9-Investigational Agent Management

INVESTIGATIONAL AGENT MANAGEMENT
The term iin,estigational agent refers to the study medication, or study drug, or experimental device to be used in a protocol. The use of investigational agents in clinical trials is strictly outlined by Food and Drug Administration (FDA) regulations. It is imperative that the agent can be accounted for at every step of the clinical trial processfrom the sponsor's shipment to the site to its destruction by the sponsor or use by the subject. This chapter will focus primarily on investigational drug substances, although the same general principles apply to devices. The Principal Investigator (PI) is ultimately responsible for all investigational agents but may delegate authority to other individuals.
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Clinical Research Coordinator Handbook
Before you receive an investigational agent(s), be sure you have a good understanding of the protocol and know what to expect in the way of study drugs and study design. Frequently, there will be mention of an active drug (the investigational agent) as well as a placebo ("sugar pill" or some similar inactive, innocuous substance). The study drug and the placebo are usually made to look identical. In some trials, the investigational agent is being compared to an approved form of treatment (active control arm). In this case, the study drugs will be designed to look alike, e.g., similar appearing capsules. If this is not possible, such as when one drug is an intravenous fluid and the other a tablet,
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placebos for each drug will be provided. Note that all of these are considered investigational agents and must be appropriately accounted for. A study may be double blinded, meaning that neither the investigator nor the subjects knows whether they are receiving the study drug or placebo, or it may be a singleblinded study, meaning that only the subjects do not know which they are receiving. The statistical analysis section of the protocol explains how the number of study subjects was determined as well as drug randomization. A computer-generated randomization pattern "assigns" the drug to the subject by subject number. Randomization by blocks is done to assure equal enrollment into each treatment group. If a study drug is randomized in groups of four, for example, this means that each group of four consecutive subject numbers was randomized separately from other subject numbers. Each group of four has the same number of active and placebo drug assigned. Separate blocks of four are randomized in different orders: SUBJECT # DRUG ASSIGNMENT
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CODE BREAKERS
A code breaker gives the identity of the drugs assigned to each subject enrolled in a blinded study as determined by the randomization sequence. Ask the study sponsor whether there will be a code breaker for the study drug given to each study site. A code may be "broken" in the case of a serious, life-threatening event if it affects the treatment of the event. Usually, someone other than the investigator or the CRC should keep this to prevent "peeking" and bias in the study. Often it is kept by the investigational pharmacist in a place that is accessible 24 hours a day. Be sure you clearly understand the circumstances under which the code may be broken. Even if done when necessary and appropriately, statistical significance is lost each time the code is broken. Any time the code is broken, it will raise a red flag during an inspection.
INVESTIGATIONAL DRUG AGENTS IN A CLINICAL TRIAL
Most study drugs and biologics are in the form of a solid or a liquid, but you may also see investigational agents in the form of a gas, such as an inhaled anesthetic used during surgery.Additionally, an approved drug may be studied for a different usage (unapproved indication) or assembled in a way different from the approved form. Whatever the investigational agent may be, the Clinical Research Coordinator (CRC) must keep in mind these responsibilities: 1. The drug is to be used only as specified in the protocol and is to be handledl administered only under the supervision of the physician approved to do the study (Principal Investigator [PI]) (2 1 CFR 3 12.61). 2. The FDA requires the investigator to establish a record of receipt, use, and disposition of all investigational agents (2 1 CFR 3 12.62). The drug must be kept in a secure place (pharmacy or physician's office, secured clinic area) (2 1 CFR 3drug P = placebo