Shifting Research Realities After COVID-19 Place Decentralized Trials Center Stage

Decentralized Clinical Trials Will Change The Research Landscape(Source:Shutterstock)

According to some studies, 85% of clinical trials fail to retain enough patients, 70% of participants live over two hours from a research site, and in 50% of studies, participants find it difficult to stay enrolled due to poor health.

No wonder then that one of the most significant changes in the clinical trials landscape during COVID-19 has been greater adoption of decentralized approaches, with even regulators adapting to permit such trials, a recent virtual conference heard.

With decentralized trials (DCTs) here to stay, new roles in clinical research are likely to be created, or existing roles expanded, to adapt to the shift from site-focused to patient-centered trials, said panelists at the 14th annual conference of the Indian Society for Clinical Research (ISCR).

“Industry surveys indicate that around 85% of the industry is at [various] stages of adopting different levels of decentralized trials. COVID gave proof of concept. It’s a huge shift and I see it as an attitudinal evolution and digital revolution.” - Nimita Limaye, Research VP, International Data Corporation 

“It will be a continuum. Monitors will have access to a lot more data in real time and can play a more proactive approach rather than reactive," said Rajesh Jain, principal consultant clinical solutions at PharmaLex (India), a services provider to pharmaceutical, biotech and medtech industries. "New roles will come up - perhaps a patient support help desk - and there will be a shift from monitoring to patient relationship and support as technology components become more mainstream.” 

As use of technology and devices like wearables becomes commonplace, automated data analysis will play an increasingly important role in trials, he predicted.

Adoption In APAC, India

Levels of adoption of DCTs vary across the world, as regulators are at different stages of preparedness for the change, panelists felt. While the US has been at the forefront, with the Food and Drug Administration having gradually created a regulatory pathway since 2007, the European Medicines Agency has also been proactive. However, data privacy concerns have held back greater adoption in Europe.

Nimita Limaye, research vice-president at International Data Corporation (IDC), said while 52 DCTs are listed on clinicaltrials.org (17 observational and 35 interventional), “it’s a matter of terminology” and the number of such trials is significantly higher in reality.

“I haven’t seen any specific statistics published on this but I feel a significant number of trials that are being approved have a lot of components of decentralization in them,” she added.

Jain said such trials are taking place in Asia-Pacific, including in India, though not all are meant for registration studies or marketing authorization.

The Patient Will See You Now

For companies looking for a framework to enable DCTs, the panelists advised setting up an internal team with multiple stakeholders to drive the initiative, identify the right technology and consider the therapeutic areas suited to such trials. However, patient centricity is paramount.

“From get-go, it should be an adaptable and scalable approach that tries to keep patients at home," said Isaac Rodriguez-Chavez, senior vice-president, scientific and clinical affairs at PRA Health Sciences, a global contract research organization.

"Not one size fits all – look at the nature of the disease, the target population, which technology needs to be customized, what endpoints need to be measured for the trial to be synchronized with an electronic platform, can the investigational material be delivered safely, are we in compliance with regulations and can you deploy it across different geographic areas, so take a holistic approach,” 

“In India, around 80 trials are using a component of a digital tech for data collection.” - Rajesh Jain, principal consultant, Clinical Solutions, PharmaLex (India)

While the health journey of a clinical trial participant and technology customization are essential to keep in mind while designing an ecosystem for DCTs, quality assurance, communications plan and data flow also need to be paid heed to, Rodriguez-Chavez observed.

“This reminds me of the title of the book that Dr. Eric Topol wrote, 'The Patient Will See You Now,' and this is what we are really moving towards with patient experience or 'Px.' The technology for the implementation plan has to be truly centered around the patient, keeping patient optionality in mind…so keeping a modular approach. You may have situations where some patients may not be comfortable doing things remotely, while others may love it,” observed IDC’s Limaye.

Monitoring Adverse Events

While adverse or serious adverse events might seem more difficult to monitor in such studies given the virtual nature of interaction between a trial participant and an investigator, it is possible to remotely handle such events, the ISCR meeting heard.

“If we set up the pipelines right for data integration and assimilation and exposing data in near real-time to the monitoring process, it [adverse event monitoring] can be done.” - Rajneesh Patil, VP, Global Site Management, IQVIA. 

“It’s about the way we set up an alert mechanism and the way we set up a response system for an investigator or a primary care physician to act. We have healthcare delivery systems around - patients are generally in good reach of a system – so how do we build that last mile of connect. We don’t need to build such systems. They exist and it’s only a matter of connecting the right dots,” noted Rajneesh Patil, vice president, Global Site Management at IQVIA in the US.

PharmaLex (India)’s Jain also spoke about the role of "geo-fencing", which is the use of global positioning systems or radio frequency identification technology to create a virtual geographic boundary, thus enabling software to trigger a response when a mobile device enters or leaves a particular area, in creating such alerts.

“A patient is just probably walking into the nearest healthcare center instead of informing the investigator first and we used geo-fencing to create alerts for the investigator. Our patients and investigators found this to be one of the most useful tools,” he added.

The Research Site Perspective

The majority of trial participants want the enhanced convenience of a DCT, said PRA Health Science’s Rodriguez-Chavez. “The patient community is very supportive – it’s less disruptive, it's transformative, more inclusive of diverse populations breaking geographic barriers that traditionally existed – for example, in inclusion of people living in rural or difficult to access areas.” 

However, IDC’s Limaye said employees at research sites were skeptical due to an underlying fear that such sites might lose relevance and may no longer be required in DCTs.

“But we know now that they are not going away – it’s their operating model that is changing. There was a survey and two-thirds of the sites said they will be very happy to pivot to this model and do whatever it takes to adapt. They are a big piece of what is happening. Though we’re moving from a site-centric to a patient-centric approach, they are still a key component along with technology,” she observed.

However, clinical sites are concerned about access to data and at times technology is seen “as a burden”, given that investigators have not just to train patients on using a device or an application but also need to ensure compliance. While some also feel it would be difficult to establish a “connect” to patients, it could be easier in real life as the effort and time to travel to a site is cut down, Limaye added.

“However, it should be approached on a case-by-case basis as in some serious diseases or conditions, empathy and a physical connect is required. Significant pieces of DCTs are here to stay, but it won’t apply to everything.”