Investigational Drug Use
Research
Drug
• Pharmaceutical entity that is not permitted for its
general distribution and use by the health authorities
• Drug may be considered for human use but not approved for
human use
• Preclinical animal models evaluation
• Safety and efficacy has established in animals but not
evaluated in human
• Research drug or Experimental Drug
Research Drug can be
• Well known drug (old drug) with new formulation
• Formulation w.r.t Excipients, Coating solvent, Vehicles
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Stability
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Shelf life
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cost effectiveness
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Allergic Properties
• Old drugs and new Combinations
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subject to safety and efficacy evaluation
• Old Drug and new dosage forms
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Also require evaluation
Special Labeling
• Caution: New Drug-Limited to Investigational use only
• Or Caution: Research Drug
Approval for
marketing
• Require adequate proof of its effectiveness
Future aspects
Review and Approval
• Clinical research on human is risky and uncomfortable
Committee on Human
Use in Research
• Safety and benefits of clinical investigation overweight
the risk in piori review
• Approved clinical projects
Informed Patient
Consent
• Informed patient consent is willing acceptance by a
patient to be subjected in research after having a complete information on the
aim, protocol and procedures of research.
• Legal capacity to give consent
• Free power of choice to withdraw
• Hospital must have policies to protect human subject
Either written or
verbal
• Nature and purpose of the study and expected benefits
• All inconveniences, risks discomfort and hazards
reasonably expected
• Alternative treatments available with respect risk
• General description of the study procedures and expected
length of therapy
A statement that
• Patient may withdraw from the study at any time without
penalty
• The investigator may remove patient from the study if the circumstances warrant
Any compensation or treatment that will be furnished in the
event of injury
The name of the person to be person to be contacted for
answer to question about the study
A statement of whom will have to access to any study records
that contain the patient’s name
Exception for patient
consent
• Communication barrier
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Patient is in coma
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Pt’s repersentative cannot be approchable
• To be in best intrest of pt
Consent must be in
writing in Phase I and Phase II
Phase III obligation
of investigator
• It is responsibility of investigator to obatain verbal
consent
• Record that fact(s) in the medical record of the person
receiving the drug
• Physical and mental status should be considered while
obtaining data
Intimation to the
drug authorities
• Evaluation of drug in human beings have legal and ethical
issues
Duty of investigator to notify drug authorities before
initiating a research involving human
Application submission
Authority scientists
• Physician, pharmacologist, chemist, biometrician,
microbiologist (if req)
This review ensures that the pt are not exposed to
unwarranted risks
The NID (new
investigational drug) only for in-vivo studies
• Are exempted for prior notification or intimation to
authorities
• Are labeled as:
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Caution- “Contains a new drug for
investigational use only in laboratory research animals. Not for use in human
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Or Caution- “A new drug for tests in vitro. Not
for use in human”
But if
• Research drug influences or change diagnosis and treatment
then notify authorities
¨
Antibiotics … new strain sensitivity and/or
resistance
The intimation or
notification must have following information:
• Complete composition of drug, its source, and manufacturing
data, to show that appropriate standards exist to ensure its safety.
• Result of preclinical investigations, particularly on
drug’s safety, rather than its efficacy
• Data demonstrate….. No hazard on Humans
Required information
are
• Pharmacological profile
• Acute toxixcology in serveral species of animals
• The route of administration used
• Very short term studies from 2 wks to 3 months to evaluate
toxicity
A detailed outline of the planned investigation
Information regarding training and experience of the
investigator
An agreement from the sponsor to notify the drug authority
and all investigators if any adverse effects arise during either animal or
human test
The investigator’s agreement to obtain consent of the person
on whom the drug is to be tested before the test is made
Agreement to submit annual progress report and commitments
regarding disposal of drugs when studies are discontinued
An Abbreviated New
Drug Application (ANDA)
• An application for an existing licensed medication or approved
drug.
a. Identify of the compound
b. Justification for human use
c. Purpose of the use of drug and the statement of
scientific training and experience of the investigator
d. Nature of the facilities available to the investigator
No control over prescription
• But encouraged to inform when they use a drug for purpose
other than those approved
Termination of
clinical investigation
• The drug authority may direct sponser to terminate
investigation on drug after failure of one chance given to the sponser for
correction at any stage under following conditions
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Evidence of significant hazard
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Convincing evidence of drug ineffectiveness
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Submission of false data
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Omission of material information submitted to
the drug authority
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Unsatisfactory manufacturing practice
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Noncompliance of submitted and approved research
plan
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Failure to submit progress reports at specific
time
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Failure to report serious or potentially serious
adverse reactions
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Failure to meet requirement for pt consent
Continuos monitoring
• The principal investigator should prepare a continuing
Surveillance Report on quarterly basis and forward to Secretary of the
committee on use of Human in Research
Documentation
• The record should be kept and retained usually for two
years
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Reports
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Data
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Result
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Inventory
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Control
Documentation reqd
for
• Drug amount received from sponsor
• Amount dispensed to patient
• Returned to sponser
Basic
Principle for institutional clinical research
• General Guidelines
• Guidelines for Research Drug Control System
• Guidelines for investigator
• Guidelines for pharmacist
• Guidelines for nurses
General Guidelines
• Existence of clear-cut written policies and procedures for
the approval, management and control of investigational drug studies in
clinical research
• Assurance
that all clinical
studies contain adequate safe
guards for the institution itself, staff of the institution, the scientific
integrity of the study and especially for patients
• Assure that involved staff is fully informed about and
complies with these policies and procedure
• Patient consent
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Written consent
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Verbal consent
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Proxy consent
• Supervised under competent personnel
¨
qualified
• Availability of research facility
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Research equipments
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Other facilities Before initiation of research
Self-regulatory
nature of research
• Research must be self-regulated
• Should be terminated on evidence
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A significant hazards
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Drug ineffectiveness
Study result should
not be used for promotion
• Should not used for promotion
• Data can be exchanged in scientific communication
Guideline
for research drug control system
Existence for an
effective control system
• The institution’s drug control system must be efficient to
assure surplus availability, storage, proper packaging, labeling in accordance
with standards
Prescription from
authorized practitioner
• Authorized prescriber
Record keeping
• Record to maintain drug received from sponsor
• Amount dispensed to patient
• Returned to sponsor
Receiving data at
another facility
• Different wards
Guidelines
for Investigator
Competency of
investigator
• Proper education, training, experience or potentials for
such studies
• Phase-I.. Able to evaluate human toxicology
• Phase II.. The clinician should be familiar with the
conditions and methods of their evaluation
• Phase III.. Large number of patient may be treated by
different physicaians
Authorization as
co-investigator
• Principal investigator can authorized any hospital staff
for co-investigator
Patient consent
• Must obtain patient consent
Record keeping
• Same as above
• Record must be made available promptly to the drug sponsor
and to the drug authorities
Regular reporting to
sponsor, drug authorities
• On process and adverse effects
Guidelines
for Pharmacist
1. Possession of an
approved research copy
Must have copy of the institutional research
committee-approved research protocol in pharmacy
2. Development of
investigational drug data sheet
• Drug designation and common synonyms
• Dosage form and strength available
• Usual dosage range, including dosage schedule, and route
of administration
• Indications
• Expected therapeutic effect
• Expected and potential unwanted effects, symptom of
toxicity, and their treatment
• Contraindications
• Storage requirement
• Instruction of dosage preparation and administration
• Instruction for disposition of unused doses
• Name and contact number of principal and co- investigator
The drug data sheet is included with the study protocol submitted
to IRC
Copy should be distributed to the appropiate pharmacy staff
to familiarize them and all patient care units where the drug will be used
An integrated drug distribution
system
• Dispensing of IND should be integrated with Drug other
system with respect to
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Packaging
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Labeling
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Order review
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Profile maintenance
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Delivery
• Label should be???????????? Same or different
There must be system to verify that IND is being dispensed
to consented patient only upon the order of an authorized investigator
Patient education and
monitoring of therapy
• The patient education and monitoring are clinical
responsibilities of pharmacist
• Should be performed in coordination with authorized nurses
and investigator
Return of unused
drugs
• At the conclusion of the study the pharmacist should
return all the unused drugs to principal investigator or to sponsor
Preparation of
statistical summary
• The Pharmacy must prepare annual or semiannual statistical
summary of investigational drugs use
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Must include number of drugs studied
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Number of drugs investigations are in progress
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Listing of all studied during previous year
Cost allocation
• The drug cost and other expenses should be properly
allocated
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Include record keeping, storage, drug administration
and personnel
