Overview of ePRO

Make the Most of Every Patient

Barbara Marino, PhD, RNDirector Clinical Operations, Scientific [email protected]

19 March 2009

An Overview of ePROAn Overview of ePRO

Prepared exclusively for Breakfast Seminar Participants

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Agenda

• ePRO Across Technologies• Why Use ePRO• How ePRO Works• Where ePRO is Used• What We’re Learning About ePRO• ePRO Next Generation


Patient Reported Outcomes (PRO) on Paper

CHECK THE ONE RESPONSE TO EACH ITEM THAT BEST DESCRIBES YOU FOR THE PAST SEVEN DAYS.


ePRO: Interactive Web Response (IWR)


ePRO: Interactive Voice Response (IVR)

When you hear the answer that best describes youfor t he past 7 days, say "Yes" or enter 1 on yourtelephone keypad. If the answer does not describeyou, say "No" or enter 2 on your keypad.

During the past 7 days, most of the time I awakenno more than 30 mintues before I need to get up.

More than half of the time I awaken more than 30miuntes before I need to get up.

I almost always awaken at least 1 hour or so beforeI need to but I go back to sleep eventually.

I awaken at least 1 hour before I need to, and can'tgo back to sleep.

Advance toQuestion 4

Yes

No

No

No

No

Yes

Yes

Yes

.


ePRO: Tablet or Handheld Computers


Why Use ePRO? Data Quality on Paper

Four types of paper responses:

Courtesy of Dr. Stuart Donovan, Knoll Pharmaceuticals

Perfect Patient Impossible to verify response date/time

The Forgetful Patient Provides no data at all; takes weeks to notice

Selective Patient Missing data presents data analysis issues

Enthusiastic Patient Great energy, unusable data; ideal on a LogPad


Why Use ePRO: Data Accuracy on Paper

Observed vs. Purported Measurements & Errors

Observed (Objective) Compliance

Purported

(Written in Diary) Compliance

Discrepancies Between the Two

Number of Subjects

A. Stone et al, BMJ 2002; 324:1193-4

11% 90% 79% 80

G. Jonasson et al, Eur Respir J,14,1999

77% 93% 16% 163

H. Milgrom et al, J. of Allergy & Immunol.,98, 1996

58% 95% 37% 24

S. Spector et al, J. Allergy Clin. Immunol.,7,1986

47% 90% 43% 19

R.J. Straka et al, Pharmacotherapy,17,1997

55% 71% 16% 68

P. Verschelden et al, Eur Respir J,9,1996

22% 20

F.Chmelik et al, Annals of Allergy,73,1994

58% 20

M. Simmons et al, Chest, 118, 2, 2000

30% 101

R. Mazze et al, The Amer. J. of Medicine,77,1984

74% 19

Averages 59 + 13% 87 + 11% 42 + 21% 57


How ePRO Works: an ePRO System

ePRO Designer

LogPad

Subjects

SitePad

Sites

Redundant Central Servers

Hosted at two secure third-

party co-location facilities

Study Archive

Sites/Sponsors

StudyWorks

Sites/Sponsors


How ePRO Works: Take a Look

Demonstration of ePRO on a Handheld


Where ePRO is Used

eDiares Used Here

No Recent eDiary Trials


Languages and Dialects Supported

Afrikaans (South Africa)ArabicArabic (Tunisia)Armenian BulgarianCebuano-CebuChinese Simplified (China)Chinese Simplified (Singapore)Chinese Simplified (Taiwan)Chinese Traditional (Hong Kong)Chinese Traditional (Taiwan)CroatianCzechDanishDutch (Belgium)Dutch (Netherlands)English (Australia)English (Canada)English (Hong Kong)English (India)English (New Zealand)English (South Africa)English (UK)English (US)EstonianFinnishFrench (Belgium)

French (Canada)French (France)German (Austria)German (Germany)GreekHebrew HiligaynonHindiHungarianIcelandicIndonesianItalianJapaneseKannada KoreanLatvianLithuanianMalayMalayalam MarathiMongolianNorwegianPolishPortuguesePortuguese (Brazil)Romanian

RussianRussian (Israel)SerbianSlovakSpanish (Argentina)Spanish (Chile)Spanish (Colombia)Spanish (Latin America)Spanish (Mexico)Spanish (Peru)Spanish (South America)Spanish (Spain)Spanish (Universal)Spanish (US)Spanish (Venezuela)SwedishTagalogTamilTeluguThai UkrainianUrdu VietnameseXhosaZulu


Where ePRO is Used: Therapeutic Areas

Allergy Allergic rhinitis, conjunctivitis/rhinitis, cat allergy, ragweed, grass/pollen, seasonal rhinitis

Behavior Modification Smoking cessation

Cardiovascular Anti-arrhythmia, deep vein thrombosis, dyslipidemia

Endocrinology Diabetes, pregnancy prevention, vasomotor symptoms

Gastrointestinal Crohn’s disease, chronic constipation, irritable bowel syndrome, Gastroesophageal Reflux Disease , heartburn, pediatric gastrointestinal disturbances

Genitourinary PMS, dysmenorrhea, female sexual dysfunction, Erectile dysfunction, urinary incontinence

Immunology Common cold, HIV, herpes , vaccines

Neurology ADHD, ADHD with tic disorder, bipolar disorder, insomnia, mild cognitive impairment, multiple sclerosis, Parkinson’s disease, restless leg syndrome, sleep disorders, Weakness/Paralysis

Oncology Breast cancer, multiple myeloma, prostate cancer. oncology pain

CNS (including Pain) Analgesia, chronic pain, dental pain, diabetic neuropathy, low back pain,, post-surgical pain, neuropathic pain, radiculopathy, post-herpetic neuralgia, bunionectomy, fibromyalgia, migraines, rheumatoid arthritis

Respiratory Asthma, COPD

Other Infectious diseases, osteoarthritis

Trials by Phase…Pilot/Phase I: 6% Phase II: 34% Phase III: 42% Phase IV: 18%


ePRO and Objective Patient Data

eSense Measurement Devices– Appropriate and timely use of devices (e.g. PEF meters, glucometers)– Bluetooth, infrared or exclusive radio integration– Timestamps, windows for completion to assure accuracy

Cognitive Assessments– Response time and concentration as efficacy measures– Seamless integration with eDiary– Endpoint in areas like insomnia, migraine, Alzheimer's

Adverse Event Monitoring– Identify responses from subject diary that indicate possible AE– Alert subject and site– Escalating alerts for serious conditions

Kris Sarajian

Find out which cog. assessments we've done


ePRO Integration With Other Trial Information

ePRO and EDC– Populate EDC forms with diary data

– Simplify management for sites

– Use CROs to merge data from multiple streams for a paper-free trial

– CDISC ODM export certification

More Than EDC– eSense devices

– Adaptive trial designs

– Eligibility data from multiple providers

– Cognitive assessments

Seamless EDC Integration PHT has invested in CDISC ODM certification to ensure its XML eSource data are easily integrated with other compliant eClinical systems

Integration Experience


What We’re Learning: ePRO and Data Quality

– Insomnia: standard care– 35% lower standard deviation– Study power with 56% fewer subjects– Potential $340,000 in savings

– Constipation in men– Phase III trial called for 1,026 subjects– Approval granted after 322 enrolled – Efficacy was proven with 69% fewer patients

– Female Sexual Dysfunction– Comparison of ePRO and PRO– No treatment– 50% more encounters reported with ePRO


Data Variance ePRO and Paper in Merck Pilot

-20 20 60 100 140 180 220 260 300 340 380 4200

1

2

3

4

5

6

Data from Paper Diary Arm

– Clustered distribution around intervals (30, 60, 90 minutes) suggests recall bias or invented data

– Wide range of responses (from 20 minutes less to 6 hours more sleep)

Change in Sleep Time (minutes)

Nu

mb

er

of

Pa

tie

nts

Data from eDiary Arm– Statistically equivalent

mean, with significantly smaller data variance

– More Gaussian distribution, tighter around the mean


Merck Pilot: Summary of Results

Area of Interest in Trial PHT LogPad Paper Diaries

Calculated patients to yield 90% study power

N=44 N=101 (56% more than LogPad)

Potential cost savings $340,000 * --

Distribution of responses More Gaussian Suggests recall bias

Standard deviation 35% smaller --

Sleep Change estimates Nearly identical --

Coefficient of variance Significantly smaller --

Data Point Changes and Notification Forms -- 3x more of each

Compliance (% of diaries completed) 92% objective subject compliance

96% purported subject compliance

Cost:

Data Entry (hr)

Data Review (hr)

0

10.5

58

10.5

* Estimated by assuming a total per-patient cost of $6,000

Results presented at DIA 2004 and at the International Society for Quality of Life Research (ISOQOL) 2004 symposium


The Elderly and ePRO

86% 85% 90% 91%

0102030405060708090

100

Avera

ge C

om

pli

an

ce

Youngerthan 50(n=22)

50-59(n=41)

60-69(n=41)

70 orOlder(n=19)Age Group

Average Compliance by Age Group

Diabetic Neuropathy – Subjects Aged 32-93


eSense Case Study: Global Asthma Trial

Study details– Global Phase IIb trial with > 500 subjects in 15 countries using

portable electronic PEF meter– Sponsored by a Top-5 pharmaceutical company– Subjects take morning and evening PEF values using an

eSense PiKo meter by Ferraris Respiratory – Subjects complete an evening diary on an eSense LogPad– Data is available in real-time for review by site coordinators

and sponsors

eSense: 86% Manual: 13% Skipped: 1%

New Gold StandardOperational data from a global asthma study indicate subjects use eSense even when allowed to transcribe data manually.


Summary: ePRO Advantages

• Trustworthy patient data – Verified time of entry– Complete, legible, logical reports– Front-end edit checks– Improved reliability and validity

• Reduced respondent and site burden• Real-time trial and subject management• More reliable data for regulatory submissions• Smaller sample sizes in Phase II• More conclusive trials in Phase III• Adaptive trial designs• Efficient data collection process• Ability to ask new scientific questions

– eSense measurement devices– Cognitive assessments


Questions?

Barbara Marino

PHT Corporation

617-973-1612

[email protected]

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www.phtcorp.com

Thank You!

Health & Medicine

Overview of ePRO