Endpoint Adjudication Definitions, Procedures and Tools

CRO Partnering Program

by Ethical eAdjudication ®: the simplest Software Solution to manage Endpoint Adjudication Committees in Clinical Trials. 

the list of Terms and definitions related to the Clinical Endpoints Adjudication.

This Blog Article should be read in conjunction with the Endpoint Adjudication of Events Charter Template and the Endpoint Adjudication Data for Submission to FDA & EMA - What Should Be Included?

ENDPOINT ADJUDICATION

the procedure by which clinical events identified as potential endpoints are submitted to a panel of independent experts to be assessed in a blinded way.
Adjudications are applied in clinical trials based on subjective evaluations like imaging and adaptive design.

ADJUDICATION ASSESSMENT

The core operation of an Adjudication procedure.
It's usually made by combining the judgments of several (3,5 or more) Reviewers. The Assessment is collected through the adjudication forms (paper or
electronic)

ADJUDICATION CHARTER

The Adjudication Charter is the fundamental document describing the Adjudication Standard Operating Procedures of a specific Clinical Trial.

The Charter usually includes the following sections:

Study abstract/ adjudication rationale;
Adjudication Roles;
Endpoints definitions and identification criteria;
Potential Endpoints Events sources;
Event Package composition (documents, images, key data);
Event submission procedures;
Assessment workflow and timelines;
Assessment Forms structure and constraints;
The procedure to request and handle "More Data" for incomplete or unsatisfactory event information;
The procedures to handle disagreements in CEC members assessments;
The procedures to establish and run Consensus Meetings;
The procedures to handle changes in the Event information delivered after event's submission to the CEC members;
The procedures and trigger for Communication among Coordinator, Staff and CEC Members;
Adjudication deliverables and data structures;
The procedures to implement Quality Control.

ADJUDICATION CHAIRMAN

The person who presides over the Adjudication Committee and procedures.
Often is requested to deal with disagreement situations

ADJUDICATION COORDINATOR / COORDINATORS

The Staff persons that take care of coordinating all the Adjudication operations and procedures. Usually is in charge of event submission to the CEC
Reviewers.

ADJUDICATION COMMITTEE

the group of persons in charge of assessment of clinical trial subjective endpoints. It's usually composed of independent expert clinicians that operate independently
and blinded in respect to the clinical trial operations.

ADJUDICATION FORM / FORMS

The form/forms used by the Adjudication Committee Members to express and record their assessment. They can be provided as paper forms or, in an
eAdjudication software implemented Electronic Data Capture ( EDC ) online form to be filled in through an internet connection to the Cloud.

ADJUDICATION FORM / FORMS EDIT CHECKS

The tools and criteria by which the inputs of Reviewers into the eAdjudication form are checked for missed values, incoherent or wrong values or simply
fill-in mistakes by the CEC Members.

ADJUDICATION REVIEWER / REVIEWERS

The independent experts that are in charge of potential endpoint assessment.

ADJUDICATION ROLES

The identification of all the position involved in the Adjudication procedures and relative tasks. Most widespread roles are the following:

CEC Chairman;
CEC Coordinators;
CEC Staff;
CEC Reviewers.

ADJUDICATION WORKFLOW

The procedure, as described in the Adjudication Charter, by which the Adjudication assessment is made. It's usually defined by stating:

how many coincident judgments are needed for a valid assessment;
how CEC Members judgments are composed in the final assessment;
what happens in case of disagreements;
what happens in case of re-submission in consequence of changes turned up in the event information.

CEC: CENTRAL EVENTS ADJUDICATION

CEC: CLINICAL EVENT ADJUDICATION

CEC: CLINICAL ENDPOINT COMMITTEE

CEC: CENTRAL ADJUDICATION COMMITTEE

all the same as Adjudication

CLINICAL ENDPOINT / ENDPOINTS

In a clinical research trial, a clinical endpoint generally refers to the occurrence of a disease, symptom, sign or laboratory abnormality that constitutes one
of the target outcomes of the trial, but may also refer to any such disease or sign that strongly motivates the withdrawal of that individual or entity from
the trial, then often termed humane (clinical) endpoint.

A clinical trial will usually define or specify a primary endpoint as a measure that will be considered the success of the therapy being trialed (e.g. in justifying
a marketing approval). The primary endpoint might be a statistically significant improvement in overall survival (OS). A trial might also define one
or more secondary endpoints such as progression-free survival (PFS) that will be measured and are expected to be met. A trial might also define exploratory
endpoints that are less likely to be met.

CONSENSUS MEETING

The procedure, usually implemented as face to face meetings among some Adjudication Committee (selected) members, to assess the events with conflicting CEC
Members' judgments in the standard assessment procedure.

EAC: ENDPOINTS ADJUDICATION COMMITTEE

same as Adjudication Committee

EADJUDICATION ®

an online software system designed to support the Endpoint Adjudication process

EADJUDICATION ® LEGACY INTEGRATION / INTEGRATIONS

the procedures and software systems that allow for a direct communication of the eAdjudication environment with other external and pre-existing software
systems (e.g. Medidata EDC, CTMS, Oracle Argus). Integration of software is usually implemented for selection/collection of potential endpoint event information.

EVENT'S CHANGED DATA

The situation of an event for which the related information has substantially changed. Usually, these changes lead to re-submission.

EVENT DOSSIER / PACKAGE / INFO

The complete set of information that is delivered to the CEC Members to support their decision about Study Endpoints.
It's usually made of documents (medical records, laboratory reports, case histories, images, key variable values)

ADJUDICATION DOSSIER / PACKAGE ASSEMBLING

The procedures to make the Event Dossier ready for the submission to the Adjudication Committee. It usually includes the collection of Medical Records from the
Site / Source Systems and their translation, de-identification / anonymization, revision for completeness.

EVENT PENDING ADJUDICATION

A potential endpoint event that is waiting for the CEC Committee assessment decision.

EVENT RE-SUBMISSION

The process by which the Adjudication Coordinator is submitting a potential endpoint that's has been already assessed by the Committee, for a new assessment
by the Committee due to a relevant change or update in the Patient's Medical records.

EVENT SOURCE / SOURCES

The information systems, legacy software, documents or clinical procedures from which the potential endpoint event information originates

EVENT STATUS

The current status of potential endpoint events during the Adjudication workflow. Most common statuses are: to be submitted, pending decision, to be
discussed, resubmitted, changed data, close, etc.

EVENT SUBMISSION

The process by which the Adjudication Coordinator presents a potential endpoint, together with its information package, to the Reviewers for the assessment

MAJOR DISAGREEMENT

The outcome of conflicting judgments made by the Committee Members about the same event. It's usually handled by delivering the event to the Consensus face
to face Meeting for ultimate assessment.

MINOR DISAGREEMENT

A Disagreement in the Committee Members' that relates to a not-so-relevant aspect of their assessments. Usually is managed and resolved with a less complex procedure to lower its impact on the study management. E.g. the Chairman can solve the disagreement without a Consensus Meeting.

MORE DATA REQUEST

The procedure by which a Reviewer ask for more information about an event that he's currently not able to assess due to inadequate or incomplete information. Usually, the staff manages the requests by issuing a query to investigators/sites handling the related patient.

POTENTIAL ENDPOINT / ENDPOINTS

a Clinical Event that has the peculiarities to constitute a Study Endpoint.
In the Adjudication Charter are usually defined the events' attributes that identify a potential endpoint and the criteria that allow the detection of it.
The potential endpoints assessment as real Study Endpoints is made by the Committee Members and constitutes the core of the Clinical Adjudication process.

REVIEWERS QUALIFICATION

The procedures to ensure that every Reviewer included in the Adjudication Committe, after his training, is well qualified for the Clinical Assessments
requested by the Adjudication Charter. Usually is made by submitting to the Reviewers some events with a well-known interpretation and comparing their
judgements with the standard intepretation.

REVIEWERS RI-QUALIFICATION

Same as Reviewers Qualification but applied in a later time, during the Adjudication study duration, to ensure that the Reviewer is still qualified.
In case of failure leads to the Reviewer's re-training or exclusion from the Committee.

REVIEWER INTRA-VARIABILITY

A quality control metric of the Endpoint Adjudication procedure aimed at detecting and measuring the grade of consistency of a Reviewer's assessments during
time. It's usually defined by re-submitting in different times the same event to a Reviewer and comparing the results to detect any discordance in his
judgements.

REVIEWERS INTER-VARIABILITY

A quality control metric of the Endpoint Adjudication procedure aimed at detecting and measuring the level of Disagreement among the Reviewers.
It's usually defined as a percentage of events that lead to a Disagreement among the Committee Members.

ADJUDICATION QUALITY CONTROL

A set of procedures, measurements and metrics used to keeep the quality of the Endpoint Adjudication results under control.
Is usually applied by collecting and evaluating some specific and pre-defined metrics ( Intra-Variability, Inter Variability, etc) throughout the study
duration.

ADJUDICATION VALIDATION PACAKGE

The set of documents used to attest that the procedures and software systems used during the Endpoint Adjudication operation are compliant with
regulations (GxP, GAMP 5, US 21 CFR Part 11, EU GMP Vol. 4 Annex 11).
E.g. Validation Master Plan, User Requirements Specifications, Design and Functional Specifications, Traceability Matrix, Protocols and tests scripts for
Installation Qualification (IQ), Operational Qualification (OQ) and Performance Qualification (PQ) acceptance phases, Change Management, Backup and Recovery
and Users access SOPs and procedures.

SUBJECTIVE ENDPOINT / ENDPOINTS

A clinical Endpoint whose assessment requires a subjective judgement different from a simple quantitative data evaluation (e.g. evaluation of images).

_____________________________________________________________________________

DISCOVER How eAdjudication® can simplify your work: