Endpoint Adjudication of Events Charter Template: What Should Be Included?

December 13, 2016

Endpoint adjudication is gaining importance in pharma today, however, no guidance on endpoint adjudication currently exists. The LinkedIn Endpoint Adjudication Community has generated an Events Charter Template to shed light on the subject for those in need of guidance.

Endpoint adjudication is gaining importance in the industry, however, no guidance on endpoint adjudication exists. In order to shed light on endpoint adjudication, the LinkedIn Endpoint Adjudication Community generated an Events Charter Template for endpoint adjudication to assist those in need of guidance.

1. Approval Page

The Adjudication Committee (AC) Chair and Members submit their dated signature to ensure that they have read and approved of the following Charter and its contents.

2. Study Abstract/Proposal/Introduction Page

Description of the Clinical Trial related to Adjudication, Study objectives (primary, secondary, exploratory) and the rationale behind the Endpoints Assessments adoption.

3. Purpose of an Adjudication

The objective of an adjudication is that a well-recognized group of experts in the area of the <study indication> confirms that an event took place and that for each event it fulfills the per protocol definitions. The members of the committee are not participating in the trial as principal or coinvestigators and their review ensure well reported, unbiased, blinded to treatment, count of events. When an adjudicator also participates - directly or indirectly - in the study, due diligence needs to be in place by the sponsor to avoid either adjudication of self-reports and unintentional unblinding of that adjudicator. The process should take place on a continuous timely fashion. Source documents need to be submitted on time together with the report shortly thereafter.

4. Scope of Adjudication

The Adjudication Committee is responsible for reviewing each event as defined in the protocol. Their work is independent and impartial. Such type of review is to ensure accurate counting, assessing, rating, etc. of protocol defined "events".

Unless defined by the Charter and supported by the composition of the Committee review of safety signals or of benefit - risk assessments are out of the scope of the Adjudication Committee.

5. Adjudication Committee Membership

Identification of the Committee Chair along with his/her required expertise and related experiences should be described in detail. Roles and responsibilities of the Committee Chair should be described.

The chair should as a minimum write/update or, respectively, oversee writing/updating the Charter and the decision rules. S/he chairs the Adjudication Committee meetings, arbitrates, documents, reviews and approves meeting minutes, decisions and results, and communicates with the sponsor/Steering Committee and clinical sites, as appropriate.

The Charter will include a list of the Adjudication Committee Members including their contact information (work address, telephone number, fax number or email address), credentials and experience qualifying them for their assigned role(s). Adjudication Committee members will sign a potential conflict of interests declaration.

The roles of the Adjudication Members are to be summarized, including their responsibilities throughout the course of the clinical trial, timelines, and participation in the Adjudication Committee meetings.

Procedures are to be in place in the event that it is necessary to replace a Committee Member. The Charter keeps on file the reasons for replacing an Adjudication Committee member, such as inadequate performance and lack of communication with other members, lack of participation in consensus meetings, or inability to meet the responsibilities detailed in the Charter. Decision and communication are to be kept internal but are made available to auditors and regulatory inspectors.

6. Adjudication Committee Training

An adequate description of the training processes for new members of the Committee to adjudicate clinical endpoints will include how system access controls and blinding of reviewers will be addressed. Training will include processes, provisions and measures to prevent intentional or unintentional unblinding of trial participants/data.

7. Endpoint Adjudication Software

A description of the Endpoint Adjudication software to be used throughout the life-cycle of the clinical trial including how systems' security (user ID, electronic signature, passwords to access), customization, and validation controls have been addressed.

8. Endpoint Adjudication Processes

This section is to include the following elements:

  • Endpoint definition(s); what constitutes an endpoint, methods of endpoint identification.

  • Note: an event can be an endpoint (e.g., classification of the severity of a cardiac event) or a measurement of a tracing (e.g., ECG) or an image (e.g., tumor size). In the following the term event will be used to describe both types of adjudication processes/tasks.

  • Is the event a primary or secondary endpoint.

  • What are the event sources, on what source documents will the Adjudication Committee deliberate.

  • Event identification codes for making the events anonymous.

  • Blinding provisions to clinical trial center team members and sponsors.

  • Management of participants' identifiers and relation to allocation of treatment.

  • A statement that adjudication of an event where the rater had any involvement is nullified.

  • If used, the process for post-hoc analyses or data re-analysis using an adjudication process and how this will be managed within the study planning.

  • The use of an adjudicated result will be clarified as to whether this is planned as the primary data analysis, is concurrent and in addition to or separate from analysis and publication of primary results or original results (such as intent-to-treat).

  • Adjudication committee members' roles in authorship or acknowledgment in a publication is to be pre-specified and defined in the Adjudication Committee Charter.

 

9.  Endpoint Assessments

The Assessment process consists of the following steps:

9.1 Event Submission

  • Description of the event submission procedure and rules applied for assignment to a specific reviewer.

  • Provisions made to avoid adjudication of self-events.

  • The coordinating center will ensure that each event is complete as a package including the reporting CRF and all relevant supporting source documents. This can be a paper or an electronic process. Packages are to reach the designated adjudicators independently via courier/or/electronic password protected workflows. Adjudicators might send back their decisions also by courier or register themselves in the electronic "adjudication space" especially created for that.

  • The workflow shall include a process by which the rater can ask for additional information/data, e.g., a request form for the adjudicator to request. The complete package would then consist of all original information/data plus the supplemental information/documents/data).

  • The workflow may support the raters with automated edit checks, fill-in instructions.

9.2 Disagreement Management

  • Description of the procedures to handle Disagreements among Reviewers.

  • Classification of disagreement (example: major or minor, event or not event) and respective resolution procedures. As mentioned in paragraph 8.1, if in doubt the rater needs to request more information to make an unequivocal decision.

9.3 Event Changed Data

  • When a site re-submits an event and this has not been adjudicated yet, only the resubmission goes to adjudication.

  • When the re-submitted event has been already adjudicated, the last information should be reanalyzed anew and the re-adjudication result superseeds any prior adjudication.

  • The Chair can review the entire reporting, if deemed necessary.

10. Adjudication Deliverables

The following are examples of deliverables of the Adjudication Process:

  • Format and content of the Adjudication Assessment Report by rater and consolidated finalized Adjudication Assessment Report as well as any periodic/final summary reports.

  • Format of data and meta-data transfers/exports, e.g., as SAS, XML or other formats.

  • Statement of preservation of blindness of sponsor and clinical trial center staff members, if applicable.

11. Communications

A list of people involved in the adjudication process with their respective role (e.g., Adjudication Coordinator, Chair of the Adjudication Committee, Adjudication Committee Member), their responsibility and contact information will be maintained.

A Communication Plan is maintained to define upfront the following scenarios/requirements:

  • Description of the situations that trigger an exchange of communication between sponsor staff and Committee Members, between Committee members, etc.

  • It is recommended to develop and use communication templates such as standard meeting teleconference agendas and minutes that is as standard agenda items topics that are of particular importance to the adjudication process.

  • The Adjudication status will be tracked by means of periodical reports, and according to the needs of the study, indicating, for example, how many of the total reported events have been adjudicated, how many were reported but are not complete yet, and number of refuted  from the completed ones.

12. Timelines - Assessment of Workflow

A description and flowchart of the Endpoint Assessment Standard Procedures and Workflows should be prepared upfront and these should take into consideration key study milestones such as submission and assessment timelines as well as any other milestones defined in the trial protocol.

The sponsor's coordinator should actively manage these timelines and ensure that the adjudication process runs according to the agreed plan and, where required, issue reminders to the adjudication committee members.

13. Quality Control: Data Sources, Procedures, Analysis

A complete list of data sources and their specified format is to be defined, for example the following aspects should be addressed:

  • Data points where the CRF is the source of the entry, i.e., CRF is the source document.

  • Option of .pdf upload of scanned data forms or .pdf upload of medical record elements, upload of CT or MRI imaging

  • Roles and responsibilities in transferring adjudication information/assessments into the CRF or clinical database, i.e., is information related to adjudication entered into the CRF, a separate document, a separate data collection platform. Who performs these data entry tasks: sponsor representatives, adjudicators or who else.

  • It is recommended to define media involved in the adjudication process (either as data capture or storage media), roles and responsibilities in entering data onto these media in a matrix table identifying explicit roles and accountabilities.

  • How missing data and adjudication decisions will be tracked, solicited and finally incorporated into analyses.

  • Objective criteria/rules allowing the adjudicators to refute, disregard, discount an event.

  • Decision making criteria and process to resolve a conflict when a clinical trial center disagrees on grounds of objective evidence with the adjudicators on the assessment of an event. For example, the entire file should be made (again) available to allow the adjudicators to make a thorough, objective and educated decision instead of just refuting the event.

14. Appendices

  • List of Adjudication Questions and a description of the available answers for selection by Reviewers.

  • List of data forms and/or data elements and how each is defined for entry purposes.

  • For adjudication Committees involved in a safety/benefit - risk review, identification of the applicable RSI (Reference Safety Information) or if no RSI is available a list of anticipated (expected) adverse events as noted in previous research and how these are defined. 

15. Contributions

Working group Members that are contributing to this document:

  • Mark Gichuru, B.Sc. (Hons), CCRP Research Associate

  • Kathryn France, BA, RN, PHN, CCRC, CCRA University of Minnesota Medical School Department of Neurology

  • Laura Bonilla, Senior Research Coordinator, McMaster University, PHRI

  • Mimmo Garibbo, Ethical GmbH – Director Endpoint Adjudication Linkedin Group Manager

  • Beat Widler, PhD, dipl. pharm. med. Ethical GmbH - Quality Assurance

 

Learn More at the 4th Annual Endpoint Adjudication Conference 

www.cbinet.com/endpoint

 and hear from FDA Senior Reviewer Andrew Farb, MD.