The document discusses the benefits of using electronic patient-reported outcomes (ePRO) over traditional paper methods for clinical trials, noting that ePRO provides higher quality data through features like time-stamping and validation, and can reduce costs through efficiencies like eliminating manual data entry, resulting in studies requiring fewer patients and faster completion times. Case studies are presented showing sponsors achieving similar statistical power with only one-third to half the planned sample size when using ePRO rather than paper.

1. PHT Insights — First Quarter 2009
Improving Trial Efficiencies: Making the Business Case for ePRO
How to Quantify ePRO ROI: The Four Types of Paper Patients
What Does Paper Cost?
Most organizations haven’t assigned a cost to paper 1. Perfect Patients
PROs, unless they’re outsourcing the entire function complete every field clearly, and
of data collection and management to CROs. Here in the proper format. Even in this
are the numbers: rare best case scenario, the only
way to know it was completed at
• A typical study includes 250–300 patients who are 8:00 pm is because the subject
in trial for 3 months, required to complete 1 diary said so.
daily. This translates into 90 diaries per patient.
• Processing each diary involves form creation,
printing, translation, binding and shipping
to sites; followed by data entry, transfer, 2. Forgetful Patients
reconciliation, queries and changes; and finally are a data manager’s dream, but
return shipment. The estimated cost is $20/page. a clinical researcher’s nightmare.
The worst part is, you have no way
Per Patient Cost Paper PRO $1800 of knowing that you’re losing data
Per Patient Average Cost PHT ePRO $1300 until it’s too late.
Electronic capture savings per patient $500
• Average savings on a typical study using ePRO
vs. paper is $125,000 – $150,000.
3. Selective Patients
Does ePRO Data Quality Differ from Paper? force you to make assumptions -
Improvements in data quality provided by electronic did the subject mean December
patient-reported outcome systems are widely or February? Was the medication
reported and accepted throughout the clinical taken? Doing anything other
research community. Patient diary data collected than throwing this away could be
electronically is time-stamped, legible and logical dangerous.
with real-time validation provided to patients while
entering diary information. ePRO supports multi-site
international trials with remote data monitoring via
the web with real-time status reporting overall and 4. Enthusiastic Patients have
per site, participant status tracking and on-demand tremendous energy and want
subject randomization. to provide as much information
as they can. But it is illogical,
Contrary to paper diaries, ePRO data collection
illegible and likely contains AEs.
can ensure complete patient responses. With
This is an ideal patient for an
trustworthy data, trial sponsors no longer run the
eDiary!
risk of having a promising compound rejected due
to unreliable paper PRO data.
Paper diary examples courtesy of Dr. Stuart Donovan

2. 2
Enhanced data integrity further enables What is the FDA position on ePRO? Which Trials are Best Suited for ePRO?
1. Attributable, legible, contemporaneous, The FDA has reviewed ePRO vs. PRO, and cites Trials with patient-reported endpoints–
original and accurate (ALCOA) patient data that unsupervised data entry as a major drawback whether in home or in medical offices–report
is complete and time-stamped through the use to paper reported outcomes. PRO instruments rapid gains in efficiencies and data integrity
of alarms, branching logic and edit checks; [paper] that require patients to rely on memory, with ePRO. Trials within these therapeutic areas
2. Reduced data variance for improved quality especially if they must recall over a period of time, (TAs) have been early adopters of ePRO:
of study results and reduced number of or to average their response over a period of
• Neurology/CNS
patients to show efficacy; time, may threaten the accuracy of the PRO data.
• Respiratory
3. Real time access to diary data between According to the FDA, “If a patient diary or • Behavior Modification
visits for enhanced safety and compliance some other form of unsupervised data entry is • Gastrointestinal
monitoring; used, the FDA plans to review the protocol to • Genitourinary
determine what measures are taken to ensure • Immunology
4. Adaptive trial designs with pre-programmed
that patients make entries according to the
adaptations and reduced standard deviation for PHT has also demonstrated ePRO efficiencies
study design and not, for example, just before a
more conclusive planned interim analyses; and within
clinic visit when their reports will be collected.”1
5. Libraries of experience and metrics with • Oncology
data including compliance and data variance/ The European Medicines Agency (EMEA) has
• Endocrine and metabolic disorders
standard deviations for specific indications. also commented on ePRO vs. PRO, providing
• Dermatology
this Guidance on endpoints in asthma: “If home
How Does ePRO Enable Faster Trials? • Ears, nose, throat, eye and teeth
recording equipment is used, reproducibility is
Cycle times and therefore trial times can be • Musculo-skeletal
particularly important and an electronic diary
reduced with electronic patient-reported record should be considered to validate the Trials across TAs where patient-reported data
outcomes. Electronic data capture eliminates timing of measurements.”2 ; and on efficacy for is sensitive in nature, where it’s critical to
manual data entry times and other data point steroid contraceptive, “The separate calculation track adverse symptoms between visits such
changes. Final data analysis sets can be of the Pearl Index for method failure requires as worsening symptoms, rescue medications,
provided within days after a trial’s conclusion. reliable methods for recording of compliance specific events such as suicide ideation also
By reducing data variance, fewer patients (e.g. electronic patient diaries) not to include received increased ROI when utilizing ePRO.
are required especially in Phase II trials. non-compliers in the denominator.”3 Summary
Scientific outcomes are more conclusive, Sponsors, trial managers and health outcome
and greater power of study is achieved by directors continue to obtain greater degrees
reduced standard deviation. of data quality, program efficiency and patient
ePRO does not eliminate the need for accurate safety with ePRO. For more information, contact
data review and monitoring, but it does enable PHT at 1.877.360.2901.
trial sponsors to improve power of study with
smaller samples, and to reach no-go decisions 1) Lines 334-337, ‘Guidance for Industry. Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. DRAFT GUIDANCE.’
U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and
much faster than they could otherwise. Research (CBER), Center for Devices and Radiological Health (CDRH). February 2006 2) Section 8.1, ‘Note for Guidance on the Clinical Investigation of Medicinal
Products in the Treatment of Asthma’, The European Agency for the Evaluation of Medicinal Products, Evaluation of Medicines for Human Use, November 2002. 3)
Section 3.1, ‘Note for Guidance on Clinical Investigation of Steroid Contraceptives in Women, The European Agency for the Evaluation of Medicinal Products, Evaluation
of Medicines for Human Use, February 2000.
Case Study: Novartis
The FDA approved a Novartis drug for chronic Once the study was already underway, the FDA surprised
constipation for use with women, but indicated more Study power was Novartis by deciding to approve the drug for men without
data would be needed for men. Therefore, Novartis reached with less further data. Novartis stopped the trial, but allowed the 322
planned another study and estimated a sample size enrolled subjects to complete treatment. To the amazement
than one-third
of 1,026 male subjects would be required to prove of the clinical team, study power was reached with 69%
efficacy based on traditional paper variance statistics. the planned- fewer subjects - representing less than one-third the planned
Subsequently, the pharmaceutical company elected to sample size! sample size!
use PHT’s LogPad® System instead of paper.

3. 3
Case Study: Merck Research Laboratories
Merck initiated the first randomized trial to evaluate the relative
MORNING
QUESTIONA
IRE (Continued
capacities of paper diaries and electronic patient diaries
8. How would )
you describ
e the quality
of your sleep
1= Excellent
❑ 2= Good
❑ 3= Fair ❑
last night? (ch
4= Poor ❑
eck only one
box.) (Figure 1) to prove efficacy. 101 patients were randomized to two
arms based on data capture method (paper or LogPad) and treated
with an approved drug for insomnia. The study examined primary
endpoint data of change in minutes of sleep time and compared
results from the arms in many categories.
Figure 1: A study question on the LogPad and paper diary
Figure 2: Paper Distribution Figure 3: LogPad Distribution Figure 4: Distribution Overlay
Data Analysis Results
Data captured from both arms revealed statistically equivalent Analysis performed by Merck showed a 35% lower standard deviation
means (118 minutes from paper, 109 minutes from the LogPad), but for LogPad data as compared to paper. Merck calculated that this
the ranges were different. As shown in Figure 2, the distribution of reduced variance would have enabled them to reach study power with
responses on paper varied widely from -20 to 380. This means one 56% fewer patients–saving an estimated $340,000 (assuming $6,000
subject claimed to have average 20 minutes less sleep per night, while per patient).
another reported an additional 6 hours. Further, the distribution tends In addition, Merck had to process three times more data changes
to cluster around 30-, 60- and 90-minute intervals. This suggests and notification forms to clarify paper data, and incurred 58 hours
evidence of recall bias, as responses are more general and less precise of data entry compared to zero for the LogPad arm. Compliance was
when made after-the-fact. high in both arms (96% for paper, 92% for LogPad), but as discussed
Conversely, the LogPad distribution in Figure 3 is much tighter around earlier only ePRO compliance can be verified as opposed to purported
the mean and more Gaussian, with fewer and less extreme outliers. by subjects.
Meanwhile, continuous responses indicate more accurate data These findings were presented by Jay Pearson, Senior Director at Merck.
reporting. A visual inspection of Figure 4 shows the comparison
of variance.

4. Electronic Patient-Reported Outcome (ePRO) Solutions
Read About:
Banning Paper Diaries
Why Paper Diaries Should Be Banned in
Clinical Trials
Pharmaceutical Executive Europe, March, 2009
PHT author Valdo Arnera, MD, outlines specific
reasons why pharmaceutical and biotechnology
companies should replace paper diaries
with ePRO.
Read it online at: www.phtcorp.com.
PHT Electronic Patient-Reported Outcome
(ePRO) System Components
For more information:
LogPad
US Account Executives: 1.877.360.2910 SitePad®
PHT LogPad – The mobile
European Account Executives: 41.22.879.91.00 StudyWorks® Hand Held for home eDiaries
eSense™ Sensors
ePRO Designer
About PHT Corporation Study Archive
PHT is the global innovator in ePRO (electronic patient-reported
PROVision™ Scientific Services
outcome) systems that simplify clinical data management and
streamline eClinical trials. Since 1994, patient experiences Trial Success Program™ (TSP)
captured by PHT’s ePRO System have been used successfully PHT Support Center
in over 440 global trials by more than 100 biopharmaceutical Scientific Review and Validation
companies, resulting in at least 14 regulatory submissions Site Telecom Assessments
and 11 approvals. By capturing high-quality and time-stamped
Technology Transfer
assessments, trial sponsors are able to run smaller, safer and
more conclusive clinical research programs resulting in significant
R&D cost savings. For more information, review the educational
content and interactive PHT ePRO System demonstrations at “I believe the SitePad Tablet
is something that can
PHT’s award-winning site www.phtcorp.com.
help our entire industry,
and patients, as well,” says Joachim Löwin,
Clinical Information Science Leader, AstraZeneca.
PHT Corporation PHT Corporation Sàrl Insights Q1 2009
500 Rutherford Avenue 2, chemin Louis-Hubert www.phtcorp.com
Boston, MA 02129 USA 1213 Petit-Lancy, Geneva, Switzerland Copyright © 2010 PHT Corporation
Toll-Free: 877.360.2901 Phone: 41.22.879.91.00 v8.2010