Transcript Clinical Research and Development in the Pharmaceutical

Clinical Research and Development
in the Pharmaceutical and
Biotechnology Industry
Robert Anderson, MHA, CCRA, CCRCP
Director, Clinical Trials Administration
www.cratraininginstitute.com Houston Texas
11/11/04
Objectives
• To understand the drug development
process
• To understand the phases and components
of the clinical research process
• To appreciate the history behind the
regulations in the clinical development
process
• To understand the current regulations
involved with the clinical research process
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Healthcare Industry Players
Insurance
Company
Physician
Patient
Care
Hospital
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Pharmaceutical
Industry
Drug Discovery Process
Target Selection
Compound
Selection
Target Validation
& lead
optimization
Proof of Concept
Clinical Trials
Proof of Concept
Outcome
(250)
2 – 4 Years
(5,000 – 10,000)
Clinical Phases I, II
III, IIIB*
Drug
Registration
FDA Approval
*Key variable guiding
development time
(5)
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Pre-clinical
Phase
4 – 7 Years
(1)
Marketing
(Phase IV
Clinical Trials)
Marketing
Introduction
Clinical Trials: What Are They?
• An organized research study designed to
investigate new methods of preventing,
detecting, diagnosing, or treating an illness
or disease (such as cancer).
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The Players in Clinical Research
Investigator
Site
Sponsor
CRO
SMO
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Patient
IRB
Clinical Trials Process and
Associated Regulatory Process
Pre-IND Meeting
IND Application
Phase III
Pre-NDA
Meeting
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Phase
I
Phase
IV
Phase
II
Phase II
End of Phase II
Meeting
File NDA
Drug
Approval
Phases of Clinical Trials
Category
# of Participants
Purpose
Phase I
Less than 10
Tests how to administer a new therapy, exam, or
preventive option
Phase II
30-40
Test patients responses to a new therapy, exam, or
preventive option
Phase III
100-1000+
Compares new therapy exam or preventive option
to a standard one
Phase IV
Varies
For marketing purposes, to compare the
effectiveness of two therapies already on the
market or to study new uses of therapies
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Tasks Involved to Develop/Support
Clinical Trials
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Protocol development
Volunteer recruitment
Clinical conduct (management)
Monitoring
Data management
Clinical statistics
Medical writing
Quality assurance
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What is Involved in a Clinical Trial?
File IND application
Sites enroll patients
Develop protocol
Submit to FDA for comment or
no action
Patients cycle through study
Capture: Adverse events, vital
signs, study drug adherence,
QOL questionnaires captured
on Case Report Forms
Select investigational sites
based on # of patients
needed for the study
Regulatory requirements for
each trial at each site
•1571 or 1572
•PI’s CV
•Financial disclosure forms
•Informed consent
•IRB approval
Initiate site(s)
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Patients exit study
Data collected and cleaned
Sites closed
Write study report
Add study to NDA
Clinical Trials Benefits & Risks
Possible Benefits of Trials
Possible Risks of Trials
• Having access to potentially more
effective therapies than those currently
available
• Receiving quality medical care from
leading physicians
• Being closely monitored for possible
negative effects
• Sometimes receiving treatment at a
reduced rate or free of charge
• Helping to further new research that may
result in significant medical advances
• For patients in cancer therapy trials
assigned to control groups, they still
receive the top standard therapy available
today
• Patients may not receive the therapy
under investigation (may receive a
placebo – inactive pill – instead)
• The new therapy may not be more
effective than the standard, thoroughly
tested therapy
• In Phase I trails, not knowing the safety
consequences of the new therapy (risk is
less in Phase III trials)
• New therapy may have unexpected,
possibly severe side effects or may be
less effective than standard of care
• Insurance companies may not cover all
costs of clinical trials
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Clinical Trial Standard Language
Protocol
The planned course of action for the clinical trial. The protocol is
established prior to the start of the trial and states the number of
participants, eligibility requirements, agents that will be used,
dosages, duration, how data is collected, etc.
Investigator
A researcher in a clinical trial.
Sponsor
The part of parties responsible for funding the clinical trial.
Institutional
Review Board
(IRB)
An independent board of scientists, physicians, and nurses who
review the clinical trial protocol to ensure patient safety.
Informed Consent
A patient’s decision to participate in the clinical trial after being
informed of the potential benefits and risks of participation.
Participants may withdraw their consent at any time and leave the
trial.
Double blind
Term used to describe a clinical trial in which neither the patient nor
the researcher knows which agents are being administered to
which patients. This helps prevent bias.
Invention group
The group of participants receiving the new preventive or treatment
agent that is being evaluated in the clinical trial.
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Clinical Trial Standard Language, continued
Control group
The group of participants receiving a standard treatment or placebo
(see below) that is being compared to the new agent in the clinical
trial.
Randomization
Assigning participants by chance to either the intervention group or
the control group. Randomization is often done with a computer.
Placebo
An inactive substance that may be given to participant sin a clinical
trial. Sometimes called a sugar pill.
Follow-up
Monitoring of participants for a specified time after the clinical trial
is completed.
Prospective study
A study of a group of patients that is conducted as they are
undergoing a treatment or preventive measure.
Retrospective
study
A study of a group of patients after they have already undergone a
treatment or preventive measure. “Recall bias,” unintentional
inaccurate reporting of certain information, can sometimes
influence a retrospective study.
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History Behind Regulations of Clinical Trials
• Regulations often result in response to abuse of human
research subjects and concerns about the validity of data
and conclusions from clinical trials.
• The primary vehicles for human subject protection are
IRBs and informed consent.
• The Declaration of Helsinki and the Belmont Report are
critical documents for the protection of human subjects in
research.
• The FDA, by means of PDUFA and FDAMA, has made
significant gains in speeding the process of making new
drugs available for patients who need them.
• Current problems with clinical trials and trial oversight
may well lead to increased regulation.
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Regulations for Clinical Trials
• The FDA regulations pertaining to clinical trials
are found in 21 CFR Parts 11, 50, 54, 56, 312
and 314.
• The ICH Guidelines for Good Clinical Practice
should be followed in clinical trials.
• The FDA publishes many guidelines and
information sheets pertaining to the appropriate
conduct of clinical trials.
• Good clinical practices are the ethical and
clinical standard for designing, conducting,
analyzing, monitoring and reporting on clinical
trials.
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Health Outcomes
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Health outcomes studies examine the clinical, economic and quality-oflife outcomes of pharmacotherapy.
Health outcomes research expands upon the FDA-mandated efficacy
and safety endpoints to give a fuller picture of the outcomes
experienced by a patient. It is a relatively new discipline that combines
a number of fields of study, including medicine, epidemiology, statistics,
economics and psychometrics.
Early in development, companies may be interested in documenting the
epidemiology and cost burden of a particular disease state.
As a compound moves through to Phase II and II, behavioral,
humanistic and economic endpoints may be incorporated into
registration trials.
Concurrently, economic models may be created to quantify the
economic benefit of the new therapy.
Once a compound is launched, a variety of research services may be
utilized, including registries, Phase IIIb/IV comparative studies and
claims analyses.
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Other Issues in the Clinical Research
Process
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National Institutes of Health
Special populations
Data Safety Monitoring Boards
Orphan drugs
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