While the direct-to-patient (DtP) model in clinical trials offers compelling advantages, there are still logistical complexities to work through. As one sponsor discovered recently, the shipment of dangerous goods is one of them.
Decentralized clinical trials (DCTs) have continued to gain momentum since the pandemic. As both an overall distribution strategy and as a mitigation, DtP seems set to remain an important tool within clinical supplies.
The industry has seen a clear shift toward decentralized models, with one source reporting that the average number of studies including at least one decentralized technology was 43% before the pandemic, rose to 55% currently, and is predicted to be 66% in five years’ time. While this isn’t solely DtP, it reflects the growing embrace of methods that reduce or eliminate site visits, including DtP.
In 2025, the percentage of clinical trials incorporating a direct-to-patient (DtP) component is difficult to pinpoint with a single definitive figure. However, the trend clearly indicates a significant increase in the adoption of direct to patient in clinical trials as part of the broader rise of decentralized clinical trials (DCTs).
With this solution now part of modern-day study designs, there are still many nuances to consider, and as Mike MacNeir, Vice President, Business Development at Sharp Services, reminds us: “the devil is in the details.”
What do you do, for example, if your trial supplies are classified as a ‘dangerous good’ (DG)? This is exactly the situation that one sponsor found themselves in when planning a Phase III hybrid trial where patients were supplied with compressed gas canisters and cannulas, as well as an investigational device used to deliver the IMP.
“The IMP was heavy and bulky, and many sites did not have sufficient room to store the product,” says MacNeir, recalling some of the initial logistical challenges that prompted the sponsor to consider a DtP model. Moreover, while patients were given a seven-day supply of IMP during their initial screening visit, handling the resupplies was another matter – and frontloading wasn’t appropriate given the patient population, which suffered from chronic obstructive pulmonary disease (COPD) and pulmonary arterial hypertension (PAH).
“Due to the patients’ health conditions, they were already burdened with the transport challenges that oxygen tanks and cannula lines bring,” explains MacNeir. “Carrying a one-to-two-month supply on top of that was too much additional burden on the patient.”
Further challenges were posed by the reusable nature of the gas canisters, which needed to be shipped to another site for cleaning and refilling before returning to the depot.
“Product was classified as a dangerous good because of the compressed gas aspect within the canisters,” notes MacNeir. This was the same for the returning cannisters, which may be empty or pressurized – at the point of collection, there was no way to check.
The sponsor’s solution was to leverage an experienced distribution partner – Sharp – who was able to pack the supplies from the depot/central pharmacy and send them directly to patients. According to MacNeir, this part was straightforward, as the depot had the necessary training, packaging, and labels to support compliant distribution of the initial site supply and the DtP resupplies within five days of screening.
The more challenging solution was to handle the returns of the canisters from patients, who were not certified to pack the potentially dangerous goods themselves, and nor could the courier.
“Most drivers are not trained to pack and complete the DG declaration,” says MacNeir. “These trained staff were all physically at the depot/CP and it would be incredibly costly to have them fly to every patient’s home to pack up the material in compliance with the International Air Transport Association’s regulations.”
The team began investigating whether there was any accepted number of canisters that could be shipped via air or ground. While IATA regulations declared this impossible for even a single canister, thus ruling out air transport, a workaround was found under the Department of Transport regulations which confirmed a maximum number of canisters that could be transported via roads at any one time.
Key takeaways and considerations when leveraging DtP pathways for DGs
MacNeir notes that while excepted quantities solved the supply chain complexity in this case, the open conversations made this a success. Had those conversations not happened, there would have been issues after study start. Like in the case study above, it’s critical that sponsors do their due diligence upfront and explore options across the entire supply chain. Be clear with partners and involve them early with active, strategic discussions.
“Even when your IMP is not a DG, there are still other things that are easily overlooked,” adds MacNeir. “It is impossible to know the unknown, especially if DtP is a new strategy you are working through. I cannot tell you how many calls I’ve been on where I have heard ‘it’s just a US trial, so it should be easy, right?’ But if, for example, a patient comes from Canada to a US site for treatment, this can cause issues when doing a DtP resupply to that patient if the protocol is not approved in Canada. Waiting for Health Canada’s approval to allow a shipment into Canada without a no-objection letter or without an established importer of record are just some of the things that keep us up at night.”
When leveraging direct-to-patient pathways for dangerous goods, six key considerations include:
- Specialized packaging and labeling: Can the central pharmacy support the DG at their site? Do they have the appropriate packaging to maintain its temperature, as well as the correct UN-compliant packaging and specific hazard labeling? The packaging must protect both the product and anyone who comes into contact with it, especially non-professional end users like patients or caregivers.
- Trained personnel at site and pharmacy/depot: All parties involved—from packaging to courier services—must be certified in DG handling. This includes knowing how to respond to spills or leaks and how to ensure paperwork is completed correctly to avoid legal and safety issues.
- Courier selection and mode of transportation: Specialty couriers can typically handle DG products, package them, and complete the necessary declaration. However, specialty couriers often use commercial flights which can further limit what can be moved on the plane. Integrators use their own network of cargo planes which may be a better option. If a sponsor is still not able to fly a product, as in the case study above, ground transport may be the only option but could mean additional costs and/or timelines for resupplies to be considered. As such, always check if the amount of product being shipped could be considered an acceptable quantity for a flight. Selecting a partner with this critical knowledge will help ensure patients receive their product and that the shipment is compliant, reducing the risk of unexpected costs or delays in resupply.
- Patient communication and handling instructions: Clear, simple instructions must be provided to patients at the site or within the shipper. If the box contains dry ice, patients must know how to handle it without getting burned. They must be informed to keep it away from children and pets and not to contain it in a confined area. Overall, patients need to know how to safely open, use, and store the product, as well as what to do in case of damage or emergency.
- Reverse logistics: The world of clinical supplies is focused on getting drugs to site/patients and avoiding stock outs. What is often overlooked is the strategy of getting the used product back to the site/depot/pharmacy for accountability and reconciliation. With a DG product, this is even more critical – who will complete the DG declaration? If the product was considered a DG at the initial supply, it will also be considered a DG for the returns, even if they are used kits.
- State and local restrictions: In the US, certain states may impose additional limitations. It’s important to evaluate state-specific rules that could impact how and where a DG shipment can be delivered.
Final thoughts
While DtP shipments of dangerous goods in the US present regulatory and logistical hurdles, they are not impossible. With the right partners, proper training and information, along with tackling each piece of the journey with an eye for detail, sponsors can safely bring life-saving therapies directly to patients’ doors—without compromising compliance.
