Instituto de Ortopedia e Traumatologia
do Hospital das Clínicas
Faculdade de Medicina da Universidade de São Paulo
Prof. Tarcísio
Eloy P. Barros Filho / Prof. Arnaldo Valdir Zumiotti
/ Prof. Olavo Pires de Camargo
CLINICAL TRIALS COURSE – 2008
Offered by Scholars in Clinical Science
Program, Harvard Medical School
Organization:
Scholars in Clinical Science Program, Harvard Medical School
Ajay Singh, MD, PhD; Felipe Fregni, MD, MBA; Lauren Dewey-Platt, PhD
Center of Acupuncture IOT, University of Sao Paulo, School of Medicine
Wu Tu Hsing, MD, PhD; Marta Imamura, MD, PhD
Start: March 13th 2008
TARGET: Academics for the health care
system, researchers, health care legislators, professionals from pharmaceutical
companies.
COURSE
OBJECTIVES: Provide theoretical
understanding of the design, conduction, analysis and interpretation of
randomized controlled trials of health interventions. Develop skills to scrutinize information,
critically analyze and carry out research, and to communicate effectively.
Other clinical research courses are offered in
Boston by the Scholars of Clinical Science Program from Harvard Medical School www.hms.harvard.edu/gradprograms/scsp/ (45 days: US$ 15,000; 2-year course:
US$60,000, with a 26% approval rate for foreign students); Department of Health
Policy, Management and Evaluation at University of Toronto http://www.hpme.utoronto.ca/ (one
year: CND$14,252.82 to 18,452.82 for international applicants).
DURATION: 7
months (March 13rd to October 26th 2008)
FACULTY MEMBERS: Harvard
Medical School, Harvard School of Public Health, Harvard Business School
SCHEDULE: (the
course will be in English, without translation)
• Weekly
lectures by teleconference:
Every
Thursday 6pm to 9pm
Brasilia
time zone (GMT-3:00)
U.S.
Eastern time 5pm to 8pm.
From
March to September/2008
• Live 4-day
intensive course:
October
23rd-26th, 2008
Monday to Thursday 8am to 6pm
Classes will be given at Maksoud
Plaza Hotel – São Paulo, Brazil
FEES: Registration fee: US$ 3,500.00
Monthly fee: US$ 500.00 (6
months: March to September/08)
ELIGIBILITY: Health
care PhD holder or director of a health care service
NECESSARY DOCUMENTATION:
2 recent photos ID,
professional license, PhD diploma, a statement of chief or director of a health
service letter
Submit curriculum vitae for
approval by e-mail to mpattylima@hcnet.usp.br
In order to receive a certification letter at the end of the course, the
student must accomplish:
1. Attendance in at least 5 (out of 6) lectures of each module (total of at
least 20 lectures);
2. Full attendance in the 4-day onsite intensive course;
3. score of 80% or more in the final examination to be performed at the end
of the 4-day onsite intensive course.
INFORMATIONS:
Centro de
Estudos Godoy Moreira
Instituto de
Ortopedia e Traumatologia
HC/FMUSP
8:00am to 4:00pm by phone: 55-11 3086-4106
fax: 55-11
3086-4105
E-mail: martaimf@gmail.com
/ wu@fmusp.org.br / mpattylima@hcnet.usp.br
Rua Ovídio Pires de Campos, 333 2º andar
Cerqueira César – São Paulo – SP
CEP
05403-010 BRAZIL
Scholars in
Clinical Science Program, Harvard Medical School
Clinical
Trials Course
March/2008 –
October/2008
Course
Syllabus
Course
directors:
Ajay Singh, MD, MBA
5 Francis Street
Boston, MA 02115 -
Tel:
617-732-5951
Email: asingh@partners.org
Felipe Fregni, MD, PhD
330 Brookline Ave – KS 158 – Boston, MA – Tel:
617-667-5272
Email: ffregni@bidmc.harvard.edu
Executive
director:
Lauren Dewey-Platt, PhD
260 Longwood Avenue, Suite 157 - Boston, MA
02115 – tel: 617-432-1387
Email: lauren_deweyplatt@hms.harvard.edu
Course Description
This course
is relevant both for those wishing to gain an overall understanding of clinical
trials before moving into the field and for those who have general or
specialist experience in this area and aim to broaden their role in the design,
management, analysis, and reporting of clinical trials.
Course Organization:
This is a
video-conference course in which 24 lectures (divided in 4 modules) will be
broadcast to students in University of Sao Paulo (Sao Paulo, Brazil). This
course is a prerequisite for the intensive, live 4-day course in Brazil
(October, 2008). Students will be prepared for lectures that will comprise
1-hour lecture followed by 1-hour period of discussion.
Course Objectives
The course
aims to provide participants with a theoretical understanding of the issues
involved in the design, conduct, analysis, and interpretation of randomized
controlled trials of health interventions.
It is suitable for students working in a country like Brazil. Students will be trained to develop skills to
scrutinize information, to critically analyze and carry out research, and to
communicate effectively.
The course
is divided in four modules – each module having 6 lectures each:
Module 1 – Basics of Clinical Research
Will provide
students with a solid understanding of the basic issues in the design of
clinical trials. Outline the fundamental
principles of clinical trials including study population, selection of
questions, basic study design, randomization process and blindness.
Module 2 - Basic Statistics
Will
introduce the basic statistical methods used in clinical trials. How to select and apply appropriate
statistical methods to analyze data from clinical trials and presenting,
interpreting, and discussing the analyses clearly and concisely.
Module 3 - Assessment, Data Collection and Reporting
The main
features of clinical trials, including methodological and organizational
considerations, and the principles of trial conduct and reporting will be
discussed. Preparing the protocol for a
trial, including data collection forms, logistical and budgetary issues are
critical issues when designing a clinical trial.
Module 4 – Study Designs
Will introduce the main study designs used in clinical
trials. Advantages and drawbacks of each design will be presented; including
also the analytical methods and issues of different study designs.
Text and
Required Readings
Required book:
1. Foundations
of Clinical Research: Applications to Practice (3rd Edition) (Foundations Of
Clinical Research) by Leslie Gross Portney, Mary P. Watkins. Pearson Prentice
Hall.
Optional books:
1. Clinical
Epidemiology: How to Do Clinical Practice Research (third edition) by R. Brian
Haynes, David L Sackett, Gordon H Guyatt, Peter Tugwell. Lippincott Williams & Wilkins.
2. Clinical
Epidemiology: The Study of the Outcome of Illness (third edition) by Noel S.
Weiss. Oxford University Press.
Additional readings and assignments will be
distributed in the course package.
Exams and
final project:
Pass-fail grading will be based on exams at the end of
each module and a grant application that the student will develop along the
course and hand in at the end of the course. A certification letter at the end
of the course will be given only to participants with satisfactory attendance
and grade.
PROGRAM:
DISTANCE-LEARNING CLINICAL RESEARCH TRAINING
(24 weekly lectures of 2
hours of duration)
Module 1: Basics of Clinical Research |
|||
|
Lecture 1 |
13 March |
Introduction
to Clinical Trials |
Steven
Freedman, MD, PhD |
|
Lecture 2 |
20 March |
Study
Population |
Ajay
Singh, MD, MBA |
|
Lecture 3 |
27 March |
Selection
of the Questions |
Felipe
Fregni, MD, PhD, MMSc, MPH |
|
Lecture 4 |
3 April |
Basic
Study Design |
David
Wypij, PhD |
|
Lecture 5 |
10 April |
The
Randomization Process |
David
Wypij, PhD |
|
Lecture 6 |
17 April |
Blindness |
Joe
Massaro, PhD |
|
Module 2: Statistics |
|||
|
Lecture 7 |
24 April |
Statistics
– Basics |
Roger
Davis, Sc.D. |
|
Lecture 8 |
8 May |
Statistical
Tests |
Felipe
Fregni, MD, PhD |
|
Lecture 9 |
15 May |
Sample
Size |
Roger
Davis, Sc.D. |
|
Lecture 10 |
29 May |
Survival
Analysis |
Roger
Davis, Sc.D. |
|
Lecture 11 |
5 June |
Other
Issues in Data Analysis 1 |
Felipe
Fregni, MD, PhD, MMSc, MPH |
|
Lecture 12 |
12 June |
Other
Issues in Data Analysis 2 |
Felipe
Fregni, MD, PhD, MMSc, MPH |
|
Module 3: Assessments and Data Collection |
|||
|
Lecture 13 |
19 June |
Recruitment
of Study Participants |
Paul
Conlin, MD |
|
Lecture 14 |
26 June |
Participant
Adherence |
Michael
Corwin, MD |
|
Lecture 15 |
3 July |
Assessing
and Reporting Adverse Events |
John
Ferguson, MD |
|
Lecture 16 |
21 August |
Data
collection and quality control |
Andrina
Hougham, Medtronic |
|
Lecture 17 |
28 August |
Design
and Analysis of Surveys |
Ellen
McCarthy |
|
Lecture 18 |
4 September |
Manuscript
submission |
Caren
Solomon (deputy editor – New England Journal of Medicine) |
|
Module 4: Study Designs |
|||
|
Lecture 19 |
11 September |
Overview of Study Design |
James Ware, PhD |
|
Lecture 20 |
18 September |
Observational Studies |
Clarissa Valim |
|
Lecture 21 |
25 September |
Experimental Design - issues of uncontrolled
studies |
Clarissa Valim |
|
Lecture 22 |
2 October |
Confounders
in observational studies: using the method of propensity score |
Fran Cook |
|
Lecture 23 |
9 October |
Other
designs |
Rick
Kuntz |
|
Lecture 24 |
16 October |
Experimental Design – Randomized Clinical Trials |
Wafaie Fawzi |
|
October 23rd - 26th Live 4-day intensive course: Monday
to Thursday 8am to 6pm Classes
will be given at Maksoud Plaza Hotel – São Paulo, Brazil |
|||
Detailed Program
Distance-Learning
Clinical Research Training
(24 weekly
lectures of 2 hours of duration)
Module 1: Basics of Clinical Research
Lecture 1, 13 March 2008 – Steve Freedman (confirmed)
Introduction
to Clinical Trials:
1.
· Why perform a clinical trial?
2.
· What is a clinical trial?
3.
· Phase I studies; Phase II studies;
Phase III/IV studies
4.
· Introduction to ethics of Clinical
Trials
Steven Freedman, MD, PhD
Associate Dean of Translational Medicine, Harvard
Medical School
Associate Professor of Medicine, Harvard Medical
School
Director, Pancreas Center
Chief, Translational Research, Beth Israel Deaconess
Medical Center
Lecture 2, 20 March 2008 – Ajay
Singh (case method example) (confirmed)
Study
Population:
- Definition of study population
- Issues on generalization
- Practical aspects: recruitment
Ajay Singh, MD, MBA
Associate Professor of Medicine, Harvard
Medical School
Clinical Chief, Renal Division, Brigham and Women's
Hospital
Director, postgraduate Harvard Medical School CME
courses in nephorplogy and internal medicine
Lecture 3, 27 March 2008 – Felipe
Fregni (confirmed)
Selection
of the Questions:
- Primary question
- Secondary question
- Adverse effects
- Ancillary questions
- Natural history
- Frequent errors
Felipe Fregni, MD, PhD, MMSc, MPH
Assistant Professor of Neurology, Harvard Medical
School
Instructor in Population and International Health,
Harvard School of Public Health
Director, Clinical Trials Network, Beth Israel
Deaconess Medical Center
Lecture 4, 3 April 2008 – David
Wypij (confirmed)
Basic
Study Design:
(note that detail of each study will not be
given at this lecture)
- Observational studies
- Randomized control studies
- Nonrandomized concurrent
control studies
- Historical controls/databases
- Cross-over designs
- Factorial design
- Studies of equivalence
- Large clinical trials
David
Wypij, PhD
Senior
Lecturer on Biostatistics, Harvard School of Public Health
Lecture 5, 10 April 2008 – David
Wypij (confirmed)
The
Randomization Process:
- Fixed allocation randomization
- Simple randomization
- Blocked randomization
- Stratified randomization
- Adaptive Randomization
Procedures (baseline adaptive randomization procedures)
- Mechanisms of randomization
David
Wypij, PhD
Senior
Lecturer on Biostatistics, Harvard School of Public Health
Lecture 6, 17 April 2008 – Joseph
Massaro (confirmed)
Blindness:
- Type of Trials – unblinded
trials
- Single Blind Trials
- Double-blind Trials
- Triple blind trials
- Special problems in double
blind studies – matching of drugs, coding of drugs and assessment of
blindness
Joe Massaro, PhD
Assistant Professor
of Biostatistics, Mathematics and Statistics, Boston University
Managing Director
of Biostatistics and Data Management. Harvard Clinical Research Institute
Module 2: Statistics
Lecture 7, 24 April 2008 – Roger
Davis (confirmed)
Statistics
– Basics:
- Data classification
- Data distribution
- Descriptive methods for
categorical data
- Descriptive methods for
continuous data
Roger Davis, Sc.D.
Associate Professor in the Department of Biostatistics
Harvard School of Public Health
Lecture 8, 8 May 2008 – Felipe
Fregni (confirmed)
Statistical
Tests:
(note: only basics of statistical tests will be
covered)
- Estimation of parameters
- Comparison of population
proportions
- Comparison of population means
- Correlation and regression
Felipe Fregni, MD, PhD, MMSc, MPH
Assistant Professor of Neurology, Harvard Medical
School
Instructor in Population and International Health,
Harvard School of Public Health
Director, Clinical Trials Network, Beth Israel
Deaconess Medical Center
Lecture 9, 15 May 2008 – Roger Davis
(confirmed)
Sample
Size:
- Dichotomous response variables
(two independent samples, paired dichotomous response)
- Sample size for continuous
response variables (two independent samples)
- Sample size for repeated
measures
- Sample size for equivalency of
interventional studies
- Estimating sample size
parameters
Roger Davis, Sc.D.
Associate Professor in the Department of
Biostatistics
Harvard School of Public Health
Lecture 10, 29 May 2008 – Roger
Davis (confirmed)
Survival
Analysis:
- Estimation of the survival
curve (Kaplan Meier estimate)
- Comparison of two survival
curves
- Covariate adjusted analysis
- Use of survival analysis in
clinical research
Roger Davis, Sc.D.
Associate Professor in the Department of Biostatistics
Harvard School of Public Health
Lecture 11, 5 June 2008 – Felipe
Fregni (confirmed)
Other
Issues in Data Analysis 1:
- Poor quality or missing data
- Intention-to-treat analysis
- Competing events
- Covariate adjustment
Felipe Fregni, MD, PhD, MMSc, MPH
Assistant Professor of Neurology, Harvard Medical
School
Instructor in Population and International Health,
Harvard School of Public Health
Director, Clinical Trials Network, Beth Israel
Deaconess Medical Center
Lecture 12, 12 June 2008 – Felipe
Fregni (confirmed)
Other
Issues in Data Analysis 2:
- Subgroup analyses
- Comparison of multiple
variables
- Use of cutpoints
- Meta-analysis of multiple
studies
Felipe Fregni, MD, PhD, MMSc, MPH
Assistant Professor of Neurology, Harvard Medical
School
Instructor in Population and International Health,
Harvard School of Public Health
Director, Clinical Trials Network, Beth Israel Deaconess
Medical Center
Module 3: Assessments and Data Collection
Lecture 13, 19 June 2008 – Paul
Conlin (confirmed)
Recruitment
of Study Participants:
1.
·
Strategies and Sources
2.
·
Monitoring
3.
·
Problems
4.
·
Reasons for
participation
5.
·
Reducing dropout rates
Paul Conlin, MD
Associate Professor of Medicine, Harvard
Medical School
Chief , Endocrinology section, VA Boston Health
Care System
Course Director, Scholars in Clinical Science
Program, Harvard Medical School
Lecture 14, 26 June 2008 – Michael
Corwin (confirmed)
Participant
Adherence:
1.
·
Considerations before
participant enrollment
2.
·
Maintaining good
participant adherence
3.
·
Adherence monitoring
4.
·
Special populations
Michael Corwin, MD
Associate Professor of Pediatrics, epidemiology
and biostatistics, Boston University School of Medicine and Public Health
Lecturer, Scholars in Clinical Science Program,
Harvard Medical School
Lecture 15, 3 July 2008 – John
Ferguson (confirmed)
Assessing
and Reporting Adverse Events:
- Determinants of adverse
effects (length of follow-up, frequency of events and individual
susceptibility)
- Reporting adverse events
John Ferguson, MD
Vice President
and Global Head of Pharmacovigilance and Medical Safety at Novartis Vaccines
and Diagnostics
Lecture 16, 21 August 2008 – Andrina
Hougham
Data
collection and quality control:
1.
· Problems in data collection (major
problems)
2.
·
Minimizing poor quality
data
3.
·
Training, pre-testing
4.
·
Techniques to reduce
variability
5.
·
Data entry
6.
·
Quality monitoring
Lecture
17, 28 August 2008 – Ellen McCarthy
Design
and Analysis of Surveys:
· Instrument design
· Design of survey administration
· Sample design
·
Data collection
· Analysis
Lecture 18, 4 September 2008 – Caren Solomon (deputy editor – New
England Journal of Medicine)
Manuscript submission:
· What makes a great paper
·
Tips
to get your research published in high-impact journals
·
What
high impact journals are interested to publish?
·
Is
there bias in the review process?
Module 4: Study Designs
Lecture 19, 11 September 2008 – Jim
Ware (confirmed)
Overview
of Study Design:
1.
·
Observational studies
2.
·
Experimental studies –
uncontrolled studies
3.
·
Experimental studies -
RCTs
4.
· Other designs – equivalence,
non-inferiority studies
James Ware, PhD
Dean for Academic
Affairs, Harvard School of Public Health
Frederick
Mosteller Professor of Biostatistics, Department of Biostatistics, Harvard
School of Public Health
Statistical
Consultant, New England Journal of Medicine
Lecture 20, 18 September 2008 –
Clarissa Valim
Observational
Studies:
1.
·
Basic designs of
observational studies
2.
·
Retrospective studies
or cohort studies
3.
·
Sample size
1.
·
Bias and confounding
2.
·
Control of bias
3.
· Control of the phenomenon of
confounding
Lecture
21, 25 September 2008 – Clarissa Valim
Experimental
Design - issues of uncontrolled studies:
·
Before
and after comparison in a single group
· Temporal variation of disease
·
Temporal
variation of the staff, equipment and environment
· Statistical regression to mean
· Learning effect
· Psychological effect
Lecture 22, 2 October 2008 – Fran Cook
Confounders
in observational studies: using the method of propensity score:
·
The
issue of confounders in observational studies
· Methods to control for confounders
· The method of propensity score
Lecture
23, 9 October 2008 – Rick Kuntz
Other
designs:
· Equivalence and non-inferiority studies
· Interim analyses
· Adaptive (flexible) design
· Studies with repeated measurements
Lecture 24, 16 October 2008 – Wafaie Fawzi
Professor
of Nutrition and Epidemiology
Experimental Design – Randomized
Clinical Trials:
· Parallel-group design
· Stratified parallel group design
· Parallel group randomized block design
· Complete cross-over design
· Simultaneous treatments design
· Factorial design