EU picks up pace on home delivery of study drugs
The industry is keenly awaiting such guidance as, at this stage, any regulation is better than nothing. In most EU member states, trial sponsors are currently having to negotiate with regulators, protocol by protocol, for permission to use DtP shipments in justified cases.
A case in point is the high-profile RADIAL (Remote and Decentralised Innovative Approaches to clinical triaLs) study being undertaken by the Trials@Home consortium, which is funded by the Innovative Medicines Initiative — a public-private partnership between the EU and the European pharmaceutical industry body EFPIA.
The RADIAL trial is targeted at people living with type two diabetes in which all 600 participants will be treated with the same drug, Sanofi’s Toujeo (insulin glargine), in three different settings — 300 at their homes in a fully virtual arm, 150 in a hybrid setup (part home, part trial site) and 150 at a trial site.
With respect to DtP IMP shipments, there are several challenges faced by the RADIAL trial. In Germany for example, although the RADIAL trial protocol was accepted, federal inspectors had objected to DtP IMP shipments for the virtual arm from one dispensing pharmacy, claiming there was no legal basis.
Later, Spain and Poland also objected against accepting DtP IMP shipments from dispensing pharmacies in Germany or anywhere else across their borders to patients in their countries. However, the RADIAL trial team was able to overcome key roadblocks and the study is currently being executed.
The success achieved by the RADIAL team on this front shows that despite the lack of harmonized EU regulations on DtP IMP shipments, trial sponsors are currently able to get approval for using this approach on a case-by-case basis.
World Courier has made DtP IMP shipments in all European countries, even to those which were considered as “red”, for example in Belgium. This refers to an EU DCT recommendation paper issued last year, which includes an annex on the national acceptability of various decentralized elements, including DtP IMP shipments.
A recent study undertaken by researchers on behalf of the Trials@Home consortium also showed that it is feasible to employ DtP IMP supply models in Europe despite the lack of harmonized regulations.
From skepticism to filling the regulatory gap in the EU
During the pandemic, it was a positive thing to see for the first time in writing requirements by EU, U.S., and other regulators on DtP IMP shipments as part of emergency measures to help manage new and ongoing trials. They all temporarily allowed DtP IMP shipments to help sustain clinical research.
U.S. regulators have always taken a more positive view of DtP IMP shipments, even before the COVID-19 pandemic, as a way of promoting diversity in clinical trials. Following the end of the emergency phase of the pandemic, the U.S. Food and Drug Administration (FDA) is still supportive of it and even allows the IMPs to be stocked at a centralized depot when a licensed pharmacist is involved, she explained.
In contrast, the approach of EU regulators pre-COVID-19 was completely different. There was more skepticism and they have always maintained that it should be the exception, it was clear that they did not want it. After the emergency regulations for COVID-19 expired, the use of DtP IMP shipments is again not explicit in the EU.
However, EU regulators have identified this as a regulatory gap and are making efforts to address it. This was also confirmed at a recent DCT conference where Ditte Zerlang Andersen of the Clinical Trials Coordination Group (CTCG) said EU regulators were keen to support all possibilities to ease patient access to the study drug.
Some EU member states have already initiated steps to address the issue at national level. On this front, Denmark had been a rising star as it was the first to adopt national guidance on DCTs which clarified that DtP IMP shipments could continue beyond the pandemic.
Last year, Denmark also launched a national initiative to establish a national, public-private framework to support the implementation of patient-centered DCTs. World Courier is among several stakeholders taking part in this DCT initiative, which is being supported by Innovation Fund Denmark with an investment of DKK15.6m (US$2.27m).
Eventually, it can be expected all countries will develop frameworks for enabling DtP IMP shipments as pharma companies truly want to offer this possibility to their trial participants. Reducing the need to travel for treatment can make it easier for sponsors to recruit and retain participants and also target a broader patient population for their studies. Most big pharma companies have created dedicated DCT teams and are well organized when it comes to incorporating patient-centric elements either on their own or via vendors.
Confidentiality and coordination
Better product stability
One argument in favor of allowing DtP IMP shipments could be that it offers better product stability than traditional trials in which participants are administered the drug at the clinical site and then given additional doses to take at home. This is common in cases where a drug has to be taken more than twice a day. While this allows the treatment to be continued at home, no thought is given to how a participant transports this drug. They may travel by car or by public transport for many hours without temperature control.
In contrast, through DtP IMP shipments it is possible to extend the temperature-controlled environment, in accordance with good clinical, manufacturing and distribution requirements, right up to the patient’s doorstep. For studies involving temperature-critical medication, it is better to use DtP models in terms of patient safety and drug integrity.
Evolving tech to support DtP modelsThe technology behind DtP IMP shipments is also rapidly evolving to reduce the burden on staff at clinical trial sites, who are at the forefront of organizing the logistics for this procedure.
For randomized trials, most trial sites use an Interactive Response Technology (IRT) system to automate the randomization process and to dispense drugs to participants. As a result, when site staff have to order DtP IMP shipments, the product is often on site, but they have no control over which kit is given to which patient as this information comes out of the automated randomization system.
The staff are only involved in organizing the shipment of the package, which carries a unique identifier/serial number dispensed by the IRT system, and they do not know if the package is a placebo or contains the test drug.
During the COVID-19 pandemic, when DtP IMP shipments became necessary, site staff complained about the heavy burden of organizing shipments. To help address this, IRT system providers have started developing functionalities to support DCTs.
For example, some IRT providers allow the dispensing order to be translated into a shipment order, which can be directly picked up by the courier company’s system. Though a shortcut, it releases the clinical site staff from related organizational logistic activities.