eSource, DIA EuroMeeting, Lisbon, March 2005

transcript

eSDI Group 7 March 2005, Lisbon Becky Kush, CDISC Jane Scott, FDA Dave Iberson-Hurst, Assero & CDISC

Contents eSDI Group

Areas of Interest Work to Date

Psychometric Validation Interim Analysis

eSource Next Steps Discussion

eSDI Group

•  The eSource Data Interchange Group was formed to provide a forum for gathering input from the biopharmaceutical industry and the development of recommendations that could help address existing issues with the collection and use of eSource Data for clinical trials; the initial focus was on electronic Patient Reported Outcomes.

eSDI Group •  FDA and sponsors currently share a

feeling that there is no clear direction on regulatory issues related to eSDI/ePRO

•  CDISC was asked to initiate the eSDI group

•  It was considered very important for this group to have a vendor-neutral, platform-independent perspective.

eSDI Group •  Formed in October 2004 •  FDA requested input from industry

representatives (specifically trials sponsors, site representatives and CDISC representatives) regarding the issues

•  Comprised of two representatives from major pharmaceutical companies, one validation expert, three representatives of investigative sites, two CDISC representatives and five FDA liaisons

Areas of Interest •  Interim Analysis

– What are the issues? •  Psychometric Validation

– What are the issues? – Touch points with System Validation?

•  eSource – How does industry move forward?

Progress to Date (1) •  eSDI Group Communications

–  Teleconferences ~ every two weeks; minutes/e-mails to share ideas and identify issues

–  Face to face meeting on 31 January •  Development of a Draft White Paper

–  Rationale –  eSource Data Interchange

•  (issues, relationship to regulations for paper, recommendations for adherence to regulations for ePRO/eSource)

–  Psychometric and System Validation –  Interim Analyses –  Issues for the Future

Progress to Date (2)

•  Expert Focus Groups Invited for Comment – 23 February, Philadelphia – 7 March, Lisbon

Next Steps •  Revise White Paper and Solicit Broader

Comment –  4-5 April, DIA ePRO Conference, Arlington –  11 April, SAS Users Forum –  CDISC Website

•  Complete White Paper and Present Widely with FDA Representatives –  DIA Annual Meeting, Washington DC, June 2005 –  Potential Guidance on ePRO –  Webinars, other venues

Issues •  Collection of data without adequate

psychometric validation •  Inadequate validation and control of

systems used for data collection •  How to transition from the paper world to

the ‘eWorld’ in terms of audits, reviews, compliance to regulations

•  No regulatory basis for Trusted Third Parties

Sense of Urgency •  ePRO data going directly from patient to

trial sponsor (bypassing the investigator) •  Investigators not having a copy of or

control of the source data •  Collection of data without Data analysis ‘on the fly’ – during the collection process, without adherence to ICH E9 guidance on interim analyses

Interim Analysis •  Present the issues resulting from the

concerns about the introduction of bias •  Detail the guidance

–  ICH E9 •  Section 4.5 - Interim Analysis and Early Stopping

– FDA Guidance for Clinical Trial Sponsors (Draft Guidance – November 2001)

•  Section 4.2 - Confidentiality of Interim Data and Analyses

Validation •  Examining the touch points between

system and psychometric validation •  Psychometric aspect of ePRO instruments •  System validation aspects of ePRO

systems •  FDA PRO draft guidance coming in April

eSource •  Motivation and Aims •  Method •  Analysis •  Recommendations

Motivation and Aims •  Motivation

–  Desire to solve the issue –  Increase adoption

•  Aims –  Something tangible to shoot at –  Detailed enough to allow debate –  Practical

•  End Point –  Simple check list, well understood (what not how) –  Allows all stakeholders (FDA, Sponsors, Vendors &

Investigators) to assess current and future technologies

Method •  Examine the paper process; if well

executed, it meets the regulatory requirements

•  What are the requirements that source documents must meet?

•  What do the FDA, Sponsors and Investigators need (key requirements) from source documents?

Method •  Examine the life cycle of paper source

documents •  Stand back and extract the requirements •  Consider

– Regulations – Data Quality & Integrity – Subject Safety

POPULATED

ARCHIVED

Paper Life Cycle

OBSOLETE

Select

Capture

Clarify, View, Monitor or Inspect

Study Ends

Make Copy

End of Retention Period

View or Inspect

Create

Destroy

Analysis of Process •  What are we doing? (The What)

–  What is the action? •  Why are we doing it? (The Why)

–  What is the purpose? •  What does it achieve?

–  What are the drivers? •  What are the regulations? •  How does it contribute to data quality (ALCOA) and integrity? •  What impact on subject safety?

•  Purpose is to identify the significant operations and the core requirements/needs of the various stakeholders (FDA, Sponsors and Investigator)

POPULATED

ARCHIVED

Paper Life Cycle

OBSOLETE

Select

Capture

Clarify, View, Monitor or Inspect

Study Ends

Make Copy

End of Retention Period

View or Inspect

Create

Destroy

Analysis of Process •  What are we doing? (The What)

–  What is the action? •  Why are we doing it? (The Why)

–  What is the purpose? •  What does it achieve?

–  What are the drivers? •  What are the regulations? •  How does it contribute to data quality (ALCOA) and integrity? •  What impact on subject safety?

•  Purpose is to identify the significant operations and the core requirements/needs of the various stakeholders (FDA, Sponsors and Investigator)

Requirements •  Initial analysis resulted in 9 requirements •  Requirements examined in the context of

21 CFR 11 – Additional requirement

•  Re-examined in the context of existing technologies/architectures – Additional two requirements

Architectures/Technologies •  Case Report Form

– Paper CRF – eCRF (Thin & Thick Client)

•  Diaries – Paper Diary – eDiary (PDA, IVRS etc)

Requirements •  12 in total •  As they stand today •  Open for review, discussion and debate •  The detail is in the white paper •  All are mapped to regulations

Requirement 1

An instrument used to capture source data shall be an accurate

representation of the protocol ensuring that the data as specified

within the protocol is captured correctly.

Requirement 2

Source data shall be Accurate, Legible, Contemporaneous, Original, Attributable, Complete and

Consistent (the ALCOA and Data Integrity requirement).

Requirement 3 Source documents shall provide the

ability to maintain an audit trail for the original creation and subsequent

modification of the source data.

Requirement 4 The storage of source documents shall

provide for their ready retrieval.

Requirement 5 The investigator shall store the original

source document or a certified copy.

Requirement 6 The mechanism used to hold source

documents shall ensure that source data cannot be modified without the knowledge or approval of the

investigator.

Requirement 7 The storage of source documents shall

ensure they cannot be destroyed.

Requirement 8 The source document shall allow for

accurate copies to be made.

Requirement 9 Source documents shall be protected

against unauthorised access.

Requirement 10 The sponsor must never have exclusive

control of a source document.

Requirement 11 The location of source documents, and the

associated source data, shall be clearly identified at all points within the capture

process.

Requirement 12 When source data are copied, the process

used shall ensure that the copy is an exact copy having all of the same

attributes and information as the original.

Subject Investigator

Trusted Third Party

Example – eDiary

Data entered by subject using a PDA and is saved to non-

volatile storage on the PDA. Sent to TTP

database as and when communications

available.

Data stored by TTP, viewed by investigator via the web.

Example – eDiary Requirement An instrument used to capture source data shall be an accurate representation of the protocol ensuring that the data as specified within the protocol is captured correctly.

Source data shall be Accurate, Legible, Contemporaneous, Original, Attributable, Complete and Consistent (the ALCOA and Data Integrity requirement).

Source documents shall provide the ability to maintain an audit trail for the original creation and subsequent modification of the source data.

The storage of source documents shall provide for their ready retrieval.

The investigator shall store the original source document or a certified copy.

The mechanism used to hold source documents shall ensure that source data cannot be modified without the knowledge or approval of the investigator.

Requirement The storage of source documents shall ensure they cannot be destroyed.

The source document shall allow for accurate copies to be made.

Source documents shall be protected against unauthorised access.

The sponsor must never have exclusive control of a source document.

The location of source documents, and the associated source data, shall be clearly identified at all points within the capture process.

When source data are copied, the process used shall ensure that the copy is an exact copy having all of the same attributes and information as the original.

Trusted Third Party

Example – eDiary

available.

Trusted Third Party

Example – eDiary

available.

The mechanism used to hold source

documents shall ensure that source

data cannot be modified without the knowledge or approval of the

investigator.

Trusted Third Party

Example – eDiary

available.

The sponsor must never have

exclusive control of a source document.