Rutgers Cancer Institute of New Jersey
195 Little Albany Street
New Brunswick, NJ 08903-2681
Preparation and handling for all investigational agents: The Research Pharmacy develops methods and manages the preparation and delivery of investigational agents. Policies and procedures are in place that ensure (1) proper storage, handling, and dispensing of investigational agents according to protocol; (2) dose modifications (escalation or reductions) occur as described in the protocol; and (3) all federal and state regulatory requirements are met. The Research Pharmacy also developed policies for the management of investigational/study agents used in Cancer Institute multicenter trials through the Cancer Institute of New Jersey Oncology Group hospital network (CINJOG) for clinical trials. All policies and procedures are based on NCI guidelines and the recommendations of the Research Pharmacy Advisory Committee.
Drug accountability, dosing, and administration: The Research Pharmacy reviews all protocols before submission to the Institutional Review Board (IRB) to ensure that drug accountability, preparation, dosing, and administration are clearly defined. This helps to minimize the risk of medication errors and protocol deviations. Policies and procedures are in place in the Research Pharmacy to ensure drug accountability to supplying agencies.
Procurement: The Research Pharmacy works with principal investigators and sponsoring organizations to coordinate the procurement of investigational drugs. Upon receipt of the investigational agent, all shipping documents are verified against materials received, lot numbers, and expiration dates. The Research Pharmacy also obtains, tracks, and supplies commercial agents for clinical trials and for laboratory use by Cancer Institute members.
Storage and security: The Research Pharmacy, wherein all investigational agents are stored, is double-locked at all times, and is accessible only by Research Pharmacy staff. There is adequate room-temperature storage space, refrigeration, and freezers (a -30oC and a -86oC). Monitoring of these temperatures occurs hourly and is documented with Temp Trak™, a wireless remote temperature monitoring system with daily backup to the Cancer Institute server. Additionally, the refrigerators and freezers are programmed to trigger an alarm with backup, if the temperature is out of range for more than five minutes.
Dispensing: The Research Pharmacy ensures that all investigational agents are used in accordance with FDA and NCI guidelines for investigational drug use. Michael Kane and Jennifer Nishioka, Research Pharmacists, directly oversee the handling of investigational agents and ensure that preparation of agents is performed according to the respective protocol. The Research Pharmacy staff is responsible for verifying that study agents are dispensed only for patients on IRB-approved clinical trials, that the most up-to-date informed consent is signed by both the patient and an approved investigator, and that the patient is eligible and has been enrolled by OHRS. A chemotherapy order form, which includes the IRB protocol number, must be completed and signed by an approved investigator before dispensing any protocol therapy. This form will be subsumed within our new EMR, and order-entry for each protocol will be developed by the Research Pharmacy staff. All medication orders are cross-referenced to the protocol for verification of dosing and administration. Additionally, the Research Pharmacy staff verifies all dose modifications against the protocol after reviewing patient specific laboratory data and other toxicity data. For all phase I trials, patient dose assignment is verified by the Research Pharmacy staff against the dose assignment memorandum.
Drug accountability: Drug accountability is performed as outlined in the NCI Drug Accountability guidelines. All dispensed drugs are accounted for on NCI Drug Accountability Forms. Verification of inventory for quality assurance is performed monthly, and each time an agent is dispensed by the Research Pharmacy staff. Monthly verification of inventory includes comparison of the quantity of investigational agents in stock compared to the quantity at the time of the last monthly verification, cross-checked with the amounts recorded on the Drug Accountability Forms. In addition, the monthly verification of inventory includes a check of lot numbers and expiration dates. Each time a drug is dispensed, there is a check of the expiration date and a cross-check of the patient registration list with the Drug Accountability Forms to verify that patient initials and study numbers match, and to ensure that all patients scheduled to receive an investigational drug are registered on the protocol. This system will be expanded (see Future Directions) to incorporate OnCore® for drug accountability documentation.
Adverse event report filing: Reportable adverse events are defined for each clinical trial according to NCI recommended guidelines. The Research Pharmacy assists OHRS staff, in concert with the principal investigator, in the reporting of toxicities. Toxicity forms, which must be completed at specific intervals, are included as part of the Cancer Institute's clinical research record. A research nurse ensures that toxicities are documented in the clinical chart and, along with the Research Pharmacy staff, assists the responsible principal investigator with toxicity grading and assessing the relationship between the adverse event and the study drug. Reportable adverse event forms are completed by the research nurse and verified and signed by the principal investigator.
Expert consultation for clinical trial development: The Research Pharmacy provides expert consultation during the development of clinical trials. The staff focuses on the development of exclusion criteria for concomitant medications that may interact with the protocol agent, exclusion criteria and dose modifications for renal, pulmonary, liver or cardiac function based on the preclinical toxicity profile of a new agent for a phase I trial, and collaborate on the sequence of administration of protocol agents in the treatment plan. The Research Pharmacy also directs supportive care medications on investigator-initiated trials. This Shared Resource takes part in the weekly Phase I Group meetings and in protocol activation meetings to continuously and prospectively address these issues.
Drug formulation: The Research Pharmacy has the capacity to formulate and handle new agents including biologicals (e.g., panvac, fowlpox vaccines), natural products (e.g., methylselenocysteine, tocopherols, caffeine cream), and foods (e.g. green tea lozenges). Research Pharmacy staff work with OHRS and sponsoring regulatory agencies to achieve approval of new formulations.
Quality assurance: The Research Pharmacy staff is responsible for ensuring that all study agents are dispensed only for patients on IRB-approved clinical trials and only after the most recently IRB-approved consent form has been signed by both the patient and an approved investigator. The Research Pharmacy verifies that a signed and dated consent form is in the chart, re-verifies patient eligibility, and confirms with OHRS that the patient is enrolled onto a study before dispensing a protocol agent. Additionally, a pharmacist obtains a comprehensive medication history from the patient to minimize the risk of drug interactions.
IRB approved investigator-initiated clinical trials are translated into the ARIA electronic medical record (EMR) by the Clinical Trials Informatics Specialist from OHRS and the investigational agents are input by the informatics pharmacist, and verified by the Research Pharmacy. The Research Pharmacy provides further quality assurance by verifying that the medication orders translated into the system conform to those specified in the protocol. For randomized investigator-initiated clinical trials, the Research Pharmacy obtains the randomization schema from the Biometrics Shared Resource. The Research Pharmacy performs the randomization and maintains the randomization codes for possible decoding in the event of a medical emergency.
Research Pharmacy services for multicenter investigator initiated clinical trials: For network trials conducted at affiliate institutions, the Research Pharmacy is responsible for training the staff and inspecting the pharmacy at these sites. A Research Pharmacist, under the Centralized Education and Training Service (CETS) Shared Resource, provides educational initiatives involving the pharmacy. Patient enrollment is verified through OHRS and a facsimile copy of the signed informed consent is forwarded to the Research Pharmacy. Investigational agents managed by the Research Pharmacy are distributed to these institutions as outlined in standard operating policies developed by this Shared Resource. Cancer Institute investigational agents dispensed at Robert Wood Johnson University Hospital (RWJUH) are also under the direction of the Research Pharmacy. Pharmacists at RWJUH are in-serviced for each trial on drug accountability by a Cancer Institute Research Pharmacist, and the Research Pharmacy performs monthly audits on active studies involving investigational/study agents.