Center stage to stage left

Featured Blog by Denni O. Day

An experimental therapeutic undergoes many years of development and testing to confirm its safety, efficacy, and dose range. However, once it is ready for field trials, the focus shifts to other activities. Finding qualified and interested investigators, planning and conducting study training, site initiations, and subject enrollment all take their turn in the limelight, while test article accountability often slips into the shadows. Allowing this to happen can set the stage for future problems.

Here are just a few of the things that can go wrong:

  1. Test article is shipped by the sponsor but not received by one or more study sites;
  2. The amount oftest article received by the site does not match the shipping record;
  3. Test article arrives opened, damaged, or leaking;
  4. The wrong test article is shipped and received;
  5. A study subject is randomized to the wrong treatment group;
  6. A study subject receives the wrong dose (too much or too little); and
  7. Study site inventories of test article cannot be reconciled.

GCP Section 3.1.1 holds the investigator responsible for “the dispensing and administration of the investigational and control veterinary product(s)” and Section 3.2.20 dictates that the test article be stored as specified by the protocol. Implicit in both of these guidelines is the requirement that each investigative site maintain a complete and accurate accounting of test article received, dispensed, and stored. To minimize the risk of loss or misuse, all test article should be stored in a locked space separate from the site’s regular supplies inventory and with access limited to staff participating in the corresponding study.

Once a study begins, there are several steps that site staff can take to ensure an accurate test article inventory throughout the study. When the first shipment oftest article arrives, the dispenser and another staff member should document what was received and then confirm that the quantity, dose, and packaging match the information on the shipping documentation.

They also should verify that the shipment conforms to the specifications of the protocol. Any discrepancies should be reported to the sponsor immediately. As soon as the discrepancies are resolved, the shipping receipt should be updated with the correct information and a copy of the revised receipt should be sent to the sponsor. The original shipping receipt should be filed in the study binder for inclusion with the final study documents at close-out.

Before the first subject enrolls, the dispenser should establish a test article reconciliation schedule to maintain tight control as the study progresses. Ideally, the test article should be counted before it is dispensed to each subject and the owner should acknowledge, in writing, the amount that they have received.

Whenever possible, the study subject’s identifier should be written or attached to each container or package before it is dispensed. Partially-used and empty containers should be collected from owners at subsequent visits, with the quantity of any unused test article noted on the corresponding container. All containers should be stored with remaining test article to aid in future reconciliations.

Depending on the pace of enrollment, but at least weekly, the dispenser should perform a complete reconciliation of the test article inventory. In addition, the field monitor should perform a complete reconciliation during each monitoring visit and retrain the site staff in proper accounting methods whenever warranted. These practices will help the various study team members catch discrepancies quickly, which will increase the likelihood of their resolution.

In an effort to reduce study costs, some companies are exploring risk-based and remote monitoring. Each of these formats offers advantages, but each also requires added vigilance when it comes to test article accountability. Since there will be fewer physical counts performed on site by a field monitor, the project team may need to devise alternate methods of ensuring that the site staff are maintaining accurate counts. Options such as real-time telephone counts or photographic verification of inventories via smartphone may provide effective documentation between actual monitoring visits. Such extra steps could be especially important for studies employing controlled substances.

While test article inventory is unlikely to take center stage, it can play a critical supporting role to the many other parameters that must be properly executed to achieve a successful clinical trial. How important that role turns out to be will depend on the design of each individual study and the requirements of the respective protocol. However, the accuracy of each study site’s test article accounting can give you an advance review of their performance on all of the other study parameters.

Break a leg!