The pharmaceutical industry is moving toward siteless/hybrid clinical trials. Implementing such complex studies requires participation from all members of the supply chain and the support of an experienced service provider that can ensure the development of appropriate protocol designs. 

Patient Centricity and the Growing Interest in Siteless/Hybrid Trials

In virtual or siteless trials, patients do not go to investigator sites to receive treatment. A single large investigator site or multiple sites, with a GMP warehouse for drug storage, offers options for these types of trials. Treatment is delivered and/or administered at each patient’s home through a Direct-To-Patient (DTP) and nursing network protocol, often with the inclusion of a Central Pharmacy component. Hybrid trials comprise investigator sites visited by some patients, combined with treatment of some patients directly in their homes.

Currently, fully siteless and hybrid trials are being conducted in the United States and are feasible in several European countries. More and more countries are exploring the potential for such trials and what regulations are needed to ensure that they are implemented safely.

The demand for siteless/virtual trials is steadily increasing as pharmaceutical companies, doctors and patients recognize the benefits they provide to all parties involved. For patients and their families/caregivers, treatment in the home is much more convenient than having to travel to a hospital, particularly for people suffering severe illnesses, the elderly and children. For pharmaceutical companies, access to patients in remote locations helps address difficulties with patient recruitment, particularly for trials involving rare/orphan diseases. The treatment of patients at their homes, utilizing either a doctor or nursing network, offers more convenience for the patient and may potentially increase patient compliance and retention.

The Supply Chain and Trial Design

In siteless/hybrid DTP/Direct-From-Patient (DFP) clinical trials, trial materials are delivered directly to a patient’s home, and biological samples are picked up with minimal interruption to the patient’s life. The supply chain thus becomes the most vital link between the manufacturer and patient. The clinical logistics provider and nursing network have the greatest interaction with the patient and, like all other parties who are involved in the supply chain, are charged with protecting patient privacy.

The key to a successful siteless/hybrid trial is understanding in advance which aspects of the trial will include patient home care and the establishment of DTP/DFP trial components.

Once a protocol has been established, adding DTP/DFP services means amending and resubmitting the protocol for approval. Although Marken provides DTP services in 51 countries, approval varies by protocol and is often reviewed by individual country health authorities on a per-protocol basis. Past approval is no guarantee that the next trial protocol with a DTP/DFP component will be automatically approved.

In addition, siteless/hybrid trials involve many more interactions and interfaces, so IT solutions must be considered to facilitate seamless communication and transfer of information and materials. For instance, systems must be in place to make data gathering easy for the patient, yet also ensure that all information provided to the central laboratory and pharmaceutical companies is appropriately blinded. Again, this information can only be available to the necessary and appropriate parties and must be blinded to all others.

All members of the supply chain must be involved in the protocol design. Clinical logistics can no longer be treated as a transactional part of the business once the protocol has been established. Questions to be resolved include: Is it possible to establish virtual and/or hybrid trials in the countries of interest? Will there be one mega investigator site? How will the drug be dispersed and distributed? Will the drug be physically stored at the manufacturer site or a GMP depot? How will it be shipped, and how will overages be avoided?

Trials involving DTP/DFP services must also be designed to cover the last mile. How will the drug get to patients, who will be the patient caregivers and how will data be managed so that it is visible for patient delivery but blinded to the pharmaceutical company? What contingency plans are in place if a nurse misses an appointment or if the patient isn’t at home at the agreed upon time? What options exist for risk mitigation if a temperature excursion occurs for a cold storage drug during shipment?

All of these issues must be clarified in detail before the protocol is finalized. As a comprehensive, patient-centered clinical logistics provider, Marken takes a holistic approach to protocol development for siteless/virtual trials. We work closely with our clients and the entire supply chain to ensure that the right questions are asked and adequately answered to design a protocol that provides benefits to the patient and ensures success for the drug maker and investigator. We make sure that appropriate wording is used to enable in-home treatment and consider the potential pitfalls that may occur to plan responses in advance.

The Importance of End-to-End Visibility

In the traditional clinical trial model, patients visit the investigator site. These sites have full control of where and when drug administration or dispensing takes place. In virtual/hybrid trials, many patients receive treatment in the home, and so the level of control is handled remotely. A logistics approach must be adopted that can guarantee the direct delivery of the drug to the patient without any opportunity for adulteration. Chain of custody and documentation control is essential in this setup.

The more virtual a clinical trial, therefore, the greater the need for systems that provide oversight at all times. Immediate access to data is essential to ensure that the right decisions are made quickly for optimal operation and reduced cost.

Marken uses advanced technologies and IT systems that work with clients’ Interactive Response Technologies (IRTs). Marken’s Sentry GPS Tracker technology is used to track and manage our supply chain. With improved supply chain intelligence, we are able to avoid damage or loss of drug products and samples, reduce medication waste and ship much smaller quantities. In addition, Marken offers Viseo, an app that allows patients to track their home deliveries of clinical trial materials and the pickup of their biological specimens via their mobile device or personal computer. Real-time driver and nurse traceability translates into improved patient expectations and DTP/DFP confidence. 

Don’t Forget Return Logistics

Return logistics is challenging for any clinical trial, but even more so in siteless/hybrid trials. In the traditional model, any unused drug product must be collected at the investigator site, accounted for and destroyed. This is contingent upon individual country regulations; some allow shipment of unused product back to the manufacturer, while others do not, and disposal must take place locally with appropriate documentation from the manufacturer.

These issues must be considered for siteless/hybrid trials, in addition to the challenge of collecting materials from many individual patient homes. These materials can include unused drug product and any special drug delivery devices or sharps containers. Dangerous goods training is required for the drivers collecting and transporting these materials.

Experience Matters

As the clinical supply chain subsidiary of United Parcel Service (UPS), Marken is committed to continuous enhancements of its service offerings for all clinical trials. The company’s new hybrid logistics service leverages its position as a wholly owned subsidiary of UPS, providing an enhanced network, superior visibility and the dedicated customer care that has always been a hallmark of Marken’s services.

Our commitment to quality underlies all of these activities. Marken has designed our quality system to mimic the high-performance quality systems of our pharmaceutical customers. This system influences everything we do and ensures that we provide strong support for our customer through the last mile. We have taken quality to the next level with the introduction of a new certification program for our drivers. No other logistics provider has a global program like this in place. It is but one example of Marken’s commitment to being the supply chain partner of choice for the clinical trials market.

While there may be challenges to conducting siteless/hybrid trials, the benefits can outweigh the considerations — as long as the challenges are understood and perhaps avoided from the start. An experienced clinical logistics provider like Marken can make all the difference in ensuring a successful outcome.

We have been conducting DTP trials since 2012 and have adapted systems and processes based on our experiences with different vendors and pharmaceutical companies. No other company provides DTP/DFP services in 51 countries, an opportunity to integrate home health nursing services and an extensive global depot network offering on-time delivery to patient homes and the opportunity for late-stage customization. In our exclusive nursing network, the nurse has the ability to become the driver, which optimizes flow and reduces costs while providing better patient support.

The industry is moving toward siteless/hybrid trials. Marken has recently seen a steady increase in demand for our DTP services. From 2016 to 2017, the number of DTP trials and the volume of patients participating in DTP trials supported by Marken tripled.

The unique requirements of siteless/virtual trials need careful attention to ensure the development of suitable protocols and their ultimate success. Marken offers workshops with ideas, lessons learned and the factors that must be considered when designing siteless/hybrid trials. We outline the steps and process from initial discussions with all supply chain partners through protocol design, ensuring that patient needs are addressed and no steps are missed that could create problems during execution of their clinical trials. More progress and research are needed so that further benefits may continue to crystalize.

Personalized Solutions

Marken prides itself on creating solutions that are personalized for the pharmaceutical industry and for each of our clients. No other clinical logistics provider offers the range of services and global support for traditional and siteless trials that Marken provides. We are always seeking new opportunities to create more and better services for our clients.

The world is moving toward siteless trials, a trend we recognized years ago and for which we have been preparing ever since. We combine our existing knowledge and expertise with a drive for continuous improvement. This strategy is clearly evinced by our many recent innovations: our nursing network, electronic solutions for data gathering, our DTP White Book Industry Guide, the development of additional interactive response technologies and the addition of a home healthcare nursing network, with much more planned for the future.