Transcript Clinical Trials – PHASE III

CLINICAL TRIALS – PHASE III
What are phase III trials
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Confirmatory phase (Therapeutic confirmatory
trial)
Trials are done to obtain sufficient evidence about
efficacy and safety
Conducted in larger number of patients
In comparison with standard drug/placebo
OBJECTIVES
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To establish efficacy of the drug against existing
therapy
To establish the safety in relatively large number of
patients
To establish method usage in clinical practices
To identify contraindications, warnings
SUB-TYPES
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Phase III a
Before submission of NDA
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Phase III b
After submission of NDA but before
approval
STUDY- SITES
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Conducted at community hospitals
Other facilities
Nursing home
Private clinics
Multicentric
High costs involved
AGREEMENTS
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Agreements with investigator (time lines,
responsibilities, financial support, archives,
publication of results etc)
Agreements with laboratories (time lines, costs,
quality)
Agreements with hospitals (for use of facilities and
payments if any
Agreements with courier companies for shipments
STUDY POPULATION
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Patients with target disorder
Patients for whom drug may be indicated
Number of patient upon
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Statistical requirement
Availability of patients
Regulatory requirements depends
Avoid patient with severe medical conditions
STUDY DESIGN
Need of study design in phase III
 Randomization
 Blinding
 Control
Control is needed to have comparison
of test drug with other
A- Active control
B- Placebo control
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CONTD…
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Inclusion criteria is more flexible as large number of
patients are recruited
COMPLIANCE
Should noncompliant patients be discontinued from
study ?
ESSENTIAL DOCUMENTS
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Trial Protocol with identifiable date and version
Informed consent form with translations and back
translations
Case Record Forms
Brochures- Investigators and Patients
Patient recruitment aids
SITE PREPARATIONS
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Ensure that IRB exists and functions as per
regulatory requirements
Ensure personnel are adequately trained, both in
technology and GCP
Collect all documents pertaining to the site eg.
 CVs
of investigators
 Conflict of Interest Forms
 Training certificates if required
TRIAL MANAGEMENT
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Manage supply of trial related documents, trial
supplies
Recruitments schedules and time lines
Co-ordination with laboratories
Timely receipt and completion of CRFs
Resolution of queries
Payment to sites
PATIENT VISIT
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Patient visits should be as per visit schedule
Match patient visits with logs
Deviations are followed up
Remedial action identified and communicated
Patient withdrawals- identify and remedy the
causes
INITIATION MEETING
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Held after all trial material reaches sites
Held on site or by phone or video conference
Discuss all procedures again
Confirm total understanding and availability of trial
material
If all is clear declare site open for recruitment
Monitoring
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To check/watch study
To evaluate progress of trial
To check compliance with SOPs, Protocol and
Regulatory requirements
If any fault that should be brought in notice of
sponsor
INVESTIGATORS MEETING
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Held after all documents are complete
To be attended by Investigator’s and co-ordinators
Discuss protocol, ICF administration, CRF entry,
randomization and recruitments, trial procedures,
financial agreements and any study related
activities
AUDITING
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To check compliance with protocol, SOP’s, and GCP
Observation and finding of auditor should be
documented
Auditors may audit GMP conditions under which the
drug was manufactured
Auditors may audit electronic systems for
compliance with 21CFR 11.
CLOSE OUT
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After ensuring the study is complete.
All CRF received
All study material is accounted for
All investigational product is accounted for and
balance returned to sponsor
Ensure payment completion
TIME PERIOD & FEE
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Study generally lasts anywhere from 2 to 10 years
(with an average length of 5years)
According to Sch. Y the fee required for Phase III is
Rs.25000