Introducing the decentralized trial format to a clinical research organization is much more complicated than flipping a switch from “onsite” to “offsite.” According to Katherine Vandebelt, global vice president of clinical innovation for Oracle Health Sciences, the process requires the right technology, the right mindset, and more to achieve a successful transition.
OSP: Could you please provide an overview of the rise of DCTs, before COVID-19 hit?
KV: Prior to the pandemic, most companies treated decentralized trials as pilots or proofs-of-concept. They may have added some decentralized components to traditional trials or even in a few instances and conditions undertaken trials that were largely decentralized.
However, dipping into this approach was largely experimental. With established procedures providing a level of comfort and familiarity – and regulatory acceptance – there was no sense of urgency in making decentralized components more mainstream.
OSP: Then, what about after the pandemic started?
KV: The pandemic created huge challenges for conducting traditional clinical trials, and with the urgency surrounding COVID-19 vaccines and treatments, it highlighted the need for and accelerated the move to decentralized trials. The industry pivoted very quickly to adopt new approaches, such as decentralized clinical trial methods, to keep clinical research going in these unprecedented times.
According to research conducted by Oracle and Informa in 2020, 76% of clinical trial teams say they have sped up the use of decentralized trials methods during the pandemic. Sponsors took varying approaches to implementing these new models but some of the most common steps taken by respondents to our survey were the adoption of patient-facing technologies or alternatives (64%) and protocol redesign (63%), followed by the adoption of investigator-facing technologies or alternatives (53%).
To illustrate this, we’ve seen sponsors employ more and more technology for remote data collection, and adopt new technology platforms to design and manage decentralized trials, while also employing advanced techniques to analyze all the resulting data.
OSP: Could you please share some of the barriers sites and sponsors typically encounter when looking to increase DCT adoption in their operations?
KV: Perhaps the biggest barrier to decentralized trials has been the status quo mindset. With established procedures providing a level of comfort, familiarity, and regulatory acceptance —there was no real sense of urgency to make decentralized trials more mainstream prior to the pandemic. Another challenge overall has been the reluctance by the industry to incorporate new approaches and innovations or modify operational practices. But we are slowly seeing a shift.
From a technological standpoint, the increase of patient-facing technology (i.e. electronic informed consent, known as eConsent, electronic patient-reported outcome—ePro—and wearables) has made decentralized trials a real option for sponsors and CROs over the past couple of years. It also enables sponsors and investigators to have a richer and more complete picture of patients than is possible in a traditional clinical trial.
However, the amount of data generated in trials today is far more information than humans can process, and it is also much more complex. In our research respondents cited ensuring data reliability and quality (50%) and data collection (45%) as key barriers to implementing decentralized models.
Luckily, great strides in the areas of artificial intelligence (AI), and machine learning have been applied to automate many data-heavy processes to lessen the pressure. AI and machine learning have two massive advantages – they can process data faster and they can identify patterns and trends that humans can’t see. This will ideally lead to a more accurate and detailed view of safety and how patients are responding in trials – which can lead to faster time to market and better treatments.
OSP: Could you please share some insight as to what types of changes in mindset need to happen in order to make the change to greater DCT adoption possible? Do these challenges related to changing over to DCT look different to executives in the corner office than they would to trial admins, and to CRA-level staff?
KV: The pandemic forced the entire life sciences industry – which has been notoriously slow to innovate – to take a hard look and determine how to break the barriers that were standing in the way of innovation.
In order to make this happen, everyone – from chief executives to chief science officers and chief medical officers within all organizations involved -- had to adjust their mindset. The pandemic provided a catalyst for new ways of working. It moved everyone — sponsors, sites, and regulators — to embrace, use, test, and implement many new ideas, approaches, and technology in clinical trials.
Watching the industry come together to keep the vaccine clinical research moving has been one of the high points of the last 18 months. There has been tremendous support to keep this forward momentum and not fall back into “the old ways” of conducting clinical trials when the pandemic is over.
The duration of the pandemic has been long and many of the initial growing pains have been surpassed. There remains a lot of optimism for change.
OSP: What type of investment—in new technology, training, etc.—should an organization expect when increasing DCT adoption?
KV: One of the most critical elements of a decentralized trial is a unified eClinical platform that can maintain a single data set that feeds a variety of functions. In such an environment, studies are only built once, data is only entered one time, and everything is available in one place. Staff no longer need to waste time entering data into multiple systems, which not only reduces the risk of human error but frees them to focus on more important work.
A unified platform, like Oracle Health Sciences Clinical One, is capable of harmonizing the vast volume of data collected from disparate sources such as patient-worn sensors. In our research with Informa, half of the respondents reported that effectively tracking all that data is one of their biggest concerns with decentralized trials. A unified platform brings data together into a coherent view and across the different functions of the trial – again, streamlining operations and enabling staff to focus on high-value tasks.
For example, with Clinical One, data collection activity happens in the same environment as randomization and trial supply management activity, so sites can randomize, dispense therapies, and collect patient data in one place, which makes their job a lot easier.
Sponsors must also seek out new data sources like mHealth devices that collect data from patients remotely, often automatically. These types of patient-worn sensors are available to measure everything from heart rate, blood glucose levels, electrical activity in the brain, activity level, and sleep.
Our study found nearly two-thirds of those surveyed have implemented remote data collection in their trials – with the bulk coming from patient apps, ePRO, and wearable devices. More than half the respondents reported they use, or will introduce, wearable devices within 18 months.
OSP: What regulatory considerations should trial teams be aware of regarding DCTs?
KV: The willingness of regulators to be flexible in the face of the pandemic enabled study teams to adopt many new technologies and obtain approvals. As the situation changed quickly, regulators also moved with speed to issue guidance to enable sponsors to introduce new approaches and protocols for trials.
A clear example of this is the free FDA MyStudies app for investigators to obtain informed consent securely from patients for eligible clinical trials when face-to-face contact is not possible or practical due to COVID-19 control measures. This pivot enabled sponsors to conduct clinical trials in a safe manner, and at an accelerated pace to develop the COVID-19 vaccines.
Yet, for all the effort and flexibility that was demonstrated, half the respondents to our survey still feel that “regulatory issues are holding them back” from developing trials that have more virtual elements.
At the same time, the pandemic has yielded some insights on how to create better regulations around decentralized trials, so a deliberate effort to create new or revised regulations covering decentralized methods may result in a better long-term direction. In addition, as the industry itself develops more data around decentralized trials and can present that to regulators, it will demonstrate that regulations can be revised to accommodate these new approaches.
OSP: How can companies like Oracle help study professionals make the transition from onsite to DCT more effective and seamless?
KV: Oracle has long been one of the world’s leading suppliers of clinical trial systems. Oracle Health Sciences Clinical One supports the move to the cloud and the shift to decentralized trials. Clinical trials require a single source of truth for data that is available to data managers, statisticians, medical monitors, and regulatory authorities.
In the past, sponsors and CROs have used point solutions designed to improve specific processes in clinical trials, such as data capture, drug randomization, and supplies management. But these systems weren’t built to work together, so a lot of process redundancy and data quality issues have been introduced.
Clinical One is not point solutions stitched together but rather provides a unified workflow with capabilities such as a single study build, self-service control, event-based data collection, and a single source of truth. A major component of Clinical One is the ability to support data collection from anywhere, which allows users to configure and monitor external data collection from any source — forms, wearable sensors, patient apps, electronic health records (EHR), labs. These expanded data give sites and study teams optionality and a more complete picture of the patient’s experience, and ultimately, more reliable safety and efficacy information of the investigative therapy.
OSP: Do you have anything to add?
KV: There’s no denying we have entered a new era in the life sciences industry. COVID-19 put enormous pressure on the entire healthcare system and organizations running clinical trials, and at the same time, provided the impetus for moving at least some aspects of decentralized trials out of pilots and into the mainstream. The experience has shown the benefits of the approach, and few sponsors or CROs are considering turning back as they may not be as well equipped to adapt to risk.
Modernization of ICH E8, General Considerations for Clinical Trials, linked with E6, Good Clinical Practice, guidelines will soon be here. They will support the agility and adaptability we need to reach the levels of study design, management, and conduct closest to the data and trial participants. Many have the desire and passion to take their experiences into flexible, reliable, and accountable practices and conduct more effective trials.
With the many questions the pandemic has raised, it has also brought to the mainstream an increased awareness around clinical trials and how vital they are to bringing treatments to patients in need. In the end, the patients are what is most important.