1. Research & Pharmacy Profession PHCL 311 Hadeel Al-Kofide M.Sc

2. Why do we need research? Promotion Better services to patients Better for our career Investigate problem Gain knowledge Prosper for the country/humanities…

3. Research & Pharmacy Practice Pharmacist is involved in the characterization, optimization & selection of new drug candidates Pharmacists develops & tests new formulations & drug delivery systems Pharmacists develops analytical methods for new active principles & pharmaceutical forms

4. Different Research Fields in Pharmacy Profession Universities Research institutes Industrial (drug companies) Hospitals Others

5. Qualifications Needed to Work in Research Area The normal path to a career in research is to gain high academic achievement in the BPharm programme to earn direct entry to PhD studies PhD studies can be undertaken entirely within a university or jointly with industry or a research institute

6. Types of Studies Used in Hospital Pharmacy Survey Clinical trials Questionnaires Case control Cross-sectional & follow-up approach

7. Important Elements of a Research Paper Abstract Introduction Methodology Results Discussion Conclusion

8. Important Elements of a Research Paper Abstract An abstract is a brief summary of a research article, thesis, review, conference proceeding or any in-depth analysis of a particular subject or discipline It is often used to help the reader quickly ascertain the paper's purpose When used, an abstract always appears at the beginning of a manuscript, acting as the point-of-entry

9. Important Elements of a Research Paper Introduction Usually contains background information for the study:  Current treatment paradigms for the disease  Reasons why treatment under investigation may offer benefit Contains study objectives

10. Important Elements of a Research Paper Methodology Usually contains:  Study design: Randomization, blinding & controls  Study population (Inclusion & exclusion criteria)  Sample size  Data collection  Statistical analysis

11. Important Elements of a Research Paper Results Contains results (data) of the study Could be in written or table format No interpretation of data

12. Important Elements of a Research Paper Discussion Interpretation of data (explains why you are getting these results) & how it relates to clinical practice Relates to previous studies in the same field Recommendation for future research Limitations?

13. Important Elements of a Research Paper Conclusion Summary of the results, usually 1 – 2 statements May be mentioned in the end of discussion section

14. Challenges That Face Research in Saudi Arabia Group Discussion

15. Investigational Drugs & The Role of Pharmacists PHCL 311 Hadeel Al-Kofide MSc

16. Topics to be covered today Definitions FDA regulations in regards to drug approval The clinical investigations Investigational review board The role of hospital pharmacists Single & double blinded studies Formulation & Development of A Dosage Form In summary Drug withdrawal

17. What is Investigational New Drug? Investigational New Drug (IND) program is the means by which a pharmaceutical company obtains permission to ship use an investigational drug before a marketing application for the drug has been approved. The FDA reviews the IND application for safety to assure that research subjects will not be subjected to unreasonable risk. If the application is approved, the candidate drug usually enters a Phase 1 clinical trial

18. Clinical Trial or Study Any investigation in human subjects that is intended to discover or verify the clinical, pharmacological or other pharmacodynamic effects of an investigational product, to identify any adverse reactions or to study absorption, distribution, metabolism & excretion of an investigational product with an object of ascertaining its safety, efficacy or both Definitions

19. FDA Regulations Before an investigational drug be can be used in clinical settings the sponsor must submit a Notice of Claimed Investigational Exemption for a New Drug (FDA form 1571) It contains 15 points

20. FDA Regulations 1.Complete composition of the drug, its source & manufacturing data 2.Results of all preclinical investigations 3.Background information of each clinical investigators (training, experience & facilities) 4.An outline or protocol of the phases for clinical investigation Also other requirements (total of 15)

21. Drug Development 1.Preclinical development 2.The clinical Investigation  Extensive research that is done on compounds before therapeutic indication found  Millions of compounds are tested in an attempt to find one that may have a pharmaceutical or medicinal use

22. The Clinical Investigation Phase 1 Phase 2 Phase 3

23. Phase 1 They are designed to determine a safe dose for phase 2 trials The purpose of these studies include: the determination of human toxicity, absorption, metabolism, elimination, pharmacodynamic, preferred route of administration & safe dosage range It involves a small number of persons (20-80) The Clinical Investigation

24. Phase 2 Limited number of patients (100-200) Designed to investigate drug efficacy & relative safety Want to determine if the new drug has activity against a particular disease The Clinical Investigation

25. Phase 3 These trials will be initiated if the information obtained from the first two phases demonstrate reasonable assurance of safety & effectiveness or suggests that the drug may have a potential value outweighing possible hazards Done to determine a new drug’s safety, effectiveness & most desirable dosage in treating a specific disease in a large group of subjects Phase 3 trials are mostly conducted as a multi-centered trials The Clinical Investigation

26. Institutional Review Board (IRB) IRB is an administrative body established to protect the rights & welfare of human subjects (including patients) recruited to participate in research activity The IRB has the authority to approve, require modification (in order to approve), or disapprove all research activities involving humans that fall under 1 or more justification criteria

27. Institutional Review Board (IRB) Justification criteria for IRB: 1.The research is sponsored by the organization 2.The research is conducted by or under the direction of any employee or agent of the organization in connection with institutional responsibility 3.The research interventions or interactions are performed at an organization property &/or this research involves the use of this institution's nonpublic information

28. Institutional Review Board (IRB) Information related to the study proposal is submitted to the IRB investigators For submission usually use an IRB cover sheetIRB cover sheet Also must report any problems like serious adverse effects, changes in the protocol that may affect the status of the investigation & the willingness of patients to participate in it

29. The Role of Hospital Pharmacists The extent of the role of hospital pharmacists in investigational drugs depend upon:  Type of hospital  Hospital facilities  Equipments  Specialized services  Expertise of the pharmacy department

30. The Role of Hospital Pharmacists The basic roles of hospital pharmacists in investigational drugs:  Registration  Control  Storage  Dispensing  Maintenance of disposition records  Drug information for every investigational drugs In order to carry on these basic roles it is imperative that the hospital adopt certain policies for the use of investigational drugs

31. The Role of Hospital Pharmacists Although the FDA does not require that investigational drugs be stored & dispensed through a hospital pharmacy, many hospitals require that all clinical investigational drugs to be stored & dispensed by the hospital pharmacy Some hospitals have established a policy that no investigational drug be administered to a patient unless it bears a pharmacy department control or registration number

32. The Role of Hospital Pharmacists Some advantages of having a role for hospital pharmacies in investigational drugs include:  Drugs can be stored, dispensed & accounted for  They can be observed for shelf-life & stability and then if needed it could be sent back to the manufacturer Investigational drug pharmacists are now being an essential part of the use of new agents in different hospitals

33. The Role of Hospital Pharmacists When the clinical investigator has written a clinical research protocol they meet with the pharmacy to discuss the handling & dispensing of the drug Certain points should be obtained at this stage

34. The Role of Hospital Pharmacists Information obtained at first encounter with the investigator: 1.Name of the drug 2.Dosage form & strength 3.Pharmacology 4.Purpose of the investigation (including copy of the proposal which was already approved by the FDA & other required committees)

35. The Role of Hospital Pharmacists Information obtained at first encounter with the investigator: 5.Route of administration 6.Dosage 7.Side effects, toxicity & any known antidote 8.Storage conditions 9.Stability of product

36. The Role of Hospital Pharmacists Information obtained at first encounter with the investigator: 10.Manufacturer 11.Name of the principal investigators & co-investigators authorized to prescribe 12.Nursing unit 13.Sponsor 14.How the drug will be written or called

37. The Role of Hospital Pharmacists Information obtained at first encounter with the investigator: 15.Re-label or special label (with a caution saying: New Drug: limited by Federal Law to Investigational Use) 16.Arrangement for obtaining additional drug along with tentative utilization rate

38. The Role of Hospital Pharmacists These initial information should be recorded on a special form called Investigational Drug Service Request Form: IRB cover sheet After the pharmacist meet with the physician the product is labeled with a control number, a disposition record is prepared & the drug is stored

39. The Role of Hospital Pharmacists Then the clinician can prescribe the new drugs for participating patients Before dispensing the medication pharmacy must check the disposition record to see if the physician writing the order is an authorized investigator

40. Single & Double Blinded Studies Pharmacists can be very helpful in establishing a single or double blinded studies Single blinding Double blinding

41. Single & Double Blinded Studies The role of pharmacist in single blinded studies:  Develop a simple system for coding drugs  Assigning a series of numbers or letters with the drug & placebo  Example: compound name 429 assign series A, C & T for the drug, & B, E & Y for placebo, how?

42. Single & Double Blinded Studies The role of pharmacist in single blinded studies:  Sometimes it is requested to break the blinding for medical emergencies, so if pharmacist was asked to break the blinding he must determine the reason

43. Single & Double Blinded Studies The role of pharmacist in double-blinded studies:  Use random generating tables, how?  Sometimes manufacturer does all the blinding & sends the drug & placebo to be directly given to the patient

44. Formulation & Development of A Dosage Form If an investigator which to carry on a study but no manufacturer is interested in sponsoring Pharmacists can formulate the new dosage form for this drug Must initially conduct studies to insure the identity, strength, quality & purity of the compound

45. Formulation & Development of A Dosage Form If an investigator which to carry on a study but no manufacturer is interested in sponsoring Pharmacists can formulate the new dosage form for this drug Must initially conduct studies to insure the identity, strength, quality & purity of the compound

46. Expanded Role for Hospital Pharmacists Other than the basic role they play in investigational drug within a hospital they have additional value in:  Study blinding  Formulating a new dosage form

47. In Summary Pharmacists play a role in investigational drug development With their expertise they participate in labeling, storage & dispensing of all drugs in the hospital Pharmacy is the logical place for the central repository for all investigational drug information including the investigational new drug number

48. WAIT…. We want to talk a little about the drug withdrawal

49. FDA & Drug Approval During the 1980s & early 1990s, the FDA was criticized for taking too long to review & approve drugs Then Congress, the FDA, & the pharmaceutical industry negotiated the Prescription Drug User Fee Act (PDUFA) of 1992 Under PDUFA, drug companies pay fees that allow the FDA to add more resources & speed up drug review time

50. Myths About Drug Withdrawals & User Fees  The reality is that it's a rare occasion when a drug is taken off the market.  The drug withdrawal rate has been constant over the last two decades, when comparing the time before user fees & after, there has been no change in the rate of drug withdrawals (2.7% before user fees & 2.8% after user fees)  Faster reviews to get valuable & life-saving drugs on the market does not translate into safety shortcuts  It isn't that the same number of FDA reviewers are working faster  It also isn't the case that shorter FDA review times mean abbreviated clinical drug trials  The reality is that it's a rare occasion when a drug is taken off the market.  The drug withdrawal rate has been constant over the last two decades, when comparing the time before user fees & after, there has been no change in the rate of drug withdrawals (2.7% before user fees & 2.8% after user fees)  Faster reviews to get valuable & life-saving drugs on the market does not translate into safety shortcuts  It isn't that the same number of FDA reviewers are working faster  It also isn't the case that shorter FDA review times mean abbreviated clinical drug trials

51. Myths About Drug Withdrawals & User Fees

52. But Still FDA is Facing Serious Problems for Fast Drug Approving

53. Example of Significant Drug Withdrawals Drug nameWithdrawnRemarks Thalidomide1950s–1960s Withdrawn because of risk of teratogenicity; returned to market for use in leprosy & multiple myeloma under FDA orphan drug rules Fen-phen (popular combination of fenfluramine & phentermine) 1997 Phentermine remains on the market, dexfenfluramine & fenfluramine – later withdrawn as caused heart valve disorder Cerivastatin (Baycol, Lipobay) 2001 Withdrawn because of risk of rhabdomyolysis Rofecoxib (Vioxx)2004 Withdrawn because of risk of myocardial infarction

55. Thank you