"Another way to ensure that these tools get used is to require it," suggested Bomba. "Language in the clinical protocol can
specify that site coordinators review patient compliance daily using the ePRO system." However achieved, whether by training
or mandate, the full advantages of ePRO can only be realized if sites leverage the tools at their disposal.
eLearning for ePRO
The ePRO training process typically includes personal interaction and hands-on training for sites at the investigator meeting.
Increasingly, training includes a combination of live and online options, including initial Web-based training on basics,
prior to the live session, detailed trial-specific training at the investigator meeting, and supplemental training close to
the "first patient in" date at a given site. As more sponsors move to online investigator meetings, the virtual training options
for making sites comfortable with ePRO solutions will continue to expand.
"Given the scope, expense and logistical requirements of investigator meetings for multi-center studies, conducting training
online is a natural solution," says Louis Monti, executive vice president at Pherin Pharmaceuticals. "This is an interactive
method to get sites excited about leveraging the tools provided in an ePRO solution."
Online training methods are highly effective and cost-efficient. On-demand access to training modules and product demos are
being increasingly leveraged by sites to facilitate subject education throughout the trial.
Site coordinators can only do so much. They can't force subjects to comply with the protocol. Many subjects come into clinical
trials unfamiliar with handheld technologies, and may at first be anxious about using these sophisticated devices. The two
patient populations that tend to worry about this most are pediatrics and geriatrics, despite that geriatric patients up to
the age of 90 have exhibited higher compliance in ePRO trials than other populations. (See "Geriatrics More Compliant Than
The best method of dealing with this is with simple designs. "It is important to incorporate simple eDiary designs into your
trial protocol," says Dynavax's Bomba. The best interface relies on a single, continually repeated method of entering information.
Devices can be customized for geriatric subjects, using larger fonts, touch-screen buttons, and high-resolution displays.
Some have even used removable magnifying glasses. For pediatric trials, a caregiver option can be implemented. This allows
an authorized caregiver to answer on a child's behalf.
Some ePRO users suggest implementing site-to-subject messages on the PDA to inform patients about how they are doing at certain
milestones throughout the trial. Especially during long studies, this helps keep patients' motivation high. These messages
appear on the subject's eDiary, and can be archived in the audit trail.
Early Phase Studies
ePRO solutions are used most often to collect data for primary or secondary endpoints in Phase II and III clinical trials.
However, Rinat Neuroscience and Greer Laboratories are two innovative companies leveraging an ePRO solution earlier in the
research process—as early as Phase I.
"With smaller biotechnology companies, the time to proof of concept is critical," says Patricia Walicke, MD, PhD, vice president
of clinical development at Rinat Neuroscience. "We have a strong desire to demonstrate activity in Phase I, and yet we are
also resource constrained. Real-time data access and improved ePRO data quality enable us to perform more frequent interim
analyses with a smaller group of patients, which keeps costs low and timelines short."
In Greer's case, ePRO is being used to determine the safety and dosing schedule of allergy treatments that are common in Europe,
but new to the United States.
"We feel the use of electronic patient diaries in our sublingual oral immunotherapy safety and dosing trials will assist us
in collecting and analyzing data in a timely manner," says Brad Whitlow, clinical project manager at Greer.
As clinical budgets shrink and the pressure to push products through the research pipeline increases, drug companies need
to save steps. By reducing the errors and inefficiencies that are so common with paper diaries, ePRO solutions enable sponsors
to collect compelling and statistically significant data from patients in Phase I through IV clinical trials around the world.
This results in better data, more manageable trials, quicker progress to the next phase of research, and ultimately, a shorter
road to FDA approval.
Phil Lee is president of PHT Corporation. He can be reached at firstname.lastname@example.org