1. Copyright © CRF Box, Ltd. All rights reserved. 1 Introduction to Electronic Data Collection Methods; Improving Data Quality and Integrity in Epidemiological Safety Studies and Patient Registries Greg Gogates VP, Quality Management & Regulatory Affairs

2. Copyright © CRF Box, Ltd. All rights reserved. 2 Overview: Pharmacoviligance requires that information assurance be securely managed. It also requires that risk management is being applied in a reasonable & practical manner. Current challenges include the collection and reporting of spontaneous patient-level safety data, improved timeliness, and increased public awareness. Electronic methods (PDAs & mobile phones) can be used to collect safety data directly from patients and pharmaceutical industry practitioners to provide means of collecting and reporting important data. Pros and cons of mobile technology vs. more traditional methods are discussed leveraging on current and emerging technology solutions.

3. Copyright © CRF Box, Ltd. All rights reserved. 3 Current Typical Compliance  Good compliance exists with;  Clinical Trials - (GCP driven)  Hospitals - (salaried position)  Pharmacies - (salaried position)  Why – AE reporting is part of the daily salaried job.  Sporadic compliance exists with;  Citizens – because of lack of knowledge, care, etc.  Private physicians – “broke-fix people contractors” – no added benefit to their bottom line. Being squeezed by higher costs, lower billing. No real incentives.  By it’s nature, all voluntary reporting.

4. Copyright © CRF Box, Ltd. All rights reserved. 4 Traditional MedWatch AE Methods  Clinical Study  Use of mail-in form 3500A  Online 3500A form  Pharma AE system  These are all codified and mandatory!  Post-marketing  Use of toll and toll-free numbers  Use of FDA mail-in forms 1639, 3500  Online 3500 form  Additional systems for vaccines and veterinary products  Dependent on forms that are not mandatory!  Custom On-line reporting tools exist, but do not travel home with patients.

5. Copyright © CRF Box, Ltd. All rights reserved. 5 Current Challenges:  Increased desire to collect and report spontaneous patient-level safety data.  Regulatory demand for improved timeliness of the reported safety data.  Stay within HIPAA rules.  Increased public awareness of potential safety concerns related to pharmaceutical products.  How respond to these important new challenges cost-effectively?  The key term is spontaneity!

6. Copyright © CRF Box, Ltd. All rights reserved. 6 Electronic Tools to Collect Safety Data Directly from Patients Data is stored centrally and submitted for regulatory review Patients can use a variety of different remote technologies To report the data Sponsor safety departments, regulatory bodies and patient advocacy organizations can access the data “near real-time”

7. Copyright © CRF Box, Ltd. All rights reserved. 7  Patient can use their proprietary electronic devices when available (e.g. a cellular phone).  Budgets permitting, patients may be given a proprietary device for data reporting (e.g. a cellular phone or cellular PDA).  All that is recorded from the patient is their cellular phone number. This can be done at point of prescription.  Periodic Safety questions are sent and answers collected using text messaging technology (text-based, no voice) to ensure consistent data quality and ease of use.  Safety data is aggregated into a central database for standardized reporting.  Voice follow-up can be done upon request and permission. Implementation Issues

8. Copyright © CRF Box, Ltd. All rights reserved. 8  Patient does not need (necessarily) to visit the physician to report adverse events.  Sponsor has a system that enables ”near real-time” collection and analysis of important safety data.  Timeliness of regulatory reporting and action is improved.  Questions can be changed on-the-fly.  Cost of the electronic technology adds to the program budget.  Electronic tools may not be applicable to all patient populations (elderly, disabled).  Detailed adverse event analysis still needs to be conducted by the physician/ nurse. Pros & Cons of Personal e-Safety Data Reporting

9. Copyright © CRF Box, Ltd. All rights reserved. 9 Example: Electronic safety data reporting in a pre-marketing clinical trial  Study phase: III  Therapeutic area: vaccination for a viral infection.  Patient population: Currently 12,000 children in Europe recruited across 75 sites.  Patient monitoring process: after receiving the vaccine, patients are monitored for safety reasons.  Electronic technology: patients are using their personal cellular phones to report symptoms and adverse events.  Length of the monitoring period/ patient: 1.5 years.  Follow-up frequency/ patient after vaccination: 4 weeks, on average.

10. Copyright © CRF Box, Ltd. All rights reserved. 10 Conclusions  Existing Mobile phone infrastructure can be used to collect patient data.  EU mobile systems are mature with good interoperability.  US mobile systems have sporadic coverage with constant improvements and interoperability upgrades.  Considerations should be given to this type of pharmacoviligiance as it is viable today.

11. Copyright © CRF Box, Ltd. All rights reserved. 11 For further information or questions Contact: greg.gogates@crfbox.com