Investigational Drug Use

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

¨       Stability

¨       Shelf life

¨       cost effectiveness

¨       Allergic Properties

• Old drugs and new Combinations

¨       subject to safety and efficacy evaluation

• Old Drug and new dosage forms

¨       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

¨       Patient is in coma

¨       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:

¨       Caution- “Contains a new drug for investigational use only in laboratory research animals. Not for use in human

¨       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

¨       Evidence of significant hazard

¨       Convincing evidence of drug ineffectiveness

¨       Submission of false data

¨       Omission of material information submitted to the drug authority

¨       Unsatisfactory manufacturing practice

¨       Noncompliance of submitted and approved research plan

¨       Failure to submit progress reports at specific time

¨       Failure to report serious or potentially serious adverse reactions

¨       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


• The record should be kept and retained usually for two years

¨       Reports

¨       Data

¨       Result

¨       Inventory

¨       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

¨       Written consent

¨       Verbal consent

¨       Proxy consent

• Supervised under competent personnel

¨       qualified

• Availability of research facility

¨       Research equipments

¨       Other facilities Before initiation of research

Self-regulatory nature of research

• Research must be self-regulated

• Should be terminated on evidence

¨       A significant hazards

¨       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

¨       Packaging

¨       Labeling

¨       Order review

¨       Profile maintenance

¨       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

¨       Must include number of drugs studied

¨       Number of drugs investigations are in progress

¨       Listing of all studied during previous year

Cost allocation

• The drug cost and other expenses should be properly allocated

¨       Include record keeping, storage, drug administration and personnel

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