An integrated approach to successful eClinical trials CCRA Seminar: Standards in Electronic Data Capture London 1 November 2005 Dr Bill Byrom Product Strategy Director, ClinPhone Group Ltd.

Presentation contents Common application of IVR/IWR in today’s clinical trials Why integrate EDC and IVR? Integration overview Case study: Procter & Gamble Pharmaceuticals Demonstration movie Conclusions

Common IVR / IWR application Typical application areas in today’s clinical trials

IVR/IWR application Secure telephone / web access for the performance of various site-based, sponsor-based, or patient-based activities. Randomization Emergency Code Break Medication Dispensing and Supply Chain Management Electronic Patient-Reported Outcomes (ePRO) Patient Pre-qualification and Recruitment

Recent Survey ClinPhone webinar April 2005 (n=300) What is the largest issue or challenge you face with randomisation and blinding in today’s clinical trials? Ensuring sites follow the randomization process correctly Preventing tampering of code break envelopes Providing 24h on-call code break staff Managing more complicated randomization e.g.. stratification Ensuring randomization methods are followed in open label studies Demonstrating internal staff are blinded to randomization schedule Other

Recent Survey ClinPhone webinar April 2005 (n=300) What is the largest issue or challenge you face with medication management in today’s clinical trials? Accurately forecasting the amount of drug required Managing the logistics of large multinational trials Managing drug expiration Limitations on supplies due to manufacturing Efficient use of medication in titration studies Other

Medication labelling/dispensing IVR / IWR approach Unique Medication Numbering Can be applied to ‘Kit’ of supplies Can be applied to the Individual Dispensing Unit Any unit can go to any patient (randomised to same treatment group) Any unit can be used for any treatment period Using the smallest dispensing unit gives the most flexibility Pooling medication across studies possible When performing medication management using an IVR or IWR approach, each pack is now uniquely numbered – packs no longer are assigned to specific subjects or to visits. This means that any pack can be dispensed to any subject for any visit, for subjects assigned to the same treatment group. This is most advantageous – in terms of wastage – if packs are dispensed in the smallest dispensing unit. A 1-month pack dispensed each month will result in less wastage than dispensing a 3-month pack every 3 months. The IVR and IWR approach can also provide substantial saving in medication for protocols running simultaneously for which the same packs can be used for any of the protocols.

Medication dispensing and re-supply ClinPhone Inventory database Notification: Arrival / Damaged packs Dispensing call Consignment details Consignment request Pack numbers Drug distribution depot Investigational site Shipment A B Stock levels fall to trigger level

The benefits of eClinical integration Why Integrate? The benefits of eClinical integration

eClinical solutions EDC IVR CDMS Safety System CTMS DSMS

Why Integrate? Remove duplication of data and activities Ensure all systems contain the most up-to-date information at all times Simplify processes for the end-user Enhanced data access Facilitate reporting and consolidation of project management data through the solution of choice Eliminate manual processes

Integration principles The main objectives of any integrations: Do each task once – remove resource duplication and the errors introduced by transcription Do it in the place that makes sense – decide on the best overall process and configure systems to fit Study specific

The breadth of integration Example 1: patient enrolment EDC IVR CDMS Safety System CTMS DSMS Patient Identifiers, demography and visit frequency data Drug supply / re-supply request Randomisation Event Data for randomisation (eg. stratification variables) Randomisation and Pack Number Drug Shipment Patient Data Patient Enrolment

The breadth of integration Example 2: IVR diary call EDC IVR CDMS Safety System CTMS DSMS Tracking Primary Efficacy data Drug re-supply request Safety alerts Data validation Patient completes IVR Diary Diary Data Diary Data Data validation

Common overlap of data IVR CTMS EDC Randomization Dispensing ePRO Screening data Site contact details

How real-time eClinical integration is achieved at ClinPhone Integration overview How real-time eClinical integration is achieved at ClinPhone

Data interchange overview F I R E W A L L F I R E W A L L FTP site Application-specific message format XML message IVR / IWR database Application database Event Exporter Importer Transformer Database update XML message Application-specific Message format FTP site Application

IVR-CTMS Integration EDC IVR CDMS Safety System CTMS DSMS

Integration touchpoints: CTMS Site details Delivery addresses Patient number ranges Site initiation / qualification Site activation FSFV (screening) Randomisation Re-dispensing Withdrawal / completion LSLV Site / study close Study timeline IVR / IWR CTMS Ethics approval Regulatory approval Date first drug shipped Patient tracking data Patient tracking data Patient tracking data Patient tracking data Patient tracking data Site de-activation

IVR–EDC integration EDC IVR CDMS Safety System CTMS DSMS

Integration Touchpoints: EDC Site initiation / qualification Site activation FPFV (screening) Randomization Re-dispensing Withdrawal / completion LPLV Site / study close Study timeline IVR / IWR EDC Initial shipment? Subject no. Initials / d.o.b. Stratification data Pack dispensed Diary data Pack dispensed Withdrawal

Case study IVR-EDC integration Procter and Gamble Pharmaceuticals

P&GP’s Best Practices entry

Case study overview Two almost identical study protocols IDDM and NIDDM Sites USA only 17 sites Patients 180 across both studies IVR application (ClinPhone) Real-time activities whilst with patient Randomisation Medication dispensing Medication supply chain management Patient reported outcomes data collection (am and pm diary) EDC application (Phase Forward’s InForm)

Integration objective 1 Manage 6 common data points between systems Patient demographic information Date of birth Initials Gender IVR generated data Randomisation number Randomisation date Randomisation time

Integration objective 2 Remove duplication in end-user activities Following randomisation call via IVR Pass data to InForm Enrol an new subject within InForm Populate screening and randomisation eCRFs with IVR delivered data

Integration objective 3 Populate eCRFs with patient diary data in real-time AM fasting blood glucose reading PM sum of three daily dosing insulin volumes Eliminate site data entry of paper diary data Satisfy regulatory requirements for Investigators to take responsibility for diary data Monitor diary compliance in real-time Review and report diary data alongside other clinical data

P&GP key benefits realised Site coordinators have less data entry to perform The P&GP data management group do not have to check for discrepancies between common data points in the IVR and EDC systems Queries from discrepancies are eliminated Time and financial benefit for Sponsor and site staff Patient diary compliance proactively monitored Investigators have immediate access to diary data via EDC Regulatory requirements Improvements in patient care and monitoring More efficient workflow May improve database lock time

Demonstration movie EDC - IVR integration

Integration example Screening data entered within EDC application Randomization performed using IWR Data received by EDC Patient diary event sent from IVR / IWR to EDC Play movie

Summary and conclusions

The Future of Clinical Trials A multitude of eClinical technologies are in use today All are being used in some trials Some are tightly integrated with others Others still used in isolation Integration can provide powerful Sponsor and site end-user benefits eClinical Trials of the future? Evolution … not Revolution Increased adoption will lead to increased requirement to integrate Highly integrated “seamless” solutions

Clinical Trial Management System Clinical Trial Management System New study site details Site contact detail amendments Regulatory / ethics approval IVR central hub of real-time data CTMS IVR/web Clinical Trial Management System Clinical Trial Management System New patient enrolled / withdrawn/ completed Site medication inventories Patient tracking data IVR / web CTMS EDC DSMS New study site Patient withdrawal Patient completion Randomization data Dose adjustment / calculation data Electronic Data Capture System Electronic Data Capture System Medication pack dispensed New patient enrolled New study site EDC IVR/web Randomization number Medication pack number(s) IVR diary data Dispatch notification Pack list and pack list updates Expiry date updates New patient enrolled Drug Supply Chain Management System DSMS New study site / details IVR/web Shipment requests

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