Perspectives in Multidisciplinary Clinical & Translational Research
Date & Time: Winter Quarter 2013
Department: NUCATS
Location: Lake View Conference Room 11th Floor Rubloff; Thursdays 5:30pm-8:30pm except on 1/16: 6pm9pm and the final class is on 3/10, a Monday, same time/location
Course Director:
Matthew J Smith, PhD, Research Assistant Professor, Psychiatry and Behavioral Sciences,
Abbott Hall, 13 Floor, 710 N. Lake Shore Dr., Chicago, IL 60611
matthewsmith@northwestern.edu
Course Teaching Assistant:
Matthew P Schroeder, PhD Candidate NU Interdepartmental Neuroscience Program
mp.schroed@gmail.com
Office Hours: By Appointment
Course Description:
This multidisciplinary course will introduce MSCI students to scientific methods used for clinical translational
research as well as provide a framework for the other courses required from completing the MSCI degree. The
course will stress the importance of multidisciplinary approaches to solving clinical questions and will
incorporate multiple examples of research discoveries that were advanced through multidisciplinary
collaborations. The course will emphasize a variety of research study designs and approaches that involve
quantitative research methods to study clinically relevant research questions and problems. It will provide a
perspective to help prepare students for more advanced research courses.
The course will meet once per week for 3 hours; each session will be divided into 3 components. The first hour
will consist of a lecture focused on a specific research area or methodology related to translational research.
The lectures will be given by the course director and/or guest faculty members. The lecture will be followed by
a brief 5 minute break and then 50 minutes of small group work. Afterwards we will reconvene as a class and
discuss the small group work.
Readings will be devoted to lecture topics and small group work. Students will also be expected to read articles
posted on NU’s BlackboardTM (https://courses.northwestern.edu/webapps/login) that correspond to the syllabus.
Evaluation and Grading will be as follows.
1. Attendance and small group participation: 10%. Part of the overall vitality of the course will depend on
students’ active participation. The course director will strive to create a stimulating environment in which to
discuss issues raised in didactic sessions and to move written projects forward. Participation will be assessed
in an ongoing manner.
2. Short writing assignments: 30%. Readings are to be completed prior to a given lecture. Generally there are 2-3
required papers to read. Occasionally there are optional readings considered important as well. A brief write-up
(300-500 words) is due the following week Monday. Each write-up will attempt to discuss how the reading and
lecture content might relate or influence the student’s area of interest. Six reviews are required and can be chosen
from lectures 2-9. Each write-up will be scored on a 0-5 scale.
3. Longer written project: 60%. The final assignment requires an aims page (1-page) and a 6-page proposal. The
goal of the assignment is for the student to present a series of 3 studies that answer a translational research
question. A rough draft is due in week 5 and will be read and reviewed by peers. (single spaced, ½ inch margins,
11pt arial font)
The final project is due by the last day of class, when each student gives a brief 7-10 minute oral presentation on
their work.
Grade Points
100-93: A
92-88: A-
87-83: B
82-78: B-
77-70: C
69-60: D
<60: F
1
Course Goal and Learning Objectives:
The overall goal of this course is to present an overview of clinical investigation. Students will achieve the major
objectives listed below.
Develop the ability to:
a. Compare and contrast various study designs throughout the translational spectrum.
b. Identify the strengths and limitations of various study designs.
c. Articulate appropriate research questions and formulate hypotheses for different study
designs.
Develop knowledge of:
a. The overall spectrum of Translational Research from “Bench to Bedside to Curbside”
and clinical problems that can be addressed by research at each location on the
spectrum
b. A broad range of research designs and approaches that involve quantitative research
methods to study clinically-related research questions and problems.
c. Basic assumptions regarding various study designs.
d. Types of research problems that lend themselves to interventional study designs.
e. Gender, racial, ethnic and disciplinary differences in values and perspectives as
applicable to patient-oriented research.
Course Calendar and Reading List:
Course coordinators and guest faculty expert in a given topic will give the lectures. Each week’s session will
include a lecture presentation and small group interaction and discussion on research applications.
2
Week 1 (January 9th, 2014): Course Overview: The potential of clinical and translational research to
improve the human condition: (Matthew Smith)
Hour 1: Lecture
Hour 2: Lecture/Class Project Discussion
This introductory lecture will review the topics covered during the course as well as introduce the concept of
translational research, and the patient’s perspective on becoming a research subject. This seminar will also
review the basic definitions of measurement, reliability, and validity. We will discuss these various types of
research in the context of recent changes in NIH funding priorities, grant mechanisms and review criteria.
Required Reading:
Sokol, D.K. (2008). The essence of medicine: Writers may tell us their theories on what the essence of
medicine is, but it takes actual contact with patients to bring it home to us, BMJ, 336, 1163
Woolf SH. The meaning of translational research and why it matters. JAMA 2008:266(2); 211-213.
Crump, B. (2008). Should we use large scale healthcare interventions without clear evidence that benefits
outweigh costs and harms? British Medical Journal, 336, 1276-1277
Susan Lowell Butler; Principles and Practice of Clinical Research 2nd ed. (2007). Chapter 13: Clinical
Research: A patient Perspective, p. 143-153
For Group Activity:
Davis L, Brekke J. (In Press). Social support and functional outcome in severe mental illness: The
mediating role of proactive coping. Psychiatry Research
Recommended Reading:
Khanna C, Paoloni M. Translation of new cancer treatments from pet dogs to humans. Nature Rev Cancer.
2008;8:7-16.
Week 2 (January 16th, 2014): Experimental and quasi-experimental designs and their roles in clinical
research: (Matthew Smith)
Hour 1: Lecture
Hour 2: Small Group/Discussion
Experimental designs are often used to test specific hypotheses. Over the last 30 years Randomized Control
Trials (RCTs) have become the gold standard to test new medications, surgical treatments, behavioral therapies
and devises. Quasi-experimental designs are also used in clinical and community based research where random
assignment of groups is not feasible. The strengths and weaknesses of these various designs will be presented
using case examples.
Required Reading:
Chapter 5 ‘Basic Study Design’ from Fundamentals of Clinical Trials 4th Edition by Friedman LM, Furberg
CD, and DeMets DL. 2010
Chapter 10 ‘Recruitment of Study Participants’ from Fundamentals of Clinical Trials 4th Edition by Friedman
LM, Furberg CD, and DeMets DL. 2010
For Group Activity:
Karst M, et al., 2003. Analgesic Effect of the Synthetic Cannabinoid CT-3 on Chronic Neuropathic Pain. JAMA,
290, 1757-62.
Curtis et al ., 2007. A randomized controlled trial of sucrose and/or pacifier as analgesia for infants receiving
venipuncture in a pediatric emergency department. BMC Pediatrics, 7, 27.
Nolan et al., 2010. Behavioral neurocardiac training in hypertension a randomized, controlled trial.
Hypertension, 55: 1033-1039.
3
Week 3 (January 23rd, 2014): Efficacy (type 1) vs. Effectiveness (type 2) research (Mark Huffman)
Efficacy studies are often used to treat new therapies such as new medication or surgical procedures. Efficacy
studies are often conducted in specialty clinics, inpatient settings or research units in controlled research settings.
Effectiveness studies on the other hand are often conducted in large health care systems or in communities. Each
type has different strengths and weaknesses. We will use a number of landmark studies that illustrate the kinds of
research questions that can be addressed with these two types of research.
Hour 1: Lecture
Hour 2: Small Group/Discussion
Required Reading:
Hogarty et al, (1997). Taking Issue: Efficacy vs. Effectiveness. Psychiatric Services, 48, 1107.
Thom et al., (2013) Effects of a Fixed-Dose Combination Strategy on Adherence and Risk Factors in Patients
with or at High Risk of CVD: The UMPIRE Randomized Control Trial. JAMA, 310, 918-29.
TIPS Team., (2009). Effects of a polypill (Polycap) on risk factors in middle-aged individuals without
cardiovascular disease (TIPS): a phase II, double-blind, randomised trial. Lancet, 373, 1341-51.
Kaczorowski et al (2011). Improving cardiovascular health at population level: 39 community cluster
randomisedtrial of Cardiovascular Health Awareness Program (CHAP). British Medical Journal, 342, 442-50.
Jamerson et al (2008). Benazepril plus Amlodipine or Hydrochlorothiazide for Hypertension in High-Risk
Patients. New England Journal of Medicine, 359, 2417-28.
Week 4 (January 30th, 2014): Pharmacotherapy trials (Herb Meltzer):
This lecture will discuss how to set up and carry out phase 1, 2, and 3 pharmacotherapy studies. The session will
include a discussion on sampling, patient recruitment and medical ethics. We will discuss the relationship of PI’s,
physician recruitment partners, universities and industry in developing and testing new medications.
Hour 1: Lecture
Hour 2: Small Group/Discussion
Required Reading:
Kane et al (1988). Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with
chlorpromazine. Archives of General Psychiatry, 45, 789-96.
Meltzer et al (2001). Melperone in the treatment of neuroleptic-resistant schizophrenia. Psychiatry
Research, 105, 201-209.
Meltzer et al (2004). Placebo-controlled evaluation of four novel compounds for the treatment of
schizophrenia and schizoaffective disorder. American Journal of Psychiatry, 161, 975-84.
Recommended Reading:
Meltzer et al (2003). Clozapine Treatment for Suicidality in Schizophrenia International Suicide Prevention
Trial (InterSePT). Archives of General Psychiatry, 60, 82-91.
Meltzer et al (2010). Pimavanserin, a Serotonin2A Receptor Inverse Agonist, for the Treatment of Parkinson’s
Disease Psychosis. Neuropsychopharmacology, 35, 881-892.
Meltzer et al (2012). Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy
and safety of risperidone, 2 mg/day, but does not enhance efficacy of haloperidol, 2 mg/day: Comparison with
reference dose risperidone, 6 mg/day. Schizophrenia Research, 141, 144-52.
4
Week 5 (February 6th, 2014): Translational Use of Magnetic Resonance Imaging (Reilly)
Observational research includes a variety of research designs including case series, case control, cross sectional,
national surveys of various populations, prospective cohort studies. Observational studies are often used to
generate hypotheses and to detect relationships between health related variables. The strengths and weakness of
these designs will be discussed using case examples.
Hour 1: Lecture
Hour 2: Small Group/Discussion
Required Reading:
Vansburger MH, Epstein FH (2011). Emerging MRI Methods in Translational Cardiovascular Research. J
of Cardiovascular Translational Research, 4, 4: 477 - 492.
Touscher, JT & Schwarz AJ (2011). Imaging biomarkers in drug development: Case Studies. In BH
Litmann & R Krishna (Eds), Translational Medicine and Drug Discovery, (222- 264). Cambridge University
Press: New York (2011).
Whitten, L. A. (2012). Functional magnetic resonance imaging (fMRI): An invaluable tool in translational
neuroscience. RTI Press publication. No. OP-0010-1212. Research Triangle Park, NC: RTI Press.
Retrieved from http://www.rti.org/rtipress.
Week 6 (February 13th, 2014): Educational Interventions: A special type 2 (Michael Fleming)
Evaluation the effect of educational interventions is a special area of research. The NIH considers Educational
interventions as a type 2 translational research method. There are unique research methods, instruments and
sampling procedures that can be used to test the efficacy and effectiveness of educational interventions. RCT’s
as well as quasi-experimental designs are used to test educational programs.
Hour 1: Lecture
Hour 2: Discussion 2
Required Reading:
Fleming M, Balousek S, Grossberg P, Mundt M, Brown D, Wiegel J, Zakletskaia L, Saewyc E. Brief
physician advise for heavy drinking college students: A randomized controlled trial in college health
clinics. J Stud Alcohol Drugs 2010 January; 71(1):23–31.
Fleming M, Olsen D, Stathes H, Boteler L, Grossberg P, Pfeifer J, Schiro S, Banning J, Skochelak
S. Virtual reality skills training for health care professionals in alcohol screening and brief intervention. J
Am Board Fam Med. 2009; 22(4): 387–398.
Week 7 (February 20th, 2014): Introduction to Bioinformatics (Richard Neapolitan)
This seminar will give a brief introduction to Bioinformatics. The session will provide a broad overview of how
bioinformatics develops and improves on methods for storing, retrieving, organizing, and analyzing biological data.
Hour 1: Lecture
Hour 2: Discussion/Small Group
Required Reading:
Neapolitan R, Jiang X, Contemporary Artificial Intelligence. Boca Raton, FL: Taylor and Francis, 2012.
Chapter 1, Chapter 2.3, Chapters 9-10
Nease RF Jr, Owens DK. Use of influence diagrams to structure medical decisions. Med Decis Making; 1997;
7(3):263-75
5
Week 8 (February 27th, 2014): Health Disparities (Karen Abram)
This seminar will focus on conducting research with women and minorities. There are a number of unique
challenges to conducting research with these populations related to the frequency of different disease processes,
lack of trust of the research community, and measurement of disparity issues.
Hour 1: Lecture
Hour 2: Group Exercise
Required Reading:
Carter-Pokras, O.& Baquet, C (2002). What is a health disparity. Public Health Rep. Sep-Oct; 117(5), 426.
Nelson, A. (2002). Unequal treatment: confronting racial and ethnic disparities in health care. Journal of the
National Medical Association, 94(8), 666
Recommended Readings:
Shavers‐ Hornaday, V. L., Lynch, C. F., Burmeister, L. F., & Torner, J. C. (1997). Why are African Americans
under‐ represented in medical research studies? Impediments to participation. Ethnicity & health, 2(1-2), 3145.
McCarthy, Charles R. (1994). Historical background of clinical trials involving women and minorities. Academic
Medicine 69(9), 695.
Week 9 (March 6th, 2014 ): Community initiated interventions (Michael Fleming)
This session will discuss methods used to survey community health care priorities, develop collaborative
relationships with community leaders and to develop joint interventions of mutual benefit to communities and
scientists. Alex Adams has developed strong community relationships with American Indian groups in northern
Wisconsin and is conducted community initiated interventions on childhood obesity.
Hour 1: Lecture
Hour 2: Lecture/Discussion
Required Reading:
Solberg L, et al. 2013. The DIAMOND initiative: implementing collaborative care for depression in 75 primary
care clinics. Implementation Science, 8:135.
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0005160/
Week 10 (March 10th, 2014) (MONDAY): A brief presentation (~10 minutes) by each student on their final
paper.
6