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© CDISC 2015

Presented by Simone Suriano

Contact info:Ethical GmbHWartenbergstrasse 40,CH-4052 Basel - SWITZERLANDinfo@ethical.ch - +41 (0) 61 271 30 30

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Clinical Endpoint Adjudication: could a dedicated CDISC standard improve quality?

© CDISC 2015

Topics

• What is Clinical Endpoint Adjudication?• In which trials is it used?• Typical adjudication process and players• Adjudication Data Submission• Proposal for a standard approach

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© CDISC 2015

Clinical Trial vs. Adjudication

Study Protocol

Patient Data

CRF data collection

Study coordinators, Monitors, Investigators…

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Clinical Endpoint Adjudication Charter

Adjudication information package(data related to the patient from different sources

including documents, images, videos)

Adjudication form assessment

Process coordinators, Reviewers, Central Evaluation Committee (CEC)

Chairman…

Rules of the game

Playground

Goal

Players

© CDISC 2015

Trials where adjudication is used• It is used in trials where an endpoint is determined by clinical

or radiological examinations requiring interpretation by expert(s) rather than by means of pre-defined laboratory measurements or other objective / measurable methods

• More generic: when an endpoint assessment is solely based on the opinion of a rater / assessor, i.e., is subject to personal interpretation

• A more scientific description of use scenarios can be found in the article “An Overview and Analysis Regarding the Use of Adjudication Methods in EU and US Drug Approvals” freely available on DIA Journal (dij.sagepub.com) at the following link:

http://dij.sagepub.com/content/early/2015/04/21/2168479015580382.full.pdf?ijkey=pXnQG9hhgzmG59u&keytype=finite

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© CDISC 2015

Adjudication – the players (an example)

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Coordinator: Sponsor responsible for patient cases submission to the CEC, document organization and upload, Quality Control.

Batch Process: Programs loading data, preparing CRS (Case Report Summary), detecting changes (optional)

Primary Reviewer(s): The CEC member who makes the primary review of a subject case and completes a CEC Form.

Consensus Reviewer: The CEC member who leads the consensus meeting and completes the Consensus Form.

Chairman: Is responsible to indicate whether changes occurring after the subject case was submitted should trigger a re-review of the case.

Adjudicator: The one who decides when no unanimity could be reached during a consensus meeting and completes the Adjudication Form

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1. Batch Jobs or Coordinator detecting cases

2. The Coordinator submits ready cases to a trio of Reviewers

3. Dr. A Reviews submitted patient cases

3. Dr. B Reviews submitted patient

cases

3. Dr. C Reviews submitted patient

cases

4. Decision Dr.A

4. Decision Dr.B

4. Decision Dr.C

5. More Data Needed

6. Batch Jobs or Coordinator detecting changes

Adjudication – process example(Centralized Online Process)

…continue on next slide…

© CDISC 2015

Adjudication – process example

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4. Decision Dr.A

4. Decision Dr.B

4. Decision Dr.C

Identical decision?

Yes

No

7. Results stored on DB

Yes

No

8. Consensus Meeting

9. Adjudicator

Unanimity?

…completes previous slide…

© CDISC 2015

Adjudication – the charter- Number and “mix” of reviewers

- usually 3 but could be 1,2 or more- “mix” of reviewers can be required. Mix can be on the reviewer professional role (i.e. 2 medical experts + 1

radiologist) or mixing and balancing between cases a set of “equivalent” reviewers

- Number and type of adjudication forms- could be specific for each case type – one for hospitalization, one for worsening, one for death, etc…- or one form only for all cases;

- Rules to define concept/rule

- Rules to define concept/rule

- Resubmission rules for the coordinator

- Possibility to consider minor disagreement on an assessment (or different levels in disagreement) with related flow management in the process

- The kind of process (centralized/distributed; paper/electronic/web based)

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Identical decision?

Unanimity?

© CDISC 2015

Adjudication – the data- Main source is usually a subset of CRF data - coming from paper or EDC / Medical

Records / Source documents / Patients Profiles systems / ePRO / etc… (with related “data quality” management issues and the possibility to need a process which handles re-submissions to reviewers.

- External providers (Laboratory data and similar) – sometimes rendered in graphical format

- Other documents related to the patient/case(hospitalization/discharge summary,

death certificate, diagnostic results/reports,

scorecards, etc…)

- Images / videos(ECG, tomography, RMN, echography,

angiography, gastroscopy, etc…)

- Full or specifically designed CRS (case report summary)

- Many different formats

(mainly scanned PDFs,

many specific image formats – DICOM, jpeg, others…)

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Adjudication – other aspects- Not always the “full” set of events to be submitted can be foreseen at the

beginning of the study

- Blinded/unblinded adjudication process

- Multiple submission of the same case (not a “must”, but an added value when dealing with potential data quality issues)

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© CDISC 2015

Adjudication – the assessment- The final assessment is the result of the matching of each

reviewer’s assessment following the “rules” stated in the charter

- The final assessment can be represented as a dataset with the content of the “adjudication form” filled-in by the reviewers:

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Adjudication – data submission

• At the end of the process and upon study closure, data have to be sent to regulatory authorities.

• Data to be presented includes: The data presented to the adjudicators on the last “submission round”

for each case (including all kind of data: variables from CRF/EDC, documents, images…);

The final assessments on the last submission round for each case AND for each reviewer;

The final assessment result for each case Full audit trail / history of submissions and assessments

• Currently I can find two main approaches to represent assessments results in electronic format:

With a custom / legacy data format decided directly with the receiver; Using a CDISC-like approach adapting the “free” available domains

(i.e. XX, XY, ZX…) to represent the final result of the assessments

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© CDISC 2015

The proposal to improve standard approach

• There is a lack of “standard” approach in many phases of the process

• Also where CDISC approach is used to submit data in the “free” domains, this is not “really” standard…

Proposal: to build a more standard approach to organize and harmonize the process could be a benefit

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Clinical Trial CDISC Endpoint adjudication ?Stydy protocol Protocol Endpoint Adjudication Charter ?CRF forms CDASH Assessment Forms ? - CDASH-like, specific per TA?CRF data SDTM Assessment Data ? - SDTM-like?

    Adjudication submission package:      - data ? - SDTM-like? LAB-like?

    - folder structure ? – eCTD-like?

CT Analysis data ADaM Endpoints assessment Analysis data ? - ADaM-like?

Terminology Controlled terminology Terminology ? - Controlled terminology?

...Other I am not aware of...   ...Other I am not aware of... ?

© CDISC 2015

Special thanks to:

• Massimo Raineri - Senior Director, Head Clinical Development Integration Competency Center – Actelion Ltd.

• Beat Widler – Quality Assurance and Head of CSV – Ethical GmbH

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© CDISC 2015

Questions (& answers?)

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