EDC AND PATIENT SAFETY

1. EDC AND PATIENT SAFETY Are we doing our best in 2005 to fulfill ethical commitments to patients by waiting to collate information in clinical trials using paper? Dr. Jeffrey A. Green President & Chief Executive Officer DATATRAK International, Inc.

2. Economic & Efficiency Benefits are Nice, But…. Patient Safety in Clinical Trials Should be Paramount • Isn’t patient safety being handled perfectly right now? • 90% of clinical trials use paper with a known 4-6 month delay in order for data to be available in an analyzable format • What you don’t know – you can’t react to • The 24-hour call requirement from PIs is inadequate because: • They have no access to an accumulated database – they are only responsible for their patients • Most AEs that result in market removal are “under the radar screen” and are not the result of SAEs which require phone calls from PIs

3. Actual Case Studies of the Impact of Insufficient Data Awareness in Clinical Trials • With EDC, you can delay, but you can’t hide – MetriX reviews of CRO monitoring practices • What you don’t know – you can’t react to – And, if you don’t look for weeks to months, it’s impossible to know! • If no one “raises the bar of performance”, everyone’s compliant and there is no new standard of practice • Vioxx and Celebrex (more?) case examples – Two problems • Failure to react – Criminal consequences • Failure to know – Standard of practice consequences

5. Trial characteristics used in MetriX Analysis

6. Patient Visit –> Data Entry –> Query Raised –> INV reaction –> Query closed Contracts stated that data entry should happen within 5 days

7. Patient Visit –> Data Entry –> Query Raised –> INV reaction –> Query closed 18% to 40% of queries were raised more than 90 days after data entry

8. Patient Visit –> Data Entry –> Query Raised –> INV reaction –> Query closed Investigator reaction to queries is much slower than initial data entry

9. INCONSISTENCIES OF CLINICAL TRIAL DATA COLLECTION WITH PARALLEL EXAMPLES • Patient care parallel • EKG Parallel • Investment parallel • Pharmaceutical company & retail parallels • Prescription launch and sales tracking • Revenue figures down to the zip code tracked electronically • There’s a disturbing lack of urgency for timely data awareness in clinical trials that would never be tolerated in the examples above • One would logically think that with the uncertainties of administering investigational agents, the ethicalness of urgency would be greater • Is it appropriate that our “excuse” for not having maximal “data awareness” is that we have to re-organize data management departments?

10. Patient, Investigator & Societal Views Moving Forward • Patients would find the realities of data processing in clinical trials “surprising”. They would believe the industry is more innovative. • Concerns of physician investigators on the “front lines”. • Is it a conflict of interest to have the complete control of the availability of a marketed drug left up to the entity that benefits from its sales? 3 month delay of Vioxx = $500 million • Suggestions for a Safety Model of the future leveraging technology and real-time “data awareness” • “Real-time “data awareness” is possible today • FDA should take a lead role in defining a new “standard of practice” • “Data awareness” with investigational agents should be summarized and reviewed weekly to avoid unnecessary exposure

11. SAS DATASETS IN 24 Hours Today’s Paper Based DATA Collection to Analysis Process FedEx CRF SAS CDMS Research Site Data Management Bio Stats SAS Programmer Process With AWARE Powered By SAS SAS Research Site Research Site BioStats/Safety Data Mgmt SAS Programmer