Main Course
Principles and Practice of Clinical Research
What to expect
Our collaborative distance-learning training program in clinical research is offered to participants from Boston and throughout the world. It is designed for individuals who wish to gain basic and advanced training in clinical trials before moving into the field and for those who have experience in this area and aim to broaden their role in the design, management, analysis, and reporting of clinical trials.
Learning Objectives: At the end of the program, participants will be able to design clinical trials in an effective manner, collect data appropriately, use the basic functions of a statistical software package, choose appropriate basic statistical tests, run statistical analysis, critically read and understand a research paper, develop clinical research based on integrity principles, discuss the basics of article publication and the reviewing process, and describe more complex clinical trial designs.
Format
This program is a distance-learning program; however, participants have to attend weekly 3-hour interactive video-conference sessions with participants from the same location (for instance, participants from Dresden, Germany meet at University of Dresden for the live connection with Harvard). The videoconference sessions are broadcast from Harvard to different centers across the world (individual participants can also participate via web-conference). Participants are required to participate in forum discussions, read articles and complete assignments and statistical exercises. At the end of the 9-month program, there will be a recommended 5-Day Immersion Course to practice the concepts learned in this program. An optional 3-Day Advanced Statistical Workshop and 2-Day Research Manuscript Writing workshops will also be held in Boston, MA.
In order to participate in this distance-learning program, participants will need regular access to a computer with excellent internet connection, email, a PDF viewer, and possibly a webcam and microphone connected to the computer.
Overview
Who should attend
Applicants usually have a graduate degree or a health care professional degree (MD, MPH, biostatistics, epidemiology, nursing, physical and speech therapy, pharmacy, and dentistry) and come from several countries, given that participants can partake in the program remotely in their own city. Although participants can take this program locally, interaction with other students and instructors as well as participation in the program activities is a requirement for the successful completion of the program. On-site participants are required to be present during the videoconference activities.
Investment in the future
By helping researchers improve their skills in clinical research in a highly interactive environment, this program will promote personal and professional growth and help participants become more effective in their work. We also expect that the interactive environment of the program will promote connections between participants and help foster future collaborative, multi-center projects. Our goal is to offer a highly interactive learning environment for international clinical research training while creating a global network of clinical researchers to foster future collaboration in clinical research.
Program content
Our program covers topics from the basics of clinical research (such as how to formulate a research question, how to select a study population, and randomization and blinding methods) to statistical methods (data distribution and classification, statistical tests, sample size calculation, survival analysis, missing data, and meta-analysis); data collection, monitoring, and reporting (including training in manuscript writing); and study designs (observational studies, non-inferiority and adaptive designs, and randomized clinical trials).
Learning objectives
At the end of the program, participants will be able to design clinical trials and interpret results from statistical analysis in an effective manner, collect data appropriately, use the basic functions of a statistical software package, choose appropriate basic statistical tests, run statistical analysis, critically read and understand a research paper, develop clinical research based on integrity principles, discuss the basics of article publication and the reviewing process, and describe more complex clinical trial designs.
Learning tools
The following learning tools are used in our program:
- Live connection with Harvard (videoconference lectures): our program consists of 24 lectures taught by faculty from Harvard T.H. Chan School of Public Health, Harvard Medical School, and Tufts Medical Center. Each weekly lecture includes a 60-minute interactive module led by the program director to discuss the online poll and case study written specifically for the program, a 60-minute teaching/lecture module, and 60-minute live question/answer discussion module in which participants interact directly with faculty.
- Discussion forum: Each weekly lecture/topic includes a required online discussion forum.
- Online polls: Participants respond to weekly polls addressing the topic of the subsequent lecture.
- Assignments: Participants are required to submit practical assignments related to weekly lectures, including statistics assignments as part of the statistical training component of the program.
- Asking questions: Participants have intensive interaction with faculty and staff via office hours and the website forum.
- Group Project: Participants are required to participate in a group project in which they work together to write a grant application. The project is created using the online interactive tool. Most participants choose to submit their final project after review with faculty members to our online peer-reviewed international journal for publication (www.ppcr.org/journal)
- Long-term Vision for Participants: Participants are strongly encouraged to continue their interaction through our Alumni community (https://www.facebook.com/groups/ppcralumni/) created to maintain interaction between participants for the discussion of clinical research topics.
Hardware and software requirements
Computers: Any computer running Windows or Mac OS are supported.
Internet Connection: Your computer should be configured to access the Internet. A high speed internet connection (preferably by ethernet) is required during live lectures (Thursdays from 4pm to 7pm Boston time) and recommended for the online weekly activities (i.e. forum of discussion).
Browsers: Although our website may work with Internet Explorer and Safari, we recommend:
- Google Chrome
- Mozilla Firefox 11.x or above
- Internet Explorer 10.x or above
Location and directions
Harvard T.H. Chan School of Public Health
677 Huntington Ave, Boston, MA 02115
By Public Transportation:
Green Line (E Train) - Brigham Circle
Policies
DISCLOSURE POLICY
All relevant financial relationships with commercial entities will be disclosed. These disclosures will be provided in the activity materials along with disclosure of any commercial support received for the activity. Additionally, faculty members have been instructed to disclose any limitations of data and unlabeled or investigational uses of products during their presentations.
CANCELLATION POLICY FOR PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH
All requests for cancellations must be made in writing. Cancellations on or before February 2, 2023 will be issued a refund less a $150 administrative fee per person. Cancellations received between February 3, 2023 and March 2, 2023 will be issued a refund of 50%. After March 2, 2023, no refund will be issued. There will be no exceptions to this policy.
CANCELLATION POLICY FOR PPCR RESEARCH MANUSCRIPT WRITING WORKSHOP
All requests for cancellations must be made in writing. Cancellations on or before June 8, 2023 will be issued a refund less a $150 administrative fee per person. Cancellations received between June 9, 2023 and July 6, 2023 will be issued a refund of 50%. After July 6, 2023, no refund will be issued. There will be no exceptions to this policy.
CANCELLATION POLICY FOR PPCR 3-DAY STATISTICAL WORKSHOP
All requests for cancellations must be made in writing. Cancellations on or before June 5, 2023 will be issued a refund less a $150 administrative fee per person. Cancellations received between June 6, 2023 and July 3, 2023 will be issued a refund of 50%. After July 3, 2023, no refund will be issued. There will be no exceptions to this policy.
Program Schedule
This is the 2023 schedule for the 3-hour weekly lectures in the distance-learning
Main Course component of the PPCR program.
Module 1 - BASICS OF CLINICAL RESEARCH
BASICS OF CLINICAL RESEARCH
Tutorial Lecture - March 23, 2023 – Program Staff and PPCR Program Director – Felipe Fregni
• Opening remarks
• Syllabus and discussion of the program format
• Team introduction
• Sites introduction
• Using the Collaborative Learning Method: An overview
• Website tutorial
• Discussion
Lecture 1 - April 6, 2023 – Albert Hofman
Introduction to Clinical Trials:
• Overview of clinical research
Lecture 2 - April 13, 2023 – Michele Hacker
Study Population:
• Definition of study population
• Issues on generalization
• Trade-off: Internal validity vs. external generalizability
• Examples from landmark studies
Lecture 3 - April 20, 2023 – David Wypij
Basic Study Design:
• Observational studies
• Randomized control studies
• Nonrandomized concurrent control studies
• Historical controls/databases
• Cross-over designs
• Factorial design
• Studies of equivalence
• Large clinical trials
Lecture 4 - April 27, 2023 – David Wypij
The Randomization Process:
• Fixed allocation randomization
• Simple randomization
• Blocked randomization
• Stratified randomization
• Adaptive randomization procedures (baseline adaptive randomization procedures)
• Mechanisms of randomization
Module 2 - OBSERVATIONAL STUDIES
OBSERVATIONAL STUDIES
Lecture 5 - May 4, 2023 – Felipe Fregni
Selection of the Question and Group Project Introduction:
• Primary question
• Secondary question
• Adverse effects
• Ancillary questions
• Natural history
• Frequent errors
Lecture 6 - May 11, 2023 – Heather Baer
Observational Studies:
• Basic designs of observational studies
• Retrospective studies or cohort studies
• Sample size for observational studies
• Bias and confounding
• Control of bias
• Control of the phenomenon of confounding
Lecture 7 - May 18, 2023 – Heather Baer
Confounders in Observational Studies: Using the Method of Propensity Score:
• The issue of confounders in observational studies
• Methods to control for confounders
• Method of propensity score
Module 3 - BASIC STATISTICS
BASIC STATISTICS
Lecture 8 - May 25, 2023 – Roger Davis
Statistics – Basics:
• Data classification
• Data distribution
• Descriptive methods for categorical data
• Descriptive methods for continuous data
Lecture 9 - June 1, 2023 – John Orav
Statistical Tests I:
• Estimation of parameters
• Comparison of population means (student t-test, ANOVA)
Lecture 10 - June 8, 2023 – John Orav
Statistical Tests II:
• Chi-square and Fisher’s exact test
• Trend test for categorical data
Lecture 11 - June 15, 2023 – Felipe Fregni
Statistical Tests III:
• Parametric and Nonparametric tests for more than two group comparisons (Analysis of variance (ANOVA) and Kruskal-Wallis)
• Correlation (Pearson and Spearman correlation coefficient)
Lecture 12 - June 22, 2023 – Jessica Paulus
Sample Size Calculation:
• Dichotomous response variables
• Sample size for continuous response variables
• Sample size for equivalency of interventional studies
• Estimating sample size parameters
• Practical example: How to calculate sample size for a grant application
Lecture 13 - June 29, 2023 – Roger Davis
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
GROUP PROJECT - July 7 – August 11, 2023
Module 4 - APPLIED STATISTICS
APPLIED STATISTICS
Lecture 14 - August 17, 2023 – Felipe Fregni
Missing Data and Covariate Adjustment:
• Missing data
• Intention-to-treat analysis
• Covariate adjustment
Lecture 15 - August 24, 2023 – Felipe Fregni
Meta-analysis and Subgroup Analysis:
• Subgroup analysis
• Comparison of multiple variables
• Meta-analysis of multiple studies
Lecture 16 - August 31, 2023 – David Wypij
Non-Inferiority Designs:
• Superiority trials
• Non-inferiority designs
• Goals of non-inferiority designs
• Choosing the non-inferiority margin
Lecture 17 - September 7, 2023 - Felipe Fregni
Adaptive Designs & Clinical Research in the Context of Individualized Medicine (N-of-1 Designs)
• Interim analysis
• Adaptive (flexible) design
• Basics and goals of N-of-1 designs: When to use
• Basics and goals of adaptive designs: When to use
• Introduction to individualized medicine
• Statistical issues
• Examples and discussion
Module 4 - PRACTICAL ASPECTS OF CLINICAL RESEARCH
PRACTICAL ASPECTS OF CLINICAL RESEARCH
Lecture 18 - September 14, 2023 – Mark Barnes
Integrity in Research:
• Disputes about authorship - when authorship fails
• The right or otherwise to publish data, patents, and grant funding
• Scientific integrity and misconduct
• Publication practices
• Conflict of interest
Lecture 19 - September 21, 2023 – Joseph Massaro
Study Blinding:
• 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
Lecture 20 - September 28, 2023 – Lotfi Merabet
Recruitment of Study Participants & Participant Adherence:
• Monitoring
• Reasons for participation
• Participant adherence
• Reducing dropout rates
• Considerations before participant enrollment
• Maintaining good participant adherence
• Adherence monitoring
• Special population of patients: The “skeptic”, the “pleaser”, “the information seeker”, “the hopeless”, “the money seeker”, “the professional research participant”, “the high maintenance participant”, “the noncompliant participant”
Lecture 21 - October 5, 2023 – Felipe Fregni
Safety, Clinical, and Surrogate Outcomes:• Reliability of measurements
• Validity of measurements
• Introduction to safety, clinical, and surrogate outcomes
Lecture 22 - October 12, 2023 – Donald Halstead
Effective Communication in Clinical Research:
• Principles of good writing
• How to write a paper
• IMARD
Lecture 23 - October 19, 2023 - Howard Sesso
Multicenter Trials and industry-academia collaboration:
• Challenges for multicenter trials
• Data monitoring
• Site selection
• Funding and regulatory issues
Lecture 24 - October 26, 2023 – Felipe Fregni
Special Panel: RCT vs. Observational Designs – How to choose?
• RCTs – why should we choose this design?
• Observational studies – why should we choose this design?