Decentralized clinical trials (DCTs) have ramped up since the advent of the pandemic, and in the process, drug development professionals have learned a number of important lessons. Outsourcing-Pharma recently spoke with Isaac Rodriguez-Chavez, senior vice president of scientific and clinical affairs with ICON, about the rapid evolution of DCTs and the role that technological advancement has played.
OSP: Could you please share your perspective on the evolution of decentralized trials in the years leading up to the pandemic?
IRC: There have been changes in connection to the evolution of decentralized clinical trials. In the years that happened before the pandemic, before COVID-19, and since the early 2000s, there was a low frequency of DCTs occurring, as the industry really didn't realize or understand the importance of and the value that decentralized clinical trials would add to the entire clinical research enterprise. This was happening in an episodic manner, not really much in the public eye, and it was really happening on a limited basis and in a few therapeutic areas.
The industry has been classically risk-averse, and that played a factor. Thus, traditional trials have been the gold standard for many, many years to assess the safety and efficacy of investigational medical products.
There was not a major need, if you will, to implement components of decentralization and conduct trials remotely, and the understanding wasn’t there. There was a lack of knowledge about decentralized clinical trials and how to operationalize DCTs and DCT approaches. There was a lack of a regulatory and legal framework to deploy decentralized clinical trials across different jurisdictions, across multiple countries, across multiple regions in the country, in the world, and so there was a very different scenario in the clinical research space compared to what we have gone through during COVID.
All of those factors really played a role in the evolution of DCTs leading up to the pandemic, and then the pandemic came. There was a need created to rescue the traditional clinical investigations, and the way to do it was by implementing DCT solutions by conducting all or some of these clinical-related activities remotely, so there was a surge of requests from the regulatory standpoint to change protocols to amend protocols to rescue the traditional clinical investigations. That is what happened at the very beginning of the pandemic, and whether or not, the protocols for traditional trials needed to be amended. That was a second point and second question.
Regulatory agencies provided the clarity for that. The FDA [US Food and Drug Administration] provided the information and guidance on when the protocol needed to be amended for a traditional clinical investigation and when it wouldn't. Many of these protocols did end up being amended and many of them and components of decentralization to do activities remotely later on.
After 2 1/2 years of the COVID-19 pandemic, the industry is absorbing and adapting, and understanding more the value proposition of decentralized clinical trials. We’re still in a transition phase. We are still in the adoption phase, and we're still learning about DCTs as an overall enterprise and field.
However, nowadays there are use cases and there is more understanding in terms of proactively designing DCTs—not necessarily to rescue traditional clinical investigations but understanding that this is a solution that the industry and the space of clinical research are going through a historical transformation that was catalyzed by COVID-19, but it is here to stay.
That transformation is really permanent and it brings many important benefits to implementing DCTs. Some of those benefits include increasing efficiencies in all the steps of a clinical trial so that the time to market to assess the safety and efficacy of an investigation on a medical product is shortened, so efficiency is important.
Equally important is the inclusion of the patient's voice early on during the design stage to understand what is feasible and realistic and what is not feasible and realistic. These are deployed in communities, cities, towns, and rural communities across the world, and they leverage the local healthcare infrastructure. We need to understand what is possible and what is not possible in all of this; the way to do it is by listening to the patients and understanding what they want from early on.
The last piece to this: another value proposition of DCTs is the overall optimizing efficiencies of the investigation, the leveraging of the communities, and the leveraging of the DCTs with the healthcare infrastructure and the participant voice early on during the design to assess feasibility and reality of this being deployed in communities importantly and critically, is diversity.
The inclusion of diverse populations across geographies is a value proposition that is not just because it's a DCT that is going to be deployed, is because there has to be a plan. DCTs really are all about collaboration between multiple organizations and entities that are key to deploying these trials in a feasible and operationalized fashion.
OSP: Could you talk about what sorts of innovations and trial technology have helped in driving decentralized clinical trial success?
IRC: We are in a very exciting time in terms of innovation and technology. Clearly, technology is the enabler of the implementation of DCTs in the field in multiple geographies and globally there is increased development of and testing of digital health technologies in the world, something that is unprecedented, something that is really amazing.
There is the diversification of digital health platforms with capabilities that include interoperability, multi-functionality, and integration. More than ever before, the technology that we have right now is improved compared to the technology that we had three or five years ago. There is more overall acceptance of the utilization of technology, ecosystems, or architectures to design and conduct DCT-related activities such as telehealth, home health services, direct-to-participant shipment of investigation and medical products, remote training, and so on and so forth. These are critical and improvements are happening as we speak.
When we look at the current trends connected to DCTs and technology and different sectors that are connected to DCTs—when we look at the compound annual growth rate or the AGR of key sectors connected to DCTs, for DCTs alone it is estimated between 6.7% to 14.8% during the period of 2021 to 2027. The CAGR for digital health technologies, the use of digital sensors, and digital wearable devices are estimated to grow at a CAGR of 26.9% from 2022 to 2030.
Digital health technologies are an enabler of DCTs—the use of all these sensors to have digital endpoints (which is the big search in the clinical research space), software as a medical device (another sector connected to DCTs)—is expected to grow 15.6% from 2022 to 2030. Another sector that is connected to DCTs, digital therapeutic devices, is expected to grow 41.3% from 2021 to 2028. These trends based on CAGR tell you how exponential growth is happening for DCTs and the enablers of DCTs.
We can also offer participants to follow them longitudinally and have a more holistic understanding of not only clinical research per outcomes and endpoints but also utilization of the standard healthcare system, something that participants of DCTs really appreciate because we are individuals with one health journey in life. We are not split between the standard healthcare system and the clinical research enterprise.
All these key sectors connected to DCTs are posed to grow from here until 2028 or 2030 and the growth is solid. This again is a transformation that is happening. Because of changes and improvements in technology, there is exponential growth and diversification of the technology and utilization of technologies in ways never done before—for example, the use of digital composite novel endpoints; I can measure your heart rate and I can measure your level of activity in the day.
Those are the kind of things happening in technology and innovation that are supporting DCTs and the transformation that we are experiencing is going beyond COVID-19. Strategically, when we lower the burden of individuals initially enrolled in the clinical investigation, participants now in the DCT remain engaged in the clinical investigation.
The DCTs offer unprecedented opportunities to capture information outside of the clinical research sites in a more holistic way, in a more continuous way, and in real-time, and all of this happens because of the use of technologies that represent the architecture that is designed, that is tested before the trial is deployed and that is critical. The use of digital health technologies (the regulatory term used for all of these sensors and wearables that we are discussing) is critical because they are connected to the specific digital endpoints that measure health outcomes per protocol in a decentralized clinical trial.
OSP: Can you share any advice for trial teams that might be new to the DCT concept who are looking to make the switch about technology that can help streamline the transition?
IRC: My suggestion is to take a step-wise approach, especially when you are new and you're trying to make the transition. There is a spectrum from hybrid to fully decentralized clinical trials. Hybrids are those in which some activities are conducted remotely from the investigator. In fully decentralized clinical trials, all activities are conducted remotely. If you are a new organization trying to implement the DCTs, it makes sense to test the space by implementing a hybrid decentralized approach—increasing the number of DCT components that will be deployed remotely and building sequentially upon your own experience.
I started designing with a final end in mind to carefully select the technology needed in the DCT that is going to be conducted, and not just in one trial. It's important to think about the technology architecture that will be meeting the needs of that specific organization that is entering into the DCT space and evidently testing digital health technologies. That means the sensors and wearables that will be utilized in that clinical investigation in that DCT for verification validation can be analytical and clinical validation. The usability before all of these wearables are deployed in a DCT is equally important.
It's a stepwise approach, as I said, in which hybrid services may be recommended to be implemented first, then go with their full DCT when possible--keeping the scientific rigor, the feasibility of operationalizing the trial to check in reality, and deploying these trials with regulatory intelligence in mind, and with knowledge on what can and cannot be done across multiple geographies, regulatory and legal intelligence.