College of Public Health University of South Florida. Department of Epidemiology and Biostatistics Syllabus COPH 1038B.

Transcription

1 Department of Epidemiology and Biostatistics Syllabus Course Name: Design and Conduct of Clinical Trials Prefix & Number: PHC 6020 Semester: Summer, 2012 Course Description: Credit hours: 3 Pre-Requisites: Co-Requisites: Location: Instructor Information: The course will familiarize students with the issues in the design and conduct of clinical trials. Factors involved in organizing a trial, randomizing subjects, implementation, and analyzing data from the study will be considered. Biostatistics I and Epidemiology I Please note that students should be familiar with Statistical Software such as SAS, SPSS, R, or S+ ; For SAS package, read and study this web before the class starts; COPH 1038B Ji-Hyun Lee Instructor 1 Instructor 2 Instructor 3 MRC 226, Biostatistics Core, Moffitt Cancer Center Tel: Ji-hyun.lee@moffitt.org * No USF Teaching Assistant Information: TA 1 TA 2 TA 3 Required Materials: Lecture outline notes will be distributed through web, 1 day before class. Permission to Use Lecture Materials: Materials used in this course are the property of the instructor. Students are not permitted to sell notes, tapes, outlines, Syllabus Page 1

2 syllabi or any other material used in this course with out written permission of the instructor. Recommended Materials: Course Format: Text books (the following books are placed on reserve for the class at Shimberg Health Sciences Library): 1. Friedman, L. M., Furberg, C.D., and DeMets, D. L. (1998). Fundamentals of Clinical Trials, Springer: New York. 2. Meinert, C. L. (1986). Clinical Trials: Design, Conduct, and Analysis. New York: Oxford University Press. 3. Wang, D. and Bakhai, A. (2008) Clinical trials: Practical guide to design, analysis, and reporting, Remedica. 1. Some classes will have a guest speaker (1 hour lecture). See the lecture schedule below. All speakers are from Moffitt Cancer Center or USF. 2. Some classes will involve student s activity using computer (maximum 25 min.) Learning Objectives: (Objectives must be numbered) Course Objective: The goal of this class is to introduce the basic statistical concepts and methods for clinical trials. This course will cover Phase I, II, and III clinical trials, but focusing on Phase III and on treatment comparisons. Other topics that will be emphasized include randomization, sample size calculation, meta-analysis, and basic data analyses for clinical trials including survival analysis. Specific learning objectives are: 1. Concepts of clinical trials 2. Classification of clinical trials 3. Basic designs of clinical trials 4. Ethical issues in clinical trials 5. Estimation and hypothesis testing 6. Randomization 7. Sample size and power calculation 8. Systemic review and meta analysis 9. Social behavioral research in medicine 10. Survival analysis 11. Data analysis issues Syllabus Page 2

3 Assessment Strategies: (Strategies must be numbered) Assessment Strategies are based on three exams, 5 homework assignments, Group presentation, and attendance. The weight of each type of assessment is below. At least 80% attendance is required to receive a grade. 1. Mid exam 1 20% 2. Mid exam 2 20% 3. Homework 10% 4. Final exam 40% 5. Group presentation 10% At the end of the course, each student will have a WAS (Weighted Average Score), which is obtained by multiplying his/her numeric score (range 0-100) on each of grading events, e.g. homework, mid-term exam, final exam, etc, by its corresponding weight (percentage), and then summing them up. Note: All exams will be in-class, closed book exams. Also, there will be a peer group evaluation as a part of the group work. This course meets the following MPH (Biostatistics concentration) competencies. Competency Apply biostatistical methods to the design of experimental/observational studies and clinical trials with respect to sample selection, randomization, and statistical power. Demonstrate knowledge of ethical issues related to the use of biostatistics in public health. Learning Assessment Objectives Strategies 1,3,4,5,8, and ,3, and 4 This course meets the following MSPH (Biostatistics concentration) competencies. Apply biostatistical methods to the design of experimental and observational studies with respect to sample selection, randomization, and statistical power. 1, Critique statistical and public health literature Demonstrate knowledge of ethical issues related to the use of biostatistics in public health. 2 1, 3-5 Syllabus Page 3

4 Grading Scale and Criteria: Three exams, 5 homework assignments, Group presentation, and attendance. The weight of each type of assessment is below. At least 80% attendance is required to receive a grade. Table 1 Percentage (%) for each grading event Grading event Mid exam 1 Mid exam 2 HW Final Group Presentation Percentage Note: All exams will be in-class, closed book exams. Also, there will be a peer group evaluation as a part of the group work. Grading Policies: At the end of the course, each student will have a WAS (Weighted Average Score), which is obtained by multiplying his/her numeric score (range 0-100) on each of grading events, e.g. homework, mid-term exam, final exam, etc, by its corresponding weight (percentage) according to Table 1, and then summing them up. A letter grade will then be determined according to the Table 2. In-class examinations are closed book, unless otherwise specified by the instructor. Students may not use any electronic devises (except a calculator) or leave the classroom during the examination without the instructor s permission. Students who fail to appear for the examination or other course grading event, who did not receive permission in advance for the absence, will only be allowed to retake the examination or other grading event based on documentation of the serious and unanticipated nature of the absence. The justification must acceptable to the instructor and approved by the Department Chair. Table 2. Scoring code (this will be changed) Points Grade A+ A A- B+ B B- C+ Points < Grade C C- D+ D D- F Attendance: COURSE POLICIES At least 80% attendance is required to receive a grade. See Institutional Policies section for Emergency Preparedness for Academic Continuity. Syllabus Page 4

5 Permission to Use Lectures: Instructor Expectations: Incomplete Policy: Field Trip Policy: Class Participation: All unauthorized recordings of class are prohibited. Recordings that accommodate individual student needs must be approved in advance and may be used for personal use during the semester only; redistribution is prohibited. No cell phones are allowed; No computer use is allowed expect the use for the class. COPH policy: N/A At least 80% attendance is required to receive a grade. 5/15 Course Calendar Date Topics Notes Introduction I: HW1 will be 1. Scope of PHC 6020 posted 2. Introduction and History of Clinical Trials 3. What is Question? Required readings (FFD Chap. 1, 2; MEI Chap 1; WB Chap 4) 5/17 5/22 Introduction II: 1. Elements of Clinical Trial Protocol (Required readings WB, Chap 3) 2. Brief Introduction to Epidemiology (Review) Earlier Phase Clinical Trials: Phase I & Phase II Phase III Clinical Trials 5/24 5/29 5/31 6/5 Phase III Clinical Trials (continue) Guest speaker: Jonathan R. Strosberg,, MD (5:00pm) Required readings (FFD Chap 1; WB Chap 10-12, 14) Ethical Issues in Clinical Trials Fraud and Misconduct in Clinical Trials Guest speaker: Gwen Quinn, PhD (5:00pm) Required Reading Paper (Flanagin et al.,1998) Estimation and Hypothesis Testing - Baseline Assessment - Basic Map for Statistical Tests Required readings: FFD Chap 8 Randomization and laboratory Guest speaker: Xiuhua Zhao, MPH (6:00pm) Required readings: FFD Chap. 5 and 6; Meinert Chap. 10 HW1 Due HW2 will be posted Syllabus Page 5

6 6/7 6/12 6/14 6/19 6/21 6/26 6/28 7/3 7/5 7/10 7/12 7/17 7/19 Midterm Exam I Sample Size Calculation/Power Consideration Required readings: FFD Chap 7; FFD. Chap 14. Sample size/power calculation laboratory Guest speaker: Kate Fisher, MA (5:00pm) Methods of Meta Analysis : Guest speaker: Ambuj Kumar, M.D., M.P.H (6:00pm) Required readings: FFD Chap pp ; WB Chap 38 and Social Behavior Research in Medicine: - Quality of Life / Alternative and Integrative Medicine Guest speaker: Jim Heather, PhD (6:00pm) Midterm Exam II/ In-Class Exam Survival Analysis I Survival Analysis II Application Guest speaker: Steven Eschrich, PhD (5:00pm) 1. Data and Safety Monitoring Board (DSMB) 2. CONSORT Flow Diagram/Template for CT report Required readings: WB Chapter 32-37; Paper (Giltinan, 2000) 1. Data Analysis Issues I : ITT population/pp analysis/sub-group analysis/confounding/missing Data /Interim Monitoring and Stopping Rules/ Multiple comparison issues 2. Data Analysis Issues II : Parametric vs. nonparametric/ Assumptions for statistical tests Required readings: FFD. Chap 10 (Data collection & Quality Control) & Chap 16. Group Presentations Group Presentations Final Exam: Comprehensive Exam 2 hours In-Class Exam HW2 Due HW3 will be posted HW3 Due HW 4 will be posted HW4 Due HW5 will be posted Group presentation abstract/slide Due HW5 Due Syllabus Page 6

7 Required/Recommended reading papers: Reference List 1. Bailey, K.R. (1990), Detecting Fabrication of Data in a Multicenter Collaborative Animal Study, Clinical Controlled Trials, 12: Giltinan, D., Giving an Effective Presentation (from the Biometric Bulletin, January-March 2000) 3. Flanagin et al. (1998). Prevalence of articles with honorary authors and ghost authors in peerreviewed medical journals, JAMA 280, Pollock, A.V. and Evans, M. (1985). Bias and fraud in medical research: a review, Journal of the Royal Society of Medicine, 78: Meis, P. J. et al. (2003), Prevention of Recurrent Preterm Delivery by 17 Alpha- Hydroxyprogesterone Caproate. The New England Journal of Medicine, 348 (24): PLoS Clinical Trials: for manuscript format for clinical trials 7. Slutsky, A. S. and Lavery J. V. (2004), Data Safety and Monitoring Boards. The New England Journal of Medicine, 350 (11): Weijer, C. (1995). The Breast Cancer Research Scandal: addressing the Issues. Cancer Medical Association Journal. 152: Nuremberg Code and Helsinki Declaration on medical experiments. Software and Computation: 1) SAS Help: 2) Earlier Phase Clinical Trials: Phase II trials using Simon's two-stage design from 3) Data Analysis and Issues (in SAS) PROC MEANS/PROC FREQ/PROC UNIVARIATE/PROC TTEST/ PROC NPAR1WAY 4) Randomization: * PROC PLAN in SAS 5) Sample size calculations: Software PS 6) Survival Analysis * PROC LIFETEST/PROC PHLEG in SAS INSTITUTIONAL POLICIES The most recent version of the Institutional Policies information can be found on the Academic Affairs Forms page at (Fall 2010) Syllabus Page 7

8 Student Handbook: Student Conduct: Disruption of Academic Process/Academic Integrity of Students: Academic Dishonesty/ Plagiarism: USF Student Rights/Responsibilities: USF Student Code of Conduct: Disruption of the academic process and violations of the policies regarding academic integrity will not be tolerated. Review USF policies on Disruption of the Academic Process and the Academic Integrity of Students at: Plagiarism will not be tolerated and is grounds for failure. Review USF Academic Dishonesty and Disruption of Academic Process Policy at: Undergraduate: Graduate: The has an account with an automated plagiarism detection service (SafeAssign), which allows instructors and students to submit student assignments to be checked for plagiarism. I (the instructor) reserve the right to 1) request that assignments be submitted as electronic files and 2) submit students assignments to SafeAssign, or 3) request students to submit their assignments to SafeAssign through myusf. Assignments are compared automatically with a database of journal articles, web articles, the internet and previously submitted papers. The instructor receives a report showing exactly how a student s paper was plagiarized. NOTE: An institution may not release a paper to a plagiarism detection software without the student s prior consent unless all personally identifiable information has been removed, such as a student s name, social security number, student number, etc.. Note that a paper/essay is considered an educational record and an institution may not ask a student to waive their rights under FERPA for the purpose of submitting papers to a plagiarism detection software. For more information about Plagiarism and SafeAssign, visit: Plagiarism tutorial: SafeAssignl: Cheating Statement: The USF College of Public Health expects students to maintain academic honesty in all courses. By virtue of being registered in an public health course, students agree to refrain from cheating. If cheating in any form (academic dishonesty) is detected, appropriate action will be taken. (Refer to USF Academic Dishonesty Policy). Undergraduate: Graduate: Syllabus Page 8

9 files/usf_grad_catalog_2010_2011.pdf#page=42 Undergraduate Academic Policies and Procedures: Special Accommodations: Holidays and Religious Observances: Emergency Preparedness: Student Grievance Procedure: Students in need of academic accommodations for a disability may consult with the office of Services for Students with Disabilities to arrange appropriate accommodations. Students are required to give reasonable notice (typically 5 working days) prior to requesting an accommodation. Students with Disabilities Services: Students: Faculty: In the event of an emergency, it may be necessary for USF to suspend normal operations. During this time, USF may opt to continue delivery of instruction through methods that include but are not limited to: Blackboard, Elluminate, Skype, and messaging and/or an alternate schedule. It s the responsibility of the student to monitor Blackboard site for each class for course specific communication, and the main USF, College, and department websites, s, and MoBull messages for important general information. Review USF Academic Grievance Policy at: Undergraduate: Graduate Student assistance is provided by Division of Student Affairs, Office of the Student Ombudsman. Syllabus Page 9

10 RESOURCES FOR STUDENTS Library Resources: Creating Citations & Using Refworks: Netiquette (online communication etiquette for online courses): Plagiarism & Safe Assign: USF Accounts: Blackboard Tutorials: Elluminate Live Tutorials: (for online courses) USF Library Resources and Services: Shimberg Health Sciences Library: Shimberg Health Sciences Library Tutorials: (follow links under Instructional Services section) See Academic Dishonesty/Plagiarism Section Syllabus Page 10