VI. Description of all MMSCI Courses

Color Key for this table:

COR: Core Foundational courses common to all tracks and pathways CI: Clinical Investigation Track courses common to all CI pathways CT: Clinical Trials Pathway courses only for CT pathway CR: Comparative Research Pathway courses only for CR pathway TI: Translational Investigation Track courses

Year I VI. Description of all MMSCI Courses Workshop 1 (July)

COR CI742: Fundamental Skills for Academic and Student Success (1 cr) COR CI701: Clinical Data Science: Design and Analytics I (3 cr)

Fall Longitudinal Courses (September to December)

COR CI700: Ethics and the IRB (1 cr) COR CI706A: Mentored Research Experience - Harvard-based mentor (5 cr) COR CI704A: Scientific Communication (1 cr) COR CI708A: Clinical Data Science: Design and Analytics II (1.5 cr) COR CI709A: Intro to Clinical and Translational Thesis Preparation (1 cr) CI CI702: Clinical Trials Part 1 (1.5 cr) TI CI760: Investigative Models for Translational Research (1 cr)

Workshop 2 - January Term (January)

COR CI724: Genetic Epidemiology (1 cr) COR CI740: Leadership and Teamwork (2 cr)

Spring Longitudinal Courses (January to April)

COR CI706B: Mentored Research Experience - Harvard-based mentor (5 cr) COR CI704B: Scientific Communication (1 cr) COR CI708B: Clinical Data Science: Design and Analytics II (1.5 cr) CI CI702B: Clinical Trials (1.5 cr) TI CI 764A: System Biology & Omics Analysis (2 cr)

Workshop 3 (April - May)

CR CI 722: Comparative Effectiveness Research I (3 cr) TI CI 762: Cell and Molecular Biology (2 cr)

Year II Fall Longitudinal Courses (September to December)

COR CI706C: Mentored Research Experience under the supervision of Harvard-based mentor (5 cr) COR CI714A: Scientific Communication (1 cr) CT (optional for TI) CI 710: Special Topics in Clinical Investigation (2 cr) CT CI726A: Advanced Topics in Clinical Trials A (2 cr) CR CI 732A: Comparative Effectiveness Research II (1.5 cr) TI CI 764B: System Biology & Omics Analysis (2 cr)

Workshop 4 (January)

Optional Elective: CI 716: R Workshop (1 cr) Optional Elective: BCMP301QC: Translational Pharmacology (2 cr)

Spring Longitudinal Courses (January - May)

COR CI706D: Mentored Research Experience under the supervision of Harvard-based mentor (5 cr) COR CI714B: Scientific Communication (1 cr) CT CI726B: Advanced Topics in Clinical Trials B (2 cr) CR CI 732B: Comparative Effectiveness Research II (1.5 cr) TI CI 766: Translating Innovation into Practice (1 cr)

Year III Fall Longitudinal Courses (September to December)

COR CI706: Mentored Research Experience under the supervision of Harvard-based mentor (10 cr) COR CI709B: Clinical and Translational Investigation Thesis Preparation (2 cr)

Spring Longitudinal Courses (January - May)

COR CI706: Mentored Research Experience under the supervision of Harvard-based mentor (10 cr)

Required Core Courses in all tracks and pathways CI701: Clinical Data Science: Design and Analytics I

Course Directors: Pamela Rist, MD; Brian Claggett, PhD This course introduces methods for the generation and analysis of data for clinical research through seamless integration of epidemiology, biostatistics, and machine learning. The course is structured in three components that correspond to the three main objectives of clinical research: description, prediction, and causal inference. The descriptive component introduces different data types and study designs, summary measures (including frequency and occurrence measures), and statistical inference (hypothesis testing, confidence intervals). The predictive component introduces association measures, regression (linear, logistic) and other learning algorithms with applications to screening and clinical classification. The causal component introduces a causal inference (counterfactual) framework via randomized clinical trials, which covers survival analyses, sample size calculation, biases, and effect heterogeneity. The course emphasizes critical thinking and practical applications, including assignments based on articles published in medical journals and a case study at the end of each week. All methods are taught along with Stata software.

CI742: Fundamentals Skills for Academic Success

Course Directors: Martina McGrath, MBBS, Anjala Tess, MD, and Melissa Campos Zamora, MBBS This course is designed to give students an overview of some of the key skill set that will support their experience as graduate students. We will review how we learn as adults and why having a growth mindset is essential in graduate school and professional life. Students will analyze and discuss key challenges in professionalism (communication, respect, biases, academic honesty, etc.). Furthermore, we will focus on build and strengthen teamwork essential skills like perspective taking, contribution to group dynamics and best practices when working in groups. Building on organizational behavior and coaching principles, this course will also examine key aspects of leadership, and relationship building with a key focus on the mentor-mentee relationships.

CI700: Ethics and the Institutional Review Board

Course Directors: Susan Kornetsky, MPH and Pearl O’Rourke, MD This course reviews some common challenges in the conduct of patient-oriented research. Lectures examine the history and evolution of ethical codes and regulations; the role and responsibility of physicians as investigators; the preparation of research protocol applications and informed consent documents; and the challenges of conducting research involving children and adolescents.

CI704 (A&B) & CI714 (A&B): Scientific Communication in Clinical / Translational Investigation

Course Director: Martina McGrath, MBBCh, Youssef Farag MD, MPH, Ph.D. This course examines different aspects of working with, managing, and leading a team. Lectures will discuss the skills and techniques that are needed to manage a talented group of people effectively, pilot successful collaborations within and outside a group, navigate the complexities of the institution, and manage the inevitable conflicts that arise in a high-stakes environment.

CI708 (A&B): Clinical Data Science: Design and Analytics II

Course Directors: Finnian Mc Causland, MBBCh, MMSc This course extends the topics introduced in Design and Analytics I for each of the three goals of clinical research: description, prediction, and causal inference. The description sessions discuss data wrangling, data visualization, and unsupervised learning with a focus on clustering. The prediction sessions discuss building and evaluation of predictive models via regression and other learning algorithms. The causal inference sessions discuss advanced design of randomized clinical trials (factorial, non-inferiority, adaptive, crossover, cluster-randomized trials), and evidence synthesis using meta-analysis. The course emphasizes critical thinking and practical applications, including assignments

based on articles published in medical journals. All methods are taught along with Stata software to implement them.

CI706 (A, B, C, & D): Mentored Research Experience

Course Director: Ajay Singh MBBS, MBA, FRCP(UK) and Finnian Mc Causland, MBBCh, MMSc All students undertaking the MMSCI degree are required to complete a thesis, as a culmination of the mentored research experience. The purpose of this requirement is two-fold, to highlight the importance of publishing quality research in peer-reviewed academic journals; and to promote excellence in the practice of scientific communication. The thesis requirement must be completed in a Harvard-affiliated research group under the direct supervision of the thesis committee that consists of the student, the primary mentor, one external content advisor and an MMSCI Program Representative. Please see section below for further details on the mentored research experience.

CI 709 (A&B): Clinical and Translational Investigation Thesis Preparation Part 1 and 2

Course Directors: Finnian Mc Causland, MBBCh, MMSc; Ajay Singh, MBBS, MBA During the course of the MMSCI program students work with their mentors on two thematically linked research projects, which form the basis for two first-author publications or a body of work. The Clinical & Translational Investigation Thesis Preparation course provides guidance on topics critical to the preparation and presentation of the written and oral forms of the thesis defense. Topics include review of analytic strategies for qualitative and quantitative data; presenting skills for qualitative and quantitative data; writing an academic paper; writing an op-ed (opinion) piece for the popular press; tips for writing and grammar. Weekly writing advising allows students to receive continuous feedback on their thesis composition. In addition to academic advising from the program directors, thesis committee and other faculty, supplemental instruction in statistical programming is also available.

CI 724: Genetic Epidemiology

Course Directors: Benjamin Raby, MD, Michael Cho, MD and Su Chu Ph.D., M.S. This course provides clinical researchers with the skills to incorporate genetic studies as part of their research program. The course focuses primarily on the use of genetic association methods to identify disease-susceptibility variants in well-characterized patient populations. The course is structured as an intensive workshop with lectures about the principles of genetic study design; pertinent concepts in population genetics, including linkage disequilibrium and population stratification; the principles of genetic association and their application in genome-wide association studies (GWAS) and large-scale sequencing studies; integrative genomics; and Mendelian Randomization. Students will use prepared datasets and genetic software tools to analyze large-scale genetic data, they will also acquire hands-on skills in data quality control and cleaning; linkage disequilibrium mapping; case-control association analysis; principal component analysis; GWAS analysis; sequence alignment and rare variant association testing; and use of bioinformatic tools and public databases.

CI740: Leadership and Teamwork

Course Director: Ajay Singh MBBS, MBA, FRCP(UK)and Chris Fortier, PharmD., FASHP This course examines different aspects of working with, managing, and leading a team. Lectures discuss the skills and techniques that are needed to manage a talented group of people effectively, pilot successful collaborations within and outside a group, negotiation in the context of authorship of manuscripts, navigate the complexities of the institution, manage oneself, and how to make decisions and negotiate change.

Clinical Investigation Courses (Clinical trials & Comparative Research pathways) CI702 (A & B): Clinical Trials Part 1 & 2

Course Directors: Pamela Rist, MD; Brian Claggett, PhD; Aneesh Singhal, MD; Finnian Mc Causland, MBBCh, MMSc

This course focuses on how to conduct clinical trials effectively. The course content includes lectures on study design and implementation, including different designs, endpoints, study protocol, study population, recruitment, baseline assessment, randomization, stratification, and blinding. Other key issues that are covered include data analysis and sample size and power, treatment regimens and followup procedures, and monitoring and interim analysis plans. Lastly, other areas covered include data management and ethical issues, including protection of human subjects.

Clinical Trials Pathway Courses CI710: Clinical Trials Course: Special Topics in Implementation

Course Director: Ajay Singh, MBBS, MBA, Youssef Farag MD, MPH, Ph.D This course focuses on relevant special topics in the effective conduct of clinical trials. The course includes lectures on practical issues in clinical trials management, namely: statistical monitoring of trials, data safety monitoring boards (DSMBs), working with CROs, evaluation of quality in a clinical trial, clinical endpoints monitoring, and organization and functioning of a trials executive steering committee. This course will also include topics related with special topics in drug development such as: drugs discovery and pre-clinical stages of drug development, moving a compound through the drug development process, good manufacturing practices--a global perspective.

CI726 (A & B): Advanced Topics in Clinical Trials

Course Directors: Ajay Singh, MBBS, MBA, Steven Piantadosi, MD, PhD This course delves into greater detail on advanced study designs and statistical issues in clinical trials. The course objectives include the following: Describe how designed experiments with human subjects are used in therapeutic development; Summarize principles of clinical trial design including bias control, random error control, randomization, blocking, and masking; Describe quantitative properties of clinical trials including precision of estimation, power, sample size, and accrual dynamics; Compare and contrast specific types of designs of practical and historical interest including translational, dose-finding, safety and efficacy, and comparative trials; Discuss the importance of design and its relation to the analysis of clinical trials; Demonstrate knowledge of clinical trial methods by discussing specific design and/or analysis problems expertly.

Comparative Research Pathway Courses

CI722: Clinical Data Science: Comparative Effectiveness Research I

Course Directors: Lourdes Perez-Chada, MD, MMSc This course introduces causal inference methodology when randomized trials are not feasible. The course focuses on the use of epidemiologic studies, electronic health records, and other big data sources for comparative effectiveness and safety research. Key concepts of bias (confounding, selection bias, measurement bias) are described via causal diagrams. Methods for confounding adjustment (stratification, outcome regression, propensity scores, matching, standardization) are introduced along with an emphasis on formulating well-defined questions in clinical research. The course emphasizes critical thinking and practical applications, including assignments based on articles published in medical journals. All methods are taught along with Stata software to implement them.

CI732 (A & B): Clinical Data Science: Comparative Effectiveness Research II

Course Directors: Lourdes Perez-Chada, MD, MMSc This course extends the topics introduced in Comparative Effectiveness Research I. The course covers efficient epidemiologic designs (case-control, case-cohort, case-crossover), advanced methods for confounding adjustment (inverse probability weighting, parametric g-formula) for the comparison of sustained treatment strategies, and instrumental variable estimation. The course also covers techniques for the secondary analysis of randomized clinical trials in the presence of deviations from protocol. The 11