Why Paper Diaries Should be Banned in Clinical Trials

1. Article Reprinted from www.pharmexeceurope.com March 2009
Why Paper Diaries Should
Be Banned in Clinical Trials
By Dr Valdo Arnera
E very now and then, a shift in technology
revolutionizes an entire industry. Consider the
advent of email and automatic banking machines.
batches, invent data, forward-fill, and mark multiple
responses in the same question. All these situations
present serious data analysis problems.
Once the mainstream adopts these processes, it is We are all familiar with “parking lot syndrome,”
difficult to imagine how we managed without them. in which patients retrospectively complete days or
Today a similar transformation is taking place in the weeks of diaries just prior to a site visit. Patients also
pharmaceutical world, as more companies worldwide forward fill paper diaries. A study published in the
replace paper diaries with electronic patient diaries in British Medical Journal showed that 45 percent of
clinical research.
Electronic patient reported outcome (ePRO)
solutions capture self-reported data directly from
patients at home or at investigator sites around
the world. Most often patients use PDA devices
which transmit these data to a central
server. An ePRO system provides
sponsors with higher quality data
than paper, accurate timestamps
and real-time access to vital
compliance, enrollment and
safety information.
If market adoption
continues at its current
pace, in ten years
paper diaries no
longer will exist for
studies using PRO as
primary or secondary
endpoint data. I propose that
we accelerate the pace and call
for paper diaries to be banned.
If your study depends on what
patients tell you, you have no
choice but to use electronic diaries.
It very well could be the difference
between making your study a huge
success or a failure.
It is impossible to get high quality
data from paper
Paper diaries offer no controls over timeliness or
quality. Subjects make entries that are incomplete
(skipped items), illegible (poor handwriting),
captioncredit_
and illogical (inappropriate responses). Further,
patients respond days later, complete diaries in

2. subjects in a pain study invented data to be able to ask patients how they as compared to paper. This enables
by forward filling at least once. feel at a precise moment and get an smaller, more conclusive studies.
With paper, the burden is placed immediate, accurate answer. Biostatisticians could adjust
on patients to remember diary and lower estimates on how many
response times. Paper diaries can be Electronic diaries empower patients are needed to prove efficacy
confusing for patients to understand subjects to be more in Phase II studies, based on the
and accurately answer. In many compliant expected variance of paper data at
studies, the questionnaires branch An elderly female fibromyalgia hand. This can create a significant
into different paths depending on the patient in the UK once reported that savings in money and time. In Phase
patient’s responses. The burden is on her electronic diary alert sounded III studies, such high quality data
the patient to understand which set during a wedding reception. She provide more reliable scientific
of questions to answer based on their simply laughed, excused herself, and conclusions. Instant access to up-
reactions or symptoms. took five minutes to complete and to-the-minute ePRO data allows
Electronic diaries allow sites to send her diary. It did not occur to adaptive trial designs which are
obtain accurate, real time information her that this activity was a burden. almost impossible with paper.
on patients’ reactions during a trial. It is highly unlikely that she would
They are the best way to collect both have carried a paper diary with her Electronic diaries are the
objective and subjective assessments to the wedding. History tells us that future, today
of patient experiences. she would have completed her diary Paper might do well enough in
retrospectively, or not at all. rare exceptions, such as when
Paper is slow Patients using electronic diaries time sensitivity is not an issue
If a patient is not performing well in enjoy a much higher degree of and a question relates to patient
a study by failing to complete diaries privacy. They can respond more experiences over a week. But when
regularly — or more importantly, freely than on a piece of paper that it matters if a subject completes
because of worsening symptoms will be read by others. In a study on the diary on Monday instead of next
— it can take weeks or months for female sexual dysfunction using a Thursday, it is certain that paper data
sites to notice. Site personnel have to cross-over design, patients reported ultimately will fail.
spend time reviewing paper diaries 80 percent more sexual episodes Despite continued increasing
and making manual, error-prone on the electronic diary than they adoption in the ePRO industry,
calculations and measurements where reported on paper. some companies still are reluctant
needed. These activities detract Electronic diary patients say that to change. Managers may worry
from time that could be spent caring they are encouraged to comply that if there is a problem with
for patients — one of the reasons because they feel that someone is electronic diaries it will hurt their
site investigators become study paying attention to their symptoms careers, because no one was ever
coordinators in the first place. whenever they transmit their data. reprimanded for using paper — yet.
Electronic patient diaries allow They are aware also that their study The real danger lies in spending
responses only during the appropriate coordinators are supposed to review millions on trials that failed because
times specified by the protocol. They their data, which compels them to of outdated, inaccurate paper diaries.
use controls to ensure complete, complete reports as expected. If the primary efficacy endpoint
legible and logical reports; encourage Patients in a year-long lower is coming from the patient it makes
compliance through alarms; reduce back pain trial showed 90 percent no sense to use paper diaries. Trials
respondent burden; and provide compliance because they could hold are all about data. It is the only thing
real-time site management of patient the electronic diaries in any position they produce.
performance. In short, electronic they pleased. One man said he would For efficacy and faster, smaller,
diaries solve the problems of not have been able to fill in detailed less expensive trials it is time to put
paper diaries. responses with paper because he away the paper and pick up what
was too uncomfortable to write. has proven to be extremely effective
Electronic diaries promote a These patients completed electronic technology: the electronic diary.
fast, honest response diaries six times a day, seven days
In a Merck Research Laboratories a week because they could use the Dr Valdo Arnera
insomnia study comparing paper and device even when lying down. And Dr Valdo Arnera has more than 18 years
electronic diaries, one patient reported they felt encouraged because they of experience in the pharmaceutical
that he enjoyed using the paper diary were actively involved in managing industry. He is skilled in both science
because he only had to play catch-up their pain and health. and management, and speaks frequently
about 60 percent of the time. This kind on these topics. Dr Arnera has been
of statement that should convince all Electronic diaries enable an active co-chair of the DIA’s Special
of us involved in data quality that paper more reliable, smaller, faster, Interest Area Communities (SIAC)
diaries are nightmares. safer trials eClinical and Standards committee.
Studies prove that electronic diaries One of the major advantages of
motivate subjects to complete their ePRO solutions is that they have
diaries. It is much more efficacious been shown to reduce data variance