Trial audits

- Importance and organization of internal clinical audits
- Preparing for and managing audits of state and federal agencies
- The Quality Assurance Unit: Functions and structure

Module 10: Clinical Research Organizations and Clinical Laboratories

- Comparison of clinical research organizations, academic research centers, and industry based research?
- Advantages and disadvantages of contracting clinical research
- Working with a CRO, academic center.
- Assessing clinical laboratories
- Organizing and validating clinical lab tests

Module 11: Clinical Trials in Europe

- International standards and European GCPs
- Translation and language issues
- Clinical trials and product marketing in the third world

Module 12: Professional behavior and Ethics

- Sustaining literacy in the field: journals, conferences,
- Cultural aspects of CRO vs Academic Center
- Team building
- Communication among and across stakeholder groups
- Role of professional organizations: networking, certification
- Writing letters, memos and reports
- Traveling and working at foreign sites

Course Requirements and Grades:

Modular testing 30%
Midterm exam 30%
Final exam 40%

Students will be able to demonstrate a competent knowledge of the subject matter by formal examination. Students will also write three short research papers on policy issues or case studies assigned by the course instructors. The papers will be evaluated on the basis of the following criteria:

- Clear explanation of the issue or problem under study
- Review of current guidelines and identification of regulatory requirements
- Identification of other issues including policy issues
- Appropriate knowledge of ethical and professional behaviors
- Appropriate literature citations

Recommended Text books:

Ginsberg, David (1999) The Investigator’s Guide to Clinical Research. 2nd ed. Centerwatch Inc: Boston, MA

Spilker, B. (1991) Guide to Clinical Trials. Lippincott-Raven, Philadelphia

Reference material will also be provided in the form of a reading list appended to a CD ROM, and by appropriate web-page references.

Attendance and Conduct:

The Student Handbook, SCampus and University Catalogue provide guidance regarding academic policies and procedures. Students will regard the program as a part of their professional development in which courtesy and responsibility are significant factors in success. Thus, students are expected to communicate absences from class and are expected to attend all examinations and class presentations. Under normal circumstances, papers and exams must be submitted on or before the scheduled deadlines. Failure to make appropriate arrangements in case of justifiable delay will result in a penalty of 10% in the assigned mark for the first two weeks of delay, and further penalties for additional unapproved delays.

Students with disabilities are to inform the instructor at the first class session of any accommodations they require.