Even before the COVID-19 pandemic, virtual clinical trials (otherwise referred to as decentralized clinical trials) were lauded as the next great clinical trial disruption. Now, what was once considered a shiny new tool—a “side show”—has become “business as usual.”

The rise of virtual trials can be easily sourced: Virtual solutions have effectively addressed many of the most enervating and pervasive barriers to success in centralized clinical trials. As with any innovation, however, virtual studies are not without their own set of challenges.

In this post, we provide a comprehensive breakdown of virtual clinical trials challenges and opportunities, examining the nuances of virtual components and how their implementation might affect each stage and touchpoint of the clinical trial journey.

Key Challenges Associated with Virtual Clinical Trials

In the transition from legacy to innovative methods, clinical trial stakeholders are likely to confront a number of challenges associated with virtualization. Common issues include:

1. Inconsistent regulatory acceptance across the globe

2. Complicated systems integrations

3. Sponsor and site risk aversion

4. Inequitable user accessibility

Let’s explore these key challenges, and how they might be resolved when planning a clinical trial with virtual components.
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1. Inconsistent regulatory acceptance across the globe

In the U.S., the FDA’s acceptance of virtual and decentralized clinical trials, such as eCOA clinical trials is well known: The recent COVID-19 pandemic forced an acute pivot towards virtualization and away from the organization’s formerly measured approach to the use of digital tools in clinical trials.

But, outside the U.S., regulatory reception of virtual clinical trials is more reserved and less well-defined. In Europe, for example, the EMA (European Medicines Agency) released guidance permitting the implementation of some virtual modules in clinical trials—including direct-to-patient shipping, telemedicine, and remote monitoring. However, these measures—which were motivated by the onset of COVID-19—were intended to be temporary. Guidance relating to the broader adoption of virtual methods in Europe remains unclear.

In APAC and LATAM, deciphering digital health technology acceptance is even more challenging—regulations vary widely across these regions, requiring careful conversations with ethics committees in each territory to measure adoption.  
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2. Complicated systems integrations

Fit-for-purpose technologies are essential to the success of any clinical trial. But, in their struggle to match the rapid rise of virtualization, many CROs have attempted to embed technologies and digital components into traditional clinical trial methods—without first adapting study structures or addressing siloed data systems. The result has not been the streamlined, high-yielding clinical trial process the industry strives for, but rather increased trial complexity.

Clumsy—or nonexistent—systems integrations often require patients to report data using multiple, maladapted study tools and sources (ePRO, devices, EHR records, etc.), increasing their burden and the risk of participant noncompliance and noncompletion. This lack of integration is also a burden for project managers: When systems aren’t optimized to adapt to—or manage—multiple data sources and streams, workflows can become unwieldy, resulting in damaging data errors and prolonged study timelines.
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3. Sponsor and site risk aversion

One of the greatest challenges associated with virtual clinical trials isn’t technological—it’s behavioral. More specifically, and as is the case with most innovations, the virtualization of clinical trials has been met with apprehension—an inertia emerging from sponsor and site risk aversion.

The process of handing off virtual methods to legacy clinical operations teams is not always a smooth one. Site staff are under immense pressure to adopt new procedures and practices. But, when the transition to virtual includes non-intuitive technologies or insufficient training, conducting these studies becomes particularly onerous to sites, and resulting negative experiences—for sites and sponsors alike—only increase resistance to adoption.

Despite these hurdles, operational teams in large organizations continue to demonstrate their willingness to adapt. It’s imperative to encourage this acceptance, providing reassurances that the transition period will be well managed and teams well equipped.
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4. Inequitable user accessibility

The breakdown of geographic boundaries, which is a known benefit of clinical trial virtualization, does not automatically translate into unimpeded access. Digital literacy is not ubiquitous—neither is access to digital mediums. As a result, patient-facing clinical trial tools must be adapted to suit the target to improve patient compliance and user accessibility.

For example, it’s been demonstrated that older participants can deliver even higher ePRO compliance than their younger counterparts. However, the ePRO tools they use—and the training they receive—must be refined to include specific features (i.e. larger screen fonts) that address the unique needs of this demographic. Similarly, users located in certain regions or belonging to certain socioeconomic situations may not have access to broadband Internet. In such cases, clinical trial teams must develop methods and tools that will allow these participants to complete study tasks offline.

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Key Opportunities Associated with Virtual Clinical Trials 

As with any successful innovation, the challenges associated with virtual clinical trials should be weighed against the wealth of opportunities virtual studies—and digital health technologies—can provide. The main benefits associated with clinical trial virtualization include:

1. Reduced participant burden

2. Improved compliance and retention

3. Improved data accuracy for more robust evidence

4. Accelerated trial timelines and delivery

5. More data at lower costs

6. Expanded access for patients and researchers

7. Improved patient safety with real-time data monitoring  

8. More efficient and less burdensome long-term follow-ups

9. Empowered decision making
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Let’s take a deep dive into these key opportunities, exploring how the implementation of virtual methods can benefit any and all stages of the clinical trial journey.
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1. Reduced participant burden

COVID-19 disrupted business as usual in most industries, and the clinical trial space is no exception. But, the rise of virtual clinical trials cannot be credited solely to the pandemic. The demand for analogous but less strenuous alternatives to traditional clinical research methods has long been a concern for patients and clinical researchers alike—and this demand is only growing. Virtual solutions offer a reprieve.

• Fewer site visits: ePRO and “bring your own device” models, as well as the proliferation of wearable technologies, allow participants to record and submit data remotely reducing—or even eliminating—the need to travel to sites. If site visits are required, participants can be provided with a number of less burdensome options, including visits to local labs and partner pharmacies or home health visits conducted with a nurse.
• ‍Remote consent processes: Informed consent often requires a site visit in traditional clinical trials, taking up valuable patient time. Electronic consent (eConsent) allows patients to review these forms on their own devices and at their own pace.  
• ‍On-demand multi-media training: Training videos are made available to patients and accessed easily throughout the clinical trial, providing participants and caregivers with precise guidance regarding their responsibilities and how to complete their study tasks.  
• Integrated sensors and devices: Sensors and devices can be integrated into the study team’s clinical trial platform, automatically collecting and transferring continuous or point-in-time data and reducing the need for patients to self-report vitals or other measurements.  
• Virtual check-ins: Since the start of the pandemic, telehealth has increased in popularity, and patients' comfort with the practice has increased. Instead of requiring patients to travel to a clinic, required visits can be conducted with physicians or nurses virtually.
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2. Improved compliance and retention 

Because virtual solutions simplify the process of patient reporting—and reduce participant burden—compliance and retention rates are subsequently improved. Participants are far more likely to see virtual clinical trials through to completion—and to complete their study tasks correctly and throughout.  

• Streamlined patient tracking: Real-time electronic data capture provides increased visibility into participant behaviors, allowing study teams to monitor engagement and provide greater support to patients before they become noncompliant.  
• More engaged participants: The integration of gamification principles encourages patients to maintain or increase their compliance levels day over day, week over week, or compared to other study participants. Similar eClinical technologies also facilitate a feedback loop that supplies participants with access to their own data, helping them to feel more actively involved in the study.  
• Automated reminders and notifications: Programmed alerts and click notifications are sent directly to patients’ smartphones, reminding them to complete study tasks or take their medications.
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3. Improved data accuracy for more robust evidence

The traditional method of on-site reporting has a critical limitation: Its reliance on participants to fill in study diaries with diligence is impractical. Participants are far more likely to fall prey to parking lot syndrome—filling in questionnaires just before site visits rather than as directed, resulting in misreporting, biased recall, and the inaccurate reporting of events. Virtual methods help to address this challenge by optimizing data collection in numerous ways.    

• Reduces the occurrence of incorrect or missing data: ePRO and BYOD clinical trial models are demonstrably more successful than traditional modes of data collection. By allowing patients to leverage intuitive digital technologies—including their own smartphones—to report symptoms, experiences, and perceptions as they occur, study teams and sponsors have access to real-time data, which generates evidence that is both more robust and more accurate. Virtual solutions also help to improve adherence to clinical trial protocols while also reducing the occurrence of human error factors—a benefit made possible by, for example, automated reporting tools such as digital instruments. The result is reduced risk of missing or incorrect data entry.  
• More contemporaneous data: The more real time data is, the more accurate it’s likely to be. Inversely, the more time that passes between an event and its reporting, the more likely it is that reported data will be impacted by recall bias. (In the case of pain ePRO, for example, patients may struggle to accurately report the duration and intensity of an event as time passes.) Real-time data collection helps to minimize the occurrence of recall bias as well as the risk of misreported outcomes.  
• Continuous data collection: Some studies will require more frequent, or even continuous, data collection. But, asking participants to report outcomes or take measurements with such frequency is both burdensome and impractical. Wearables and sensors can be integrated to circumvent this hurdle, capturing data continuously and without participant input. Averages and outliers can then be recorded, providing a richer data set for analysis.
• Reduced “white coat” influence: Empowering patients to report in real time and from home increases data accuracy: Because these outcomes are collected as patients live their everyday lives, they are a reflection of patients’ real-life behaviors. “White coat” influence is therefore reduced, subsequently decreasing the risk that patient reporting will be negatively impacted by performative impulses.
• Reduced patient subjectivity: Inevitably, any patient-reported data is going to be subject to patient bias. But, the increased deployment of devices and digital instruments in clinical trials has helped to address this subjectivity, facilitating the collection of more accurate data. For example, rather than asking caregivers to score their babies’ stools, rashes, or coughs themselves, patient-friendly apps supported by AI technologies can simply guide participants to snap and send photos, videos, or audio recordings directly via their devices. These media outcomes can then be assessed by expert raters, which radically reduces the risk of bias.
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4. Accelerated trial timelines and delivery

There’s no denying it: The virtualization of clinical studies has accelerated trial timelines. In fact, every stage and touchpoint of the clinical trial journey has been improved with the integration of virtual and digital enhancements, from recruitment and enrollment to data lock and delivery.  

• Optimized recruitment and enrollment: In a trial deploying virtual methods, participant recruitment and enrollment timelines are often two- to four-times faster than in traditional studies. Following seamless pathways, participants are diverted from digital advertisements through to an informational landing page and into prescreening. If qualified, they can then download the clinical trial app and proceed through the enrollment process, including eConsent and multi-media training. If—at any point—participants have questions or concerns, the virtual site team is available to provide support. This process of digital recruitment, enrollment, and onboarding takes minutes or hours rather than days or weeks, decreasing participant burden and trial timelines.  
• Faster data collection: Electronic patient reporting is easier, faster, and more accurate than paper reporting. Combined with automated notifications and reminders, eClinical tools help to increase compliance and retention, enabling trials to be completed more quickly.  
• Rapid time to database lock:  Virtual clinical trials may be decentralized, but the data gathered in these studies is not—it’s all centralized. Data collected from patient reporting, devices, patient history, medical assessments, and other sources is housed in a single, cloud-based platform known as an Electronic Data Capture (EDC) system. Because this data is centralized, it can then be seamlessly managed and cleaned in real time, allowing study teams to get to database lock sooner.  
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5. More data at lower costs

The virtualization of clinical trials has a profoundly positive impact on study cost. For example, transitioning from provisioned ePRO devices to BYOD ePRO removes the need for physical infrastructure. Similarly, direct data entry by patients reduces the need for, and cost of, source data verification. Removing brick-and-mortar sites and site visits from clinical trial design subsequently removes the expense of maintaining staff at multiple sites. Additionally, digital recruitment using pay-per-click advertising techniques can be substantially cheaper than traditional media buys. Because virtual trials can be conducted across geographic regions, the patient pool is often much larger, making it easier, and therefore cheaper, to recruit.
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6. Expanded access for patients and researchers

The implementation of digital measures has expanded access to clinical trials exponentially, particularly to those demographics who have historically been underrepresented in clinical research. Patients without the time or resources to travel to sites or to engage fully and as needed are now able to participate from their homes. And, digital recruitment strategies—powered by targeted ads—help to increase cohort diversity, enabling outreach to populations who were previously unaware of clinical trial opportunities and delivering relevant messaging to both skeptical and underserved communities. But, increased access isn’t confined to patients. Researchers, too, are benefiting from virtual and distributed trials, which create opportunities for academic professionals to become principal investigators without the administrative burden or cost.
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7.  Improved patient safety with real-time data monitoring

In traditional clinical trials, adverse events (AEs) may go undetected for days, even weeks, due to the extended intervals between scheduled site visits. But, real-time reporting helps to address this safety concern, enabling study teams to track behaviors in real time and to monitor reported data for any irregularities or potential AEs. As part of this process, patients respond to daily health status questionnaires. If their health status has changed, the study system automatically directs them to a set of additional questions to determine the scope of the concern. Automated alerts, which are built into the system, notify study teams of any aberrations, allowing team members to quickly identify patients who require support or urgent follow-up. A virtual clinical study team member then reaches out via email, phone call, or chat to determine whether an AE has occurred and to create an electronic case report.
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8. More efficient and less burdensome long-term follow-ups

The key to successful clinical trials—both short-term and long-term—is reducing participant burden wherever possible. This is especially true for long-term studies, which are particularly burdensome for patients and are subject to substantial drop-off. Because most pharma, drug, and device trials require long-term follow-ups (LTFUs) to track both effectiveness and safety over time, these sponsors and their study teams are turning to virtual solutions to address common challenges associated with LTFU clinical trials—mitigating drop-off and improving retention by reducing participant burden.
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9. Empowered decision making

Virtual clinical trials facilitate the speed, accuracy, and visibility that enable sponsors to make well-informed decisions more quickly. Historically, sponsors were unable to access their data until a formal interim analysis, or the study itself, was complete. Now, with virtual tools such as real-time dashboards, sponsors are able to obtain the insights they need to gauge the status of their study and plan accordingly. Empowered by this visibility, sponsors can react quickly if hurdles arise or get to market faster when a study delivers positive endpoints.
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The Future of Virtual Clinical Trials

Virtual solutions have the power to overcome common challenges and improve processes at every stage and touchpoint of the clinical trial journey. However, despite their demonstrated benefits and the wealth of opportunities they provide, virtual trials are not without their own set of challenges.

Companies that adopt virtualized methods but also equip themselves with an awareness of the potential hurdles of virtualization, will be well-positioned to adapt to the future of therapeutic development—and to support the innovations that improve patients’ lives more effectively than ever before.