Transcript Michael Ross Presentation on Clinical Trials

CLINICAL TRIALS IN NEW DRUG
DEVELOPMENT
Michael A Ross,M.D.
President CPL Inc.
Feb’ 2007
What is a Clinical Trial?
A biomedical or health related research
study in humans that follows a predefined protocol
HISTORY
Avicenna’s Cannons of Medicine (1025)
• "The drug must be free from any extraneous accidental quality."
• "It must be used on a simple disease."
• "The drug must be tested with two contrary types of diseases, because
sometimes a drug cures one disease by Its essential qualities and another
by its accidental ones."
• "The quality of the drug must correspond to the strength of the disease.."
• "The time of action must be observed, so that essence and accident are
not confused."
• "The effect of the drug must be seen to occur constantly or in many cases,
for if this did not happen, it was an accidental effect."
• "The experimentation must be done with the human body, for testing a
drug on a lion or a horse might not prove anything about its effect on
man."
TIME LINES
IND (investigation new drug) PROCESS
Types of Clinical Trials
Treatment trials test experimental treatments, new combinations of drugs, or new
approaches to surgery or radiation therapy.
Prevention trials look for better ways to prevent disease in people who have never
had the disease or to prevent a disease from returning. These approaches may
include medicines, vaccines, vitamins, minerals, or lifestyle changes.
Diagnostic trials are conducted to find better tests or procedures for diagnosing a
particular disease or condition.
Screening trials test the best way to detect certain diseases or health conditions.
Quality of Life trials (or Supportive Care trials) explore ways to improve comfort
and the quality of life for individuals with a chronic illness.
Who participates in Clinical Trials?
• The participants are dictated by the protocol
– Inclusion criteria
– Exclusion criteria
• The Criteria are designed to
– Protect the health and safety of the volunteer
– Ensure the clinical question can be answered
Institutional Review Board (IRB)
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Ethical arm of study
Physicians, statisticians and advocates
Can be local/centralized/both
Monitors supervision, consents, screening
Phases
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Preclinical
Phase 0
Phase I
Phase II
Phase III
Phase IV
Preclinical
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Animal study to test medical use
Doses
Toxicity
Preliminary pharmicokinetics
Phase 0
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First in human studies
10-15 subjects
Sub therapeutic doses
PK values and a bridge between animal and
human
• Not frequently done
Phase I
• Usually less than 50 and usually healthy
volunteers
• Usually done to test safety, PK, dose ranging
• Types
– Single ascending dose
– Multiple ascending dose
– Food effect(fed/fast)
Phase II
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Larger groups in 100’s
Really studies effectiveness of drug
Most failures occur here
Sub groups
– A-dosing
– B-Efficacy
Phase III
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100’s to 1000’s
Long duration
Because of the above VERY EXPENSIVE
Frequently multicentered
Usually lead to approval in about 2/3
Frequently 2 studies needed for approval
Intent to Treat (ITT)
Usually managed by a CRO
Phase IV
• Post marketing surveillance studies
• Can be required by new FDA legislation
• Mandatory particularly with expedited
approval process
• For safety and expanding indications(e.g.
pregnant women)
Data Safety Monitoring Board
• Separate from investigating team that can
monitor safety, efficacy and can stop trial.
OTHER ISSUES
• Electronic Data Management (EDM)
• eCTD filing(electronic common technical document)
– The Electronic Common Technical Document (eCTD) allows for the
electronic submission of the Common Technical Document (CTD) from
applicant to regulator. While the table of contents is consistent with
the harmonized CTD, the eCTD also provides a harmonized technical
solution to implementing the CTD electronically. This group has
developed and begun to implement the eCTD across the ICH partner
and observer regions. The group has developed a change control
process to monitor implementation progress and provide solutions
and added flexibility found necessary during implementation. Using
the change control process, several topics including study report
structure, lifecycle management, and consistency with the CTD are
being addressed and resolved. This defined change control process
ensures that the future of the eCTD is managed in a clear, harmonised
manner within the ICH process.