Investigational Drugs

in the hospital

+What is Investigational Drug?

Investigational or experimental drugs are new drugs that have not yet been approved by the FDA or approved drugs that have not yet been approved for a new use, and are in the process of being tested for safety and effectiveness.

new drugs old drugs- new indications, new combinations, new route, new

dosage investigational use of commercially available drugs

+Investigational New Drug Applications (INDs)

The industry must submit a form called Investigational New Drug IND to the FDA

The form include: chemical information, preclinical data including animal studies, detailed description of planned clinical trials.

Purpose: to get approval to begin clinical trials in humans. It can only be filed after the study sponsor has identified

the pharmacological profile of the drug and has results from both acute and short term toxicity studies in animals.

+Investigational New Drug Applications (INDs)

NO experimental agents administered to patients for research without an IND

All IND sponsors have obligations which are specified in the FDA regulations

+

+ New Agent Development process

+Preclinical Development

Pre-Clinical Drug testing

Animal Pharmacology and Toxicology Studies

Permit an assessment as to whether the product is reasonably safe for initial testing in humans.

Provide the starting dose for clinical trials & prediction of the likely effects of the agent on normal tissue.

Must be performed before IND submission

+The clinical Investigation

Divided to three phases

Aim: producing substantial proof for the safety and efficacy of the drugs

+The clinical InvestigationPhase I

Purpose: to determine pharmacokinetics, pharmacodynamics, preferred route, safe dosage range, toxicity information.

Population : 20-80 healthy adult volunteers with no pre-existing conditions, or in patients who have exhausted all other options (cancer patients, AID’s patients)

Duration: over 6 months -1 year

Doses increased gradually until tolerable adverse events &/or clear sign of therapeutic activity

+The clinical InvestigationPhase II

Purpose: to determine whether the new agent has activity against particular disease

Population: 100-200 patients

Duration: over 2 years

+The clinical InvestigationPhase III

Purpose: Further define efficacy, safety, and treating dose.

Population : 600-1000 patients

Trials usually multicenter studies

Duration: Last 3+ years

+

FDA should receive constant reports on the progress of each Phase

If hazard the patient, discontinue the clinical testing.

If significant activity is observed in any disease during Phase II, controlled trials conducted to compare the new therapy with the available or standard therapy

+New Drug Application NDA

After completion of phase 3 trial (safe & effective), sponsor submits NDA to the FDA requesting approval for marketing to be available to patients and physicians.

Includes: pre-clinical data, clinical data,2 well designed controlled clinical trials info, manufacturing methods, kinetics, pharmacology, product quality assurance, relevant foreign clinical testing, published reports, proposed package insert for drug.

+Phase IV (Post Surveillance Studies)

Drug is on the market.

Purpose: gather more data on safety and efficacy and identify an advantage over other therapies

These are conducted for the approved indication, but may evaluate: different doses effects of extended therapy drug’s safety in other populations (pregnancy, children,

elderly) New indications

+Treatment INDs (investigational new drugs )

to make certain investigational new drugs available to desperately ill patients before the FDA approves them for marketing.

These treatment INDs used if:- no comparable drug available- immediately life threatening or serious disease- drug under investigation & shows promise of therapeutic benefit

+Institutional Review Board Approval IRB

An administrative body established to protect the rights and welfare of human subjects (including patients) recurited to participate in research activities

IRB has the authority to approve, require modification or disapprove all research including humans.

Information related to the study proposal is submitted to the IRB

+Informed Consents

A document should signed by the patient

Purpose: to educate the patient about the objectives of clinical trial including the known risk & benefit of each therapy or procedure and any alternative therapies available

Investigational agents may be used emergently or not under the format of a clinical trial.

Informed consent and IRB approval or notification is required for emergent use.

+Single- and Double- Blind studies

Evaluate an investigational drug by comparing its action to a placebo or controlled drug.

Single-blind Study: patient is unaware of drug therapy course.

Double-blind Study: the patient, nurse and physician are unaware of which therapy the patient receives. Better Drug therapy are randomized Randomization helps to eliminate the bias

+The role of Hospital Pharmacist in Investigational drugBasic Activities:

registration of investigational drug in hospital

procurement

Storage, preparing, & dispensing

maintenance of records

Provision of drug information

Reordering Investigational Drugs

+The role of Hospital Pharmacist in Investigational drug Disposal of Used or Unused drug

Computerization of drug ordering and control

IRB Membership

Pharmacotherapeutic monitoring of invest. Therapy

Patient counseling and education

Data manager

Adverse Drug Reaction Reporting

+