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Case study of eCRF implementation Case study of eCRF implementation in a neurological clinical trial in a neurological clinical trial

with CT scanswith CT scans

Case study of eCRF implementation Case study of eCRF implementation in a neurological clinical trial in a neurological clinical trial

with CT scanswith CT scans

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• Randomised, double-blind, placebo controlled study

• Phase IIIb

• 100 centers in 15 european countries

• 800 patients to be included in 3 years3 months follow-up per patient

• 2 to 4 CT-scans per patient (2400 scans planned in total)

Study type

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Data Chart

Visit 1A 1B 1C 2 3 4 5

Hour / Day Window

Baseline (3 Hrs <X 4 Hrs)

D0

Trial Drug Admin

1 Hour # 5 Min

2 Hrs# +15 Min

24 Hrs# +1 Hr

D1

7 Days# +1 Day

D7

30 Days# +2 Days

D30

90 Days# +14 Days

D90

Drug / Placebo X

Demographics x Medical History x In- / Exclusion Criteria x Informed Consent and subject information x

IVRS Contact

x

Physical Exam. x x

Pregnancy Test x (+)

Vital Signs x x x x x x x

Concomitant Therapy x x x x x x x Adverse Events x x x x x x x

12-Lead ECG x x

CT Scan x x x (*) x (*)

NIHSS x x x x x x x

Pat. Termination Record x

(+) if applicable - (*) in case of clinical deterioration

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• 3 experts must review all CT scans to check inclusion criteria, adverse events and make radiological measurements

• Experts 1 and 2 review CTs independantly

• Expert 3 will review Experts 1 and 2 evaluations, and in case of discrepancy, will give final decision

Review Commitee

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• Paper CRF

• Radiographic films

• Paper evaluation forms

Classical solution : paper and films

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InvestigatorInvestigator

IVRSIVRS

CROCRO

Expert 1Expert 1

Expert 2Expert 2

Expert 3Expert 3

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• Hypothesis : - 2400 scans (800 + 800 + 400 + 400)- 10 % will forget anonymization- CT 1 & 2 sent together, CT 3 & 4 sent together

• => 7200 CT copies800 + 400 initial EM by investigator120 requests for lack of anonymization720 additional CTs120 additional EM by investigator1200 + 1200 EM from CRO to experts 1 & 21200 + 1200 EM by experts 1 & 2 to CRO1200 EM from CRO to expert 31200 EM by expert 3 to CRO

• Total : 7920 CT copies + 8520 express mails

Classical solution : measurements

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• Optimistic hypothesis : - invest to CRO : 2 days

- CRO analysis and data entry : 2 days - EM to experts 1 & 2 : 1 day - review by experts 1 & 2 : 1 day - EM by experts 1 & 2 to CRO : 1 day - CRO analysis and verification : 1 day - EM to expert 3 : 1 day - review by expert 3 : 1 day - EM by expert 3 to CRO : 1 day

=> Best case : 11 daysif anonymization required : + 3 days = 14 days

• Pitfalls : - difficult measurements with films- requires double data entry by CRO

Classical solution : measurements

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• Paper CRF for investigator

• Electronic images copied onto CD-Rom

• Electronic evaluation forms

Electronic solution (75 %)

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InvestigatorInvestigator

IVRSIVRS

Expert 1Expert 1

Expert 2Expert 2

Expert 3Expert 3

CROCRO

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• Hypothesis : - 2400 scans (800 + 800 + 400 + 400)- 10 % will forget anonymization- CT 1 & 2 sent together, CT 3 & 4 sent together

• => 1200 CD roms burnt by investigator800 + 400 initial EM by investigator240 anonymization by CROno additional CD-Romsno additional EM by investigator2400 upload by CRO in databaseno EM from CRO to experts 1 & 2no EM by experts 1 & 2 to CROno EM from CRO to expert 3no EM by expert 3 to CRO

• Total : 1200 CD-roms + 1200 express mails

Electronic solution : measurements

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• Optimistic hypothesis : - invest to CRO : 2 days

- CRO analysis and data entry : 2 days - EM to experts 1 & 2 : 0 day - review by experts 1 & 2 : 1 day - EM by experts 1 & 2 to CRO : 0 day - CRO analysis and verification : 0 day - EM to expert 3 : 0 day - review by expert 3 : 1 day - EM by expert 3 to CRO : 0 day

=> Best case : 6 daysif anonymization required : + 1 day = 7 days

• Advantages : - electronic images allow digital measurements- anonymization can be done by CRO electronically

Electronic solution : measurements

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• Direct access to data for all authorized users

• Real-time follow-up

• Audit trail

• Alarms

• Performance measurements

• Investigators can access experts evaluation

• Electronic images and measurement tools

Other advantages

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• Encryption

• Electronic signature

• Profile management

• Audit trail

• Database protection (firewall, physical security)

• Back-ups

Security issues