Meeting the Challenge of Patient-Centered Clinical Trials

Clinical trials are the proving ground for any new pharmaceutical. On average, these trials take approximately seven and a half years to complete (1). For manufacturers, who can spend anywhere from $161 million to $2 billion to bring a new drug to market, the returns from investing in this important work have been diminishing. Patient recruitment and retention, which cost $2.3 billion per year (1), have become a major challenge. Typically, one out of every four patients drops out of the average clinical trial. In addition, problems with recruitment and retention can often result in longer and more expensive trials, less statistically valid results, and poor morale among clinical staff, healthcare providers, and patients (2). 

As the population continues to age and pharmaceutical manufacturers shift their focus to chronic and degenerative disease research (1), resolving patient recruitment and retention problems has become a key priority. Seven years ago, armed with online technology, advances in cloud computing, and wireless communication tools, pharmaceutical companies that include Pfizer and Sanofi turned the traditional clinical trial model on its head, bringing the trial direct to the patient (3). 

In this direct-to-patient (DTP) approach, trials follow the same blinded protocols, but patients receive medication in their homes, so they do not have to travel to medical facilities or wait for services. For pediatric patients and the elderly, the convenience of DTP trials can determine whether they choose to remain in the clinical study or not. 

The DTP approach has also been shown to reduce overall costs. Research suggests that it can help reduce costs by up to 16% in Phase I trials, by up to 22% in Phase II, 17% in Phase III, and by up to 13% in Phase IV (1). 

According to a 2017 survey by Arena International, DTP clinical trials are growing rapidly, and should increase from 24% of all clinical trials in 2017 to 33% by the middle of 2019 (4). Table I shows one logistics services provider’s top DTP destinations globally, while Figure 1 shows its volume of DTP shipments from March 2017 to 2018. 

Figure courtesy of Michael Sweeney, World Courier.

Coordinating drug and lab sample deliveries 

For cold-chain logistics specialists, the DTP model poses many additional challenges, especially since precision medicine also requires regular patient laboratory tests. Scheduling lab sample drop-offs and pickups adds to the challenges of delivering patient doses.  

Other new changes stem from going “off the grid,” with drivers leaving the main highways and navigating local streets and residential locations, and learning how to interface most effectively with healthcare providers and patients, without compromising patient privacy. 

The most basic challenge, ensuring that treatments remain safe and viable, has also become more pronounced, since today’s clinical trials increasingly involve novel therapies such as immunogenic, cell, and gene therapies. 

Today, a typical pharmaceutical manufacturer may take a variety of approaches to clinical trials. Some companies are working on developing end-to-end DTP clinical trials. In May 2018, exemplifying this trend, Science 37 and UCB Parma launched a partnership to use Science 37’s MetaSite approach and cloud-based Network Oriented Research Assistant (NORA) network to develop site-less clinical trials (5). 

In other cases, within the same trial, different approaches may be used with different portions or phases, with some being run traditionally, and others using the DTP model. However, as the DTP approach becomes more important to the industry, logistics companies are stepping up their services to support this growing business. 

In March 2018, Marken, now part of UPS, launched a service that will allow nurses to drop off clinical trial samples from patients at any UPS store location. The company already offers DTP services in 51 countries. 

World Courier, part of AmerisourceBergen, began to expand its involvement in DTP clinical trials back in 2012, and established a partnership with the Medical Research Network (MRN) in 2015. The alliance aims to create a more highly integrated model for community-based clinical trials that increases patient recruitment and retention. 

The company is currently revamping its global transportation management system worldwide, a process that has involved a lot of localized DTP work, explains Michael Sweeney, senior director of patient-centric logistics at World Courier. Sweeney was formerly director of global service development, with a broader concentration on high touch personalized supply chain services, including cell and gene therapy. His role shifted to a steady focus on DTP a few months ago, reflecting the increased importance of the model in the industry and World Courier’s business plans. Sweeney shared some insights into the overall market, and World Courier’s activities, with BioPharm International. 

Explosive growth since 2014 

BioPharm: How long and how extensively have you been working with DTP clinical trials? 

Sweeney: We’ve been supporting these types of trials for a number of years, but demand for DTP has dramatically increased since 2014. In fact, it more than doubled between 2015 and 2016 alone.  

Since 2012, we have handled DTP shipping for 424 customers in 52 countries involving 386 different trial protocols. We also ship DTP for expanded access and compassionate use products. This means that we handle hundreds of DTP shipments weekly. 

There is no ‘typical’ client for DTP work. Customers include traditional Big Pharma companies, as well as contract research organizations (CROs), clinical trial home care nursing firms, contract development and manufacturing organizations (CDMOs), clinical packaging service companies, central laboratories, and small innovator biotech companies. 

BioPharm: How does the relationship work with home care nursing providers such as MRN? 

Sweeney: Collaborations, like ours with MRN, are designed to simplify patient participation in clinical trials. A qualified nurse visits the patient in his or her home and performs all medically necessary procedures required by the clinical trial, which may include infusion and collecting blood or urine samples. World Courier delivers or picks up related materials to and from the patient’s home and the clinical trial site. We have created detailed standard operating procedures to ensure compliance with the regulations, patient confidentiality, and protocol support. 

BioPharm: What are some new technologies that can enable the DTP approach to operate most effectively? 

Sweeney: One innovation that we offer through a collaboration with our sister company, Cubixx Solutions, is CubixxCT, a small access-controlled refrigerator that stores drug products at an optimal 2–8 °C temperature in the patient’s home. It tracks usage, provides reports to researchers, and enables real-time temperature monitoring and PIN-controlled access. Plus, it eliminates the need for frequent deliveries where relevant and ensures the product is available when medical staff arrive to administer it. 

In addition, World Courier’s Bio-STAR system provides real-time access to protocols and special handling instructions, helping to anticipate and prevent costly shipping issues problems that can come up during any clinical trial. 

BioPharm: Does your new job title reflect any change within the company and the industry? 

Sweeney: As healthcare moves towards a patient-centric approach and clinical trials expand in growing markets, the DTP model is becoming increasingly popular. In March, World Courier launched international personalized supply chain teams that support three specialty areas, all of which experienced double-digit growth, that include DTP. The technical experts work directly with our customers, offering a combination of project management and customer service to deliver a service tailored to specific requirements and, ultimately, connect patients with the vital treatments they need. 

Planning for complexity 

BioPharm: What are the most important aspects of planning a DTP clinical trial logistics program? 

Sweeney: The most important part is getting the initial plan right, and making sure that it is broad enough. The planning process, and the plan, should involve everyone who will be involved in the project. It should spell out clearly the scope of work, the resources that will be needed, when the project is expected to be completed, and, generally, ensure that everything within the plan ties back into (and works in) the real world. 

Planning is extremely important in dealing with complexities. In some cases, patients are just receiving medications. In other cases, their drawn specimens will need to be delivered to labs. This requires careful coordination and timing. 

Quality control and assurance are also paramount, particularly temperature monitoring. Basics need to be established very early on (e.g., in case of an emergency, who must be informed, and is there a contingency plan in place if drug safety is compromised?) 

There is also the challenge of randomizing the supply, interfacing with nurses, and handling the logistics of specimen testing at the central lab. All of these factors must be taken into account in the original plan. 

BioPharm: How has the timeframe required for clinical trial logistics changed under this new DTP model? 

Sweeney: We’re interfacing directly with patients at home in some cases, and also often with nursing companies. And we’re working on just-in-time delivery. In the past, we were used to a broader timeframe. Now, nurses are often prepping patients while deliveries are on the way. Drug quality verification is extremely important, and verifying temperature results to ensure that the drug is safe before the patient receives it.  

BioPharm: How has your company changed its approach to transportation management? 

Sweeney: We’ve been developing a new platform, corporate-wide, for some time to replace our previous transportation management programs worldwide. This platform encompasses everything from local DTP projects to highly complex international projects. 

We began its initial deployment in Canada. Sample shipments were handled within certain market segments, and, eventually, we plan to use this approach throughout the world as we assess timelines and functions. So, right now, we are at Release 1, and are planning to add countries and broaden the deployment scope in the weeks and months ahead.

Global trials use DTP approach 

BioPharm: Do you see global clinical trials moving to a DTP model? 

Sweeney: They are already being run that way in some cases, for example, in projects where we have expanded access to compassionate use drugs. We are seeing a greater degree of centralization of distribution and dispensing, at least, if legally permissible and licenses allow for central dispensing of drugs across borders. This is not always the case, however, and the law can even vary within the same country (e.g., from state to state). 

BioPharm: What basic technology innovations are driving improvements to DTP, and what new technology platforms is your company currently using? 

Sweeney: The biggest shift is that we are using global positioning systems (GPS) and Bluetooth Low Energy (BLE) technologies. These approaches have proven to be very helpful in managing the supply chain, to monitor shipments at each point in the supply chain, from when products are placed in the storage facility or pharmacy, to when they are picked up by a driver, and, finally, when they are delivered to the nurse at the patient’s home. 

We have already piloted use of Bluetooth technology at various checkpoints in transit within DTP. We are using it to ensure that there are no temperature control issues during product shipment, and then we push the data from Bluetooth out to the cloud, and results are available before and after delivery. 

Occasionally we can run into issues when, say, a large pharma company has already validated a temperature monitoring product and process that does not consider newer technologies. It can be a challenge to get the buy-in or any necessary validation completed in order to take advantage of these innovative solutions, but we continue to make headway with many pharmaceutical companies. 

BioPharm: Are there any issues using advanced monitoring technologies with air transportation?  Don’t monitoring devices have to be shut off during transit? 

Sweeney: We have an in-house team that vets and tests various technologies, whether Bluetooth and GPS or GSM (Global System for Mobile communication). They examine different and often very specific use cases from customers, while also considering our internal challenges. We must be able to confirm that delivery expectations are achievable as more and more information is available instantaneously. There are other issues to address as well. For instance, do the solutions meet requirements set by the US Code of Federal Regulations (CFR) (i.e., are they 21 CFR Part 11 compliant?)

It is crucial to use monitoring technologies that allow for full audit capability. Basically, within DTP, we need results that indicate whether the drug is useable or not. If it is all packaged and a traditional temperature monitor is inside the package, we won’t know there is a problem until just before or upon delivery. We are working to change that, and airlines are working closely with some of these device manufacturers to consider allowing data recording, for example, using wireless networks on board flights.

The lack of in-flight visibility does not have a major impact on what we do, although it would help us identify issues earlier and allow for planning corrective actions sooner. Once a plane lands, we are then able to enact the most impactful contingencies. Location coordinates allow us to ensure the shipment reached the intended destination, which brings peace of mind to everyone involved. For flights that involve cell- and gene- therapy shipments, which are now routine, GPS monitoring technology has already become a standard.

BioPharm: What were the challenges at the very earliest stages of DTP work, and how have they changed since then?

Sweeney: Our work in DTP began organically quite a while ago. Our efforts to track the activity go back to 2012. However, prior to that, we found that investigator site nurses were going way beyond the call of duty. For example, after a long day at the hospital, they would sometimes take patient specimens home with them. We began making pickups from their residences. Site nurses also went to patient homes in cases that required, and we began to support them in these activities years ago.

With DTP today, partnerships are extremely important. MRN is one example for us, and another is our connection with Cubixx Solutions. Originally, Cubixx’s radio-frequency identification (RFID)-enabled technology was used in larger hospital and clinic fridges. Now, smaller medical grade refrigerators are being used at patients’ homes in DTP projects.

BioPharm: Are all the big pharma companies using the DTP approach for clinical trials?

Sweeney: Some big pharma companies haven’t converted fully to DTP, others are supporting the concept at different levels. There is a lot of interest, but a significant amount of diligence and risk assessment is required. The approach requires resourcing, researching of industry trends and partnerships.

With growth comes the need to be able to support a wider array of therapeutics. Growth is being seen in all therapeutic areas but particularly where key factors include age of patient, site location, degree of patient mobility, and the time required for treatment and transport to and from site centers. The DTP approach eliminates potential access barriers for many patients.

BioPharm: What kind of training is needed to get logistics professionals up to speed on the new model?

Sweeney: Details that might seem small have become very important, such as training drivers to work in residential neighborhoods (Figure 2), make a big difference. For example, drivers cannot park for too long outside any one patient’s home, and they need to consider interactions with patients and nurses quite carefully to ensure that patient confidentiality and data privacy are protected.

Figure 2. Drivers handling direct-to-patient deliveries must be trained to protect patient data security [Figure 2 is courtesy of World Courier].

References

1. A. Serttraya et al., Examination of Clinical Trial Costs and Barriers for Drug Development, July 25, 2014, aspe.hhs.gov, Eastern Research Group report.

2. Applied Clinical Trials editors, “Subject Recruitment and Retention: Barriers to Success,” Appliedclinicaltrials.com, April 1, 2004.

3. Z.Syed, “Is the DTC Model the Future of Clinical Trials,” MedCityNews.com, December 23, 2016.

4. Arena International Research, “Assessing the current and Future State of Clinical Trial Supplies,” clinicaltrialsarena.com, March 8, 2017.

5. Press Release, “Science 37 Partners with UCP to Fundamentall Change the Clinical Trials Ecosystem,” Businesswire.com, May 3, 2018.

Article Details

BioPharm International
Vol. 31, No. 6
June 2018
Pages: 38, 40–41, 44–45

Citation

When referring to this article, please cite it as A. Shanley, "Meeting the Challenge of Patient-Centered Clinical Trials," BioPharm International 31 (6) 2018.