Download Innovations

Innovations
N e w s a n d H i g h l i g h t s f r o m T h e U n i v e r s i t y o f Ve r m o n t C a n c e r C e n t e r
inside
2
3
Risks and Benefits of
Supplemental Screening
for Women with Dense Breasts
Epigenetics and Cancer ■
Men’s Health and Cancer
Conference
5
UVM Cancer Center’s 17th
Annual Breast Cancer
Conference ■ Farina Receives
Federal Grant to Study Prostate
Cancer Biomarkers
6
Enhancing Survivorship:
Oncology Rehabilitation at the
UVM Cancer Center ■ UVM Cancer
Center Recognized as National Lung
Cancer Screening Center
7
Perelman Family Philanthropy
Creates Two Endowed Funds
at the UVM Cancer Center ■ A
Community Behind Us ■ Keegan
Bradley Charity Golf Classic
Benefits UVM Cancer Center and
UVM Children’s Hospital
8
Clinical Trials at the UVM
Cancer Center
Spring 2015
Ahern Receives Susan G. Komen Grant to Study
Chemical Exposure and Breast Cancer
Letter from the University of
Vermont Cancer Center Directors
4
■
Thomas Ahern, Ph.D., M.P.H.
C
hemical exposure and cancer
risk is the focus of ongoing
research at the UVM Cancer Center,
led by Thomas Ahern, Ph.D., M.P.H.,
assistant professor of epidemiology
at the UVM College of Medicine
and member of the UVM Cancer
Center. Ahern was selected by Susan
G. Komen for the Cure to carry out
a study on exposure to phthalates,
synthetic chemicals often found in
modern consumer products, and
subsequent risk of breast cancer. The
$450,000 grant represents significant
investment by the national foundation to fund the 3-year study already
underway at the University of Vermont Cancer Center.
Phthalates are used in an abundance of common products including toys, plastic goods, automobiles,
baby care products, lotions, and
medications. While nearly 85% of
continued on page 3
American Cancer Society Grant Awarded to
the UVM Cancer Center
P
rogress in cancer research over
the past two decades has been
remarkable. Five-year survival rates
for cancer types such as prostate and
breast have nearly doubled in the
last 50 years, and cancer is becoming
a survivable disease for many. However, more progress is needed, and
the work of early-career researchers
is critical in that effort. Junior investigators at the UVM Cancer Center
will have a new opportunity to be a
part of that progress, thanks to funding from a 2015 American Cancer
Society (ACS) Institutional Research
Grant (IRG).
At UVM, teams are looking at
cancer from all angles, working to
find novel ways to identify causes of specific cancers, determine
individual risk for certain cancers,
target therapy to cancer-type and
to individuals, as well as find ways
to support and enhance the quality
of life for the increasing numbers of
cancer survivors. “This competitive
grant recognizes the innovative,
team approach to cancer research
that is taking place here at the UVM
Cancer Center,” says UVM Cancer
Center Director Gary Stein, Ph.D.
Funding from the prestigious
award (only 10 percent of applications are funded) will be aimed at
advancing innovative laboratory and
behavioral science and translating
findings into clinical applications.
At the same time, the grant supports
rising stars in the field of cancer
research here in Vermont. ■
News & Highlights
The UVM Cancer Center:
Advancing Cancer
Research and Care
Risks and Benefits of Supplemental Screening
for Women with Dense Breasts
Since its founding in 1974, the University
of Vermont (UVM) Cancer Center has been
dedicated to advancing the prevention, detection,
treatment, and survivorship of cancer. The
physicians, scientists, caregivers and staff at the
UVM Cancer Center are committed to providing
state-of-the-art cancer diagnosis and treatment,
delivering compassionate cancer care and
support, providing education to patients and the
community, and advancing innovative research
from the laboratory to the patient. Through a
unique partnership between the University of
Vermont and the University of Vermont Medical
Center, the UVM Cancer Center has built a team
approach to science that brings patients the most
advanced cancer care—right here in Vermont.
The UVM Cancer Center
Leadership
Gary Stein, Ph.D., Co-Director
UVM Cancer Center
Claire Verschraegen, M.D., Co-Director
UVM Cancer Center
Innovations Contributors
Sarah Keblin, Communications Manager
UVM Cancer Center
Jennifer Nachbur, Public Relations Director
UVM College of Medicine
Ed Neuert, Creative Services Director
UVM College of Medicine
Sylvie Vidrine, Graphic Designer
UVM College of Medicine
J
Letter from the Directors
The University of Vermont Cancer Center is pleased to share with our
community, near and far, news of the important progress being made
here in cancer research, care, and education. Through this Innovations
newsletter, our goal is to bring our many stakeholders, including the
patients we serve, examples of how we, and they, are making a difference in advancing the prevention, detection, treatment and survivorship of cancer.
Our strength lies in the amazing individuals who work collaboratively at the UVM Cancer Center. Whether in the clinic or in a research
laboratory, they strive to provide compassionate, state-of-the-art care
to patients and to advance our understanding of this disease that
affects so many people. Through a team-based approach to care and
research we are improving outcomes for patients, and finding new
ways to treat cancer. Each day we learn something new, and through
strong partnerships between physicians, other caregivers, and our
scientists, those discoveries are being translated to patient care in many
ways. This means access to the most advanced cancer care and support
services for our patients and their families right here in Vermont.
We couldn’t do what we do here without the amazing faculty,
staff, patients and supporters we consider part of our community.
Here are just a few highlights of their contributions.
Sincerely,
The Courtyard at Given
4th Floor North
89 Beaumont Avenue
Burlington, VT 05405
Phone ❯ 802.656.4414
Fax ❯ 802.656.8788
www.vermontcancer.org
Gary Stein, Ph.D.
Claire Verschraegen, M.D.
Co-DirectorCo-Director
P.S. We have changed our name! As of November 12, 2014 the Vermont Cancer Center became the University of Vermont Cancer Center,
reflecting the strong partnership between the University of Vermont
Medical Center and the University of Vermont.
ust how common is dense breast
tissue in women, and how effective
are screening approaches for women
with dense breasts? These are questions being answered by UVM Cancer
Center member Brian Sprague, Ph.D.
In a recent study published in the Annals of Internal Medicine Sprague concludes that supplemental ultrasound
screening for women with dense
breasts would substantially increase
costs with little improvement in overall outcomes. The research provides
needed evidence on the benefits and
harms of breast cancer screening options for women with dense breasts,
and informs the discussion of national
legislation that would mandate the
disclosure of breast density information to women.
Mammographically-dense
breasts – those that show more
glandular and connective tissue
versus fat in a mammogram image
– are recognized as a risk factor for
developing breast cancer and can
also diminish an accurate reading of
a mammogram. Additional research
by Sprague and colleagues, published in the Journal of the National
Cancer Institute, found that there is
a high prevalence of women in the
U.S. with mammographically-dense
breast tissue, with more than 40
percent of women between the ages
of 40 and 74 affected.
Sprague and his collaborators
provide important information for
policy makers considering national
breast density notification laws.
“The fact that minimal health gains
are projected with a substantial
increase in biopsies and costs when
ultrasound is used in screening
underscores the need for further research into effective imaging strategies for women with dense breasts,”
says Sprague, who is a cancer epide-
Brian Sprague, Ph.D.
miologist and assistant professor of
surgery at the University of Vermont
and co-director of the Cancer Control and Population Health Sciences
research program at the University
of Vermont Cancer Center. “This
should include the evaluation of
new imaging technologies such
as digital breast tomosynthesis,
which holds promise for increasing
cancer detection while also reducing
false-positive results.” ■
Ahern Receives Susan G. Komen Grant
continued from page 1
Americans have detectable levels
of these compounds in their bodies,
individuals who ingest phthalates
through daily medications, or, who
have daily exposure through their
job/vocation, have dramatically
higher exposure.
The chemicals are thought
to disrupt hormonal signaling in
the body, and may be involved
in cancer development, as well as
pose other potential health risks.
Preliminary studies suggest a link
between phthalates and breast
cancer risk, but the Institute of
Medicine has stressed the need
for definitive evidence of this link.
Ahern’s project, an epidemiologic
study focused on chronic, high-lev-
el phthalate exposure through
medications in collaboration with
Aarhus University in Denmark,
will provide strong evidence for
whether such a link exists.
“Should we find an association
between phthalate exposure and
breast cancer risk, our study would
motivate a change in clinical practice
so that women are treated with
phthalate-free versions of the drugs
they require,” Ahern said. “It may
also motivate a change in pharmaceutical manufacturing so that
phthalates are replaced with safe
alternatives.”
The local Komen affiliate for
Vermont-New Hampshire is enthusiastic about the grant. “It’s an
important and very topical project
being conducted here in Vermont
which may have ramifications on
breast cancer thinking and possible prevention the world over,”
said Komen Vermont-New Hampshire Affiliate President, Becky
Burke. “It’s also a very tangible
example of what becomes of some
of the funds raised through Races
for the Cure and other events
nationwide.”
Ahern, who is a Vermont native, is thrilled to have his research
recognized through Komen, and to
be carrying out important research
here in Vermont that could have a
world-wide impact on breast cancer
prevention. ■
i n n o v a t i o n s
•
W INT E R
2 0 1 5
3
Research & Education
▼
Epigenetics and Cancer
T
he fundamental understanding
of the role that genes and genetic
material play in cancer development
is evolving, and researchers at the
UVM Cancer Center are at the forefront of investigating epigenetics—a
new area of cancer research focus,
which looks at those factors that influence gene expression rather than
the genetic code itself.
Marie Wood, M.D., professor of
medicine, hematologist/oncologist
at the UVM Medical Center and
director of the UVM Cancer Center’s
Familial Cancer Program, is leading
new epigenetic research focused on
early detection of breast and prostate
cancer. Wood’s recent publication,
Epigenetics Symposium junior investigator
speakers (left to right): Mulu Lubula,
Terri Messier, and M. Ahmad Chaudry, Ph.D.
looking at non-coding RNAs, was
featured on the cover of the Journal
of Cellular Biochemistry. Partnering
with Drs. Jane Lian, Janet Stein, Gary
Stein, Nicholas Farina, Chris Francklyn, Scott Perrapato, Mark Plante
and Steven Ades, all of the UVM
Cancer Center, her work looks at
noncoding RNAs as biomarkers for
risk assessment and early detection
of cancer as well as risk for recurrence of cancer. This work is the
next generation of early screening
capabilities, indicating that someday
soon a simple blood test may reveal
early biomarkers for cancer risk.
Kaleem Zaidi, Ph.D., assistant
professor of biochemistry and UVM
Cancer Center member is a cancer
cell biologist whose work focuses on understanding epigenetic
mechanisms that are compromised
in human leukemia. He is currently principal investigator for an
NCI-funded grant to study the role
Men’s Health and Cancer Conference
Friday, June 26, 2015
The University of Vermont College of Medicine
Burlington, VT
The University of Vermont Cancer Center is proud to present the inagural Men’s
Health and Cancer Conference.This half-day event will focus on increasing education
and awareness of men’s health issues and the cancers which most often affect men.
Our experts will present information about cancer detection, prevention, treatment,
and survivorship in order to empower participants to invest in their own health.
The event is FREE and open to the public. Registration opens in early April.
For more information, please go to www.vermontcancer.org or contact:
Charles Brooks, Events Coordinator
The University of Vermont Cancer Center
(802) 656-2176
[email protected]
4
universit y
of
vermont
cancer
center
Upcoming Events
For a full listing of UVM Cancer Center
events, including educational events,
research symposia, fundraising events
and more, please visit
VermontCancer.org
of microRNAs in human leukemia. Partnering with UVM Cancer
Center collaborators such as Karen
Glass, Ph.D., assistant professor
of pharmaceutical sciences at
the Albany College of Pharmacy
and Health Sciences and adjunct
assistant professor of biochemistry
at UVM, Zaidi’s current research
has far-reaching implications for
devising safe and specific therapeutic strategies for treatment of
human leukemia.
A $2.1 million grant from
Pfizer Pharmaceuticals to establish epigenetic signatures for risk
assessment of drug-related induction of cancer and tumor progression is driving a major initiative in
the Stein Lab. Led by UVM Cancer
Center members Jane Lian, Ph.D.,
Janet Stein, Ph.D. and Gary Stein,
Ph.D., the research is harnessing
state-of-the-art genomic analysis
capabilities at the Cancer Center’s
Advanced Genome Technologies Core to investigate cancer
treatment-related alterations in
epigenetic control. With these
highly sensitive analyses the Stein
Lab aims to develop epigenetic
signatures that will inform the
next generation of options to treat
tumors that do not respond well to
conventional approaches.
This body of epigenetic research at the UVM Cancer Center
is leading to new collaborations,
clinical trials, and key information
critical to advancing new therapeutics, public health approaches
to cancer prevention, and enhancing quality of life after cancer. ■
UVM Cancer Center’s 17th Annual Breast Cancer Conference
“C
hoices and Voices in Breast and Women’s Health” was the theme for the
University of Vermont Cancer Center’s 17th Annual Breast Cancer Conference.
This year’s conference, which took place on October 10, 2014, included more than
80 sessions and interactive experiences for cancer patients, survivors, caregivers,
physicians, researchers and members of the general public concerned about breast
health and breast cancer. The event, which drew just over 800 people, was presented
with support from the University of Vermont (UVM), UVM Medical Center, Susan
G. Komen for the Cure Vermont-New Hampshire Affiliate, BlueCross BlueShield of
Vermont, and Front Porch Forum.
Event co-chairs and UVM Cancer Center members Patricia O’Brien, M.D., UVM
associate professor of medicine, and Kathy McBeth, M.A., psychologist with the UVM
Cancer Center, shared that the program was aimed at “[providing] information to
people in a variety of formats so that everyone can seek knowledge and support that
will help them make healthy choices for
themselves, their loved ones, or their
patients.” O’Brien and McBeth hoped to
empower patients to have an active voice
in their health or cancer journey. They
believe an informed voice is a strong
voice, and that when you or someone
you care for is facing a cancer diagnosis,
getting the information isn’t always easy.
UVM Cancer Center members and
other providers from the UVM Medical
2014 Breast Cancer Conference co-chairs
Center, as well as guest presenters from Patti O’Brien, M.D. and Kathy McBeth, M.A.
around the region, shared information
and expertise across a spectrum of topics. Featured topics throughout the day included
“Sex after Cancer” to “Understanding How Diet and Weight Affects Prevention,
Survivorship and Caregiving,” to “Looking for Avoidable Causes of Breast Cancer: No
Trivial Pursuit,” presented by assistant professor of epidemiology andUVM Cancer
Center member Thomas Ahern, Ph.D., M.P.H., this year’s keynote speaker. Among
sessions addressing some of the choices patients face were: “Conversations and
Choices for the Caregiver,” presented by McBeth; “Choices in Prophylactic Mastectomy:
Figuring out what is right for YOU,” presented by a panel of physicians and researchers
from the UVM Cancer Center; “Integrative Therapies in Cancer Care: An Expert Panel
Discussion”; “Screening: When, How Often, and Why?,” moderated by Vermont’s former
Acting Commissioner of Health, Tracy Dolan, M.S., and “What to Expect When You Get
Called Back from Your Routine Screening Mammogram,” presented by UVM Medical
Center radiologist Elise Hotaling, M.D.
This unique event, the largest of its
kind in the Northeast, provides a venue
SAVE THE DATE!
for professionals in health care, patients
October 2, 2015
and the general public and community to
18th Annual Women’s Health &
come together to build awareness and
support around breast cancer. In 2015 the
conference hopes to expand its offerings to
include a broader persepctive on women’s
Learn more about the
health and cancer, but continue to address
Breast Cancer Conference at
education around breast cancer prevention,
VermontCancer.org
detection, treatment and survivorship. ■
BREAST CANCER
CONFERENCE
Nicholas Farina, Ph.D.
Farina Receives Federal
Grant to Study Prostate
Cancer Biomarkers
A
ccording to the National Cancer
Institute (NCI), prostate cancer
is the second most common cancer
and second leading cause of cancer-related death in the United States.
The NCI estimates more than 230,000
men will be diagnosed with prostate
cancer in 2014, and nearly 30,000 men
will die from the disease this year.
Nicholas Farina, Ph.D., a
post-doctoral associate in the University of Vermont Department of
Biochemistry and member of the
University of Vermont (UVM) Cancer
Center, is looking to impact these statistics with new research funded by a
United States Department of Defense
(DoD) Prostate Cancer Research Program (PCRP) grant. His research is
aimed at identifying novel biomarkers in the blood to more effectively
diagnose the most aggressive forms
of prostate cancer. The aim of the
study is to facilitate the development
of a simple blood test to ensure easier
and earlier detection of the disease
and improve prostate cancer diagnosis and outcomes for patients.
Farina was one of 22 investigators
out of an international field of 104
to be awarded a 2014 Post-Doctoral
Training Award by the Prostate Cancer Research Program at the Congressionally Directed Medical Research
Programs. The two-year, $115,000
award recognizes Farina as one of the
“next generation of prostate cancer investigators” as presented by the PCRP
in its program announcement. ■
i n n o v a t i o n s
•
W INT E R
2 0 1 5
5
Patient Care & Support
Supporting the Mission
Enhancing Survivorship: Oncology Rehabilitation at the UVM Cancer Center
Perelman Family Philanthropy Creates Two
Endowed Funds at the UVM Cancer Center
A
cancer diagnosis – not to mention
the treatments that follow – is
physically and emotionally draining,
and ideally, patients rely on a support
team to get them through the process.
Helping cancer survivors regain
strength and energy after treatment
requires a team effort, too. At the
UVM College of Medicine marathon team.
Kim Dittus, M.D., Ph.D. (right) with a patient.
UVM Cancer Center that team includes physicians, physical therapists,
nutritionists and others who provide a
comprehensive approach to hematology/oncology rehabilitation, much
like that provided for cardiac patients.
Together, this team works with patients to improve strength, endurance,
diet and mental health in an effort to
mitigate the impact cancer and cancer
treatment has on overall wellness.
“Cancer patients go through so
much and cancer therapy can be physically and emotionally challenging, yet
rehabilitation services to support this
population are not in place,” says Kim
Dittus, M.D., Ph.D., UVM assistant
professor of medicine and medical
director of Steps to Wellness, the
oncology rehabilitation program at the
UVM Cancer Center. Dittus adds that
while more research is needed to measure the impact of rehabilitation on
cancer survivorship, she, and others
in the field, believe it could positively
impact risk of cancer recurrence and
reduce risks for other health concerns
associated with cancer and cancer
treatment--such as increased risk for
cardiovascular disease.
In 2012, the program, which
was launched in 2011 with support
from the Victoria Buffum Fund at the
UVM Medical Center and a lead gift
from Eric Lande, gained a new set
of teammates and along with them,
a welcome stream of funding. Now,
for a third year, the UVM College of
Medicine Running and Marathon
Team will be raising funds for oncology rehabilitation services and research
at the UVM Cancer Center. This
student-led effort will be bolstered this
year as the UVM Medical Center joins
the College of Medicine student team
effort in raising funds and awareness.
To date, the running and marathon
team, whose members participate
annually in the Vermont City Marathon and Relay, has raised more than
$50,000 for the program. They aim to
add to that total again this year.
Oncology rehab patients are
encouraged to join the students in
raising funds, awareness--and, even
running. ■
UVM Cancer Center Recognized as National Lung Cancer Screening Center
L
ung cancer remains the leading cause
of cancer-related death in the United
States for both women and men. Unlike
breast or colorectal cancer, a screening
test for lung cancer has not been
available until recently. In 2011, a large
study called the National Lung Cancer
Screening Trial (NLST) was published.
This study demonstrated that a yearly
low-radiation CT scan of the chest in
people at increased risk for lung cancer
can significantly reduce the number of
people dying from the disease. As a
result, lung cancer screening has been
recommended by the US Preventive
Services Task Force (USPSTF) for people
in the following group:
6
universit y
of
■
Age 55-80 years
A
rthur J. Perelman, M.D.’52, of
Summit, N.J., sons Robert, Jon
and Carl and their children have added to their philanthropic legacy at the
UVM Cancer Center by establishing
the Arthur Jason Perelman, M.D.’52
Endowed Professorship. In establishing
this fund the family wishes to both
From left: Jon Perelman, Arthur J. Perelman, M.D.’52, recognize and support, in an ongoing
and Robert Perelman, M.D.
way, the invaluable work of cancer
research happening at the UVM Cancer Center. The Perelman family celebrated
the new gift with UVM Cancer Center leadership in February, and looks forward to the naming, in the coming year, of the first Perelman Professor.
In 2012 the family’s generous support created the Charlotte E. Perelman
Cancer Research Fund, also known as the “Charlotte Fund,” at the UVM Cancer Center in honor of their late wife, mother, and grandmother. The Perelman family’s investments in supporting cancer research here in Vermont have
been extraordinary and will have a lasting impact on patients in Vermont,
Northern New York and beyond.
“The Perelman Family has provided this Cancer Center, the community it
serves and the larger scientific community dedicated to cancer research with a
tremendous investment,” shared UVM Cancer Center Co-Director, Gary Stein,
Ph.D., at an event to honor the Perelman’s recent gift. “Their gift recognizes the
importance of cancer research and we are incredibly grateful.” ■
A Community Behind Us
L
ocal businesses throughout Vermont and New York have made it a part of
their mission to support the mission of the UVM Cancer Center. Below, we
recognize some of the many local businesses who have demonstrated a significant commitment to the UVM Cancer Center.
History of smoking at least 30 packyears (average of 1 pack per day for
30 years)
■ Actively smoking or quit within the
last 15 years
■ The American College of
Radiology (ACR) recently designated
the UVM Cancer Center a national
lung screening center. The screening
program is one of only a handful of
sites in the United States currently
accredited by the ACR to perform and
interpret the results of the lung cancer
screening test. Individuals who meet
the above criteria, can speak with a
vermont
cancer
center
health care provider about lung cancer
screening.
The most important risk factor for
developing lung cancer remains a history
of tobacco smoking. If you are smoking
and looking to quit, contact the Vermont
Quit Line at (802) QUIT-NOW or online at
802quits.org. ■
SD Ireland • Leunigs’ Bistro • Windows and Doors by Brownell
Farrell Distributing • The Vermont Agency • Green Mountain Landscaping
Newman’s Own • Hornet’s Nest Pub • Peebles Ticonderoga
To learn more about making a philanthropic contribution to benefit the
UVM Cancer Center, please contact Manon O’Connor, Sr. Director of Development,
at (802) 656-4471 or by email at Manon.O’[email protected].
Keegan Bradley Charity
Golf Classic Benefits
UVM Cancer Center and
UVM Children’s Hospital
Keegan Bradley (left) and Al Homans, M.D.
V
ermont native Keegan Bradley,
the 2011 PGA Tour Rookie of
the year and a star of the 2012
U.S. Ryder Cup team, returned
to the Woodstock Inn & Resort in
Woodstock, Vermont, on Aug. 25,
2015 with fellow PGA Tour winner
Brendan Steele to host the third
annual Keegan Bradley Charity
Golf Classic.
The event, benefitting
the Pediatric Cancer Research
Foundation in its support of the
University of Vermont Cancer
Center and University of Vermont
Children’s Hospital, raised more
than $60,000 in net proceeds for
pediatric cancer research.
“We’re proud to support
Vermont causes and children’s
cancer is an important one,” said
Bradley. “Our outing last year was
a great success and we hope to
have as much fun and raise even
more money for children’s cancer
research this year.” ■
i n n o v a t i o n s
•
W INT E R
2 0 1 5
7
The Courtyard at Given
4th Floor North
89 Beaumont Avenue
Burlington, VT 05405
Clinical Trials at the
UVM Cancer Center
The UVM Cancer Center provides patients with the opportunity to enroll in clinical trials across all types of cancer. Clinical trials are
controlled research studies that test new ways to treat cancer, enhance quality of life for cancer patients, and mitigate side-effects of
cancer treatment and more. Successful cancer treatments in use today are the result of clinical trials work.
HIGHLIGHT
Steve Ades, M.D., M.Sc.
A multi-site clinical trial at the UVM Cancer Center,
led by Steven Ades, M.D., M.Sc., UVM associate
professor of medicine, tested a supportive care
drug combination aimed at reducing vomiting and
nausea in patients undergoing cancer treatment.
Clinical site partners on the trial included Mayo
Clinic in Arizona, Wake Forest University in
North Carolina, Norris Cotton Cancer Center at
Dartmouth in New Hampshire, and UMass Medical
Center in Massachusetts. Patients here in Vermont
had local access to a promising new therapeutic,
and also had the chance to help physicianinvestigators advance treatment options and
improve quality of life for future cancer patients.
MYTH
Clinical studies are not safe, I’d be
gambling with my health if I signed up.
FACT
New treatments are tested on
human subjects only after there is
valid scientific evidence that the
treatments are likely to be effective
and safe. If you take part in a phase
III clinical trial, the drug or treatment
has already been tested on small
groups of patients for both safety and
effectiveness.