MMSCI Plan of Instruction

I. Background and Overview of Program

The Harvard Medical School Master of Medical Sciences in Clinical Investigation (MMSCI) program provides training in the methods and conduct of clinical and translational investigation for future leaders in patient-oriented research. This two-year degree program combines innovative forms of pedagogy from leading Harvard faculty with an individual mentored research experience in a Harvard Medical Schoolaffiliated laboratory.

Mission Statement and Goals

MMSCI provides outstanding didactic and mentored-research training to early career clinical and translational investigators to prepare them for leadership roles in patient-oriented research.

The major goal of the program is to provide an innovative comprehensive curriculum that allows trainees to develop skills and direct experience in the performance of clinical and translational investigation while simultaneously, through didactic course work, providing them with a strong foundation in the tools and techniques required to be successful clinical and translational investigators.

Program Objectives

1. To provide a strong didactic curriculum that includes training in computational and statistical sciences, epidemiology and study design, biomedical ethics, genetic epidemiology, scientific communication, drug development and safety, statistical programming, leadership, and management in clinical research

2. To enable students to conduct clinical and translational research with an HMS faculty member mentor

3. To provide students with the core skills necessary to write successful grant applications that will help them initiate research careers as independent investigators

Upon completion of the program, graduates will be able to apply contemporary research tools to clinically relevant areas of investigation and be highly competitive for careers in patient -oriented research in academic medicine, industry, and regulatory affairs.

Program Outline / Courses

The program in Clinical Investigation and Translational Investigation is organized as follows:

1. Mentored Research Experience: The core feature of the MMSCI program is the mentored research experience in a Harvard-affiliated research group. During the two years of the program, each student is required to develop and execute research projects under the guidance of a primary mentor and a dedicated thesis committee

2. Intensive workshops: The central pillars of the MMSCI program consist of intensive workshops and didactic sessions that are complemented by journal clubs, office hours, computer laboratory classes, team-based projects, and presentations.

3. Longitudinal teaching: Between each workshop, further exploration of contemporary research topics will occur at weekly interactive sessions. Novel pedagogic approaches for this longitudinal series include the use of “flipped classroom” methods, where students review and dissect learning material in advance of facilitated discussions.

4. Scientific Communication: This course is designed to complement the didactic and longitudinal curricula through team-based database analysis: presenting the data in figures and tables in various formats (poster, short presentation, and a research presentation) as well as state-of-the-art talks.

5. Individualized Learning: Opportunities for customized learning include two tracks: one in translational investigation and the other in clinical investigation, with the clinical investigation track containing individual pathways in clinical trials and comparative research. Elective course opportunities at HMS and other Harvard schools are available with the permission of the Program Director.

II. Degree(s) Offered

The Master of Medical Sciences (MMSc) degree in Clinical Investigation is offered. This is a 64-credit two-year full-time or three-yearlow residency program that consists of academic training, mentored research training, team-based projects and career-development activities. Part-time options are not offered in this program (See Section 2.06 for definitions of full- and part-time.)

III. Prerequisites for Admission

Applicants must hold an MD, MBBS, or an equivalent doctoral degree and be pursuing research in clinical disciplines. Applicants in clinical training programs must have no more than 25% effort allocated to nonacademic activities during the two-year period. On a case-by-case basis, the program will consider candidates with a PhD degree for admission.

In addition to the requirements listed above, a language proficiency test is required for applicants for whom English was not the medium of instruction for their undergraduate or graduate degree. The master’s programs accept TOEFL iBT, TOEFL Essentials, IELTS Academic, or the Duolingo English Test. To be considered for admission, applicants must meet the following minimum test score requirements:

TOEFL iBT: 103

TOEFL Essentials: 11

IELTS Academic: 7.5

Duolingo English Test: 125

Instructions to submit official test scores:

TOEFL iBT and TOEFL Essentials:

Code 3151: Harvard Medical School Graduate Education Master’s Programs

IELTS Academic:

Contact the test center where you took the IELTS test to request that your scores be sent via E-Delivery to:

Account Name: Harvard Medical School Graduate Education Master's Programs

Address: Graduate Education Master's Programs

25 Shattuck Street

Boston, MA 02115

United States

Duolingo English Test: Search for “Harvard Medical School” and select the appropriate program.

IV. Academic Residence Requirements

The MMSCI requires that all didactic coursework and mentored research take place on Harvard’s campus (HMS or other Harvard Schools) or at an HMS-affiliated hospital.

V. Course of Study

A. Concentrations offered

The program is divided into two tracks that outline the student’s coursework over the program length The program contains a translational investigation (TI) track and a clinical investigation (CI) track. The CI track has two pathways, one in Clinical Trials and one in Comparative Research. The figures below outline the program curricular map including all concentrations offered in the traditional 2-year format.

a. Master of Medical Sciences in Clinical Investigation 2-year Program

The program has traditionally been offered in a 2-year format with a progressive scaffolding of coursework and mentored research experience. The image below outlines the 2-year program courses across all tracks and pathways.

b. Clinical Investigation Track Curriculum Map

This track is co-led by Finnian R. Mc Causland and Ajay K. Singh, who both have extensive experience in observational research and clinical trials. The clinical investigation track allows customized learning for students through the pursuit of either a comparative research pathway or a clinical trials pathway. Guided by a dedicated thesis committee, each student completes two first-author manuscripts based on the work from their individual research projects.

c. Translational Investigation Track Curriculum Map

The translational investigation track was created to fill an unmet need to provide training for individuals pursuing a career in basic and/or translational research (i.e. in the T0 to T2 spectrum of translational investigation). Incorporating the translational track within the MMSCI program is consistent with our overall goal to train future global leaders in clinical and translational research. Broadening of the MMSCI program to incorporate these additional students will ensure diversity of experience, skills, and ideas, while promoting collaboration across the spectrum of clinical and translational research.

B. Curriculum by term, 2-year program

The 2-year program begins in July of the first year, with the first intensive workshop, and ends in May of the second year, with the awarding of the degree following the final workshop. The list below shows all the courses in the program listed by term.

Master of Medical Sciences in Clinical Investigation 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

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)

COR CI700: Ethics and the IRB (1 cr)

Fall Longitudinal Courses (September to December)

COR CI706A: Mentored Research Experience - Harvard-based mentor (10 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 2January Term (January)

TI (optional for CI) CI 716: R Workshop (1 cr)Spring Longitudinal Courses (January to April)

COR CI706B: Mentored Research Experience - Harvard-based mentor (10 cr)

COR CI704B: Scientific Communication (1 cr)

COR CI708B: Clinical Data Science: Design and Analytics II (1.5 cr)

COR CI724: Genetic Epidemiology (2 cr)

CI CI702B: Clinical Trials Part 2 (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

Workshop 4 (September)

CT (optional for TI) CI 710: Special Topics in Drug Development and Evaluation (2 cr)

Fall Longitudinal Courses (September to December)

COR CI706C: Mentored Research Experience under the supervision of Harvard-based mentor (10 Cr)

COR CI714A: Scientific Communication (1 cr)

COR CI709B: Clinical and Translational Investigation Thesis Preparation (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 5 (January)

COR CI740: Leadership and Teamwork (2 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 (10 cr)

COR CI714B: Scientific Communication (1 cr)

CT CI726B: Advanced Topics in Clinical Trials B (2 cr)

CR CI 732B: Comparative Effectiveness Research II (1.5cr)

TI CI 766: Translating Innovation into Practice (1 cr)

C. Curriculum by term, 3-year program

A three-year option is being offered to eligible candidates who receive approval from the program leadership. The figures below illustrate the distribution of the same 64 credits and courses over a 3-year period for all the program offerings

Master of Medical Sciences in Clinical Investigation Courses in 3-year program

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

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)

COR CI700: Ethics and the IRB (1 cr)

Fall Longitudinal Courses (September to December)

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 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)

COR CI724: Genetic Epidemiology (2 cr)CI CI702B: Clinical Trials Part 2(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

Workshop 4

CT (optional for TI) CI 710: Special Topics in Drug Development and Evaluation (2 cr)

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 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 5 (January)

TI (optional for CI): 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)

VI. Description of all MMSCI Courses

Required Core Courses in all tracks and pathways

CI701: Clinical Data Science: Design and Analytics I

Course Directors: Elizabeth Mostofsky, Sc.D; Brian Claggett, PhD

Clinical research requires the generation and analysis of data for three tasks: description, prediction, and causal inference. This course introduces the methods to accomplish these tasks through seamless integration of materials usually taught separately in epidemiology and biostatistics courses. This course includes recorded and live lectures as well as interactive assignments to introduce students to core principles and concepts in epidemiology and biostatistics. The epidemiology component will introduce students to measures of frequency and association, epidemiologic study designs, and basic epidemiologic methods. The biostatistics component will introduce students to data types, data summaries, hypothesis testing, the essentials of statistical inference, and statistical methods for calculating summary estimates, measures of variability, confidence intervals, sample size calculations, and concepts for modeling. All methods are taught along with STATA software to implement them.

The course emphasizes critical thinking and practical applications, including online assignments and interactive case study discussions. This course is the first course in the sequence of core courses of the Master of Medical Sciences in Clinical Investigation. It is followed by the core course Clinical Data Science: Design and Analytics II.

CI742: Fundamental Skills for Academic Success

Course Director: Martina McGrath, MBBCh

This course is designed to share with students an overview of some of the key skill sets that will support their experience as graduate students. We will review how adults learn better and why having a growth mindset is essential for 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 strengthening leadership and 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, time management as a graduate student and relationship building with a key focus on mentor-mentee relationships. Finally, students will evaluate their strengths and weaknesses in regard to professionalism, teamwork, and leadership, and develop a strategy to enhance their academic and professional performance.

CI700: Ethics and the Institutional Review Board

Course Directors: Susan Kornetsky, MPH and Pearl O’Rourke, MD

This course will examine the regulatory and ethical oversight of the history and evolution of ethical research codes and regulations. The role and responsibility of principal investigators will be discussed. The course will include the history of research ethics and touch upon the ethics of animal research which often is the precursor to trials in human beings. Information about how to prepare research protocol applications and informed consent documents for clinical research will be provided. The course

will also review some current and common challenges in the ethical conduct of research including consideration of diversity and equity and inclusion, recruitment practices, vulnerable populations and topics such as AI and machine learning, genomics and use of social media in research. The importance of considering the perspectives of subjects and patients in clinical research will also be explored. The course will include didactic and group work that will emphasize critical thinking and practical application of ethical considerations while developing and implementing patient-oriented research.

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

Course Directors of 704 A&B: Martina McGrath, MBBCh, Youssef Farag MD, MPH, Ph.D.

Course Directors of 714 A&B: Rosalyn Adam, PhD and Amil Shah, MD, MPH

The ability to clearly articulate scientific ideas and communicate data is a core skill for any researcher. CI 704 is the first of a two-part course that is delivered longitudinally each year. Part I (year one; CI704 A&B) focuses on dissemination of scientific results, while Part II (in year two, CI 714 A&B) focuses on grant preparation.

Specifically, CI704 A&B focus on developing skills in formulating a research question, organizing and analyzing data, data visualization, and preparing and presenting data. Topics covered include presentation skills, developing a research talk, preparing a clinical and a translational research manuscript, and understanding the journal editorial process. In a longitudinal exercise in communicating science, students are given a teaching dataset (the SEEK India study) and work in teams to develop a research question, perform the analysis and present their study in both poster and oral presentation forms, with extensive faculty feedback.

The annual MMSCI Research Day is a core component of Scientific Communication Parts I and II, where Year 1 students are required to present a formal poster based on their ongoing thesis work, while Year 2 students are required to present an oral abstract of their thesis projects. All presentations will be reviewed and graded by a faculty panel.

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

Course Director: Finnian Mc Causland, MBBCh, MMSc

This course extends the topics introduced in Design and Analytics I and continues to integrate epidemiology and biostatistics with the goal of conducting well-designed, rigorous clinical research. All methods are taught along with STATA software to implement them. This course covers several major areas relevant for clinical investigation: 1) Modeling approaches, including multivariable regression; 2) Evidence synthesis using systematic reviews and meta-analyses, which lays the groundwork for identifying clinically significant research questions; 3) Evaluation of screening tests, and 4) Common biases in clinical research, presented through an epidemiologic as well as causal inference framework.

The course emphasizes critical thinking and practical applications. Students will complete a team project for this course: a publishable systematic review, meta-analysis paper, and a screening test proposal. This is the second course in the sequence of core courses of the Master of Medical Sciences in Clinical Investigation.

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

During the course of the MMSCI program learners 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 a successful mentored research experience, as well as focusing on the preparation and presentation of the written and oral forms of the thesis defense.

Year 1 topics include: Preparing for your thesis committee meetings; Preparing your thesis committee report; Individual Development Plan; Giving and receiving feedback; conflict in clinical research; Dealing with uncertainty; Time management.

Year 2 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. This class will occur on Wednesdays from 8 – 10am throughout the fall semester.

CI 724: Genetic Epidemiology

Course Directors: Michael Cho, MD and Su Chu, Ph.D., M.S.

This course provides clinical researchers with the skills to thoughtfully incorporate genetic studies into their research programs and clinical practice. The course focuses primarily on the use of genetic association methods to identify variants associated with disease risk in unrelated individuals and familybased studies. Students will learn foundational concepts in population genetics, e.g. linkage disequilibrium and population stratification; frameworks for the design of rigorous genetic epidemiologic studies; and how to interpret and ethically translate the findings from genome-wide association studies (GWAS) and large-scale sequencing studies. Students will also learn the fundamentals of using prepared datasets and genetic software tools to analyze large-scale genetic data in lab sessions, as well as how to use bioinformatic tools and public databases in research and clinical settings. At the end of the course, advanced principles of integrative omics study design will be briefly introduced.

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 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.

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 is the first of a four-course series on clinical trials. The purpose of this first course (CI702.1) is to provide an introduction to the tools needed to effectively design, conduct, analyze, and interpret clinical trials. The course content will include topics such as: why are clinical trials important; ethical issues in trials; design and implementation components of a trial including recruitment, randomization, blinding, endpoint ascertainment, adverse events, compliance, and follow-up; an introduction to preparing

a grant application; and interpreting and communicating trial results. Examples will be provided from the published literature and presentations by active investigators who are conducting trials. Course components will include live sessions, readings, and a group project.

The “nuts and bolts” of clinical trials is best learnt in the doing. In this course, the goal will be to understand the complexity of how trials get started, implemented, and ultimately completed. This 9-week course will cover the “nuts and bolts” of clinical trial design, implementation, and interpretation. Sessions will focus on both conventional and innovative trial designs, on the governance and implementation of clinical trials using examples, statistical aspects (statistical analytic plan, statistical monitoring, sample size and power), practical aspects such as recruitment and retention and data collection, and interpretation of data. Methods of instruction will include lectures, exercises, and seminars.

Clinical Trials Pathway Courses

CI710: Special Topics in Drug Development and Evaluation

Special Topics in Drug Development and Evaluation introduces students to key concepts relevant to development of novel therapeutic agents. Across two parts, this course will cover topics ranging from target discovery and early stage development, to first-in-human studies and milestones on the road to commercialization. This material will provide insights on the phases of drug development, and is complementary to course materials in both the translational investigation track and the clinical trials pathway of the clinical investigation track.

This 2 credit course, offered in the Fall semester of the second year of MMSCI, follows a workshop format, taking place over 3 weeks. Students are provided with pre-reading material for each session, and using a flipped classroom model, students are required to actively participate in group discussions in class. Each session will follow a lecture and/or discussion format, where faculty guide discussions based on pre-reading material and case studies provided.

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

Course Director: 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: Joy Shi, PhD, Geetha Iyer, PhD, and 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.

The course emphasizes critical thinking and practical applications and the discussion of two case studies. This is the first core course in the Comparative Effectiveness track of the Master of Medical Sciences in Clinical Investigation. It is followed by the 2-part course Clinical Data Science: Comparative Effectiveness Research II.

CI732

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

Course Directors: Joy Shi, PhD, Geetha Iyer, PhD, and Lourdes Perez-Chada, MD, MMSc

This is a two-part course that applies the core concepts introduced in CI722 to real-world comparative effectiveness research. Part A in the fall introduces the target trial framework for designing and analyzing comparative effectiveness and safety studies, with focus on different methods of confounding control, instrumental variable methods, time-varying treatment strategies and handling of missing data. Part B in the spring continues with emphasis on advanced study designs, use of electronic health records in realworld comparative effectiveness research, sensitivity analysis and causal mediation analysis. In addition to the new topics covered, students will continue to develop their critical thinking and scientific communication skills through the completion of course assessments that will aid in integrating the knowledge acquired throughout the two-part course. The fall course project will be two written critiques of selected journal articles and one article presentation. The spring course project will be the completion of a research proposal designed to address a hypothetical comparative effectiveness research question using a target trial framework. The course emphasizes critical thinking and practical applications, including assignments based on articles published in major clinical journals. Part A is the penultimate course in the sequence of 3 core courses of the Master of Medical Sciences in Clinical Investigation, while Part B is the

final course in the sequence

Description of Translational Investigation Track Courses

CI760: Investigative Models for Translational Research

Course Directors: Rosalyn Adam, PhD and Martina McGrath, MBBCh

This course provides translational researchers with an introduction to the range of investigative models within the translational research spectrum, with emphasis on the advantages and limitations of each system. Introductory sessions focus on developing well-designed research questions and selecting appropriate analytical methods to interpret results. Case studies will be used to illustrate the different approaches to experimental design. The course will also provide practical information on the range of bench techniques and in silico approaches used in current biomedical research.

CI764

(A & B): Systems Biology and Omics Analysis

Course Directors: Ashwini Jambhekar, PhD and TBD

The goals of this course are to introduce participants to fundamental concepts in systems biology and to provide a basis for experiments that generate large genomic, transcriptomic or proteome datasets. An introduction to DNA and RNA sequencing, as well as fundamental concepts in gene expression and regulation, is followed by exploration of experimental design for generation of large datasets and their integration using systems biology principles. Mass spectrometry-based proteomics and related technologies are discussed in the context of biomarker discovery and the course concludes with investigation of the microbiome and its relevance in health and disease. Throughout the course, consideration will be given to the specialized statistical analyses required when using high-dimensional data and how this influences experimental design for omics-based studies.

The goals of this course are to build upon concepts introduced in Part I and focus on application of methods to identify genes that are involved in human disease and how to develop diagnostics, drugs and therapies. The course features in depth discussion of the translation of genetic/genomic information into novel diagnostics and therapies, including DNA based, RNA based and protein-based analyses. The instruction will employ real-world examples of the development of therapeutics using precision medicine

approaches. These cases will illustrate specific teaching points relevant to the application genetic and genomic investigation to precision medicine.

CI762: Cell and Molecular Biology in Medicine

Course Directors: Jing Zhou, PhD

This course will provide translational investigators with a broad understanding of the fundamental processes that drive cell function in health and disease. An overview of the cell biology will be followed by introduction to specific cell functions that play key roles in disease processes, including viral entry, cellular uptake of lipoproteins, cilia function, inflammation, protein degradation, autophagy, and fibrosis. The course will focus on cutting edge techniques for cell biological investigation. Specific disease entities including ciliopathy, cancer, cardiovascular and neurodegenerative diseases are e xplored as examples of studies in cellular and molecular medicine.

The course will be complemented with a description of methods used to investigate biological processes. Learners will gain experience in interpreting data from cellular and molecular biology studies and apply it to answer research questions. Furthermore, students will develop skills to design a research approach to study a clinical question using cell and molecular biology techniques.

The course will comprise lectures, case-based learning sessions, journal clubs and other interactive activities to guide students through basic cell biological processes and behaviors, and then to apply that knowledge to pathophysiology of common diseases. Key concepts will be emphasized with examples from the literature.

CI766: Translating Innovation into Practice

Course Director: Martina McGrath, MBBCh

This course is designed to provide learners with an introduction to the process of translating research innovations into clinical practice. It will examine the design of first in human studies (including integration of translational medicine approaches, biomarker discovery and validation), the regulatory process to bring an innovation to the clinic, and academic/industry partnerships. Securing funding through industry networks, and how to approach commercializing a discovery will be discussed, illustrated through case examples from guest lecturers.

CI716: R Workshop Training Course (optional for all students)

Course Director: Rosalyn Adam, PhD, Jesse Raffa, PhD

This 1 credit course, comprising eight 90-minute sessions, during the J term of Year 1 of MMSCI program will introduce participants to using R and RStudio. R is a simple programming environment that enables the effective handling of data, while providing excellent graphical support. RStudio is a tool that provides a user-friendly environment for working with R.

This practical, hands-on course is intended to provide basic R programming knowledge. Participants will learn the basics of R for reproducible data wrangling and visualizations (ggplot2), how to perform data analyses requiring a basic knowledge of R and use R to produce data tables and graphics. This course will act as an introduction to R and will provide foundational teaching upon which subsequent courses, CI764 Systems Biology and Omics Analysis, will build.

BCMP301QC: Translational Pharmacology (Optional course for all students)

Course Director: David Golan, MD and Donald Coen, PhD

This is an intensive course held during January (ten days) covering basic principles of pharmacology and how they are translated into the development of new drugs. Students participate actively in project groups composed of both graduate students and post-graduate M.D.'s to propose a strategy for drug development from target choice through clinical trials. There are two hours of lectures each of the first eight mornings; in the afternoons, there are case studies discussed by guest faculty from the pharmaceutical and

biotechnology industries, a research paper discussion, or time to work on the group project. Evaluation is based on the project and class participation.

VII. Expectations for students by term or year

Students are expected to participate fully in the required components of the program, including the intensive workshops and any pre-workshop mini-courses, the flipped classroom series, the longitudinal seminar, and the mentored research project. Students will be formally evaluated in each course, through participation, online quizzes and homework assignments, team projects, and written work. Attendance is required for all course meetings.

While the MMSCI will be a complete, self-standing program of study that meets all of the credit requirements for matriculation of students, MMSCI enrolled students will be able to enroll in courses at other Harvard Schools, with the permission of those schools, and with the guidance and permission of the program director, their research mentor, and relevant course directors. With respect to elective crossregistered courses, students are notified that they are expected to abide by the policies that apply to the course/school in which the elective is taken (including attendance and integrity in science) and are informed that they must receive a satisfactory grade in any for-credit elective in order to graduate, since any unsatisfactory grade on a student’s transcript precludes the student from receipt of a diploma.

Students are expected to abide by the policies, including attendance (See Section 2.02) and academic integrity (See Section 4.09), of each school in which courses are taken.

VIII. Assessment

The grading system for courses is determined by the School in which the course is offered. For MMSCI program courses based at HMS, the SAT/UNSAT system is used. Satisfactory is defined as a numeric score of 80% or better. Students are evaluated throughout each program course through regular homework assignments, online quizzes, class participation and attendance, and team-based projects that are presented orally and in written form. Students receive a final grade, in the form of "satisfactory" or "unsatisfactory", for each module they take. Students taking courses in other programs or schools will be evaluated as determined by that program or school. A student must have the equivalent of a satisfactory grade for all courses to maintain satisfactory academic progress.

Longitudinal evaluation of each student is required throughout the course of the program, which includes course grades with narrative and/or oral feedback on a variety of exercises or projects and may also include a mid-term examination. The student’s mentored research project is evaluated at least three times during a student’s tenure, and these reviews are written and submitted to the director. Students are expected to achieve satisfactory grades in all courses and the mentored research project.

IX. Length of Time to Degree

MMSCI students are expected to complete the MMSc degree program in two-to-three academic years. Students may petition the program director in writing for an extension of time. (See Section 2.06 for definitions of full- and part-time and Section 2.07 for the policy on length of time to degree

X. Mentored Research

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.

The research is generally conducted at an HMS-affiliated hospital, where the student’s HMS faculty mentor maintains principal responsibility for the conduct of all aspects of the research. With occasional exception, it is desirable that all mentors are at the assistant professor or higher rank. Prospective mentors are reviewed and approved by the program to ensure an appropriate research and training environment. Based on the individual student’s needs and objectives, and with the approval of the MMSCI Program, part of the student's research may be conducted in collaboration with faculty from other entities within or outside Harvard University; however, the HMS faculty mentor remains fully responsible for oversight of the student’s research project.

The traditional thesis requirement for MMSCI degree has taken the form of two first-author manuscripts; one accepted and one submitted to a peer reviewed journal; or a body of work of equivalent magnitude. The subject matter of the manuscripts should be thematically linked, with the aim of helping the students to develop an area of expertise. However, with expanding enrollment, MMSCI now accepts students undertaking a wider variety of research studies. In particular, translational investigation spans a spectrum of research, from studies that are primarily bench-based and require generation of primary data, to those that use novel analyses of previously collected data to generate new findings. The time from study conception to completion may vary widely across these fields. Furthermore, students who employ advanced techniques to complete their research may take longer to produce a final paper. As a result, the body of work a student is ready to present at the end of a two-year Master’s program may vary depending on research type.

Given the broad range of hypothesis-driven research that is acceptable for a thesis for the MMSCI degree, the following factors will be considered when adjudicating if a body of work meets the requirements to award the degree:

A. The type of research being carried out (e.g. bench vs. epidemiological)

B. If primary data is being generated vs. analysis of previously collected data

C. The typical timeframe for completion of a research study within the specific field

D. The level of specialist training required to complete the studies (e.g., basic statistical analysis vs. advanced bioinformatics vs. complex disease models)

Depending upon the type of research being carried out, and a reasonable timeframe for completion, students can defend a thesis that may take the following forms:

1. Two first author publications (thematically linked), one accepted and one submitted

2. A body of work that will form the basis of two thematically linked, first author publications

3. A body of work based on a single substantial project that will form the basis of a first author publication, and where the student has demonstrated the acquisition of advanced skills and research expertise within their field of study (new thesis criterion).

Students are required to give a public presentation of their work (i.e., oral thesis defense). Approval of the thesis and oral thesis defense by the student’s thesis committee is a requirement for completing the program.

The thesis requirements must be completed under the direct supervision of a thesis committee, consisting of the primary mentor, one external content member (i.e. someone who is not in the student’s primary laboratory and who is not directly involved in the student’s research) and a MMSCI program representative.

The names and contact information for the thesis committee members must be approved by the program director prior to the commencement of the mentored research experience.

The thesis committee is required to meet four times throughout the two-year program, with the final meeting consisting of the public oral thesis defense. The student is responsible for coordinating each progress meeting and for submitting a progress report to the program director after the completion of each meeting. The presence of an additional external expert in the student’s area of research is required at the public oral thesis defense.

Upon completion of the oral thesis defense and approval of the thesis, the student is required to upload a pdf of the thesis on the Harvard University ProQuest database via the Electronic Thesis and Dissertation platform.

D. Requirements for graduation

Satisfactory completion of all required courses and any elective courses and successful completion of the thesis and oral thesis defense are required for graduation. A degree will not be granted to a student who is not in good standing or against whom a disciplinary charge is pending. In addition, a student’s term bill must be paid in full before the student will be awarded the degree.

In addition, to award the degree on the basis of thesis a student should complete the following:

I. A proposal to defend a thesis based on a substantial single project should be discussed at the 2nd thesis committee meeting (May of Year 1). The student will need to petition MMSCI leadership with a request to pursue this option. The student will need to schedule by no later than Sep 1 an additional ad hoc review committee meeting that comprises a member of the program leadership team, the mentor, program rep and content mentor and discusses the rationale of a single publication. The ad hoc review committee will make a recommendation to the broader program leadership on whether a single publication and/or body of work formatted as a publication is acceptable or if a second project will be needed.

II. During thesis defense, the thesis committee and external independent review expert will assess:

a. The factors listed above (A-D) to adjudicate if the body of work is sufficient to merit the degree

b. If the quality and quantity of work presented represents an acceptable standard for four semesters of full-time mentored research.

XI. Advising

The Program Directors, Curriculum Fellow, Faculty Mentors, and Program Manager are available to students for advising and guidance. The Program Directors serve as academic advisors for each student in the program. In this capacity, the Program Directors, Director of Mentoring provide the student with guidance in the program, solicit feedback from the student, and provide the student with research and career counseling. The following timeline outlines the opportunities for formal and informal advising of students from the program perspective.

Pre-admission:

Following a provisional acceptance, students work with the Program Directors, Director of Mentoring, and program representatives to find suitable mentors. This involves the student identifying an area of interest, potential HMS-affiliated research groups working in this area, and submission of a preference list to the MMSCI program. The program then makes first contact with potential mentors to determine their interest in having a student. During the admission process the student discusses and decides which track (TI or CI) is best suited to their long-term educational goals and objectives.

On arrival:

Program Directors, Director of Mentoring, program representatives and relevant faculty are available on an as needed basis to facilitate the student’s introduction to the HMS environment. We organize several social events during this critical period of settling in. Furthermore, we actively engage alumni of the program to meet with new students. The Director of Mentoring outlines expectations to new students and mentors for the overall program, with delivery of a formal mentoring packet to each mentor, which includes the requirement for regular thesis committee meetings and the final thesis guidelines.

Fall Semester:

For those in the CI track, the student meets the Program Directors, and Director of Mentoring to consider which pathway (Clinical Trials or Comparative Research) is best suited to their long-term educational goals and objectives.

Thesis committee meetings:

There are four thesis committee meetings throughout the program, with the final meeting consisting of the oral thesis defense. Following each meeting, the student submits a progress report that is reviewed by the Director of Mentoring and discussed with the MMSCI program representative Formal and informal progress meetings are held to help guide each student towards successful completion of the mentored research experience.

Formal Annual Reviews:

Each year the Director of Mentoring and Program Director’s meet with every student to review their progress, provide feedback from an academic perspective, and to obtain feedback from the students in relation to program activities.

Ad hoc meetings:

Examples may include a student who seeks permission to cross-register for another course, or to seek an excused absence from class. Program leadership members are also available to meet for any additional issues or advice on an as needed basis.

XII. Financial Aid

Program applicants are encouraged to apply for external grants and fellowships whenever possible. MMSCI has limited scholarship resources available through discretionary resources. Application for program scholarship support is made directly to the program director

Students who are enrolled at least half-time may be eligible for other federal or private aid. See Section 5.08 for additional financial aid information.