Download Clinical Research Process

Housekeeping
Understanding the
Clinical Research Process and
Principles of Clinical Research
August 2012
This project has been funded in whole or in part with Federal funds from the Division of AIDS (DAIDS), National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Department of Health and Human Services, under contract No. HHSN272201200009C, entitled NIAID HIV and
Other Infectious Diseases Clinical Research Support Services (CRSS).
Housekeeping
Instructions for:
•
•
•
•
•
Fire drills
Rest rooms
Messages
Breaks and Lunch
Smoking
Ask
questions
Remember to:
Share
what
you
know
Understanding the Clinical Research Process and Principles of Clinical Research
Participate
in all
activities
2
Housekeeping Agenda
Morning
• Introduction
• Objectives
• Community
Advisory Boards
(CABs)
Agenda
Break
Clinical
Research
Afternoon
Clinical Research
Process
Break
Understanding the Clinical Research Process and Principles of Clinical Research
Elements and
Principles of
Clinical Research
3
Audience Response System (ARS)
Choose
your
answer
Send or
change
your
answer
•
•
•
•
Respond to questions
Change an answer
Responses are anonymous
Question cue is a
on
preceding slide
• Ensure remote is on by pressing
and holding the “On/Off” button
Please leave remotes on the tables
Understanding the Clinical Research Process and Principles of Clinical Research
4
Audience Response System (ARS)
Choose
your
answer
Send or
change
your
answer
What is the ongoing process
by which a person voluntarily
confirms his/her willingness to
participate in a trial?
A. Clinical Trial Negotiation Process
B. Informed Consent Process
C. Voluntary Confirmation Process
Understanding the Clinical Research Process and Principles of Clinical Research
5
Audience Response System (ARS)
Type
your
answer
Send or
change
your
answer
Name one type of stakeholder
that can be represented on
a Community Advisory Board
(CAB).
Please type your answer on
the key pad
Understanding the Clinical Research Process and Principles of Clinical Research
6
Introduction
This workshop will help you to collaborate with
those who work to find:
• New Human Immunodeficiency Virus (HIV)/Acquired
Immunodeficiency Virus (AIDS) prevention technologies
• Improved AIDS treatment regimens
• A vaccine against HIV
• A cure for AIDS
In this workshop you will:
Apply the
information you
learn in activities
and discussions
Ask questions
about information
you do not
understand
Understanding the Clinical Research Process and Principles of Clinical Research
Practice what you
learn
7
Housekeeping
In this workshop you will:
Describe the role of a CAB in the research process
List key partnerships
Explain the importance of worldwide AIDS research and the issues affecting AIDS
research for various stakeholders
Define clinical research
Describe the clinical research process
Describe the elements and principles of clinical research
Define ethics in clinical trials
Understanding the Clinical Research Process and Principles of Clinical Research
8
Case Studies
Case Study
1
Case Study
2
Case Study
3
Case Study
4
Thembi and her
daughter Sarah
Alex
Niran
Lina
Your table number matches the case study to which you have
been assigned.
You will be reviewing various scenarios regarding your assigned
case study throughout the day.
Understanding the Clinical Research Process and Principles of Clinical Research
9
What Do You Know?
Answer eight questions about clinical research.
Understanding the Clinical Research Process and Principles of Clinical Research
10
What Do You Know?
The CAB acts as a point of contact between the
community and _________.
A. Researchers
B. National Institute of Allergy and Infectious Diseases (NIAID)
C. Clinical Trials Networks
D. Sponsors
Understanding the Clinical Research Process and Principles of Clinical Research
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What Do You Know?
Clinical trials are sponsored or funded by various
organizations or individuals including (select all that
apply):
A. Physicians
B. Foundations and voluntary groups
C. Medical institutions
D. Pharmaceutical companies
E. Government agencies
F. CAB
G. All of the above
Understanding the Clinical Research Process and Principles of Clinical Research
12
What Do You Know?
Why is HIV/AIDS a difficult disease to research?
A. There are various routes of transmission
B. There are known cures but people do not have access to them
C. Different treatment options lead to different outcomes
D. A and B only
E. A and C only
F. All of the above
Understanding the Clinical Research Process and Principles of Clinical Research
13
What Do You Know?
What is research?
A. A job for scientists to identify the causes for disease
B. Work in a laboratory to treat disease
C. A systematic investigation to establish fact
D. A study paid for by the United Nations
Understanding the Clinical Research Process and Principles of Clinical Research
14
What Do You Know?
Before someone can participate in a clinical trial,
they need to meet which type of criteria?
A. Inclusion
B. Exclusion
C. Bot A and B
C. Both A and B
Understanding the Clinical Research Process and Principles of Clinical Research
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What Do You Know?
What is included in a research protocol?
A. How treatments are administered to study participants
B. Important facts potential participants should know about the
clinical trial before deciding to participate
C. Instructions for assigning participants to study arms
D. Both A and B
Understanding the Clinical Research Process and Principles of Clinical Research
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What Do You Know?
Ethical principles guide clinical research activities,
including (select all that apply):
A. The conduct of research
B. The analysis of research data
C. The building of new research facilities
D. The design of research studies
E. The formation of research questions
Understanding the Clinical Research Process and Principles of Clinical Research
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What Do You Know?
Which of the following are risks of participating in
an HIV/AIDS Phase I clinical trial?
A. Social stigma for participating in a trial about a
sexually transmitted disease
B. The severity of the side effects that might occur
C. The potential for a participant to become HIV-positive
during the trial
D. All of the above
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The Role of a CAB
In this section, we will describe and discuss the role of
a CAB in the research process, including:
Understanding
the functions of
NIAID Clinical
Trials Network
How
researchers and
CABs interact
Definition of
“community”
History of
CABs
CAB and the
research process
Involvement
in community
Understanding the Clinical Research Process and Principles of Clinical Research
CAB
members
19
What Is the Role of a CAB in the Research Process?
National
Community
Participant’s
Family and
Close Friends
Larger
Community
Global
Community
Understanding the Clinical Research Process and Principles of Clinical Research
Surrounding
Community
20
What Is a Community?
A community
shares common:
Geography
Racial or ethnic
makeup
Values, culture,
beliefs and
interests
People can belong to many communities at the same time.
Communities and the demographics of a target population
are always changing.
Understanding the Clinical Research Process and Principles of Clinical Research
21
Group Brainstorm and Discussion
• Who is in YOUR community?
• Why is it important to have different
kinds of people in a community?
Understanding the Clinical Research Process and Principles of Clinical Research
22
Purpose of CABs
Provide
oversight and
guidance for the
protection of
participants in
clinical trials
Help define
research
questions
Communicate
the interests
and needs of
the community
to the research
team
Represent the
community
infected with
and affected
by HIV
Understanding the Clinical Research Process and Principles of Clinical Research
23
What Is the History of CABs?
AIDS activists in the U.S. and Europe:
• Demanded that researchers and regulatory
authorities move more quickly to find medications
to fight HIV
• Looked for opportunities to review trial proposals
• Protested by letter-writing, and lobbying the U.S.
Government they succeeded
Understanding the Clinical Research Process and Principles of Clinical Research
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What Is the History of CABs? (cont’d)
This process resulted in the creation of
CABs made up of non-scientists.
These non-scientists
review protocols, monitor
trials, and help educate
and inform the rest of the
community.
Understanding the Clinical Research Process and Principles of Clinical Research
25
Who Participates on a CAB?
Volunteers with a broad range of backgrounds
Religious groups
Schools or universities
Media
Non-governmental
organizations /
community-based
organizations
Understanding the Clinical Research Process and Principles of Clinical Research
26
Who Participates on a CAB? (cont’d)
• Members often have an interest in
HIV prevention and treatment
• Ideally 50% of the CAB’s members
are from the target population of a
site’s trials
• Some CAB members are paid, but
usually they are not
• Over time, members can better
understand the discussions and
contribute to the conversations about
the clinical trial
Understanding the Clinical Research Process and Principles of Clinical Research
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What Do You Know?
Does this individual exhibit the
characteristics of a CAB member?
A 24-year-old female teacher
at a community school
A. YES
B. NO
Understanding the Clinical Research Process and Principles of Clinical Research
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What Do You Know?
Does this individual exhibit the characteristics
of a CAB member?
A 30-year-old female who is known to be
disruptive and disrespectful of others’ opinions
A. YES
B. NO
Understanding the Clinical Research Process and Principles of Clinical Research
29
How Are CABs Involved in the Community?
Play an important
role in exchanging
information
between research
teams and the
community
Research
Team
Now a significant
piece in both
prevention and
therapeutic trials
Active in both
developed and
developing
countries
CAB
Understanding the Clinical Research Process and Principles of Clinical Research
CAB members take
on active roles in
planning and
implementation
Community
30
How Do Researchers and CABs Interact?
Researchers
•Protocol development
•Protocol
implementation
•Site preparedness
•Community
preparedness
•Trial operations
•Site monitoring/data
analysis
•Human subject
safety/liability
Ethical Research
Information During
Trial
Issues Management
Understanding the Clinical Research Process and Principles of Clinical Research
CAB
•Participatory
communications
•Community
education
•Advice on
recruitment and
retention
•Representative voice
for participants
31
Group Brainstorm and Discussion
• How do you think a person’s community
affects his/her health options and
accessibility to research opportunities?
• Discuss issues of confidentiality.
• In what ways will community and CAB
support help Sarah be more likely to
successfully complete the research she is
part of?
Understanding the Clinical Research Process and Principles of Clinical Research
32
Key Partnerships
In this section we will describe and discuss:
• The Clinical Trials Network
• The Community Partners Organization
Understanding the Clinical Research Process and Principles of Clinical Research
33
The Clinical Trials Networks
Understanding the Clinical Research Process and Principles of Clinical Research
34
What Are Community Partners?
IMPAACT
HVTN
INSIGHT
Community
Partners
Community Partners
organized through
organized
throughthethe
HIV/AIDS Network
HIV/AIDS
Network
Coordination Office
Coordination Office
HPTN
MTN
ACTG
Understanding the Clinical Research Process and Principles of Clinical Research
35
What are Cross-Network Activities?
• Community Input
• Data Management
• Evaluation Measures
• Training Development
of Staff
• Scientific Leadership
and Collaboration
• Laboratory Processing
• Site Management
Understanding the Clinical Research Process and Principles of Clinical Research
36
Who Supports and Partners with
Clinical Trial Networks
Organizations that
provide support
include:
• Division of AIDS
(DAIDS)
• HIV/AIDS Network
Coordination (HANC)
• Statistical and
operation centers
• Central laboratories
• Contract Research
Organization (CRO)
Partners within
the NIH include:
• Nation Institute of Child Health
and Human Development
• National Institute of Mental
Health
• National Cancer Institute
• National Institute on Drug Abuse
• National Institute of Dental and
Craniofacial Research
• Office of AIDS Research
Understanding the Clinical Research Process and Principles of Clinical Research
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Who are Other Partners?
The Bill and
Melinda Gates
Foundation
The International
AIDS Vaccine
Initiative
The Center of
HIV/AIDS Vaccine
Immunology
The William J
Clinton Foundation
The Global Fund to
Fight AIDS,
Tuberculosis, and
Malaria
The Joint United
Nations
Programme on
HIV/AIDS
Understanding the Clinical Research Process and Principles of Clinical Research
38
The Importance of Worldwide AIDS Research
• A person who is infected with HIV develops
antibodies to fight the infection. Someone with
the antibodies in their blood is “HIV-positive.”
• HIV disease becomes AIDS when a person’s
immune system is highly compromised by the
effects of the virus.
Understanding the Clinical Research Process and Principles of Clinical Research
39
What Is the History of AIDS?
There were cases of AIDS in the 1950s.
AIDS cases grew during the late 1970s
and 1980s
AIDS is now a global epidemic.
AIDS has become one of the greatest
threats to human health and
development.
Understanding the Clinical Research Process and Principles of Clinical Research
40
What Are the DAIDS’ Top Scientific Priorities
for HIV/AIDS Research Worldwide?
DAIDS (Division of AIDS) has identified six
important areas of research to:
Unravel the fundamental
processes governing
host/virus interactions
Prevent HIV infection
Treat HIV disease
Identify and test ways to:
Understanding the Clinical Research Process and Principles of Clinical Research
Cure HIV infection
41
How Serious is AIDS?
At the end of 2007,
approximately 33 million people
were living
with HIV.
Approximately 2.7
million people
become infected
with HIV every year.
Without treatment, half of
HIV-infected infants will die
before the age of two.
Approximately 400,000
children under age 13
become newly infected with
HIV each year.
Approximately 2
million people die
of AIDS every year.
Understanding the Clinical Research Process and Principles of Clinical Research
HIV is spreading most
rapidly in Eastern
Europe and Central
Asia.
42
Why Is Worldwide HIV Research Important?
• HIV is transmitted by different routes, in different
people, at different intervals, with different
treatment options that lead to different outcomes
• No single organization has the resources to
complete the needed HIV/AIDS research
Understanding the Clinical Research Process and Principles of Clinical Research
43
What Are the
Millennium Development Goals (MDGs)?
The United Nations identified an action agenda for this
millennium — eight millennium development goals.
One of the MDGs focuses on HIV/AIDS.
It calls on the world community to halt and begin to
reverse the spread of HIV by 2015.
Understanding the Clinical Research Process and Principles of Clinical Research
44
Housekeeping
Clinical Research
August 2012
This project has been funded in whole or in part with Federal funds from the Division of AIDS (DAIDS), National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Department of Health and Human Services, under contract No. HHSN272201200009C, entitled NIAID HIV and
Other Infectious Diseases Clinical Research Support Services (CRSS).
Clinical Research
In this section, we will
describe and discuss:
Understanding the Clinical Research Process and Principles of Clinical Research
46
What Is Clinical Research?
Medical and
behavioral
research
involving
volunteer
participants
Investigations
that are
carefully
developed and
conducted
with clinical
outcomes
recorded
Identification
of better
ways to
prevent,
diagnose,
treat, and
understand
human
disease
Understanding the Clinical Research Process and Principles of Clinical Research
Trials that
test new
treatments,
clinical
management,
clinical
outcomes,
and long–
term studies
Strict
scientific
guidelines
47
What Is a Clinical Trial?
Sometimes called a clinical study
Follows testing in laboratories and animal studies
Tests how well an intervention works in a group of people
Tests for new methods of screening, prevention, diagnosis, or
therapy
Provides information about an intervention, its risks, and its
effectiveness and/or efficacy
Conducted in phases
Understanding the Clinical Research Process and Principles of Clinical Research
48
What Is a Clinical Trial? (cont’d)
Trials can only be conducted
if there is an uncertainty
about the outcome.
Trials cannot be conducted if
the outcome is already
known from a previous
study.
Understanding the Clinical Research Process and Principles of Clinical Research
49
Why Is Research Important?
Clinical research is
important because:
Clinical trials test how well new approaches
and interventions work in people.
People who take
part in clinical trials
contribute to the
knowledge of how a
disease progresses.
Approaches can be medical, behavioral, or
managerial.
Each study answers scientific questions.
Each study helps scientists prevent, screen
for, diagnose, manage, and treat a disease.
Understanding the Clinical Research Process and Principles of Clinical Research
50
Group Brainstorm and Discussion
Clinical research approaches can be medical,
behavioral, or management.
• What is an example of a medical approach?
• What is an example of a behavioral approach?
• What is an example of a management
approach?
Understanding the Clinical Research Process and Principles of Clinical Research
51
Where Do Clinical Trials Take Place?
• Health care providers’ offices
• Medical centers
• Community and university hospitals and clinics
• Veterans’ and military hospitals
Clinical trials may include participants
at one or two highly specialized
centers, or they may involve hundreds
of locations at the same time.
Understanding the Clinical Research Process and Principles of Clinical Research
52
Why Include Volunteers in a Clinical Trial?
To prove, by scientific
means, the effects and
limitations of the
experimental treatment on a
wide variety of people
Research procedures with
volunteers are designed to
develop new knowledge, not
to provide direct benefit to
study participants
Understanding the Clinical Research Process and Principles of Clinical Research
53
Who Can Participate in a Clinical Trial?
Some research studies
seek participants with
illnesses or conditions to
be studied in the clinical
trial.
• Some research studies
need volunteers who do
not have the disease being
studied.
Understanding the Clinical Research Process and Principles of Clinical Research
Before joining a clinical
trial, a person must
qualify for the study.
54
Clinical Research Case Study
Case Study
1
Case Study
2
Case Study
3
Case Study
4
Thembi and
her daughter
Sarah
Alex
Niran
Lina
With your group:
• Review the case study you are given
• Read the two questions
• Review the benefits and risks of taking part in a clinical trial page in
your Participant Guide
• Brainstorm some possible benefits for the person in the case study
• Brainstorm some possible risks for the person in the case study
• Share your group’s ideas with the class (be sure to describe the
person in your case study)
Understanding the Clinical Research Process and Principles of Clinical Research
55
Group Brainstorm and Discussion
• What are some benefits of your case study
character taking part in a clinical trial in your
country?
• What are some possible risks associated with
your case study character taking part in a
clinical trial in your country?
Understanding the Clinical Research Process and Principles of Clinical Research
56
What Are Some Benefits of Taking
Part in a Clinical Trial?
Participants have access to
promising new approaches
often not available outside
the clinical trial setting
The drug, vaccine, or other
intervention being studied
may be more effective
and/or efficacious than the
standard approach
Participants may be the first
to benefit from the study
Participants receive careful
medical attention from a
research team of doctors
and other health
professionals
Results from the study may
help others in the future
Understanding the Clinical Research Process and Principles of Clinical Research
57
What Are Some Possible Risks of
Taking Part in a Clinical Trial?
• Intervention is not always better than
standard care
• New treatments may have unexpected side
effects or be more risky than standard care
• Health insurance and managed care providers
may not cover all participant care costs
• Participants may be required to make more
visits to the doctor than they otherwise
would
• Participants in randomized trials are not able
to choose the kind of intervention they will
receive
Understanding the Clinical Research Process and Principles of Clinical Research
58
What Do You Know?
Which of the following are benefits that Sarah may
experience through participation in a study (select all
that apply)?
A. The research center will provide medical attention and share important
medical information with Sarah’s doctor
B. The study may help gain approval of a new, more effective intervention
C. There may be unexpected side effects or risks
D. Access to new interventions that may better control Sarah’s condition with
fewer medications or pills
Understanding the Clinical Research Process and Principles of Clinical Research
59
Housekeeping
Clinical Research
Process
August 2012
This project has been funded in whole or in part with Federal funds from the Division of AIDS (DAIDS), National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Department of Health and Human Services, under contract No. HHSN272201200009C, entitled NIAID HIV and
Other Infectious Diseases Clinical Research Support Services (CRSS).
What Is the Clinical Research Process?
Pre-clinical
testing
Investigational
New Drug
Application
(IND)
Phase I (assess
safety)
Licensing
(approval to
use)
Phase III (largescale testing)
Phase II (test for
safety and
effectiveness)
Approval
(available for
prescription)
Post-marketing studies
(special studies and
long-term
effectiveness/use)
Understanding the Clinical Research Process and Principles of Clinical Research
61
What Is Pre-Clinical Testing?
Required before testing in humans and involves
laboratory and/or animal studies
Often conducted on
animals
Determines if there is a
potential benefit of the
drug, vaccine, or other
product
Many studies use a review committee to
determine if the use of animals is
warranted.
The review committee also checks to see
if the research can be improved by
reducing or replacing animals.
Explores general safety
concerns
Understanding the Clinical Research Process and Principles of Clinical Research
Takes approximately 3-4
years
62
What Is an IND?
• IND Application:
― Describes the results of pre-clinical testing
― Clearly defines how future studies will be conducted
• FDA has 30 days to review the IND.
• If FDA approves it within 30 days, the vaccine, microbicide, or
other strategy can proceed to a phase I trial.
Understanding the Clinical Research Process and Principles of Clinical Research
63
What Is Phase I ? (Assess Drug Safety)
First time that the vaccine,
microbicide, or other strategy is
introduced to humans
Goals are:
Study is designed to
determine:
Assess safety for humans
How the human body reacts
to the drug
Select the dose to be used
in future studies
What side effects occur as
drug dosage levels are
increased
Understanding the Clinical Research Process and Principles of Clinical Research
64
What Is Phase I ? (Assess Drug Safety) (cont’d)
Testing occurs in a small number of
HIV-negative volunteers (20 to 100)
Phase I
About 70% of experimental
drugs pass this initial phase
Understanding the Clinical Research Process and Principles of Clinical Research
Usually lasts several
months to one year
65
What Is Phase II? (Test for Safety and Effectiveness)
Provides comparative information about relative safety, effectiveness and/or
efficacy
Most Phase II
studies are
randomized trials:
• One group receives the
experimental vaccine, microbicide,
or other strategy
• A second "control" group receives
the standard of care or placebo
Understanding the Clinical Research Process and Principles of Clinical Research
Some Phase II
studies are
“blinded:”
• Participants and researchers
do not know who receives
the experimental vaccine,
microbicide, or other
strategy
66
What Is Phase II? (Test for Safety and Effectiveness) (cont’d)
Testing involves
100 – 300
participants
Usually lasts
several months
to two years
About 30% of
experimental
drugs pass this
initial phase
Understanding the Clinical Research Process and Principles of Clinical Research
67
What Is Phase III? (Large-Scale Testing)
Involves 1,000-3,000 participants/volunteers
Provides a better understanding of:
Effectiveness and/or
efficacy
Benefits
Range of possible
adverse reactions
The comparison to
standard of care
treatment
• Most are randomized and blinded trials with specific entry criteria
• Typically last several years
• 70-90% of vaccines, microbicides, and other strategies successfully complete
testing
Understanding the Clinical Research Process and Principles of Clinical Research
68
Group Brainstorm and Discussion
• During Phase I of a clinical trial, why do
you think only HIV-negative volunteers
can participate in the trial?
• What are the potential risks of taking part
in a Phase I clinical trial?
• What are the potential risks of taking part
in a Phase II trial?
Understanding the Clinical Research Process and Principles of Clinical Research
69
What Is Licensing (Approval to Use)?
Application for approval to use/license
• After all three clinical trial phases are complete
• If research demonstrates that the vaccine,
microbicide, or other strategy is safe and
effective
• Called a New Drug Application (NDA) / Biologics License Application (BLA)
• NDA/BLA must contain all scientific information compiled over the course
of the trials
• FDA has six months to review the NDA/BLA
— Review process can sometimes take up to two years, depending on specific
country requirements
Understanding the Clinical Research Process and Principles of Clinical Research
70
What Is Approval (Available for Prescription)?
Health care providers
are able to prescribe
Even after approval, reviews continue to
ensure safety over time:
• All cases of adverse events must be
reported, and quality control standards
must be met
• Sometimes studies to evaluate longterm effects are also required
Understanding the Clinical Research Process and Principles of Clinical Research
71
What Is Approval (Available for Prescription)? (cont’d)
Accelerated Approval
• Approval process for serious diseases (like AIDS)
• Help speed development of treatments
• Speed review for serious diseases (like AIDS)
Fill an unmet medical
need to get important
new treatments to
patients faster
If a treatment will have
impact on survival and
day-to-day functioning
Likelihood that a disease,
if left untreated, will
progress from a less
severe condition to a
more serious one
Does not compromise the
standards for safety and
effectiveness
Understanding the Clinical Research Process and Principles of Clinical Research
72
What Are Post-Marketing Studies?
• Also called Phase IV studies
• Often performed in special populations not previously studied
(such as children or the elderly)
• Are designed to monitor:
— Long-term effectiveness and/or efficacy
— The impact on a person’s quality of life
• Some help determine the cost-effectiveness of a therapy
compared to other traditional and new therapies
Understanding the Clinical Research Process and Principles of Clinical Research
73
Group Brainstorm and Discussion
• An NDA/BLA is filed with the FDA. The FDA is
an organization in the United States. Why do
you think FDA approval is important for
licensing in other countries?
• Kaletra was reviewed and approved in 3.5
months (a very quick approval) in September
2000. How much do you know about the
impact of early approval of Kaletra?
Understanding the Clinical Research Process and Principles of Clinical Research
74
Clinical Research Case Study
Case Study
1
Case Study
2
Case Study
3
Case Study
4
Thembi and
her daughter
Sarah
Alex
Niran
Lina
With your group:
• Review the additional information about your case study
• Review your Participant Guide and the Glossary to find definitions
to the words assigned to you
• Select one of the assigned words
• Practice explaining the word to the person in your case study
• Demonstrate to the class how you would explain the word to the
person in your case study (be sure to include any new information
about the person)
Understanding the Clinical Research Process and Principles of Clinical Research
75
Housekeeping
Elements and Principles of
Clinical Research
August 2012
This project has been funded in whole or in part with Federal funds from the Division of AIDS (DAIDS), National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Department of Health and Human Services, under contract No. HHSN272201200009C, entitled NIAID HIV and
Other Infectious Diseases Clinical Research Support Services (CRSS).
What Are the Elements and Principles
of Clinical Research?
Protocol
Protocol
review
Sponsors
Eligibility
criteria
Informed
consent
Types of
clinical trials
Placebo,
randomization,
blinding
Good Clinical
Practice (GCP)
Ethics in
clinical trials
Understanding the Clinical Research Process and Principles of Clinical Research
77
What Is a Protocol?
• Clinical research is conducted
according to an action plan (a
protocol), led by the principal
investigator
• The same protocol is used by
every doctor, clinic, or research
center taking part in the trial
• It is designed to safeguard
The protocol is like a
participants’ health and answer
“recipe” for conducting the
specific research questions
trial.
Understanding the Clinical Research Process and Principles of Clinical Research
78
What Is a Protocol? (cont’d)
A protocol
describes:
Who is eligible to participate in the trial
What will be done in the study, including details
about tests, medications, and dosages
Why each part of the study is necessary
The length of the study and what information will be gathered
Understanding the Clinical Research Process and Principles of Clinical Research
79
What Is a Protocol Review?
Clinical trial protocol and amendments
As part of the initial and
periodic review, the
Institutional Review
Board (IRB)/Ethics
Committee (EC) receives
a copy of the
Investigator’s Brochure
and reviews the
following:
Written informed consent form and
revisions
All written information intended to be
provided to participants
Participant recruitment procedures
Available safety information
Information about participant payments
and compensation
Investigator’s brochure
Investigator’s qualifications
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IRB / EC Review
Clinical trials are
ethical
During protocol reviews,
networks review and assess
what other networks are doing
to see what information applies
to what they are doing
Rights, safety, and wellbeing of all participants
are protected
IRB ensures
that:
IRB is an independent
committee and includes
physicians, statisticians, and
members of the community
Understanding the Clinical Research Process and Principles of Clinical Research
Risks are minimal and are
worth any potential
benefits
81
What Do You Know?
Which of the following can be found in a protocol (select
all that apply)?
A. Amount of money participants will receive
B. Background and history of the disease and existing treatment
C. Tests to be conducted at study visits
D. Package insert
E. Recruitment advertisement
F. Study visit schedule
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What Is a Sponsor?
Clinical trials are
sponsored or funded by
various organizations or
individuals, including:
Physicians
Foundations
Medical institutions
Voluntary groups
Pharmaceutical companies
Federal agencies (NIH, CDC,
others)
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Eligibility Criteria
Specifies who can
and cannot
participate
May require that
participants have certain
risk factors for HIV
infection
Often requires
particular type and
stage of disease
Understanding the Clinical Research Process and Principles of Clinical Research
Differ from study
to study
May include age, gender,
medical history, current
health status and laboratory
tests
84
Eligibility Criteria (cont’d)
Help ensure that results of trial will be a result of what
is under study, not other factors
• Researchers achieve accurate and meaningful results
• Minimize risk of a person's condition becoming worse
Inclusion
criteria:
Factors that allow
someone to
participate in a
clinical trial
Exclusion
criteria:
Understanding the Clinical Research Process and Principles of Clinical Research
Factors that
exclude or do not
allow participation
in a clinical trial
85
What Do You Know?
Which of the following are inclusion criteria for the trial in
the scenario? (select all that apply)
A. Adult male between the ages of 18 and 45
B. HIV-positive, confirmed by rapid test results or previous documentation
C. Adult female between the ages of 18 and 45
D. Not currently on HIV medication and no evidence of a history of HIV treatment at
any time
E. HIV-negative, confirmed by any method
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Group Brainstorm and Discussion
•
•
•
How do you think a protocol is able to be used
by doctors and research centers taking part in
the same trial but in different countries?
In your country, where are some places that
clinical trials take place?
What are some eligibility criteria for some of
the clinical trials you are familiar with?
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87
What Is Informed Consent?
• Provides potential participants
with important facts about a
clinical trial before they decide
to participate
• Helps people make a decision
that is right for them
• Is not a contract—it is a
process
• Must be written in the
participants’ native language
and at an appropriate
educational level
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What Is Informed Consent? (cont’d)
An informed consent document
includes:
Purpose of the study
Study duration
Required procedures
Who to contact for more information
An explanation of risks and potential benefits
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Group Brainstorm and Discussion
• How can you inform potential research
participants about informed consent?
• How can you find out if a person is able to
understand the informed consent
document?
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90
What Are Some Types of Clinical Trials?
Treatment
Prevention
Diagnostic
Test new
treatments,
new
combinations,
new
approaches to
surgery or
radiation
therapy, or
clinical
management
strategies.
Look for better
ways to prevent a
disease in people
who have never
had the disease.
In the case of
diseases other
than HIV/AIDS, to
prevent the
disease from
returning. Better
approaches may
include
medicines,
vaccines, and/or
lifestyle changes.
Determine
better tests
or
procedures
for
diagnosing
a particular
disease or
condition.
Understanding the Clinical Research Process and Principles of Clinical Research
Screening
Quality of
Life
Test the
best way to
detect
certain
diseases or
health
conditions.
Explore and
measure
ways to
improve
the comfort
and quality
of life of
people with
a chronic
illness.
91
What Happens in a Clinical Trial?
Three primary components help define how trials are conducted:
Placebo
Blinding
Randomization
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92
Placebo
Inactive product that
resembles the test
product
• Placebo may not be given alone if participants would
be put at risk
• Participants are informed of the possibility of
receiving placebo prior to enrollment
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93
Blinding
Purpose is to prevent participants
and/or the research team from
influencing the results
Single-blind: the participant is not
told what is administered
Double-blind: only the
pharmacist knows what is
administered
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94
Randomization
Occurs when participants
are assigned by chance to
one of two or more
alternative treatments
• Results of each alternative treatment are compared at
specific points during a trial
• If one treatment is found to be much better or worse,
the trial is stopped to minimize the number of
participants receiving the less beneficial treatment
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95
Group Brainstorm and Discussion
How would you explain these terms to
other, less-experienced people?
• Single-blind study
• Double-blind study
• Control
• Patient volunteer
• Inclusion and exclusion criteria
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96
GCP
Includes the following:
International standards for
designing, conducting, recording,
and reporting human clinical trials
Protection of each participant’s
rights in a clinical trial and
assurance of the intervention’s
safety and efficacy
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97
What Is Ethics in Clinical Trials?
Respect for persons
Beneficence, which means to do
no harm, or to maximize possible
benefits and minimize possible
harm
Justice or fairness
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98
Belmont Report
“The path to finding out if a new drug or treatment is safe
or effective, for example, is to test it on patient
volunteers. But by placing some people at risk of harm for
the good of others, clinical research has the potential to
exploit patient volunteers. The purpose of ethical
guidelines is both to protect patient volunteers and to
preserve the integrity of the science.”
Belmont Report Video
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99
Who Is Responsible for Ethics?
Everyone is responsible. An EC or IRB must approve, monitor,
and review research involving humans. Its purpose is to:
•
Protect research participants
•
Review protocols before trials may be conducted
•
Ask researchers to change protocols, when needed
•
Supervise a study from beginning to end
•
Oversee scientific design
•
Review community interests
•
Review recruitment plans
•
Enforce informed consent
•
Enforce confidentiality
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100
Group Brainstorm and Discussion
• What does an EC or IRB do in your
location?
• Describe the different kinds of people
who are members of the EC/IRB in
your area.
Global
Comm
nity
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Elements and Principles of Clinical
Research Case Study
Case Study
1
Thembi and
her daughter
Sarah
Case Study
2
Case Study
3
Case Study
4
Alex
Niran
Lina
With your group:
• Review the additional information about your case study
• Discuss possible answers to the questions (keep in mind what you
learned about ethics and the role of the research team)
• Present your answers to the rest of the class
― Be sure to include any new information about the person in your case
study
― Provide any opinions or beliefs that helped you answer the questions in
your case study
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Housekeeping
GENETICS
Sudha Srinivasan, Ph.D.
Program Officer
TBCRB/ DAIDS/NIAID/NIH
August 2012
This project has been funded in whole or in part with Federal funds from the Division of AIDS (DAIDS), National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Department of Health and Human Services, under contract No. HHSN272201200009C, entitled NIAID HIV and
Other Infectious Diseases Clinical Research Support Services (CRSS).
Objectives
Define terms
Communicate the
benefits of genetic
research
Understand
related ethical
issues
DAIDS Clinical Research Support Services
Address questions
regarding genetics
and informed
consent
Provide resources
104
Genetics and You
Every individual (except identical twins)
has a unique DNA sequence.
Our bodies of made of cells and each cell in an
individual contains the same DNA sequence.
What is DNA ? And why is it important
DNA contains the instructions for building and
maintaining all parts of the body
DNA and reproduction
How can we get DNA from a person
We leave cells
behind where ever
we go….
Skin, hair, nails,
urine, semen,
saliva, blood…
Can easily isolate
cells from these
cells….
Why is important to participate in these genetic
studies?
Choose the appropriate
treatment/drug(s) that
is right for youpersonalized treatment
Choose the right
behavior modification
that is right for you
Are there risks?
• Low-no health risk
• Specimens already
donated
• Data may be placed
in public database,
accessible to others
Participating in genetic research
Help
yourself
and your
family
Help future
generations
Help the
HIV/AIDS
community
Give back
to society
Genetic basis of disease control
Genetic heterogeneity
• We all respond differently
• to disease
• vaccines/drugs
• environment based on our genetics
• Gender, Ethnicity/Race
• Epigenetics influence (non-genetic
factors)
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113
Genetic terms in use
• Chromosomes
• Alleles
• SNPS-GWASMicroarrays
• Whole
Genome/Exome
• CNV
• si/sh/mi RNAs
Gene structure
Sequencing
related
DAIDS Clinical Research Support Services
Genetic
modifications
•
•
•
•
Transposons
Epigenetics
Linked genes
Linkage
Disequilibrium
• Systems biology
• Population
Stratification
• Genome projects
Systems /Other
114
The Human Genome
In Greek, the word genome means
“I become, I am born, to come into being.”
~3 billion base pairs
23 pairs of chromosomes (Sizes
range from 50 million to 250
million bases)
~25-30,000 genes
mytechnologyworld.com
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Single Nucleotide Polymorphisms: SNPs
DNA Double Helix
~ 10 million SNPs in Human
Genome
Stable
Occur in coding and non coding
regions
Useful in identifying
polymorphisms in complex, multi
factorial /polygenic diseases
DAIDS Clinical Research Support Services
http://mygenetree.com
116
Genome Wide Association Studies (GWAS)
http://cpmc.coriell.org
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Whole Genome Sequencing
Cost is high, but is now rapidly decreasing…
Different than GWAS, which seeks to identify common
polymorphisms
Whole genome helps find rare variants with large
effects, such as the mutation in gene CFTR, a defect that
causes Cystic fibrosis
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118
Genetic Research
Present
day:
Due to
advances
in:
DAIDS Clinical Research Support Services
• New tools and technology can help find
both common variations or mutations
associated with more common conditions,
such as diabetes, heart disease, overall
response to infectious diseases
• Rare variants associated with common and
rare diseases
• GWAS
• Whole Genome Sequencing
• Deep Sequencing and others
119
Benefits of Participation
Develop personalized
medical treatment to
treat a disease or
other health condition
Develop personalized
plan to prevent a
disease or other
health conditions
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Benefits of Participation
Predict risks of disease for individual or
future generations
Improve lab test for early detection of
disease or other health condition
Develop new medication and treatment
options for HIV, and other communities
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Informed Consent and What It Informs
Address Informed Consent Questions
• Which may include:
Risks of taking part
in study (e.g.
privacy)
Sharing
(genetics/health)
information
Rights to control
study specimens,
once donated
DAIDS Clinical Research Support Services
Access to
(genetics/health)
information
De-identification
of study
participants’
results
122
Information Regarding Informed Consents (continued)
Costs associated
with taking part in
the study, if not
covered by study
Consequences of
withdrawing from
study
Whether release of
study findings could
affect participant
insurability
DAIDS Clinical Research Support Services
Receiving key
findings
Possibility of
families learning
information about
participant
123
ELSI Issues
Knowledge of Ethical, Legal and Social Issues (ELSI)
• Which may include:
Informed consent in developing countries
Genetic testing as an inclusion criteria for certain studies
Sample repository for samples for genetic testing
Develop policy and guidelines for information access and sharing, specific to
certain genetic methodologies, as more genetic information is decoded
Enrollment of children
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Resources
Sharing
• Reducing fears
information
• Empowering
such as Fact
individuals to
Sheets, FAQs, or
make informed
other online
decisions
resources with
participants and • Encouraging
families can
participation
help with:
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125
Genetic Research
Resources
Online Genetic Educational Resources:
http://www.genome.gov/Education/
Talking
glossary of
genetic terms
Fact sheets
Webinar series
DAIDS Clinical Research Support Services
Online
education kit
Other
Languages
126
http://www.genome.gov/Education/
127
QUESTIONS
128
Conclusion
In this workshop, we:
Described the role of a CAB in the research process
Listed key partnerships
Explained the importance of worldwide AIDS research
Defined clinical research
Described the clinical research process
Described the elements and principles of clinical research
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129
Conclusion (cont’d)
Defined ethics
Discussed issues affecting AIDS research for various
stakeholders
Applied the information learned in activities and
discussions
Asked questions to clarify information
Practiced to reinforce learning
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130
What Do You Know?
Answer eight questions about clinical research.
131
Understanding the Clinical Research
Process and Principles of Clinical Research
What Do You Know?
The CAB acts as a point of contact between
the community and _________.
A. Researchers
B. NIAID
C. Clinical Trials Networks
D. Sponsors
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What Do You Know?
Clinical trials are sponsored or funded by various organizations
or individuals including (select all that apply):
A. Physicians
B. Foundations and voluntary groups
C. Medical institutions
D. Pharmaceutical companies
E. Government agencies
F. CAB
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What Do You Know?
Why is HIV/AIDS a difficult disease to research?
A. There are various routes of transmission
B. There are known cures but people do not have access to them
C. Different treatment options lead to different outcomes
D. A and B only
E. A and C only
F. All of the above
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What Do You Know?
What is research?
A. A job for scientists to identify the causes for disease
B. Work in a laboratory to treat disease
C. A systematic investigation to establish fact
D. Study paid for by the United Nations
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What Do You Know?
Before someone can participate in a clinical trial, they
need to meet which type of criteria?
A. Inclusion
B. Exclusion
C. Both A and B
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What Do You Know?
What is included in a research protocol?
A. How treatments are administered to study participants
B. Important facts potential participants should know about the clinical
trial before deciding to participate
C. Instructions for assigning participants to study arms
D. Both A and B
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What Do You Know?
Ethical principles guide clinical research activities,
including (select all that apply):
A. The conduct of research
B. The analysis of research data
C. The building of new research facilities
D. The design of research studies
E. The formation of research questions
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What Do You Know?
Which of the following are risks of participation in an
HIV/AIDS Phase I clinical trial?
A. Social stigma for participating in a trial about a sexually transmitted
disease
B. The severity of the side effects that might occur
C. The potential for a participant to become HIV-positive during the
trial
D. All of the above
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