Virtual Trials and Real-World Evidence

Data Collection
Identifying Core Needs and Defining “Virtual Trials”
Mariah Baltezegar, MBA of new indications for previously approved therapeutics and
Executive Director, Head of PPA Virtual Trials, Real-World Evidence address post-approval study requirements. The collection
Evidera of RWE is enabled by virtual trials, or decentralized
approaches to patient identification and data collection.
Debra Schaumberg, SCD, OD, MPH To inform this approach, we must first understand who the
Vice President, Scientific Affairs, Real-World Evidence, Evidera stakeholders are and what their needs are as well as begin
speaking the same language around virtual trials; there is

T
 here is increasing recognition of the need for more no widespread consensus on terminology. Understanding
fit-for-purpose evidence in development of therapeutics these foundational needs and aligning on definition enables
(drug, device, and digital). In the US, in response early planning to incorporate such strategies.
to the 21st Century Cures Act, the US Food and Drug
Administration (FDA) has developed a framework for
evaluating real-world evidence (RWE) to support approvals

Mariah Baltezegar Debra Schaumberg

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 Understanding the Needs medical records, which many virtual trials also employ,
allow patients to integrate a trial more or less seamlessly
Reaching More Patients into their lives, therefore reducing burden and decreasing
Strict inclusion/exclusion criteria and research center-based dropout rate. The average dropout rate from trial protocols
infrastructure do not serve patients who live remotely, is 30% based on research by both the Tufts Center for
lack transportation, or lead busy lives. This separation of the Study of Drug Development and Forte Research3 and
infrastructure makes reaching a heterogenous population approximately 40% of patients do not end up adhering to
challenging. Generally, clinical care facilities do not conduct trial protocols. This can impact the outcome of a trial and
research and research facilities are either commercial may introduce bias in the assessment of efficacy and safety.
research centers or large, academic teaching centers. These technologies can also help with protocol compliance,
Patients who use providers that exist outside of those as many have the capacity to proactively remind patients to
facilities generally receive existing medical care rather than follow a study’s protocol.
participate in research. To ensure we are capturing data
from a representative sample of patients, we must find ways
to reach a wider group of patients. It stands to reason, if As virtual study models center around
patients in the research cohort are more homogeneous than
placing patients at the center of a trial
the patient population that would be likely to receive the
approved therapy, their data may not be generalizable to and allowing them to participate more
the greater population. An inherent tradeoff arises between easily, they can easily be applied to
randomized control design choices aimed at enhancing
enable pragmatic trials to collect rich,
internal validity with those more pragmatic choices that
would aid generalizability. For example, registration trials real-world data.
increasingly tend to enroll relatively small samples of highly
selected patients at sites with experienced investigators
under ideal conditions, collecting large amounts of very Reducing the cost of therapy development is also another
specific data that are often not a routine part of clinical care. key need, though it is early in the lifecycle of virtualization
to say where cost savings may be realized. Virtualizing trials
Almost 15% to 20% of trials do not enroll a single patient.1 can theoretically save time and resources by reducing the
To continue to evolve the development of fit-for-purpose number of investigators and sites. The fewer sites a trial
evidence to inform the real-world use of approved utilizes, the lower costs tend to be. Investigator fees are
therapeutics, we must make research more accessible. responsible for 40% to 60% of a trial’s budget,4 paying
Depending on the research question, a patient may be sites for patient visits costs between $3,000 and $7,000
happy to complete a patient-reported outcome (PRO) or per visit,5 and site activation and management can make
telemedicine visit in their home or at work but not willing up an additional 25% to 30%.4 What we do know is that a
to go to a brick and mortar site location to perform the virtual approach enables the conduct of large-scale studies
same activities. In this way, we must weigh the burden of that are otherwise cost prohibitive, allowing for fewer
participation versus the value of the information. In the sites or even no sites depending on the research question
United States, 70% of potential patients live over two being asked and the types of assessments needed. As
hours away from the nearest traditional study site,2 which virtualization continues to gain momentum and mature, we
limits participation and leads to higher potential for subject anticipate more proof points will emerge regarding areas of
dropout as patients can incur costs and lost time from work cost savings.
associated with traveling to the study site. As virtual trials
aim to reduce or eliminate site visits by bringing the trial Putting the Patient at the Center
closer to a patient’s home, more patients have the potential
A renewed focus on patients and their involvement in
to participate.
healthcare, treatment decisions, and increasingly in
designing research is also driving discussions of the role of
Decreasing Burden RWE and pragmatic trials. As virtual study models center
Over time, traditional randomized trial protocols around placing patients at the center of a trial and allowing
have become increasingly more complex. To increase them to participate more easily, they can easily be applied
participation and retention, we must decrease the burden to enable pragmatic trials to collect rich, real-world data.
of participation for patients and their caregivers. Many Pragmatic trials draw on the substantial methodological,
clinical trials still rely on 1990s-era processes, and many bias-reducing advantages of random allocation of health
R&D functions have yet to fully leverage real-world interventions combined with the real-world setting of
evidence (RWE), genomics information, and emerging data an observational study and naturally lend themselves to
sources such as the Internet of Things (IoT), wearables, virtual approaches. A burgeoning selection of patient/
mobile apps, and more.2 The use of digital technologies physiological monitoring devices with the potential to
such as eRecruitment, eConsent, ePROs, wearables, and provide real-time data on important indicators is an
collection of data directly through patients’ electronic emerging area of innovation with likely applications in the

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 Figure 1. Considerations When Assessing Virtualization

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Key Considerations
Regulatory | Registration | Prevalence and sample size | Indication | Assessments required

EDC = electronic data collection; ePRO/eCOA = electronic patient-reported outcomes/electronic clinical outcome assessments; DTP = direct to patient

pragmatic trial setting. For certain indications, physiological “trial,” the term has been applied in the context of both
monitoring may be highly predictive of a clinically relevant interventional as well as non-interventional studies.
endpoint, and real-time collection of symptom scores is
another potential application. Regulatory guidance on the The most common terms used to define this paradigm
use of mobile apps for reporting adverse drug reactions in which studies are conducted either partially or entirely
(ADRs) and use of social media is under development.6 remotely include:
To fully realize the value that can be added through more
• Virtual trials. An umbrella term used to describe
widespread conduct of pragmatic trials, the field must
collecting data from patients in their local healthcare
realize a paradigm shift to incorporate data and operational
environment versus requiring them to go to a clinical
platforms that can capitalize on data capture through
research site or other brick and mortar location. This can
electronic health records (EHRs), registries, patient-reported
be accomplished with or without technology and moves
outcomes (PROs), etc., and enrollment infrastructures within
research away from the traditional site visit model
integrated health systems. Already gaining traction in the
to a more disseminated model where patients can
peri- and post-approval time period, moving forward, more
participate from their homes and nearby surroundings.
pragmatic elements will begin to be introduced earlier,
Virtual trials have been conducted for decades and now,
during the formulation of the clinical development plan.
with the advent of enabling technologies, are often
digitally enabled.
The Many Names of “Virtual” Trials
Although there are examples of virtual trials that date • Digitally enabled trials. These are studies that use
back several decades,7,8 the incorporation of virtual trials digital technologies to enhance the efficiency of a
into commercial therapeutic development and product trial, including well-established technologies such as
lifecycle management is an emerging concept and there electronic clinical outcome assessments (eCOAs) or
is no uniform agreement on definitions. Although non- electronic PROs (ePROs) to newer technologies such
interventional studies are not typically considered a as telemedicine and wearables. Studies have been

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 incorporating certain digitally enabled technologies site; physical movement of the patient; and, support and
for decades. The key now is to integrate multiple digital enablement (See Figure 1).
technology solutions for a trial either with a single
vendor or, at minimum, with a solid solution for Not only does the pharmaceutical industry recognize the
integration of data from multiple technology partners. need to transform RWE collection, but regulators do as well.
In January 2019, the commissioner of the FDA at that time,
• Decentralized trials. This is a term describing the Scott Gottlieb, MD, shared his goals including supporting
movement away from the site-based trial model, in seamless integration of digital technologies in clinical trials
which all trial activities are centered on the site, to and bringing clinical trials directly to the patient. Virtual
more of a model where patients are the primary focus. trials enable efficient collection of RWE by bringing the trial
This term is used by regulatory agencies including to the patient instead of the patient to the trial. Whether
the FDA and the Medicines and Healthcare products we are referring to truly virtual trials, decentralized trials,
Regulatory Agency (MHRA) and it has been reported or digitally enabled trials, each has its merits to facilitate
that the FDA has created a working group on the topic right-sized RWE collection to support the development and
of decentralized trials that will be charged with outlining commercialization of therapeutics. n
standards for this new space.8
For more information, please contact
There are three dimensions to consider when assessing [email protected] or
virtualization, including burden on the patient, caregiver, or [email protected].

REFERENCES
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6. Schaumberg DA, Mihos M, Payne K, Chen D. The Drive Towards Pragmatism in Randomized Trials: Are We There Yet? The Evidence Forum. November 2017. Available at:
https://www.evidera.com/wp-content/uploads/2017/10/The-Evidence-Forum-2017-November.pdf. Accessed September 2, 2019.

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8. US Food and Drug Administration. Breaking Down Barriers Between Clinical Trials and Clinical Care: Incorporating Real World Evidence into Regulatory Decision Making.
January 28, 2019. Available at: https://www.fda.gov/news-events/speeches-fda-officials/breaking-down-barriers-between-clinical-trials-and-clinical-care-incorporating-
real-world-evidence. Accessed September 2, 2019.

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