Building Flexibility for Clinical Trials

End-to-end solutions at clinical trial management companies aim to support a range of study designs and improve patient compliance with reporting and supply management. Solutions claim to feature rapid deployment so as not to delay a clinical trial. Interactive Web-based response (IWR) provides an alternative reporting channel for patients and doctors or clinicians in office and hospital settings.

Patient recruiting and management services provided by interactive voice response systems (IVRS) are integrated with supply-chain processes. When demand is established at a clinical site, seamless software integration initiates manufacturing to supply depots serving clinical supply sites globally.

Aptuit (Edinburgh, Scotland) employs an IVRS solution from Clarix that integrates with its Clinicopia clinical trial supply management product. A purpose-built information system for clinical trials, Clinicopia automates GMP-compliant study design, forecasting, labeling, and packaging distribution and returns management.

“Clinicopia is a solution from our Aptuit Informatics information systems group that allows us to maximize the flexibility of clinical trial supply while minimizing waste associated with clinical trial packaging. We are bringing together a range of services addressing all steps of the drug development process that will offer customers visibility from the time a molecule is identified for Phase One trials through manufacturing and clinical trial management,” says Gerald Hepburn, president, clinical operations, Aptuit.

Systems at clinical trial management firms can manage supplies in support of the trends of adaptive clinical trials and just-in-time labeling. In this approach, drugs are purchased and labeled as demand arises.

“The increase in comparator studies and the cost of comparator drugs is driving the interest in adaptive clinical trials. With a just-in-time labeling strategy, labeling for a specific country or region is provided closer to the time of patient enrollment,” says Jeff Hallquist, Fisher Clinical Services (Allentown, PA).

“Booklet labels are an alternative that allow labels to be prepared for many countries and pooled at depots for shipment to clinical sites on demand,” he adds.

Changes in trial recruitment, countries enlisted, and implementation of titration regimens are some of the variables that can generate unusable materials.

“You need the ability based on re­cruitment in different countries to be able to flex your supplies without a lot of rework costs. We will identify situations where the same materials can be used for two entirely different studies, so you have a range of options for using different materials,” says Hepburn.

Comparator drug costs can be managed by packaging comparators separately from the investigational drug and managing them to inventory independently. Aptuit often uses generic versions of comparators, sourcing from Eastern Europe and India, Hepburn says.

“In these cases, we have to assess for false economies. Supply stability and risk of forgery are concerns. You are getting multiple small lots, which requires maintaining the lot integrity when the drugs are packaged,” he adds.

Bilcare Inc. (Phoenixville, PA) has an IVRS solution with integrated supply management functions. It’s designed for rapid configuration to support simple to complex clinical studies, says Edward Montoya, director, IVRS services.

“Pharma companies who have in-house IVRS are usually limited in both design flexibility and capacity. We have the flexibility to provide our clients with a choice, with a system designed to handle multiple design studies. In addition, we are providing the entire manufacturing, labeling, packaging, and distribution service component under one roof,” Montoya says.

Bilcare’s IVRS solution offers global site access for investigators, clinical coordinators, and patients, with responses in any language. Based on the Microsoft.net platform, the system supports phone or Web-based interactive response.

System users receive a unique ID assigned by the system at the investigator site, or when they call in directly to participate in the study. The 21 CFR Part 11–compliant system identifies callers by access code and personal ID. Users are instantaneously checked for both the specific language the caller will be using and authority to perform particular protocol functions, such as randomizing patients. The software manages patient enrollment and patient drug assignment.

“The system knows the treatment the patients are randomized to, and their visit schedule. When an investigator calls the IVRS during a patient visit, the IVRS calculates how much drug is required for the patient based on the interval between visits, and assigns enough drug to get the patient through to the next visit,” says Montoya. “In a randomized, double blind clinical trial, only the system knows what the patient’s treatment arm is. The system will manage the clinical trial strictly, based on the rules designed in the protocol.”

With real-time demand and supply response, the system predicts necessary inventory amounts based on supply-chain inventory positions and transactions at clinical sites. Drug distribution is managed off the production line, to warehouses, global depot centers, trial sites, and patients. It accounts for patient consumption, inventory levels, delivery lead times, and drug expiry dates.

“Medication in many cases in clinical trials is continuously tested as it is being used to re-establish its shelf life. We monitor this, because the medication’s shelf life can be extended based on this continuous analysis,” Montoya says.

“As the trial is progressing, the IVRS reacts to trends as they happen. If a patient is titrated up or down a dose, the system accounts for the varying demand,” Montoya adds.

Electronic patient diaries is another feature of Bilcare’s IVRS service. Montoya says that IVRS-based electronic diaries have greatly advanced patient self-reporting outcome compliance with trial reporting. When paper diaries are used, patients tend to wait until the doctor’s visit to remember their reactions to taking medications and write them down. Electronic diaries demonstrate a 90% patient compliance rating compared with about 30% for paper diaries.

IVRS call flows mimic paper diaries. They are designed to ask patients questions about their conditions after they have called in and are recognized by the system. Besides prompting patient participation, they obtain accurate reporting of patient reactions to the treatment.

“The IVRS reminds the patients to report when they are supposed to report. If patients don’t call in when the system is programmed to expect them, it will call with a friendly reminder, or send a noncompliance report to the clinical site; the site can then immediately call the patient. Investigators can be alerted if patients are reporting symptoms beyond preset limits. You can find out earlier if patients have decided not to continue with the treatment,” says Montoya.

Montoya says he helped design and manage IVRS solutions for more than 600 studies during 13 years. Bilcare works to improve IVRS solutions as it continues to build on that experience.

“IVRS service providers are often not brought into the process until only a few short weeks before the first patient date is scheduled. If the IVRS isn’t ready, the clinical trial may be delayed. We have designed a base system that can be easily configured for an IVRS application in four to six weeks. Our goal is two to four weeks, so we can keep the IVRS off the critical path, without causing any delays in the clinical study,” he says.