Electronic Clinical Record form

Moving from paper to e-CRF – the implications for audits and auditors :

Moving from paper to e-CRF – the implications for audits and auditors

Slide 2:

EDC survey of more than 6,000 industry professionals revealed: 83 % of respondents currently use EDC 25% of respondents stated EDC use in all of their clinical studies increased by more than 50% over the last two years Almost half of respondents projected EDC use will increase by more than fifty percent over the next two years *EDC survey executed by Phoenix Data Systems and PharmaVOICE 2

Slide 3:

Investment in Electronic Data Capture (EDC) solutions to increase at a 14.7 percent compound annual growth rate (CAGR) to reach more than $3.1 billion for 2006-2011 2007 was the tipping point, as the adoption rate for EDC nearly doubled from 24.2 percent in 2005 to 45.2 percent in 2007 *Health Industry Insights, EDC analyst Chris Connor 3

Objectives For Today:

Objectives For Today By the end of the meeting you will understand: How eCRFs systems work Basics of validation of eCRF systems Key differences between paper and eCRF processes How to develop an audit strategy for eCRF systems 4

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Overview of presentation Overview of (simplified) data flow with paper and e-CRFs Comparison of audit scope, timing and targets of paper and e-CRFs Definition “Source Data” for the audit Please Note: The underlying assumptions for this course is that we have a validated database, a validated e-CRF, and have validated the data transfer – therefore validation activities are not part of the course 5

Simplified Process Flow Overview Paper CRF:

Simplified Process Flow Overview Paper CRF 6 Medical Term Coding by sponsor CDM personnel Database Soft Lock by sponsor CDM personnel Check of validity of data by CRA during monitoring visit Double data entry by sponsor CDM personnel Data Management Plan CRF Collection by CRA Quality Control Checks by sponsor CDM personnel Load External Data by sponsor CDM personnel Database Hard Lock by sponsor CDM personnel Monitoring Visit Query Resolution by CRA and investigator Monitoring Plan Query Generation by sponsor CDM personnel Collection of subject data in source notes & paper CRF by investigator CRF Completion Guidelines

Simplified Process Flow Overview Paper CRF:

Simplified Process Flow Overview Paper CRF 7 Medical Term Coding by sponsor CDM personnel Database Soft Lock by sponsor CDM personnel Check of validity of data by CRA during monitoring visit Double data entry by sponsor CDM personnel Data Management Plan CRF Collection by CRA Quality Control Checks by sponsor CDM personnel Load External Data by sponsor CDM personnel Database Hard Lock by sponsor CDM personnel Monitoring Visit Query Resolution by CRA and investigator Monitoring Plan Query Generation by sponsor CDM personnel Collection of subject data in source notes & paper CRF by investigator CRF Completion Guidelines

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Audit Approach Paper CRF Timing of audit typically at soft lock stage, i.e. when clinical activities at site have been completed Location is typically the office where Clinical Data Management (CDM) activities have been performed “Source Data” of the audit are the paper CRF and queries and CDM documentation, e.g. the CDM Trial Master File (TMF) Reference Documents are e.g. Protocol, CRF Completion Guidelines, Data Management Plan, etc 8

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Audit Approach Paper CRF Scope typically focuses on Comparison of database content versus CRF and queries for selected percentage of subjects Data audited have been entered into CRF by investigator source data verified by CRA double data entered by CDM personnel undergone data discrepancy and QC checks by CDM personnel 9

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Audit Approach Paper CRF Scope further typically includes Review of results of electronic data transfer for percentage of selected subjects Review of Quality Control (QC) procedures, including review of test procedures electronic data transfer Review of Data Management Plan and related documentation 10

Simplified Process Flow Overview e-CRF:

Simplified Process Flow Overview e-CRF 11 Medical Term Coding by sponsor CDM personnel Database Soft Lock by sponsor CDM personnel Collection of subject data in source notes by investigator Online data transfer into Database by investigator Data Management Plan Completion of e-CRF by investigator Quality Control Checks by sponsor CDM personnel Load External Data by sponsor CDM personnel Database Hard Lock By sponsor CDM personnel Monitoring Visit Query resolution by investigator Monitoring Plan Query Generation by sponsor CDM personnel CRF Completion Guidelines

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Audit Approach e-CRF Data in database have been entered into CRF and database by investigator (single data entry) source data verified by CRA but after having been entered into database undergone data discrepancy and QC checks by sponsor CDM personnel discrepancy resolution is done directly with the investigator 12

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Audit Approach e-CRF Timing of audit: after soft lock of database ? What to audit against? Remember: data are entered into the database by the investigator (single data entry), and queries resolved by investigator directly into the database Other options for audit? 13

Simplified Process Flow Overview e-CRF:

Simplified Process Flow Overview e-CRF 14 Medical Term Coding by sponsor CDM personnel Database Soft Lock by sponsor CDM personnel Collection of subject data in source notes by investigator Online data transfer into Database by investigator Data Management Plan Completion of e-CRF by investigator Quality Control Checks by sponsor CDM personnel Load External Data by sponsor CDM personnel Database Hard Lock By sponsor CDM personnel Monitoring Visit Query resolution by investigator Monitoring Plan Query Generation by sponsor CDM personnel CRF Completion Guidelines

Audit Approach – e-CRF:

Audit Approach – e-CRF Process audits? or Data audits? 15

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Audit Approach e-CRF Process audits Timing: when processes are performed Location: in CDM office Scope: process audit of electronic data transfer for site data of Quality Control (QC) procedures, of test procedures electronic data transfer for other remote data, e g. labs of Data Management Plan and related documentation 16

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Audit Approach e-CRF Process audits – issues to consider Is it sufficient to audit a process without a data sample? Is the audit of one process sufficient? Or how many processes and which ones would need to be audited to assure quality? 17

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Audit Approach e-CRF Data audits: Timing: during the clinical phase of the study Location: at investigational site Scope ? 18

Slide 19:

Audit Approach e-CRF Data audits – potential scope Audit of a percentage subject files at site, which are compared against the database content (single data entry by the investigator) including queries, again resolved directly into the database by the investigator Audit trail of changes important part of audit Security aspects of access to e-CRF and database another focus of the audit 19

Slide 20:

Audit Approach e-CRF Data audit – issues to consider Combined with typical site audit activities? More travel required to audit data Has auditor required technical knowledge to assess audit trail and security aspects? Is it sufficient to audit data but not the underlying processes? Is it sufficient to audit the underlying process but not the data? 20

Slide 21:

You have more questions now than answers? Good!! The answers will be given during the next presentations. 21