The endpoint of a trial is the aspect that is being measured in order to answer the question that the trial is asking.

It is very important that the endpoints being measured are defined and reported in the same way by different clinicians working on a trial (perhaps in a single centre study and critically between sites). This is essential so as to ensure consistency between the criteria by which a specific diagnosis is made, and by which any outcome is measured. Not doing this could provide a false result in the trial. An endpoint review committee is used to ensure this consistency.

This committee is responsible for reviewing important end points reported by the trial investigators to ensure they meet the protocol-specified criteria.

The committee also known as (clinical events committees) may review laboratory, pathology and/or imaging data, autopsy reports, and any other data deemed relevant. To prevent bias, the committee are typically blinded to the assigned study arm when performing their assessments. Such committees are particularly valuable when endpoints are subjective and/or require the application of a complex definition, and when the intervention is not delivered in a blinded fashion.

Although the End Point Assessment committee do not share responsibility with DSMB, their assessments (if performed at frequent intervals throughout the trial) may help ensure that data reviewed by the DSMB is complete and “clean” for their deliberations. Such committees can ensure that a study achieves a high scientific quality. 

Methods of adjudication
Adjudication is usually performed by using the locally reported outcome as a surrogate for a subject’s endpoint status. By using data reported by the investigator, data analyses can be performed promptly but there is a risk of the DMC making a decision about the future of the trial on the basis of unadjudicated data. Further, if the results of the data barely meet study stopping criteria, the DMC may be hesitant to recommend halting the study. Another option is to use the available adjudicated data for data analyses while adjusting for any unadjudicated data, using predictive values and weighting unadjudicated events as true events. These statistical methods of adjudication rely on assumptions about future endpoint adjudications that cannot be verified until after all data have been adjudicated.

In studies involving a large number of investigative sites with considerable degree of variability, it can be difficult to determine the end point of a clinical trial study. While both methods provide some sort of adjudication, there have been disparities between locally reported and centrally adjudicated end points documented in studies.
Regulatory agencies are increasingly expecting, and in some cases requiring, centralised adjudication to assess clinical endpoints to control the impact of this variability and to produce data for use in statistical analyses that are as standardised as possible.

Centralised adjudication process can be applied to both efficacy and safety endpoints. In efficacy studies, conducted for instance for cardiovascular drugs, the objective is to evaluate whether there is compelling statistical evidence that fewer events occur in the test drug treatment group than in the control group, i.e., prove that the test drug is effective. Conversely, in safety studies, the objective is to evaluate whether the number of events occurring in the test drug treatment group is statistically significantly lower than in the control group. In both cases, the validity and integrity of the study’s results and interpretation are enhanced by the acquisition of optimal quality endpoint data which has been centrally adjudicated.

Endpoint adjudication can now be done via the web, and there are several advantages to performing adjudication through this method. Since the system is automated and utilizes electronic data capture, the EAC process can occur throughout the course of the study. The reviews are immediately incorporated into the database and are readily available for use in data analyses. The automated nature of this system also reduces errors that can be introduced while organizing EAC materials, assigning cases and tracking reviews. Additionally, similar to electronic data capture (EDC) systems for capturing clinical data; the system has built-in edit checks and dynamic control logic to reduce errors introduced during the data entry process, all of which lead to higher quality EAC review data.

These features work together to allow the analyses of data and DMC reviews use data that are both current and adjudicated. The Web-based adjudication process also allows for monitoring of EAC performance as the web based reports can be used to ensure that members complete all assigned reviews promptly. It also tracks trends to determine if any of the EAC members are consistently interpreting cases differently from other members. Since all data related to the reviews are captured in the database in real time, up-to-date reports can be created to manage the endpoint adjudication. Obviously the efficiency of the web-based adjudication process is predicated on the fact that data review takes place on an ongoing basis and is therefore limited by inefficient data collection and verification processes. Also in circumstances where additional source documentation is required, obtaining this information in a timely manner can be challenging.

References and further reading
MRC - TRIALS STEERING COMMITTEE (TSC
http://www.eme.ac.uk/investigators/pdfs/TSCGuidelines.pdf

Guidance for Clinical Trial Sponsors Establishment and Operation of Clinical Trial Data Monitoring Committees
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm127073.pdf

Nolen T.L, Dimmick B.F, Ostrosky-Zeichner L, Kendrick A.S, Sable C, Ngaii A and wallace D “A Web-based endpoint adjudication system for interim analysis in Clinical Trials” Clinical Trials 2009 6 (1) 60-66
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000902/

Turner R.J, Somaratne R, Cabell C.H, Tyner C.A. “Centralised Endpoint Adjudication in cardiovascular outcomes studies” Journals for clinical studies 3 (2) 46-49
http://jforcs.com/jcs/downloads/centralised-endpoint-adjudication-in-cardiovascular-outcomes-studies-composite-endpoints-risk-ratios-and-clinical-endpoint-committees/