Transcript Clinical Trial Process: Overview

Clinical Trial Process: An
Overview
Dennis R. DeRosia, PA, MA
Director, Business Development
Profil Institute for Clinical Research
[email protected]
Past President & COB
Association of Clinical Research Professionals
www.acrpnet.org
What Is a Clinical Trial?
Effectiveness of intervention to treat a
disease
 Safety of a new drug or device
 Defining dose administration
 Testing drug formulation
 Exploring combination therapies
 Evaluating effect of therapies on quality of
life

Types of Clinical Trials

Treatment
– Test new approaches to treat a disease
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Prevention
– What approaches can prevent disease

Early-detection/screening
– What are new ways to find hidden disease

Diagnostic
– How can new tests or procedures ID disease
Phases of Drug Development
Phase 1
Phase 2
Phase 3
Phase 4
No. of
15-30
Participants
100-300
100 to
thousands
Several
hundreds to
several
thousands
Purpose
First in
humans
safe dose
POC
Determine
efficacy
Safety
Post –market
Long-term
safety and
efficacy
1/3 fail
50% fail
Compare
new agent
with
standard
treatment
Safety
1/3 fail
Who are the Players?
Human Subject Volunteers
 Physician Investigators & Staff
 NIH – National Institutes for Health
 Manufacturing companies (Sponsor)
 OHRP - Office for Human Research Protections
 FDA – Food & Drug Administration (CDER, CBER, CDRH)
 Settings: Academic, Private Practice, Professional

Evolution of Regulations
1938 – Food, Drug & Cosmetic ACT
 1962 – Kefauver-Harris Amendment
 1968 – Drug Efficacy Study Implementation
 1981 – IRB Review Required
 1983 – Orphan Drug Act
 1997 – ICH-E6 Good Clinical Practice (GCP)
 1998 – Pediatric Rule
 2000 – NIH launches www.clinicaltrials.gov

Human Research is Highly
Regulated

Code of Federal Regulations (CFR)
– Title 21- Food and Drugs
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Part 50
Part 56
Part 312
Part 314
Part 600, 6001
Part 812, 813, 814
Informed Consent
IRB
IND
NDA
Biologics
Medical Devices
– Title 45- Public Welfare
» Part 46 (subparts B, C, D) DHHS, Protection of Human subjects
What About International
Regulation?
International Conference on Harmonization
 E6 Good Clinical Practice (GCP):
Consolidated Guidance

– International ethical and scientific quality
standard for designing, conducting, recording
and reporting trial results. (US, EU & Japan)
Why is Human Research Highly
Regulated?

Past transgressions lead to the need for laws
that protect the rights and welfare of human
subjects.
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Nuremberg Doctors Trial of 1946 (Nuremberg Code)
Thalidomide Tragedy (Kefauver-Harris Amendment)
Tuskegee Experiments (Belmont Report)
Human Radiation Experiments
Gene Transfer Experiment
Research Protocol: Roadmap
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Detailed Research Plan that Includes:
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Objectives
Background and Rationale
Subject Selection Criteria
Treatment Plan
Study Procedures
Response Evaluation Criteria
Statistical Section
Protocols
A Phase I, Double-blind, Placebocontrolled, Dose-escalation Study of the
Safety and Pharmacokinetics of Drug A31
in Subjects with Type 2 Diabetes Mellitus
 A randomized, double-blind, placebocontrolled study assessing the effect of
(study drug) Controlled-Release Tablet on
hypoglycemia in type 1 diabetic subjects
intensively treated with insulin

Protocol Mouthful
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A PHASE 1, RANDOMIZED, PLACEBOCONTROLLED, SEQUENTIAL PARALLEL
GROUP, MULTIPLE DOSE ESCALATION
TRIAL TO EVALUATE THE SAFETY,
TOLERABILITY, PHARMACOKINETICS,
AND PHARMACODYNAMICS OF 28 DAYS
OF ADMINISTRATION OF ND- 00254
TABLETS TO SUBJECTS WITH TYPE 2
DIABETES MELLITUS
Study Flow Chart
Study Flow Chart
Institutional Review Board
(IRB)
All clinical trials must be approved and
monitored by an IRB.
 IRB is an independent committee of
physicians, nurses, statisticians, community
advocates and others.
 The function of the IRB is to ensure that a
clinical trial is ethical and the rights welfare
of study participants are protected.

Informed Consent

Learning the key facts about a trial before
deciding whether to participate.
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Research study purpose
Risks/Benefits
Alternative treatments
Confidentiality of records
Medical treatment available if injury occurs
Whom to contact for answers to questions
Statement that participation is voluntary
Patient Recruitment Challenge
Poor patient recruitment is the number one
reason that trials fail.
 Only 3 to 5 percent of newly diagnosed
adult cancer patients participate in a clinical
trial.
 Reasons for this relatively low number are
many.

Recruitment Strategies
Physician trust and contact
 Study staff contact
 Speaking to community groups
 Newspaper and radio Ads
 Internet websites
 Physician referrals

Subject Data Collection
Data is collected on case report forms
(CRF)
 Much of clinical data is taken from the
subjects medical record (source documents)
 Pharmaceutical and device trials, data is
verified by multiple players
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Serious Adverse Events
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Events that results in any of the following:
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Death or life-threatening
Hospitalization or prolonged hospitalization
Persistent or significant disability/incapacity
Congenital anomaly/birth defect
Events that are serious, unexpected, and
related or possibly related to participation in
the research must be reported to the
Sponsor, FDA and IRB in a timely manner.
Clinical Trial End Product
Ideal: Unambiguous conclusion regarding
the clinical outcome of the test
treatment/device.
 Always strive for the ideal, but in most
cases have to settle for the best comprise.

Positive-leaning articles tend to focus on
gains made in fighting particular diseases.
“Alzheimer’s vaccine study promising”
“Treatment for cancer advances in trials”
“A promising weapon in the fight against MS”
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“Medical Miracles or Misguided Media”
The Los Angeles Times
“It sometimes seems as if there are Page 1 stories, television news reports and
magazine cover stories almost daily on medical breakthroughs - new treatments
for everything from the flu, obesity, AIDS and heart disease.”
News Update
“Medical clinical research slows for lack of patients”
Los Angeles Times – March 14, 2009
• Enrollment problems delay more than 70% of clinical trials
from one to six months
• In cancer care, less than 5% of patients enter clinical trials
• 700 cancer therapies in pipeline
News Update
“It’s time to speed up drug approvals”
The San DiegoUnion-Tribune – July 11,2008
by Sally C. Pipes
• FDA approved just 18 cancer drugs in past three years
• CyberKnife shoots beams of radiation at tumors
• Every day 1,500 Americans die from cancer
Coalition of National Cancer
Cooperative Groups
Pay Attention to the Clinical
Research Around You
You may be the
beneficiary some day!
Thank you