Dave Holly, Senior Manager, IRT Development and Operations, Sharp Clinical Services10.10.18
Interactive response technology (IRT) and randomization and trial supply management (RTSM) systems provide clinical trials with essential software services such as subject enrollment, inventory management, and study drug dispensing. IRT is used to manage patient interactions and drug supplies during clinical trials and perform a range of functions for sponsors, drug depots, and investigative sites. But is that all it can do? Are today’s IRT Systems just performing the same services of 10 or even 20 years ago?
Increasingly elaborate international clinical trials demand a smart, streamlined approach and, in the right hands, IRT can provide just that. They’re a powerful tool for accelerating a product’s progress to launch and making the management of trials simpler. However, the selection of an IRT vendor is often considered late-on in the planning of a clinical trial, which leaves sponsors at great risk of spending money on wasted drug and unplanned resupply shipments.
Supply chain efficiency
Simply adding IRT to a trial does not guarantee an efficient supply chain solution. Depending upon the complexity, number of kit types, regions, countries, and dosing schedules, the resulting supply chain solution may function, but questions will remain around its efficiency and cost effectiveness. What the IRT system must be able to do is help reduce waste, limit resupply shipments, and prevent site stock-outs.
One of the most expedient ways to achieve a successful supply chain solution is to leverage the real-world experience and advice of IRT Professionals. IRT is at the intersection of drug assignments, inventory, and resupply management, this provides professionals in the field with a very specific skill set resulting from clinical trial experiences.
IRT providers get to observe, first-hand, the many use case scenarios that result when sites are randomizing and dispensing study medications to trial subjects. These observational insights can prove very useful, especially when deciding how a drug will be manufactured and packaged. The advice provided by IRT vendors may prove especially useful to the small to medium-sized pharmaceutical companies that may not have in-house supply chain staff.
Deciding how much drug to put in one package
Early in the trial planning phase, a packaging company may suggest that money can be saved by putting more drug in one package. If a subject is to use one blister card per week for the duration of a 10-week study, putting all 10 cards into one package may look like a logical solution. IRT systems can be configured to import the kit list and dispense a 10-pack at randomization. On the surface, this also appears to be beneficial for the IRT system by eliminating the need for extra dosing visits over the 10 weeks.
But experience reveals that trial subjects are only human and are prone to lose kits. Site users—doctors and nurses—may accidentally damage drugs, forget to refrigerate medications, or have other mishaps over the course of the trial. These human-nature factors can result in the 10-pack packaging solution costing more money, rather than the intended saving. Bulk packaging sometimes results in more shipments and more drug being wasted.
It is important to consider how much drug would be wasted if a site, or subject, lost a 10-pack of blister cards and a replacement kit was needed. With all drug boxed in packs of 10, the subject must be issued another 10-pack kit. This means trial sites must have several 10-pack kits in reserve (buffer stock) for emergency resupplies. If the replacement is needed towards the end of the trial, most of the replacement kit will be wasted. This may also cost more if many of the 10-pack kits are left over and must be returned to the depot.
IRT professionals can advise that dispensing one or two blister cards over several trial visits is more cost effective. The loss of a single blister card is much easier to replace than the 10-pack of blister cards and costs significantly less. Even though more IRT dispensing visits are required, there is a significant cost savings in kit replacement needs. While highly recommended for most all similar dispensing scenarios, this solution is essential for trials with expensive drugs, or with drugs in limited supplies.
Deciding how much drug to manufacture or package
Trying to decide how much drug to manufacture and/or package for a new trial can be very challenging. Some clients decide to package only enough for the enrollment phase of their trial. But without considering IRT and drug usage, the stock could quickly drop by half just supplying sites with their initial inventories.
Discussing drug requirements with IRT professionals at an early phase brings supply chain staff together with the clinical team so that drug usage expectations can be discussed. If half of the packaged drug will be delivered to the sites upon study startup, then the inventory may not cover the expected resupply projections. Once this expectation is known it may lead to an increase of the initial supply amount.
The reverse scenario, packaging too much drug for study startup, can result in drug expiring before it can be used. This too is more clearly seen through IRT with the scheduling of subjects and the resupply model being used. Projections for enrollment and subject dosing visits may reveal that the initial drug inventory will expire before all subjects have completed the study. Two or more smaller manufacturing runs at key milestones will prevent site stock-outs.
Deciding what dose levels to manufacture
For dose escalation and titration studies, deciding what combinations of dosing quantities may also require investigation into actual drug usage and dispensation. For example, a protocol using four dosing levels of 10mg, 15mg, 20mg, and 25mg vials may require manufacturing one vial type of each dose level. Sponsors will need to explore whether it is necessary to manufacture all four vial dosing sizes, or if there is there a more cost-effective solution.
Once again, IRT can bridge the gap between manufacturing, packaging, and the clinical team. The dispensing and resupply patterns can be discussed, which can reveal expected subject needs compared with site available inventory and capacity. Due to space limitations, especially for refrigerated medications, requiring sites to maintain an inventory of 25mg vials may reduce the site’s inventory space for other dose amounts. This can lead to shortages if emergency kit replacements are needed. The discussion may result in a decision to packing just 10mg and 15mg vials and allow the IRT system to select the correct combination of vials to dispense i.e. 20mg subjects can receive two 10mg vials, and 25mg subjects can receive one 10mg bottle and one 15mg bottle. This adjustment also provides the sites with inventory that can be used for all subjects, including any replacements. All subject can use one or both dosing sizes. But a 25mg vial could only be used by subjects requiring the 25mg dose.
Summary
As IRT systems bring together sites, study medications, and subjects, IRT professionals can bring together supply chain and clinical team staff for discussions on actual trial needs. Including IRT professionals earlier in the planning phase of clinical trials may result in a better understanding of supply chain needs. This can increase the efficiency of inventory management and lead to unforeseen cost savings over the course of the trial.
Dave Holly is senior manager of IRT development and operations at Sharp Clinical Services. He has worked in clinical data management for over 30 years, designed several major clinical IRT systems and provided SAS programming support for many clinical trials.
Increasingly elaborate international clinical trials demand a smart, streamlined approach and, in the right hands, IRT can provide just that. They’re a powerful tool for accelerating a product’s progress to launch and making the management of trials simpler. However, the selection of an IRT vendor is often considered late-on in the planning of a clinical trial, which leaves sponsors at great risk of spending money on wasted drug and unplanned resupply shipments.
Supply chain efficiency
Simply adding IRT to a trial does not guarantee an efficient supply chain solution. Depending upon the complexity, number of kit types, regions, countries, and dosing schedules, the resulting supply chain solution may function, but questions will remain around its efficiency and cost effectiveness. What the IRT system must be able to do is help reduce waste, limit resupply shipments, and prevent site stock-outs.
One of the most expedient ways to achieve a successful supply chain solution is to leverage the real-world experience and advice of IRT Professionals. IRT is at the intersection of drug assignments, inventory, and resupply management, this provides professionals in the field with a very specific skill set resulting from clinical trial experiences.
IRT providers get to observe, first-hand, the many use case scenarios that result when sites are randomizing and dispensing study medications to trial subjects. These observational insights can prove very useful, especially when deciding how a drug will be manufactured and packaged. The advice provided by IRT vendors may prove especially useful to the small to medium-sized pharmaceutical companies that may not have in-house supply chain staff.
Deciding how much drug to put in one package
Early in the trial planning phase, a packaging company may suggest that money can be saved by putting more drug in one package. If a subject is to use one blister card per week for the duration of a 10-week study, putting all 10 cards into one package may look like a logical solution. IRT systems can be configured to import the kit list and dispense a 10-pack at randomization. On the surface, this also appears to be beneficial for the IRT system by eliminating the need for extra dosing visits over the 10 weeks.
But experience reveals that trial subjects are only human and are prone to lose kits. Site users—doctors and nurses—may accidentally damage drugs, forget to refrigerate medications, or have other mishaps over the course of the trial. These human-nature factors can result in the 10-pack packaging solution costing more money, rather than the intended saving. Bulk packaging sometimes results in more shipments and more drug being wasted.
It is important to consider how much drug would be wasted if a site, or subject, lost a 10-pack of blister cards and a replacement kit was needed. With all drug boxed in packs of 10, the subject must be issued another 10-pack kit. This means trial sites must have several 10-pack kits in reserve (buffer stock) for emergency resupplies. If the replacement is needed towards the end of the trial, most of the replacement kit will be wasted. This may also cost more if many of the 10-pack kits are left over and must be returned to the depot.
IRT professionals can advise that dispensing one or two blister cards over several trial visits is more cost effective. The loss of a single blister card is much easier to replace than the 10-pack of blister cards and costs significantly less. Even though more IRT dispensing visits are required, there is a significant cost savings in kit replacement needs. While highly recommended for most all similar dispensing scenarios, this solution is essential for trials with expensive drugs, or with drugs in limited supplies.
Deciding how much drug to manufacture or package
Trying to decide how much drug to manufacture and/or package for a new trial can be very challenging. Some clients decide to package only enough for the enrollment phase of their trial. But without considering IRT and drug usage, the stock could quickly drop by half just supplying sites with their initial inventories.
Discussing drug requirements with IRT professionals at an early phase brings supply chain staff together with the clinical team so that drug usage expectations can be discussed. If half of the packaged drug will be delivered to the sites upon study startup, then the inventory may not cover the expected resupply projections. Once this expectation is known it may lead to an increase of the initial supply amount.
The reverse scenario, packaging too much drug for study startup, can result in drug expiring before it can be used. This too is more clearly seen through IRT with the scheduling of subjects and the resupply model being used. Projections for enrollment and subject dosing visits may reveal that the initial drug inventory will expire before all subjects have completed the study. Two or more smaller manufacturing runs at key milestones will prevent site stock-outs.
Deciding what dose levels to manufacture
For dose escalation and titration studies, deciding what combinations of dosing quantities may also require investigation into actual drug usage and dispensation. For example, a protocol using four dosing levels of 10mg, 15mg, 20mg, and 25mg vials may require manufacturing one vial type of each dose level. Sponsors will need to explore whether it is necessary to manufacture all four vial dosing sizes, or if there is there a more cost-effective solution.
Once again, IRT can bridge the gap between manufacturing, packaging, and the clinical team. The dispensing and resupply patterns can be discussed, which can reveal expected subject needs compared with site available inventory and capacity. Due to space limitations, especially for refrigerated medications, requiring sites to maintain an inventory of 25mg vials may reduce the site’s inventory space for other dose amounts. This can lead to shortages if emergency kit replacements are needed. The discussion may result in a decision to packing just 10mg and 15mg vials and allow the IRT system to select the correct combination of vials to dispense i.e. 20mg subjects can receive two 10mg vials, and 25mg subjects can receive one 10mg bottle and one 15mg bottle. This adjustment also provides the sites with inventory that can be used for all subjects, including any replacements. All subject can use one or both dosing sizes. But a 25mg vial could only be used by subjects requiring the 25mg dose.
Summary
As IRT systems bring together sites, study medications, and subjects, IRT professionals can bring together supply chain and clinical team staff for discussions on actual trial needs. Including IRT professionals earlier in the planning phase of clinical trials may result in a better understanding of supply chain needs. This can increase the efficiency of inventory management and lead to unforeseen cost savings over the course of the trial.
Dave Holly is senior manager of IRT development and operations at Sharp Clinical Services. He has worked in clinical data management for over 30 years, designed several major clinical IRT systems and provided SAS programming support for many clinical trials.
