In a recent webinar, Calyx’s Peter Tarbox shared the unique RTSM factors oncology trial sponsors should consider in their IRT design, focusing on how advanced IRT systems can accommodate changes in centrally and locally sourced medication for optimal clinical trial supply management.
Here he addresses some of the questions that arose during the webinar and explains how Calyx IRT addresses these unique RTSM challenges to keep these important trials on track.
Is the sourcing strategy only by country or can you set it by site level?
A common setup seen is that sourcing is selected at the country level as the suitability for local sourcing is usually consistent across sites within the same country.
However, if there is a specific need to vary the sourcing between different sites within the same country then the switch can be defined down to the site level.
If a site/country is locally sourcing all treatment components, would you advise that the medication assignment visits still be recorded within the IRT?
Typically, we advise caution when registering scheduled visits during the treatment phase within IRT that do not result in the allocation of medication through the IRT. The reason is that issues can arise with site compliance on registering the visit in IRT in a timely fashion.
However, if there is a need for the visit data to be stored within the IRT (for example, if you want to see these visits listed on a report within IRT) then these can be included but we would recommend that sites are made aware of the importance of these being registered accurately to avoid reconciliation issues at the end of the study.
Will the system be able to confirm the volume of the solution withdrawn to dilute in an infusion bag? Also, what about Cisplatin dose, could a calculator be uploaded in the system?
Calculations to support dosing can be included within the IRT and these can be included on the final readouts of the transaction, email notifications, and patient-level reports as required.
There is a decision to be made as to whether the IRT is the best place to perform these calculations – we have seen a mixture of approaches depending on whether the sponsor wants this handled within the IRT or left up to the sites themselves to calculate.
Generally, where a calculation is performed for a dosage, this is included within the programming of the IRT itself, however, we have seen occasions where if there is third-party software to perform the calculation then it may be possible for the IRT to integrate information for the calculation to be performed outside of the IRT with the result returned for storage in the IRT.
How would you handle dose reductions or dose increases for patients within the IRT?
Dose level can be tracked within the IRT – there are various rules that can be managed by the IRT (e.g. the IRT can ensure that a permitted dose adjustment is made in a stepwise fashion where the protocol dictates, or that there are a maximum number of times a patient can be dose reduced, etc.).
We always want to understand how much of a role the sponsor expects the IRT to have as a gatekeeper of the rules within the protocol, in comparison with their being less management of the rules within the IRT and the responsibility on the sites supported by adequate training, etc. to only select suitable dose level adjustments that comply with protocol procedures. But if the IRT is best placed to manage the titration rules, then protocol rules can be incorporated. Calyx’s intent is to identify the medical flexibility needed in the rules for a safety situation when setting up the system. This is so that the system is not made too rigid for unexpected safety cases or individual investigator decisions.
Outside of the mechanism for dose reduction and escalation itself, we would also recommend that the impact of potential dose escalation/reduction is considered to ensure optimal setup for buffer stock and prediction. For example, we have the option to predict enough medication to cover all options available at a visit, or we can rely on buffer stocks for the selection of the least common option.
Regarding expensive ECPs, do you have any experience on how to manage extra central supply at the depot level for a potential switch from local to central sourcing? We have a country that wants to locally source but would like to have central supply as a backup, but this would require us to always keep extra stock at the local depot for a potential switch, which is not desirable from our side.
The functionality described in this webinar would support the ability of the country to start off as locally sourced and provide the opportunity for the switch to central supply.
In terms of how the stocks are maintained at the depot for the chance of running out of locally sourced medication, this is something that perhaps we’ve not been directly told about or involved in discussions on. However, in theory, if the locally sourced medication does not run out, then the contingency stocks at the depot could be used up by utilizing this IRT switch functionality as we approach its expiry.
The timing of registering the switch within the IRT is always important to ensure that once the decision has been made to move to a central supply there is perhaps time for the local depot to be stocked up to support the central supply affected by the switch before the switch has been registered in IRT.
