Jonathan Cotliar

The dramatic increase in the use of decentralized clinical trials (DCT) tools and methodologies since the beginning of the COVID-19 pandemic has produced a welcome sea change in clinical trials operations, and one that is certain to continue way beyond the pandemic. The conventional clinical trials model, which caters to investigators at physical sites, is slow, expensive and outdated; the contender is a set of approaches focused on patient’s need, and this long overdue pivot is helping to usher in a more agile development model—one that is less burdensome for patients and more efficient for biopharmaceutical sponsors. But incorporating DCT technologies and methodologies into clinical research is not a simple plug-and-play exercise, as including these tools adds another layer to an already complex process. To help mitigate this complexity, trial sponsors and CROs would be well-served to consider several key factors when designing and conducting decentralized clinical trials.

As the COVID-19 pandemic suddenly made traditional clinical research sites unfeasible for most in-person activities, DCT adoption grew substantially. According to an Industry Standard Research (ISR) survey of biopharmaceutical executives, commissioned by Science 37, more than 60% reported that, within the past year, their company had conducted a clinical trial that included at least some DCT components; with more than 80% indicating that they plan to conduct a trial with DCT components in the coming year. In addition, more than 60% of executives acknowledged that their company does not have the internal capabilities to operationalize any component of a decentralized clinical trial, a finding that suggests increased outsourcing moving forward.

While outsourcing clinical development activities is certainly not a new phenomenon, each additional element and vendor adds cost, complexity and time to an already inefficient and costly model. Perhaps most costly in the long-term, however, is the failure of incremental, bolt-on solutions to improve long-term reliable access to qualified investigators and eligible patients. Therefore, a requisite for agile clinical trials is an Operating System, capable of orchestrating activity, whether on-or-off premises, that enables access for patients and providers.

Activating an Operating System requires a proactive strategy with clear expectations and metrics.

While the biopharmaceutical industry responded to the pandemic by retrofitting existing clinical trials with decentralized elements to minimize disruption—an effort that largely validated DCT principles—many operational efficiencies will have been left on the table because these initial, isolated efforts to rescue traditional trials on the fly likely were not following a central, scalable, measurable strategy for incorporating DCT in enterprise-wide programs.

By adopting a proactive approach, however, sponsors can harness multiple investigator and patient networks to reduce site start-up times from months to mere weeks, and then utilize a centralized team of remote coordinators and mobile healthcare providers to maximize trial efficiency and enrich the patient experience. Indeed, increased patient engagement is the main advantage of a decentralized trial, and actions such as gathering patient input during the development process and using patient-reported outcomes as endpoints all work to increase patient satisfaction and retention.

According to the Science 37 survey, only 4% of biopharma executives said their company had conducted a fully decentralized trial in the past year, and only one in six respondents said they intended to do one in the coming year. Clearly, a fully decentralized trial is not always feasible for certain conditions or studies, so developers should first consider which elements can be decentralized and which elements might be more appropriate for site-based visits. Regardless of the answers, the most important thing to remember is that DCT is not an all-or-nothing, one-size-fit-all approach. A trial could be conducted, for example, using telemedicine to monitor study patients remotely, yet the same study may also include traditional site visits for things such as advanced imaging which may be more conducive to in-person review. Similarly, a trial could potentially have two arms; a traditional, site-based arm, and another, DCT-enabled arm that offers participation without geographical restrictions.

Although decentralized clinical trial tools and methodologies are not new ideas, their initially slow pace of adoption before the pandemic can be attributed in part to uncertainty around gaining regulatory support for non-traditional study designs. Indeed, in ranking a list of five factors for their organizations to consider when determining whether to decentralize parts of a clinical trials, respondents to the Science 37 survey cited “Quality of Data” and “Regulatory/Compliance Risk” as the two most important factors. But based on what we’ve seen in the regulatory landscape over the past year, concerns about acceptance and compliance for novel trial designs and methods should dissipate over time.

From the early days of the pandemic, global regulators recognized the unprecedented disruption to the clinical research apparatus. In the U.S., the Food and Drug Administration (FDA) issued a proactive guidance to industry1 for trial continuity that encouraged the use of “alternative methods” for assessments that would be sufficient to assure the safety of trial participants. Similarly, the European Medicines Agency (EMA) issued guidance in early 2020 (updated three times since) that included suggestions such as deploying remote monitoring and home nurses to ensure patient safety and safeguard data quality.

Researchers from the FDA’s Oncology Center for Excellence (OCE) later reflected on the agency’s guidance in a JAMA Oncology article2, acknowledging that the increased uptake of digital platforms “adds to the impetus to decentralize clinical trials,” and encouraging sponsors to use such tools to support remote enrollment of more diverse patient populations. It’s important to note that while regulators are generally quite supportive of decentralized clinical trial activities, they nonetheless still encourage biopharma developers to engage with regulatory agencies early and often to ensure compliance for oversight, data collection, and safety.

4. Patient centricity takes more than technology

A key benefit of DCTs is the ability to place the needs of the patient at front and center. While such an approach is only made possible because of the technology, the deployment of the tech alone does not equate to patient centricity.

Patient centricity in clinical trials means having early and continuous dialogue with patients, caregivers and advocates to learn and understand individual patients’ journeys, their trial experiences, their preferences for visits and activities, and any specific challenges they encounter. Are they willing and able to use healthcare devices and apps in their day-to-day life? Will they want to see a physician in-person? Who will answer their questions about the treatment and the trial technology?

The DCT technology platform underpins every element of the clinical trial; it operationalizes each component, harmonizes all the data, and orchestrates activities and interactions between the platform and telehealth investigators, remote coordinators, mobile healthcare providers, patient communities and connected devices. However, the level of patient centricity in a DCT is determined, not by the technology or the data, but by the actions and interactions of humans.

5. Don’t ignore traditional sites…help them out

As an agile approach to clinical development comes into focus, sponsors looking to conduct trials using a combination of physical sites and remote sites must offer training, support and ongoing communication to those physical sites. According to a November 2020 report3 from the Tufts Center for the Study of Drug Development, more than 60% of investigators were unfamiliar with remote trial processes and solutions prior to the pandemic—this is a large number of important staff who will likely require time-consuming, individualized training. Although such resource-heavy, study-specific training was/is certainly appropriate for continuity during the pandemic, converting traditional study sites to virtual study sites reactively adds significant time and cost to the clinical trial cycle time and cannot be considered a feasible long-term strategy. A proactive DCT strategy, on the other hand, would have sponsors clearly communicating with sites about how the trial will operate, what technologies will be involved, what training they can expect, and what support services will be provided throughout the study.

As no single development model will be sufficient for the clinical research ecosystem of the future, nearly every study will be highly individualized, with each requiring a unique configuration of technologies and networks. And with a wide majority of biopharma companies planning to conduct a trial with at least some DCT components in the coming year, our study indicates that the industry is increasingly understanding the potential of DCT to accelerate timelines and make trial participation less burdensome for patients and investigators. But the study also finds that most of these companies lack the internal capability and expertise to operationalize any DCT elements at all.

Clearly, they’ll need help. They’ll need help creating a proactive DCT strategy. They’ll need help designing an agile clinical trial. They’ll need help navigating the ever-changing regulatory framework. And in requiring quality more than anything, biopharma companies will also need coordinated expertise and a technology-led operating system to implement DTC technologies and methods effectively in the connected, patient-centered clinical research ecosystem of tomorrow.

is the Chief Medical Officer for Science 37

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-guidance-conduct-clinical-trials-medical-products-during-covid-19-public-health-emergency

https://jamanetwork.com/journals/jamaoncology/fullarticle/2771201

https://static1.squarespace.com/static/5a9eb0c8e2ccd1158288d8dc/t/5fad523d54d7bd32baabc63c/1605194301251/Nov+12%2C+2020+-+Remote+clinical+trials+-+Press+Release.pdf

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