Title: Epi 202:Designing Clinical Research Session 1: Introduction to the Course and to Clinical Research
1Epi 202Designing Clinical ResearchSession 1
Introduction to the Course and to Clinical
Research
- Thomas B. Newman, MD,MPH
- Professor of Epidemiology Biostatistics and
Pediatrics, UCSF - August 4, 2009
2Outline
- About this course
- Chapters 1 2
- Examples
3About This Course
- Began 30 years ago
- Also known as the "Hulley Course"
- Steve was the leader for the text (DCR) and
designed the course, homework, and instructions
to section leaders - Michael Kohn co-director last 6 years
Steve Hulley
4Website
- Google Epi 202 or find from TICR home page
- Course roster, schedule, rooms, readings,
PowerPoint files (when available) - Links to videos of lectures (we hope)
5About the Reading -1
- DCR-3 includes exercises and answers at the end
of the book - We recommend jotting down answers before reading
ours - Can discuss in section but no need to turn in
- Let us know your suggestions for improving the
book!
6About the Reading -2
- Recommended reading this week (Saha et al.
Survival guide) on the Epi 202 website - Recommended for next week an Articulate
Presentation on Marketing of Medicines with
Research - Evidence-Based Diagnosis (EBD) text also
recommended
7Course Objectives
- 1. Learn about how to design and do clinical
research - 2. Produce a protocol for a study
- 3. Help others in the workshop
- 4. Provide feedback on the workshop
- 5. Have a multiplier effect
8Course Ingredients
- August 4- Lectures (910 1000)
- Sept 15 Selected issues from DCR 3 text
- Sections (1010 1200)
- Protocol components
- More issues from the text
- Helping and getting to know your
classmates - Sept 22 5-page protocols due
- Oct 6, 13 (815 930) Protocol review sessions
(not Masters or ATCR Students) - In pairs, new faculty
9Computer skills
- You need to know how to
- Word process, attach documents
- Use PubMed
- Use citation management software such as Endnote
or RefWorks - You can learn by
- Getting a mentor or friend to show you
- Taking a course in the UCSF Library (last EndNote
course 200 PM today!) - Learning on your own
10Epi 202 Credit or DCR 2009 Certificate
- For satisfactory performance including
- Showing up for class, doing homework and helping
your colleagues (60) - Let your section leader know if you will miss any
sessions - Your 5-page clinical research protocol (must be
turned in on time 40)
Electronic available upon request
11Faculty for sections
12Faculty for sections
13Course Coordinator
- Olivia De Leon
- Olivia_at_epi.ucsf.edu
- 514-8231 (tel)
- 514-8150 (fax)
- (Please let her know if your email address
changes by sending her an email from the new
address)
Olivia De Leon
14Anatomy of research What its made of
- Research question, significance
- Study design
- Study subjects and how they will be sampled
- Variables and how they will be measured
- Predictor
- Outcome
- Analysis plan, sample size calculation
15NIH Roadmap Initiative-translating discoveries
into health
Westfall JM et al, JAMA 2007
16Translational Research and Studies for Epi 202
- Not the best choice for this course
- Animals, molecules without humans
- Data syntheses, e.g. decision analysis,
cost-effectiveness analysis, meta-analysis - Qualitative research
- Ideal
- A new observational study or clinical trial
involving humans that you could do (or at least
start) this year
17What if I am doing a secondary data analysis?
You can
- Use it for your DCR project, rethinking decisions
that were already made and getting thoughts and
suggestions for colleagues - Design a new study you arent (currently)
planning to do
18Physiology of research How it works
- Using measurements in a sample to draw inferences
about phenomena in a population
19DCR Figure 1.3
20DCR Figure 1.4
21DCR Figure 1.5
22Newman research question 1
- Do I really have to do all of those laboratory
tests before I can start phototherapy in
jaundiced babies?
23Background to Question 1
- Most babies get a little jaundiced in the first
few days after birth - A complete "hyperbilirubinemia work-up" used to
be recommended for significant jaundice - Total and direct bilirubin
- Direct and indirect Coombs tests
- Complete Blood Count
- Blood smear for red cell morphology
- Reticulocyte count
- Urine reducing substance
24Background to Question 1, contd
- In TNs experience reference ranges were poorly
defined and results rarely if ever affected
management - As a pediatric resident TN did not like having to
get out of bed to draw blood for these tests
25Background International Comparison of Spending
on Health, 19802006
Average spending on healthper capita (US PPP)
Total expenditures on healthas percent of GDP
TN concerned about costs
Data OECD Health Data 2008 (June 2008). From
Commonwealth fund
26More refined research question 1
- (i.e., what we really want to know)
- Do the expected health benefits of the
recommended tests justify their costs? - Subjects Jaundiced newborns (candidates for
phototherapy) - Predictor variable obtaining the tests
- Outcome variable measurements of health and costs
27Laboratory Evaluation of Jaundice in Newborns
(LEJN) study questions
- (i.e., questions our study can answer)
- How often are each of these tests done in
newborns at UCSF and Stanford? - How often are they abnormal?
- When they are abnormal what diagnoses are made as
a result of the test? - In what proportion is treatment altered?
- Diagnostic yield study (Chapter 12)
28Compromises
- Just 2 S.F. Bay Area teaching hospitals
- Surrogate outcome
- Discharge diagnosis of a significant disease
- Diagnosed after an abnormal jaundice work-up
- Retrospective study
- Limited to those in whom MD ordered the tests,
rather than those with a certain level of
jaundice or meeting other inclusion criteria - No control over how tests were done
29Design and Implementation
30Is RQ FINER?
- Feasible
- Interesting
- Novel
- Ethical
- Relevant
31Is RQ FINERG?
- Feasible
- Interesting
- Novel
- Ethical
- Relevant
- Good for your career
32Good for your career
- Try to identify a research question that will
allow you to - Learn more about an area of potential long-term
interest - Acquire new skills you could use on other
projects - Work with people and/or organizations with whom
you want to develop a long term relationship - Build on the project for future work
33LEJN Direct Bilirubin Results -1
- Test ordered 15 times as often per infant at UCSF
as at Stanford - Results more than twice as high
1 2 3 4
5 6 7 8
mg/dL
AJDC 19911451305-1309
34LEJN Results Direct Bilirubin Results -2
AJDC 19911451305-09
Spontaneous resolution in all 4 infants
35LEJN Conclusions
- Because of their low yield and poor specificity,
direct bilirubin tests are seldom helpful in
evaluating jaundice in term newborns.
AJDC 19911451305-1309
36August 6 is Hiroshima Day
37Newman research question 2
- Do I really have to do all of those laboratory
tests and admit infants lt 3 months old with
fevers?
38Background to Question 2
- A complete sepsis work-up and IV antibiotics used
to be required for all infants lt 3 months old
with fevers at academic medical centers - Complete Blood Count and blood culture
- Urinalysis and urine culture
- Lumbar puncture and CSF culture
- Hospital admission for 2-3 days of IV antibiotics
- Many practicing pediatricians were skeptical of
this requirement - PROS (Pediatric Research in Office Settings) is
the American Academy of Pediatrics research
network
39Study questions for the PROS Febrile Infant Study
(FIS)
- How do practicing pediatricians in manage young
febrile infants? - What variables predict testing and positive
tests? - What is the outcome of infants not initially
tested? - TN piece urine tests
40PROS FIS Design considerations
- Subjects
- Infants lt 3 months old with T gt 38.0 seen by a
Pediatric Research in Office Settings (PROS)
practitioner - Issues
- Different from infants presenting to inner city
emergency rooms - PROS practitioners may not be representative
- Not all eligible infants enrolled
41PROS FIS Design considerations -2
- Cross-sectional study
- Prevalence predictors of urine testing at first
visit - Prevalence predictors of UTI among those tested
- Cohort study
- Begin with measurements made at baseline
- Follow the infants to see what happens to them,
especially those not initially treated
42PROS FIS Design considerations -3
- Predictor variables
- Whether or not urine tests done
- Other variables results of history, physical
examination, treatments - Outcomes
- Positive urine culture at initial visit (UTI)
- Recovery from the acute febrile illness
- Late diagnosis of UTI
43PROS FIS Selected Results
- Only 54 of infants had urine tested at the
initial visit - 10 of those tested at the initial visit had a
urinary tract infection (UTI) - Uncircumcised boys were gt10 times as likely to
have a UTI but no more likely to have urine
tested - Other risk factors for UTI also predicted
testing, e.g., - Height of fever
- Lack of viral symptoms
- Lack of sick family members
44What happened to those not tested?
- N 1400 who had no urine test first visit
- N 1324 followed-up through end of illness
- N 807 not initially treated with antibiotics
- 2 (0.025) were diagnosed with UTI the next day
- Both received antibiotics and did well
- N 805 illnesses resolved without diagnosis of UTI
45Why were there so few late diagnoses of UTI in
those not initially tested?
- Those not tested were at very low risk
- Most UTIs in infants resolve spontaneously
- Based on levels of risk factors in those not
tested, 61 UTIs were expected in that group - Since only 2 were observed, either most UTIs
resolve spontaneously or the PROS practitioners
were using some secret extremely effective method
for selecting infants for urine testing
46Next
47One sentence describing anatomy of your study
- Design
- Variables
- Predictor
- Outcome
- Subjects
48Examples
- This is a randomized double-blind trial to see
whether low doses of oral diphenydramine reduce
self-reported severity of motion sickness among
elderly passengers on a cruise ship. - This is a prospective cohort study to estimate
the effects of various medical treatments for
osteoarthritis on the risk of intensive care unit
admission for H1N1 influenza among members of the
Northern California Kaiser Permanente Medical
Care Program
49Do you have a FINERG research question?
Feasible Interesting Novel Ethical Relevant Good
for your career
50Questions and comments