# Presentation: 508256

## Electronic Diaries: Impact on Drug Development

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

## 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

## Patient Reported Outcomes (PROs)

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

## 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

## Paper: Apparent Compliance

- Based on patient time/date entries

- Stone et al, BMJ, 2002
- Stone et al, CCT, 2003

## Paper: Test / Verify Apparent Compliance

- Paper: Test / Verify Apparent Compliance

- Verify patient-entered completion times

## Paper: Actual Compliance

- Based on instrumented paper diary

- Observed back-filling, hoarding, forward-filling

- Stone et al, BMJ, 2002
- Stone et al, CCT, 2003

## eDiary: Actual Compliance

- Based on electronic time stamp

- Stone et al, BMJ, 2002
- Stone et al, CCT, 2003

## Contribution of eDiary toClinical 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

## 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

## Science, Technology & Regulation are In Place & Proven

- _Science_: Improves validity, enhances power; >100 published studies
- _Technology_: Over 18 years field experience in clinical research
- _Regulation_: ALCOA, predicate rules
- Approved NDA (Allergan Acular LS)

## 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)

## 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

## Innovation

- “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

- Reporting Platforms

## 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