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Clinical Research and Development
in the Pharmaceutical andBiotechnology Industry
Robert Anderson, MHA, CCRA, CCRCP
Director, Clinical Trials AdministrationThe CRA Training Institute, Houston
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Objectives
To understand the drug developmentprocess
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
PharmaceuticalIndustry
Patient
Care
Physician
Hospital
Insurance
Company
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Drug Discovery Process
Compound
Selection
Proof of Concept
Outcome2 4 Years
4 7 Years
Marketing
Introduction
*Key variable guiding
development time
Target Selection
Target Validation
& lead
optimization
Proof of Concept
Clinical Trials
Pre-clinical
Phase
Clinical Phases I, II
III, IIIB*
Drug
Registration
FDA Approval
Marketing
(Phase IV
Clinical Trials)
(5,000 10,000) (250)
(5)(1)
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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
SponsorInvestigator
SitePatient
CRO
SMO
IRB
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Clinical Trials Process and
Associated Regulatory Process
Phase IIIPre-NDA
Meeting
Phase
IVFile NDA Drug
Approval
Pre-IND Meeting
IND Application
Phase
I
Phase
II
Phase II
End of Phase II
Meeting
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What is Involved in a Clinical Trial?
File IND application
Develop protocol
Submit to FDA for comment or
no action
Select investigational sites
based on # of patients
needed for the study
Regulatory requirements for
each trial at each site
1571 or 1572
PIs CV
Financial disclosure forms
Informed consent
IRB approval
Initiate site(s)
Sites enroll patients
Write study report
Patients cycle through study
Capture: Adverse events, vital
signs, study drug adherence,
QOL questionnaires captured
on Case Report Forms
Patients exit study
Data collected and cleaned
Sites closed
Add study to NDA
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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 possiblenegative 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 trialsassigned 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.
InstitutionalReview Board
(IRB)
An independent board of scientists, physicians, and nurses whoreview the clinical trial protocol to ensure patient safety.
Informed Consent A patients 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 clinicaltrial. 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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Regulations often result in response to abuse of humanresearch subjects and concerns about the validity of dataand conclusions from clinical trials.
The primary vehicles for human subject protection areIRBs and informed consent.
The Declaration of Helsinki and the Belmont Report arecritical documents for the protection of human subjects inresearch.
The FDA, by means of PDUFA and FDAMA, has madesignificant 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.
History Behind Regulations of Clinical Trials
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The FDA regulations pertaining to clinical trialsare found in 21 CFR Parts 11, 50, 54, 56, 312and 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 appropriateconduct of clinical trials.
Good clinical practices are the ethical andclinical standard for designing, conducting,analyzing, monitoring and reporting on clinicaltrials.
Regulations for Clinical Trials
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Health Outcomes
Health outcomes studies examine the clinical, economic and quality-of-life outcomes of pharmacotherapy.
Health outcomes research expands upon the FDA-mandated efficacyand safety endpoints to give a fuller picture of the outcomesexperienced by a patient. It is a relatively new discipline that combinesa 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 intoregistration trials.
Concurrently, economic models may be created to quantify theeconomic benefit of the new therapy.
Once a compound is launched, a variety of research services may beutilized, including registries, Phase IIIb/IV comparative studies andclaims analyses.
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Other Issues in the Clinical Research
Process
National Institutes of Health
Special populations
Data Safety Monitoring Boards Orphan drugs