Worth the Expense? Despite their apparent advantages, electronic diaries have yet to achieve significant market penetration. Estimates show
that less than 12 percent of the studies relying on patient-reported outcomes use ePRO technology. Sponsors who are reluctant
to try ePRO sometimes balk at the initial investment or express doubts about the return on investment, according to a 2004
CDSIC/CenterWatch survey. In fact, there is reliable statistical evidence that ePRO can give an immediate return on investment
by enabling sponsors to reduce sample size for certain indications.
An insomnia study by Merck Research Laboratories randomized subjects into a paper arm and an eDiary arm, the latter of which
used PHT's (proprietary) LogPad System. So far, this is the first and only randomized trial comparing paper and electronic
PRO data collection methods in terms of their relative capacity to measure a drug's efficacy. The results demonstrated efficacy
for both arms, but the standard deviation for the study's primary endpoint (change in minutes of total sleep time) was 35
percent smaller for LogPad data.
The Merck researchers calculated that such a reduced data variance could enable them to decrease the sample size of future
similar trials by 56 percent while preserving the same statistical power. This represents significant potential savings in
both time and expense, from patient recruitment to study closeout.
Both paper and ePRO patient groups in the trial had compliance rates over 90 percent, with paper at 96 percent and ePRO at
92 percent. However, many patients did not fill out their paper diaries on time and reported they had to play "catch-up."
In addition, the paper data included illogical, illegible, and incomplete entries. Electronic diaries reduced these inappropriate
responses, providing sponsors with more valuable data. Real-time access to study and subject data also simplified data management,
saving the site 58 hours of data entry.
Geriatrics More Compliant Than Younger Subjects
Although the potential benefits to sponsors are compelling, some companies worry that patients and investigators may be uncomfortable
with the technology underlying ePRO solutions.
"Training subjects is a key element in any ePRO solution," says Darrin Bomba, clinical trials manager at Dynavax. "The first
step to improving subject compliance is to make sure site coordinators are comfortable with the technology."
Bomba asks the ePRO provider to train site coordinators directly at investigator meetings. "We budget two to three hours for
that training," he says. "Investigators need to be able to help subjects use the eDiaries throughout the study."
An ePRO system involves more than just electronic diaries. User-friendly online tools help sites manage enrollment and diary
compliance on a daily basis, and better manage sites around the world.
"It is critical that sites understand not only how, but also why they should use this technology," says Kevin Bayer, a former
clinical development coordinator at Orphan Medical. "From a sponsor's point of view, ePRO can improve data quality. But, it
can also make life easier for sites. We set up reports so we could see at a glance which sites and subjects exhibited low
compliance. This allowed sites to take direct action, such as calling a non-compliant subject before the issue began to affect
the outcome of the trial."
Color-coded reports alert sponsors and site managers when a subject's performance drops below certain thresholds. For example,
a subject's compliance figure will be shaded red if it drops below 85 percent. The system also can be programmed to automatically
alert site personnel to troubles big and small, from changes in a subject's physiologic status to low batteries in a reporting
device. Such reports can also be customized. Compiling screening data helps sites make eligibility decisions based on specific
criteria, such as the percentage of diaries completed during the enrollment period.