Electronic Diaries: Impact on Drug Development

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Electronic Diaries Impact on Drug Development

• Saul Shiffman, Ph.D.
• Chief Science Officer
• invivodata, inc.
• Advisory Committee for Pharmaceutical Science
• 19-20 October, 2004

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Outline

• 25 of clinical trials use patient diaries
• Paper diaries
• Slow completion of clinical trials
• Fail to meet FDA data standards
• Electronic diaries
• Enhance efficiency and speed trials
• Meet FDA data standards
• Allow smaller, more efficient studies
• FDA can meet the goals of Critical Path
  Initiative by
• Applying standards for data quality to all
  diaries
• Removing doubt about acceptance of electronic
  diary data

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Patient Reported Outcomes (PROs)

• Subjective states
• e.g., pain, dizziness
• Symptoms observed by the patient
• e.g., asthma attacks, bowel movements

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Paper Diaries Inefficient, Poor Data Quality

• Paper diaries
• Up to 80 of paper diary
  cards contain
  significant errors (Quinn et al., 2000)
• Slows database lock

• eDiary
• 98 reduction in data cleaning
• Efficient data management
• On-line data edits
• Accelerated data lock
• eDiaries 1 day after LPO
• Paper diaries 4 weeks after LPO

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Paper Apparent Compliance
Based on patient time/date entries
Stone et al, BMJ, 2002 Stone et al, CCT, 2003
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Paper Test / Verify Apparent Compliance
Verify patient-entered completion times
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Paper Actual Compliance
Based on instrumented paper diary
Observed back-filling, hoarding, forward-filling
Stone et al, BMJ, 2002 Stone et al, CCT, 2003
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eDiary Actual Compliance
Based on electronic time stamp
Stone et al, BMJ, 2002 Stone et al, CCT, 2003
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Contribution of eDiary toClinical Development
Efficiency

• Decreases error
• Avoidance of back-filling, faked data
• Yields more definitive indication of drug effects
• Increased power
• Lower error rate
• Compared similar studies with paper diary vs.
  eDiary

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Reduced Noise, Increased Validity More
Efficient Clinical Development

• eDiaries yielded (McKenzie et al, 2004 Pearson
  et al, 2004)
• 33 reduction in variability
• 50 reduction in sample size
• Smaller trials
• Fewer Trials

More efficient, faster, cheaper clinical
development
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Science, Technology Regulation are In Place
Proven

• Science Improves validity, enhances power gt100
  published studies
• Technology Over 18 years field experience in
  clinical research
• Regulation ALCOA, predicate rules
• Approved NDA (Allergan Acular LS)

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What Is Needed?

• Apply data quality regulations consistently to
  paper and eDiary data
• Promote adoption of modern, efficient,
  scientifically valid methods for collection of
  PROs
• Make clear statement RE acceptance of electronic
  diary data (remove FUD)

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Conclusions

• Paper diaries
• Slow completion of clinical trials
• Fail to meet FDA data standards
• Electronic diaries
• Enhance efficiency and speed trials
• Meet FDA data standards
• Allow smaller, more efficient studies
• FDA can meet the goals of Critical Path
  Initiative by
• Applying standards for data quality to all
  diaries
• Removing doubt about acceptance of electronic
  diary data

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Innovation
Reporting Platforms
That it will ever come into general use,
notwithstanding its value, is extremely doubtful
because its beneficial application requires much
time and gives a good bit of trouble, both to the
patient and to the practitioner because its hue
and character are foreign and opposed to all our
habits and associations. The Source  The
London Times, 1834 The Subject  The Stethoscope
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ALCOA and Diaries
eDiaries Paper Diaries
Attributable Patient passwords, code, and device identification Handwriting?
Legibility Digital recording, human-readable output Depends upon nature of diary and subject
Contemporaneous Time/date stamping enforcement of protocol sequencing Cannot verify no enforcement of protocol sequencing.
Original Patients cannot change the data once recorded Not clear if changes made to data.
Accurate Time/date stamping Cannot confirm when completed
April 1999 FDA Guidance for Computerized
Systems Used in Clinical Trials