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 SAFETYEDC AND PATIENT SAFETY

FDA Advisory Panel on Drug Safety and Risk Management Presentation

Patient Safety in Clinical Trials Should be Patient Safety in Clinical Trials Should be ParamountParamount

• 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, Economic & Efficiency Benefits are Nice, But….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 Actual Case Studies of the Impact of Insufficient Data Awareness in Clinical TrialsInsufficient Data Awareness in Clinical Trials

FDA Advisory Panel on Drug Safety and Risk Management Presentation

Data Review Report

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Days b

etw

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Average by country of difference between data entry date vs. first date review date.

Source: DATATRAK EDC™ and Clinical Services, DATATRAK International, Inc.

FDA Advisory Panel on Drug Safety and Risk Management Presentation

Trial characteristics used in MetriX Analysis

Study Total A B C D E F G H I K L M

Study online since

05/03 06/03 04/03 09/03 01/04 05/04 06/04 04/04 08/04 08/04 08/04 11/01

No of Investigative Sites

1,233 64 63 45 292 67 57 54 115 13 39 107 317

No of INV users

3,271 111 115 85 738 130 121 116 188 32 73 188 1374

No of CRAs 339 38 36 34 48 27 27 28 29 22 10 36 85

No of Sponsor users

322 36 36 10 68 33 16 12 32 23 7 32 13

No of Countries

3 3 1 17 10 1 1 5 10 2 3 15

No of Patients enrolled / planned

16,130 375 375 375 3600 200 740 740 1725 400 300 300 7,000

No of entries in the database

2,843,316 59,860 48,577 223,034 936,393 158,455 150,063 132,212 18,571 11,482 4,526 1,485 1,098,658

FDA Advisory Panel on Drug Safety and Risk Management Presentation

0 5 1015202530354045505560657075808590StudyA

StudyB

StudyC

StudyD

StudyE

0%

5%

10%

15%

20%

25%

Visi

t dat

es e

nter

ed

days after visit

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

0 5 1015202530354045505560657075808590StudyA

StudyB

StudyC

StudyD

StudyE

0%

10%

20%

30%

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50%

Que

ries

rais

ed b

y C

RA

/CD

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days after initial data entry

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

0 5 1015202530354045505560657075808590StudyA

StudyB

StudyC

StudyD

StudyE

0%

5%

10%

15%

20%

INV

reac

tion

(cha

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data

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days after query raised

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 INCONSISTENCIES OF CLINICAL TRIAL DATA COLLECTION WITH PARALLEL EXAMPLESCOLLECTION 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 Patient, Investigator & Societal Views Moving ForwardViews Moving Forward

FDA Advisory Panel on Drug Safety and Risk Management Presentation

Research Site

CRF FedExCDMS

Data Management

SAS

SAS Programme

r

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 Programme

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Data Mgmt