In 2020, impacts of the COVID-19 pandemic resulted in pausing or halting over 28,000¹ active clinical trials, which has since created a significant study backlog that is expected to take years to alleviate. Many traditional methods of conducting clinical trials became impractical when large populations around the world were restricted to their homes with limited mobility and challenges of the pandemic gave rise to a decentralization trend in clinical trial management.
 
Since the use of central trial sites often burdens study participants with additional transportation, lodging, meals, and dependent care, the prospect of reducing these barriers made decentralized models an attractive way to accelerate patient recruitment and reduce drop-out rates. Opening recruitment to a wider patient pool also increases the diversity of the patient population.
 
What is a “Decentralized” Clinical Trial?
Decentralized clinical trials (DCTs), which can range from at-home to hybrid clinical settings, often involve the use of wearable patient monitoring technologies, patient apps and smart phones to collect and communicate data. Telemedicine, mobile healthcare providers and patients’ personal physicians are also engaged with study participants, as needed. Movement of trial infrastructure to the cloud is typically enabled by online consent, payment and management platforms, allowing more digital collaboration between sponsors, contract research organizations (CROs) and trial sites.
 
The emergence of DCTs has quickly made an impact on the clinical research community, evidenced by the recent formation of the Decentralized Trials & Research Alliance (DTRA), whose mission is to accelerate the adoption of patient-focused, DCTs and research within life sciences and healthcare through education and research. As revealed in DTRA’s stated priorities and initiatives, there are a several barriers to further growth in the adoption of decentralized clinical trials:

• Clinical trial regulations have not kept pace with the decentralized model and the digital tools that support it.
• Trial managers must develop new best practices for delivering investigational medications to patients safely in a DCT environment, with full adherence to compliance study protocols.
• New resources are needed for supporting the reliable application of ancillary products in remote and dispersed settings where biomedical and facility infrastructure is limited.

 
Enter the Flexible Ultracold Chain
As many of today’s advanced investigational medicines are increasingly temperature-sensitive, a critical infrastructure headwind for DCTs is managing the cold chain. Managing ultra-low temperature (ULT) storage has been challenging enough in conducting traditional centralized trials and will become particularly difficult as more studies are managed under decentralized and hybrid models.
 
Technologies and solutions are needed to establish a more flexible ultracold chain of custody for storing a wider range of biogenic treatment assets in a wider range of environments. This includes resources for safe transportation of temperature-sensitive medications and samples to and from residential and remote clinical sites. For example, specially-trained couriers can be equipped with self-contained, self-tracking dewars, cold packs and passive/active refrigeration storage appliances, complete with real-time temperature and GPS tracking in the cloud.
 
Once frozen, biologics are distributed to a myriad of patient, clinical and lab destinations, the cold chain must be maintained and tracked in a DCT scenario just like conventional trials. This can require long-term storage in remote locations that lack the space, electric power, HVAC or network infrastructure normally needed to effectively operate conventional ultra-low freezers. While dry ice will continue to have its place in this cold chain, its thermal instability, handling complications and potential hazards in a decentralized setting may be a challenge where procedural and validation controls are more difficult to implement.
 
An alternative solution for clinical trial storage of temperature-sensitive materials is the use of portable ULT storage appliances, which are now available. These lightweight freezer models use standard residential power outlets and make it easier to deploy, control and monitor reliable ultracold storage of biological assets virtually anywhere, without the handling concerns and limited temperature range of dry ice. By using technology that is intuitive to learn and easy to use, these ULT appliances are ideal in decentralized situations where trained personnel may not be available at the patient location.
 
With the flexibility to program setpoint temperature between -20°C and -86°C, where traditional ULT freezers are too bulky and have special infrastructure needs, these compact units are perfectly suited for disbursed trial locations and a broad range of advanced medicines now entering the drug pipeline. Portable ULT flexibility and mobility could be further enhanced with the combined use/reuse of phase change materials (PCM) and battery backup systems for continuous protection from temperature excursions and potential risk to sample integrity during limited non-powered periods.
 
Enter Cloud-Based ULT Connectivity and Compliance
The emergence of cloud infrastructure to conduct decentralized and hybrid clinical trial operations around the world also offers an effective path for IoT devices to continuously monitor ULT freezer fleets and track the ultracold chain of custody in the field. By equipping ULT freezers with cloud-based monitoring of temperatures via wireless probes and network access points, freezer cabinet temperatures can be monitored and logged from any desktop or smart device web browser. The potential to integrate this freezer data, in the cloud with clinical trial management platforms, creates opportunities for seamless Good Practice compliance and more effective DCT management.
 
Bringing Solutions and Technologies Together
ULT freezer providers can also respond to this decentralization trend by offering flexible leasing and financing terms that align with clinical trial schedules. In addition, flexible shipping options and “white glove” services can ease logistical headaches that clinical trial managers and suppliers must solve when remotely storing advanced investigational therapies and vaccines at ultracold temperatures. Expanded services and packages tailored to the needs of DCT users can assist in the deployment of ULT freezer appliance fleets in more transient and remote applications.
 
All of this can become part of a new and flexible ultracold chain infrastructure that is needed to support the growing industry focus on hybrid and decentralized clinical trials. Fortunately, there are corresponding innovations in ULT storage that can help pave the way toward DCT adoption and are uniquely adaptable to the coming revolution in advanced treatment development.
 
¹Based on data collected from clinicaltrials.gov.