WORKING WITH CLINICIANS &
OTHER SCIENTISTS
Chap Le
MY CURRENT COLLABORATIONS:
(1) P01: Biology and Transplantation of the Human Stem Cell
Director: John Wagner; NCI: 7/1/10-6/30/15
This program project has three projects, all are in Minnesota; They focus
on three important issues in the UCB transplant setting: 1) graft versus host
disease (GVHD); 2) delayed immune reconstitution with resultant late
infection; and 3) refractory or relapsed leukemia. A renewal application has
just been submitted
(2) P01: NK Cells, Their Receptors and Unrelated Donor Transplant
Director: Jeff Miller; NCI: 9/1/10-7/31/15
This Program includes a group of international experts in NK cell biology
and bone marrow transplantation; it has three projects; one is here in
Minnesota, one at Stanford University, and the third one is a multi-center
randomized Clinical Trial with a PI here. A renewal application has just been
submitted
(3) P30: Cancer Center Support Grant (CCSG)
Director: Doug Yee; NCI: 2/1/14-1/31/19
The Masonic Cancer Center is part of a network of 60 funded Cancer
Centers. It is a comprehensive center with 8 research programs in Basic,
Population, and Clinical Sciences; Biostatistics and Bioinformatics is one of its
13 Shared Resources.
(4) P30: Minnesota Obesity Center
Director: Allen Levine; NIDDK: 9/30/1995 -3/31/2016
The Center has many investigators with many funded projects related to
obesity, energy metabolism and eating disorders and is one of 12 funded
Nutrition Obesity Research Centers.
(5) P50 (SPORE): UAB/UMN SPORE in Pancreatic Cancer
Directors: Donald Buchsbaum (Alabama); NCI: 8/15/2010-6/30/2015
This SPORE has four projects; two are in Birmingham, one here in
Minnesota, and one with Co-PIs in both campuses. Perhaps it will stay
dormant for a year or so; progresses are slow, a renewal application would be
submitted early next year.
(6) U54: Evaluating New Nicotine Standards for Cigarettes
Directors: Eric Donny (Pittsburgh); NIDA-FDA: 9/15/11-6/30/16
This specialized research center has four projects; one is a multi-center
clinical trial headquartered here in Minnesota, two at Pittsburgh and one at
Brown. There are 12 Data Collection Centers around the country.
(7) U19: Models for Tobacco Products Evaluation
Director: Dorothy Hatsukami; NCI: 9/20/12-9/19/17
The overall goal of this Program Project is to provide scientists and
regulatory agencies scientifically-based guidelines with methods and
measures for the evaluation of tobacco products. The program includes four
projects – all are here in Minnesota; a new component has just been added to
study e-cigarettes.
(8) R01: Metabolism of Carcinogenic Tobacco-Specific Nitrosamine
P.I. S. Hecht; NCI: 3/1/14-2/28/19
The goal of this study is to understand mechanisms of carcinogenesis by
the tobacco-specific carcinogens NNK and NNN and to test the hypothesis
that they are human carcinogens.
(9) U54: Transdisciplinary Collaborative Center for Research African
American Men’s Health. Director: S. Vickers (UAB); NIMHD: 7/1/13-6/30/1
The goal of CHAAMPS is to develop and implement community based
research and interventions through significant and broad partnerships with the
National Baptist Convention Foundation USA, Inc., National Football League,
and 100 Black Men of America, Inc.
(10) R01: Nornicotine in smokeless tobacco as a precursor for
carcinogen exposure P.I.: Stepanov); NCI: 5/1/14-4/30/19
Smokeless tobacco users may be exposed to the potent oral and
esophageal carcinogen NNN not only from tobacco itself, but also via its
endogenous synthesis from nornicotine.
(11) R01: Benzo{a}pyrene Metabolism: Phenotyping and Genotyping
P.I.: S. Hecht; NCI: 4/1/12-3/31/17
This project is aimed to integrate genotyping data with PAH metabolite
profiles and DNA adduct levels in humans. The goal is to develop a practical
method for assessing individual differences in human PAH metabolic
activation and detoxification.
(12) Foundation Grant: Phone Multimedia Messaging Intervention for
Breast Cancer Screening. P.I. H. Lee; Susan G. Komen: 11/1/12-10/31/15
calendar months .24 (2%)Susan G. Komen
Using the Fogg Behavioral Model, this study proposes to develop a mobile
phone-based intervention designed to motivate KA women to undergo an
annual mammogram
Science is built upon rigorous observation
and experimentation. A biostatistician’s
unique contribution to a research team is
founded on quantifying uncertainty in and
generating sound inferences from data. And
on top of that, designing studies.
Biostatistics contributions take one of the two
forms: Consultation and Collaboration.
Statistical consultation is often unplanned, less
organized, and aimed at smaller projects. Groups
that focus on consultation provide a valuable
service but fail to maximize the contributions
biostatisticians can make to research. In those
organizations, biostatistics is sometimes
regarded as an ancillary service rather than an
academic discipline; investigators or clinical
departments expect biostatisticians to fill a
perceived more of a service role.
In more modern Medical Centers, especially
Academic Medical Centers, Biostatistics supports
are organized in a way where the field has a
strong identity – as an academic discipline ,
which spurs intellectual growth, values
methodological contributions to health-related
research. And contributions are made through
collaborations where biostatisticians get involved
early and in a continuing manner in each and all
projects, from developing questions, designing
studies, refining measurements, to analyzing
data, and publishing results.
All of us in applied environment still provide
some statistical consultation – because not
all investigators are experienced; but even
those gradually becoming more like
“mentoring” instead of consulting. Those
who have been around for a while are often
involved in more meaningful, more
rewarding collaborations.
The following few slides provide a simple
picture of the makeup of a research project.
Finishing
Truth in
The Universe
Research Question
Truth in
The Study
Study Plan
Starting
Findings in
The Study
Study Data
The biggest thread or the most
important component in research is
the concept of “validity”. It involves
the assessment against accepted
standards; we have to be sure that
the evaluation covers its intended
target or targets.
INFERENCES & VALIDITIES
Two major levels of inferences are involved in
interpreting the results/findings of a study:
The first level concerns Internal validity; the
degree to which the investigator draws the
correct conclusions about what actually
happened in the study.
The second level concerns External Validity
(also referred to as generalizability or
inference); the degree to which these
conclusions could be appropriately applied to
people and events outside the study.
External Validity
Truth in
The Universe
Research Question
Internal Validity
Truth in
The Study
Study Plan
Findings in
The Study
Study Data
Biostatistics contributes to both internal validity (dealing with missing
data, refining measurements, analyzing data) and external validity (helping
to develop research question, designing study, estimating sample size)
THE ANATOMY & PHYSIOLOGY
OF CLINICAL RESEARCH
We form or evaluate a research or research
project from/on two different angles or
parts: the anatomy and the physiology of
research; just like the hardware and
software to run a computer operation.
THE ANATOMY PART
 From the anatomy of the research, one
can describe/see what it’s made of; this
includes the tangible elements of the
study plan: research question, design,
subjects, measurements, sample size
calculation, etc…
 The goal is to create these elements in
a form that will make the project
feasible, efficient, and cost-effective.
THE PHYSIOLOGY PART
 From the physiology of the research,
one can describe/see how it works; first
about what happened in the study
sample and then about how study
findings generalized to people outside
the study.
 The goal is to minimize the errors that
threaten conclusions based on these
inferences.
THE PROTOCOL
• The structure of a Research Project,
both its anatomy and physiology parts,
are described in its protocol; the written
part of the study.
• The Protocol have a vital scientific
function to help the investigator
organize his/her research in a logical,
focused, & efficient way.
COMPONENTS OF THE PROTOCOL
 Research Question: What is the objective of the study,
the uncertainty the investigator wants to resolve?
 Background and Significance: Why these questions
important?
 Design: How is the study structured?
 Subjects: Who are the subjects and how they will be
selected and recruited.
 Variables: What measurements will be made: predictors,
confounders, and outcomes.
 Statistical Considerations: How large is the study and
how will data be analyzed (“Design” is an important
statistical component but listed in the Design Section).
You can see “Statistical Fingerprints”
everywhere! Let look at , for example, the
area of “Drug Development”.
Drug development is the process of finding
and producing therapeutically useful
pharmaceuticals and turning them into
effective and safe medicines. It is a
complex process starting with screening
chemicals to identify a lead compound,
going through lots of works in toxicology,
pharmacodynamics, and pharmacokinetics,
and phases of clinical trials.
A successfully completed development and
testing program results in lots of information
about appropriate doses and dosing intervals,
and about likely effects and side effects of the
treatment. It is a process carried out by
“sponsors” (mostly pharmaceutical companies
but also including major medical centers, e.g.
“Center for Drug Design” at the University of
Minnesota) and is ultimately judged by
“regulators” (e.g. FDA of the United States).
Steps to New Drug Discovery
Get idea for drug target
Develop a bioassay
Screen chemical compounds in assay
Establish effective and toxic amounts
File for approval as an Investigational New Drug
(IND) (leads to clinical trials)
There is no aspect of drug development
and testing without participation and
contributions from biostatisticians.
Statisticians and biostatisticians are
also becoming more active in the
shaping of the pharmaceutical projects.
There are statisticians even on “the
other side of the table”; for many
years FDA has employed statisticians
and biostatisticians to assist in its
review process. At medical centers,
biostatisticians participate in protocol
designs, data analysis, as well as
protocol reviews.
Issue of the Day
Some people say that working with
other scientists, as a statistical
consultant is depressing because
“the docs boss you around”, is it true?