By Deborah Borfitz 

October 12, 2022 | When it comes to balancing the need for high-quality data collection and patient-centric strategies for engaging study participants, hybrid clinical trials utilizing wearable devices and other digital health tools can be challenging to conduct, according to Rajesh Ghosh, head of digital safety and decision support at Genentech, during a presentation at last week’s Summit for Clinical Ops Executives Europe (SCOPE Europe) in Barcelona, Spain. But when carefully crafted, a digital strategy can also help accelerate trials, improve diversity in recruitment, and improve outcomes for participants.   

Patient engagement, safety monitoring, and retention are interlinked, says Ghosh. Patient retention is particularly important from a cost point of view, with safety being the driver of financial losses from patient dropouts. And enhancing safety monitoring requires improving patient engagement in trials. 

A literature review published last year highlighted the many significant benefits that arise from engaging trial participants: improved recruitment and retention, increased diversity of study participants, a better trial experience, adherence to the research protocol, and faster study completion, he notes. That translates into quantifiable value in terms of recruitment rate, number of study participants who drop out for reasons other than adverse reactions, recruitment and retention rates among hard-to-reach populations, level of diversity, satisfaction rating of study participants (including convenience of study visits and procedures), and the number of protocol amendments and studies completed within a particular timeframe.  

The U.S. Food and Drug Administration is developing a series of guidelines to introduce the patient voice into clinical trials, Ghosh says. Separately, the agency’s efforts include making clinical trial populations more diverse and shifting from “the ideal ... to the real patients.” 

Adverse events are one big reason patients drop out of trials, says Ghosh. But inconveniences related to the number of required study visits and distance to the study site, as well as forgotten appointments and unclear expectations, are also major factors. Ultimately, patients’ medical condition also helps determine if they continue with a trial.  

Proactive safety monitoring is one solution to dropouts tied to adverse events, continues Ghosh, meaning “not just observing what is happening but doing something about it ... which leads to early detection of [the safety signal].” Hybrid and decentralized clinical trials can make participation more convenient and viable.  

Forgotten study appointments can be mitigated with continuous communication, he adds. Transparency, patient education, and health literacy are also solutions with a clear value proposition. 

“A lot of us involve patients in the trials but too few of us recognize their contribution to the science,” Ghosh points out. Showing appreciation, which might be expressed by mailing study results to participants, helps build trust with patients and society and motivate research participation. 

Awareness about the clinical trial process is also crucial to study continuance, says Ghosh. Patients need to realize they might not see an immediate improvement in their symptoms and understand the value of their role from a “longer perspective.”    

Multiple Considerations 

Digital tools can be leveraged to address the major patient-facing issues with hybrid and decentralized trials—communication, engagement, education, safety monitoring, and use of wearable health monitoring technology. The trick is to develop a digital strategy that incorporates all those elements to optimize clinical development needs, says Ghosh. 

“There are multiple aspects to consider, starting with feasibility and ... design of the trial,” he continues. “You cannot apply these concepts blindly across ... different indications.” Cost and speed are other critical considerations, as are the burdens of participation on patients and sites. “We have done some experiments to show that if you ask patients to use more than two wearables ... it becomes very difficult for them to remain compliant.”  

Often overlooked is process and organization readiness to receive streaming data from digital wearables. If the information only gets looked during a study’s interim period or at its conclusion, there is no point in collecting it at all, says Ghosh. He likens the logic to using a Roku device for streaming a Netflix movie but watching it only after it has been stored into memory. 

A data strategy that covers the purpose of the information to be collected in the trial, as opposed to amassing a lot of data and then hunting for insights, is another important element to consider on the front end, Ghosh says.  

The relative value of digital tools might be assessed a few different ways, he continues, including their ability to prevent patients from being hospitalized by catching problems early. The technology might also be used to increase patient diversity, minimize patient drop off, develop a new diagnostic, or to maximize benefit and minimize risks for patients.  

Connecting The Dots 

Digital communication can help ensure participants understand the importance of using a particular health-monitoring device. A key factor is whether a device will be actively or passively monitored by patients, says Ghosh. If the latter, study sites would get the data automatically and patients wouldn’t have to actively do anything. 

The next question is what to do with all that data and what actions—e.g., a telemedicine call or a trip to the emergency room—might need to be taken, he continues. Communication, and the right amount of it, is crucial.  

A study’s data strategy is focused on reducing the number of touchpoints, devices, and expectations, says Ghosh. For global trials, the conundrum here is finding a medical-grade device that is available everywhere in the world. “It is not enough for the device to be approved only in the U.S.” 

Other questions are how to manage bias related to the impact of digital devices on study participation and if devices used in trials must also be used when the study drug is ultimately commercialized, Ghosh says.  

It’s important to “connect [all] these dots ... how you bring them together and multiply the value that this brings for the patient,” says Ghosh, in talking about digital monitoring of risk and the collection of patient-reported outcomes (PROs), “potentially on an ongoing basis.” This involved giving alerts to sites and seeing if they act on them appropriately and at the right time, as well “really thanking them from time to time for being compliant.” 

Behavioral nudges and modification are often needed to incentivize patients to continue using digital health tools and provide needed data, Ghosh says, and “communities are a very important element of this.” It is frequently necessary for patients to hear about the value of their compliance from other patients and not just the principal investigator (PI).  

Health literacy is a significant help when it comes to compliance in using digital tools and methods as well as ensuring the treatment individuals receive while in the trial has maximum impact, he adds. 

Educational Focus  

A real-world digital strategy might kick off when patients first enroll in a trial and education is the big focus—in terms of the treatment they’ll be receiving, potential safety events or risks, what to expect and be aware of, how their vitals or other blood parameters (e.g., neutrophils) will be monitored at home, and how to use those devices and report their symptoms (e.g., feeling feverish or dizzy), says Ghosh. 

An alert would go out to study sites based not just on what the device says but also how patients are feeling, he says. The site would potentially have a telemedicine call with patients to make sure their clinical symptoms are indicative of risk, and then decide what to do next (e.g., change their drug dose, bring them to the site, or send them to the emergency room). 

Digital tools could play a role at every turn, notes Ghosh, starting with an educational platform to help patients become more aware and know what to expect. Technology could also be deployed to monitor their condition in real time, track what kind of actions were taken, and how patients and sites were alerted and responded. 

When digital tools are used in combination, patients would be engaged, and serious safety events could perhaps be prevented that would cause them to drop out of the trial. As it is, trials for some indications have up to a 20% dropout rate, says Ghosh, in highlighting the potential of technology to deliver better patient outcomes as well as significant cost savings. 

‘Right Middle Path’ 

During the Q&A period with his audience, Ghosh says engagement is about talking to patients in their own language as well as providing the right information at the right time. Currently, digital media is often being manually translated. But he foresees the day when technology automatically translates some messages—especially when dealing with SMS-sized snippets rather than voluminous documents.  

Patient education pieces produced by Genetech tend to be translated into at least five languages, he adds. In the future, the company expects to communicate with patients and sites in many other languages, especially when it comes to alerts on digital devices. 

In answering a question about whether to send condolences to the family of participants in oncology trials who subsequently pass, Ghosh says he thinks the idea is worth considering, as is acknowledging the role of caregivers in cancer and Alzheimer’s disease trials. To counter any negative input patients might get from peers or family about taking part in a trial, he advises building their trust by being transparent from the start about what participation will entail and help them objectively look at study benefits on balance with the risks.  

Improving protocol compliance may simply be a matter of more frequent communication with patients reminding them when to take their study drug, the PRO questionnaires that need to be completed, and when they’re due for their next appointment, says Ghosh. “We are trying ... to integrate these into a kind of routine that happens every day,” much like people do when asking Alexa for helpful information about today’s weather and what’s on their calendar.  

From a practical point of view, hybrid trials are more likely to be embraced than fully decentralized ones because of the advantages of the traditional approach where studies are done in a standard way in a controlled environment, Ghosh says. The “right middle path” would include the collection of data through digital means between on-site visits. 

Among the major blockers to decentralized study components are concerns about liability and data privacy as well as what to do about alerts, he continues. It is critical to establish early on that investigative sites and PIs be the ones getting any alerts and bearing primary responsibility for making clinical decisions about next steps.  

To some extent, setting up the right infrastructure and platforms is helpful in dealing with data privacy requirements, says Ghosh. For example, sponsors could get anonymized reports to know which sites are doing poorly when it comes to collection via digital devices but without knowing exactly who those patients are or what data is missing. 

In some cases, proxies for patients have been used to identify them for a targeted action step without knowing exactly who and where they are, he notes. The challenges of doing this will be reflected in upcoming regulatory guidances for clinical trials, which are needed given that digital health tools are already being used in routine clinical care.