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
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
190
Days b
etw
een
Data
En
try D
ate
an
d D
ata
Revie
w D
ate
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%
40%
50%
Que
ries
rais
ed b
y C
RA
/CD
M
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
nge
data
or
give
com
men
t)
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
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SAS DATASETS IN 24 Hours
Today’s Paper Based DATA Collection to Analysis Process
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Process With AWARE Powered By SAS
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