Table Of ContentCara East
Developing a
Successful Clinical
Research Program
123
Developing a Successful
Clinical Research Program
Cara East
Developing a Successful
Clinical Research
Program
Cara East
Baylor Soltero CV Research
Baylor University Medical Center
Dallas, TX
USA
ISBN 978-3-319-54692-6 ISBN 978-3-319-54693-3 (eBook)
https://doi.org/10.1007/978-3-319-54693-3
Library of Congress Control Number: 2018948824
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Preface
Today, clinical research is a multibillion-dollar business that
produces all of the medications, devices, and procedures of
tomorrow. This endeavor encompasses academic research
institutions, medical societies, hospitals, clinics, pharmaceuti-
cal manufacturers, device manufacturers, contract research
organizations, regulatory bodies, individual clinical research
sites, and research subjects. Clinical research determines the
safety and efficacy of medications, devices, diagnostic prod-
ucts, and procedures and decides if these treatments will be
approved or rejected for the treatment of humans.
This engine has evolved from studies performed on a small
number of indigent patients in public hospitals to sophisti-
cated clinical research protocols ascertaining the benefits and
risks of complex treatments across many locales. Not only has
the number of subjects involved in clinical research increased
dramatically, but so have the number of treatments beneficial
to humans throughout the world. And it continues to be
fueled by advances in the ideas and processes for generating
high-quality clinical research, which is the purview of this
book.
Clinical research has had to evolve. We now understand
that to be applicable to the entire population, clinical research
must be done in all ages, genders, races, and ethnicities.
Clinical research has had to expand beyond academic medi-
cal centers to community hospitals and clinics; from strictly
urban to rural areas; from all-white male subjects to an ethni-
cally, genetically, and geographically diverse population; and
finally from an indigent population to include all socioeco-
nomic classes.
vi Preface
Clinical research has also had to develop efficiencies in
getting from an idea, to bench testing, to animal testing, and
then through graded phases of human testing. What began as
physicians testing drugs in their own patients is now a pano-
ply of many business endeavors. Bench research has stream-
lined the testing of new drugs from a trial-and-error system
looking at an effect to a search through thousands of drugs
for the response of one receptor, one chemical process, or a
cell culture system. Preclinical research in animals studies
new treatments in a targeted fashion based on what has been
known about animal research through scientific research in
the past. This fast-tracks animal research and requires less
resources.
Clinical research has also evolved so that the first-in-
human studies are the safest they have ever been. There are
now clear standards for how to speed human testing through
its four phases of clinical investigation to approval. Much is
understood in the science of testing in human subjects so that
the most information is garnered from the minimum number
of human subjects. And while the bench and animal work can
show the way, how humans respond to a treatment can never
be known with certainty until the human clinical research has
been completed.
Along the way, clinical research has not always been con-
ducted in an ethical manner. There have been important les-
sons to learn from how human research should not have been
performed. The principles of clinical research were embed-
ded in the Nuremberg code in 1949, expounded upon by the
Belmont Report in 1979, and culminated in the Good Clinical
Research definitions by the World Health Organization in
1995. There were disasters along the way, including the lack of
drug testing of sulfanilamide in 1937 to prevent 100 deaths
from the incipient diethylene glycol in which it was sus-
pended. In the 1960s, thalidomide was never tested in preg-
nancy and would lead to over 5000 infants being born with
deformed limbs. The Nazi medical experiments and the with-
holding of antibiotic treatment for syphilis in the Tuskegee
experiments were horrific examples of sacrificing human
safety and rights for the sake of medical advancement.
Preface vii
In addition to benefitting humanity, the rewards of clinical
research also accrue to its practitioners. It strengthens the sci-
ence of medicine, even when putative treatments fail. It
increases the knowledge base and curiosity of its practioners
as it exposes them to cutting-edge ideas. Clinical research
subjects may gain access to care they could not otherwise
receive, and their participation engages them in the evolution
of medicine. Clinical research studies best practices and qual-
ity improvement in hospital systems. Finally, it dovetails with
the mission of healthcare to advance medicine and provide
care to all members of the population.
Developing a clinical research team requires time and
experience, and it is hoped that this book will provide exper-
tise to allow a new clinical research site to start more success-
fully. This book can also guide a small site to grow into a
multidimensional site with an experienced team, an efficient
division of labor, economic stability, and the ability to launch
its own innovative research. To do this requires an under-
standing of how to negotiate a budget, complete a contract,
and shepherd a study through an institutional review board.
The site must choose a team, train them, and then expand
them into higher levels of performance. The clinical research
site must develop standard operating procedures for many of
its practices. It must interact professionally with differing
sponsors and contract research organizations (CROs). The
clinical research team should become a good partner with the
community of scientists, industry, and subjects.
This book is designed to be a manual on how to start and
succeed in clinical research. There are lessons to be learned
from the past and confidence to be had for the future. The
goal of clinical research is to be worthy of the trust and
respect to guide the practice of medicine for decades to come.
With a complex system that functions optimally, medicine
will continue to generate the advancements needed for the
insightful and high-quality care of humans for which we toil.
Dallas, TX, USA Cara East
Abbreviations
ACRP Association of Clinical Research Professionals
ACRP-CP ACRP Certified Professional
AE Adverse Event
CAP College of American Pathologists
CCRA Certified Clinical Research Associate
CCRC Certified Clinical Research Coordinator
CCRP Certified Clinical Research Professional
CDA Confidentiality Disclosure Agreement
CLIA Clinical Laboratory Improvement Act
CMS Center for Medicare and Medicaid Services
CPI Certified Principal Investigator
CRA Clinical Research Associate
CRF Case Report Form
CRO Contract Research Organization
CTA Clinical Trial Agreement
CV Curriculum Vitae
DOA Delegation of Authority
DSMB Data Safety Monitoring Board
eCRF Electronic Case Report Form
EDC Electronic Data Capture
EMR Electronic Medical Record
FDA Food and Drug Administration
FPFV First Patient First Visit
GCP Good Clinical Practice
HIPAA Health Insurance Portability and Accountability
Act
IB Investigational Brochure
IC Informed Consent
ICH International Council for Harmonization
x Abbreviations
IDE Investigational Device Exemption
IND Investigational New Drug
IRB Institutional Review Board
IV Intravenous Line
LE Late Entry
MAGI Model Agreement & Guidelines International
NAI No Action Indicated
NDA New Drug Application
OAI Official Action Indicated
PCP Primary Care Physician
PD Protocol Deviation
PI Principal Investigator
RCT Randomized Clinical Trial
SAE Serious Adverse Event
SIV Site Initiation Visit
SMO Site Management Organization
SoCRA Society of Clinical Research Associates
SOP Standard Operating Procedure
SUSAR Suspected Unexpected Serious Adverse Event
TLC Tender Loving Care
VAI Voluntary Action Indicated
Contents
1 Why Do Clinical Research? . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 How Clinical Research Used to Be . . . . . . . . . . . 3
1.2 How Clinical Research Is Practiced Today . . . . . 4
1.3 Bench to Clinical: Mice, Humans, and Viagra . . 5
1.4 Benefits: Prevention, Treatment,
and New Therapies . . . . . . . . . . . . . . . . . . . . . . . . 7
1.5 Reasons to Participate in Clinical Research . . . . 7
1.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
2 How Clinical Research Should Never Have
Been Done: Ethical Measures for Protection
and Respect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2.1 The Nuremberg Code . . . . . . . . . . . . . . . . . . . . . . 12
2.2 Unethical Medical Experimentation
in the United States . . . . . . . . . . . . . . . . . . . . . . . . 13
2.3 The Belmont Report . . . . . . . . . . . . . . . . . . . . . . . 15
2.3.1 Respect for Persons . . . . . . . . . . . . . . . . . 16
2.3.2 Beneficence . . . . . . . . . . . . . . . . . . . . . . . 16
2.3.3 Justice . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
3 Choosing a Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.1 Area of Interest . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.2 Optimal Recruiting . . . . . . . . . . . . . . . . . . . . . . . . 20
3.3 Consider the Staff . . . . . . . . . . . . . . . . . . . . . . . . . 21
3.4 Consider the Institution . . . . . . . . . . . . . . . . . . . . 22
3.5 Consider the Mission . . . . . . . . . . . . . . . . . . . . . . . 23
3.6 Pay the Bills . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
