Using IVRS in Clinical Trial Management

Transcription

1 Using IVRS in Clinical Trial Management Bill Byrom Interactive voice response systems can work for project managers as an inventory management tool, a real-time project information tool, and a subject recruitment tool. The industry s drive to bring new drugs to market faster with less financial risk is increasing the number of challenges clinical trials face. At the same time, individual studies have become more complex, involving greater geographical coverage and higher numbers of subjects and study sites. This growth adds significant logistical complexity that the study team must manage. Many pharmaceutical companies are routinely applying technological solutions to simplify study management processes and maintain up-to-date study management information. By providing automated logistics management, drug supply savings, and realtime project information, interactive voice response (IVR) systems can provide a sophisticated method of optimizing and managing the clinical drug supply chain in clinical trials. More recently, IVR has been employed in combination with direct advertising for trial participants to accelerate subject recruitment, a process often difficult to control and a common cause of unplanned study delays. This article overviews the use of IVR in clinical study management, and considers the benefits of integration of IVR with other study management solutions and applications. IVR systems use the telephone as a means of inputting data. Prerecorded prompts that list the various options available or that request responses to particular questions are played for the user. Data are entered and written to the underlying databases by using the telephone touchtone keypad. An IVR system can improve the management of the medication supply chain, but it requires changing the way medication is packed and labeled. Automating study medication management using IVR In an IVR system, medication packs are uniquely numbered not by subject number, but by medication pack number. Any pack can be assigned to any subject within the same treatment group. Rather than containing the entire medication supply for an individual subject within a pack, optimal application of this approach involves packing medication in packs sufficient to treat a subject for a complete dispensing interval. Because complete dispensing units may be allocated to other subjects in the same treatment group, using IVR can reduce wastage of medication that would traditionally occur when a subject withdraws from the study. Dispensing medication and maintaining stock at site. Figure 1 illustrates how an IVR system is used to dispense medication packs to subjects, and how to maintain appropriate stock levels at site. This figure depicts the three main interaction locations the IVR inventory database, the drug distribution depot (usually either a pharmaceutical company or an external packing and distribution agency), and the study site. When a subject seeking medication arrives at a site, 36 APPLIED CLINICAL TRIALS actmagazine.com October 2002

2 Drug distribution depot Update inventory Automated electronic communication 5 Consignment details 4 Consignment request Figure 1. Medication dispensing and automated site inventory control using IVR. the investigator or site coordinator makes a toll-free call into the IVR system, indicating that he or she wishes to dispense medication and identifying the subject who requires the medication. The system then reports back the medication pack number that should be dispensed to that subject, with reference to the known inventory of stock held at that site. An automated fax or confirms this information. One of the benefits of using a computerized system to control the dispensing of medication is being able to maximize the use of the study supplies by allocating packs in expiry date order. After medicine has been dispensed, the involvement of the site staff is finished. Consider the following scenario as an example, however. The IVR system dispenses the current medication pack, identifies that the stock at the site for that treatment has fallen to a predefined minimum level (trigger level), and sends an electronic request to the drug distribution depot for a consignment of additional supplies to be sent to the site. This request lists the number of packs of each treatment that should comprise the consignment. Sometimes the IVR system will dictate the pack numbers that should be sent; other times the drug distribution depot will report back electronically which pack numbers were issued in the consignment. Next, the medication is shipped to the site, where the site coordinator or pharmacist makes another call into the IVR system to register the consignment s arrival. Missing or damaged packs can be identified during this call, possibly triggering an additional consignment. Finally the IVR database updates the study site inventory to include the new packs that are then available for dispensing to future clinical trial subjects. This example shows how the IVR system can help dispense medication, and how site inventories can be managed using a simple trigger and resupply process. Clearly, only sites using their medication supplies by enrolling subjects will meet their trigger levels and be resupplied thus the trial medication is targeted only to where it is required by the study. Other, more sophisticated algorithms for medication supply management exist. 1,2 The IVR approach not only The IVR database contains precise information about the whereabouts of every package of medication assigned to the study. IVR inventory database 6 Shipment limits wastage in medication due to subject withdrawals, it also focuses trial supplies to active sites limiting wastage traditionally resulting from preloading all study sites with quantities of medication before their recruitment performance is known. Using Physical shipment Telephone communication via IVR 1 Re-dispense call 2 Pack number 7 Notification call: arrival/ damaged packs Figure 2. Real-time drill-down Web reports of IVR tracking data. 3 Stock levels fall to trigger level Study site 8 Update list of available packs IVR makes possible additional savings in medication by pooling medication supplies across more than one protocol that share common treatment groups. This pooling of supplies can enable studies to commence in parallel when insufficient medication is available up front to supply each study. IVR as a real-time project information tool. In controlling randomization and medication dispensing, the IVR database represents a real-time record of the study s status. Making this information available to the project manager provides a powerful study management tool. In large multinational studies, maintaining accurate and upto-date study progress information can be difficult. A real-time Web report (Figure 2) provides this information instantly without Level 1. Study level summary Country breakdown Number of approved centers Number of active centers Number of subjects recruited Level 2. Country level summary Site breakdown Date site approved Activity window First subject entered date Last subject entered date Number of subjects recruited Level 3. Site level summary Subject breakdown Subject number Date of birth Date randomized Date of subsequent visits Medication packs assigned Withdrawn/completed October 2002 actmagazine.com APPLIED CLINICAL TRIALS 37

3 the limitations of awaiting a site contact or monitoring visit. In simple form, the IVR database may provide up-to-the-minute information on the number of subjects randomized, picking up medication, withdrawing from, and completing the study. The activity of individual centers can be presented giving dates of first and last subjects randomized, and total number recruited, for example and are helpful in decision making regarding whether to close or maintain individual study sites. More complex systems may summarize screening data, present screening failure rates and reasons for failure, and automatically inform sites when screening should stop so that the target number of randomized subjects is achieved without significant over-recruitment. Reduction of overrecruitment represents one of the major potential cost savings an IVR system can offer, often exceeding savings in medication overage. 3 In addition to subject tracking and progress reports, the IVR database contains precise information regarding the whereabouts of every pack of medication assigned to the study. Similar reports to those above can be used to track the packs available for use in the inventories of the main depot, local depots, and individual study sites. In addition, these reports can be used to identify the location of packs by production batch, thus facilitating, for example, the management of expiry date relabeling activities or batch recall. In studies requiring production runs throughout the study, the IVR data on overall medication pack usage and (unblinded) pack usage by treatment group can be used to forecast both the timing and content of future production runs. The observed recruitment and withdrawal rates and the known medication usage requirements of existing subjects across the entire study can be used to predict future usage and demand for supplies. Combined with knowledge of the leadtimes involved in production and also packing and labeling activities, this information can be used to predict both the date at which current supplies will be insufficient to supply the study, and the date at which production runs should commence, to be sure of meeting the IVR has been used to collect subject-recorded data, both in prequalification activities during the recruitment period and during the study. future study demands. These bespoke reports can be an invaluable aid to the study managers within the drug supplies team. Region 1 Site 1 Regional advertising Region 2 Region 3 Toll-free access IVR System Subject consent Eligibility assessment Site 2 Site 3 Eligible subjects IVR System Record subject contact details.wav/other files Web report/ access/ transcription report Subject contact details Region 4 Site 4 Individual sites served subject contact details Figure 3. Recruitment of potential subjects: from advertisement to study site clinical assessment. Using IVR in subject recruitment Efficient recruitment campaigns can be carried out using advertising and IVR. Collecting subject-recorded data via IVR systems. Subject recruitment is often difficult to control, and techniques able to reduce recruitment time are of great value to many studies. Although IVR systems are traditionally used to perform randomization, emergency code-break, and medication supply management, they have been used more recently to collect subject-recorded data, both during the study and in the study prequalification activities during the recruitment period. The key benefits of IVR use in subject data collection center around real-time data access and having a centrally held database and application. 4,5 Real-time data access means, for example, that subject compliance in making diary entries can be assessed prior to clinic visits. In the event of a subject failing to make a scheduled diary entry, the IVR system can generate an automatic alert to inform the study site or trained telephone callers to contact the subjects and encourage their future compliance. The main advantages of the application and database being held centrally are twofold. First, data are not held locally and so cannot be lost by the subject. Second, midstudy changes to the diary itself can be simply and quickly administered. Advertising and IVR. In subject recruitment, IVR represents a cost-effective prescreening method that can be used alone or in combination with a call center. Advertising for participants for clinical trials is commonplace in the United States and possible in many other countries, although the nature of advertising in other countries may be quite different from that permitted in the United States. Many pharmaceutical companies are realizing the benefits of using subject recruitment firms to speed up the enrollment period and make it more predictable. Through IVR, subjects responding to an advertisement can telephone a toll-free number and answer a series of questions to determine their potential eligibility to participate. IVR can be used either to deliver very complex prescreening interviews, such as the assessment of depression severity, 6 or more simple prequalification questionnaires designed to assess key disease and inclusion criteria. Previous studies have shown that this approach significantly reduces both the recruitment period compared to conventional clinic referrals, and also the screening failure rate among subjects attending clinical screening visits. 7 Figure 3 illustrates how the process might be implemented in practice. Potential subjects respond via a toll-free telephone number to an advertisement placed in local media normally newspaper, radio, or clinic leaflets. The process for selection to attend a screening visit, the 38 APPLIED CLINICAL TRIALS actmagazine.com October 2002

4 CTMS EDC DSMS New study site details Site contact detail amendments New subject enrolled/withdrawn/completed Site medication inventories Subject tracking data Subject withdrawal Subject completion Randomization data Dose adjustment/calculation data New subject enrolled New study site Randomization number Medication pack number(s) IVR diary data Dispatch notification Additional pack lists Expiry date updates New study site/details Consignment requests Figure 4. Integrated study management solution. type of information the subject will be asked to provide, and how the information will be used are explained to the subject, and his or her consent to continue is sought. The system then runs through a sequence of questions to assess potential eligibility to participate in the study. Those passing the prequalification process are asked to record their contact details, which are then passed to the closest study site so that a clinical screening assessment can be arranged. Those failing can be given information about how to seek further advice about their condition. Used in this way, an IVR system should also be configured to determine the type of advertisement to which each caller responded, making it possible to obtain real-time information regarding the number and quality of contacts generated from each advertising medium. This information can be used to focus future studyadvertising efforts. IVR is an alternative or combination solution to a staffed call center, and may represent a highly cost-effective and simple-to-apply option, particularly in New subject enrolled EDC CTMS New study site Medication pack dispensed DSMS multinational studies requiring multilingual capabilities. Integrated trial management solutions IVR can be used as a central component of an integrated study management and clinical data collection solution. In addition to IVR, clinical project managers use a variety of software tools, databases, and ad hoc solutions to assist study management. Within a large pharmaceutical company, the clinical team may use one or more solution, the drug supplies team another, and the project planning team yet another. Each represents an independent island of information that requires updating as information changes. The true benefits of all these systems are realized when they are integrated in such a way that the most up-to-date information is shared and accessible by each. Some of the data contained within an IVR system is the most current, up-to-date information about the clinical trial. IVR databases also share much information with other solutions that are also in place to assist trial management. Integration can enable the sharing of information between each application and IVR, and also indirectly between all solutions, using IVR as the information management hub. Integration with CTMSs. Many pharmaceutical companies use clinical trial management systems (CTMSs) as the main source of information regarding their studies. These may contain recruitment and withdrawal information for each site, details of each site, drug inventory levels at each site, monitoring reports, and other information. Updated as more information becomes available, these systems provide regular progress reports for the study manager. The IVR database contains a real-time snapshot of information regarding subject tracking, as opposed to the CTMS, which requires manual update from the clinical research associates following monitoring visits and telephone contacts with sites. Integrating these databases is possible, so that, for example, after a randomization call into the IVR system, the details are written to the IVR database and immediately copied into the CTMS database, even when the two databases reside on geographically remote servers in different organizations (IVR systems are often hosted by external service providers, whereas CTMSs may be in-licensed by the pharmaceutical company). As illustrated in Figure 4, real-time data residing in the IVR system that can autopopulate the CTMS includes new subject enrollments, subject withdrawals, subject completions, the activity status of sites, and details of the medication inventory held at each site. Clinical trial management systems often contain the most up-to-date information regarding the contact details for each site and investigator. These data are required by the IVR system when sending consignment requests to resupply sites, or confirmatory fax or notifications to investigators following randomization or dispensing events. In a similar way, changes to contact information within the CTMS, including the setup of new study sites, can be copied directly into the IVR database, removing the requirement to continually ensure that each database contains identical information. Integration with DSMSs. Pharmaceutical company drug supply groups and drug distribution CROs employ software solutions to manage the packing, labeling, and 40 APPLIED CLINICAL TRIALS actmagazine.com October 2002

5 distribution of supplies for each study. Consignment requests issued by IVR systems are often manually entered into these drug supply management systems (DSMSs). In an integrated environment, the IVR consignment request would be automatically written into the DSMS database, automatically triggering the actions required to dispatch the consignment. When a consignment is dispatched, the DSMS can inform the IVR system, which will assist in the tracking of consignments between depot and site. In addition, updates to the study pack list resulting from additional production runs or expiry date extensions can automatically populate the IVR system, reducing the requirement to maintain two identical databases. Based upon the real-time usage of medication in the study, the IVR system will be able to feed back the data useful in optimizing the timing and content of future production runs. Integration with EDC. Electronic data capture (EDC) systems provide the means to capture, report, and interrogate clinical data collected at study sites more rapidly than by traditional, completely paper-based means. Being sitefocused, EDC systems do not have the functionality to perform the complex central randomization and medication supply management that IVR systems deliver. The ability to combine this wider study management functionality provided by IVR with EDC provides a powerful solution. Much of the functionality performed over the telephone can also be performed via a Web interface to the IVR application. This enables users to perform randomization and medication dispensing via the telephone or via a Web form, for example, depending on which is most convenient. Web application makes integration with EDC more seamless from an end-user viewpoint, but in either case the sharing of information between databases is key. New subjects enrolled in the EDC system can create database records within the IVR database. At randomization, clinical data important in the randomization or dose calculation can be copied from EDC to IVR databases, and subject number and medication pack number information copied back into the electronic case report forms (ecrfs). Diary data collected using IVR can automatically feed the ecrfs. Ultimately all study data and IVR can be used as a central component of an integrated study management and clinical data collection solution. study management information can be reported and interrogated through the same channel. Three-dimensional integration. With these two-system integrations in place, it is possible for information created in a single solution to populate all other solutions using the IVR database as a conduit. As illustrated in Figure 4, for example, a new site created within the CTMS could create a new record within the IVR database, which itself could trigger the identical record to be created in the other solution databases. Alternatively, a new subject enrolled for screening within the EDC system could create a corresponding record within the IVR system that itself would feed the CTMS with updated subject recruitment progress data. A valuable tool Interactive voice response systems represent a valuable tool to the clinical study manager. Medication management and randomization using IVR provides a vital source of up-to-date and accurate study progress information. In addition, automation of site and depot inventory control and drug supply forecasting removes much of the complexity and management resource from the logistics of maintaining supplies for a clinical trial. In addition to qualitative benefits, IVR provides quantitative benefits, both in terms of savings in drug supply requirements and by limiting the additional cost of over-recruiting. By assuring that targeted timelines are met, IVR in combination with advertising for study participants can be useful in shortening the study recruitment period when used as a prequalification tool, and in reducing the cost of screening failures. Integration with other key trial management and data capture systems is a major area of future development. The efficiencies and power that can be gained by having a single source of data, and by sharing information between systems and solutions in an informative way, ensures that all study team members have access to the most up-to-date information. The inherent redundancy involved in maintaining systems that share a degree of common data is reduced. Through effective integration, the true power of all study management applications can be realized. References 1. N. Dowlman, Intelligent Medication Management Using IVR to Optimise the Drug Supply Process, Pharmaceutical Manufacturing and Packing Sourcer, Summer 2001, Bill Byrom, Managing the Medication Supply Chain Process Using Interactive Voice Response Systems, Life Science Today, February 2002, N. Dowlman, The Cost Benefits of Using IVR Systems in the Supply Chain, Pharmaceutical Manufacturing and Packing Sourcer, Autumn 2001, M. Camilleri et al., Efficacy and Safety of Alosetron in Women with Irritable Bowel Syndrome: a Randomized, Placebo-Controlled Trial, The Lancet, 355: (2000). 5. Bill Byrom, Collecting Data Electronically from Patients, Pharmaceutical Physician, 12: (2001). 6. K. Kobak et al., Computer Assessment of Depression: Automating the Hamilton Depression Rating Scale, Drug Information Journal, 34: (2000). 7. Bill Byrom, Practical Experience of Using Interactive Voice Response Systems as a Tool to Accelerate Patient Recruitment in Clinical Trials, presented at the DIA Annual European Meeting, Basel, 5 8 March Bill Byrom, PhD, is product development manager for ClinPhone Group Ltd., Lady Bay House, Meadow Grove, Nottingham, UK, , fax , info@clinphone.com. 42 APPLIED CLINICAL TRIALS actmagazine.com October 2002