What is Pharmacy’s Role in Investigational Studies?

1. Ruth LaCasse, RPh Investigational Pharmacist Investigational Drug Service April 14, 2009 University of Connecticut Health Center Farmington, Connecticut What is Pharmacy’s Role in Investigational Studies?

2. How Can We Help You?

3. Objectives • The purpose of John Dempsey Hospital (JDH) Investigational Drug Service (IDS) • Policies for JDH Investigational Drug Service • The services we can provide to the Investigator and support team • Billing overview for JDH Investigational Drug Service • Information JDH Investigational Drug Service requires prior to study initiation • Common Questions JDH Investigational Drug Service is asked • Contact Information

4. Purpose • JDH has an Investigational Drug Service (IDS) for the following reasons: • To provide safe, effective, and responsible handling of investigational medication • To provide assistance and support to the Investigator & Support team • IDS assures compliance with all federal (FDA, NIH), state, JCAHO (Standard MM.7.40), and IRB/HSPO regulations concerning investigational medication

5. Policies • HSPO/IRB Administrative Policies • JDH Administrative/Nursing/Pharmacy Policies • Medication Administration: Investigational Drug: Inpatient Utilization of • This hospital policy can be accessed through the nursing website under Nursing Practice Manual http://nursing.uchc.edu/

6. Services • Clinical study dose verification • (prior to IRB approval) • Randomization • Drug Accountability (Ordering, Maintaining appropriate stock, checking for expired drug, inventory control) • Drug Storage/ Temperature Monitoring (Storage in area with limited access) • Refrigerator • - 20 ºC and - 80 ºC Freezers • Drug Destruction if unable to return to sponsor • Oral Medications • Matched Placebo if needed • Intravenous Medications • Inpatient/Outpatient • Physician Orders • Billing for Pharmacy Services • Maintenance of Discontinued Study Files • Staff Education and Assistance

7. Billing Although there is a standard billing structure, financial arrangements are negotiated to meet the specifications of each individual project. • Estimated Charge Worksheet • Completed prior to study initiation • http://octr.uchc.edu/forms/ • Study Set-Up and Close-Out Fees ($600 initial fee), Dispensing Costs (Varies), Drug and Supply Costs (Varies), Off-hour fees, and Study Maintenance ($300 per subsequent year) • Monthly Charge Worksheet • Investigational Study charges are billed monthly via transfer vouchers. Please contact us with appropriate FRS coding and contact information.

8. Protocol Requirements • Prior to initiation of a study, JDH Investigational Drug Service requires: • A copy of the current protocol. • Ruth LaCasse, RPh is responsible for IRB Pharmacy approval • For any future changes or amendments, please be sure to forward these to pharmacy as well. • A copy of the Investigator’s Brochure if the medication is not commercially available • Prescription orders or CPOE orders have been done • Billing charges have been agreed upon • Ruth LaCasse, RPh is responsible for billing charges • If needed, a study initiation meeting is highly encouraged to discuss workflow.

9. Question OneWhy can’t we re-use Medication returned to the pharmacy for cost savings? Sec. 460.300 Return of Unused Prescription Drugs to Pharmacy Stock (CPG 7132.09) POLICY: A pharmacist should not return drugs products to his stock once they have been out of his possession. It could be a dangerous practice for pharmacists to accept and return to stock the unused portions of prescriptions that are returned by patrons, because he would no longer have any assurance of the strength, quality, purity or identity of the articles. Many state boards of pharmacy have issued regulations specifically forbidding the practice. We endorse the actions of these State boards as being in the interest of public health. The pharmacist or doctor dispensing a drug is legally responsible for all hazards of contamination or adulteration that may arise, should he mix returned portions of drugs to his shelf stocks. Some of our investigations in the past have shown that drugs returned by patrons and subsequently resold by the pharmacist were responsible for injuries. Issued: 10/1/80 http://www.fda.gov/ora/compliance_ref/cpg/cpgdrg/cpg460-300.html Per FDA Guidelines and State Regulations, we cannot re-use medications once they are dispensed for patient safety.I cannot verify storage conditions were met when the medication has been stored outside the JDH Investigational Pharmacy.

10. Question TwoDoes JDH Investigational Drug Service store Investigational Medications with hospital medication supply? • NO! We store all of our medication separately from hospital supply medication All of our room temperature medication (except for 24 hour studies) are stored in locked cabinets that only the Investigational Technician and Investigational Pharmacist can access. If an emergency, a staff pharmacist would be able to get keys for access. All of our refrigerated and freezer medication are stored in devices clearly indicated for investigational use only.

11. Question ThreeHow does JDH Investigational Drug Service monitor the temperature for all investigational products in the pharmacy? • Room Temperature - Daily Manually Recorded Temperatures We record once daily a random temperature with the date, time, and initials of the person taking the recording • Investigational ONLY Refrigerator, -80 Freezer, and -20 Freezer - Daily Manually Recorded Temperatures - Electronic Alarm System JDH Pharmacy will be notified by the operator via the 24 hour pharmacy pager (825-3945) that there has been a reading out of range for more than 30 minutes. JDH Pharmacy could move investigational stock to hospital storage. JDH Pharmacy will then contact facilities.

12. Question FourWhat do you make your placebo oral medications with? • Our most common compounding procedure is to take an empty gelatin capsule and fill it with an inert substance. • Empty Gelatin Capsules come in a variety of colors and sizes (Size 000 to Size 5). We will most often pick an opaque color in order to maintain the blind. Most of our capsules come from Gallipot Compounding Supply or Capsugel. • www.gallipot.com • www.capsugel.com • We use either Lactose powder or Starch as an inert substance to fill the capsule. JDH Investigational Pharmacy recommends to use starch for placebo capsules in patients with Lactose Intolerance. Does the lactose content of medications pose a problem in patients who are lactose intolerant? Jan 28, 2008 Drug Topics

13. Question FiveSo- How do you blind oral active medication if have a matching placebo? Over-encapsulation is our preferred method. If necessary, we will also fill with inert substance if capsule rattles. Disadvantages include the possibility of the subject opening the capsule. See Example Below:

14. Question SixHow do we dispose of Investigational Medication? • Any Investigational Medication is destroyed at JDH Investigational Drug Service in compliance with state and federal regulations. • IDS contacts Research Safety when we have Investigational Medication ready for disposal. They transport the medication in a red biological waste bucket. It is then given to Clean Harbors for incineration. • IDS is more than willing to take any medication from any clinics performing studies if they are unable to send back to the sponsor. DO NOT FLUSH. • Any medication that is returned to us is counted and recorded before disposal.

15. Question SevenWhy do I need a prescription to dispense a product? What is the definition of dispense? • A prescription is necessary in order to dispense a product. A prescription drug should only be given out with written instructions from a licensed healthcare provider. See definitions below from the Connecticut Comprehensive Drug Laws: • “Prescription” means a lawful order of a prescribing practitioner transmitted either orally, in writing or by electronic means for a drug or device for a specific patient • “Dispense” means those acts of processing a drug or device for delivery or for administration for a patient pursuant to a prescription consisting of: (A) comparing the directions on the label with the directions on the prescription to determine accuracy; (B) the selection of the drug or device from stock to fill the prescription; (C) the counting, measuring, compounding or preparation of the drug or device; (D) the placing of the drug or device in the proper container; (E) the affixing of the label to the container and; (F) the addition to a written prescription of any required notations. “Dispense” does not include the acts of delivering a drug or device to a patient or of administering the drug or device to the patient. http://www.ct.gov/dcp/cwp/view.asp?a=1620&Q=275966&PM=1&dcpNav=|&dcpNav_GID=1541&dcpNav=|&dcpNav_GID=1541

16. Question EightWhy do we label any medication to be dispensed? • http://www.ismp.org/Newsletters/acutecare/articles/20071101.asp • ISMP (The Institute for Safe Medication Practices) reported that current packaging by sponsors can lead to medication errors. • Drug Names • Drug Labels • Drug Packaging • Tablet Markings • Expiration Dates • Space Limitations ISMP Recommends that the pharmacy should provide a supplemental label that meets all standards for prescription dispensing that are applicable in the state. http://www.ct.gov/dcp/cwp/view.asp?a=1620&Q=275966&PM=1&dcpNav=|&dcpNav_GID=1541

17. Question NineHow do you randomize subjects? • In order to reduce bias, we have a few ways to randomize subjects • URN Randomization • Method of randomly assigning subjects to groups • www.randomization.com • Random Allocation Software

18. Question TenDo we mark up the price of any medication acquired for an investigational study? • NO! • Investigators are charged actual drug cost for any studies that require pharmacy to purchase medication • We obtain supply from Cardinal wholesaler • For billing purposes – pharmacy must recoup medication cost

19. Question ElevenHelp! I have a study that will be used inpatient and will starting shortly – What do I do? • Contact Ruth LaCasse, RPh • I can help provide teaching information for nursing/pharmacists • I am unable to program medications into Computerized Physician Order Entry (CPOE), but I will contact appropriate help in Information Technology (IT) Services. • Currently, the hospital is nearly completely on CPOE (exceptions include NICU, OB, L+D, Psych1 and Psych3)

20. Question TwelveHow long do you store records? • Currently, we have been storing records indefinitely • Most recently closed studies (within the past year are kept on site) • Older studies at stored at Iron Mountain

21. Helpful Websites and References • Below is a list of websites and references that I have found helpful www.drugsimple.com (Access nearly every package insert available) www.globalrph.com (Pharmacist driven website with useful calculators and information) LexiComp Online (Accessible through UCHC Library Database) www.ashp.org (American Society of Health-System Pharmacists. They offer a email list serve just for investigational pharmacists. I am able to reach other sites to find out what advice they may offer.)

22. Contact InformationMonday  Friday 7:30am-4pm • Investigational Pharmacist • Ruth LaCasse RPh rlacasse@uchc.edu • Investigational Technician(s) • Margaret ( Meg ) Philippi philippi@uchc.edu • Francis (Fran) Roman has retired • Pharmacy is on Second Floor C: 2016 • Mail Code: 2205 • Technician Phone: (860) 679-8707 or • Pharmacist Phone: (860) 679-2085 • Fax: (860) 679-1231 • Pager for Research Technician: (860) 825-7583 • Pager for Pharmacist: (860) 473-2217 • Pager for Hospital Pharmacist (After Hours): (860) 825-3945

23. Mailing Address Dr. Principal Investigator C/O Ruth LaCasse RPh University of Connecticut Health Center Department of Pharmacy 263 Farmington Avenue Farmington, CT 06030-2205

24. Any Questions? Thank You.