1. Investigational Drugs in the hospital

2. + 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

3. + 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.

4. + 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

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6. + New Agent Development process Preclinical studies (Animals) IND Clinical studies (Humans- 3 phases)

7. + 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

8. + The clinical Investigation Divided to three phases Aim: producing substantial proof for the safety and efficacy of the drugs

9. + The clinical Investigation Phase 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

10. + The clinical Investigation Phase II Purpose: to determine whether the new agent has activity against particular disease Population: 100-200 patients Duration: over 2 years

11. + The clinical Investigation Phase III Purpose: Further define efficacy, safety, and treating dose. Population : 600-1000 patients Trials usually multicenter studies Duration: Last 3+ years

12. + 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

13. + 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.

14. + 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

15. + 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

16. + 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

17. + 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.

18. + 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

19. + The role of Hospital Pharmacist in Investigational drug Basic Activities: registration of investigational drug in hospital procurement Storage, preparing, & dispensing maintenance of records Provision of drug information Reordering Investigational Drugs

20. + 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

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