PROGRAM

Module 1 - BASICS OF CLINICAL RESEARCH

Tutorial Lecture - 21 February, 2013 4:00pm
Course Staff and Course Director*
• Opening remarks
• Syllabus and discussion on the course format
• Team introduction
• Sites introduction
• Using the Collaborative Learning Method: an overview
• Website tutorial
• Discussion

Lecture 1, 14 March 2013 4:00pm
Steve Freedman*
Introduction to Clinical Trials:
• Why perform a clinical trial?
• What is a clinical trial?
• Phase I studies; Phase II studies; Phase III/IV studies
• Introduction to ethics of Clinical Trials

Lecture 2, 21 March 2013 4:00pm
Jonathan Williams*
Selection of the Questions:
• Primary question
• Secondary question
• Adverse effects
• Ancillary questions
• Natural history
• Frequent errors

Lecture 3, 28 March 2013 4:00pm
Felipe Fregni*
Study Population:
• Definition of study population
• Issues on generalization
• Trade-off: Internal validity vs. external generalizability
• Examples from landmark studies

Lecture 4, 04 April 2013 4:00pm
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
Online discussion: Ethical and regulatory issues
• Distinguishing Clinical Research from Clinical Practice
• Equipoise and ethics of clinical research
• Ethical considerations in Randomized Clinical Trials
• Ethics of phase I research
• A moral theory of informed consent
• Children in Research
• Confidentiality
• Scandals and tragedies of research with human participants: Nuremberg, the Jewish chronic hospital and Tuskegee
• Special topic: ethical dilemmas in clinical research
• Special topic: Reasons patients refuse to participate in Clinical Trials
• Special topic: effective patient communication - challenges and recommendations
• Special topic: Psychiatric symptom-provoking studies: an ethical appraisal

Lecture 5, 11 April 2013 4:00pm
Joseph Massaro*
Study Blinding:
• 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

Lecture 6, 18 April 2013 4:00pm
David Wypij*
The Randomization Process:
• Fixed allocation randomization
• Simple randomization
• Blocked randomization
• Stratified randomization
• Adaptive Randomization Procedures (baseline adaptive randomization procedures)
• Mechanisms of randomization

Lecture 7, 25 April 2013 4:00pm
Priscilla Driscoll-Schempp*
Recruitment of Study Participants:
• Strategies and Sources
• Monitoring
• Problems
• Reasons for participation
• Reducing dropout rates
Lotfi Merabet*
Participant Adherence:
• 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"

Exam Module 1

Module 2: STATISTICS

Optional tutorial in Stata I, 30 April 2013
Rui Imamura*
• Getting started
• Entering data
• Working with commands, do-files and results

Optional tutorial in Stata II, 02 May 2013
Suely Matsubayashi*
• Descriptive statistics
• Regression and correlation
• ANOVA

Lecture 8, 09 May 2013 4:00pm
Roger Davis*
Statistics - Basics:
• Data classification
• Data distribution
• Descriptive methods for categorical data
• Descriptive methods for continuous data

Clinician Statistical Corner
Munir Boodhwani*
Case study 1: Data classification in clinical research
Case study 2: Sample size calculation

Lecture 9, 16 May 2013 4:00pm
Felipe Fregni*
Statistical Tests I:
• Estimation of parameters
• Comparison of population proportions (Chi-square test and Fisher's exact test)
• Comparison of population means (Student t-test, ANOVA)
• Linear Regression

Lecture 10, 23 May 2013 4:00pm
Felipe Fregni*
Statistical Tests II:
• Correlation (Pearson and Spearman correlation coefficient)
• Nonparametric tests for two group comparisons (Mann-Whitney and Wilcoxon Signed Rank Test)
• Nonparametric tests for more than two group comparisons (Kruskal-Wallis and Friedman Two-Way
Analysis of Variance)

Lecture 11, 30 May 2013 4:00pm
Jessica Paulus*
Sample Size:
• Dichotomous response variables (two independent samples, paired dichotomous response)
• Sample size for continuous response variables (two independent samples)
• Sample size for equivalency of interventional studies
• Estimating sample size parameters
Practical example: How to calculate sample size for a grant application

Lecture 12, 06 June 2013 4:00pm
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

Lecture 13, 13 June 2013 4:00pm
Felipe Fregni*
Other Issues in Statistics I:
• Missing data
• Intention-to-treat analysis
• Covariate adjustment

Lecture 14, 20 June 2013 4:00pm
Felipe Fregni*
Other Issues in Statistics II:
• Subgroup analyses
• Comparison of multiple variables
• Meta-analysis of multiple studies

Exam Module 2

Module 3: PRACTICAL ASPECTS OF CLINICAL RESEARCH

Lecture 15, 27 June 2013 4:00pm
Gretchen Brodnicki*
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

July 2 - August 08 - SUMMER STATISTICS STUDY PERIOD

Lecture 16, 15 August 2013 4:00pm
Dennis LaCroix*
The business of Clinical Research - negotiating contracts
• Budgeting for ancillary services
• Budgeting for personnel
• Budgeting for patient fees
• Budgeting for quality assurance
• Budgeting for overhead
• Negotiating the study budget (intellectual property, confidential information, publication and termination, and payment terms)
Vera Novak*
Being a Clinical and Translational Scientist: Practical Challenges and Recommendations
• Are we translating findings from Basic Research into Clinical Practice?
• Insights for working with special populations in clinical research
• Challenges for the young clinical investigator
• Challenges for the senior clinical investigator
• Setting up an international collaborative network in clinical research
• Future of translational science research

Online only - manuscript and grant writing
• Writing with clarity
• Writing in a non-native language
• Tables
• Figures
• Figures legends
• Rewriting the paper: reviewing style, spelling and second opinions

Lecture 17, 22 August 2013 4:00pm
Alan Zaslavsky*
Design and Analysis of Surveys:
• Instrument design
• Design of survey administration
• Sample design
• Data collection
• Analysis

Lecture 18, 29 August 2013 4:00pm
John Ferguson*
Assessing risk and adverse effects in clinical research:
• Reporting of adverse effects
• Determinants of adverse effects (length of follow-up, frequency of events and individual susceptibility)
• Signal detection in pharmacovigilance - challenges and recommendations
• Safety risk management and clinical development
• Risk management principles for pharmacovigilance
Suzanne George
Phase III and Multicenter Trials
• Challenges for large clinical trials
• Data monitoring
• Site selection
• Funding and regulatory issues

Lecture 19, 05 September 2013 4:00pm
Caren Solomon*
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?

Exam Module 3

Module 4: STUDY DESIGNS

Online discussion: International/global research
• HIV trials in developing countries
• Ethical Imperialism? Ethics in International Collaborative Clinical Research

Lecture 20, 12 September 2013 4:00pm
Jessica Paulus* & Felipe Fregni*
Special Panel: RCT vs. Observational Designs – how to choose?
While RCTs are non-efficient in terms of cost and time, observational studies are associated with selection bias, unmeasured confounders and lack of blinding – how to choose them?
• RCTs – why should we choose this design?
• Observational studies – why should we choose this design?

Lecture 21, 19 September 2013 4:00pm
Clarissa Valim*
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 22, 26 September 2013 4:00pm
Laura Mauri
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

Lecture 23, 03 October 2013 4:00pm
Richard Kuntz*
Designs with Medical Devices and Interim Analysis:
• Clinical Trials with Medical Devices
• Interim analyses
• Adaptive (flexible) design

Lecture 24, 10 October 2013 4:00pm
Scott Evans
Non-inferiority designs:
• Superiority trials
• Non-inferiority designs
• Goals of NI designs
• Choosing the non-inferiority margin

Final Exam will be scheduled in November after the 4-Day Live intensive course.

For information on our workshops and additional courses please visit www.ppcr.hms.harvard.edu