FDA Advisory Panel on Drug Safety and Risk Management Presentation 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. EDC AND PATIENT SAFETY

FDA Advisory Panel on Drug Safety and Risk Management Presentation 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 Economic & Efficiency Benefits are Nice, But….

FDA Advisory Panel on Drug Safety and Risk Management Presentation 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 Actual Case Studies of the Impact of Insufficient Data Awareness in Clinical Trials

FDA Advisory Panel on Drug Safety and Risk Management Presentation

Trial characteristics used in MetriX Analysis Study TotalABCDEFGHIKLM Study online since 05/0306/0304/0309/0301/0405/0406/0404/0408/04 11/01 No of Investigative Sites 1, No of INV users 3, No of CRAs No of Sponsor users No of Countries No of Patients enrolled / planned 16, ,000 No of entries in the database 2,843,31659,86048,577223,034936,393158,455150,063132,21218,57111,4824,5261,4851,098,658

FDA Advisory Panel on Drug Safety and Risk Management Presentation Contracts stated that data entry should happen within 5 days Patient Visit –> Data Entry –> Query Raised –> INV reaction –> Query closed

FDA Advisory Panel on Drug Safety and Risk Management Presentation 18% to 40% of queries were raised more than 90 days after data entry Patient Visit –> Data Entry –> Query Raised –> INV reaction –> Query closed

FDA Advisory Panel on Drug Safety and Risk Management Presentation Investigator reaction to queries is much slower than initial data entry Patient Visit –> Data Entry –> Query Raised –> INV reaction –> Query closed

FDA Advisory Panel on Drug Safety and Risk Management Presentation 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? INCONSISTENCIES OF CLINICAL TRIAL DATA COLLECTION WITH PARALLEL EXAMPLES

FDA Advisory Panel on Drug Safety and Risk Management Presentation 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 Patient, Investigator & Societal Views Moving Forward

FDA Advisory Panel on Drug Safety and Risk Management Presentation Research Site CRF FedEx CDMS Data Management SAS SAS Programmer Bio Stats SAS DATASETS IN 24 Hours Today’s Paper Based DATA Collection to Analysis Process SAS BioStats/Safety Research Site Process With AWARE Powered By SAS Research Site SAS Programmer Data Mgmt